clozapine and Bipolar-Disorder

The primary aim was to systematically review the literature regarding the effectiveness of clozapine in reducing symptoms of primary psychotic and bipolar disorders in older adults. The secondary aim was to describe other reported patient and caregiver outcomes of clozapine treatment in older adults.. MEDLINE, Embase, PsychINFO, ProQuest, and PubMed databases were searched according to PRISMA guidelines for original empirical research examining the effectiveness of clozapine in adults aged 65 years or more with primary psychotic and bipolar disorders. Identified studies were assessed for methodological quality using the QualSyst tool.. 1121 records were screened, of which 7 studies met the inclusion criteria. In total, 128 subjects participated in the included studies (111 of whom were from a single study), with an age range of 65-86 years, and diagnoses including schizophrenia, schizoaffective disorder, bipolar disorder, and delusional disorder. Indications for clozapine use included treatment resistance and inability to tolerate other treatments. While six out of seven studies reported some improvement on the primary measure of psychopathology after treatment with clozapine, the group effects were modest and based on low-level evidence. Additional reported outcomes included discharge destination, death, and relapse. Most of the included studies were only of adequate methodological quality, with significant risks of bias identified.. Clozapine may have positive effects for primary psychotic and bipolar illnesses in some older adults, but the group effects reported were modest and based on low-level evidence studies with methodological limitations. Based on these findings, clinical decision-making about whether or not to trial clozapine should involve an individualized analysis of potential benefits and risks in collaboration with patients and their families and caregivers.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Bipolar Disorder; Clozapine; Humans; Psychotic Disorders; Schizophrenia

A recent increase in the literature regarding the evidence base for clozapine has made it increasingly difficult for clinicians to judge "best evidence" for clozapine use. As such, we aimed at elucidating the state-of-the-art for clozapine with regard to efficacy, effectiveness, tolerability, and management of clozapine and clozapine-related adverse events in neuropsychiatric disorders. We conducted a systematic PRISMA-conforming quantitative meta-review of available meta-analytic evidence regarding clozapine use. Primary outcome effect sizes were extracted and transformed into relative risk ratios (RR) and standardized mean differences (SMD). The methodological quality of meta-analyses was assessed using the AMSTAR-2 checklist. Of the 112 meta-analyses included in our review, 61 (54.5%) had an overall high methodological quality according to AMSTAR-2. Clozapine appears to have superior effects on positive, negative, and overall symptoms and relapse rates in schizophrenia (treatment-resistant and non-treatment-resistant subpopulations) compared to first-generation antipsychotics (FGAs) and to pooled FGAs/second-generation antipsychotics (SGAs) in treatment-resistant schizophrenia (TRS). Despite an unfavorable metabolic and hematological adverse-event profile compared to other antipsychotics, hospitalization, mortality and all-cause discontinuation (ACD) rates of clozapine surprisingly show a pattern of superiority. Our meta-review outlines the superior overall efficacy of clozapine compared to FGAs and most other SGAs in schizophrenia and suggests beneficial efficacy outcomes in bipolar disorder and Parkinson's disease psychosis (PDP). More clinical studies and subsequent meta-analyses are needed beyond the application of clozapine in schizophrenia-spectrum disorders and future studies should be directed into multidimensional clozapine side-effect management to foster evidence and to inform future guidelines.

Topics: Antipsychotic Agents; Bipolar Disorder; Clozapine; Humans; Psychotic Disorders; Schizophrenia

The use of ketamine for depression has increased rapidly in the past decades. Ketamine is often prescribed as an add-on to other drugs used in psychiatric patients, but clear information on drug-drug interactions is lacking. With this review, we aim to provide an overview of the pharmacodynamic interactions between ketamine and mood stabilizers, benzodiazepines, monoamine oxidase-inhibitors, antipsychotics, and psychostimulants.. MEDLINE and Web of Science were searched.. Twenty-four studies were included. For lithium, no significant interactions with ketamine were reported. Two out of 5 studies on lamotrigine indicated that the effects of ketamine were attenuated. Benzodiazepines were repeatedly shown to reduce the duration of ketamine's antidepressant effect. For the monoamine oxidase-inhibitor tranylcypromine, case reports showed no relevant changes in vital signs during concurrent S-ketamine use. One paper indicated an interaction between ketamine and haloperidol, 2 other studies did not. Four papers investigated risperidone, including 3 neuroimaging studies showing an attenuating effect of risperidone on ketamine-induced brain perfusion changes. Clozapine significantly blunted ketamine-induced positive symptoms in patients with schizophrenia but not in healthy participants. One paper reported no effect of olanzapine on ketamine's acute psychotomimetic effects.. Current literature shows that benzodiazepines and probably lamotrigine reduce ketamine's treatment outcome, which should be taken into account when considering ketamine treatment. There is evidence for an interaction between ketamine and clozapine, haloperidol, and risperidone. Due to small sample sizes, different subject groups and various outcome parameters, the evidence is of low quality. More studies are needed to provide insight into pharmacodynamic interactions with ketamine.

Topics: Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clozapine; Depression; Drug Interactions; Female; Haloperidol; Humans; Ketamine; Lithium; Male; Olanzapine; Psychotropic Drugs; Risperidone; Schizophrenia; Treatment Outcome

Clozapine is superior to other antipsychotics as a therapy for treatment-resistant schizophrenia and schizoaffective disorder with increased risk of suicidal behavior. This drug has also been used in the off-label treatment of bipolar disorder, major depressive disorder (MDD), and Parkinson's disease (PD). Although usually reserved for severe and treatment-refractory cases, it is interesting that electroconvulsive therapy (ECT) has also been used in the treatment of these psychiatric disorders, suggesting some common or related mechanisms. A literature review on the applications of clozapine and electroconvulsive therapy (ECT) to the disorders mentioned above was undertaken, and this narrative review was prepared. Although both treatments have multiple actions, evidence to date suggests that the ability to elicit epileptiform activity and alter EEG activity, to increase neuroplasticity and elevate brain levels of neurotrophic factors, to affect imbalances in the relationship between glutamate and γ-aminobutyric acid (GABA), and to reduce inflammation through effects on neuron-glia interactions are common underlying mechanisms of these two treatments. This evidence may explain why clozapine is effective in a range of neuropsychiatric disorders. Future increased investigations into epigenetic and connectomic changes produced by clozapine and ECT should provide valuable information about these two treatments and the disorders they are used to treat.

Topics: Antipsychotic Agents; Bipolar Disorder; Clozapine; Depressive Disorder, Major; Electroconvulsive Therapy; Humans; Parkinson Disease; Schizophrenia

To assess the clinical efficacy of clozapine in bipolar disorder and its adverse effect profile.. A literature search with no year and no language restriction was conducted. The search yielded 3858 articles, with 2453 remaining after duplicate removal; 9 were suitable for the systematic review. From the 9 included studies, 3 (100 patients treated with clozapine and 102 patients treated with other antipsychotics) could be included in a meta-analysis to test clozapine efficacy in the treatment of manic episodes.. Clozapine's efficacy was similar to other antipsychotics (Mean difference (MD): 0.03 [95%CI: 0.86-0.92], p = 0.59) in manic episodes. The systematic review also suggested that clozapine is faster at improving symptoms in manic episodes. In addition, two studies included patients with treatment resistant bipolar disorder (TRBD) and showed that clozapine is superior to other treatments for this specific population. Sedation was the most frequent side effect (49.6%), followed by constipation (31.8%) and tachycardia (23.2%).. Clozapine's efficacy was similar to other antipsychotics in manic episodes and is superior to other antipsychotics among TRBD patients.

Topics: Antipsychotic Agents; Bipolar Disorder; Clozapine; Humans; Treatment Outcome

The COVID-19 pandemic is a particularly relevant threat to mentally ill patients, and it constitutes a new challenge for health care providers. To the best of our knowledge, there is not any embracing published review about the use of psychotropic drugs during the COVID-19 pandemic.. Non-systematic literature review. A search in the PubMed database was performed, with the terms 'psychotropic drugs', 'COVID-19', 'psychiatry' and 'pandemic'. Consensus and clinical guidelines about psychotropic drugs and COVID-19 approach, published by scientific societies, governmental entities and drug regulatory agencies were included.. We present the recommendations about the use of psychotropic drugs during the COVID-19 pandemic, in the outpatient and inpatient settings. The treatment of affective bipolar disorder and schizophrenia have now added increased difficulties. Some psychotropic drugs interfere with the pathophysiology of the novel coronavirus infection and they could interact with the drugs used in the treatment of COVID-19. Some patients will need pharmacological interventions due to the presence of delirium. Smoking cessation changes the serum levels of some psychotropic drugs and may influence their use.. The COVID-19 pandemic has created new challenges in clinical practice. Psychiatric patients are a vulnerable population and often a careful clinical, laboratorial and electrocardiographic evaluation may be needed, particularly in those diagnosed with COVID-19. The regular treatment of mentally ill patients with COVID-19 presents increased complexity.. Introdução: A pandemia de COVID-19 constitui uma ameaça particularmente relevante para os portadores de doença mental e um novo desafio para os profissionais que os acompanham. Até à data, tanto quanto sabemos, não existe qualquer revisão abrangente publicada relativamente à utilização de fármacos psicotrópicos durante a pandemia COVID-19. Material e Métodos: Revisão não sistemática da literatura. A pesquisa na PubMed foi realizada com os termos ‘psychotropic drugs’, ‘COVID-19’, ‘psychiatry’ e ‘pandemic’. Foram incluídos os consensos e as normas publicadas pelas sociedades científicas, entidades governamentais e agências regulamentares de medicamentos. Resultados e Discussão: Apresentam-se recomendações relativamente à utilização de psicofármacos durante a pandemia COVID-19, em contexto de ambulatório e de internamento. O tratamento da perturbação afetiva bipolar e da esquizofrenia tem agora dificuldades acrescidas. Alguns psicofármacos interferem com os mecanismos fisiopatológicos envolvidos na infeção pelo novo coronavírus e têm interações com os fármacos utilizados no tratamento da COVID-19. Em doentes com COVID-19 e com delirium, a utilização de psicofármacos poderá ser necessária. A cessação tabágica altera os níveis séricos de alguns psicofármacos e pode condicionar a sua utilização. Conclusão: A pandemia de COVID-19 coloca novos desafios na prática clínica. Os doentes psiquiátricos constituem uma população vulnerável, sendo frequentemente necessária uma avaliação clínica, laboratorial e eletrocardiográfica cuidadosa, naqueles com o diagnóstico de COVID-19. Os doentes mentais com COVID-19 apresentam uma complexidade acrescida na gestão da sua terapêutica habitual.

Topics: Antiviral Agents; Benzodiazepines; Betacoronavirus; Bipolar Disorder; Body Temperature Regulation; Buprenorphine; Clozapine; Coronavirus Infections; COVID-19; Delayed-Action Preparations; Drug Interactions; Hospitalization; Humans; Lithium Compounds; Mental Disorders; Methadone; Narcotic Antagonists; Pandemics; Pneumonia, Viral; Psychotropic Drugs; SARS-CoV-2; Schizophrenia; Smoking Cessation Agents; Valproic Acid

In this paper, we aimed at reviewing evidence-based treatment options for bipolar mania and proposed tentative evidence-based clinical suggestions regarding the management of a manic episode, especially regarding the choice of the proper mood stabilizer and antipsychotic medication.. A narrative review was undertaken addressing 'treatment of bipolar mania'. Findings have been synthesized and incorporated with clinical experience into a model to support different treatment choices.. To date, there is solid evidence supporting the use of several medications, such as lithium, divalproex, and carbamazepine, and antipsychotics, such as chlorpromazine, haloperidol, risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, inhaled loxapine, asenapine, and cariprazine in acute mania, and some evidence supporting the use of clozapine or electroconvulsive therapy in treatment-refractory cases. However, in clinical practice, when making decisions about treatment, personalized treatment is needed, according to the different clinical presentations and more complex clinical situations within the manic episode and considering a long-term view and with the objective of not only a symptomatic but also functional recovery. After remission from acute mania, psychoeducation strategies are useful to ensure adherence.. Despite the evidence forefficacy of many currently available treatments for mania, the majority of RCTs provide little direction for the clinician as to what steps might be optimal in different presentations of mania as well as in the presence of specific patient characteristics. Manic episodes should be managed on a personalized basis considering the clinical course and patient criteria and with the expectation of maintaining that treatment in the long-term.

Topics: Antipsychotic Agents; Bipolar Disorder; Clozapine; Humans; Mania; Olanzapine

Clozapine is one of the most widely used antipsychotics for treating psychiatric illnesses such as schizophrenia and bipolar disorder. This drug, however, is associated with adverse effects such as weight gain, metabolic syndrome, and blood dyscrasias. The manifestations of mental illness may differ between men and women. Yet, there is little evidence on the influence of sex on treatment response or the occurrence of AEs. To fill this gap of knowledge, we carried out a systematic review of the literature on sex differences in the effectiveness and adverse effects of clozapine. Scant evidence has been published on differences in effectiveness of clozapine between men and women. Indeed, to the best of our knowledge, this issue has only been addressed in a published study. Regarding adverse effects, males have been reported to be more likely to develop metabolic abnormalities such as cholesterol or triglycerides, hypertension, and cardiovascular risk, while females are at a higher risk for gaining weight, developing diabetes, and needing laxatives. Nevertheless, given the scarcity of sex-based studies on this drug, further studies are needed to explore sex-based differences, as the results obtained may be crucial to clinical practice and help improve the quality of life of patients.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Cohort Studies; Female; Humans; Male; Metabolic Syndrome; Quality of Life; Schizophrenia; Sex Characteristics; Treatment Outcome; Weight Gain

Bipolar disorder is associated with the highest risk of completed suicide of all mental disorders. The suicide mortality of people with bipolar disorder is approximately 25 times higher than the general population. No approved pharmacological strategies for suicidality in bipolar disorder have been introduced so far. There is evidence for anti-suicidal effect of clozapine in schizophrenia. Clozapine with its unique pharmacology, anti-aggressive and anti-impulsive properties is potentially an effective strategy for suicidality in bipolar disorder.

Topics: Bipolar Disorder; Clozapine; Humans; Suicide; Suicide Prevention

Women with bipolar disorder may benefit from continuation of their medications during pregnancy, but there may be risks to the fetus associated with some of these medications. This article examines the evidence relating to the effect of bipolar disorder and pharmacologic treatments for bipolar disorder on pregnancy outcomes.. MEDLINE, CINAHL, ProQuest Dissertation & Theses, and the Cochrane Database of Systematic Reviews were searched for English-language studies published between 2000 and 2017, excluding case reports and integrative reviews. Twenty articles that met inclusion criteria were included in this review.. Women with bipolar disorder have a higher risk for pregnancy complications and congenital abnormalities than do women without bipolar disorder. In addition, illness relapse can occur if psychotropic medications are discontinued. There are limited data to recommend discontinuing lithium, lamotrigine, or carbamazepine during pregnancy. Valproic acid is not recommended during pregnancy due to increased odds of neural tube defects associated with its use. Atypical antipsychotics are used more frequently during pregnancy, with mixed evidence regarding an association between these agents and congenital malformations or preterm birth.. The knowledge of benefits and risks of bipolar disorder and its treatment can help women and health care providers make individualized decisions. Prenatal care providers can discuss the evidence about safety of medications used to treat bipolar disorder with women in collaboration with their mental health care providers. In addition, women being treated for bipolar disorder require close monitoring for depressive and manic/hypomanic episodes that impact pregnancy outcomes.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clozapine; Female; Humans; Lithium Carbonate; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prenatal Care

Trapeziometacarpal osteoarthritis is associated with more pain and restrictions than other hand osteoarthritis due to the functional importance of the thumb. While the effectiveness of surgical and pharmacological interventions has been widely examined, there is a lack of specific evidence about conservative non-pharmacological trapeziometacarpal osteoarthritis therapies. The objective of this systematic review was to provide evidence-based knowledge on the effectiveness of physiotherapy and occupational therapy on pain, function and quality of life.. A literature search of Medline, CINAHL, PEDro, OTseeker, EMB Dare Cochrane Database of Systematic Reviews and Cochrane CENTRAL was performed. Randomized and quasi-randomized controlled trials and corresponding systematic reviews, observational studies, pragmatic studies and case-control studies were included. The risk of bias was assessed.. Physical and occupational therapy-related interventions, especially multimodal interventions, seem to be effective to treat pain in patients with trapeziometacarpal osteoarthritis. Pre-fabricated neoprene splints and custom-made thermoplastic splints may reduce pain equally. Single interventions seem not to be effective. Significant evidence for effectiveness on function and quality of life could not be found.. The sole Na. The SUV. Genetic variants of

Topics: AC133 Antigen; Acenaphthenes; Acer; Acrosome Reaction; Adult; Agaricales; Aged; Aged, 80 and over; Animals; Animals, Zoo; Anti-Bacterial Agents; Anticoagulants; Antifungal Agents; Antimanic Agents; Antioxidants; Aortic Valve; Area Under Curve; ATP Binding Cassette Transporter, Subfamily G, Member 2; Bacillus; Bacterial Toxins; Bacterial Typing Techniques; Base Composition; Beauveria; Binge Drinking; Biomarkers; Bipolar Disorder; Blood Coagulation; Blotting, Western; Brachytherapy; Calcium Channels, L-Type; Carcinoma, Non-Small-Cell Lung; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cell Transformation, Neoplastic; Cell Wall; Cells, Cultured; Ceramics; Chi-Square Distribution; China; Chlorophyll; Chlorophyta; Chloroplasts; Cholesterol, HDL; Chromatography, High Pressure Liquid; Chromobacterium; Clostridium perfringens; Clozapine; Constriction, Pathologic; Coronary Artery Bypass; Corticotropin-Releasing Hormone; Cross-Sectional Studies; Cytochrome P-450 CYP2C9; Dental Porcelain; Dental Restoration Failure; Dental Stress Analysis; Designer Drugs; Diaminopimelic Acid; DNA Fingerprinting; DNA, Bacterial; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Drug Dosage Calculations; Drug Evaluation, Preclinical; Drug Resistance, Bacterial; Elasticity Imaging Techniques; Epsilonproteobacteria; Equipment Design; Ericaceae; Excitatory Amino Acid Antagonists; False Negative Reactions; Fatty Acids; Female; Food Analysis; Fresh Water; Gene Expression Regulation, Neoplastic; Glutathione; Graft Occlusion, Vascular; Heart Valve Prosthesis Implantation; Heart Ventricles; HEK293 Cells; Hemolymph; Humans; Hyaluronan Receptors; Hydrogen Peroxide; Hydrothermal Vents; Indoles; Inflammation Mediators; Inhibitory Concentration 50; Insecta; International Normalized Ratio; Isotope Labeling; Itraconazole; Kidney; Kinetics; Kruppel-Like Factor 4; Kruppel-Like Transcription Factors; Lamotrigine; Lanthanoid Series Elements; Limit of Detection; Linear Models; Lipid Peroxidation; Liver; Liver Cirrhosis; Logistic Models; Lung Neoplasms; Lymph Node Excision; Lymphatic Metastasis; Male; Malondialdehyde; Mediastinum; Metronidazole; Mice; Mice, Nude; Mice, Transgenic; Microbial Sensitivity Tests; Microscopy, Fluorescence; Middle Aged; Monocytes; Monomeric GTP-Binding Proteins; Multivariate Analysis; Myocytes, Cardiac; Neoplasm Staging; Neoplastic Stem Cells; Neural Pathways; Nitrates; Nucleic Acid Hybridization; Octamer Transcription Factor-3; Odds Ratio; Oxidation-Reduction; Oxidative Stress; Peptidoglycan; Phantoms, Imaging; Pharmacogenetics; Pharmacogenomic Variants; Phenotype; Phospholipids; Photolysis; Photosynthesis; Phylogeny; Plant Extracts; Polychaeta; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Positron Emission Tomography Computed Tomography; Predictive Value of Tests; Preoperative Care; Prostatic Neoplasms; Pseudomonas aeruginosa; Pyrimidines; Pyrroles; Quorum Sensing; Radiology, Interventional; Radiopharmaceuticals; Radiotherapy Dosage; Rats; Rats, Sprague-Dawley; Receptors, Corticotropin-Releasing Hormone; Reference Values; Regression Analysis; Retrospective Studies; Reverse Transcriptase Polymerase Chain Reaction; Rhizosphere; Risk Factors; RNA, Ribosomal, 16S; ROC Curve; Rutin; Saphenous Vein; Seawater; Selenium; Semen Preservation; Sensitivity and Specificity; Septal Nuclei; Sequence Analysis, DNA; Serum Albumin; Serum Albumin, Human; Shear Strength; Sodium Pertechnetate Tc 99m; Sodium-Hydrogen Exchangers; Soil Microbiology; SOXB1 Transcription Factors; Spain; Species Specificity; Sperm Motility; Spermatozoa; Spheroids, Cellular; Spores, Fungal; Stroke; Superoxide Dismutase; Swine; Tandem Mass Spectrometry; Technetium Compounds; Technetium Tc 99m Exametazime; Technetium Tc 99m Sestamibi; Temperature; Thiosulfates; Thrombosis; Thyroid Neoplasms; Transducers; Transfection; Transplantation, Heterologous; Treatment Outcome; Triazines; Tumor Burden; Urocortins; Uterine Cervical Neoplasms; Vacuoles; Valproic Acid; Ventral Tegmental Area; Vitamin K 2; Vitamin K Epoxide Reductases; Warfarin; Water Microbiology; Young Adult

To evaluate the efficacy and safety of clozapine for treatment-resistant bipolar disorder (TRBD).. A systematic review of randomized controlled studies, open-label prospective studies, and retrospective studies of patients with TRBD was carried out. Interventions included clozapine monotherapy or clozapine combined with other medications. Outcome measures were efficacy and adverse drug reactions (ADRs).. Fifteen clinical trials with a total sample of 1,044 patients met the inclusion criteria. Clozapine monotherapy or clozapine combined with other treatments for TRBD was associated with improvement in: (i) symptoms of mania, depression, rapid cycling, and psychotic symptoms, with many patients with TRBD achieving a remission or response; (ii) the number and duration of hospitalizations, the number of psychotropic co-medications, and the number of hospital visits for somatic reasons for intentional self-harm/overdose; (iii) suicidal ideation and aggressive behavior; and (iv) social functioning. In addition, patients with TRBD showed greater clinical improvement in long-term follow-up when compared with published schizophrenia data. Sedation (12%), constipation (5.0%), sialorrhea (5.2%), weight gain (4%), and body ache/pain (2%) were the commonly reported ADRs; however, these symptoms but did not usually require drug discontinuation. The percentage of severe ADRs reported, such as leukopenia (2%), agranulocytosis (0.3%), and seizure (0.5%), appeared to be lower than those reported in the published schizophrenia literature.. The limited current evidence supports the concept that clozapine may be both an effective and a relatively safe medication for TRBD.

Topics: Antipsychotic Agents; Bipolar Disorder; Clozapine; Humans

Olanzapine is one of the SGAs (second-generation antipsychotics) which have been used for the treatment of patients with schizophrenia and bipolar disorder in Japan. Olanzapine has various affinities for multiple receptors, including dopamine D2 receptor, serotonin 5-HT2A, 5-HT2C, 5-HT6 receptors, and adrenaline alpha1, histamine H1, muscarine M1-M5 receptors as well. Therefore, olanzapine is known as MARTA(multi-acting receptor targeted antipsychotics). Numerous studies have been conducted to compare the effectiveness of olanzapine between SGAs and FGAs (first-generation antipsychotics). According to the head-to-head meta-analysis and large-scale studies like CATIE and EUFEST, olanzapine seems to have not only higher efficacy but also less discontinuation comparing to other anti-psychotics.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clozapine; Humans; Male; Olanzapine; Schizophrenia; Treatment Outcome

To examine the pharmacokinetic implications and potential clinical effects of tobacco smoking cessation in patients on stable clozapine or olanzapine treatment.. A literature search of MEDLINE (1950-November 2009) and EMBASE (1980-November 2009) was conducted using the search terms smoking, tobacco, cigarette, cannabis, smoking cessation, cytochrome P450, antipsychotic, clozapine, and olanzapine. In addition, reference lists from publications identified were searched manually.. English-language articles and human studies were identified, yielding 111 returns. Articles that reported clinical outcomes following smoking cessation were selected. Pharmacokinetic data for these drugs were reviewed and articles that provided relevant background information were also included.. Pharmacokinetic studies have demonstrated more rapid clearance of olanzapine and lower clozapine and norclozapine (desmethylclozapine) concentrations in smokers compared to nonsmokers. These studies also found that smokers require higher doses of these agents than nonsmokers. There are case reports of adverse clinical outcomes following smoking cessation in patients being treated with olanzapine and clozapine. Reports that included serum concentrations consistently found elevations following smoking cessation, and dosage reductions of 30-40% were required to achieve pre-cessation concentrations. Worsening psychiatric symptoms, somnolence, hypersalivation, extreme fatigue, extrapyramidal effects, and seizures have all been reported following smoking cessation in this patient group.. Pharmacists need to be aware of potential risks associated with smoking cessation in patients stabilized on clozapine or olanzapine. Toxicity as a result of recent smoking reduction or cessation may be a reason for hospital admission. For hospitalized patients, pharmacists should obtain information concerning smoking status, including cessation attempts. Nonspecific signs and symptoms of elevated clozapine or olanzapine concentrations should be considered in relation to clinical status while the patient is hospitalized. Measurement of baseline serum clozapine concentrations and/or empiric dosage adjustment in patients expected to have a prolonged hospital stay with forced smoking cessation may be appropriate.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clozapine; Humans; Male; Middle Aged; Olanzapine; Psychotic Disorders; Schizophrenia, Paranoid; Smoking Cessation

To review extant literature implicating inflammation in the pathophysiology of bipolar disorder. Furthermore, we review evidence regarding the anti-inflammatory actions of mood-stabilizing medication, the putative reciprocal association of inflammation with behavioral parameters and medical burden in bipolar disorder, and the potential role of anti-inflammatory agents in the treatment of bipolar disorder.. MEDLINE and PubMed searches were conducted of English-language articles published from 1950 to April 2008 using the search terms bipolar disorder, manic, or mania, cross-referenced with inflammation, inflammatory, interleukin, cytokine, C-reactive protein, or tumor necrosis factor. The search, which was conducted most recently on August 20, 2008, was supplemented by manually reviewing reference lists from the identified publications.. Articles selected for review were based on adequacy of sample size, the use of standardized experimental procedures, validated assessment measures, and overall manuscript quality.. Studies were reviewed for statistical comparisons of cytokines among persons with and without bipolar disorder, during symptomatic and non-symptomatic intervals and before and after pharmacologic treatment. Significant and nonsignificant findings were tabulated.. Available evidence indicates that bipolar disorder and inflammation are linked through shared genetic polymorphisms and gene expression as well as altered cytokine levels during symptomatic (i.e., mania and depression) and asymptomatic intervals. However, results are inconsistent. Several conventional mood stabilizers have anti-inflammatory properties. The cyclooxygenase-2-selective anti-inflammatory celecoxib may offer antidepressant effects. Inflammation is closely linked with behavioral parameters such as exercise, sleep, alcohol abuse, and smoking, as well as with medical comorbidities including coronary artery disease, obesity and insulin resistance, osteoporosis, and pain. Methodological limitations precluding definitive conclusions are heterogeneity in sample composition, cytokine assessment procedures, and treatment regimens. The inclusion of multiple ethnic groups introduces another source of variability but also increases the generalizability of study findings.. Inflammation appears relevant to bipolar disorder across several important domains. Further research is warranted to parse the reciprocal associations between inflammation and symptoms, comorbidities, and treatments in bipolar disorder. Studies of this topic among youth are needed and may best serve this purpose.

Topics: Anti-Inflammatory Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Brief Psychiatric Rating Scale; Celecoxib; Clozapine; Comorbidity; Cytokines; Humans; Inflammation; Lithium Carbonate; Pyrazoles; Risperidone; Sulfonamides; Surveys and Questionnaires; Treatment Outcome

To retrospectively examine published cases of neuroleptic malignant syndrome (NMS) in patients aged 18 and below who had been treated with atypical antipsychotics (clozapine, risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole).. Information was collected via MEDLINE searches in February 2006 and May 2007. The term neuroleptic malignant syndrome was used and cross-referenced with individual atypical antipsychotics. The authors also contacted (by telephone and in writing) pharmaceutical companies that produce and market atypical antipsychotics for any data on NMS.. Twenty case reports (written in English only and published from 1991-2007) were identified and reviewed. These publications all described symptoms of NMS in patients aged 18 or younger who had been treated with atypical antipsychotics.. Data were reviewed and compared with 3 diagnostic criteria (DSM-IV-TR, Levenson's, and Caroff and Mann's) for NMS. Interventions and outcomes were also reviewed.. Twenty case reports were identified and presented with a descriptive approach. Sixteen cases met criteria for NMS, with at least 1 of the diagnostic sets utilized. The majority of cases involved male subjects. All patients recovered.. Young patients can develop NMS during treatment with atypical antipsychotics. Symptoms of this disorder are consistent with those described in adults. Although NMS is rare in this population, clinicians should maintain a high index of suspicion. Appropriate caution in treating children and adolescents with any antipsychotic is warranted.

Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Child; Child, Preschool; Clozapine; Dibenzothiazepines; Humans; Neuroleptic Malignant Syndrome; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Retrospective Studies; Risperidone; Thiazoles

Topics: Acute Disease; Antipsychotic Agents; Bipolar Disorder; Clozapine; Colitis, Microscopic; Female; Humans; Middle Aged

Second generation antipsychotic agents are increasingly used in the management of acute mania. A systematic review of the efficacy and safety of these agents, as both monotherapy and in combination with mood stabilisers, was performed to establish the evidence for their use. Randomised controlled trials (RCTs) were critically appraised in more detail than studies that presented lower levels of evidence such as case reports, case series and open label follow up studies. We found 11 RCTs reporting on patients treated with second generation antipsychotics for acute bipolar mania, of which three included randomisation between the second generation antipsychotic and placebo, and eight between a mood stabiliser combined with either the second generation antipsychotic or placebo. Data from non-randomised trials is also presented.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clozapine; Dibenzothiazepines; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Risperidone; Thiazoles; Treatment Outcome

A key goal of the pharmacologic treatment of acute bipolar mania is rapid symptom improvement. Medications commonly used to attain this goal include lithium, several anticonvulsants, and both first- and second-generation antipsychotics. Second-generation antipsychotics, which are associated with substantially lower rates of extrapyramidal side effects than first-generation agents, are becoming a mainstay in the treatment of acute mania. Although their efficacy appears to be comparable, second-generation antipsychotics may differ in time to onset and in their side effect profiles. Therefore, selecting a second-generation antipsychotic requires consideration of how an agent's efficacy, onset of action, and adverse events profile influence its appropriateness for each patient.

Topics: Acute Disease; Anticonvulsants; Antipsychotic Agents; Aripiprazole; Basal Ganglia Diseases; Benzodiazepines; Bipolar Disorder; Clozapine; Dibenzothiazepines; Double-Blind Method; Humans; Lithium; Olanzapine; Piperazines; Placebos; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Risperidone; Treatment Outcome

To assess the potential role of atypical antipsychotics as mood stabilizers.. A MedLine, PsychLIT, PubMed, and EMBASE literature search of papers published up to December 2004 was conducted using the names of atypical antipsychotics and a number of key terms relevant to bipolar disorder. Additional articles were retrieved by scrutinizing the bibliographies of review papers and literature known to the authors. Data pertinent to the objective was reviewed according to the various phases of bipolar disorder.. The data is most substantive for the use of atypical antipsychotics in mania, to the extent that an argument for a class effect of significant efficacy can be made. This does not extend to bipolar depression, however, good data is now emerging for some agents and will need to be considered for each individual agent as it accumulates. As regards mixed states and rapid cycling the evidence is thus far sparse and too few maintenance studies have been conducted to make any firm assertions. However, with respect to long-term therapy the atypical antipsychotics do have clinically significant side-effects of which clinicians need to be aware.. Based on the evidence thus far it is perhaps premature to describe the atypical antipsychotics as mood stabilizers. Individual agents may eventually be able to claim this label, however, much further research is needed especially with respect to maintenance and relapse prevention.

Topics: Affect; Amisulpride; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Clozapine; Dibenzothiazepines; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Risperidone; Secondary Prevention; Sulpiride; Thiazoles

During recent years there has been a dramatic increase in the use of psychotropic medication for the treatment of bipolar disorder (BPD) in children. There is an emerging set of data to support this use.Mood stabilizers, including lithium and valproic acid (valproate sodium), have generally formed the mainstay of treatment in children and adolescents with BPD. However, the atypical antipsychotics, such as risperidone, aripiprazole, and quetiapine may be more effective as first-line treatment options and in some ways easier to use than the traditional mood stabilizers. As in adults, mood stabilization is often difficult to achieve in pediatric patients with BPD, and combined treatment with mood stabilizers and atypical antipscyhotics is commonly used. Data from controlled trials of psychotropic medications in children and adolescents with BPD are very limited, and hence, in the majority of cases physicians base their treatment decisions on data from case reports, case series, or open trials. More controlled studies of both monotherapy and polypharmacotherapy for BPD in children and adolescents are needed.

Topics: Adolescent; Benzodiazepines; Bipolar Disorder; Carbamazepine; Child; Clozapine; Dibenzothiazepines; Humans; Lithium; Olanzapine; Quetiapine Fumarate; Risperidone; Valproic Acid

Many people who attempt suicide or succeed at it visit their physicians shortly before the act; thus, primary care physicians have a key role in preventing suicide. The first step is to suspect that the patient might be at risk, and the second step is to ask about it. Nevertheless, one cannot predict whether any particular person will or will not attempt suicide.

Topics: Bipolar Disorder; Clozapine; Crisis Intervention; Depressive Disorder; Diagnosis, Differential; Hospitalization; Humans; Physician's Role; Risk Factors; Serotonin; Serotonin Antagonists; Suicide; Suicide Prevention

Atypical antipsychotics offer superior safety and similar efficacy compared with conventional agents in adults with psychotic disorders. Consequently, atypical antipsychotics have been increasingly used in children and adolescents. Because most information now available on pediatric use comes from case reports and small open-label studies rather than large controlled trials, treatment in pediatric patients is often guided by experience with adults or based on limited evidence in youths. Although the literature contains reports on the use of each agent in this class in children, risperidone has been the focus of the greatest number of reports. However, the atypical antipsychotics are not interchangeable; each has a unique pharmacologic profile and may differ considerably in terms of adverse effects. Evidence on the use of atypical antipsychotics in children and adolescents is summarized in this review.

Topics: Adolescent; Age Factors; Antipsychotic Agents; Attention Deficit and Disruptive Behavior Disorders; Benzodiazepines; Bipolar Disorder; Child; Child Development Disorders, Pervasive; Clozapine; Dibenzothiazepines; Humans; Mental Disorders; Olanzapine; Piperazines; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles; Tic Disorders

Topics: Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clozapine; Diabetes Mellitus; Dibenzothiazepines; Dyskinesias; Haloperidol; Humans; Hyperglycemia; Hyperprolactinemia; Olanzapine; Pirenzepine; Quetiapine Fumarate; Risperidone; Thioridazine; Weight Gain

The role of lithium carbonate in the maintenance treatment of bipolar disorder is well established. Unfortunately, many patients fail to respond adequately to this agent or are unable to tolerate its adverse effects. Divalproex has become a commonly used alternative to lithium, but it also is ineffective or poorly tolerated in many patients. This article attempts to review the available data on maintenance therapy in bipolar disorder with a variety of anticonvulsants and antipsychotics (both conventional and novel), with reference to relevant studies in acute mania and bipolar depression as well.. Evidence on maintenance therapy and relevant acute-phase data were collected using MEDLINE database searches.. Data on maintenance therapy with agents other than lithium and divalproex are sparse, and often derived from open, uncontrolled studies. Implications and flaws of available data are discussed.. Other than lithium, there are few robust double-blind data to support the use of a variety of agents in the maintenance phase. However, uncontrolled data suggest that a number of agents merit further study.

Topics: Acetates; Amines; Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Calcium Channel Blockers; Carbamazepine; Clozapine; Cyclohexanecarboxylic Acids; Dibenzothiazepines; Donepezil; Fatty Acids, Omega-3; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Indans; Lamotrigine; Lithium Carbonate; Olanzapine; Piperazines; Piperidines; Pirenzepine; Quetiapine Fumarate; Risperidone; Thiazoles; Topiramate; Treatment Outcome; Triazines; Valproic Acid

Psychotic symptoms are seen in numerous psychiatric illnesses afflicting the elderly. This article reviews the efficacy of the pharmacologic management of psychotic symptoms in primary psychotic disorders, affective disorders, and neurodegenerative disorders.. A comprehensive literature review.. Evidence to support the use of pharmacologic interventions to manage psychotic symptoms in elderly patients afflicted with primary psychotic disorders and affective disorders is limited by the absence of randomized, placebo-controlled trials (RCTs). The use of low-dose clozapine is supported by RCTs in Parkinson's disease. The efficacy of risperidone and olanzapine for the treatment of psychotic symptoms has been demonstrated by large RCTs in Alzheimer's disease.. There is evidence of the efficacy of antipsychotic medications to manage psychotic symptoms in elderly patients. However, the absence of published evidence from RCTs in primary psychotic and affective disorders, and the limited evidence in the neurodegenerative illnesses, is notable.

Topics: Aged; Alzheimer Disease; Benzodiazepines; Bipolar Disorder; Clozapine; Depressive Disorder; Drug Administration Schedule; Humans; Lewy Body Disease; Olanzapine; Parkinson Disease; Pirenzepine; Psychotic Disorders; Risperidone

Antidepressants and antipsychotics are frequently used as mood stabilizers in the treatment of bipolar disorder. As common as these agents appear to be in bipolar treatment, the literature contains little research on their efficacy and safety in the long term. Most of the available literature on long-term antidepressant treatment focuses on tricyclic antidepressants, which have been shown to induce mania or hypomania. Rapid cycling is another side effect that is associated with antidepressant treatment in bipolar disorder. Antidepressants do not appear to be any more effective than mood stabilizers in treating bipolar depression. Conventional antipsychotics in depot formulations have been shown to be an effective treatment, but conventional antipsychotics may cause tardive dyskinesia. The novel antipsychotics clozapine, risperidone, and olanzapine appear to be efficacious; however, their side effect profiles include agranulocytosis and weight gain. Given the frequency with which antidepressants and antipsychotics are used in bipolar disorder and that bipolar disorder is a chronic disease requiring maintenance treatment, more research on the use of these types of agents in long-term treatment is needed. Until more evidence is available on the long-term treatment outcomes, clinicians should be aware that the adverse events associated with antidepressants and antipsychotics may outweigh the benefit, if any, of the use of these agents in bipolar disorder.

Topics: Agranulocytosis; Antidepressive Agents; Antipsychotic Agents; Bipolar Disorder; Clinical Trials as Topic; Clozapine; Delayed-Action Preparations; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Humans; Long-Term Care; Treatment Outcome; Weight Gain

Bipolar disorder, despite being a common and debilitating illness, has remarkably few pharmacological therapeutic options, the majority of which, with the exception of lithium, have been borrowed from other medical indications. Furthermore the quantity and quality of controlled clinical data are considerably smaller than in conditions of comparable severity and frequency. Not surprisingly, the clinical outcome of bipolar disorder is frequently suboptimal. Fortunately there are a growing number of novel therapeutic options for its treatment such as atypical antipsychotics, calcium channel blockers and omega-3 fatty acids. This paper summarizes some of the data regarding these "experimental" therapeutic options, focusing principally on atypical antipsychotics as these are now widely prescribed in the management of bipolar disorder.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Calcium Channel Blockers; Clozapine; Dibenzothiazepines; Humans; Olanzapine; Pirenzepine; Quetiapine Fumarate; Risperidone

Cumulative data indicate that atypical antipsychotics can serve as adjunctive as well as alternative agents in the treatment of drug-resistant mood disorders. Olanzapine and risperidone add-on treatment was found to be effective for major depression with psychotic features and good results were achieved with currently available atypical antipsychotics (clozapine, risperidone, olanzapine, quetiapine and ziprasidone) in reducing symptoms of acute mania, especially when added to mood stabilizers. The role of atypical antipsychotics in maintenance and prophylactic treatment is not yet clear. Although there are differences in the side effect profiles of the various atypical antipsychotics, their use is limited by adverse effects such as extrapyramidal symptoms, weight gain, somnolence and sexual dysfunction.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Clozapine; Depressive Disorder, Major; Dibenzothiazepines; Humans; Olanzapine; Piperazines; Pirenzepine; Quetiapine Fumarate; Risperidone; Thiazoles

While the efficacy of antipsychotics as a maintenance treatment for bipolar patients has not been systematically studied, these drugs are commonly used in the long-term treatment of bipolar patients, and it is not unusual for a bipolar patient to be taking 3 to 4 medications, including antipsychotics. Conventional antipsychotics may be comparable to lithium for acute mania, but have limitations when used in the long-term treatment of bipolar disorder. Their adverse effects, which include extrapyramidal side effects, tardive dyskinesia, weight gain, sedation, and sexual dysfunction, often lead to non-compliance; their use may have a negative impact on the overall course of illness; and they may not be as effective as lithium in treating the core manic symptoms over the long term. Atypical antipsychotics may prove useful for bipolar patients who require antipsychotic treatment because of their favorable side effect profile, thymoleptic properties, and positive effect on overall functioning.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Clozapine; Dibenzothiazepines; Humans; Olanzapine; Pirenzepine; Quetiapine Fumarate; Risperidone

Bipolar disorder is a recurrent and relapsing mood disorder characterized by cycles of depression and mania. This article addresses the treatment of patients with bipolar mania, which remains one of the most difficult challenges facing clinicians. Patients require safe and effective therapeutic approaches for acute episodes of mania and depression, as well as chronic prophylaxis against future episodes. Monotherapeutic approaches are rarely effective, and combination approaches are associated with an increased risk of adverse events. Lithium is the only agent currently approved for the treatment of both acute episodes of mania and maintenance therapy; however, it is associated with a relatively poor response rate, high relapse rate, and less-than-optimal side effect profile. Other recent approaches have included several anticonvulsant agents, as well as conventional and atypical antipsychotic agents.

Topics: Acetates; Amines; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Carbamazepine; Clozapine; Cyclohexanecarboxylic Acids; Drug Therapy, Combination; Electroconvulsive Therapy; Electromagnetic Phenomena; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Lithium; Olanzapine; Pirenzepine; Risperidone; Topiramate; Treatment Outcome; Triazines; Valproic Acid

Atypical neuroleptic agents are an excellent, safer, and more effective alternative to the widespread practice of maintenance adjunctive treatment with traditional neuroleptic agents in patients with bipolar disorder. Currently, a number of prospective studies are available with clozapine, risperidone, olanzapine, and quetiapine in the treatment of bipolar disorder. Most are short-term studies, although longer-term data are becoming available. Four double-blind studies of acute mania have been conducted with risperidone and olanzapine, leading to recent Food and Drug Administration approval for olanzapine in the indication of acute mania. Given the limited longer-term data, and the evidence for mostly adjunctive benefits with these agents, it seems unlikely that these agents will prove to be primary mood stabilizers in their own right. Nonetheless, they serve an important role as adjunctive treatments along with standard mood stabilizers in the rational polypharmacy of bipolar disorder. To date, differences in efficacy have not been established. However, differences in the side effect of weight gain may be even more relevant in bipolar disorder than in schizophrenia due to the need to use standard mood stabilizers that often potentiate such weight gain.

Topics: Acute Disease; Algorithms; Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clozapine; Dibenzothiazepines; Drug Therapy, Combination; Humans; Lithium; Olanzapine; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Treatment Outcome; Valproic Acid

Polypharmacy is common in the treatment of refractory bipolar disorder. The purpose of this article is to review the safety and efficacy of mood stabilizers in combinations.. A manual and computer (MEDLINE) search was performed for combinations of the most commonly used mood-stabilizing agents.. The authors review safety and efficacy data on the more frequently encountered combinations of established and putative mood stabilizers.. There have been few controlled studies of the use of combinations of mood stabilizers. The interactions of such combinations are sometimes complex, often very useful, and potentially dangerous. One general rule that may reduce the risks of toxic drug interactions is to add medication to the patient's current regimen in modest doses and increase the dose slowly. The safest and most efficacious mood stabilizer combinations appear to be the mixtures of anticonvulsants and lithium, particularly valproate plus lithium. Once the mechanisms of the mood stabilizers are identified, it is possible that a more rational approach to combination therapy will emerge, based on synergism at the sites of action.

Topics: Acetates; Amines; Anticonvulsants; Antipsychotic Agents; Bipolar Disorder; Calcium Channel Blockers; Clinical Trials as Topic; Clozapine; Cyclohexanecarboxylic Acids; Drug Therapy, Combination; Gabapentin; gamma-Aminobutyric Acid; Humans; Lithium; Risperidone; Valproic Acid

Antipsychotic agents have been used commonly in the treatment of bipolar disorder. This article reviews the evolution of the use of antipsychotic agents and their role in the acute and maintenance treatment of bipolar disorder. The focus is on neuroleptic drugs, the atypical antipsychotic drugs (risperidone and clozapine), and two fo the new atypical antipsychotic drugs that were recently approved.

Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Clozapine; Delayed-Action Preparations; Drug Therapy, Combination; Humans; Lithium; Olanzapine; Pirenzepine; Psychotic Disorders; Risperidone; Treatment Outcome

Traditional neuroleptics are often utilized clinically for the management of bipolar disorder. Although effective as antimanic agents, their mood stabilizing properties are less clear. Additionally, their acute clinical side effect profile and long term risk of tardive dyskinesia, particularly in mood disorder patients, portend significant liability. This review focuses on the use of atypical antipsychotics in the treatment of bipolar disorder focusing on clozapine as the prototypical agent. Although, preclinical research and clinical experience suggest that the atypical antipsychotics are distinctly different from typical antipsychotics, they themselves are heterogeneous in profiles of neuropharmacology, clinical efficacy, and tolerability. The early clinical experience of clozapine as a potential mood stabilizer suggests greater antimanic than antidepressant properties. Conversely, very preliminary clinical experience with risperidone suggests greater antidepressant than antimanic properties and some liability for triggering or exacerbating mania. Olanzapine and sertindole are under investigation in psychotic mood disorders. The foregoing agents and future drugs with atypical neuroleptic properties should come to play an increasingly important role, compared to the older classical neuroleptics, in the acute and long term management of bipolar disorder.

Topics: Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clozapine; Humans; Imidazoles; Indoles; Olanzapine; Pirenzepine; Risperidone; Trimipramine

The authors' goal was to analyze reported cases of neuroleptic malignant syndrome in patients given clozapine and risperidone.. They assessed 19 cases of clozapine-induced neuroleptic malignant syndrome and 13 cases of risperidone-induced neuroleptic malignant syndrome against three criteria sets and against extent of exclusionary workup and then designated them as high or low probability of being neuroleptic malignant syndrome.. Nine of the 19 cases of clozapine-related neuroleptic malignant syndrome and eight of the 13 cases of risperidone-related neuroleptic malignant syndrome were designated as having high probability of being neuroleptic malignant syndrome. The remainder were designated as having low probability because presentations were not linked to treatment or failed to meet criteria for the syndrome.. Neuroleptic malignant syndrome can occur in patients given atypical antipsychotics and resembles "classical" neuroleptic malignant syndrome. However, side effect profiles overlap considerably with neuroleptic malignant syndrome criteria, and atypical antipsychotics may cause neurotoxicities unrelated to (but misattributed as) neuroleptic malignant syndrome. Insufficient evidence exists for "atypical" neuroleptic malignant syndrome with novel antipsychotics.

Topics: Adolescent; Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Confidence Intervals; Female; Humans; Male; Middle Aged; Neuroleptic Malignant Syndrome; Probability; Psychotic Disorders; Risperidone; Schizophrenia

Depression in schizophrenia may be partially responsible for the increased suicide rate in schizophrenic patients, which is more than 20 times higher than that found in the general population. Affective disorders in patients with schizophrenia are associated with a poor outcome, an increased risk of relapse, and a high rate of suicide. There is evidence that atypical antipsychotics may contribute to a reduction in suicidality, and although the new drugs are marketed for the treatment of schizophrenia, their novel psychopharmacologic effects suggest the possibility of other therapeutic applications. Recent studies of the efficacy of the novel antipsychotics found that these agents may produce an antidepressant effect in schizophrenia and may be used as either an adjunctive medication or an alternative to mood stabilizers in patients with affective disorders.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Clozapine; Comorbidity; Depressive Disorder; Humans; Mood Disorders; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Risperidone; Schizophrenia; Schizophrenic Psychology; Suicide; Suicide Prevention

Atypical antipsychotics have become the treatment of choice for patients experiencing a first episode of schizophrenia. In addition, they are often prescribed for conditions such as bipolar disorder and dementia. While clinical trials have not yet established the efficacy of the atypical antipsychotics for these uses, a number of reports offer preliminary evidence that the atypical antipsychotics may be beneficial for affective disorders, substance abuse disorder, senile dementia, and pathologic aggression. Atypical agents may be particularly effective and tolerable in elderly patients who are especially susceptible to the adverse effects of conventional antipsychotic medication. Lower dosages are more necessary for the elderly than for younger adults. Current evidence suggests that clozapine is the most effective atypical antipsychotic for neuroleptic-resistant patients. Risperidone, olanzapine, and quetiapine may also be effective in a subset of these patients.

Topics: Adult; Age Factors; Aged; Algorithms; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Clozapine; Decision Trees; Dementia; Dibenzothiazepines; Female; Humans; Male; Mood Disorders; Olanzapine; Pirenzepine; Quetiapine Fumarate; Risperidone; Schizophrenia

A now 73-year-old female patient suffered from bipolar affective disorder for the first time at the age of 28. Despite treatment with all known phase-prophylactic agents (i.e., lithium, carbamazepine, valproate, and various antidepressants) she relapsed frequently. To render matters even more difficult, she easily developed side effects with most medications, particularly anticholinergic ones. In order to reach effective longterm prophylactic treatment, we tried several not yet established therapeutic regimens like clozapine, high-dose L-thyroxine, and maintenance ECT. In this case report we discuss the available literature with special respect to clozapine and maintenance ECT.

Topics: Aged; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Clozapine; Combined Modality Therapy; Electroconvulsive Therapy; Female; Humans; Long-Term Care; Recurrence; Treatment Failure

Although psychotic symptoms often occur in the manic phase of bipolar disorder, psychotic mania has been and continues to be frequently misdiagnosed as schizophrenia or other psychotic illnesses. In addition, the role of antipsychotic agents in the acute and maintenance treatment of psychotic mania remains unclear. In this paper, we present an overview of studies of psychosis in mania. We also review studies of conventional and newer antipsychotic agents in the acute and maintenance treatment of psychotic mania to help clarify the role of these agents in treating this illness.

Topics: Adolescent; Adult; Age of Onset; Antipsychotic Agents; Bipolar Disorder; Clozapine; Humans; Prognosis; Psychiatric Status Rating Scales; Risk Factors; Risperidone; Severity of Illness Index

To present a critical overview of the selected literature published in the past 7 years on the efficacy and safety of psychoactive agents in conduct disorder, schizophrenia, separation anxiety disorder, selective mutism, obsessive-compulsive disorder, panic disorder, major depressive disorder, bipolar disorder, and sleep and eating disorders.. Reports of double-blind and placebo-controlled trials and open studies were reviewed and selected studies presented.. Employment of larger samples of diagnostically homogeneous patients and a more sophisticated design and methodology led to progress in the treatment of most of these conditions. Data have been accumulated on dose range and safety of lithium in this age group, and there is supportive evidence that lithium is useful in reducing aggression.. For a rational treatment approach, further studies are needed, particularly in depression and conduct disorder; psychosocial-environment contributions and possible biological markers should be investigated in order to identify children who require psychopharmacological treatments and those who will respond to psychosocial interventions or the combination of both. Symptoms targeted to require pharmacotherapy and symptoms targeted to respond to psychosocial interventions have to be identified.

Topics: Adolescent; Alprazolam; Anticonvulsants; Antipsychotic Agents; Anxiety, Separation; Bipolar Disorder; Carbamazepine; Child; Child Behavior Disorders; Child, Preschool; Clonidine; Clozapine; Depressive Disorder; Dose-Response Relationship, Drug; Feeding and Eating Disorders; Fluoxetine; Humans; Imipramine; Lithium; Mutism; Obsessive-Compulsive Disorder; Phenobarbital; Phenytoin; Phobic Disorders; Schizophrenia; Sleep Wake Disorders; Tranquilizing Agents

A growing literature suggests that the atypical antipsychotic agent clozapine may be effective in schizoaffective and psychotic mood disorders.. To evaluate the efficacy and tolerability of clozapine in severe mood disorders, we reviewed published studies on clozapine in schizophrenia, bipolar disorder, schizoaffective disorder, major depression, and organic disorders with psychotic or major affective syndromes, identified through the MEDLINE data base.. Patients in manic or psychotic phases of schizoaffective or bipolar disorder were significantly more likely to respond to clozapine than patients with schizophrenia (p = .006) or severe depressive syndromes (unipolar, bipolar, and schizoaffective depression combined; p = .001). There was no significant difference in the side effect profile secondary to clozapine in patients with severe mood disorders compared to patients with schizophrenia.. Clozapine appears to be effective and well-tolerated in the short-term and maintenance treatment of severe or psychotic mood disorders, particularly in the manic-excited phases of schizoaffective and bipolar disorders, even in patients who have not responded well to conventional pharmacotherapies.

Topics: Bipolar Disorder; Clozapine; Controlled Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; MEDLINE; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Treatment Outcome

Drug-induced psychiatric states occur frequently in PD. In the prelevodopa era, depression and other psychiatric disorders were described in PD, but in untreated patients psychosis was rare. Since the development of levodopa and other pharmacological treatments for PD, however, psychotic symptoms have become much more common (10-50%). In some individuals these problems can be more disabling than the motor features of PD and, as a result, pose a serious threat to the patient's ability to maintain independence. The drug-induced psychoses consist of several distinct psychiatric syndromes that can be divided broadly into those occurring on a background of a clear sensorium and those which are accompanied by confusion and clouding of consciousness. Benign organic hallucinosis is the most common of these syndromes (30%). It usually occurs on a background of a clear sensorium and may not be a particularly troublesome problem if the patient is able to retain insight into the nature of these symptoms. More disabling syndromes usually include delusional thinking that is frequently paranoid, confusion and even frank delirium. Although all these psychotic syndromes can occur in isolation, there is a tendency for mild symptoms to progress to more disabling ones if adequate and timely treatment is not instituted. Abnormal dreaming and sleep disruption often precede these difficulties by weeks to months and may provide an important early clue to their onset. The mechanisms responsible for drug-induced psychotic symptoms in PD are unknown, but dopaminergic (especially mesolimbic) and serotoninergic systems are likely to be involved. The treatment of the drug-induced psychoses in PD should be undertaken in a stepwise manner. A detailed discussion of this approach, including the use of anti-PD medication adjustment, clozapine, and other medications (neuroleptic and nonneuroleptic) and ECT is provided (see Fig. 1). Although drug-induced psychoses are the most important of the drug-induced psychiatric states, mania, anxiety, and hypersexuality may also occur. Depression is also common in PD, but it is unlikely to occur as a side effect of antiparkinsonian medications.

Topics: Aged; Anxiety; Bipolar Disorder; Clozapine; Depression; Electroconvulsive Therapy; Humans; Levodopa; Lisuride; Male; Ondansetron; Parkinson Disease; Psychoses, Substance-Induced; Sexual Dysfunctions, Psychological

Individuals with the rapid cycling form of bipolar disorder represent 13% to 20% of the bipolar population. Although lithium remains the treatment of choice for classic bipolar disorder, failure rates as high as 72% to 82% have been reported for lithium among those who have the rapid cycling variant. Treatment alternatives, including the use of divalproex sodium and carbamazepine, have shown promise for this often treatment-refractory group of patients. Predictors of positive outcome for the acute and prophylactic management of mania with divalproex sodium have emerged; they include nonpsychotic mania, the occurrence of decreasing or stable episode frequencies, mild mania, and mixed states. Predictors for positive acute and prophylactic antidepressant responses to divalproex sodium include nonpsychotic mania, increasingly severe mania, and the absence of borderline personality. Mixed results have been reported for studies using carbamazepine therapy for the treatment of rapid cycling bipolar disorder. Some investigators have reported success with carbamazepine in conjunction with other medications, while others have not. A psychopharmacologic algorithm for the treatment of rapid cycling bipolar disorder is proposed. There is a growing opinion among psychiatrists that patients who rapidly cycle should be treated with an anticonvulsant prior to lithium. However, until homogeneous cohorts of rapid cyclers undergo at least random assignment to different open treatments, these recommendations remain controversial.

Topics: Algorithms; Bipolar Disorder; Carbamazepine; Clozapine; Controlled Clinical Trials as Topic; Drug Administration Schedule; Drug Therapy, Combination; Electroconvulsive Therapy; Humans; Lithium; Treatment Outcome; Valproic Acid

Lithium remains the mainstay of treatment for patients with bipolar affective disorder; however, nearly half of patients with bipolar disorder fail to respond to lithium. Recently, there have been an increasing number of preliminary clinical reports that clozapine, an atypical antipsychotic agent, has potential efficacy in patients with mood disorders. We review the available clinical data supporting the potential use of clozapine in these psychiatric disorders and report our preliminary data from a study that used clozapine in the acute treatment of mania in treatment-refractory patients. Twenty-five patients meeting the DSM-III-R criteria for the manic phase of either bipolar or schizoaffective disorder entered a 13-week open prospective trial of clozapine. These patients either had failed to respond to or had been intolerant to treatment with lithium, an anticonvulsant, and at least two typical neuroleptics. Eighteen of 25 patients demonstrated a greater than 50% decrease in the Young Mania Rating Scale score. These preliminary data as well as the clinical reports reviewed indicate that the efficacy of clozapine in treatment-resistant patients is not limited to patients with schizophrenia.

Topics: Affective Disorders, Psychotic; Bipolar Disorder; Clinical Trials as Topic; Clozapine; Depressive Disorder; Humans; Prospective Studies; Psychiatric Status Rating Scales; Psychotic Disorders; Retrospective Studies

Two patients with prolonged postictal encephalopathy lasting 63 and 72 hours, respectively, following seizures with clozapine are reported. Clozapine alters the EEG in a majority of patients treated, with seizure frequency as high as 5-10% in doses above 600 mg/d. Prolonged postictal encephalopathy following a clozapine-induced seizure has not been previously reported but may be an important side effect of this medication. Pharmacologic and clinical issues are discussed.

Topics: Adult; Bipolar Disorder; Cerebral Cortex; Clozapine; Delta Rhythm; Electroencephalography; Epilepsy, Tonic-Clonic; Follow-Up Studies; Humans; Male; Psychoses, Substance-Induced; Schizophrenia, Paranoid

The effect of lamotrigine on the steady-state plasma concentrations of the atypical antipsychotics clozapine, olanzapine, and risperidone was investigated in patients with schizophrenia or bipolar disorder stabilized on chronic treatment with clozapine (200-500 mg/day; n = 11), risperidone (3-6 mg/day; n = 10) or olanzapine (10-20 mg/day; n = 14)). Lamotrigine was titrated up to a final dosage of 200 mg/day over 8 weeks, and pharmacokinetic assessments were made at baseline and during treatment weeks 6 and 10, at lamotrigine dosages of 100 and 200 mg/day respectively. The plasma concentrations of clozapine, norclozapine, risperidone, and 9-hydroxy-risperidone did not change significantly during treatment with lamotrigine. The mean plasma concentrations of olanzapine were 31 +/- 7 ng/mL at baseline, 32 +/- 7 ng/mL at week 6, and 36 +/- 9 ng/mL at week 10, the difference between week 10 and baseline being statistically significant (P < 0.05). Adjunctive lamotrigine therapy was well tolerated in all groups. These findings indicate that lamotrigine, at the dosages recommended for use as a mood stabilizer, does not affect the plasma levels of clozapine, risperidone, and their active metabolites. The modest elevation in plasma olanzapine concentration, possibly due to inhibition of UGT1A4-mediated olanzapine glucuronidation, is unlikely to be of clinical significance.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clozapine; Drug Interactions; Female; Humans; Lamotrigine; Male; Middle Aged; Olanzapine; Risperidone; Schizophrenia; Triazines

Open, uncontrolled studies suggest clozapine can have mood-stabilizing effects in treatment-resistant bipolar disorder. Unfortunately, the side effect profile limits clozapine's use at high doses. We report a series of nine bipolar I disorder patients who improved on relatively low doses of clozapine add-on therapy (250 mg or lower). Retrospectively abstracted clinical data identified nine patients with bipolar I disorder, as defined by DSMIV criteria, treated with low-dose clozapine at inpatient and outpatient settings. Monthly symptom evaluations were collected prospectively using standard assessments. Symptoms of mania and mood lability improved in all patients. Three patients demonstrated striking mood stabilization and returned to previous levels of functioning; five patients evidenced moderate improvement in mood stabilization and functioning; and one patient showed a minimal response. Overall, clozapine did not have a significant antidepressant effect. The mean clozapine dose at the end of the study was 156.3 +/- 77.6 mg/day, and duration of treatment was 12 months. Residual side effects were mild. The symptomatic improvement in these prospectively evaluated patients is consistent with our clinical impression in the majority of patients with bipolar disorder taking clozapine.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Demography; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Prospective Studies; Psychiatric Status Rating Scales; Retrospective Studies; Time Factors; Treatment Outcome

This study aims at identifying potential predictors of clinical response and functional outcome in 101 neuroleptic-refractory patients with a DSM-III-R diagnosis of schizophrenia (N = 34), schizoaffective disorder (N = 30) or bipolar disorder with psychotic features (N = 37), naturalistically treated with clozapine over a 48-month period. The "clinical response" and "functional outcome" criteria were respectively defined a priori as: a reduction of at least 50 % in the Brief Psychiatric Rating Scale total score in one evaluation with respect to baseline; and a Global Assessment of Functioning Scale score of at least 50. Several clinical and socio-demographic variables were assessed at baseline and only the diagnosis of bipolar disorder was significantly related with the clinical response. Variables significantly related with the functional outcome were female gender, university education and early age at onset.

Topics: Age of Onset; Antipsychotic Agents; Bipolar Disorder; Clozapine; Cross-Over Studies; Demography; Educational Status; Female; Follow-Up Studies; Humans; Male; Outcome Assessment, Health Care; Predictive Value of Tests; Proportional Hazards Models; Prospective Studies; Psychiatric Status Rating Scales; Psychotic Disorders; Regression Analysis; Retrospective Studies; Schizophrenia; Severity of Illness Index; Time Factors; Treatment Outcome

Residual depression and medication-induced sedation remain significant problems for many patients with bipolar disorder (BD). Some evidence indicates that bipolar depression may be more responsive to dopaminergic agents, suggesting that adjunctive stimulant medication may be an effective treatment for bipolar depression as well as for medication-induced sedation. However, there are few data regarding the use of these medications in BD, likely due in part to concerns regarding potential stimulant-induced switching and stimulant abuse.. In order to evaluate the effectiveness and safety of psychostimulants in BD, we retrospectively reviewed the cases of eight consecutive individuals from our clinic (five with bipolar I and three with bipolar II) who received adjunctive stimulants (either methylphenidate or amphetamine) within the last 2 years. Primary target symptoms of stimulant therapy included residual depression and medication-induced sedation. The degree of clinical change in target symptoms was estimated, and the Clinical Global Impression-BP Version scale (CGI-BP) was used to evaluate the overall severity of illness at baseline, 6 months after stimulant initiation, and at last visit.. The eight patients generally showed moderate clinical improvement in their target symptoms and substantial improvement of overall bipolar illness (mean change in CGI-BP overall score 2.9). There was no evidence of stimulant-induced switching or abuse. The stimulants were well tolerated.. The present case series suggests that adjunctive stimulants may be a reasonable therapeutic option for treating residual depression and medication-induced sedation in some patients. Controlled trials are needed to assess the safety and effectiveness of stimulant augmentation in BD.

Topics: Adult; Aged; Amphetamine; Antipsychotic Agents; Bipolar Disorder; Central Nervous System Stimulants; Clozapine; Consciousness Disorders; Depression; Diagnostic and Statistical Manual of Mental Disorders; Drug Therapy, Combination; Female; Humans; Male; Methylphenidate; Middle Aged; Retrospective Studies

Sleep disturbances are strongly associated with mood disorders, although the majority of data have been obtained in patients with major depressive disorder. Studies reporting results in bipolar disorder are few, and results have not been consistent. Clozapine is a prototype of atypical antipsychotics, which is effective in improving symptoms of manic episodes in patients with bipolar disorder, or schizoaffective disorder, bipolar type and has been shown to influence sleep in other psychiatric disorders. The present study evaluated the sleep effects of clozapine in bipolar and schizoaffective disorders.. Participants were 11 women and 4 men (range:28-53 years of age, mean 40.9+/-8.6 years), all with a history of mania by DSM-IV criteria for either bipolar I disorder or schizoaffective disorder, bipolar type. They participated in a sleep study at baseline and again after 6 months initiation of clozapine add-on therapy.. Sleep latency was longer on clozapine and the number of awakenings were increased, whereas time in bed (TIB) and total sleep period (TSP) were increased (range: F=6.2-17.9; df=l,12; p<0.05). Although none of the individual sleep stage showed significant treatment changes, both Stage 2 and slow-wave sleep were increased and Stage 2 decreased on clozapine. Subjective sleep measures improved on clozapine with a small but significant improvement in how rested patients felt upon awakening (t=-2.1; df=26; p<0.05).. Clozapine prolonged sleep latency, improved restedness, and increased total sleep time. Although lack of a control group limits interpretation of these results, they are in general agreement with studies in other psychiatric populations, and support the view that clozapine is primarily a NREM sleep enhancer. The improvement in restedness may be of positive clinical consequence.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Polysomnography; Psychiatric Status Rating Scales; Psychotic Disorders; Sleep Stages; Sleep Wake Disorders

The aim of this study was to evaluate the long-term efficacy and safety of clozapine in patients with treatment-resistant schizophrenia, schizoaffective disorder, or bipolar disorder with psychotic features.. 101 patients with a DSM-III-R diagnosis of schizophrenia (N = 34); schizoaffective disorder, bipolar type (N = 30); or bipolar disorder with psychotic features (N = 37) were naturalistically treated with clozapine at flexible doses over a 48-month period. Data were collected from 1994 to 2000. The Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impressions-Severity of Illness scale total predicted scores over time were estimated with random-effects regression models. Time to response to clozapine, defined as 50% reduction of BPRS score, was analyzed in the 3 diagnostic groups using the Kaplan-Meier method. Survival curves were compared using the log-rank test.. The BPRS total predicted score halved its baseline value in 3 months for bipolar disorder patients, in 6 months for schizoaffective disorder patients, and in 24 months for schizophrenia patients. The proportion of subjects who satisfied the criterion for response to clozapine after 48 months of follow-up was significantly (p <.01) higher in the schizoaffective and bipolar disorder groups (90.0% and 83.8%, respectively) than in the schizophrenia group (64.7%). Baseline scores on the Global Assessment of Functioning (GAF) showed low levels of psychosocial and occupational functioning in all 3 groups. After 48 months of treatment, GAF scores showed a functional improvement in all 3 groups, with significantly (p <.01) greater improvement in the bipolar disorder group compared with the other groups.. The findings of this study confirm the efficacy and safety of clozapine for treatment-resistant patients with a diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder with psychotic features. Patients with schizoaffective disorder and those with bipolar disorder show greater clinical improvement than those with schizophrenia. Patients with bipolar disorder have the shortest time to response and the highest psychosocial and occupational functioning levels. Patients with schizoaffective disorder have the lowest treatment discontinuation rate.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Brief Psychiatric Rating Scale; Clozapine; Female; Follow-Up Studies; Humans; Male; Patient Dropouts; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Severity of Illness Index; Survival Analysis; Treatment Outcome

Gabapentin (GBP) may be useful in bipolar disorders, including as adjunctive therapy for bipolar depression, although controlled studies suggest inefficacy as primary treatment for mania or treatment-resistant rapid cycling.. We performed a 12-week trial of open GBP (mean dose 1725 mg/day) added to stable doses of mood stabilizers or atypical antipsychotics in 22 (10 women, mean age 38.4 years) depressed (28-item Hamilton Depression Rating Scale (HDRS) > 18] bipolar (10 bipolar I, 12 bipolar II) disorder outpatients. Mean illness duration was 18.6 years, current depressive episode duration was 18.0 weeks. Prospective 28-item HDRS, Young Mania Rating Scale (YMRS) and Clinical Global Impression-Severity (CGI-S) ratings were obtained.. Overall, HDRS ratings decreased 53% from 32.5 +/- 7.7 at baseline to 16.5 +/- 12.8 at week 12 (p < 0.0001). Twelve of 22 (55%) patients had moderate to marked improvement (HDRS decrease = 50%) with HDRS decreasing 78% from 27.9 +/- 6.2 to 6.2 +/- 4.5 (p < 0.0001). Eight of 22 (36%) patients remitted (HDRS > or = 8). In non-responders, HDRS decreased from 38.0 +/- 5.4 to 28.9 +/- 6.7 (p = 0.005). Ten of 13 (77%) mild to moderately depressed (baseline HDRS > 18 and <35) patients responded, while only two of nine patients (22%) with severe depression (HDRS > or = 35) responded (p < 0.03). Both groups, however, had similar, statistically significant HDRS decreases. GBP was well tolerated.. Open adjunctive GBP was effective and well tolerated in patients with mild to moderate bipolar depression. This open pilot study must be viewed with caution, and randomized controlled studies are warranted.

Topics: Acetates; Adult; Amines; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Clozapine; Cyclohexanecarboxylic Acids; Drug Therapy, Combination; Female; Gabapentin; gamma-Aminobutyric Acid; Humans; Lithium Carbonate; Male; Pilot Projects; Prospective Studies; Severity of Illness Index; Surveys and Questionnaires

There is a paucity of data on the use of clozapine in patients with mental retardation and comorbid psychiatric illness. The authors describe their recent clinical experience using clozapine in treatment-refractory patients with mental retardation and severe psychiatric illness.. A retrospective review was performed on the records of all patients admitted to a university-affiliated, specialized inpatient psychiatry service who were selected for clozapine therapy from March 1994 through December 1997 (N = 33). Patients had DSM-IV diagnoses of schizophrenia, schizoaffective disorder, bipolar disorder, delusional disorder, or psychotic disorder NOS and were considered treatment resistant. All had deficits in functioning well beyond those expected for their degree of cognitive deficits and adaptive delays.. Of 33 initial patients, 26 remained on clozapine therapy for a follow-up duration of 5 to 48 months (mean = 24.8 months). Evaluation at follow-up revealed Clinical Global Impressions-Improvement (CGI-I) scores from 1 to 4 with a mean +/- SD improvement of 2.0 +/- 0.8 (much improved). The mean +/- SD rating of the CGI-Efficacy Index was 5 +/- 2.6 (decided improvement and partial remission of symptoms with no interference from side effects). The 6 patients who were not maintained on clozapine therapy over the study period did not significantly differ from the clozapine group in gender, race, age, side effects, or diagnosis. One patient was lost to follow-up. Side effects were mild and transient with constipation being the most common (N = 10). There were no significant cardiovascular side effects and no seizures. No patients discontinued treatment due to agranulocytosis.. The current investigation lends support to the conclusion that clozapine appears to be safe, efficacious, and well tolerated in individuals with mental retardation and comorbid psychiatric illness.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Comorbidity; Female; Follow-Up Studies; Humans; Intellectual Disability; Male; Middle Aged; Psychotic Disorders; Retrospective Studies; Schizophrenia; Schizophrenia, Paranoid; Treatment Outcome

The efficacy of clozapine was examined in a group of patients with treatment-refractory bipolar disorder, manic type with psychotic features.. Twenty-two subjects with treatment-refractory bipolar disorder with active manic and psychotic symptoms participated in a 12-week open-label trial of clozapine. After a 2-10-day drug washout period, patients began treatment with clozapine at 25 mg/day; the dose was increased 25 mg/day (as tolerated) to a maximum level of 550 mg/day. Patients were evaluated longitudinally over the course of the study with the Brief Psychiatric Rating Scale (BPRS), the Young Mania Rating Scale, and the Clinical Global Impressions (CGI) scale.. Fourteen of the 22 subjects in the study continued taking clozapine for at least 10 of the 12 weeks. Among the entire group, mean improvements of 56. 7%, 56.6%, and 39.1% were seen on the BPRS, Young Mania Rating Scale, and CGI, respectively. Seventeen of the 22 subjects (77.3%) experienced at least a 20% improvement in scores on all three scales.. The findings from this open-label study, which are consistent with previous retrospective studies, case reports, and one other open-label prospective study, suggest that clozapine is an effective agent for patients with treatment-refractory psychotic mania.

Topics: Adult; Age Factors; Antipsychotic Agents; Bipolar Disorder; Brief Psychiatric Rating Scale; Clozapine; Drug Administration Schedule; Female; Humans; Male; Patient Dropouts; Prospective Studies; Psychiatric Status Rating Scales; Regression Analysis; Sex Factors; Treatment Outcome

The aim of this study was to evaluate the 24-month response to clozapine in patients with schizophrenia, schizoaffective disorder, or psychotic bipolar disorder.. Ninety-one psychotic patients with a principal DSM-III-R diagnosis of schizophrenia (N = 31), schizoaffective disorder (N = 26), or bipolar disorder with psychotic features (N = 34) were treated naturalistically with clozapine at flexible dosages over a 24-month period. Improvement was assessed by the 18-item Brief Psychiatric Rating Scale and the Clinical Global Impressions-Severity of Illness scale.. All patients showed significant improvement 24 months from intake (p < .001). Such an improvement was significantly greater among patients with schizoaffective disorder or bipolar disorder than in patients with schizophrenia (p < .05). The presence of suicidal ideation at intake predicted greater improvement at endpoint.. Clozapine appears to be effective and relatively well tolerated in acute and long-term treatment of patients with psychotic bipolar disorder or schizoaffective disorder who have not responded to conventional pharmacotherapies.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Comorbidity; Female; Follow-Up Studies; Humans; Male; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Suicide; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Female; Humans; Male; Middle Aged

Our purpose was to evaluate the overall efficacy and tolerability of novel antipsychotic medications for patients with bipolar disorder type I.. A retrospective study of the Massachusetts General Hospital Bipolar Clinic database was carried out to identify 50 consecutive treatment trials in patients with DSM-IV bipolar disorder type I who had received adjunctive treatment with risperidone, olanzapine, or clozapine, along with standard mood stabilizers. The treatment charts of those patients (N = 42) were reviewed for details of adverse effects, tolerability, and efficacy of medication.. Overall results indicated equivalent efficacy in novel antipsychotic treatments according to change in Clinical Global Impressions scale score. Levels of extrapyramidal symptoms were similar in all groups and occurred in 12/42 patients (28.6%). Prolactin-related side effects were not observed in any patients. There were no cases of affective switch or worsening of mania. Substantial weight gain of more than 10 lb (4.5 kg) was significantly greater in patients treated with olanzapine.. These results suggest that the efficacy and tolerability of risperidone, olanzapine, and clozapine are similar in patients with bipolar disorder. One major differentiation factor of these drugs appears to be weight gain, particularly between olanzapine and risperidone. This may, in part, also be related to the need to use mood-stabilizing agents, like lithium or divalproex sodium, which may potentiate the weight-gain effect of novel antipsychotics.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Bipolar Disorder; Body Weight; Clozapine; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Lithium; Male; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Retrospective Studies; Risperidone; Treatment Outcome; Valproic Acid

We present the case of a 60-year old bipolar-I-patient showing a rapid antimanic response to gabapentin after having been non-responsive to lithium and perazine. This case encouraged us to further evaluate the antimanic potency of gabapentin in an open label trial. 20 patients with acute mania were treated for up to 21 days with gabapentin in a dose range from 1200 to 4800 mg/day. Ten patients were treated with gabapentin as add-on medication and ten patients were treated with a high dose of gabapentin alone. The BRMAS score declined significantly in patients with moderate mania, whereas gabapentin alone was not efficacious in patients with very severe mania. Keeping in mind the limitations of an open study, it can still be said that gabapentin as add-on medication with other effective mood stabilizers appears to be safe and efficacious in the treatment of moderate mania.

Topics: Acetates; Amines; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Clozapine; Cyclohexanecarboxylic Acids; Gabapentin; gamma-Aminobutyric Acid; Humans; Lithium; Male; Middle Aged; Psychiatric Status Rating Scales

Case series and follow-up studies suggest that clozapine may have mood-stabilizing properties in addition to antipsychotic action in patients with schizoaffective disorder, bipolar type, and bipolar I disorder, but the generalizability of these findings is limited. This article describes a randomized, open study of clozapine add-on therapy versus treatment as usual for patients with treatment-resistant illness and a history of mania.. Thirty-eight patients meeting the DSM-IV criteria for schizoaffective or bipolar disorder that was deemed treatment-resistant were randomly assigned to clozapine add-on treatment (N = 19) or treatment as usual (no clozapine) (N = 19) and followed up for 1 year. Patients received monthly ratings on the Brief Psychiatric Rating Scale, Clinical Global Impression scale, Bech-Rafaelsen Mania Scale, Hamilton Depression Rating Scale, Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms, Abnormal Involuntary Movement Scale, and a 40-item side effect checklist. Differences between treatment groups were assessed according to a pattern-mix random-regression model. An additional analysis compared group differences in rating scale scores against relative time in the study.. Significant between-group differences were found in scores on all rating scales except the Hamilton depression scale. Total medication use over 1 year significantly decreased in the clozapine group. No significant differences between groups in somatic complaints were noted. The subjects with nonpsychotic bipolar I disorder who received clozapine showed a degree of improvement similar to that of the entire clozapine-treated group. Clozapine dose was significantly higher for the patients with schizoaffective illness than for those with bipolar disorder.. The results of this study support clozapine's independent mood-stabilizing property. They demonstrate that clozapine use was associated with significant clinical improvement relative to treatment as usual.

Topics: Adult; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clozapine; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Prospective Studies; Psychiatric Status Rating Scales; Psychotic Disorders; Regression Analysis; Treatment Outcome

The cost, side effect profile, and required weekly blood draws associated with clozapine may dissuade some clinicians from prescribing this atypical neuroleptic to mentally retarded patients. All publications on clozapine use in mentally retarded patients are reviewed and the treatment of 10 such patients is described, bringing the total number of published cases to 84. Clozapine is efficacious and well tolerated in this population and should be considered for those patients with psychosis or bipolar illness who are intolerant of or unresponsive to other agents.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Female; Follow-Up Studies; Humans; Intellectual Disability; Male; Middle Aged; Psychiatric Status Rating Scales; Psychotic Disorders

In an open trial, clozapine was used to treat 3 elderly (mean age 72 +/- 2.5 years) institutionalized male patients with bipolar I disorder, most recent episode manic, severe with psychotic features. All patients were refractory or intolerant of treatment with lithium, valproate, benzodiazepines, and traditional neuroleptics both alone and in combination. Response to clozapine was determined using the Severity of Illness score on the Clinical Global Impression (CGI) scale (1 = normal, not at all ill, 7 = among the most extremely ill). Pre-clozapine severity of illness scores on the CGI averaged 6.33 +/- 0.6; post-clozapine CGI scores averaged 2.0 +/- 1.0 (t = 13.00, df = 2, p < .01). The therapeutic dosage of clozapine varied (range = 25-112.5 mg/day). There were no significant drops in granulocyte counts. Followup revealed sustained improvement over an average of 11 months. These dramatic results suggest that clozapine may be an effective alternative treatment for similar patients and that prospective trials are warranted.

Topics: Aged; Antipsychotic Agents; Bipolar Disorder; Clozapine; Humans; Inpatients; Male

The purpose of the present study was to compare the efficacy of clozapine with that of chlorpromazine in an open label manner (both given in association with lithium salts) in the treatment of acute mania. Thirty hospitalized manic patients were entered into the study. All patients met DSM-IV criteria for bipolar disorder, Manic Episode; 27 patients completed the study and three patients dropped for noncompliance. The duration of the study was 3 weeks. Patients were randomly assigned to two treatment groups; group 1 (n = 15) was treated with clozapine at a mean dose of 166 mg/day and group 2 (n = 12) was treated with chlorpromazine at a mean dose of 310 mg/day. Manic symptomatology was rated on Young Rating Scale for Mania (YRSM) each week; side effects were recorded on dosage records and treatment emergent symptoms; extrapyramidal acute side effects were rated on the Simpson-Angus Rating Scale performed at the beginning of the study and after 3 weeks of treatment. A two-way repeated measures analysis of variance on YRMS scores showed a significant time effect (p < 0.0001) and a significant time-group interaction (p < 0.0001). Post-hoc comparison between the two groups showed a significant difference after 2 weeks of treatment (p = 0.0001), with clozapine treated patients showing lower YRSM scores than chlorpromazine treated patients. YRSM scores at the end of the study were not significantly different. Patients treated with clozapine showed a more rapid trend toward amelioration. No clinically relevant side effect was observed during the study.

Topics: Acute Disease; Adult; Antipsychotic Agents; Bipolar Disorder; Chlorpromazine; Clozapine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Lithium; Male; Middle Aged; Psychiatric Status Rating Scales; Treatment Outcome

The efficacy of clozapine for treatment-resistant mania was examined in a prospective trial for patients with bipolar or schizoaffective disorder.. The subjects were 25 acutely manic patients with either bipolar disorder (N = 10) or schizoaffective disorder-bipolar subtype (N = 15) for whom lithium, anticonvulsants, and neuroleptics had been ineffective, had produced intolerable side effects, or both. After a 7-day washout, the patients were treated with clozapine monotherapy. They were evaluated over 13 weeks with the Young Mania Rating Scale and the Brief Psychiatric Rating Scale (BPRS).. Of the 25 patients, 18 (72%) exhibited marked improvement on the Young Mania Rating Scale, and eight (32%) exhibited marked improvement on the BPRS. The bipolar patients as compared to schizo-affective patients, and the nonrapid as compared to rapid cyclers, had significantly greater improvement in total BPRS score.. These results suggest that clozapine is an effective therapy for treatment-resistant bipolar and schizoaffective mania.

Topics: Adult; Aged; Anticonvulsants; Antipsychotic Agents; Bipolar Disorder; Clozapine; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Lithium; Male; Middle Aged; Prospective Studies; Psychiatric Status Rating Scales; Psychotic Disorders; Treatment Outcome

Clozapine has been increasingly shown to be effective in the acute and maintenance treatment of bipolar disorders. For this reason, we studied whether clozapine alone is effective as a mood stabilizer in patients with refractory bipolar disorders.. Subjects were part of a long-term follow-up study cohort of 193 patients with refractory mood disorders who were treated with clozapine at McLean Hospital prior to July 1, 1992. Patients included in this study were those older than 16 years with bipolar disorder (manic or mixed) and schizoaffective disorder, bipolar type, discharged taking clozapine alone (N = 17). Hospital records on all patients were reviewed by trained raters blind to "best-estimate" diagnoses. Response to clozapine was determined by the Clinical Global Impressions-Improvement (CGI-I) scale. Patients were contacted at least 6 months after clozapine initiation for semistructured follow-up interviews by raters blind to diagnosis and baseline information.. Seventeen subjects were contacted 16.1 +/- 5.6 months after clozapine initiation. Most of the 17 patients had previously failed trials of lithium, valproate, carbamazepine, neuroleptics, combinations of these, and electroconvulsive therapy; or had tardive dyskinesia. Of these patients, 65% (11/17) continued to be on clozapine therapy alone at follow-up and had no subsequent rehospitalization or affective episode. At follow-up, there was a significant decrease in the rehospitalization rate (p = .025) than before starting clozapine and a significant improvement in CGI-I scores (p = .02).. Clozapine monotherapy is an effective mood stabilizer, reducing both the number of affective episodes and rehospitalizations in patients with severe refractory bipolar illness.

Topics: Adult; Bipolar Disorder; Clozapine; Female; Follow-Up Studies; Humans; Male; Middle Aged; Patient Readmission; Psychiatric Status Rating Scales; Psychotic Disorders; Recurrence; Retrospective Studies; Schizophrenia; Treatment Outcome

Emerging evidence indicates that inflammation plays an important role as a mechanism underlying mental disorders. However, most of the research on inflammatory mechanisms focuses on serum levels of interleukins and very few studies have investigated molecules that initiate and expand innate immune pathways such as damage-associated molecular patterns (DAMPs).. This study investigated the levels of DAMPs among patients diagnosed with major depressive disorder (MDD), bipolar disorder (BD) I and II, schizophrenia (SCZ), and generalized anxiety disorder (GAD). We quantified serum levels of heat shock proteins (HSPs) 70 and 60 and of S100 calcium-binding protein B (S100B).. Serum levels of HSP70, HSP60, and S100B were assessed in a sample of participants with psychiatric disorders (n = 191) and a control group (CT) (n = 59) using enzyme-linked immunosorbent assay (ELISA).. Serum HSP70 concentrations were significantly higher in the MDD group compared to the CT, SCZ, and BD groups. The GAD group had higher concentrations of HSP70 than the SCZ group. Exploring associations with medications, lithium (p = 0.003) and clozapine (p = 0.028) were associated with lower HSP70 levels. Approximately 64% of the sample had DAMPs levels below the limits of detection indicated by the respective ELISA kit.. This was the first study to assess DAMPs levels in a transdiagnostic sample. Our preliminary findings suggest that HSP70 may be associated with MDD pathophysiology. Medications such as lithium and clozapine were associated with lower HSP70 levels in BD and SCZ groups, respectively. Therefore, it is worth mentioning that all participants were medicated and many psychotropic drugs exert an anti-inflammatory effect, possibly reducing the signs of inflammation.

Topics: Bipolar Disorder; Clozapine; Depressive Disorder, Major; HSP70 Heat-Shock Proteins; Humans; Inflammation; Lithium

Availability of the dopamine and noradrenaline precursor tyrosine is critical for normal functioning, and deficit in tyrosine transport across cell membrane and the blood-brain barrier has been reported in bipolar disorder and schizophrenia. Clozapine and lithium are two psychoactive agents used to treat psychosis, mood disorders and suicidal behavior, but their mechanism of action remains largely unknown.. To characterize immediate and delayed differences in tyrosine uptake between healthy controls (HC) and bipolar patients (BP) and see if these differences could be normalized by either clozapine, lithium or both. A second objective was to see if clozapine and lithium have additive, antagonistic or synergistic effects in this.. Fibroblasts from five HC and five BP were incubated for 5 min or 6 h with clozapine, lithium, or combination of both. Radioactive labelled tyrosine was used to quantify tyrosine membrane transport.. There was significantly reduced tyrosine uptake at baseline in BP compared to HC, a deficit that grew with increasing incubation time. Clozapine selectively increased tyrosine uptake in BP and abolished the deficit seen under baseline conditions, while lithium had no such effect. Combination treatment with clozapine and lithium was less effective than when clozapine was used alone.. There was significant deficit in tyrosine transport in BP compared to HC that was reversed by clozapine but not lithium. Clozapine was more effective when used alone than when added together with lithium. Potential clinical implications of this will be discussed.

Topics: Antipsychotic Agents; Bipolar Disorder; Clozapine; Humans; Lithium; Psychotic Disorders

Pharmacological treatment patterns for bipolar disorder have changed during recent years, but for better or worse?. To investigate the comparative real-world effectiveness of antipsychotics and mood stabilisers in bipolar disorder.. Register-based cohort study including all Finnish residents aged 16-65 with a diagnosis of bipolar disorder from in-patient care, specialised out-patient care, sickness absence and disability pensions registers between 1996 and 2018, with a mean follow-up of 9.3 years (s.d. = 6.4). Antipsychotic and mood stabiliser use was modelled using the PRE2DUP method and risk for hospital admission for psychiatric and non-psychiatric reasons when using versus not using medications was estimated using within-individual Cox models.. Among 60 045 individuals (56.4% female; mean age 41.7 years, s.d. = 15.8), the five medications associated with lowest risk of psychiatric admissions were olanzapine long-acting injection (LAI) (aHR = 0.54, 95% CI 0.37-0.80), haloperidol LAI (aHR = 0.62, 0.47-0.81), zuclopenthixol LAI (aHR = 0.66, 95% CI 0.52-0.85), lithium (aHR = 0.74, 95% CI 0.71-0.76) and clozapine (aHR = 0.75, 95% CI 0.64-0.87). Only ziprasidone (aHR = 1.26, 95% CI 1.07-1.49) was associated with a statistically higher risk. For non-psychiatric (somatic) admissions, only lithium (aHR = 0.77, 95% CI 0.74-0.81) and carbamazepine (aHR = 0.91, 95% CI 0.85-0.97) were associated with significantly reduced risk, whereas pregabalin, gabapentin and several oral antipsychotics, including quetiapine, were associated with an increased risk. Results for a subcohort of first-episode patients (26 395 individuals, 54.9% female; mean age 38.2 years, s.d. = 13.0) were in line with those of the total cohort.. Lithium and certain LAI antipsychotics were associated with lowest risks of psychiatric admission. Lithium was the only treatment associated with decreased risk of both psychiatric and somatic admissions.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Cohort Studies; Female; Humans; Lithium; Male

Topics: Bipolar Disorder; Brain; Clozapine; Humans; Iron; Mania

Emergency psychiatry has the main role of resolving suicidal behavior and aggression. These severe psychiatric symptoms can be found in many psychiatric disorders such as schizophrenia, bipolar disorder, major depression, personality disorders, cognitive disorders, intellectual disability and substance abuse. Although indications for the use of antipsychotics are limited to a specific group of diseases, they are frequently used as rescue medication in high-risk or nonresponsive cases. Clozapine, the gold standard for TRS (treatment resistant schizophrenia) is effective in controlling aggression. The aim of the research was to identify the use of clozapine for treatment-refractory aggressive behavior in psychiatric emergency. A retrospective study based on the paper files of patients admitted between 2010 and 2019 in the Clinical Hospital of Psychiatry and Neurology of Brasov, Romania. Were included all the patients admitted as a psychiatric emergency and treated with clozapine for aggressive behavior. The hospital is an academic institution with 150 beds for acute patients, serving an area of over 600,000 inhabitants. It is the main public institution where patients with psychiatric emergencies are hospitalized. Off 19,000 patients admitted during the study period, 504 patients (2,4%) with a diagnosis other than schizophrenia or schizoaffective disorder received clozapine for aggressiveness (89.5%). The first four diagnoses identified were bipolar disorder (n = 172), intellectual disability (n = 128), cognitive impairment (n = 112), and personality disorder (n = 92). Other disorders identified but with a smaller number of cases were major depressive disorder (n = 3), adjustment disorders (n = 2), delusional disorder (n = 2), obsessive compulsive disorder (n = 2) and postpartum psychosis (n = 1). Clozapine was used as 3rd or 4th choice. The dose was greater for manic patients (350.29 ± 98.01 mg/day) compared with all the other diagnoses. Clozapine was effective and safe in cases of patients with treatment-refractory aggressive behavior.

Topics: Adult; Aged; Aggression; Bipolar Disorder; Clozapine; Cognition; Cognition Disorders; Female; Humans; Intellectual Disability; Male; Personality Disorders; Psychotic Disorders; Retrospective Studies

Topics: Antipsychotic Agents; Bipolar Disorder; Clozapine; Humans

The potential of clozapine in severe bipolar disorder is suggested by its efficacy in refractory schizophrenia, but the evidence is limited thus far. This report utilizes data from the standard care pathway of the Systematic Treatment Enhancement Program to examine the clinical impact of clozapine in bipolar disorder, comparing it to two groups, one that received olanzapine and an additional group that received neither drug.. A total of 4,032 outpatients were available for this analysis. Groups for longitudinal analyses are based on the medication used at each visit. Outcomes assessed were clinical status, symptoms subscales, hospitalizations, and death. We utilized mixed models and generalized estimating equations to adjust for baseline differences and investigate longitudinal differences in symptoms, clinical status, and hospitalization rates between groups.. During the study, 1.1% (. Although prescribed to very few patients, the impact of clozapine was notable, with fewer symptoms in patients who had more severe illnesses at baseline. Clozapine could prove to be as successful an intervention for late-stage bipolar disorder as it has been in schizophrenia.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Female; Hospitalization; Humans; Longitudinal Studies; Male; Middle Aged; Olanzapine; Outcome Assessment, Health Care; Outpatients; Program Development; United States

Topics: Affective Disorders, Psychotic; Aged; Antipsychotic Agents; Bipolar Disorder; Clozapine; Enuresis; Female; Humans; Psychotic Disorders

To compare the rate of hospitalizations for pneumonia in patients with a psychotic or bipolar disorder who were prescribed 1 of 4 second-generation antipsychotics prior to admission.. This retrospective cohort study included patients who were medically admitted for pneumonia to a 2,059-bed academic medical center or its associated health system hospital. Medical records of 872 admissions from November 1, 2016 to December 15, 2018, were included for all adults with a diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder prescribed clozapine, olanzapine, quetiapine, or risperidone prior to admission.. There was no significantly increased risk of pneumonia for patients taking olanzapine (odds ratio [OR] = 1.08, 95% CI, 0.48-2.41) or quetiapine (OR = 0.97, 95% CI, 0.42-2.25) prior to admission compared to risperidone. When controlling for various factors, treatment with a combination of antipsychotics including clozapine (OR = 2.28, 95% CI, 1.13-4.62, P = .022) and clozapine alone (OR = 2.37, 95% CI, 1.30-4.32, P = .005) was associated with an increased risk of pneumonia-related hospitalization compared to treatment with risperidone, olanzapine, or quetiapine alone.. The findings of this study in combination with other published literature support an association of an increased risk of pneumonia with the use of clozapine, although this cannot be interpreted as causal. These data show that use of clozapine alone or in combination with other antipsychotics significantly increases risk of pneumonia, although this finding cannot be deemed causal due to study design.

Topics: Adult; Aged; Antipsychotic Agents; Bipolar Disorder; Clozapine; Female; Hospitalization; Humans; Male; Middle Aged; Pneumonia; Psychotic Disorders; Retrospective Studies; Risk; Schizophrenia

In this study, we aimed to investigate the effect of the clozapine on the course of the rapid cycling Bipolar Affective Disorder.. The study group was formed with the patients aged between 18 and 65 years of age, who met the criteria for the diagnosis of Bipolar Affective Disorder according to the Diagnostic and Statistical Manual of Mental Disorders 4th Edition, with rapid cycling characteristics. Variables like the number of mania and depressive episodes, the days spent in mania and in depression and the number of hospitalization and attempted suicide, in the year before starting clozapine were determined and compared with the annual data after starting the clozapine.. Eleven female and two male patients who met the inclusion criteria were included in this study. The group`s average daily use of clozapine was 180 mg (25-600 mg). There was a statistically significant difference in the number of days spent in the depression, the days spent in the mania, the number of depressive episodes and manic episodes, the number of hospitalizations and the suicide attempts after the clozapine use.. In this study, it was determined that clozapine was effective as a mood stabilizer in Bipolar Affective Disorder treatment. The results show that clozapine reduces the episode frequency and the duration in rapid cycling Bipolar Affective Disorder which does not respond to all conventional treatments, including lithium, valproic acid, carbamazepine and antipsychotic drugs.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Bipolar Disorder; Clozapine; Diagnostic and Statistical Manual of Mental Disorders; Female; Humans; Male; Middle Aged; Mood Disorders; Young Adult

Rebound cholinergic syndrome is a rare, but well known unwanted phenomenon occurring after abrupt clozapine discontinuation. There have been previous reported cases of cholinergic rebound in the literature; however, these reports described cholinergic rebound following cessation of high doses of clozapine in patients diagnosed with schizophrenia. Here, we report a case of rebound cholinergic syndrome and catatonia in a male patient three days after abrupt discontinuation of 50 mg of clozapine prescribed for type I bipolar affective disorder.. A 66-year old male of Spanish origin, treated for type I bipolar affective disorder for 15 years and for Crohn disease, was brought to the emergency department because of a sudden onset of mutism, dysphagia and trismus. He was described catatonic and presented hypertension, tachycardia and tachypnea. His body temperature was normal and the laboratory tests were unremarkable at presentation. A head CT and an EEG were in the normal range. While reviewing his history, it appeared the he was on clozapine 50 mg a day, first introduced 2 months ago, during a previous hospitalization for a manic episode resistant to other mood stabilizers. For an unknown reason, the patient's psychiatrist stopped clozapine three days before the admission and replaced it by risperidone 5 mg and quetiapine 200 mg daily. A cholinergic rebound syndrome was then evoked. The patient's ability to speak recovered dramatically and fast after the intravenous administration of 2.5 mg of biperiden supporting the diagnosis. Risperidone and quetiapine were also stopped. The patient fully recovered in 20 days after the reintroduction of 50 mg of clozapine and 2.5 mg of biperiden daily.. This case report underscores that cholinergic rebound syndrome may occur in patients suffering from bipolar affective disorders, being on clozapine as a mood stabilizer. The low dose clozapine does not preclude severe manifestations of the phenomenon. Progressive tapering should therefore be adopted in any case.

Topics: Aged; Antipsychotic Agents; Bipolar Disorder; Catatonia; Cholinergic Agents; Clozapine; Humans; Male; Substance Withdrawal Syndrome; Withholding Treatment

This retrospective observational study was performed to investigate electroencephalogram abnormalities in clozapine-treated patients with refractory schizophrenia or bipolar disorder. The electroencephalogram and plasma clozapine and norclozapine levels in 71 patients were measured on the same day. Fifty-nine patients (85.9%) had a diagnosis of schizophrenia, and 12 patients (14.1%) had a diagnosis of bipolar disorder. The mean daily clozapine dose was 242.9 ± 105.5 mg (range 25-500 mg), and the mean plasma clozapine and norclozapine levels were 429.4 ± 264.1 and 197.8 ± 132.6 ng/ml, respectively. Twenty-five patients (35.2%) were taking valproate in combination with clozapine. electroencephalogram abnormalities were found in 51 (71.8%) patients. No patient reported clinical seizures. Plasma clozapine level was significantly associated with electroencephalogram abnormalities and was identified as a significant predictor of electroencephalogram abnormalities in a logistic regression analysis. The plasma norclozapine levels of patients taking both clozapine and valproic acid were significantly lower than those of patients treated with clozapine alone. These results demonstrate that electroencephalogram abnormalities are closely correlated with plasma clozapine levels. Valproate reduced plasma norclozapine levels. Simultaneous monitoring of electroencephalogram and plasma clozapine levels was useful for adjusting clozapine doses, improving clinical efficacy, and preventing the side effects of clozapine treatment.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Drug Monitoring; Electroencephalography; Female; Humans; Male; Middle Aged; Retrospective Studies; Schizophrenia; Treatment Outcome; Valproic Acid

Topics: Adolescent; Antipsychotic Agents; Bipolar Disorder; C-Reactive Protein; Clozapine; Eosinophilia; Female; Fever; Humans

Treatment-resistant schizophrenia (TRS) is a major cause of disability. Clozapine is currently the only antipsychotic medication licensed for its treatment. However, the rate of treatment resistance among outpatients with schizophrenia or other psychoses, and the rate of use of clozapine among them, is not known.. The aims of this study are (a) to determine the point prevalence of treatment-resistant psychosis in a community sample, and (b) to determine the number of patients with TRS who have never had a clozapine trial.. Clinico-demographic data were extracted from the case notes for 202 patients from two community mental-health teams.. These findings suggest that TRS is common in the community mental-health team, and a large proportion of these patients have not received clozapine. These findings indicate that identifying and treating treatment resistance should be a focus of community services for schizophrenia.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Female; Humans; London; Male; Middle Aged; Prevalence; Psychotic Disorders; Schizophrenia

Using national Danish registers, we estimated rates of clozapine-associated cardiac adverse events. Rates of undiagnosed myocarditis were estimated by exploring causes of death after clozapine initiation.. Through nationwide health registers, we identified all out-patients initiating antipsychotic treatment (January 1, 1996-January 1, 2015). Rates of clozapine-associated myocarditis and pericarditis within 2 months from clozapine initiation and rates of cardiomyopathy within 1-2 years from clozapine initiation were compared to rates for other antipsychotics. Mortality within 2 months from clozapine initiation was extracted.. Three thousand two hundred and sixty-two patients of a total 7932 patients initiated clozapine as out-patients (41.12%). One patient (0.03%) developed myocarditis, and no patients developed pericarditis within 2 months from clozapine initiation. Two (0.06%) and four patients (0.12%) developed cardiomyopathy within 1 and 2 years respectively. Rates were similar for other antipsychotics. Twenty-six patients died within 2 months from clozapine initiation. Pneumonia (23.08%) and stroke (11.54%) were the main causes of death. We estimated the maximum rate of clozapine-associated fatal myocarditis to 0.28%.. Cardiac adverse effects in Danish out-patients initiating clozapine treatment are extremely rare and these rates appear to be comparable to those observed for other antipsychotic drugs.

Topics: Adult; Aged; Ambulatory Care; Antipsychotic Agents; Bipolar Disorder; Cardiomyopathies; Clozapine; Denmark; Female; Humans; Male; Middle Aged; Myocarditis; Pericarditis; Psychotic Disorders; Registries; Schizophrenia

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Antipsychotic Agents; Bipolar Disorder; Clozapine; Drug Interactions; Dystonia; Female; Humans; Middle Aged; Posture; Thiazoles; Urinary Incontinence

The aim of the present study was to appraise retrospectively the influence of valproate (VPA) and antidepressants (ADs) on the steady-state plasma concentrations of clozapine (CLZ), the prototype of various second-generation antipsychotics, norclozapine (NCLZ, its main metabolite), and their ratio (NCLZ:CLZ).. Sixty-seven psychotic patients with a prevalent diagnosis of bipolar disorder were studied. We then analyzed data altogether and subdivided them into 4 groups, according to pharmacological treatments: #1 CLZ (n = 21), #2 CLZ plus ADs (n = 13), #3 CLZ plus VPA (n = 16), and #4 CLZ plus ADs plus VPA (n = 17).. First, significant positive between CLZ and NCLZ plasma levels (in nanograms/milliliter) and the drug daily dosages (in milligrams/kilogram of body weight) (n = 67) were observed (Spearman: rCLZ = 0.49; rNCLZ = 0.61; P < 0.001). We then normalized by given doses CLZ and NCLZ plasma levels, natural log transformed them, and performed analysis of variance factor analyses followed by pairwise comparisons, performed on the 4 groups and the 3 CLZ parameters. We identified significant drug effects on (1) CLZ plasma levels, significantly higher in group #2 versus group #1, and (2) NCLZ:CLZ ratio, lower in group #2 versus groups #1 and #3. Significant drug × gender interactions were observed in group #3, showing higher NCLZ levels and NCLZ:CLZ ratios in men compared with women.. Despite its inherent limitations, this observational study confirms the significant increase in plasma CLZ concentrations and reduction in NCLZ:CLZ ratio when this drug was coadministered with ADs (group #2), an effect apparently counteracted by VPA (group #4). The drug × gender interactions in patients taking both CLZ and VPA (group #3) warrant further prospective study.

Topics: Adolescent; Adult; Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Clozapine; Drug Interactions; Female; Humans; Male; Middle Aged; Retrospective Studies; Sex Factors; Valproic Acid; Young Adult

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Clozapine; Drug Therapy, Combination; Female; Humans; Lithium; Treatment Outcome

Antipsychotics produce electroencephalogram (EEG) modifications and increase the risk of epileptic seizure. These modifications remain sparsely studied specifically for atypical antipsychotics. In this context, our study focuses on EEG modifications associated with atypical strict antipsychotic monotherapies.. Electroencephalogram recordings of 84 psychiatric patients treated with atypical antipsychotics in strict monotherapy (clozapine, n = 22; aripiprazole, n = 22; olanzapine, n = 17; risperidone, n = 9; quetiapine, n = 8; risperidone long-acting injection, n = 4; and paliperidone long-acting injection, n = 2) were analyzed. The modifications were ranked according to both slowing and excitability scores.. Electroencephalogram modifications (in 51 subjects, 60.71%) were graded according to 4 stages combining general slowing and sharp slow waves and/or epileptiform activities. The presence of sharp or epileptiform activities was significantly greater for clozapine (90.9%) compared with other second-generation antipsychotics (aripiprazole, 50%; olanzapine, 58.8%; quetiapine, 37.5%; risperidone, 44.4%). Age, duration of disease progression, and diagnosis were not associated as risk factors. Electroencephalogram modifications were associated with lower doses for treatment with quetiapine but not for specific antipsychotics. Electroencephalogram modifications and severe excitability were associated with higher chlorpromazine equivalent doses.. Atypical antipsychotics (clozapine, aripiprazole, quetiapine, olanzapine, and risperidone) induce EEG modifications, and these are significantly greater for clozapine and appear dependent on chlorpromazine equivalent dose. No encephalopathy was observed in these antipsychotic monotherapies, whatever dose.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Cerebral Cortex; Clozapine; Depressive Disorder, Major; Electroencephalography; Female; Humans; Male; Mental Disorders; Middle Aged; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Young Adult

Clozapine is the drug of choice for treatment-resistant schizophrenia. While pediatric clozapine use is not contraindicated, the literature describing its clinical application is limited. The primary objective of this study was to assess the use of clozapine in a child and adolescent population by characterizing the documented safety and clinical benefits of the medication.. A multicenter retrospective study at sites in the United States and Australia included children and adolescents admitted to a psychiatric unit who were administered at least one dose of clozapine. Information related to demographics, patient history, past treatments, clozapine, and adverse events was collected.. Eighty-two patients from eight sites were included in this study. Patients were predominantly clozapine naive (76.8%), and most had a discharge diagnosis of a primary psychotic disorder (61%) or bipolar disorder (25.6%). Four clozapine discontinuations occurred during hospitalization due to severe neutropenia, ileus, need for diagnostic clarification, and significant psychomotor retardation. The remainder (n = 78) were discharged on a mean clozapine dose of 218.1 ± 142.2 mg. Sedation (26.8%) and sialorrhea (17.1%) were the most common documented adverse events. The mean number of previously trialed antipsychotics before clozapine was 3.5 ± 1.4 (range 1-10). Improvement with clozapine was documented as significant (31.7%), moderate (32.9%), minimal (12.2%), no improvement (2.4%), and not described (20.7%).. In this cohort, 95% of pediatric patients admitted with or started on clozapine during an acute psychiatric hospitalization were discharged on the medication. The high incidence of adverse events should reinforce to clinicians the need for vigilant monitoring. Pediatric guidelines recommend clozapine for refractory schizophrenia but stress the critical need to ensure an accurate diagnosis. Limited data exist for the use of clozapine in pediatric patients with other diagnoses.

Topics: Adolescent; Antipsychotic Agents; Australia; Bipolar Disorder; Child; Clozapine; Female; Humans; Male; Neutropenia; Psychiatric Department, Hospital; Psychotic Disorders; Retrospective Studies; Sialorrhea

Antipsychotics are recognised as a critical intervention for schizophrenia and bipolar disorder. Guidelines globally endorse the routine practice of antipsychotic monotherapy, at the minimum effective dose. Even in treatment-resistant schizophrenia, clozapine use is endorsed before combining antipsychotics. This aim of this study was to review antipsychotic polytherapy alone, high-dose therapy alone, polytherapy and high-dose prescribing patterns in adults discharged from an inpatient mental health unit at two time-points, and the alignment of this prescribing with clinical guideline recommendations. Additionally, associations with polytherapy and high-dose antipsychotic prescribing, including patient and clinical characteristics, were explored.. A retrospective clinical audit of 400 adults (200 patients at two different time-points) discharged with at least one antipsychotic. Preliminary findings and education sessions were provided to physicians between Cohorts. Outcomes (polytherapy alone, high-dose therapy alone, polytherapy and high-dose therapy) were compared between study Cohorts using chi-squared and rank-sum tests. Associations between outcomes and covariates were assessed using multivariable logistic regression.. Most patients (62.5%) were discharged on a single antipsychotic within the recommended dose range. There was a clear preference for prescribing second generation antipsychotics, and in this respect, prescribing is aligned with current evidence-based guidelines. However, sub-optimal prescribing practices were identified for both Cohorts in relation to polytherapy and high-dose antipsychotic rates. Involuntary treatment, frequent hospitalisations and previous clozapine use significantly increased the risk of all three prescribing outcomes at discharge.. In a significant minority, antipsychotic prescribing did not align with clinical guidelines despite increased training, indicating that the education program alone was ineffective at positively influencing antipsychotic prescribing practices. Further consideration should be given when prescribing antipsychotics for involuntary patients, people with frequent hospitalisations, and those who have previously trialled clozapine.

Topics: Adult; Antipsychotic Agents; Australia; Bipolar Disorder; Clozapine; Female; Hospitals, Psychiatric; Humans; Male; Medical Audit; Middle Aged; Practice Patterns, Physicians'; Retrospective Studies; Schizophrenia; Vulnerable Populations

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Drug Hypersensitivity Syndrome; Humans; Male

The aim of this retrospective study is to examine the clinical outcomes and safety of clozapine in children and adolescents with schizophrenia or other psychotic disorders/autism spectrum disorder (ASD) or affective disorders.. The inpatient and outpatient files of all children and adolescents treated with clozapine over a period of 34 months (from October 2011 to July 2014) were reviewed. Demographic and clinical data were examined to describe clinical and metabolic findings, dosing, and tolerability of clozapine treatment in youth with schizophrenia, other psychotic disorders, ASD, or bipolar disorder.. The 37 pediatric patients included 26 patients with schizophrenia or other psychotic disorders, 7 patients with ASD complicated by schizophrenia or other psychotic disorders or affective disorders, and 4 patients with ASD only. In all groups (n = 37) there was a significant reduction (p < 0.001) in Brief Psychiatric Rating Scale (BPRS) points after clozapine treatment during the inpatient period (38.78 ± 27.75 days). In patients with schizophrenia or other psychotic disorders co-occurring with ASD or not (n = 31), there was a significant improvement in psychotic symptoms according to Positive and Negative Syndrome Scale (PANSS) total scores and subscores (p < 0.001). Of the 26 patients with schizophrenia or other psychotic disorders, 8 (30.8%) showed a positive response (>30% symptom reduction on BPRS). In patients with ASD complicated by schizophrenia or other psychotic disorders or bipolar disorders (n = 7), there was a significant reduction (p = 0.017) in BPRS scores after clozapine treatment. The discontinuation rate for clozapine was 10.8%, and the most frequently observed side effect was hypersalivation (54.1%). Neutropenia associated with clozapine was observed in only one patient (2.7%).. Clozapine seems to be effective and safe in children and adolescents with schizophrenia or other psychotic disorders co-occuring with ASD or not. There is a need for further studies for determining the efficacy of clozapine in children and adolescents with bipolar affective disorder or ASD.

Topics: Adolescent; Antipsychotic Agents; Autism Spectrum Disorder; Bipolar Disorder; Child; Clozapine; Female; Humans; Inpatients; Male; Psychiatric Status Rating Scales; Psychotic Disorders; Retrospective Studies; Schizophrenia; Treatment Outcome; Turkey

Relieving catatonia helps identify the underlying etiology and its treatment. However, catatonia may reemerge after some time, but there are few data on the relapses and recurrences of catatonia. We aimed to investigate the characteristics of patients with relapses or recurrences of catatonia as well as the efficacy of the lorazepam-diazepam protocol on them.. Patients with catatonia who had more than one episode of catatonia and were treated with the lorazepam-diazepam protocol were identified. Their medical charts were reviewed, and interview was conducted.. Thirty patients were identified. Nineteen (63.3%) were diagnosed with schizophrenia, five (16.7%) with major depressive disorder, two (6.7%) with bipolar disorder, and four (13.3%) with general medical conditions. In the 68 relapses and relapses the lorazepam-diazepam protocol was used, full response was reported in 54 (79.4%) of them. Twelve of 19 (63.2%) patients with schizophrenia were treated with clozapine. Twenty (66.7%) out of 30 patients were maintained on oral lorazepam by the time of discharge. Literature review showed similar prevalence of schizophrenia in patients with more than one episode of catatonia, and a wide variety of treatment options.. The lorazepam-diazepam protocol was mostly effective in managing relapses and recurrences of catatonia. Maintenance clozapine and oral lorazepam were beneficial in a significant number of patients.

Topics: Adolescent; Adult; Antipsychotic Agents; Bipolar Disorder; Catatonia; Clozapine; Depressive Disorder, Major; Diazepam; Drug Therapy, Combination; Female; Humans; Hypnotics and Sedatives; Lorazepam; Male; Middle Aged; Recurrence; Schizophrenia, Catatonic; Young Adult

Topics: Antipsychotic Agents; Bipolar Disorder; Clozapine; Humans; Psychotic Disorders

Topics: Antipsychotic Agents; Australia; Bipolar Disorder; Clozapine; Drug Resistance; Humans; Off-Label Use; Psychiatry

Clozapine can cause severe adverse effects yet it is associated with reduced mortality risk. We test the hypothesis this association is due to increased clinical monitoring and investigate risk of premature mortality from natural causes. We identified 14 754 individuals (879 deaths) with serious mental illness (SMI) including schizophrenia, schizoaffective and bipolar disorders aged ≥ 15 years in a large specialist mental healthcare case register linked to national mortality tracing. In this cohort study we modeled the effect of clozapine on mortality over a 5-year period (2007-2011) using Cox regression. Individuals prescribed clozapine had more severe psychopathology and poorer functional status. Many of the exposures associated with clozapine use were themselves risk factors for increased mortality. However, we identified a strong association between being prescribed clozapine and lower mortality which persisted after controlling for a broad range of potential confounders including clinical monitoring and markers of disease severity (adjusted hazard ratio 0.4; 95% CI 0.2-0.7; p = .001). This association remained after restricting the sample to those with a diagnosis of schizophrenia or those taking antipsychotics and after using propensity scores to reduce the impact of confounding by indication. Among individuals with SMI, those prescribed clozapine had a reduced risk of mortality due to both natural and unnatural causes. We found no evidence to indicate that lower mortality associated with clozapine in SMI was due to increased clinical monitoring or confounding factors. This is the first study to report an association between clozapine and reduced risk of mortality from natural causes.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Bipolar Disorder; Clozapine; Cohort Studies; Drug Prescriptions; Electronic Health Records; Female; Humans; London; Male; Middle Aged; Psychotic Disorders; Registries; Schizophrenia; Young Adult

The efficacy of clozapine in bipolar disorder remains to be systemically examined. In the current study, we sought to disentangle the effect of clozapine from that of improved treatment regularity and to compare the effect of clozapine with the effect of regular treatment for bipolar disorder by exploring the complete 10-year clozapine prescription data from a Taiwanese total population health claims database.. In the period between 2000 and 2009, 3,874 (3.3%) out of the 117,785 patients identified as having bipolar disorder in a Taiwanese total population health claims database were ever prescribed clozapine. Among them, 920 patients with bipolar disorder who had good pre-clozapine medication compliance and received at least two clozapine prescriptions were further categorized according to their clozapine medication possession ratio (MPR) as regular users (MPR ≥ 0.8; n = 476) and irregular users (MPR < 0.8; n = 444). Using a mirror-image design, we compared the numbers of emergency room (ER) visits, hospitalizations and hospital days, and the average durations of a single hospitalization during the pre- and post-clozapine mirror periods with a follow-up time of up to three years, controlling for time-variant course confounders.. The patterns of change in outcome indices from the pre-clozapine period to the post-clozapine period differed significantly between the two clozapine-user groups. Clinical outcome indices improved only in regular users, while they deteriorated in irregular users. Over the three-year follow-up period, the irregular users consistently had a higher adjusted risk for increased numbers of ER visits [odds ratio (OR): 2.06-2.43], hospitalizations (OR: 2.52-3.22), and total hospital days (OR: 2.42-2.91) when compared to the regular users. Thus, effects of clozapine were consistently demonstrated in one- to three-year mirror comparison periods.. Clozapine, when used with high treatment regularity (MPR > 0.8), was effective in reducing the numbers of ER visits, hospitalizations, and total hospital days in patients with bipolar disorder with previous frequent hospitalizations and ER visits despite regular pre-clozapine treatment for bipolar disorder. However, high early attrition and suboptimal treatment compliance need to be rectified in order to optimize the outcome of clozapine treatment in bipolar disorders.

Topics: Adult; Aged; Antipsychotic Agents; Bipolar Disorder; Clozapine; Emergency Service, Hospital; Female; Follow-Up Studies; Hospitalization; Humans; Length of Stay; Male; Medication Adherence; Middle Aged; Taiwan; Utilization Review

Patients with schizophrenia or bipolar disorder treated with antipsychotic medication can frequently experience lack of efficacy and persistent side-effects, so much so that switching from one antipsychotic to another with a different side-effect profile has become a recommended strategy for improving the tolerability and safety of long-term antipsychotic treatment. Aripiprazole is an atypical antipsychotic with proven efficacy in schizophrenia and bipolar I disorder, with a pharmacological profile distinct from other available antipsychotics and a side-effect profile that is different from other agents in the class; these characteristics make it a possible alternative in patients requiring a change in antipsychotic treatment due to lack of efficacy or persistent side-effects.. A panel of Italian experts in psychiatry met to discuss the appropriateness of current strategies for the switch to aripiprazole in patients with schizophrenia or bipolar disorder once a clinician has decided to adopt this choice and also to propose alternate strategies where required. The strategies for the switch to aripiprazole presented in this position paper consider various scenarios encountered in clinical practice, highlight the importance of tapering the prior antipsychotic based on its pharmacological characteristics and provide detailed guidance throughout the entire switching process. Literature searches were conducted using the PubMed database and the search strategy (aripiprazole and switching); additional references were added from the reference lists of the papers obtained and also from the authors' knowledge of the topic.. Few studies have addressed the indications for antipsychotic switching and the best practical strategies to achieve the desired goal in the clinical practice setting. Studies on antipsychotic switching should clarify why, when and how a switch should be done. The results should standardize the reasons for switching an antipsychotic, assess the optimal time to switch and evaluate the best ways to switch. Both clinical and pharmacological factors should be considered when a patient needs to switch antipsychotics, and specific guidelines for antipsychotic switching that address all these factors are needed.

Topics: Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Clozapine; Drug Substitution; Humans; Italy; Piperazines; Quinolones; Schizophrenia

Second-generation antipsychotics (SGAP) and mood stabilizers (MS) are prescribed widely for the treatment of bipolar disorder, but they are associated with the risk of relevant side-effects, among which is weight gain. The identification of genes that predispose to weight gain would represent a useful tool to evaluate the risk-benefit ratio of treatment.. This study investigated the genetic factors associated with weight gain in bipolar patients treated with SGAP, MS and their combinations (n=486). Single-nucleotide polymorphisms belonging to 16 candidate genes supported by the literature were investigated in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) genome-wide dataset. Linear regression models were constructed including age, sex, initial weight and prescription of SGAP at high risk for inducing weight gain (olanzapine or clozapine) as covariates. Genes harbouring single-nucleotide polymorphisms associated with phenotypes were investigated by a pathway analysis.. No association was found between phenotypes and individual polymorphisms or pathways after multiple-test correction. HTR2C, LEP, FTO and TBC1D1 represented the top genes for weight gain during treatment with a SGAP and/or MS. A genome-wide signal (FTO rs9930506) associated previously with obesity was associated with psychotropic-induced weight gain. The genes that influenced both SGAP and MS weight gain were FTO, TBC1D1, MTHFR and HRH1. ADCY9, ADCY5 and PRKAG2 were interesting candidate genes that emerged from the pathway analysis.. This study was the first to compare the genes involved in SGAP-induced and MS-induced weight gain. Individual genes probably play a limited role in psychotropic-induced weight gain; further studies should focus on the extension from known candidate genes to wider groups of molecular pathways.

Topics: Adipose Tissue; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clozapine; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Homeostasis; Humans; Male; Olanzapine; Polymorphism, Single Nucleotide; Psychotropic Drugs; Weight Gain

Constipation occurs in 25-60% of the subjects during administration of the antipsychotic drug (AP) clozapine (CLZ).. We used a colonic transit diagnostic test that quantifies in a single abdominal X-ray the number of silver O-ring markers out of 25 units ingested five days before. The quantity of markers is directly proportional to the degree of gastrointestinal hypomotility, and elimination of over 80% of the markers is considered normal. The test was applied to three groups of AP-treated subjects for at least three consecutive months: CLZ alone (n=45), CLZ+Other APs (n=28), and Other APs (n=64).. The number of remaining markers at day 5 (mean±S.D.) was significantly higher in the CLZ alone (10.8±10.6) and in the CLZ+Other APs (9.7±9.7) groups than in the Other AP group (4.5±6.7), Kruskal-Wallis test: p=0.004. No significant associations were found between the number of markers, age, AP dose and treatment duration. All subjects who passed <80% of markers - which approximately corresponds to the 60th percentile of marker elimination - showed a scattered marker distribution along the colon, thus suggesting colon inertia. In subjects with hypomotility, 38.5% of the CLZ group, 25% of the CLZ+Other APs group, and 25% of the Other APs group were negative for the Rome III clinical criteria of constipation, thus showing objective, not subjective, hypomotility.. This study objectively confirms significant gastrointestinal hypomotility associated with CLZ administration.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Constipation; Diagnostic Techniques, Digestive System; Female; Gastrointestinal Tract; Humans; Male; Middle Aged; Radiography, Abdominal; Schizophrenia; Silver Compounds

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Female; Graves Disease; Humans; Treatment Outcome

Two patients each developed a single, fixed somatic delusion complicating their existing bipolar disorder. Both failed to respond to a range of antidepressant and antipsychotic medications. They each showed a partial response to clozapine and to electroconvulsive therapy, with resolution of mood symptoms and diminution of their ongoing somatic preoccupation. A review of case reports suggests a possible relationship between somatic delusions and affective disorders.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Delusions; Diagnosis, Differential; Electroconvulsive Therapy; Female; Humans; Male; Middle Aged; Mood Disorders; Mouth Diseases; Sleep Wake Disorders; Somatoform Disorders

Rapid reduction of suicidal thoughts is critical for treating suicidal patients. Clinical trials evaluating these treatments require appropriate measurement. Key methodological issues include: 1) the use of single or multi-item assessments, and 2) evaluating whether suicidal ideation measures can track rapid change over time. The current study presents data from two randomized, placebo-controlled, crossover clinical trials evaluating ketamine in individuals with treatment-resistant depression (n = 60). Participants were assessed for suicidal thoughts using the Hamilton Depression Rating Scale (HAM-D), Montgomery-Asberg Depression Rating Scale (MADRS), Beck Depression Inventory (BDI), and Scale for Suicidal Ideation (SSI) at eight time points over three days. Assessments were compared using correlational analyses and effect sizes at 230 min and three days after ketamine infusion. Linear mixed models evaluated change in ideation across all time points. The HAM-D and MADRS suicide items demonstrated correlations of r > .80 with the first five items of the SSI (SSI5). On linear mixed models, an effect for ketamine was found for the HAM-D, MADRS, BDI items, and SSI5 (p < .001), but not for the full SSI (p = .88), which suggests a limited ability to assess change over time in patients with low levels of suicidal thoughts. Taken together, the results suggest that repeated suicidal assessments over minutes to days appear to detect improvement in suicidal thoughts after ketamine infusion compared to placebo. The MADRS suicide item, BDI suicide item, and SSI5 may be particularly sensitive to rapid changes in suicidal thoughts.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Bipolar Disorder; Clozapine; Cross-Over Studies; Depressive Disorder, Major; Female; Humans; Ketamine; Male; Middle Aged; Psychiatric Status Rating Scales; Randomized Controlled Trials as Topic; Statistics as Topic; Suicidal Ideation; Time Factors; Young Adult

Acute interstitial nephritis is a common cause of acute kidney injury. Acute interstitial nephritis is most commonly induced by drug although the cause may also be infective, autoimmune, or idiopathic. Although eosinophilia and eosinophiluria may help identify this disease entity, the gold standard for diagnosis remains renal biopsy. Prompt diagnosis is important because discontinuation of the culprit drugs can reduce further kidney injury. We present a patient with an underlying psychiatric disorder who was subsequently diagnosed with clozapine-induced acute interstitial nephritis. Monitoring of renal function during clozapine therapy is recommended for early recognition of this rare side-effect.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Female; Humans; Kidney; Nephritis, Interstitial; Schizophrenia, Paranoid

Aripiprazole can cause irreversible tardive dystonia in some individuals, and additional intervention is sometimes needed. Here, we report the first case of aripiprazole-induced irreversible tardive dystonia in which complete recovery of motor function was achieved using the antipsychotic drug clozapine.. A 24-year-old man with bipolar disorder was treated with aripiprazole and gradually developed tardive dystonia. Thorough medical and neurological examinations were performed to rule out other possible causes of tardive dystonia. Clozapine was administered when the patient did not improve following long-term withdrawal of aripiprazole or adjuvant medications. Before administration of clozapine, the patient was experiencing severe dystonia as assessed by the Extrapyramidal Symptom Rating Scale. Dystonic symptoms began to improve about 1 month after starting administration of clozapine and were completely resolved 3 months after clozapine administration.. Clinicians should note the risk of aripiprazole-induced tardive dystonia and consider clozapine as an alternative and effective treatment modality in cases of irreversible tardive dystonia, particularly when concomitant treatment of psychotic symptoms is required.

Topics: Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Clozapine; Dyskinesia, Drug-Induced; Humans; Male; Movement Disorders; Neurologic Examination; Psychotic Disorders; Treatment Outcome; Young Adult

Clozapine is the drug of choice for patients with an unsatisfactory response to routine antipsychotic treatment. Side effects such as sedation, weight gain, hypotension and hypersialorrhea are frequently reported whereas clozapine-induced parotitis is a less known complication.. We report the case of a 32-year-old woman with a refractory schizoaffective disorder, bipolar type. The failure to respond to at least two well-conducted antipsychotic trials with flupentixol and risperidone, led clinicians to prescribe clozapine, which was started three years earlier. Since its introduction, clozapine induced sialorrhea, which has been managed until now with anticholinergic medication. Recently, Mrs B. was hospitalized for a new relapse. Once treatment compliance checked (good level of plasmatic dosage), we decided to increase the dose of clozapine from 350 mg/d to 500 mg/d. Twenty days later, Mrs B. exhibited improvement of symptoms but complained of acute bilateral auricular pain and odynophagia. The bilateral and comparative clinical exam displayed a bilateral filling of the retromandibular depression, the painful swelling of the parotid gland, along with ptyalism and a slight inflammatory oedema of the Stenon duct orifice. Mrs B. was apyretic, with physiological constants within the limits of normal values. The biological analyses displayed a discrete inflammatory syndrome (mild hyperleucocytosis and anemia), a negative mumps IgM test and positive mumps IgG test, and a 1050 ng/mL clozapine blood level. Once viral parotitis was ruled out, the involvement of clozapine was evoked. Symptomatic medication was prescribed with per os analgesic (paracetamol) and antiseptic mouthwash (Éludril). Clozapine dosage was lowered to 400 mg/d. A week later, clinical examination confirmed improvement of the medical and psychiatric conditions.. We report the case of a patient who developed a parotitis following clozapine dose adjustment. Clozapine induced parotitis was retained once the infectious and other organic etiologies had been ruled out. Previous cases of clozapine-induced parotitis have already been reported and we have some arguments to suspect this etiology in our case. First, Mrs B. experienced more hypersialorrhea with the increase in clozapine dosage. Second, the anticholinergic medication was interrupted 3 days before the episode of parotitis. Two main pathophysiological hypotheses, immune and inflammatory, have already been proposed to explain clozapine-induced parotitis. In the former, the immunomodulating properties of clozapine may sensitize the mononuclear blood cells, leading to the sialadenitis. The latter hypothesis is the more documented and proposes that clozapine-induced hypersialorrhea may be responsible for a chronic inflammatory state that can lead to the formation of a parotid lithiasis and consequently parotitis. This case report illustrates clozapine induced-parotitis, a poorly known complication of this compound. Clinicians should be aware of its hypersialorrhea and inflammatory consequences in order to better prevent the occurrence of this complication.

Topics: Adult; Bipolar Disorder; Clozapine; Dose-Response Relationship, Drug; Female; Humans; Parotitis; Psychotic Disorders; Recurrence; Sialorrhea

Topics: Antipsychotic Agents; Bipolar Disorder; Clozapine; Combined Modality Therapy; Electroconvulsive Therapy; Female; Humans; Middle Aged; Recurrence; Substance Withdrawal Syndrome

This study investigated the MPV of patients with major psychoses before and after 1year of clozapine exposure. Data were obtained from chart reviews of patients who were initiated on clozapine at the Centre of Addiction and Mental Health (CAMH) in Toronto. 100 patients were eligible for this study; 65 remained on clozapine after 1year. Prior to clozapine initiation, MPV was 10.79±0.91fL and there was no difference in MPV after 1year of clozapine exposure (p=0.777). We found high MPV in patients with schizophrenia and related psychoses, which was unaltered after 1year of clozapine treatment.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Female; Humans; Male; Mean Platelet Volume; Ontario; Psychotic Disorders; Registries; Schizophrenia; Schizophrenia, Paranoid

Clozapine is effective in treatment-refractory bipolar disorder (BD). Guidelines recommend slow titration to prevent seizures, hypotension and myocarditis, but this stance is not supported by comparative data.. To evaluate the safety and effectiveness of rapid clozapine titration in BD.. Analysis of a consecutive cohort of treatment-refractory BD patients with mixed/manic episode admitted on alternate days to one of two units of a psychiatric hospital. On one unit, clozapine was started at 25mg followed by 25-50mg as needed every 6h (maximum=100mg/day) on day 1, followed by increases of 25-100mg/day. On the other unit, clozapine was initiated with 25mg in day 1, followed by increases of 25-50mg/day. The primary outcome was the number of days from starting clozapine until readiness for discharge, adjusted in logistic regression for the number of antipsychotics tried during the hospitalization, psychotropic co-treatments and presence of psychotic features.. Patients subject to rapid (N=44) and standard (N=23) titration were similar in age, gender, smoking status, body mass index, illness severity at baseline and discharge, and highest clozapine dose. Clozapine was discontinued due to hypotension (N=1) and pneumonia (N=1) during rapid titration, and for excessive sedation (N=1) in each titration group. The number of hospital days from starting clozapine until readiness for discharge was 3.8 days shorter in the rapid titration group (12.7±6.3 vs. 16.5±5.8, p=0.0077).. Rapid clozapine titration appeared safe and effective for treatment-refractory BD. The potential for shorter hospital stays justifies prospective trials of this method.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Cohort Studies; Day Care, Medical; Drug Administration Schedule; Female; Hospitalization; Hospitals, Psychiatric; Humans; Length of Stay; Male; Medical Records; Middle Aged; Retrospective Studies; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Clozapine; Colectomy; Humans; Intestinal Obstruction; Male; Piperazines; Quinolones

Prior studies have demonstrated reduced dendritic spine density in the dorsolateral prefrontal cortex (DLPFC) in schizophrenia. However, it remains unclear how generalizable this finding is in schizophrenia and if it is seen in bipolar disorder, a historically distinct psychiatric condition.. To assess whether spine loss is present in the DLPFC of individuals with schizophrenia and individuals with bipolar disorder.. This study used postmortem human brain tissue from individuals with schizophrenia (n=14), individuals with bipolar disorder (n=9), and unaffected control participants (n=19). Tissue samples containing the DLPFC (Brodmann area 46) were Golgi-stained, and basilar dendrites of pyramidal cells in the deep half of layer III were reconstructed.. The number of spines per dendrite, spine density, and dendrite length were compared across groups. We also assessed for the potential effects of clinical and demographic variables on dendritic parameters.. The mean (SD) spine density was significantly reduced (ie, by 10.5%) in individuals with bipolar disorder (0.28 [0.04] spines/μm) compared with control participants (0.31 [0.05] spines/μm) (P=.02). In individuals with schizophrenia, the mean (SD) spine density was also reduced (by 6.5%; 0.29 [0.03] spines/μm) but just missed significance when compared with control participants (P=.06). There was a significant reduction in the mean (SD) number of spines per dendrite in both individuals with schizophrenia (72.8 [24.9] spines per dendrite) and individuals with bipolar disorder (68.9 [12.9] spines per dendrite) compared with controls (92.8 [31.1] spines per dendrite) (individuals with schizophrenia vs controls: 21.6% reduction [P=.003]; individuals with bipolar disorder vs controls: 25.8% reduction [P=.005]). In addition, both individuals with schizophrenia and individuals with bipolar disorder had a reduced mean (SD) dendrite length (246.5 [67.4] and 245.6 [29.8] μm, respectively) compared with controls (301.8 [75.1] μm) (individuals with schizophrenia vs controls: 18.3% reduction [P=.005]; individuals with bipolar disorder vs controls: 18.6% reduction [P=.005]).. Dendritic spine loss in the DLPFC was seen in both individuals with schizophrenia and individuals with bipolar disorder, suggesting that the 2 disorders may share some common pathophysiological features.

Topics: Animals; Atrophy; Bipolar Disorder; Case-Control Studies; Clozapine; Dendritic Spines; Female; Frontal Lobe; Haloperidol; Humans; Male; Middle Aged; Prefrontal Cortex; Pyramidal Cells; Rats; Schizophrenia

To explore the pattern of clozapine use in persons with severe mental illness and in persons with Parkinson's disease and the characteristics associated with early discontinuation in naturalistic conditions.. A historical fixed cohort study of persons newly treated with clozapine was performed on a representative community-based sample of persons affiliated to the French health insurance system (n = 611,393). Treatment for Parkinson's disease was used as a proxy for this condition and lack of such treatment as a proxy for severe mental illness (SMI).. The prevalences of antipsychotic and clozapine use were 4.4% and <0.1% respectively. Of the 237 persons with a new outpatient prescription of clozapine, 25% were prescribed an antiparkinsonian treatment. In persons with SMI, the median duration of the index episode of clozapine treatment was 4.9 months (Interquartile range 1.0-20.5). Longer duration was independently associated with coprescription of anxiolytics or antidepressant. Few new additions of antipsychotics were observed during the clozapine episode.. Efforts have to be made to optimize clozapine treatment in real-world conditions. Considering the high frequency of persons with Parkinson's disease among clozapine users, further studies have to be performed in this population.

Topics: Adult; Affective Disorders, Psychotic; Aged; Anti-Anxiety Agents; Antidepressive Agents; Antiparkinson Agents; Antipsychotic Agents; Bipolar Disorder; Case-Control Studies; Clozapine; Cohort Studies; Female; France; Humans; Male; Middle Aged; Parkinson Disease; Psychotic Disorders; Schizophrenia

Overweight and obesity are common in patients with bipolar disorder. Rates of up to 70% are described in scientific publications. There is sufficient evidence that these conditions are associated with a worse course of the disease (more episodes, higher suicide and hospitality rates, worse response to lithium, somatic comorbidities). Most of the mood stabilisers lead to weight gain. This is also true for clozapine, which can be effective in therapy-refractory courses of bipolar disorder. This case report demonstrates the complexity of the treatment of bipolar disorder. A young patient in depressive stupor following a severe suicide attempt after 5 months of hospital treatment was sent to our department to perform ECT. This was not possible because of the severity of his injuries. We were able to cure the acute condition and interrupt the course of rapid cycling with a combination of clomipramine, lithium and clozapine. A stable course of four years under this medication and psychoeducation has been achieved. In this period the patient was able to lower his body mass index from 38 to 26 because of a consequent lifestyle modification.

Topics: Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Clozapine; Humans; Male; Obesity; Overweight; Suicide, Attempted; Young Adult

Like mood stabilizers, most second-generation antipsychotics are widely used to treat patients with bipolar disorder, yet their safety is still a concern. This study explored the association between antipsychotics and mood stabilizers and the risk of pneumonia, and it provides evidence-based information for clinical practice.. In a nationwide cohort of bipolar patients (ICD-9 codes 296.0 to 296.16, 296.4 to 296.81, and 296.89) derived from the National Health Insurance Research Database in Taiwan, who were admitted between July 1, 1998, and December 31, 2006 (N = 9,999), we identified 571 patients who developed pneumonia (ICD-9 codes 480 to 486 and 507) requiring hospitalization defined as cases. On the basis of risk-set sampling in a 1:4 ratio, 2,277 matched controls were selected from the same cohort. We used conditional logistic regression to assess the association between drug exposure and pneumonia and sensitivity analyses to validate the association.. Current use of several antipsychotics separately, including olanzapine (adjusted risk ratio [RR] = 2.97, P < .001), clozapine (RR = 2.59, P < .01), and haloperidol (RR = 3.68, P < .001), is associated with a dose-dependent increase in the risk of pneumonia. Interestingly, lithium has a dose-dependent protective effect from pneumonia. Among certain drug combinations, olanzapine plus carbamazepine had the highest risk (RR = 11.88, P < .01), followed by clozapine plus valproic acid (RR = 4.80, P < .001).. Several antipsychotics, but not mood stabilizers, were associated with the risk of pneumonia, which deserves our concern regarding patient safety. Some of the combinations of therapy resulted in synergy of risk.

Topics: Adolescent; Adult; Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Carbamazepine; Case-Control Studies; Clozapine; Cohort Studies; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Evidence-Based Medicine; Female; Hospitalization; Humans; Lithium Carbonate; Male; Middle Aged; Multivariate Analysis; Olanzapine; Pneumonia; Propensity Score; Risk Factors; Taiwan; Valproic Acid; Young Adult

Topics: Adult; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Clozapine; Drug Therapy, Combination; Humans; Male; Piperazines; Quinolones; Tourette Syndrome

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Resistance; Drug Substitution; Drug Therapy, Combination; Humans; Male; Middle Aged; Obsessive-Compulsive Disorder; Quetiapine Fumarate; Recurrence; Sertraline

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Aspirin; Bipolar Disorder; Clozapine; Dose-Response Relationship, Drug; Drug Interactions; Humans; Male; Valproic Acid

The Schizophrenia Psychiatric Genome-Wide Association Study Consortium (PGC) highlighted 81 single-nucleotide polymorphisms (SNPs) with moderate evidence for association to schizophrenia. After follow-up in independent samples, seven loci attained genome-wide significance (GWS), but multi-locus tests suggested some SNPs that did not do so represented true associations. We tested 78 of the 81 SNPs in 2640 individuals with a clinical diagnosis of schizophrenia attending a clozapine clinic (CLOZUK), 2504 cases with a research diagnosis of bipolar disorder, and 2878 controls. In CLOZUK, we obtained significant replication to the PGC-associated allele for no fewer than 37 (47%) of the SNPs, including many prior GWS major histocompatibility complex (MHC) SNPs as well as 3/6 non-MHC SNPs for which we had data that were reported as GWS by the PGC. After combining the new schizophrenia data with those of the PGC, variants at three loci (ITIH3/4, CACNA1C and SDCCAG8) that had not previously been GWS in schizophrenia attained that level of support. In bipolar disorder, we also obtained significant evidence for association for 21% of the alleles that had been associated with schizophrenia in the PGC. Our study independently confirms association to three loci previously reported to be GWS in schizophrenia, and identifies the first GWS evidence in schizophrenia for a further three loci. Given the number of independent replications and the power of our sample, we estimate 98% (confidence interval (CI) 78-100%) of the original set of 78 SNPs represent true associations. We also provide strong evidence for overlap in genetic risk between schizophrenia and bipolar disorder.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Alpha-Globulins; Antipsychotic Agents; Autoantigens; Bipolar Disorder; Calcium Channels, L-Type; Clozapine; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Major Histocompatibility Complex; Male; Middle Aged; Neoplasm Proteins; Polymorphism, Single Nucleotide; Schizophrenia; White People; Young Adult

A 41-year-old man with comorbid binge-eating disorder, severe obesity, and bipolar disorder since the age of 20 years, resistant to drug and psychotherapy combinations, worsened progressively. Relentless weight gain forced him to immobility and dependence on others. He was hospitalized for a mixed-mood episode with anxiety, mystical delusions, and auditory hallucinations. To overcome treatment resistance, we suggested electroconvulsive therapy. After 1 electroconvulsive therapy cycle, psychological symptoms promptly improved. He received clozapine and lithium. After 2 years, he reached normal weight and fair psychopathological compensation.

Topics: Adult; Affect; Antipsychotic Agents; Anxiety; Binge-Eating Disorder; Bipolar Disorder; Clozapine; Delusions; Disease Progression; Drug Resistance; Electroconvulsive Therapy; Hallucinations; Humans; Male; Obesity, Morbid

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for Parkinson's disease, but can lead to adverse effects including psychiatric disturbance. Little is known about the risk factors and treatment options for such effects. Here, we describe a patient who reproducibly developed stimulation-induced hypomania when using ventrally located electrodes and responded well to pharmacological intervention while leaving the stimulation parameters unchanged to preserve motor benefits. In spite of clinical remission, [¹⁵O]-positron-emission-tomography (PET) demonstrated activation patterns similar to those reported during mania. This case, therefore, highlights an important treatment option of adverse effects of DBS, but also points toward the need for investigations of its risk factors and their underlying neurobiological mechanisms.

Topics: Antimanic Agents; Bipolar Disorder; Clozapine; Deep Brain Stimulation; Humans; Male; Middle Aged; Parkinson Disease; Treatment Outcome; Valproic Acid

To present a case of clozapine-induced peripheral and pleural fluid eosinophilia (PFE).. A 28-year-old man who was taking clozapine for bipolar disorder presented with a 2-week history of increasing shortness of breath. A large right-sided pleural effusion was identified, and eosinophilia was noted in peripheral and pleural fluid. An extensive workup ruled out other etiologies of PFE, and an objective causality assessment revealed that an adverse reaction to clozapine was probable. Clozapine was discontinued and the patient had complete resolution of symptoms, peripheral eosinophilia, and pleural effusion.. Drug-induced pleural disease is uncommon. Nearly 30 drugs have been implicated as causation of pleural disease. Much less common is PFE, with only 8 drugs implicated since 2004. Clozapine is a second-generation antipsychotic approved for treatment of resistant schizophrenia. It is often also used to treat bipolar disorder. Common adverse effects include tachycardia, somnolence, weight gain, and sialorrhea. Uncommon adverse reactions include pancreatitis and agranulocytosis. Through 2009, 11 cases of clozapine-induced pleural effusion, with and without polyserositis, have been reported; however, pleural fluid studies to demonstrate eosinophilia have not been done.. To our knowledge, this is the first documented report of clozapine-induced peripheral eosinophilia and PFE. Clinicians should consider clozapine as a possible cause of these reactions.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Eosinophilia; Humans; Male; Pleural Diseases

Clozapine remains the drug of choice for treatment-resistant schizophrenia but the evidence for its use in severe bipolar disorder (BD) remains sparse.. A pharmaco-epidemiologic database study was carried out in Denmark, investigating the effectiveness of clozapine in BD patients (without a schizophrenia-spectrum disorder), between 1996 and 2007, using a two-year mirror-image design.. A total of 21473 patients with a lifetime diagnosis of International Classification of Diseases-10 (ICD-10) BD were identified, of which only 326 (1.5%) were treated with clozapine and were included in the mirror-image analysis. The mean follow-up time was 544 ± 280 days, the mean clozapine dose was 307.4 mg [95% confidence interval (CI): 287.9-328.2], and 39.3% were male. During clozapine treatment, the mean number of bed-days decreased from 177.8 (95% CI: 149.4-211.6) to 34.6 (95% CI: 24.8-48.2) (p < 0.001). The mean number of admissions was reduced from 3.2 (95% CI: 2.9-3.7) to 2.0 (95% CI: 1.6-2.4) (p < 0.001). Overall, 240 patients (73.6%) had reduced bed-days and 130 (39.9%) were not admitted while treated with clozapine. Moreover, the number of psychotropic co-medications was reduced from 4.5 defined daily doses (DDD) (25-75 percentiles: 2.4-8.2) to 3.9 DDD (25-75 percentiles: 2.4-6.1) (p = 0.045). Somatic hospital visits for intentional self-harm/overdose reduced significantly from 8.3% to 3.1% (p = 0.004). However, non-psychotropic co-medication use for medical conditions did not increase; 0.7 DDD (25-75 percentiles: 0.0-2.9) to 0.8 DDD (25-75 percentiles: 0.1-2.89) (p = 0.3).. Clozapine use for BD was associated with a significant and clinically relevant reduction in the number of bed-days, psychiatric admissions, psychotropic co-medications, and hospital contact for self-harm/overdose, without increased medical treatments. Clozapine seems to be an appropriate choice for treatment-resistant BD and should be investigated in randomized controlled trials.

Topics: Adult; Aged; Antipsychotic Agents; Bipolar Disorder; Clozapine; Denmark; Female; Humans; Longitudinal Studies; Male; Middle Aged; Outpatients; Retrospective Studies; Treatment Outcome

Topics: Affect; Antipsychotic Agents; Bipolar Disorder; Clozapine; Female; Humans; Meningeal Neoplasms; Meningioma; Middle Aged; Schizophrenia

Topics: Aged; Bipolar Disorder; Carbamazepine; Clozapine; Deep Brain Stimulation; Female; Humans; Male; Middle Aged; Parkinson Disease

To examine (1) arrest outcomes for adults with schizophrenia and bipolar disorder who were treated with first-generation antipsychotics (FGAs) or second-generation atypical antipsychotics (SGAs) and (2) the interaction between medication class and outpatient services in a Florida Medicaid program.. In a secondary data analysis, Florida Medicaid data covering the period from July 1, 2002, to March 31, 2008, were used to identify persons diagnosed with schizophrenia, schizoaffective disorder, and bipolar disorder and to examine antipsychotic medication episodes lasting at least 60 days. There were 93,999 medication episodes in the population examined (N = 36,519). Medication episodes were coded as (1) SGA-aripiprazole, clozapine, olanzapine, paliperidone, quetiapine, risperidone, risperidone long-acting therapy, or ziprasidone; or (2) FGA-any other antipsychotic medication. Outpatient services were defined as the proportion of 30-day periods of each medication episode with at least 1 behavioral health visit. Survival analyses were used to analyze the data, and they were adjusted for the baseline propensity for receiving an SGA.. Second-generation antipsychotic episodes were not associated with reduced arrests compared to FGA episodes; however, the interaction between outpatient services and SGA episodes was significant (hazard ratio [HR] = 0.68; 95% CI, 0.50-0.93; P = .02) such that an SGA episode with an outpatient visit during at least 80% of every 30-day period of the episode was associated with reduced arrests compared to SGA episodes with fewer outpatient services. There was no significant effect for concurrent FGA episodes and outpatient treatment (HR = 0.81; 95% CI, 0.60-1.10; P = .18). Substance use, poor refill compliance, and prior arrest increased risk of subsequent arrest.. The interaction between outpatient visits and treatment with SGAs was significantly associated with reduced arrests. These findings indicate the importance of concurrent antipsychotic medications and outpatient services to affect arrest outcomes for adults with schizophrenia and bipolar disorder.

Topics: Adolescent; Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Clozapine; Crime; Delayed-Action Preparations; Dibenzothiazepines; Female; Florida; Humans; Isoxazoles; Male; Medicaid; Middle Aged; Olanzapine; Outpatients; Paliperidone Palmitate; Piperazines; Propensity Score; Pyrimidines; Quetiapine Fumarate; Quinolones; Risk Factors; Risperidone; Schizophrenia; Treatment Outcome; United States; Young Adult

To describe a case of clozapine-induced sialorrhea alleviated by immediate-release oxybutynin.. A 53-year-old female with schizoaffective disorder-bipolar type was admitted to a psychiatric unit and initiated on clozapine. During titration to a dose of 300 mg daily and despite taking concomitant oral benztropine 1 mg twice daily, the patient began to experience mild sialorrhea. The sialorrhea became profuse when the clozapine dose reached 400 mg daily, and the patient was routinely seen with a saliva-soaked shirt. Additionally, she had become self-conscious and wanted to stop clozapine therapy. Immediate-release oxybutynin 5 mg daily was started, resulting in significant reduction of the sialorrhea within 24 hours. The patient was discharged on clozapine 300 mg daily, risperidone 6 mg at bedtime, immediate-release oxybutynin 5 mg twice daily, and oral benztropine 1.5 mg daily, with only mild sialorrhea.. It is unknown why clozapine induces sialorrhea. One speculation is that clozapine interrupts muscarinic receptor homeostasis. Immediate-release oxybutynin is an anticholinergic agent with high affinity for salivary gland M₃ receptors that may have restored muscarinic receptor imbalance in our patient. N-Desethyl-oxybutynin, an active metabolite of oxybutynin, is largely responsible for oxybutynin's anticholinergic activity. The activity of oxybutynin and its metabolite may result in dry mouth in over 80% of patients taking the immediate-release formulation, while producing dry mouth in only 40% and 7.5% of patients taking the extended-release and topical formulations, respectively.. To our knowledge, this is the first report of immediate-release oxybutynin successfully reducing clozapine-induced sialorrhea. If oxybutynin is considered for this indication, use of the immediate-release formulation seems prudent. Additional data, including randomized controlled trials, are needed to confirm whether immediate-release oxybutynin has a significant role in the management of this stigmatizing adverse effect.

Topics: Antipsychotic Agents; Bipolar Disorder; Clozapine; Female; Humans; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Psychotic Disorders; Sialorrhea

Although numerous reports suggest that different atypical antipsychotics can exacerbate or induce (de novo) obsessive-compulsive symptoms, there is no report of the development of ego-dystonic, suicidal obsessions during treatment with these medications. Here, the authors report the first case of clozapine-induced suicidal obsessions.. The authors report a case of a patient diagnosed with bipolar disorder and who developed suicidal obsessions in the weeks after the dose of clozapine was increased from 150 mg/day to 300 mg/day.. Symptoms quickly resolved after the treatment with clozapine was changed to the treatment with quetiapine and sodium valproate. Suicidal obsessions decreased promptly, within a few days, and disappeared completely when the dose of clozapine was 100 mg/day, quetiapine 600 mg/day, and sodium valproate 900 mg/day, 16 days after the initiation of changes in the medications.. The case report emphasizes the crucial need of differentiation between genuine suicidal desires and ego-dystonic suicidal obsessions. The authors suggest that in similar cases a change in antipsychotic medications to those with stronger antidopaminergic properties and lower 5HT2 receptor affinity should be considered, but also assume that the use of sodium valproate in treatment of obsessive-compulsive symptoms deserves further study.

Topics: Antipsychotic Agents; Bipolar Disorder; Clozapine; Humans; Male; Middle Aged; Obsessive Behavior; Suicidal Ideation

A complete atrioventricular block (CAVB) can be a lethal complication when it is not treated directly with isoprenaline and pacemaker therapy. The overall incidence of CAVB varies between 4 to 8 per cent with a mortality OR of 3.2 within 30 days if untreated. Main causes of CAVB are inferior myocardial infarction, congenital AV node malformation, mitral valve insufficiency and valve surgery, metabolic disorders and intoxications. The authors describe a case with a CAVB due to lithium-clozapine therapy and relapsing multiple sclerosis.

Topics: Antipsychotic Agents; Atrioventricular Block; Bipolar Disorder; Cardiotonic Agents; Clozapine; Female; Humans; Isoproterenol; Lithium; Middle Aged; Multiple Sclerosis; Pacemaker, Artificial; Recurrence

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Clozapine; Dyskinesia, Drug-Induced; Humans; Lithium Chloride; Male

Topics: Analgesics; Antipsychotic Agents; Bipolar Disorder; Clozapine; Exanthema; Humans; Lamotrigine; Male; Triazines; Young Adult

The challenges in the management of treatment-resistant rapid-cycling bipolar disorder are multifaceted and represent a significant burden to the patient. There is a need for more exploration into the potential utility of various combination therapies in the setting of severe affective states. A 52-year-old woman with a history of severe treatment-resistant rapid-cycling bipolar affective disorder (BPAD) was hospitalized for the treatment of a severe mixed episode. The introduction of lamotrigine and clozapine in combination proved remarkably effective and well tolerated in both the acute management and in subsequent maintenance. The patient has remained asymptomatic during the 5-year follow-up without any further mood disturbance. Lamotrigine and clozapine are among the less-prescribed agents for BPAD and there is as yet little research into their use in combination. It is possible that these agents have complementary modes of action on various facets of the affective pathology, resulting in superior mood stabilization in this patient.

Topics: Antipsychotic Agents; Bipolar Disorder; Calcium Channel Blockers; Clozapine; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Lamotrigine; Middle Aged; Severity of Illness Index; Time Factors; Treatment Outcome; Triazines

Malignant neuroleptic syndrome (MNS) is a serious and potentially fatal side-effect of neuroleptic treatment. Beside antipsychotic drugs, other psychotropic drugs such as antidepressants and lithium carbonate can cause this life threatening side-effect. Underlying mechanism of this side-effect is still unknown and debated. So far some risk factors have been identified, with clinical observations and recent pharmacogenetic research suggesting (with inconsistent findings) correlation between genetic mechanisms and predisposition to MNS. Polymorphisms of CYP2D6 enzyme through which most psychotropic drugs are metabolized and TaqIA DRD2 which is target for antipsychotic drugs could be the link between pharmacogenetic factors and potential for development of MNS. In this paper we present two case reports with clinical presentation of three consecutive MNS. One patient developed MNS while he was taking combination of drugs: first time haloperidol, promazine and fluphenazine, second time fluphenazine and perazine and third time clozapine, promazine and valproic acid consecutively. The other patient developed MNS while taking following combination of drugs: first time haloperidol and lithium carbonate, second time risperidone and third time clozapine consecutively. Pharmacogenetic analysis for CYP2D6 and TaqI A DRD2 polymorphisms for both patients was done. Genotypisation of CYP2D6*1*3*4*5*6 in both patients showed no evidence of poor metabolizer phenotype. On the other hand, first patient was heterozygous for CYP2D6*4 (genotype *1/*4). CYP2D6 polymorphisms could have clinical significance because may lead to toxicity and unwanted side-effects in standard usual antipsychotic dose ranges. Analysis Taql A DRD2 polymorphism for first patient showed that he is heterozygous for A1 allele (genotype A1A2) which is commonly associated with predisposition to MNS. According to our literature three consecutive MNS are rarely described, and incidence of MNS generally is too low to perform clinical research. Many patophysiological mechanisms may probably underlie this complex and potentially fatal syndrome, still unknown etiology. But, genetic mechanisms could be significant. Further pharmacogenetic research, findings and analysis in patients who develop single or repeated MNS are strongly recommended. In long term, pharmacogenetic analysis, implemented in daily clinical practice, could help in prevention of this extremely serious side-effect.

Topics: Adult; Alleles; Antipsychotic Agents; Bipolar Disorder; Clozapine; Cytochrome P-450 CYP2D6; Dibenzothiazepines; Drug Therapy, Combination; Fluphenazine; Genetic Carrier Screening; Genotype; Haloperidol; Humans; Lithium Carbonate; Male; Neuroleptic Malignant Syndrome; Perazine; Polymorphism, Genetic; Psychotic Disorders; Quetiapine Fumarate; Receptors, Dopamine D2; Recurrence; Risperidone

Idiosyncratic reactions are serious, unpredicted adverse effects of antiepileptic drugs which are in use in psychiatry as mood stabilizers. Severe idiosyncratic reactions can manifest as systemic symptoms or Dress syndrome clinically manifested with increased body temperature, peripheral lymphadenopathy and potential one or multiple organ failure. We present a 36 years old patient, who was hospitalized for the first time in our hospital after he attempted suicide by hanging. Patient was diagnosed as Bipolar affective disorder, current episode depressive with psychotic features and high suicidal risk. At the time of admission he was taking olanzapine and venlafaxine. Psychopharmacs were cross titrated to clozapine, valproic acid and lamotrigine. Two weeks later, patient's mood was stabilized but his somatic status worsened dramatically. He was forwarded to Clinic for Infective Diseases where he was diagnosed with severe sepsis. Dress syndrome, although initially suspected was not verified, but has to be taken into consideration in each patient prescribed with antiepileptic drugs.

Topics: Adult; Anticonvulsants; Antipsychotic Agents; Bipolar Disorder; Clozapine; Diagnosis, Differential; Drug Therapy, Combination; Humans; Lamotrigine; Male; Pericarditis; Respiratory Insufficiency; Systemic Inflammatory Response Syndrome; Triazines; Valproic Acid

Topics: Age of Onset; Aged; Antipsychotic Agents; Bipolar Disorder; Brain; Clozapine; Humans; Magnetic Resonance Imaging; Male; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Child Development; Clozapine; Female; Humans; Infant, Newborn; Lithium Compounds; Obstetric Labor Complications; Obstetrics; Physician's Role; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prenatal Care; Psychiatry

High prevalence of metabolic syndrome (MS) and related metabolic disturbances in patients with schizophrenia and bipolar affective disorder have been in main focus of interest in recent years since the introduction of second-generation antipsychotics. This study aims to examine these questions: 1) Is there a relation between antipsychotic treatment and MS prevalence? 2) Which antipsychotic users have higher MS prevalence? 3) Do patients on antipsychotic polytherapy have higher rates of MS than patients on antipsychotic monotherapy? 4) Which metabolic parameters are considerably disturbed on which antipsychotic users?. 242 Patients with schizophrenia, schizoaffective disorder and bipolar disorder without any other psychiatric comorbidity according to DSM-IV and using the same antipsychotic(s) and/or mood stabilizers at least for the last 6 months included to the final assessment.. The sample was divided into 7 drug groups. The MS prevalence was highest in the combined antipsychotic (AA) group (48.1%) according to ATP III criteria. According to IDF criteria clozapine (C) group had the highest MS prevalence (74%).. When metabolic parameters evaluated overall, metabolic risk with antipsychotics is found to be highest in clozapine group, followed by combined AP group. Olanzapine and risperidone have intermediate risk while zuclopentixole has lowest.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Chi-Square Distribution; Clopenthixol; Clozapine; Cross-Sectional Studies; Female; Humans; Male; Metabolic Syndrome; Middle Aged; Olanzapine; Prevalence; Risk Assessment; Risk Factors; Risperidone; Schizophrenia; Turkey; Young Adult

Asenapine is a novel psychopharmacologic agent under development for the treatment of schizophrenia and bipolar disorder. We determined and compared the human receptor binding affinities and functional characteristics of asenapine and several antipsychotic drugs. Compounds were tested under comparable assay conditions using cloned human receptors. In comparison with the antipsychotics, asenapine showed high affinity and a different rank order of binding affinities (pKi) for serotonin receptors (5-HT1A [8.6], 5-HT1B [8.4], 5-HT2A [10.2], 5-HT2B [9.8], 5-HT2C [10.5], 5-HT5 [8.8], 5-HT6 [9.6] and 5-HT7 [9.9]), adrenoceptors (alpha1 [8.9], alpha2A [8.9], alpha2B [9.5] and alpha2C [8.9]), dopamine receptors (D1 [8.9], D2 [8.9], D3 [9.4] and D4 [9.0]) and histamine receptors (H1 [9.0] and H2 [8.2]). It had much lower affinity (pKi

Topics: Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Cloning, Molecular; Clozapine; Dibenzocycloheptenes; Heterocyclic Compounds, 4 or More Rings; Histamine Release; Humans; Inhibitory Concentration 50; Molecular Structure; Olanzapine; Psychotropic Drugs; Radioligand Assay; Receptors, Adrenergic; Receptors, Dopamine; Receptors, Dopamine D2; Receptors, Muscarinic; Receptors, Serotonin; Schizophrenia; Substrate Specificity

Topics: Adult; Bipolar Disorder; Clozapine; Follow-Up Studies; Humans; Male; Retrospective Studies; Time Factors; Treatment Outcome

The international consensus conferences concerning schizophrenia and the authorization to market (French AMM) reserve this molecule for the treatment of resistant schizophrenia. Resistant schizophrenia, as defined by the marketing authorisation, corresponds to the absence of improvement in a patient's state despite two successive treatments with antipsychotics, or at least an atypical drug at an adequate dose for a sufficient length of time.. Our investigation compares hospital practices to the marketing authorisation and guidelines regarding resistant schizophrenia.. All clozapine prescriptions delivered by the pharmacists at the Charles Perrens Hospital were recorded during the month of February 2007. General information concerning the patient and his or her treatment were collected, based on different support teams set up in the hospital. First, the hospital administrative program was used to manage the patients. Then, the treatment establishment form, filled out by psychiatrists before the beginning of the treatment, listed all previous treatments given to the patient and indicated any inefficacy or intolerances to prior treatments. Then, a program monitored the delivery of this molecule and finally, prescriptions were recorded to describe present treatment.. Our study consisted of 61 patients, mostly male subjects averaging 40 years of age, single, who had been under psychiatric care for about 15 years, and were, for the most part, professionally inactive. Clozapine was prescribed for schizophrenic (90%) and for bipolar patients (10%). Clozapine was also often prescribed for patients whose illness had not improved with prior treatments. The average dose was of 489 mg/day for patients considered stable, i.e., those for whom clozapine was prescribed with efficacy observed for a sufficiently long time. It was associated in 88% of all cases with another psychotropic: anxiolytic (68% of cases), normothymic (26% of cases), antidepressant (16%) and antipsychotic (42%).. In practice, clozapine seems to be efficient in bipolar disorders, although the marketing authorisation does not envisage this indication. It is never prescribed first, as some recommendations indicate, even though the follow-up of certain treatments does not always seem adequate to appreciate their non-effectiveness. Seldom prescribed alone, clozapine is often associated with another antipsychotic, a practice not favoured by many experts. Our investigation thus confirms the increase in co-prescriptions, particularly in hospital, for patients who have not improved with clozapine alone, a case that is barely taken into consideration in consensus conferences. With the lack of innovative molecules, psychiatrists are prompted to associate several antipsychotics, with the risk of supporting iatrogenic medication, whereas the experts reserve the relevance of such associations because of a lack of randomised studies.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Drug Resistance; Drug Therapy, Combination; France; Humans; Male; Product Surveillance, Postmarketing; Psychotropic Drugs; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Altered glutamate transmission has been found in the medial temporal lobe in severe psychiatric illnesses, including major depressive disorder (MDD) and bipolar disorder (BD). The vesicular glutamate transporters (VGLUTs) have a pivotal role in presynaptic release of glutamate into the synaptic cleft. We investigated this presynaptic marker in major psychiatric illness by measuring transcript expression of the VGLUTs in the medial temporal lobe.. The study sample comprised four groups of 13 subjects with MDD, BD, or schizophrenia (SCZ), and a comparison group from the Stanley Foundation Neuropathology Consortium. In situ hybridization was performed to quantify messenger RNA (mRNA) expression of VGLUT 1, 2, and 3 in medial temporal lobe structures. We also examined the same areas of rats treated with antidepressants, a mood stabilizer, and antipsychotics to assess the effects of these medications on VGLUT mRNA expression.. We found decreased VGLUT1 mRNA expression in both MDD and BD in the entorhinal cortex (ERC), decreased VGLUT2 mRNA expression in MDD in the middle temporal gyrus, and increased VGLUT2 mRNA expression in SCZ in the inferior temporal gyrus (ITG). We also found a negative correlation between age and VGLUT1 mRNA expression in BD in the ERC and ITG. We did not find any changes in VGLUT mRNA expression in the hippocampus in any diagnostic group. We found decreased VGLUT1 mRNA expression in rats treated with haloperidol in the temporal cortex.. These data indicate region-specific alterations of presynaptic glutamate innervation in the medial temporal lobe in the mood disorders.

Topics: Adult; Aged; Analysis of Variance; Animals; Antidepressive Agents, Tricyclic; Antipsychotic Agents; Bipolar Disorder; Clozapine; Depressive Disorder, Major; Female; Gene Expression Regulation; Haloperidol; Hippocampus; Humans; Imipramine; Male; Mesothelin; Middle Aged; Rats; Rats, Sprague-Dawley; RNA, Messenger; Schizophrenia; Statistics as Topic; Temporal Lobe; Vesicular Glutamate Transport Proteins

Leptin dysregulation has been implicated in the body weight gain and metabolic dysfunction observed with the second generation antipsychotic drugs (SGAD) olanzapine and clozapine.. This study quantified the frequency of subjects with abnormal correlation between leptin and the body mass index controlling for gender (defined as being out of the upper or lower 95% confidence interval in the regression line when combining each group with the drug-free subjects) after prolonged treatment with olanzapine (n=126), clozapine (n=62), first generation antiypsychotics (n=91), other SGAD (n=22), other psychotropic drugs (n=65) and drug-free subjects (n=229).. None of the analysis was significant (p>0.05). In fact, in 17 out of 20 comparisons, the drug-free group had numerically higher frequencies of outliers than the corresponding treatment group. There were 28 outliers (4.7% of the total sample). In agreement with previous studies, cross-sectional analysis did not report gross alterations in serum leptin levels during olanzapine or clozapine administration.. Longitudinal studies should focus on leptin regulation early on treatment, on the frequency of abnormal leptin receptor sensitivity and/or specific polymorphisms in the leptin allele and on several confounding factors in order to design personalized preventive and therapeutic measures.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Body Mass Index; Body Weight; Clozapine; Cross-Sectional Studies; Female; Humans; Insulin Resistance; Leptin; Male; Mental Disorders; Middle Aged; Olanzapine; Outliers, DRG; Receptors, Leptin; Schizophrenia; Sex Factors; Weight Gain

Topics: Antipsychotic Agents; Bipolar Disorder; Clozapine; Humans; Male; Middle Aged; Parkinson Disease

To determine the incidence, characteristics, and predictors of clozapine-induced fever in a sample of patients in a local psychiatric unit.. A retrospective review of case notes of 227 inpatients newly started on clozapine from March 2003 to December 2006 was conducted. Demographic characteristics, presence of fever, investigations carried out, fever characteristics, and complications of fever were recorded and analyzed. Patients with clozapine-induced fever were compared with their fever-free counterparts on demographic and clinical factors. Multivariate logistic regression was performed to identify predictors of clozapine-induced fever.. Thirty-one out of 227 patients (13.7%) developed clozapine-induced fever. The means for day of onset of clozapine-induced fever after clozapine initiation and duration of fever were 13.7 and 4.7 days, respectively. The mean highest body temperature was 38.8 degrees C. Fever resolved within 48 hours after clozapine discontinuation in 79% of the patients with clozapine-induced fever. One out of 7 patients (14.3%) had fever on re-challenge. Clozapine-induced fever was associated with rate of titration more than 50 mg/wk (OR 18.9; 95% CI 5.3 to 66.7; P < 0.01), concomitant use of valproate (OR 3.6; 95% CI 1.5 to 8.9; P = 0.01), and presence of physical illnesses (OR 3.2; 95% CI 1.2 to 8.3; P = 0.02).. Clozapine-induced fever is common. Temporary withdrawal of clozapine may result in resolution of fever, and clozapine re-challenge may be considered after fever subsides. Slower rate of clozapine titration may be helpful in patients with underlying physical illness and concomitant valproate treatment.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Antipsychotic Agents; Bipolar Disorder; Clozapine; Cross-Sectional Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Fever; Hong Kong; Humans; Incidence; Male; Middle Aged; Psychiatric Department, Hospital; Psychotic Disorders; Retrospective Studies; Risk Factors; Schizophrenia; Valproic Acid; Young Adult

To examine clinical characteristics and treatment responses of patients presenting with delirium and mania to a psychiatric inpatient unit.. Chart review of 16 cases admitted to McLean Hospital with delirium and mania was conducted. We examined the demographics, psychiatric symptoms, clinical course, and response to treatment with medications and electroconvulsive therapy (ECT).. Patients with delirium and mania had negative medical and neurological work-ups and were more likely to be younger, female and with a prior diagnosis of bipolar disorder. Sudden onset of symptoms, incontinence/inappropriate toiletting, and denudativeness are distinctive features of the syndrome. Consistent and significant benefit was seen with ECT. In many cases, high dose benzodiazepines were helpful. In a small number of cases, clozapine was also beneficial but this effect took an average of four weeks to be seen, while atypical antipsychotics, lithium and valproate produced variable results and took an average of three and a half weeks to work, if at all. Typical antipsychotics and anticholinergic drugs led to clinical worsening.. Most patients were on more than one medication and hence treatment responses cannot be definitively ascribed to a specific intervention. Studies of larger groups of such patients in different clinical settings need to be done to confirm our observations.. Delirious mania is a severe psychiatric syndrome which can be accurately recognized and effectively treated. The definitive treatment for this condition is ECT. In cases where ECT is not available, high dose benzodiazepines should be used. Clozapine, quetiapine, lithium and valproate cannot be considered first-line treatments and these medications take an unacceptably long time to work even when helpful; typical antipsychotics and anticholinergic drugs should be avoided.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Combined Modality Therapy; Delirium; Electroconvulsive Therapy; Humans; Middle Aged; Retrospective Studies; Severity of Illness Index

There are few independent studies comparing atypical or second-generation antipsychotics (SGAs).. To compare the patterns of use and discontinuation of commonly used SGAs.. Retrospective review of 11,250 case records (2002-2005) of all mental health care contacts in a discrete geographical setting in Scotland. Patterns of use, mean dose, psychotropic co-prescription, duration of treatment, discontinuation rates, and admission rates were examined for amisulpride, clozapine, olanzapine, quetiapine, and risperidone.. Clozapine had a significantly lower discontinuation rate in individuals with schizophrenia, compared to the other 4 SGAs. Off-license prescribing and polypharmacy were common.. SGAs are variously used for schizophrenia and mood disorder and have heterogeneous outcomes, with clozapine being most effective in this study. Independent observational studies such as this complement randomized controlled trials.

Topics: Adult; Aged; Amisulpride; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clozapine; Dibenzothiazepines; Drug Administration Schedule; Female; Humans; Male; Medical Records; Middle Aged; Olanzapine; Patient Admission; Polypharmacy; Practice Patterns, Physicians'; Quetiapine Fumarate; Research Design; Retrospective Studies; Risperidone; Schizophrenia; Scotland; Sulpiride

Although a highly effective medication, the usage of clozapine is limited mostly by its 2.7% incidence of neutropenia. It is often a treatment of last resort for patients with severe psychiatric illnesses, and therefore often the only medication to which a patient has responded. There has thus been a great deal of interest in ways to continue the medication in spite of emergent blood dyscrasias. There have been several reports documenting the successful continuation of clozapine in spite of neutropenia by adding granulocyte colony-stimulating factors such as filgrastim. This strategy was unsuccessful for a 63-year-old man, resulting in severe, prolonged agranulocytosis. Although a promising strategy for such refractory patients, its inherent dangers should not be underestimated.

Topics: Agranulocytosis; Antipsychotic Agents; Bipolar Disorder; Clozapine; Drug Administration Schedule; Drug Resistance; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Injections, Subcutaneous; Male; Middle Aged; Recombinant Proteins; Recurrence; Retreatment

Topics: Agranulocytosis; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Clozapine; Drug Approval; Drug Resistance; Drug Therapy, Combination; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Informed Consent; Legal Guardians; Recombinant Proteins

To determine whether the coprescribing of two or more antipsychotics, a relatively frequent practice with little data to support its safety and efficacy, is associated with an increased prevalence of metabolic syndrome.. 364 newly admitted adults treated with second-generation antipsychotics underwent assessments evaluating antipsychotic polytherapy, and of the presence of metabolic syndrome and triglycerides/high-density lipoprotein cholesterol ratio>3.5 (TG/HDL), a sensitive marker of insulin resistance. The correlates of antipsychotic polytherapy and associations with metabolic syndrome and TG/HDL were determined by univariate comparisons and multiple logistic regression analyses.. Antipsychotic polytherapy was present in 70 patients (19.2%) and was significantly more likely in patients with schizophrenia and those treated with clozapine, quetiapine or ziprasidone (p<0.0001). Compared with antipsychotic monotherapy, polytherapy was associated with elevated rates of metabolic syndrome (50.0% vs. 34.3%, p=0.015) and TG/HDL (50.7% vs. 35.0%, p=0.016). However, in logistic regression analyses, metabolic syndrome was significantly associated with higher body mass index (BMI), older age, a diagnosis of bipolar disorder or schizophrenia, and cotreatment with a first-generation antipsychotic (r(2): 0.25, p<0.0001). The TG/HDL marker of insulin resistance was associated with higher BMI, male sex, Caucasian race and absence of aripiprazole treatment (r(2): 0.14, p<0.0001). Antipsychotic polypharmacy dropped out of both multivariate models.. Compared with patients receiving antipsychotic monotherapy, patients on antipsychotic polytherapy have higher rates of metabolic syndrome and lipid markers of insulin resistance. However, antipsychotic polytherapy is not independently associated with the prevalence of these abnormalities, which are related to known demographic, clinical and anthropometric risk factors.

Topics: Adult; Age Factors; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Body Mass Index; Cholesterol, HDL; Clozapine; Cross-Sectional Studies; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Insulin Resistance; Male; Metabolic Syndrome; Middle Aged; Piperazines; Quetiapine Fumarate; Quinolones; Risk Factors; Schizophrenia; Thiazoles; Triglycerides

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Humans; Male; Restless Legs Syndrome

To study the prescribing practices of atypical antipsychotic drugs in French psychiatric hospitals.. A 1-day cross-sectional observational survey was performed in seven psychiatric hospitals to study prescribing practices of the four atypical antipsychotics (AAP) marketed in France. These hospitals are members of the PIC network, a pharmacists' working group based in southwestern France.. Type and dosages of prescribed atypical antipsychotics, indication and concomitant prescriptions.. The study included 1475 adult inpatients' prescriptions with an antipsychotic drug; 647 prescriptions included an AAP with risperidone and olanzapine accounting for about 70% cases. AAP prescriptions concerned psychotic patients in 65% of cases. Patients receiving an AAP in this indication were more likely to be male, were younger, and received higher daily doses than patients treated for other troubles. They were also more likely to receive associated neuroleptic and anticholinergic antiparkinsonian agents. There were 59 prescriptions (9.1%) for bipolar disorders. Clozapine wasn't used in this indication. In 76.3% of cases, mood stabilizers were associated to the AAP prescribed in this indication.. This observational survey underlines the significant place taken by AAP for the treatment of psychiatric diseases in hospital prescribing practices. They show usage patterns of these drugs: dose, indications and concomitant medications, in line or not with current recommendations and reference guidelines. In bipolar disorders, AAPs seem more likely to be associated to an ongoing therapy using mood stabilizer than to replace it.

Topics: Adult; Age Factors; Amisulpride; Antimanic Agents; Antiparkinson Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clozapine; Cross-Sectional Studies; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; France; Hospitals, Psychiatric; Humans; Male; Mental Disorders; Middle Aged; Olanzapine; Practice Patterns, Physicians'; Psychotic Disorders; Risperidone; Sex Factors; Sulpiride

Topics: Adult; Antineoplastic Agents; Antipsychotic Agents; Bipolar Disorder; Clozapine; Comorbidity; Hodgkin Disease; Humans; Male; Stem Cell Transplantation

We investigated the effect long-term clozapine add-on therapy has on rehospitalization rate and mood polarity patterns in patients with bipolar disorders.. Clinical data from medical records of 51 patients with bipolar disorder (DSM-IV) treated with clozapine add-on for more than 6 months at the Refractory Bipolar Disorders Clinic of Seoul National University Hospital were retrospectively analyzed. Patients had been registered from 1995 to 2004. Rehospitalization rates were compared before and after clozapine add-on. The clinical polarity of episodes resulting in hospitalizations was also compared. Twenty-seven bipolar patients treated with clozapine add-on for more than 3 years were further analyzed for long-term stability.. The number of hospital days per year was reduced in 90.2% of patients after clozapine add-on. Total number and duration of hospitalizations per year decreased, and the effect size of clozapine add-on was substantially large (Wilcoxon z = -5.48, p < .01 for number of hospitalizations/year; Wilcoxon z = -5.32, p < .01 for hospital days/year; r = -0.54 and -0.53, respectively). Significant reductions were found in the number and duration of hospitalizations associated with manic, depressive, and hypomanic episodes. Number and duration of hospitalizations associated with mixed episodes did not show significant changes. The long-term efficacy of clozapine add-on was supported by continuous reduction in hospital days per year in the 27 selected patients.. Long-term clozapine add-on therapy was effective in reducing the number and duration of rehospitalizations of bipolar patients resistant to conventional treatment. A significant reduction was found in rehospitalizations associated with manic, depressive, and hypomanic episodes, whereas mixed episode-associated rehospitalizations did not show significant changes.

Topics: Adolescent; Adult; Affect; Antipsychotic Agents; Bipolar Disorder; Clozapine; Drug Therapy, Combination; Female; Follow-Up Studies; Hospitalization; Humans; Length of Stay; Longitudinal Studies; Male; Medical Records; Middle Aged; Patient Readmission; Psychiatric Status Rating Scales; Retrospective Studies; Treatment Outcome

FGF-2 is important for stem cell proliferation, neocortical development and adult neuronal survival and growth. Reduced frontal cortical FGF-2 expression is described in major depression and is attenuated by antidepressants. We determined the distribution of hippocampal FGF-2 and its receptor (FGFR1) mRNA in post-mortem brains of people who suffered from major depression, bipolar disorder and schizophrenia and those of controls.. FGF-2 and FGFR1 mRNA were measured within hippocampal CA1, CA4 regions and the dentate gyrus (DG), using in situ hybridization. Within hippocampal regions, cellular staining was compared between diagnostic groups, using repeated measures analysis of variance.. The density of FGF-2 mRNA+ cells in CA4 was reduced in depression compared to controls. The percentage of FGFR1 mRNA+ cells was higher in depression (CA1 and CA4) and schizophrenia (CA4) than in controls. FGFR1 mRNA expression was higher in depression than in the other groups in CA1, CA4 and DG. Overall FGF-2 mRNA expression was higher in DG than in CA1 and CA4.. We found raised measures of FGFR1 mRNA+ in major depression and, less so, in schizophrenia, along with reduced FGF-2 mRNA density in depression. Perturbations of FGF regulation could be relevant to the pathogenesis of both disorders as FGF-2 and FGFR1 are implicated in normal hippocampal synaptology, stem cell recruitment, and connectivity, and are modulated by corticosteroids.

Topics: Adult; Aged; Antipsychotic Agents; Bipolar Disorder; Clozapine; Depressive Disorder, Major; Female; Fibroblast Growth Factor 2; Gene Expression; Hippocampus; Humans; Image Processing, Computer-Assisted; In Situ Hybridization; Male; Middle Aged; Receptor, Fibroblast Growth Factor, Type 1; RNA, Messenger; Schizophrenia

To assess the perceptions of clinicians in the psychiatric community about pharmacotherapy and its impact on weight gain and adverse metabolic effects in patients with bipolar disorder.. In November 2005, self-administered questionnaires were sent to 7000 psychiatrists who treat bipolar disorder in their clinical practice. An additional mailing of these questionnaires was sent in January 2006 to a different group of 7000 psychiatrists who treat bipolar disorder in their clinical practice. The first 298 completed surveys were analyzed.. Almost half of the respondents (48%) were psychiatrists in individual private practice and 32% were in community mental health centers. About two-thirds of respondents reported that 30-60% of their bipolar patients were overweight. Thirty-eight percent of respondents reported metabolic syndrome present in 20-40% of their patients. Almost all respondents (96%) reported a 20 lb increase in patients' weight as a troublesome potential adverse event associated with the use of some agents. After initiating a new medication, more than 80% of respondents monitored their patients' weight, fasting plasma glucose level, and fasting lipid profile at regular intervals. However, 80% did not monitor waist circumference. Overall, respondents viewed several agents (aripiprazole, ziprasidone, carbamazepine, and lamotrigine) as not (or minimally) problematic in terms of weight gain and adverse metabolic concerns. Clozapine and olanzapine were viewed as highly problematic due to their propensity to induce weight gain and negatively influence lipid and glucose metabolism. Other agents considered to be minimally to moderately problematic in terms of weight gain and metabolic issues were quetiapine, risperidone, lithium, and valproate. Respondents reported that the profile of a bipolar agent in terms of weight gain and adverse metabolic effects was an important consideration in the management of bipolar disorder.. Although the study is limited by a low response rate and self-selection of respondents, clinicians who did respond were concerned about the risks of weight gain and metabolic disturbances in their patients treated with bipolar agents. For most parameters, such concerns were being integrated into clinical care. However, it appears that there is a need to increase clinicians' appreciation of the importance of abdominal obesity and the need to monitor waist circumference. A growing recognition of the differences in weight-gain potential and adverse metabolic effects among agents appears to have had a definite impact on prescribing patterns in the management of bipolar disorder.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Blood Glucose; Clozapine; Female; Humans; Lipids; Male; Metabolic Syndrome; Olanzapine; Overweight; Perception; Practice Patterns, Physicians'; Weight Gain

Topics: Acute Disease; Antipsychotic Agents; Bipolar Disorder; Clozapine; Female; Humans; Middle Aged; Urinary Tract Infections

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Breast Feeding; Clozapine; Female; Guidelines as Topic; Humans; Milk, Human

A panel consisting of academic psychiatrists and pharmacist administrators of the Texas Department of State Health Services (formerly Texas Department of Mental Health and Mental Retardation), community mental health physicians, advocates, and consumers met in May 2004 to review new evidence in the pharmacologic treatment of bipolar I disorder (BDI). The goal of the consensus conference was to update and revise the current treatment algorithm for BDI as part of the Texas Implementation of Medication Algorithms, a statewide quality assurance program for the treatment of major psychiatric illness. The guidelines for evaluating possible medications, the criteria for selection and ranking, and the updated algorithms are described.. Principles from previous consensus conferences were reviewed and amended. Medication algorithms for the acute treatment of hypomanic/manic or mixed and depressive episodes in BDI were developed after examining recent efficacy and safety and tolerability data. Recommendations for maintenance treatments were developed.. The panel updated the 2 primary algorithms (hypomanic/manic/mixed and depressive) based on clinical evidence for efficacy, tolerability, and safety developed since 2000. Expert consensus was utilized where clinical evidence was limited. Prevention of new episodes or prophylaxis treatment recommendations were developed based on recent data from longer-term trials. Maintenance recommendations are provided as levels versus a specified staged algorithm, as for acute treatment, due to the relatively limited database to inform treatment.. These algorithms for the treatment of BDI represent the recommendations based on the most recent evidence available. These recommendations are meant to provide a framework for clinical decision making, not to replace clinical judgment. As with any algorithm, treatment practices will evolve beyond the recommendations of this consensus conference as new evidence and additional medications become available.

Topics: Algorithms; Antipsychotic Agents; Bipolar Disorder; Clozapine; Consensus; Decision Trees; Drug Therapy, Combination; Evidence-Based Medicine; Humans; Lithium; Patient Care Planning; Practice Guidelines as Topic; Psychotropic Drugs; Quality Assurance, Health Care; Selective Serotonin Reuptake Inhibitors; Texas

Malignant neuroleptic syndrome is a complication of antipsychotic medication use. Clozapine use is also associated with polyserositis and eosinophilia. We report a 17 years old female treated with clozapine, valproic acid, lithium carbonate and lorazepam that consulted in the emergency room for confusion, lethargy, catatonia, rigidity, myalgya and fever. Complete blood count showed eosinophilia. An abdominal CAT scan showed ascites and pleural effusion. Clozapine was discontinued and bromocriptine was started. One week after admission, the patient remained febrile and liver enzymes were elevated. Valproic acid was discontinued. Inflammatory parameters stated to subside and the patient was discharged afebrile days after admission.

Topics: Adolescent; Antipsychotic Agents; Bipolar Disorder; Clozapine; Female; Humans; Neuroleptic Malignant Syndrome

Topics: Agranulocytosis; Antipsychotic Agents; Bipolar Disorder; Clozapine; Dibenzothiazepines; Female; Humans; Leukopenia; Middle Aged; Quetiapine Fumarate

Topics: Administration, Intranasal; Administration, Sublingual; Aerosols; Bipolar Disorder; Clozapine; Drug Administration Schedule; Female; Humans; Ipratropium; Male; Schizophrenia; Sialorrhea; Treatment Outcome

Topics: Adult; Anti-Obesity Agents; Antipsychotic Agents; Bipolar Disorder; Clozapine; Drug Interactions; Drug Therapy, Combination; Fructose; Humans; Leukopenia; Male; Topiramate; United Kingdom; Weight Gain

There are limited data in the literature regarding clozapine use in adolescents with diagnoses other than schizophrenia. This report describes the use of clozapine in adolescents with diagnoses of bipolar disorder, intermittent explosive disorder (IED), and posttraumatic stress disorder (PTSD).. A chart review of 39 adolescents treated with clozapine at two residential facilities was undertaken. Data extraction included demography, illness variables, medication information, and clinical outcomes. Categorical outcomes were analyzed using contingency statistics, and continuous variables were analyzed using a paired t test.. The cohort included 26 females and 13 males with a mean age of 14 years. Clozapine was titrated slowly, and the mean daily dose was 102 mg. The diagnoses included bipolar disorder (n = 7), IED (n = 9), and PTSD (n = 19). There were significant reductions in polypharmacy once the clozapine dosage was stabilized. Prior to clozapine treatment, nearly 70% of the subjects were receiving either mood-stabilizing or antidepressant agents in combination with the previous antipsychotic drug. Once the clozapine dosage was stabilized, only 24% of the subjects required concomitant mood stabilizers (p < 0.001), and only 21% of the subjects required concomitant antidepressants (p < 0.001). Anxiolytic medication use was also significantly reduced during clozapine treatment. Most patients were discharged to a less restrictive setting. Eight subjects discontinued clozapine due to agranulocytosis (n = 1), neutropenia (n = 2), excessive weight gain (n = 2), or not requiring it long term (n = 1), and data were unavailable in 2 subjects. Significant weight gain (5% or greater change from baseline) was noted in 20 subjects.. Clozapine, in relatively modest doses, appears to have clinical benefits for adolescent with bipolar disorder, IED, and PTSD. There is no labeled indication for clozapine use in these disorders. Clozapine is also associated with serious side effects in subsets of individuals. Therefore, a very careful evaluation of the risk-to-benefit ratio in each individual subject being considered for clozapine is highly recommended.

Topics: Adolescent; Bipolar Disorder; Chi-Square Distribution; Child; Clozapine; Disruptive, Impulse Control, and Conduct Disorders; Female; Humans; Male; Retrospective Studies; Stress Disorders, Post-Traumatic; Weight Gain

Rapid cycling (RC) bipolar disorder (BD) patients often do not respond fully to mood-stabilizers. Atypical antipsychotics including clozapine may be good candidates as an alternative mood-stabilizer for these patients.. Twenty-eight treatment-resistant patients with either Bipolar Disorder Type I (n = 20), or Schizoaffective Disorder Bipolar Type (n = 8) received clozapine add-on therapy. Patients were followed for up to 1 year. Patients were seen monthly and assessed on a number of symptom domains.. Fifteen of 28 patients met RC criteria. Differences between groups was non-significant for reported age of onset, age at study entry, past history of treatment or hospitalization, or diagnosis. However, significantly more women were RC. More than 80% of patients in either group showed at least some improvement over the 1-year study. Random regression analyses found the non-rapid cycling (NRC) group experienced significantly greater improvement than RC patients (p < 0.0001).. Clozapine is more effective in NRC patients with a history of mania in comparison to patients with a recent history of RC.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Diagnostic and Statistical Manual of Mental Disorders; Female; Follow-Up Studies; Humans; Male; Severity of Illness Index; Treatment Outcome

There are not many studies on the use of clozapine in patients with intellectual disability (ID). The authors describe a case series of patients treated with clozapine, drawn from a medium secure unit, a low secure assessment and treatment service and a community team in the London region.. A retrospective file-review of patients treated in these three settings during the time period March-June 2002 was performed (n = 24). Information was collected using a semistructured proforma.. Of the 24 patients, 67% had schizophrenia, 17% had schizoaffective disorder and 8% had bipolar disorder. Patients had been unwell for a mean of 6 years and had been tried on a mean of four antipsychotics. The mean maximum dose of clozapine was 488 mg. The outcomes on the clinical global impression (CGI) scale showed 29% very much improved, 42% much improved, 21% minimally improved and 8% no change. 54% of the whole sample and 53% of those from the medium secure unit were discharged to homes in the community. The drug had to be stopped in four patients, of which three were because of neutropaenia.. Clozapine appears to be safe and efficacious in many people with ID. Careful monitoring of side-effects is needed during therapy.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Child; Child Development Disorders, Pervasive; Clozapine; Cognition Disorders; Drug Resistance; Drug Utilization; Epilepsy; Female; Humans; Male; Middle Aged; Personality Disorders; Psychotic Disorders; Retrospective Studies; Schizophrenia; Substance-Related Disorders

A case report describes an adolescent girl with a treatment-resistant bipolar disorder, who developed pericarditis and polyserositis while being treated with clozapine. The sparse literature about this rare, severe side effect of clozapine is discussed. Clinical recommendations with regard to monitoring are given. If myocarditis/polyserositis occurs, clozapine has to be discontinued immediately.

Topics: Adolescent; Agranulocytosis; Antipsychotic Agents; Bipolar Disorder; Clozapine; Female; Humans; Pericarditis; Psychiatric Status Rating Scales; Serositis

Topics: Adult; Aged; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Clozapine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Male; Piperazines; Psychotic Disorders; Quinolones; Schizophrenia, Paranoid; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Black People; Blood Glucose; Clozapine; Diabetic Ketoacidosis; Drug Interactions; Fatal Outcome; Humans; Hyperglycemia; Male; Risk Factors

Some bipolar patients with acute manic episodes can be refractory to conventional treatment with mood stabilizers. Clozapine, an atypical antipsychotic, has been reported to be effective in adults with treatment-resistant bipolar disorder. We describe the therapeutic effect of clozapine in 10 adolescent inpatients (12- to 17-year-olds) with severe acute manic or mixed episodes who did not improve after treatment with conventional drugs (mood stabilizers, antipsychotics). At hospital discharge, 15 to 28 days after clozapine treatment, all patients had responded positively according to the Clinical Global Impression-Improvement Scale scores. The mean changes in Mania Rating Scale, Brief Psychiatric Rating Scale, Children's Global Assessment Scale, and Clinical Global Impression-Severity Scale were significant (p < 0.001). Clozapine dosage was 142.5 +/- 73.6 mg/day (range 75-300 mg/day). Side effects (increased appetite, sedation, enuresis, sialorrhea) were frequent but not severe enough to require reduction of dosage. Mean weight gain after 6 months was 6.96 +/- 3.08 kg (10.7%). Neither decrease of white cells nor epileptic seizures were reported during follow-up (12-24 months). These preliminary findings suggest that clozapine may improve the clinical picture in adolescents with treatment-refractory manic or mixed episodes. Controlled studies on larger samples are warranted.

Topics: Adolescent; Bipolar Disorder; Child; Clozapine; Female; Humans; Inpatients; Male; Psychiatric Status Rating Scales

Atypical neuroleptics are increasingly used in the treatment of bipolar and schizoaffective disorders. Currently, numerous controlled short-term studies are available for clozapine, olanzapine, risperidone or quetiapine, but long-term data are still missing. Three patients (2 with bipolar disorder, 1 with schizoaffective disorder) are described who showed a marked reduction of affective symptomatology after clozapine had been added to mood stabilizer pretreatment. The patients were seen once a month before and after the introduction of clozapine for at least 6 months. Treatment response was evaluated using different rating scales (IDS, YMRS; GAF; CGI-BP) and the NIMH Life Chart Methodology. All patients showed a marked improvement after the add-on treatment with clozapine had been initiated. Clozapine was tolerated well with only transient and moderate weight gain and fatigue as only side effects. This case series underlines the safety and efficacy of clozapine as add-on medication in the treatment of bipolar and schizoaffective disorders.

Topics: Adult; Affect; Antipsychotic Agents; Bipolar Disorder; Clozapine; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Psychotic Disorders

Controversy persists about links between psychotropic drug use, obesity, and consequent menstrual irregularities. Although these interrelationships have been suggested to possibly explain polycystic ovarian syndrome among women taking valproate, less is known about menstrual irregularities associated with weight gain caused by other psychotropics. Clozapine, sparing of prolactin-related menstrual effects yet often associated with weight gain, offers a model psychotropic from which to test such hypotheses. We studied outpatient premenopausal women from a clozapine clinic to preliminarily assess the association between menstrual cycle patterns and body mass index (BMI). Records were reviewed for 13 female premenopausal schizophrenic, bipolar, or schizoaffective outpatients who took clozapine with no conventional antipsychotics for >6 months. Mean 6-month menstrual cycle lengths were compared with BMIs and relative weight changes since starting clozapine. Subjects took clozapine (mean +/- SD dose 392.2 +/- 195.7 mg/day) for a mean +/- SD of 4.4 +/- 3.2 years, with a mean preclozapine weight increase of 27%. Twenty-three percent had menstrual irregularities in the preceding 6 months (mean +/- SD cycle length = 36.4 +/- 18.1 days), although no significant associations were observed between cycle length and (a) mean +/- SD BMI (32.0 +/- 8.4) (r = -0.09, p = 0.78) or (b) weight change since starting clozapine (r = -0.10, p = 0.75). The observed lack of association between clozapine-induced weight gain and menstrual disturbances would provisionally suggest that iatrogenic weight gain does not robustly explain the emergence of irregular menses among premenopausal women taking clozapine.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Data Collection; Female; Humans; Medical Records; Menstruation Disturbances; Middle Aged; Pilot Projects; Psychotic Disorders; Schizophrenia; Weight Gain

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Drug Therapy, Combination; Female; Hodgkin Disease; Humans; Leukopenia; Remission Induction; Risperidone; Treatment Outcome; Valproic Acid

Topics: Anti-Infective Agents; Bipolar Disorder; Chronic Disease; Clozapine; Drug Synergism; Female; Humans; Middle Aged; Neutropenia; Panic Disorder; Selective Serotonin Reuptake Inhibitors; Thrombocytopenia; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clozapine; Cognitive Behavioral Therapy; Counseling; Exercise; Female; Humans; Male; Obesity; Olanzapine; Pirenzepine; Relaxation Therapy; Schizophrenia; Treatment Outcome; Weight Gain

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Humans; Male; Neurocognitive Disorders; Neurosyphilis; Treatment Outcome

Converging evidence indicates that, in controlled drug trials, individuals receiving novel antipsychotic medications have fewer adverse effects than those receiving conventional antipsychotic medications. This in turn may lead to greater patient treatment satisfaction. This study examines patient satisfaction and burden of adverse effects in a county-wide epidemiologic study of first admission psychotic persons with psychosis who were receiving novel antipsychotic drugs (n = 42). Comparisons were made within this group, and between 25 of these persons and 25 others with the same diagnosis and sex, from the same epidemiologic study, who were receiving a comparable regimen of conventional antipsychotic drugs. Patients receiving novel antipsychotics were significantly more satisfied and were significantly less burdened by adverse effects than those receiving conventional antipsychotics. Among the group receiving novel antipsychotics, dosage was not related to satisfaction or burden of adverse effects. For those treated with risperidone (n = 27), there was a difference, approaching statistical significance, for greater satisfaction and less adverse effect burden among those persons with dosages less than 5 mg daily as compared to higher dosages.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clozapine; Depressive Disorder, Major; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Neurologic Examination; Olanzapine; Patient Satisfaction; Pirenzepine; Risperidone; Schizophrenia; Schizophrenic Psychology

Three patients with psychoses and concomitant prolactin-secreting pituitary tumours are described. Patients A and B had bipolar and schizoaffective disorders, respectively. They had both been treated with neuroleptics for 20 years before the prolactinomas were revealed. Patient C developed a paranoid psychosis after two years of continuous bromocriptine treatment for a pituitary tumour. In patient A the prolactin level was successfully normalized and a good antipsychotic effect was maintained by combined therapy with haloperidol and quinagolide but not bromocriptine. In patient B the prolactinoma was removed by surgery, in view of the serious nature of the psychotic disorder, to avoid psychotic relapse by treatment with a dopamine agonist. In patient C a good result was obtained with the combination of clozapine and bromocriptine. These case reports support the view that neuroleptics being dopamine antagonists and dopamine agonistic agents which are the primary treatment of prolactinomas can cancel out each other's effects. The combination of clozapine and quinagolide is recommended as the treatment of choice for most patients.

Topics: Adult; Aminoquinolines; Antipsychotic Agents; Bipolar Disorder; Bromocriptine; Clozapine; Comorbidity; Dopamine Agonists; Dopamine Antagonists; Drug Interactions; Drug Therapy, Combination; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Prolactinoma; Psychoses, Substance-Induced; Psychotic Disorders

1. Some reports have suggested an increase in symptoms when switching patients with psychosis from clozapine to other atypical antipsychotics. 2. No data are available on switching between atypical antipsychotics other than clozapine, though this is common in clinical practice. 3. Six patients with schizophrenia or schizoaffective disorder, bipolar type were switched to quetiapine after finishing a clinical trial of sertindole. 4. During the observation period of two to ten weeks no subjects worsened and one improved. Side effects were mild. 5. These preliminary data suggest that switching between some atypical agents may be well tolerated. Larger controlled trials are needed to confirm this observation.

Topics: Adult; Aged; Antipsychotic Agents; Bipolar Disorder; Clozapine; Female; Humans; Male; Middle Aged; Outpatients; Schizophrenia; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Female; Humans; Kidney; Leukocyte Count; Liver; Vomiting

A treatment-resistant manic patient failed to respond to conventional treatment, adjunctive olanzapine (20 mg/day), clozapine (600 mg/day), or ECT alone, but did respond to ECT combined with low dose clozapine (200 mg/day). Maintenance ECT combined with clozapine resulted in a remission over the 18-month period.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Combined Modality Therapy; Electroconvulsive Therapy; Humans; Long-Term Care; Male

The serotonergic system is targeted by both antidepressants and atypical antipsychotic drugs such as clozapine. Genetic variation in the 5-HT5A gene might be involved in susceptibility to depression, the major psychoses or in influencing clinical response to treatment. To examine this hypothesis we genotyped two polymorphisms (-19G/C; 12A/T) in the human 5-HT5A receptor gene in a sample of 269 unrelated schizophrenic patients treated with clozapine, 112 bipolar patients, 75 unipolar patients and 187 controls. After five-fold correction for multiple testing, allelic association was found with the -19G/C polymorphism and bipolar affective disorder, (p = 0.025; OR 0.56), unipolar depression (p = 0.004; OR 0.52) and schizophrenia (p = 0.036; OR 0.67) indicating a potential protective effect of the G19 allele. For the 12A/T polymorphism allelic association was observed with unipolar depression only (p = 0.004). We conclude that allelic variation in the human 5-HT5A receptor gene may be involved in susceptibility to schizophrenia and affective disorders but not in determining response to clozapine.

Topics: Alleles; Antipsychotic Agents; Bipolar Disorder; Clozapine; Depression; Humans; Polymorphism, Genetic; Psychotic Disorders; Receptors, Serotonin; Reference Values; Schizophrenia

Topics: Antidepressive Agents; Antipsychotic Agents; Bipolar Disorder; Clozapine; Drug Therapy, Combination; Humans; Lamotrigine; Male; Middle Aged; Treatment Outcome; Triazines; Valproic Acid

Topics: Antipsychotic Agents; Bipolar Disorder; Clozapine; Female; Humans; Middle Aged; Parotitis

A combination of clozapine and lithium can be used in the treatment of refractory schizophrenia, schizoaffective disorder and bipolar disorder with rapid cycling. We report a patient with refractory bipolar disorder who developed side-effects after combination therapy with clozapine and lithium at usual therapeutic dosages. Reversible neurotoxicity developed twice during the therapeutic course, once with the restarting of lithium, the other with increasing the dose of lithium, despite the lithium concentrations being less than 0.5 mEq/l. Neurotoxicity manifested as ataxia, coarse tremor, myoclonus, facial spasm and increased deep tendon reflex. While the mechanism causing toxicity is not clear, interaction between the serotonergic effect of clozapine and lithium may be the cause. This report is evidence that a combination of clozapine and lithium may increase the risk of neurotoxicity. We suggest the need to keep clozapine and lithium at lower dosages and closely monitor their side-effects as necessary when these drugs are used concomitantly.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Brain; Clozapine; Female; Humans; Lithium

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Diabetic Ketoacidosis; Follow-Up Studies; Glucose Tolerance Test; Humans; Insulin; Male; Psychotic Disorders

In spite of some inherent limitations, naturalistic data can provide information on populations that have greater heterogeneity than can controlled clinical trials and on functional outcomes that may be especially important in clinical practice. In the present retrospective naturalistic study, we evaluated key clinical outcomes among the first wave of risperidone-treated patients at a state psychiatric hospital.. Outcome data were extracted from the charts of 142 patients 2 years after initiation of treatment with risperidone. Their diagnoses included DSM-III-R schizophrenia (57%), schizoaffective disorder (22%), dementia and other organic conditions (7%), bipolar disorder (5%), and other psychiatric disorders (9%).. During the 2-year period, 92 of 142 patients were discharged from the hospital: 61 (43%) were discharged on risperidone treatment and 31 (22%) were discharged on treatment with other drugs. At the time of the study, 50 of 142 patients were still in the hospital: of these, 18 (13%) were still receiving risperidone. The modal maximum daily dose of risperidone was 4.1 mg in patients discharged on risperidone treatment and 7.5 mg in patients still in the hospital. All groups were granted more ward privileges after starting risperidone, the most being granted to patients discharged from the hospital on risperidone treatment (p<.05 versus patients discharged on treatment with other drugs) and those still receiving risperidone in the hospital. Significantly fewer patients discharged on risperidone treatment than on treatment with other drugs were readmitted to the hospital within 2 years after discharge (p<.01).. Improved privilege levels and a reduced readmission rate indicate that risperidone was an effective antipsychotic agent among a heterogeneous patient population in a state hospital. These factors may be especially important to justify use of this agent in the current fiscal climate.

Topics: Adult; Antiparkinson Agents; Antipsychotic Agents; Bipolar Disorder; Clozapine; Dementia; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Hospitalization; Hospitals, Psychiatric; Hospitals, State; Humans; Length of Stay; Male; Mental Disorders; Patient Readmission; Psychotic Disorders; Retrospective Studies; Risperidone; Schizophrenia

Topics: Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Clozapine; Diabetic Ketoacidosis; Drug Therapy, Combination; Female; Humans; Middle Aged; Valproic Acid

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Dose-Response Relationship, Drug; Female; Humans; Secondary Prevention; Severity of Illness Index; Suicide Prevention; Suicide, Attempted

Topics: Antipsychotic Agents; Bipolar Disorder; Clozapine; Cost-Benefit Analysis; Drug Costs; Health Care Costs; Humans; Mental Disorders; Schizophrenia

A 15 year-old adolescent boy with a severe treatment refractory bipolar disorder type I, most recent episode manic, severe with psychotic features had previously required hospitalizations and treatment with lithium and/or carbamazepine and high doses of standard neuroleptics without any response. A treatment with a combined clozapine-lithium therapy was progressively started in a hospital setting (clozapine 300 mg/day; lithium 1350 mg/day). After 15 days a dramatic improvement in mood and psychotic symptoms was evident. After four weeks there was 50% improvement on the BPRS (from 74 to 37). The mean CGAS score changed from 25 to 72. At the CGI-Severity of Illness subscale, a 57% decrease was evident; at the CGI-Global Improvement subscale there was a 75% increase. The only significant side effects were sedation and fatigue, but they were not so severe as to induce a reduction of dosage. The boy was discharged from the hospital after three weeks and successfully returned to school with no modifications in treatment. After a nine-month treatment there was no reoccurrence of psychotic or manic symptoms. The implications of pharmacological therapy in treatment refractory manic episodes with psychotic features are discussed.

Topics: Adolescent; Antipsychotic Agents; Bipolar Disorder; Clozapine; Drug Therapy, Combination; Humans; Lithium; Male

Previous studies of clozapine pharmacokinetics have shown a wide intra- and inter-individual variability of plasma levels in patients on stable clozapine doses. We investigated dose-plasma level relationships and intra-individual variability of plasma levels during maintenance treatment with clozapine.. Forty-one patients on clozapine were followed for 26 weeks with repeated plasma level measurements and assessments of co-medication and clinical symptoms. In a second step, 15 patients on stable clozapine doses between treatment Weeks 12 and 52 were followed in the same way. Coefficient of variation was used as a parameter of plasma level deviation.. Dose-plasma level correlations stayed significant from Week 6 to Week 26 (n = 41). The group of patients followed up to Week 52 showed a mean intra-individual coefficient of variation of 52.8% (s.d. = 20.6), and remained stable psychopathologically.. Even though clozapine plasma levels may show a significant degree of variation, this is not necessarily reflected in a change in psychopathology.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Cross-Sectional Studies; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Male; Prospective Studies; Psychotic Disorders; Schizophrenia

We present the case of a 35-year-old patient suffering from schizoaffective psychosis. After 4 weeks on clozapine he developed acute priapism. Possible explanations and pathophysiology are discussed as well as the requirement for sufficient information of the patient. Delay of urgent urologic treatment increases the risk of irreversible impotence. The patient's history should be evaluated with respect to former unphysiological prolonged erections.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Humans; Male; Priapism; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology

Topics: Adult; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Bipolar Disorder; Clozapine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Female; Humans; Neurologic Examination; Paroxetine; Serotonin Receptor Agonists; Sumatriptan

To test the efficacy of clozapine in treatment-resistant manic episodes.. Three cases, two with bipolar disorder (manic) and one of schizoaffective disorder (manic), were treated with clozapine.. Clozapine was used after the failure of standard antipsychotics and mood stabilizers.. All three cases were successfully treated.. A controlled trial of clozapine in treatment-resistant bipolar and schizoaffective manic episodes is indicated.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Combined Modality Therapy; Drug Resistance; Electroconvulsive Therapy; Female; Humans; Male; Middle Aged; Psychotic Disorders

[123I]Iodobenzamide (IBZM) is an iodine-labeled dopamine receptor ligand and can be used to visualize brain D2 receptors in humans with single photon emission computerized tomography (SPECT). The ratio of striatal IBZM uptake to uptake in frontal cortex (ST/FC ratio) represents a semiquantitative measure of D2 receptor binding in the striatum. Our study sample included six patients treated with haloperidol (3.0-8.0 mg/day orally; one patient with an average of 0.9 mg/day intramuscularly), five patients with benperidol (9.0-15.0 mg/day orally) and nine patients treated with clozapine (200.0-600.0 mg/day orally). Typical neuroleptics (TNs) and atypical neuroleptics (ANs) were significantly different in their ST/FC ratios. The ST/FC ratios indicated that patients treated with benperidol exhibited the lowest ST/FC ratios, with increasingly higher ratios in patients on haloperidol or clozapine. We found a curvilinear relationship between the ST/FC ratios and the dose/kg body wt. of TNs and ANs on the basis of a dose-normalization according to Ki-values of the neuroleptic at D2 receptors and a weaker, but also curvilinear relationship between ST/FC ratios and normalized dosages according to clinically defined chlorpromazine equivalents. The specific uptake of IBZM did not correlate with the plasma levels of the TN haloperidol at the present dose range (0-12.4 ng/ml). For clozapine, a meaningful negative correlation between plasma levels and ST/FC ratio could be established. There was a negative continuous correlation between uptake of IBZM and extrapyramidal side effects, which is different from the threshold-based relationship between extrapyramidal side effects and IBZM uptake reported previously.

Topics: Adult; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Benperidol; Benzamides; Bipolar Disorder; Brain; Clozapine; Corpus Striatum; Depressive Disorder, Major; Dopamine Antagonists; Dose-Response Relationship, Drug; Female; Frontal Lobe; Haloperidol; Humans; Male; Middle Aged; Neurologic Examination; Psychiatric Status Rating Scales; Pyrrolidines; Receptors, Dopamine D2; Schizophrenia, Paranoid; Tomography, Emission-Computed, Single-Photon

Topics: Bipolar Disorder; Clozapine; Combined Modality Therapy; Electroconvulsive Therapy; Hospitalization; Humans; Male; Middle Aged; Treatment Outcome

The purpose of this study was to test the hypothesis that minor EEG abnormalities predict a favorable response to clozapine. Eighty-six psychotic clozapine-treated psychiatric inpatients with EEG records before starting clozapine were included in the study. When all diagnostic groups were combined, there were no significant differences in clinical outcome between patients with abnormal EEGs and patients with normal EEGs. However, female patients with abnormal EEGs had a significantly greater improvement in Global Assessment of Functioning (GAF) scores compared to female patients with normal EEGs. In addition, patients with major depressive episodes (bipolar, schizoaffective, unipolar) and abnormal EEGs had a significantly greater improvement in GAF scores compared to the same subgroup of patients with normal EEGs. The results suggest that EEG abnormalities before clozapine treatment many predict a favorable clinical response in specific groups of patients.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Depressive Disorder; Electroencephalography; Female; Humans; Male; Psychiatric Status Rating Scales; Psychotic Disorders; Retrospective Studies; Schizophrenia; Sex Factors; Single-Blind Method; Treatment Outcome

Topics: Adult; Aged; Antipsychotic Agents; Bipolar Disorder; Clozapine; Diagnosis, Dual (Psychiatry); Female; Humans; Male; Middle Aged; Psychotic Disorders; Substance-Related Disorders

Topics: Adult; Aged; Analysis of Variance; Antipsychotic Agents; Bipolar Disorder; Clozapine; Female; Humans; Male; Middle Aged; Prevalence; Risk Factors; Schizophrenia; Triglycerides

The goal of this study was to use PET and 11C-N-methylspiperone (11C-NMSP) to measure the difference in relative occupancy of serotonin (5-hydroxytryptamine-2 or 5-HT2A) and dopamine-2 (D2) neuroreceptors in subjects being treated with typical or atypical antipsychotic drugs.. We used PET and single-dose 11C-NMSP to measure receptor indices and relative receptor occupancy of 5-HT2A receptors in frontal cortex and D2 receptors in basal ganglia in five subjects who were neuroleptic free, five subjects who were being treated with typical antipsychotic drugs and five subjects who were being treated with clozapine, an atypical antipsychotic drug.. Among the three groups, there were significant differences in 5-HT2A indices, D2 indices and the ratio of 5-HT2A to D2 indices. With no overlap, the 5-HT2A index separated all subjects who received clozapine and the D2 index separated the remaining two groups.. Typical antipsychotic and atypical antipsychotic subjects do have differing patterns of 5-HT2A and D2 relative receptor occupancy when measured with a single PET scan, single 11C-NMSP radiotracer dose and no separately injected "cold" pharmaceutical.

Topics: Adult; Antipsychotic Agents; Basal Ganglia; Bipolar Disorder; Carbon Radioisotopes; Case-Control Studies; Cerebral Cortex; Clozapine; Dopamine Agonists; Female; Humans; Male; Receptors, Dopamine D2; Receptors, Serotonin; Schizophrenia; Spiperone; Tomography, Emission-Computed

A study of a 16.8-yr.-old female is presented to highlight aspects of Asperger's Syndrome as distinguished from cognate developmental and mood disorders. Brief therapy and pharmacological implications are mentioned.

Topics: Adolescent; Autistic Disorder; Bipolar Disorder; Clozapine; Combined Modality Therapy; Diagnosis, Differential; Female; Humans; Patient Admission; Psychotherapy; Residential Treatment

Topics: Adult; Arousal; Bipolar Disorder; Clozapine; Confusion; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Humans; Lithium; Male; Orientation; Psychotic Disorders; Speech Disorders; Valproic Acid

Four patients with treatment-resistant euphoric mania characterized by elevated mood, hyperactivity, and rapid speech, refractory to standard treatments and anticonvulsants, showed dramatic improvement in symptoms when treated with clozapine. All developed enhanced functioning and new insight into previous psychopathology. This degree of improvement suggests that clozapine can be considered in the treatment of not only schizophrenia, schizoaffective disorder, and dysphoric mania but also classic euphoric mania unresponsive to traditional treatments.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Euphoria; Female; Humans; Male; Psychiatric Status Rating Scales

Few investigators have focused on the response of individuals with mental retardation to clozapine. In the general population, some people who have responded to no other psychotropic have had a tremendous positive response, including increased positive scores "quality of life" measures. Clozapine, however, can cause fatal side effects. At least six people in the United States have died from agranulocytosis despite weekly blood counts. The use of clozapine in the general population was reviewed, potential difficulties in prescribing it for individuals with mental retardation discussed, and three relevant case histories presented.

Topics: Adult; Bipolar Disorder; Clozapine; Dose-Response Relationship, Drug; Female; Humans; Intellectual Disability; Male; Middle Aged; Psychotic Disorders; Refractory Period, Psychological; Treatment Outcome

Topics: Adult; Bipolar Disorder; Clozapine; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Lithium; Middle Aged; Periodicity; Psychiatric Status Rating Scales

Two patients with long-standing idiopathic Parkinson's disease (PD), without individual or family histories of affective disorders, developed bipolar mood disorders. Both were treated with lithium and clozapine, and one responded favorably. These may be the first reported cases in which mania was treated with clozapine in PD patients.

Topics: Bipolar Disorder; Clozapine; Drug Therapy, Combination; Female; Humans; Levodopa; Lithium Carbonate; Male; Middle Aged; Parkinson Disease; Psychoses, Substance-Induced; Recurrence

To determine the efficacy and tolerance of long-term clozapine therapy in refractory affective illness.. Hospital records were reviewed for 193 treatment-resistant patients with a discharge diagnosis of bipolar disorder (N = 52), schizoaffective disorder (N = 81), unipolar depression (N = 14), schizophrenia (N = 40), or other disorders (N = 6) started on clozapine therapy as inpatients at McLean Hospital. An independent "best-estimate" diagnosis, based on DSM-III-R criteria, was established for each patient. Patients were contacted at least 6 months after clozapine initiation for structured follow-up interviews by raters blind to diagnosis. Patients were stratified by diagnosis, and a variety of patient characteristics and outcome measures were compared.. Subjects were followed up a mean of 18.7 months after clozapine initiation. Bipolar manic and schizoaffective bipolar subjects had significantly better outcomes than unipolar, bipolar, and schizoaffective depressed patients on a variety of measures. One or more episodes of depression prior to clozapine predicted clozapine discontinuation (p = .01). Affective and schizoaffective subjects had baseline measures of social functioning similar to that of the schizophrenics but had significantly greater improvement in scores at follow-up.. Clozapine is an efficacious and well-tolerated therapy for refractory affective illness. Manic symptomatology predicts a more favorable response than depression.

Topics: Adult; Affective Disorders, Psychotic; Bipolar Disorder; Clozapine; Depressive Disorder; Female; Follow-Up Studies; Humans; Male; Probability; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Social Adjustment; Treatment Outcome

Topics: Adult; Bipolar Disorder; Clozapine; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Male; Schizophrenia, Paranoid

Topics: Agranulocytosis; Bipolar Disorder; Clozapine; Diagnosis, Differential; Female; Humans; Middle Aged; Recurrence

Topics: Adult; Bipolar Disorder; Clozapine; Humans; Male

Topics: Adult; Bipolar Disorder; Clozapine; Female; Humans

Seven patients with bipolar disorder, characterized by dysphoric mania with psychotic features and chronic disability, refractory to standard treatments and anticonvulsants, all showed marked symptomatic and functional improvement when given the atypical antipsychotic clozapine. During follow-up over 3-5 years, most of the patients sustained substantial gains in psychosocial function; and of the six patients remaining on clozapine, no further hospitalizations were needed. This remarkable improvement in a severely ill group of patients suggests that clozapine may have utility in the treatment of bipolar disorder as well as schizophrenia.

Topics: Adult; Bipolar Disorder; Clozapine; Depressive Disorder; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Male; Middle Aged; Risk Factors

This article reviews eight published studies that describe clozapine's effects on TD and examines the outcome of 30 patients with TD treated with clozapine for up to 36 months. These data indicate that TD response to clozapine is variable but that approximately 43% of cases, particularly those with dystonic features, improved after clozapine treatment. Methodological limitations of the studies described, however, preclude definitive conclusions, which must await appropriately controlled trials.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Dyskinesia, Drug-Induced; Female; Follow-Up Studies; Humans; Male; Neurologic Examination; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology

Topics: Bipolar Disorder; Clozapine; Dose-Response Relationship, Drug; Female; Humans; Middle Aged; Psychiatric Status Rating Scales

Although growing research indicates that the atypical antipsychotic agent clozapine is effective in patients with schizophrenia, little is known about the efficacy of clozapine in patients with schizoaffective disorder or psychotic mood disorders. The purpose of this study was to assess whether or not clozapine is effective in some patients with schizoaffective disorder or psychotic mood disorders.. By surveying treating clinicians and chart data, we assessed treatment response in 85 consecutive patients, including 39 with schizophrenia, 25 with schizoaffective disorder, and 14 with bipolar disorder with psychotic features, who received clozapine for at least 6 weeks at our center.. All patients were either inadequately responsive to or unable to tolerate standard somatic therapies. Compared to patients with schizophrenia, patients with schizoaffective disorder and bipolar disorder with psychotic features displayed significantly higher response rates to clozapine.. Clozapine may be a useful drug in the treatment of patients with schizoaffective disorder or psychotic mood disorders who are treatment resistant or intolerant of side effects.

Topics: Adult; Bipolar Disorder; Clozapine; Drug Evaluation; Female; Humans; Male; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology

Topics: Adolescent; Bipolar Disorder; Clozapine; Female; Humans; Malignant Hyperthermia; Middle Aged; Neuroleptic Malignant Syndrome; Neurologic Examination; Paranoid Disorders; Psychiatric Status Rating Scales; Substance Withdrawal Syndrome

Clozapine is an antipsychotic drug reported to be virtually free of extrapyramidal effects. On the basis of this, we hypothesized that it would be unlikely to cause the neuroleptic malignant syndrome (NMS), a rare but severe reaction observed with other antipsychotic drugs. However, when we administered clozapine (in conjunction with lithium) to a patient with a past history of NMS with fluphenazine, the syndrome reappeared after about 3 weeks of treatment. This represents, to our knowledge, the first report of apparent NMS with clozapine.

Topics: Adult; Bipolar Disorder; Clozapine; Dibenzazepines; Drug Therapy, Combination; Fluphenazine; Humans; Lithium; Lithium Carbonate; Male; Neuroleptic Malignant Syndrome

All patients treated at the County Hospital for Neurology and Psychiatry in Ueckermuende from 1981 to 1984 with Klopazin were included in a critical analysis of the side effects of the drug, paying special attention to those reported in the literature. Besides the symptoms already identified, delirium and hypotonic circulation dysregulation are receiving increased clinical attention, which indicates that special care methods are called for.

Topics: Administration, Oral; Adult; Bipolar Disorder; Clozapine; Dibenzazepines; Female; Humans; Injections, Intravenous; Male; Schizophrenia

The manifestation of depersonalisation, its relationship with anxiety and depression, as well as its influence on the course of endogenous psychoses were investigated. Forty patients with severe depersonalisation were treated with the benzodiazepine, phenazepam, and 14 with clozapine. The data indicate that depersonalisation results from anxiety; it follows an anxiety attack and is successfully treated with anxiolytic drugs. In the case of endogenous depression, depersonalisation leads to lingering depressive phase, increasing the patients' resistance to antidepressive therapy. The protective and the harmful role of depersonalisation is discussed.

Topics: Adult; Anti-Anxiety Agents; Anxiety Disorders; Benzodiazepines; Benzodiazepinones; Bipolar Disorder; Clozapine; Depersonalization; Depressive Disorder; Diagnosis, Differential; Dibenzazepines; Female; Humans; Hypochondriasis; Male; Middle Aged

A simple gas-liquid-chromatographic method employing a nitrogen selective detector for the quantitative determination of clozapine in serum is presented. The method involves after the addition of dibenzepine as internal standard the extraction into diethylether followed by analysis of the extract dissolved in methanol. Detector linearity was established over the range of 100-1000 ng/ml serum. Clozapine levels of 9 manic patients analysed by this method are presented and discussed. A linear relationship between daily intake (mg/kg body weight) and serum levels (ng/ml) was established.

Topics: Bipolar Disorder; Chromatography, Gas; Clozapine; Dibenzazepines; Drug Tolerance; Female; Humans; Male; Nitrogen

Between January 1974 and June 1975 52 in-patients with mania were treated with Clozapine. In one half of the patients this was the only drug throughout. It was so far thought to be indicated mainly for schizophrenics. Its main action mostly was immediate (partly on the first or second day) and was characterised by initial sedation and subsequent improvement of increased motivation and flight of ideas. On the basis of our present experience Clozapine appears to be superior in the treatment of mania in its main and side effects. Patients prefer it often because of the absence of extrapyramidal side-effects. The in-patient treatment was on average much shorter with Clozapine than with other drugs. These first observations demand further tests for this specific indication.

Topics: Adolescent; Adult; Bipolar Disorder; Clozapine; Dibenzazepines; Electroencephalography; Epilepsy; Female; Humans; Length of Stay; Time Factors

Clozapine, a new antipsychotic drug without extrapyramidal side effects and with strong sedating potency, can produce acute symptoms of central anticholinergic toxicity. The authors report that physostigmine, a reversible anticholinesterase agent, which can pass the blood-brain barrier, was effective in reversing the clozapine-induced brain syndrome in two patients. Physostigmine also reduced one patient's tachycardia.

Topics: Adult; Bipolar Disorder; Clozapine; Delirium; Dibenzazepines; Female; Humans; Male; Physostigmine

Until now the "neuroleptic threshold" (Haase) was considered to be the efficiency criterion of the antipsychotic effect of a neuroleptic substance and it was thought therefore that the extrapyramidal symptoms were a necessary although undesired side effect. The benodiazepine derivative Leponex developed by Sandox - Basel upsets this view because it has an excellent antipsychotic effect without creating definite extrapyramidal symptoms. It is noted for its quick soporfic effect after only a few minutes, for subdueing psychopathological productivity in a very impressive way, for acting rapidly on the "plus"-symptomatology typical of psychosis, as early as in the first days of treatment, and for its equally visible effect on the "minus"-symptoms, typical of psychosis, in the last third of an average period of treatment lasting 40 days. The clinic using Leponex (Dresden, Halle, Brandenburg-Görden) belonged to the clinical application programme of the Sandox - Basel firm. The article gives a summary of essential results and particulars about the treatment. A detailed evaluation of the case sheets which are at present being statistically reviewed will be given in the next paper.

Topics: Adult; Basal Ganglia Diseases; Bipolar Disorder; Clozapine; Dibenzazepines; Humans; Schizophrenia; Time Factors