clozapine and Hallucinations

Over half of Parkinson's disease (PD) patients develop psychotic symptoms, and PD psychosis (PDP) is associated with significant distress to patients, caregiver burden, and impairs quality of life. Pharmacological therapy is limited to atypical antipsychotics.. This review will summarize efficacy but will focus on the safety of antipsychotics for treating PDP, and in particular the off-target safety issues including cognitive impairment, sleep disturbance, cardiovascular effects, and motor function.. Pimavanserin is the only medication approved in the US for treating PDP, however clozapine is also considered efficacious. Despite lack of substantial evidence for efficacy, quetiapine is commonly used to treat PDP. Despite the effectiveness of pimavanserin and clozapine for treating PDP, a need exists for additional pharmacological agents that are effective for PDP while providing an acceptable safety and tolerability profile. Medications to treat PDP should avoid worsening motor function, and also minimize sleep disturbances, cognitive impairment, cardiovascular effects, and other non-motor safety concerns. A neutral effect or reduction in mortality risk associated with PD and PDP would be ideal, and low rate of discontinuation due to AEs is desirable. Lastly, medications that can be used safely in combination with other pharmacological agents is essential.

Topics: Antipsychotic Agents; Clozapine; Delusions; Hallucinations; Humans; Parkinson Disease; Psychotic Disorders; Quality of Life

Topics: Aripiprazole; Clozapine; Delusions; Drug Therapy, Combination; Female; Hallucinations; Humans; Middle Aged; Piperazines; Quinolones; Schizophrenia, Paranoid

Hallucinations and psychosis are common in patients with Parkinson's disease (PD), with reported prevalences of up to 48% and 80%, respectively. However, few randomized, double-blind, placebo-controlled trials evaluating the treatment options have appeared in the literature. The studies that have been published were complicated by lack of agreement on the diagnosis of psychosis in PD, poor completion rates, mixed populations that included dementia, and other issues. Several reviews, guidelines, and consensus statements have sought to establish standards for treating these symptoms of PD. In 2006, the American Academy of Neurology (AAN) published a practice guideline (based on articles published up to 2004) for management of depression, psychosis, and dementia in patients with PD. Since then, a number of relevant studies have been published.. The purpose of this article was to review data that have appeared in the literature since publication of the AAN guideline regarding the management of hallucinations and psychosis in PD.. A literature search of the PubMed, CINAHL, and PsychInfo databases was conducted for human studies published in English from January 2004 to June 2010. All clinical studies were included except case reports and case series. Studies with <20 participants were also excluded. Search terms included psychosis, hallucinosis, hallucination, delusion, Parkinson, atypical antipsychotic, neuroleptic, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone.. Thirteen studies were included in the review: 3 studies of clozapine, 7 studies of quetiapine, 2 head-to-head trials comparing quetiapine and clozapine, and 1 noncomparative trial of clozapine or quetiapine interventions. Most of the studies included participants with a mean age in the early to mid 70s and a mean duration of PD typically >10 years.. Results of the identified studies suggested that patients with PD might benefit from long-term clozapine therapy. Results of the quetiapine studies were conflicting. However, no statistically significant difference in effectiveness was found between quetiapine and clozapine in comparative trials. The significance of the differences in treatment responses between patients with dementia and those without dementia remains unclear, and it was not possible to draw conclusions for or against other atypical antipsychotics because of insufficient evidence. Further studies are needed to address the methodologic issues in the current trials and to assess safety issues in larger cohorts.

Topics: Aged; Antipsychotic Agents; Brief Psychiatric Rating Scale; Clozapine; Comorbidity; Delusions; Dementia; Depression; Dibenzothiazepines; Disease Progression; Guidelines as Topic; Hallucinations; Humans; Middle Aged; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Research Report; Risperidone

Visual hallucinations (VHs) occur frequently in Parkinson's disease (PD). VHs occur more frequently in elderly patients with longer duration of illness, cognitive impairment, and sleep disturbances. The relationship between the use of antiparkinsonian drugs and VHs is complicated, but most drugs used to treat parkinsonian motor symptoms induce VHs and psychosis in some PD patients. The "continuum hypothesis" proposing that medication-induced psychiatric symptoms in PD begin with drug-induced sleep disturbances, followed by vivid dreams, with progression to hallucinatory and delusional experiences has been challenged. In some patients, VHs may represent intrusion of REM sleep-related imagery into wakefulness. Improving REM sleep abnormalities in PD (e.g., stimulants, anticholinesterase inhibitors) is one strategy now being tested to improve VHs in PD.

Topics: Antiparkinson Agents; Cholinesterase Inhibitors; Clozapine; Dopamine Agents; Dreams; Hallucinations; Humans; Parkinson Disease; Polysomnography; Psychotic Disorders; Sleep Deprivation; Sleep Disorders, Intrinsic; Sleep, REM

Drug-induced iatrogenic hallucinations and psychosis occur in about 30% of Parkinson's disease (PD) patients and are the single most important precipitant for nursing home placement, which carries a grave prognosis. In addition, parkinsonism is a frequent accompaniment to the more common dementing syndromes, Alzheimer's disease (AD), vascular dementia, and dementia with Lewy bodies (DLB). The five most recent antipsychotic drugs approved by the Food and Drug Administration in the United States have been marketed as "atypical" antipsychotics (AA) due to their relative freedom from extrapyramidal symptoms when used in schizophrenia patients. The use of these newer antipsychotic drugs in PD and other parkinson-sensitive populations represents the most stringent test to their freedom from motor side effects. To date, clozapine, risperidone, olanzapine, and quetiapine have been studied in parkinson-vulnerable populations. This article reviews the data and highlights the differences that these four drugs have on motor function. It also emphasizes the challenges in evaluating the available data on the motor effects of AA, especially on the non-PD elderly and cognitively impaired population. Suggestions are made for future research to improve the interpretability of these studies.

Topics: Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Clozapine; Dementia, Vascular; Dibenzothiazepines; Hallucinations; Humans; Iatrogenic Disease; Lewy Body Disease; Olanzapine; Parkinson Disease; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Risperidone

Schizophrenia is a seriously disturbing disorder, both for the victim and for their families. Although treatments are available which can effectively control symptoms, their side effects are severe enough to cause many sufferers to discontinue taking them and their actions are not properly understood.

Topics: Antipsychotic Agents; Chlorpromazine; Clozapine; Delusions; Dopamine Antagonists; Female; GABA Antagonists; Hallucinations; Humans; Magnetic Resonance Angiography; Male; Neurotransmitter Agents; Receptors, Dopamine D2; Schizophrenia; Synapses; Tomography, Emission-Computed

Besides the well-known adverse effects of clozapine, such as granulocytopenia, tiredness and hypersalivation, acute pancreatitis is known to be a very rare complication of the drug. In the literature a total of five case reports have been published so far. We report a case of asymptomatic pancreatitis subsequent to clozapine treatment at therapeutic doses in a 38-year-old male patient with chronic paranoid-hallucinatory schizophrenia. The patient was rehospitalized after an acute exacerbation of the psychosis subsequent to an attempt to change medication on an outpatient basis. Treatment with clozapine was initiated again. During phases of progressively increasing the clozapine dose, serum levels of amylase and lipase were increased; after maintaining daily doses of clozapine of 300 mg and/or 600 mg the pancreatic enzymes normalized quickly within a few days. The patient did not report any pancreas-related complaints, nor did specific diagnostic studies produce any indicative result, only a minor thickening of the head and body of the pancreas in the ultrasound. It is assumed that the phenomenon of subclinical, asymptomatic pancreatitis during increasing dosage of clozapine occurs more often than previously supposed. The monitoring of serum amylase levels during slow increase in clozapine is recommended; if leukocytosis or eosinophilia is present, the possibility of even a subclinical and asymptomatic pancreatitis should be considered.

Topics: Adult; Amylases; Antipsychotic Agents; Chronic Disease; Clozapine; Drug Monitoring; Hallucinations; Humans; Lipase; Male; Pancreatitis; Recurrence; Schizophrenia, Paranoid

Significant consequences of untreated psychosis in patients with dementia have led clinicians to seek improved therapeutic options. This review presents the scope of the problem, discusses some of the underlying neurobiology, and highlights the evidence for appropriate therapies. A range of potentially effective pharmacologic therapies is available and is discussed.

Topics: Aged; Antipsychotic Agents; Clozapine; Comorbidity; Delusions; Dementia; Hallucinations; Humans; Psychotic Disorders; Risperidone; Treatment Outcome

Attempts to clarify the domains of schizophrenia gained importance when the atypical antipsychotics joined the armamentarium of schizophrenia treatments because of evidence that these agents are superior to conventional antipsychotics for the treatment of negative symptoms. Negative symptoms can be divided into 3 components: (1) deficit or primary enduring negative symptoms that may or may not respond to treatment, (2) primary nonenduring negative symptoms, and (3) secondary negative symptoms that are associated with positive symptoms, extrapyramidal symptoms, depression, and environmental deprivation. The atypical antipsychotics have generally been found to be more effective than conventional antipsychotics against the totality of negative symptoms, but their effects on specific components are still under study. Sophisticated statistical tools such as path analysis have been used in investigations of the direct and indirect effects of atypical antipsychotics on negative symptoms, but these tools have limitations. Future study is needed to identify specific components of negative symptoms that may respond preferentially to one or another of the atypical antipsychotics.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Clozapine; Delusions; Depressive Disorder; Hallucinations; Humans; Models, Statistical; Multivariate Analysis; Psychiatric Status Rating Scales; Regression Analysis; Risperidone; Schizophrenia; Schizophrenic Psychology

Three patients underwent fMRI during a word generation task before and after successful treatment of auditory hallucinations with rTMS and were compared to four control subjects. There was a significant increase and more normal task related brain activation in brain areas involved in language processing including left temporoparietal cortex after rTMS treatment.

Topics: Adult; Amisulpride; Antipsychotic Agents; Clozapine; Combined Modality Therapy; Female; Functional Laterality; Hallucinations; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Parietal Lobe; Reaction Time; Schizophrenia; Sulpiride; Temporal Lobe; Transcranial Magnetic Stimulation; Treatment Outcome

To study the therapeutic effects on auditory hallucinations refractory to clozapine with 1-Hz repetitive transcranial magnetic stimulation (rTMS) applied on the left temporoparietal cortex.. Eleven patients with schizophrenia (DSM-IV) experiencing auditory hallucinations (unresponsive to clozapine) were randomly assigned to receive either active of rTMS (N = 6) or sham stimulation (N = 5) (with concomitant use of clozapine) using a double-masked, sham-controlled, parallel design. A total of 160 minutes of rTMS (9600 pulses) was administered over 10 days at 90% motor threshold. The study was conducted from January 2003 to December 2005.. There was a reduction in hallucination scores in both groups, which persisted during follow-up in the active group for the items reality (p = .0493) and attentional salience (p = .0360). Both groups showed similar patterns of symptomatic changes on subscales (negative symptoms, general psychopathology) and total scores of the Positive and Negative Syndrome Scale, Clinical Global Impressions scale, and Visual Analog Scale.. Active rTMS in association with clozapine can be administered safely to treat auditory hallucinations, although its clinical utility is still questionable. No significant clinical effects were observed in the sample studied, possibly because it was too small and/or due to its high refractoriness.

Topics: Adult; Clozapine; Demography; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Drug Resistance; Female; Hallucinations; Humans; Male; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Transcranial Magnetic Stimulation; Treatment Outcome

Attentional deficits have been implicated in the pathophysiology of auditory hallucinations in schizophrenia. Since the latency of the P300 component of event-related potentials (ERPs) is considered to be a sensitive measure of stimulus classification speed, while its amplitude-a measure of attentional resource allocation when memory updating is engaged, the present study focuses on the comparison of P300 between healthy subjects and schizophrenic patients experiencing auditory hallucinations and treated with clozapine and olanzapine.. The auditory P300 was assessed during the anticipatory period of a short memory test, in 16 male hallucinated schizophrenic patients and 13 male normal subjects matched for age and educational level. The patients were reexamined under identical conditions when their hallucinations had resolved following treatment with clozapine (8 patients) and olanzapine (8 patients).. The patients with hallucinations exhibited significantly reduced P300 amplitude at leads Fp1, F3, (C3-T5)/2, F4, Cz and Fz, when compared to the normal controls and at leads Fp1, F3, F4, (C4-T6)/2, C4, P4, Cz and Fz when compared to themselves during the remission phase. However logistic regression models revealed that the most important leads, differentiating the patient group before treatment either with the healthy controls, or with itself after treatment, were that at the left temporoparietal and at the left prefrontal area. Memory performance of the patient group, even after treatment and in spite of its significant improvement, remained significantly less than that of healthy controls. both antipsychotic agents had similar effects on the p300 amplitude and memory performance.. These findings indicate that auditory hallucinations in schizophrenia manifest abnormal aspects of attention, mediated by a distributed network involving or affecting the left temporoparietal and left prefrontal area. Additionally, the present study points to an improvement of attentional function in schizophrenic patients experiencing auditory hallucinations, both in the clozapine group but also in the olanzapine group.

Topics: Adult; Antipsychotic Agents; Attention; Benzodiazepines; Case-Control Studies; Clozapine; Event-Related Potentials, P300; Hallucinations; Humans; Male; Memory, Short-Term; Neuropsychological Tests; Olanzapine; Psychiatric Status Rating Scales; Reaction Time; Schizophrenia

Auditory hallucinations are one the most enigmatic and hampering symptoms associated with schizophrenia. Non-invasive functional imaging techniques have begun to delineate the underlying neuronal basis. We investigated the spontaneous magnetoencephalographic activity in a 33-year-old male schizophrenic patient and compared the results to those obtained from 13 healthy controls. Despite current neuroleptic medication (clozapine) the patient was still suffering from auditory hallucinations. Using the dipole density method, we were able to demonstrate an increase of fast MEG activity (12.5-30 Hz) in the left auditory cortex associated with hallucinations. This activity was absent in healthy controls. We conclude that an increase in fast MEG activity in the auditory cortex is a neurophysiologic correlate for auditory hallucinations in schizophrenia.

Topics: Adult; Antipsychotic Agents; Beta Rhythm; Cerebral Cortex; Clozapine; Functional Laterality; Hallucinations; Humans; Magnetoencephalography; Male; Schizophrenic Psychology; Temporal Lobe

The aim of the study was to investigate patterns of the P600 component of event-related potentials (ERPs) elicited during a working memory test in 16 male schizophrenic patients experiencing auditory hallucinations before and after treatment with clozapine and olanzapine, and 13 male normal subjects matched for age and educational level. Before treatment, patients showed significantly reduced P600 amplitudes on the right parietal region compared with controls, and when in remission also showed significantly reduced P600 amplitudes located on the right parietal and temporofrontal areas, compared both to themselves before treatment and to normal controls. The patient's memory performance before and after treatment remained significantly lower than that of healthy controls. These findings may indicate that auditory hallucinations in schizophrenia are associated with impaired synchronization of the processes related to target detection, as reflected by the P600. The present study also casts doubts regarding the cognitive sparing effect of atypical antipsychotics, despite the fact that they mediate symptom improvement.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Brain; Clozapine; Cognition; Double-Blind Method; Evoked Potentials, Auditory; Hallucinations; Humans; Male; Memory; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Reference Values; Schizophrenia; Schizophrenic Psychology

To examine the long-term outcome of PD patients with psychosis requiring antipsychotic therapy; to explore predictors of mortality, nursing home placement, dementia, and persistent psychosis; and to compare outcomes of those with persistent psychosis vs those whose psychosis resolved.. Baseline data available from 59 patients enrolled in the PSYCLOPS (PSychosis and CLOzapine in PD Study) trial included age, age at onset of PD, duration of PD and psychosis, character of psychosis, medications, living setting, and scores for Mini-Mental State Examination (MMSE), Unified Parkinson's Disease Rating Scale, Hoehn and Yahr Scale, and Clinical Global Impression Scale. Longitudinal data were collected 26 months later regarding four outcomes: death, nursing home placement, diagnosis of dementia, and persistence of psychosis. Logistic regression was used to explore whether any baseline characteristics were associated with an increased likelihood of one of these outcomes.. At baseline, 56% of patients had an MMSE score of <25, 12% were in a nursing home, 95% had hallucinations, and 60% had paranoia. On follow-up, 25% were dead, nursing home placement occurred in 42%, psychosis was persistent in 69%, and dementia was diagnosed in 68%. Select baseline characteristics predicted individual outcomes: Nursing home placement was associated with the presence of paranoia and older age; persistent psychosis was associated with younger age at onset of PD and longer disease duration; dementia was associated with older age at PD onset and lower initial MMSE score; no characteristics predicted death. Whether psychosis persisted or not had no significant effect on the development of the other three outcomes. The prevalence of hallucinations at follow-up was not different between groups currently receiving antipsychotics vs those on no treatment.. Psychosis in PD requiring antipsychotic therapy is frequently associated with death, nursing home placement, development and progression of dementia, and persistence of psychosis. Still, it appears the prognosis has improved with atypical antipsychotic therapy based on the finding that 28% of NH patients died within 2 years compared with 100% in a previous study done prior to availability of this treatment.

Topics: Aged; Antipsychotic Agents; Clozapine; Dementia; Double-Blind Method; Female; Hallucinations; Humans; Longitudinal Studies; Male; Nursing Homes; Parkinson Disease; Psychotic Disorders; Treatment Outcome

The effects of transcranial magnetic stimulation (TMS) on hallucination severity and neurocognition were studied in 9 medication-resistant hallucinating patients. A statistically significant improvement was observed on a hallucination scale after 10 days of TMS at the left auditory cortex.

Topics: Adult; Antipsychotic Agents; Auditory Cortex; Clozapine; Cognition; Electromagnetic Fields; Female; Hallucinations; Humans; Male; Neuropsychological Tests; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology

To compare olanzapine and clozapine for safety and efficacy measures of psychosis and motor function in patients with PD and chronic hallucinations.. Hallucinations occur in approximately one third of patients with PD treated chronically with dopaminergic drugs. Although clozapine is known to be an effective antipsychotic agent that does not significantly exacerbate parkinsonism, its use requires frequent blood count assessment. Olanzapine is another novel antipsychotic that is not associated with blood dyscrasia, and if equally effective could become the preferred drug for treating hallucinations in subjects with PD.. A randomized, double-blind, parallel comparison of olanzapine and clozapine in patients with PD with chronic hallucinations was conducted. The primary outcome measure was the Scale for the Assessment of Positive Symptoms (SAPS) for psychotic symptoms. The Unified Parkinson's Disease Rating Scale (UPDRS) motor subscale was used as a secondary outcome measure and as a safety monitoring tool.. After 15 patients had completed the study, safety stopping rules were invoked because of exacerbated parkinsonism in olanzapine-treated subjects. UPDRS motor impairment scores from baseline to study end significantly increased with olanzapine treatment, and change scores between the olanzapine and clozapine groups significantly differed. The primary clinical domains responsible for the motor decline were gait and bradykinesia. Even with a smaller patient number than originally anticipated, clozapine significantly improved hallucinations and overall behavioral assessment, whereas olanzapine had no effect.. At the doses studied, olanzapine aggravates parkinsonism in comparison with clozapine and should not be regularly used in the management of hallucinations in patients with PD.

Topics: Aged; Behavior; Benzodiazepines; Clozapine; Double-Blind Method; Female; Hallucinations; Humans; Male; Middle Aged; Movement; Olanzapine; Parkinson Disease; Pirenzepine

Two reaction time (RT) paradigms were used to study clozapine's effects on sustained and selective attention compared to fluphenazine and placebo in 25 chronic schizophrenic patients. Sensory dominance was studied via simple and choice RTs to lights and tones, and on double-stimulus trials in which the two stimuli were presented simultaneously. Although 8 of the 25 patients could not perform the RT tasks when taking placebo, there were no effects of clozapine on simple or choice RT compared to placebo or fluphenazine. Subjects on all 3 treatments showed visual dominance: faster RT to lights than to tones on choice and double-stimulus trials. However, clozapine reduced this by means of a selective increase in RT to lights. Clozapine reduced failures to respond to the tone on double-stimulus trials. This was shown to be due to reductions in hallucinations. Clozapine does not generally improve attention, but it may increase the ability of schizophrenic persons to process nondominant or unattended stimuli possibly by increasing the efficiency of resource allocation. This may be partially mediated by a reduction in hallucinations.

Topics: Adult; Attention; Auditory Perception; Clozapine; Dominance, Cerebral; Dyskinesia, Drug-Induced; Female; Fluphenazine; Hallucinations; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Reaction Time; Schizophrenia; Schizophrenic Psychology; Visual Perception

Dementia with Lewy bodies (DLB) is characterized by neurocognitive disorders associated with core clinical features including hallucinations. There is currently no cure but a combination of symptomatic treatments: clozapine is commonly used in DLB-related psychosis. Pimavanserin is a serotonin 5HT-2A receptor inverse agonist that has recently been shown to reduce psychosis related to dementia. Trazodone is a serotonin reuptake inhibitor and a 5-HT2 receptor antagonist: it is effective in the treatment of the frontal syndrome and is commonly used in frontotemporal degeneration.. We describe three patients with DLB, hospitalized in the cognitive-behavioral unit of the University Hospitals of Strasbourg, who presented with major visual hallucinations, delusion, and an orbitofrontal syndrome including disinhibition, agitation, and irritability. The 3 patients were intolerant of low-dose Clozapine (neutropenia for one, somnolence for the other and Pisa syndrome and falls for the last one). We evaluated the Neuropsychiatric Inventory (NPI) before and after the introduction of both treatments.. Given their psychotic and frontal symptoms, we used Pimavanserin and Trazodone simultaneously. After 4 to 6 weeks of treatment, a marked improvement was observed in all 3 patients, with a decrease of the NPI scores from a mean of 88 to 38.. To our knowledge, there is no previously described combination of these two treatments in DLB. A clinical trial combining these two molecules against pervasive behavioral disorders in DLB would be interesting in view of these preliminary results.

Topics: Clozapine; Dementia; Drug Inverse Agonism; Hallucinations; Humans; Lewy Body Disease; Trazodone

The hierarchical characteristics of the brain are prominent in the pharmacological treatment of psychiatric diseases, primarily targeting cellular receptors that extend upward to intrinsic connectivity within a region, interregional connectivity, and, consequently, clinical observations such as an electroencephalogram (EEG). To understand the long-term effects of neuropharmacological intervention on neurobiological properties at different hierarchical levels, we explored long-term changes in neurobiological parameters of an N-methyl-D-aspartate canonical microcircuit model (CMM-NMDA) in the default mode network (DMN) and auditory hallucination network (AHN) using dynamic causal modeling of longitudinal EEG in clozapine-treated patients with schizophrenia. The neurobiological properties of the CMM-NMDA model associated with symptom improvement in schizophrenia were found across hierarchical levels, from a reduced membrane capacity of the deep pyramidal cell and intrinsic connectivity with the inhibitory population in DMN and intrinsic and extrinsic connectivity in AHN. The medication duration mainly affects the intrinsic connectivity and NMDA time constant in DMN. Virtual perturbation analysis specified the contribution of each parameter to the cross-spectral density (CSD) of the EEG, particularly intrinsic connectivity and membrane capacitances for CSD frequency shifts and progression. It further reveals that excitatory and inhibitory connectivity complements frequency-specific CSD changes, notably the alpha frequency band in DMN. Positive and negative synergistic interactions exist between neurobiological properties primarily within the same region in patients treated with clozapine. The current study shows how computational neuropharmacology helps explore the multiscale link between neurobiological properties and clinical observations and understand the long-term mechanism of neuropharmacological intervention reflected in clinical EEG.

Topics: Brain; Brain Mapping; Clozapine; Electroencephalography; Hallucinations; Humans; Magnetic Resonance Imaging; N-Methylaspartate; Nerve Net; Neuropharmacology; Schizophrenia

Schizophrenia is a psychiatric disorder that presents with hallucinations, delusions, thought disorders, and cognitive dysfunctions. Antipsychotic monotherapy is effective in the treatment of schizophrenia. In recent years, the main antipsychotics used have been second-generation antipsychotics, also called atypical antipsychotics, which have a slightly lower incidence of side effects. When monotherapy of two or more antipsychotics fails to produce sufficient improvement, a diagnosis of treatment-resistant schizophrenia is made, and clozapine is used.

Topics: Antipsychotic Agents; Clozapine; Hallucinations; Humans; Risperidone; Schizophrenia

There is evidence of heterogeneity within treatment-resistant schizophrenia (TRS), with some people not responding to antipsychotic treatment from illness onset and others becoming treatment-resistant after an initial response period. These groups may have different aetiologies.. This study investigates sociodemographic and clinical correlates of early onset of TRS.. Employing a retrospective cohort design, we do a secondary analysis of data from a cohort of people with TRS attending the South London and Maudsley. Regression analyses were conducted to identify the correlates of the length of treatment to TRS. Predictors included the following: gender, age, ethnicity, problems with positive symptoms, problems with activities of daily living, psychiatric comorbidities, involuntary hospitalisation and treatment with long-acting injectable antipsychotics.. In a cohort of 164 people with TRS (60% were men), the median length of treatment to TRS was 3 years and 8 months. We observed no cut-off on the length of treatment until TRS presentation differentiating between early and late TRS (i.e. no bimodal distribution). Having mild to very severe problems with hallucinations and delusions at the treatment start was associated with earlier TRS (~19 months earlier). In sensitivity analyses, including only complete cases (subject to selection bias), treatment with a long-acting injectable antipsychotic was additionally associated with later TRS (~15 months later).. Our findings do not support a clear separation between early and late TRS but rather a continuum of the length of treatment before TRS onset. Having mild to very severe problems with positive symptoms at treatment start predicts earlier onset of TRS.

Topics: Activities of Daily Living; Antipsychotic Agents; Clozapine; Female; Hallucinations; Humans; Male; Retrospective Studies; Schizophrenia

Topics: Antipsychotic Agents; Attention; Clozapine; Early Medical Intervention; Hallucinations; Humans; Male; Middle Aged; Schizophrenia

Biological strategies to improve treatment efficacy in clozapine-treated patients are urgently needed. Repetitive transcranial magnetic stimulation (rTMS) merits consideration as intervention for patients with persistent auditory hallucinations (AH) or negative symptoms (NS) not responding sufficiently to clozapine treatment.. Data from 10 international RCTs of rTMS for patients being treated with clozapine were pooled. Two levels of symptomatic response were defined: improvement of. Analyses of 131 patients did not reveal a significant difference for. rTMS as a treatment for persistent symptoms in clozapine-treated patients did not show a beneficial effect of active compared to sham treatment. For AH, the size of the NNTs indicates a possible beneficial effect of rTMS.

Topics: Clozapine; Double-Blind Method; Hallucinations; Humans; Schizophrenia; Schizophrenic Psychology; Transcranial Magnetic Stimulation; Treatment Outcome

This case report describes successful maintenance treatment with oral S-ketamine in a patient with severe depression, who previously was resistant to electroconvulsive therapy and deep brain stimulation, and who also had comorbid psychotic and obsessive compulsive symptoms.

Topics: Administration, Oral; Anti-Anxiety Agents; Antidepressive Agents; Antipsychotic Agents; Clozapine; Deep Brain Stimulation; Depressive Disorder, Treatment-Resistant; Electroconvulsive Therapy; Female; Glycopyrrolate; Hallucinations; Humans; Ketamine; Middle Aged; Muscarinic Antagonists; Nitrazepam; Obsessive-Compulsive Disorder; Treatment Failure; Venlafaxine Hydrochloride

Parkinson's disease is a chronic multi-system disease that can cause motor and non-motor symptoms, cognitive changes and variably effective medications. Optimal management of the condition requires a multi-disciplinary team of healthcare professionals to work closely with the patient and their carers. The National Institute for Health and Care Excellence published updated guidelines on managing Parkinson's disease in adults in 2017. Here we discuss the implications of this guidance to current healthcare professionals involved in the care of people with Parkinson's disease. The guidance highlights the importance of clear communication with people with Parkinson's disease. We discuss examples of this, including providing a point of contact with specialist services for people with Parkinson's disease and ensuring information about the risks of impulse control disorders are given to people on dopaminergic therapy. The breadth of services required by people with Parkinson's disease is also described, including the need for access to physiotherapy, occupational therapy and speech and language therapy as well as treatment monitoring services for Clozapine. In addition, we emphasise the continued importance of ensuring people with Parkinson's disease receive their medications on time when in hospital or a care home.

Topics: Antiparkinson Agents; Clozapine; Hallucinations; Humans; Levodopa; Parkinson Disease; Patient Care Team; Patient Education as Topic; Practice Guidelines as Topic

Clozapine was the widely accepted gold standard treatment for treatment resistant psychotic symptoms. Clozapine has efficacy of about 50% and some responding patients have to discontinue it due to serious adverse effects. The search for novel agents to use for clozapine-non-responders continues. One such possible agent is the non-dopaminergic antipsychotic pimavanserin, an inverse agonist of serotonin 5-HT2A receptors which was recently approved for the hallucinations and delusions of Parkinson's Disease Psychosis. We report here the successful results of using pimavanserin in patients with refractory hallucinations and delusions who failed to respond to clozapine. We also report similar results in refractory psychosis patients who did not receive clozapine.. We present ten cases of patients with schizophrenia and schizoaffective disorder with refractory hallucinations and delusions who received a trial of pimavanserin when clozapine or multiple antipsychotics failed. Six of ten patients had not responded to a clozapine trial. The subjects' ages ranged between 21 and 77 years and were followed up for several months.. All 10 patients with refractory hallucinations and delusions showed marked response to pimavanserin 34 mg/day within 4-8 weeks, with continuation of the response for several months of follow-up. Improvements in negative symptoms and social functioning were also observed in several patients.. This series of 10 cases of patients with refractory psychosis who responded to pimavanserin is an important new finding that has never been reported before. Controlled studies comparing clozapine and pimavanserin in refractory schizophrenia are warranted to confirm these clinical observations.

Topics: Adult; Aged; Antipsychotic Agents; Clozapine; Delusions; Drug Resistance; Female; Hallucinations; Humans; Male; Middle Aged; Piperidines; Psychotic Disorders; Retrospective Studies; Schizophrenia; Serotonin 5-HT2 Receptor Antagonists; Urea; Young Adult

Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia associated with poor prognosis and high carers' burden. Neuropsychiatric symptoms worsen this prognosis and are a high source of distress for service users and their carers. However, there is currently insufficient evidence to support the pharmacological and non-pharmacological management of these symptoms. Acetylcholinesterase inhibitors are the first-line pharmacological option, but challenging risky behaviours may persist despite their use. Antipsychotic medications are indicated in such clinical scenarios, but there is very limited evidence to support the efficacy and safety of these medications for managing neuropsychiatric symptoms in DLB. Hence, we report an individual with DLB with severe distressing persistent visual hallucinations and agitation. After multiple treatment options had failed, clozapine was successfully initiated with substantial improvement in both clinical and functional outcomes. Further studies are warranted for evaluating the efficacy of clozapine in managing neuropsychiatric symptoms in DLB.

Topics: Aged; Antipsychotic Agents; Clozapine; Hallucinations; Humans; Lewy Body Disease; Magnetic Resonance Imaging; Male; Treatment Outcome

Patients with psychiatric disorders in critical condition are difficult to treat. In this study, we report on a patient with underlying schizoaffective disorder who developed catatonia, cardiac arrest, and pulmonary embolism, as well as a successful treatment strategy.. The inpatient is a 41-year-old morbidly obese male with schizoaffective disorder whose clozapine dosage was titrated from 100 mg to 175 mg due to auditory hallucination and agitation. The patient abruptly developed acute cardiopulmonary symptoms associated with an elevated troponin-I level. He was transferred to a cardiac intensive care unit, where he remained for 3 days. He was also found to have excited catatonic symptoms, and the lorazepam-diazepam protocol was initiated to quickly relieve the catatonia. Once the coronary angiogram was read as normal, the patient was transferred back to the psychiatric ward. However, the patient then suffered from in-hospital cardiac arrest. He was resuscitated and again transferred to the medical intensive care unit. Computed tomography confirmed the diagnosis of a pulmonary embolism. The patient was treated with Rivaroxaban 30 mg/d for the first 21 days, followed by 20 mg daily for 3 months. To control his severe and refractory psychotic symptoms, the patient was re-prescribed clozapine. During the 15-month follow-up period, the patient demonstrated a fair response and tolerability to clozapine 150 mg without symptoms relapse and no thromboembolic event.. This report can serve to remind psychiatrists and physicians to be aware of fatal conditions in patients with psychiatric diseases and physical illnesses.

Topics: Adult; Antipsychotic Agents; Catatonia; Clozapine; Drug Therapy, Combination; Factor Xa Inhibitors; Hallucinations; Humans; Male; Obesity, Morbid; Psychotic Disorders; Pulmonary Embolism; Rivaroxaban; Treatment Outcome

Topics: Antipsychotic Agents; Clozapine; Delusions; Hallucinations; Humans; Male; Quetiapine Fumarate; Schizophrenia; Vision Disparity

Topics: Antiparkinson Agents; Antipsychotic Agents; Brain Diseases, Metabolic; Capgras Syndrome; Clozapine; Dopamine; Hallucinations; Humans; Infusions, Parenteral; Levodopa; Male; Middle Aged; Psychoses, Substance-Induced

Dynamic relationships between the symptoms of psychosis can be shown in individual networks of psychopathology. In a single patient, data collected with the Experience Sampling Method (ESM-a method to construct intensive time series of experience and context) can be used to study lagged associations between symptoms in relation to illness severity and pharmacological treatment.. The patient completed, over the course of 1 year, for 4 days per week, 10 daily assessments scheduled randomly between 10 minutes and 3 hours apart. Five a priori selected symptoms were analysed: 'hearing voices', 'down', 'relaxed', 'paranoia' and 'loss of control'. Regression analysis was performed including current level of one symptom as the dependent variable and all symptoms at the previous assessment (lag) as the independent variables. Resulting regression coefficients were printed in graphs representing a network of symptoms. Network graphs were generated for different levels of severity: stable, impending relapse and full relapse.. ESM data showed that symptoms varied intensely from moment to moment. Network representations showed meaningful relations between symptoms, e.g. 'down' and 'paranoia' fuelling each other, and 'paranoia' negatively impacting 'relaxed'. During relapse, symptom levels as well as the level of clustering between symptoms markedly increased, indicating qualitative changes in the network. While 'hearing voices' was the most prominent symptom subjectively, the data suggested that a strategic focus on 'paranoia', as the most central symptom, had the potential to bring about changes affecting the whole network.. Construction of intensive ESM time series in a single patient is feasible and informative, particularly if represented as a network, showing both quantitative and qualitative changes as a function of relapse.

Topics: Antipsychotic Agents; Clozapine; Dose-Response Relationship, Drug; Female; Hallucinations; Humans; Middle Aged; Paranoid Disorders; Psychotic Disorders; Regression Analysis

Topics: Adult; Antidepressive Agents, Second-Generation; Bupropion; Clozapine; Drug Therapy, Combination; Electroencephalography; Hallucinations; Humans; Male; Occipital Lobe; Schizophrenia; Seizures

Visual hallucinations (VH) are sometimes difficult to treat in patients with Lewy body dementia (LBD). We describe the concurrent use of clozapine and levodopa for the treatment of persistent VH and parkinsonism in a patient with LBD and severely increased sensitivity to antipsychotics.

Topics: Aged; Antipsychotic Agents; Brain; Clozapine; Comorbidity; Hallucinations; Humans; Levodopa; Lewy Body Disease; Male; Parkinson Disease; Treatment Outcome

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

Some patients with schizophrenia suffer from continuous auditory hallucinations that are refractory to antipsychotic medications.. Transcranial direct current stimulation (tDCS) was used to treat a 24-year-old female schizophrenia patient who had severe, clozapine-refractory, continuous, psychosocially and cognitively disabling auditory hallucinations. The tDCS cathode was placed midway between T3 and P3, and the anode over F3, in the 10-20 electroencephalogram electrode positioning system.. Once daily, 20-minute tDCS sessions at 1-mA intensity produced noticeable improvement within a week: cognitive and psychosocial functioning improved, followed by attenuation in the experience of hallucinations. There was greater than 90% self-reported improvement within 2 months. Benefits accelerated when the current was raised to 3 mA; treatment duration was increased to 30-minute sessions, and session frequency was increased to twice daily. The patient improved from a psychosocially vegetative state to near-normal functioning. Once- to twice-daily domiciliary tDCS was continued across nearly 3 years and is still ongoing. Benefits attenuated or were even lost when alternate day session spacing was attempted, or when electrode positioning was changed; benefits were regained when the original stimulation protocol was reintroduced. There was confirmation of benefit in 2 separate on-off-on situations, which occurred inadvertently and under blinded conditions. There were no adverse events attributable to tDCS.. This is the first report in literature of the safe and effective use of daily to twice-daily, domiciliary, 30-min, 1- to 3-mA tDCS sessions across nearly 3 years for the treatment of continuous, disabling, clozapine-refractory auditory hallucinations in schizophrenia. Key learning points emerging from this case are presented and discussed.

Topics: Antipsychotic Agents; Clozapine; Drug Resistance; Drug Therapy, Combination; Electric Stimulation Therapy; Female; Hallucinations; Home Care Services; Humans; Inpatients; Schizophrenia; Schizophrenic Psychology; Young Adult

Marijuana (cannabis) is the most commonly abused drug by adolescents and young adults and also by people with schizophrenia or other psychotic disorders. An increasing number of studies suggest that regular cannabis users can show psychotic episodes similar to schizophrenic disorders but it still unclear if cannabis induced psychotic disorder is a distinct entity requiring special therapy or regular cannabis use consequently leads to schizophrenia. Therefore, we retrospectively compared psychotic patients with and without cannabis use by clinical profile. Clinical data of 85 patients with schizophrenia spectrum disorder were analyzed retrospectively. Cannabis use was not reported by 43 persons (Cnbs0 subgroup) and 42 patients used regularly cannabis during at least 1 year (Cnbs1 subgroup). Clinical data were collected from electronic medical documentation of patients concerning anamnesis, family history, socio-demographic condition, symptoms and psychiatric state, acute and long-term therapies. Men were over-represented in the cannabis abuser group while mean age was lower among them compared to the Cnbs0 subgroup. Prevalence of suicidal attempts was increased in men without cannabis use. Patients without cannabis use spent more time in hospital and smoking was more frequent among them. Positive and negative symptoms and family history did not differ significantly between the two subgroups. Dosage, intensity and length of pharmacotherapy was different between the two subgroups. These results revealed that certain clinical aspects were different in case of cannabis-related schizophrenia spectrum disorder compared to schizophrenia.

Topics: Adolescent; Adult; Aggression; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Dibenzothiazepines; Hallucinations; Haloperidol; Humans; Hungary; Male; Marijuana Abuse; Olanzapine; Paranoid Disorders; Piperazines; Psychomotor Performance; Quetiapine Fumarate; Quinolones; Retrospective Studies; Risperidone; Schizophrenia; Schizophrenic Psychology

Topics: Antipsychotic Agents; Catatonia; Clozapine; Delusions; Electroconvulsive Therapy; Female; Fever; Hallucinations; Humans; Recurrence; Young Adult

Topics: Amisulpride; Antipsychotic Agents; Clozapine; Cognitive Behavioral Therapy; Combined Modality Therapy; Dominance, Cerebral; Follow-Up Studies; Hallucinations; Humans; Middle Aged; Parietal Lobe; Schizophrenia, Paranoid; Sulpiride; Temporal Lobe; Theta Rhythm; Transcranial Magnetic Stimulation; Treatment Outcome

The authors report an improvement in delusions and hallucinations after antidepressant treatment (Clomipramine) in a parkinsonian patient with psychosis and comorbid depression. Their findings, which support a previous case treated with Citalopram, highlight the possible effectiveness of antidepressant therapy on psychotic symptoms in parkinsonian patients.

Topics: Affect; Antidepressive Agents; Antidepressive Agents, Tricyclic; Antiparkinson Agents; Antipsychotic Agents; Clomipramine; Clozapine; Delusions; Depressive Disorder; Hallucinations; Humans; Levodopa; Male; Middle Aged; Parkinson Disease; Pergolide; Psychiatric Status Rating Scales; Psychotic Disorders

Topics: Adult; Allopurinol; Antipsychotic Agents; Chronic Disease; Clozapine; Drug Therapy, Combination; Female; Gout; Gout Suppressants; Hallucinations; Humans; Piperazines; Psychoses, Substance-Induced; Recurrence; Schizophrenia, Paranoid; Thiazoles

Topics: Adult; Antipsychotic Agents; Clozapine; Female; Hallucinations; Humans; Pregnancy; Pregnancy Complications

Topics: Adult; Antipsychotic Agents; Clozapine; Female; Hallucinations; Humans; Thrombophilia

Abrupt clozapine withdrawal can cause rebound psychosis and severe somatic symptoms in psychiatric patients. We report on the case of an advanced Parkinson's disease patient who developed myoclonus, tremor, rigidity, hyperreflexia, and stupor after abrupt clozapine withdrawal. The patient's symptoms resolved with treatment with cyproheptadine. This clinical picture suggests serotonergic rebound as an explanation for the patient's symptoms, although other pharmacological mechanisms are possible. Clozapine should be gradually withdrawn over a period of 1 to 2 weeks when possible, and abruptly discontinued only when necessary.

Topics: Aged; Antipsychotic Agents; Carbidopa; Clozapine; Dose-Response Relationship, Drug; Drug Combinations; Drug Interactions; Drug Therapy, Combination; Hallucinations; Humans; Levodopa; Male; Neurologic Examination; Parkinson Disease; Parkinson Disease, Secondary; Substance Withdrawal Syndrome

Topics: Clozapine; Dibenzothiazepines; Dopamine Agonists; Dyskinesias; Hallucinations; Humans; Levodopa; Parkinson Disease; Practice Guidelines as Topic; United States

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Clozapine; Dyskinesia, Drug-Induced; Hallucinations; Humans; Male; Olanzapine; Parkinson Disease; Pirenzepine

Topics: Antipsychotic Agents; Benzodiazepines; Bias; Clozapine; Hallucinations; Humans; Olanzapine; Parkinson Disease; Pirenzepine

The use of generic drugs has resulted in considerable cost savings; however, whether all generics are truly bioequivalent to their brand-name counterparts is questionable. Although the efficacy of clozapine in the management of treatment-resistant schizophrenia has been well established, reports of relapse after conversion to a generic formulation are becoming more common.. This article presents 7 case studies of patients in a long-term residential care facility who experienced a relapse of psychotic symptoms when the pharmacy inadvertently switched their therapy from brand-name clozapine to a generic formulation. Neither patients, physicians, nor staff of the facility were aware of this switch. Possible reasons for the apparent increased risk of relapse in some patients switched to the generic formulation of clozapine are explored, with reference to US Food and Drug Administration bioequivalence standards and reports.. All 7 patients, whose condition had been well stabilized with brand-name clozapine, experienced a rapid and profound deterioration after the switch to the generic formulation. Five patients required hospitalization. All patients responded well when brand-name clozapine was reinstated.. The findings suggest that brand-name clozapine and the generic formulation may display important clinical differences, and a comparable therapeutic response may not be achievable despite adequate monitoring. Large, controlled, prospective trials are needed to clarify the potential for treatment failure with the use of generic clozapine.

Topics: Adult; Aged; Antipsychotic Agents; Clozapine; Depression; Drugs, Generic; Female; Hallucinations; Humans; Male; Middle Aged; Psychotic Disorders; Recurrence; Schizophrenia

Four patients affected by severe Parkinson's disease developed leucopenia (900-1200 WBC) during treatment of psychosis (3) or untreatable insomnia (1) with clozapine (37.5-75 mg/day). Clozapine withdrawal was followed by recovery of leucopenia (4000-6000 WBC) in two weeks with no need for the administration of leucokines. After 1-6 months olanzapine was administered (increasing the dose from 2.5 to 10 mg/day) to treat persisting disturbances, but the drug induced severe worsening of parkinsonism and also this drug had to be withdrawn.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Clozapine; Dose-Response Relationship, Drug; Female; Hallucinations; Humans; Leukopenia; Male; Olanzapine; Parkinson Disease; Pirenzepine; Psychotic Disorders; Sexual Dysfunctions, Psychological; Sleep Initiation and Maintenance Disorders

The atypical antipsychotic drug olanzapine has been proposed for treatment of dopaminergic psychosis in Parkinson's disease (PD). We report on a 68-year-old patient who developed a severe akinetic-rigid extrapyramidal syndrome, accompanied by additional paranoid symptoms, following olanzapine treatment of optic hallucinosis in PD. Olanzapine may also induce clinically relevant extrapyramidal side effects in PD patients.

Topics: Aged; Antiparkinson Agents; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Drug Therapy, Combination; Hallucinations; Humans; Levodopa; Male; Olanzapine; Paranoid Disorders; Parkinson Disease; Piperidines; Pirenzepine; Selegiline; Severity of Illness Index

Topics: Adolescent; Age of Onset; Antipsychotic Agents; Child; Clozapine; Dose-Response Relationship, Drug; Drug Administration Schedule; Hallucinations; Humans; Male; Schizophrenia, Paranoid

Topics: Aged; Antipsychotic Agents; Clozapine; Dementia; Hallucinations; Humans; Male; Parkinson Disease; Seizures

The delusional misidentification syndrome (DMS) has been associated with a range of neurological conditions. Three cases of DMS in patients with Parkinson's disease and dementia, treated with dopaminergic medications, are presented. It is postulated that DMS associated with parkinsonism results from a combination of dopaminergic psychosis and cognitive dysfunction involving the frontal lobe in particular. DMS in the setting of parkinsonism may be more frequent than commonly supposed.

Topics: Aged; Antiparkinson Agents; Antipsychotic Agents; Capgras Syndrome; Clozapine; Delusions; Female; Hallucinations; Humans; Male; Parkinson Disease

The authors examined the effect of prolonged clozapine treatment on central serotonergic (5-HT) function in schizophrenia.. Prolactin responses to the 5-HT releasing agent d-fenfluramine were measured in two groups of 10 schizophrenic subjects. The first group was tested twice, before and after a mean of 10 weeks of clozapine treatment. The second group was tested after a mean of 20 months of clozapine treatment.. The prolactin response was significantly blunted in these 20 patients treated with clozapine. There was a significant positive correlation between d-fenfluramine-evoked prolactin release and the overall positive symptom score and the hallucination and delusion subscores of the Scale for the Assessment of Positive Symptoms.. Blunted 5-HT-mediated prolactin responses in schizophrenic patients receiving clozapine monotherapy for up to 20 months were correlated with reductions in positive symptoms. This suggests that 5-HT antagonism is relevant to clozapine's efficacy in alleviating hallucinations and other positive schizophrenic symptoms.

Topics: Adult; Antipsychotic Agents; Clozapine; Female; Fenfluramine; Hallucinations; Humans; Male; Prolactin; Psychiatric Status Rating Scales; Receptors, Serotonin; Schizophrenia; Schizophrenic Psychology; Serotonin Antagonists; Treatment Outcome

Dopaminergic psychosis frequently complicates the pharmacological treatment of Parkinson's disease. Dose reduction of dopaminomimetic therapy or treatment with conventional neuroleptics improves psychosis but worsens parkinsonism. In an open-label 12-month trial, the clinical antipsychotic efficacy of the atypical neuroleptic clozapine was investigated in 36 parkinsonian patients (age range 46-85 years) with symptoms of dopaminergic psychosis including delusions, vivid dreams, hallucinations, frank paranoid delirium, and hypersexuality. Clozapine, given orally at bedtime, was started at a dose of 6.25 mg and titrated upward to the minimal effective dose. In all patients, psychosis responded to very low clozapine doses (mean 10.59 +/- 6.48 mg/day). Clozapine doses correlated with the severity of psychosis. During clozapine treatment, parkinsonian disabilities and levodopa dosage remained statistically unchanged. During the 12-month study, no patient had clozapine-induced agranulocytosis or other severe side effects. These findings indicate that even at low doses, clozapine effectively controls dopaminergic psychosis in Parkinson's disease patients without compromising motor function.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Clozapine; Delusions; Dopamine; Female; Hallucinations; Humans; Male; Middle Aged; Parkinson Disease; Psychoses, Substance-Induced

Topics: Aged; Clozapine; Female; Hallucinations; Humans; Levodopa; Parkinson Disease; Pergolide

A 58-year-old man with chronic paranoid-hallucinatoric psychosis had transient episodes with marked paranoid delusions, auditory hallucinations without confusion, shakiness of both upper extremities, tachycardia and sweating. EMG performed with surface electrodes revealed many silent periods in postural active muscles with maximum duration of 120 ms; blood glucose was 65-75 mg/dl. At other times, blood glucose was 135-140 mg/dl, EMG revealed few silent periods in postural active muscles with maximal duration of 50 ms and the patient noted some vibration in his outstretched hands only. Drug-induced asterixis (clozapine, benperidol) amplified by relative hypoglycemia was therefore assumed, and symptoms disappeared after oral antidiabetics were reduced.

Topics: Antipsychotic Agents; Clozapine; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Therapy, Combination; Electromyography; Fasciculation; Glyburide; Hallucinations; Humans; Hypoglycemia; Hypoglycemic Agents; Male; Middle Aged; Motor Neurons; Muscle, Skeletal; Myoclonus; Neurologic Examination; Paranoid Disorders; Tremor

On one of our rehabilitation wards, we observed several schizophrenic patients with therapy resistant hallucinations to exhibit complete recovery after being given fluphenazine (2-7.5 mg a day, orally); previously, they were found to be therapy resistant on other potent neuroleptics, including clozapine. It appears that in selected patients fluphenazine has a special antihallucinatory effect.

Topics: Clozapine; Delusions; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluphenazine; Hallucinations; Humans; Schizophrenia; Schizophrenia, Paranoid; Schizophrenic Psychology

Seven patients with idiopathic Parkinson's disease, aged 62 to 76 years, average duration of the disease approximately eleven years, suffering from severe hallucinosis and paranoid delusions of different degree, in whom conventional therapeutic strategies (administration of benzodiazepines and mild neuroleptics) had no antipsychotic effect, received clozapine, a non-classical highly potent neuroleptic, while blood count was strictly monitored. Paranoid ideas disappeared in all seven patients after a maximum of four days administration of 25-125 mg/day. No deterioration of parkinsonian symptoms, quantified according to UPDRS was seen. Given the protection of clozapine, we could increase the L-dopa dose in two cases, thereby improving the patients' motor function. Blood count showed no abnormalities in any of the patients during an average observation period of seventeen months. Our results support the assumption that clozapine has a potent antipsychotic effect in the treatment of psychotic decompensation in advanced Parkinson's disease in carefully selected patients. We saw no negative influence of the neuroleptic on extrapyramidal symptoms.

Topics: Aged; Benserazide; Blood Cell Count; Clozapine; Female; Hallucinations; Humans; Levodopa; Male; Middle Aged; Paranoid Disorders; Parkinson Disease; Psychotic Disorders

Topics: Chronic Disease; Clozapine; Delusions; Hallucinations; Humans; Psychotherapy; Schizophrenia; Schizophrenic Psychology

Topics: Adult; Auditory Perceptual Disorders; Clozapine; Hallucinations; Humans; Intellectual Disability; Male; Priapism

Topics: Aged; Clozapine; Female; Hallucinations; Humans; Male; Middle Aged; Parkinson Disease; Psychotic Disorders

The clinical efficacy of clozapine, an atypical antipsychotic, in treating levodopa-induced hallucinations was investigated in five patients with Parkinson's disease under open label conditions. Two patients could not tolerate clozapine, even in doses as low as 12.5-25 mg daily, because of extreme sedation. Three patients could tolerate clozapine and experienced improvement or elimination of their hallucinations at doses below 100 mg daily. Despite a significant risk of adverse effects, cautious use of clozapine in low doses may be beneficial for patients with levodopa-induced psychosis who do not respond to more conservative measures.

Topics: Aged; Clozapine; Dibenzazepines; Dose-Response Relationship, Drug; Hallucinations; Humans; Levodopa; Male; Parkinson Disease

A total of 13 patients with drug-induced psychosis in Parkinson's disease were treated with two non-classical neuroleptics-clozapine and fluperlapine. Patients mainly complained about severe hallucinatory symptoms and different degrees of paranoid delusions. Complete relief was observed in 8 patients, moderate improvement in 3 and no effects in 2. Parkinsonian disability did not increase under neuroleptic medication with clozapine and fluperlapine, but could be ameliorated by additional L-dopa or bromocriptine medication. The non-classical neuroleptics employed are dopamine D2 blocking agents with a preferential binding to mesolimbic, mesocortical and hippocampal D2 receptors and no substantial binding to striatal dopamine receptors. Restricted use of these two neuroleptics is necessitated because of the danger of agranulocytosis.

Topics: Aged; Antipsychotic Agents; Benserazide; Bromocriptine; Clozapine; Delusions; Dibenzazepines; Dose-Response Relationship, Drug; Drug Therapy, Combination; Hallucinations; Humans; Hydrazines; Levodopa; Male; Middle Aged; Parkinson Disease; Psychoses, Substance-Induced; Tryptophan

Leponex was used to treat 120 schizophrenic patients with doses varying from 50 to 550 mg and the course of therapy lasting for two months. Considerable specificities were revealed in the spectrum of the drug psychotropic activity and the nature of its side effects. Leponex was especially effective in cases of delirious, hallucinational and catatonic symptomatology. This drug was proved to be a method of choice in progressive protracted schizophrenic psychoses accompanied by the above disorders. The regimen of gradual and slow accretion of daily doses throughout the treatment with leponex utilized in this study is assessed as optimal for preventing the development of toxic side effects associated with the use of this drug.

Topics: Adolescent; Adult; Antipsychotic Agents; Brief Psychiatric Rating Scale; Clozapine; Delusions; Dibenzazepines; Female; Hallucinations; Humans; Male; Middle Aged; Schizophrenia; Schizophrenia, Catatonic

Topics: Brain; Brain Stem; Clozapine; Dibenzazepines; Electroencephalography; Hallucinations; Humans; Paranoid Disorders