clozapine and Neuroleptic-Malignant-Syndrome

To identify the clinical determinants of fever in clozapine users and their impact on management of clozapine treatment.. Articles published in English or French identified with a MEDLINE, Web of Sciences, Cochrane Library and PsycINFO search, from inception through February 2019, using the term "clozapine" in combination with "fever" OR "hyperthermia" OR "body temperature" OR "pyrexia" OR "febrile" OR "heat" OR "thermoregulation". Information extracted for each medical condition were frequency, time to onset after initiation of clozapine treatment, characteristics of fever, associated symptoms, laboratory tests used for diagnosis, course, lethality, discontinuation of clozapine. Data were synthesized narratively.. Our search yielded 394 unique hits published from 1993 to 2018. We included 73 articles in the review: two meta-analyses, 14 reviews, six epidemiological studies, 11 clinical studies and 40 case reports. During clozapine initiation, fever is most frequently benign and transient but should be closely monitored as it may be the first stage of potentially life-threatening adverse drug reactions (ADR) (agranulocytosis, neuroleptic malignant syndrome myocarditis, hepatitis, pancreatitis, nephritis, colitis, etc.). Other ADR associated with fever are independent of duration of exposure to clozapine (heat stroke, pneumonia, pulmonary embolism, necrotizing colitis). If fever is due to intercurrent infection, therapeutic drug monitoring is recommended to adjust clozapine daily dosage.. Benign causes of fever are much more frequent than life-threatening ADR during clozapine treatment. Discontinuation should not be considered as automatic in the event of fever, especially during the early phase of clozapine initiation.

Topics: Agranulocytosis; Antipsychotic Agents; Chemical and Drug Induced Liver Injury; Clozapine; Colitis; Dose-Response Relationship, Drug; Drug Monitoring; Fever; Hepatitis; Humans; Infections; Lupus Erythematosus, Systemic; Myocarditis; Nephritis; Neuroleptic Malignant Syndrome; Pancreatitis; Pneumonia; Pulmonary Embolism; Schizophrenia; Serositis

Neuroleptic malignant syndrome (NMS) requires emergency treatment and can be fatal. Combined aripiprazole and clozapine therapy is rarely used in clinical settings, and NMS related this combination still lacks evaluation. Herein, we present two cases of atypical NMS treated with aripiprazole and clozapine.. Case 1 was a schizophrenic male with a history of NMS under treatment with aripiprazole 20 mg. He was hospitalized and maintained with aripiprazole 5 mg and clozapine 225 mg. On the 25th day, atypical NMS occurred with rigidity, elevated creatine kinase, and stupor, which subsided with supportive therapy. He was discharged under treatment with aripiprazole 15 mg and fluoxetine 60 mg. Case 2 was a female with schizoaffective disorder without a history of NMS. She was hospitalized and maintained with clozapine 50 mg and aripirazole 30 mg. On the 11th day, atypical NMS occurred with mild fever, delirium, and rigidity, which subsided under supportive therapy.. Our cases highlight the atypical features of NMS in patients being treated with combined ari-piprazole and clozapine. Consciousness change, modest elevation of creatine kinase, and leukocytosis were the most consistent findings; hyperthermia accounts for only some of the cases. This is a reminder of the importance of earlier detection of the soft signs and atypical features of NMS under this combined treatment.

Topics: Adult; Aripiprazole; Clozapine; Creatine Kinase; Dose-Response Relationship, Drug; Drug Substitution; Drug Therapy, Combination; Female; Fluoxetine; Hospitalization; Humans; Injections, Intramuscular; Male; Middle Aged; Neuroleptic Malignant Syndrome; Piperazines; Psychotic Disorders; Quinolones; Schizophrenia; Schizophrenic Psychology

Neuroleptic malignant syndrome (NMS) is the most dangerous life-threatening complication of antipsychotic medication. It's development is connected with the blockade of dopaminergic transmission (D2 receptors) in the nigrostriatal system of the brain. Fever is one of the main symptoms of this syndrome and it's elevation is due to the activation of the immune system. Numerous studies report that treatment with clozapine (doses 37.5-600 mg) or olanzapine (doses 10-25 mg) or the use of these drugs in polytherapy cause pyrexia between 37.8-40.6 °C. Additionally, levels of proinflammatory interleukins such as IL-6, IL-1,TNF-α were increased. The aim of this article is to describe how olanzapine and clozapine influence fever development in NMS, in relation to the dose of the drug taken by schizophrenic patients including changes in immunological system.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Dose-Response Relationship, Drug; Fever; Humans; Inflammation Mediators; Interleukins; Neuroleptic Malignant Syndrome; Olanzapine; Schizophrenia

Clozapine is widely prescribed for treatment refractory patients with schizophrenia, but its use is limited by potentially life threatening adverse effects. Rechallenge after these complications has been occasionally attempted in patients with severe psychotic symptoms.. To review the outcome of clozapine rechallenge after potentially life threatening adverse effects.. Electronic, all-language, literature search (1972-2011) followed by demographic and clinical data extraction. The outcome of rechallenge was considered favorable when the lower bound of the 95% confidence interval (CI) of the proportion of patients who could continue clozapine was >50%.. Altogether, 138 patients (mean age: 36.3years, 65.7% male, 57.6% Caucasian, virtually all with schizophrenia spectrum diagnosis) underwent clozapine rechallenge after developing neutropenia (n=112), agranulocytosis (n=15), neuroleptic malignant syndrome (NMS) (n=5), myocarditis (n=4), pericarditis (n=1) and lupus erythematosus (n=1). Rechallenge strategies were heterogeneous and not systematically evaluated. Clozapine rechallenge was successful in 78/112 patients (69.6%, CI: 60.6-77.4) after neutropenia, 3/15 (20%, CI: 7.1-45.2) after agranulocytosis, 5/5 (100%, CI: 56-100) after NMS, 3/4 (75%, CI: 30-95) after myocarditis, 1/1 after pericarditis, and 0/1 after clozapine-induced lupus. Successfully rechallenged patients were followed for 16-96weeks. None of the rechallenged patients died.. Although controlled studies are clearly needed, using a priori, confidence interval-based criteria, case reports/series suggest that in refractory patients who benefited from clozapine, careful rechallenge can be considered after neutropenia and NMS, but not after agranulocytosis and myocarditis.

Topics: Adult; Antipsychotic Agents; Clozapine; Databases, Bibliographic; Female; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Myocarditis; Neuroleptic Malignant Syndrome; Neutropenia; Young Adult

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

Data from clinical trials reviewed in this article fulfill predictions based on preclinical findings that atypical antipsychotic drugs are associated with a reduced potential for inducing extrapyramidal symptoms (EPS) and other movement disorders. Atypical drugs have been shown to reduce all subtypes of acute EPS, the frequency of EPS-related patient dropouts, and the need for concomitant antiparkinsonian drug use. Clozapine remains superior to other atypicals in treating psychosis without worsening motor symptoms in patients with Parkinson's disease. Atypicals may be selectively advantageous in treating schizophrenic patients with a predisposition to catatonia. Although the risk of developing lethal neuroleptic malignant syndrome may be diminished with atypical drugs, clinicians must remain alert to the signs of this disorder. Atypicals have reduced liability for inducing tardive dyskinesia (TD) and show antidyskinetic properties in patients with preexisting TD. Passive resolution of TD may be facilitated in some patients by the use of these agents. Thus, the risk of movement disorders has become only one of several considerations in choosing among antipsychotic drugs.

Topics: Akathisia, Drug-Induced; Antipsychotic Agents; Benzodiazepines; Clozapine; Dyskinesia, Drug-Induced; Humans; Neuroleptic Malignant Syndrome; Neurotoxicity Syndromes; Olanzapine; Pirenzepine; Risperidone

Clozapine has recently been found to be associated with neuroleptic malignant syndrome (NMS) after long-term treatment. Here, I report on a 34-year-old Taiwanese woman who had been diagnosed with schizophrenic disorder 17 years previously. She had received clozapine 250 mg/day monotherapy for 7 years. She had sudden onset of NMS signs with high fever, profuse diaphoresis, severe muscular rigidity, elevated creatine phosphokinase level and consciousness disturbance. Brain computed tomography, blood culture and cerebral spinal fluid studies were negative. She had no muscle rigidity and fever after treatment with normal saline 1500 ml/day and diazepam 30 mg/day for 8 days. On day 15, a rechallenge with clozapine was done with caution because the patient was experiencing auditory hallucinations and delusions of persecution. The dose was slowly increased to 250 mg/day over 18 days. She had no active psychotic symptoms or NMS again in the following year. I reported this case to remind readers of the possibility of induced NMS with long-term use of clozapine and successful clozapine rechallenge.

Topics: Adult; Antipsychotic Agents; Clozapine; Female; Humans; Neuroleptic Malignant Syndrome

Clozapine has recently been found to be associated with neuroleptic malignant syndrome (NMS). Our objective is to determine if clozapine causes NMS, if the presentation of clozapine-induced NMS differs from that of traditional agents, and which set of diagnostic criteria will most readily allow diagnosis of NMS associated with clozapine.. Two new cases of clozapine-associated NMS are presented, along with previously reported cases from the literature, identified by using a MEDLINE search (1966-August 1998). From all cases, concomitant medications and washout periods were examined (if available) to assess clozapine as the likely cause of NMS. Characteristics of clozapine and traditional antipsychotic-induced NMS were compared. Different diagnostic criteria for NMS were applied to the cases to determine which were more likely to diagnose the syndrome.. Clozapine was deemed a highly probable cause of NMS in 14 cases, a medium probability cause in five cases, and a low probability cause in eight cases. The most commonly reported clinical features were tachycardia, mental status changes, and diaphoresis. Fever, rigidity, and elevated creatine kinase were less prominent than in NMS associated with classical neuroleptics.. Clozapine appears to cause NMS, although the presentation may be different than that of traditional antipsychotics. Levenson's original and Addonizio's modified criteria were more likely to diagnose NMS than were other criteria. Clozapine-associated NMS may present with fewer clinical features. Limitations are the lack of detailed information provided by many of the case reports and the use of "modified" diagnostic criteria for retrospective diagnosis.

Topics: Adult; Antipsychotic Agents; Clozapine; Drug Interactions; Female; Humans; Male; Middle Aged; Neuroleptic Malignant Syndrome; Schizophrenia

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

Although neuroleptic drugs have become the mainstay of treating acute and chronic psychosis, they are substantially limited by troublesome side effects. The traditional neuroleptic drugs have a wide array of central nervous system and peripheral system side effects that often lead to problems in management or patient noncompliance. Of particular difficulty are the extrapyramidal symptoms and tardive dyskinesia. However, other side effects of seizures, sedation, neuroleptic malignant syndrome and cardiovascular, hematologic, endocrinological, and weight gain problems remain as clinical management challenges posed by existing antipsychotic drug therapy. Considerable progress has been made in improving the motor side effect profile with the advent of clozapine and risperidone. However, each of these drugs has its own dose-limiting side effect profile. Two new drugs, olanzapine and sertindole, are now added to the pharmacopeia for treating psychosis. They further improve the benefit/ risk ratio because they have even fewer EPS and other side effects. Overall, these new antipsychotic agents greatly improve the treatment of psychosis by reducing drug-induced morbidity and improving the quality of life for patients.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Dyskinesia, Drug-Induced; Humans; Imidazoles; Indoles; Neuroleptic Malignant Syndrome; Olanzapine; Pirenzepine; Psychotic Disorders; Risperidone; Schizophrenia; Seizures; Sleep; Weight Gain

The published case reports of clozapine-induced neuroleptic malignant syndrome (NMS) are reviewed, to which the authors add three, and possibly four, new cases seen in Australia, occurring in and estimated 1,250 patients exposed to the drug. The review suggests that typical NMS does occur with clozapine and that its incidence may be as common as with the classic neuroleptics. The features of clozapine-induced NMS may be somewhat different, with fewer extrapyramidal side effects and a lower rise in creatine kinase levels. The occurrence of NMS with clozapine raises important issues with regard to our understanding of the pathophysiology of the syndrome.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Australia; Child; Clozapine; Creatine Kinase; Female; Humans; Male; Middle Aged; Neuroleptic Malignant Syndrome; Neurologic Examination; Schizophrenia

Since the introduction of chlorpromazine in the 1950s, neuroleptic medications have been the mainstay of treatment of schizophrenia and other psychotic disorders. These medications do not always lead to complete remission of symptoms but they have allowed many patients to lead more productive and satisfying lives away from the restrictions of chronic hospitalisation. However, neuroleptics are associated with a number of adverse effects that can compromise their effectiveness. Extrapyramidal adverse effects include acute dystonic reactions, neuroleptic-induced Parkinsonism and akathisia. They can often be treated with neuroleptic dose reduction, addition of anticholinergic or beta-blocking agents, or medication change. Later-onset movement disorders such as tardive dyskinesia or dystonia require careful evaluation and may be treated with dose reduction or change of neuroleptic to an atypical agent. Potentially fatal reactions such as agranulocytosis and neuroleptic malignant syndrome can rarely occur and often require significant medical intervention. Clozapine offers some advantages over 'typical' neuroleptics but has a unique adverse effect profile which includes agranulocytosis.

Topics: Akathisia, Drug-Induced; Antipsychotic Agents; Basal Ganglia Diseases; Clozapine; Dyskinesia, Drug-Induced; Dystonia; Humans; Neuroleptic Malignant Syndrome; Parasympathetic Nervous System; Parkinson Disease, Secondary

Clozapine is an atypical neuroleptic drug characterised by a striking lack of extrapyramidal side effects. Although these features would seem to make clozapin an unlikely agent for the induction of neuroleptic malignant syndrome (NMS), several putative clozapin-related cases of NMS have recently been reported. A reevaluation of these articles raised some doubts on the causal relationship between clozapin therapy and NMS in most cases. We report on the clinical history of nine consecutive NMS patients who required reinstitution of neuroleptic therapy and received clozapine in our clinic. We conclude (1) that the alleged NMS induction by clozapine monotherapy needs further substantiation and (2) that clozapine should be considered a drug of choice if a psychotic relapse necessitates neuroleptic treatment for patients with a history of NMS.

Topics: Adult; Aged; Clozapine; Female; Humans; Male; Middle Aged; Neuroleptic Malignant Syndrome; Psychotic Disorders; Recurrence

Topics: Adolescent; Adult; Antipsychotic Agents; Clozapine; Female; Humans; Male; Middle Aged; Neuroleptic Malignant Syndrome; Schizophrenia

The arrival of clozapine has been one of the most significant developments in antipsychotic drug treatment since the advent of chlorpromazine ushered in the psychopharmacologic era. However, its utilization has been significantly limited and complicated by its potential to cause adverse effects and agranulocytosis in particular. It must be emphasized that clozapine has a side effect profile that is in many ways distinct from standard typical antipsychotic drugs. Side effects with clozapine are common and range from the benign to the potentially lethal. The most common side effects include sedation, dizziness, and sialorrhea during sleep; the most serious are agranulocytosis, seizures and respiratory depression. Although side effects from clozapine are not necessarily preventable, they are for the most part manageable. Even with the most serious adverse effects, proper knowledge of the medication's actions, clinical vigilance, and prompt intervention can prevent the occurrence of significant morbidity and mortality as a consequence of clozapine treatment.

Topics: Adult; Aged; Agranulocytosis; Blood Chemical Analysis; Central Nervous System Diseases; Clozapine; Female; Humans; Male; Middle Aged; Neuroleptic Malignant Syndrome; Psychotic Disorders; Seizures

Topics: AIDS Dementia Complex; Clozapine; HIV Infections; HIV-1; Humans; Mental Disorders; Neuroleptic Malignant Syndrome; Parkinson Disease

A limitation in the use of classic neuroleptic drugs is the eventual appearance of extrapyramidal symptoms. Some studies, mainly based on experimental situations, have related these symptoms with a defect in the mitochondrial electron transport chain (ETC), especially with complex I (CI). One of the advantages of the "atypical" neuroleptics is a lower incidence of movement disorders. We studied peripheral blood mononuclear cells from naive schizophrenic patients (n = 25) and patients under chronic treatment with 1 "typical" neuroleptic (haloperidol, n = 15) or 1 "atypical" neuroleptic (risperidone, n = 23; or clozapine, n = 21). Patients were on standard clinical situation, on treatment for at least 28 months, and did not present signs or symptoms of extrapyramidal dysfunction. Absolute enzyme activities of ETC complexes I to IV were spectrophotometrically quantified, and oxygen consumption with substrates of different complexes was measured polarographically. As an indirect measure of oxidative damage, we quantified membrane lipid peroxidation through the loss of cis-parinaric acid fluorescence. We found differences among groups when comparing the activity of CI, which was decreased in patients receiving neuroleptics, either assessed enzymatically or through oxygen consumption. This effect was lower for atypical neuroleptics than for haloperidol. Haloperidol was also associated with a significant increase of peripheral blood mononuclear cell membrane peroxidation. We conclude that antipsychotics given at clinical standard doses, either typical or atypical, inhibit CI of the ETC. It remains to be established if this finding in a nontarget tissue for antipsychotics may account for the lower incidence of movement disorders observed in patients on atypical agents.

Topics: Adult; Antipsychotic Agents; Clozapine; Cross-Sectional Studies; Electron Transport; Electron Transport Complex I; Female; Haloperidol; Humans; Leukocytes, Mononuclear; Male; Middle Aged; Mitochondria; Neuroleptic Malignant Syndrome; Risperidone; Schizophrenia

Topics: Antipsychotic Agents; Clozapine; Creatine Kinase; Humans; Neuroleptic Malignant Syndrome; Valproic Acid

Ms. D. was a 57-year-old Caucasian female with a past psychiatric history of schizoaffective disorder bipolar type and unspecified anxiety disorder. She presented to the psychiatric unit with cognitive blunting, poverty of thought content, looseness of associations, and inability to respond to questions with meaningful responses. In addition, the patient presented with medical symptoms including rigidity, acute rhabdomyolysis, and elevated liver function tests (LFTs). She was transferred to the inpatient medical unit for stabilization. After acute stabilization, she was transferred back to the psychiatric unit for treatment. A thorough review of the patient's history revealed she had prior episodes of atypical NMS with trials of multiple typical and atypical antipsychotics at therapeutic doses and with clinically appropriate titration schedules. These trials included clozapine, which is known to have decreased likelihood of NMS symptoms. The patient was stabilized during admission, but later decompensated and required re-admission in the months following. At that time, clozapine was reinstituted at very low doses and with a slower titration schedule. This approach was successful in ameliorating the patient's symptoms and without recurrence of NMS. In this case report, we discuss the importance of identifying atypical NMS in patients treated with typical and atypical antipsychotics, and propose that successful treatment of these patients may be possible with slower and gradual titration of clozapine.

Topics: Antipsychotic Agents; Clozapine; Female; Humans; Middle Aged; Neuroleptic Malignant Syndrome; Psychotic Disorders

Stress-induced changes in pharmacokinetics can significantly alter the plasma levels of some drugs such as clozapine. This report describes the case of a middle-aged man with schizoaffective disorder, bipolar type who showed sustained elevation in clozapine levels 3 days after discontinuation. Before the clozapine levels were drawn, he had developed acute bacterial pneumonia and signs of acute bacterial meningitis followed by neuroleptic malignant syndrome after he received multiple doses of intravenous haloperidol for worsening psychosis and aggressive behavior. Existing literature on this topic is also reviewed to investigate potential reasons for sustained clozapine levels during acute inflammatory stress and neuroleptic malignant syndrome.

Topics: Acute Disease; Antipsychotic Agents; Clozapine; Humans; Male; Meningitis, Bacterial; Middle Aged; Neuroleptic Malignant Syndrome; Pneumonia, Bacterial; Psychotic Disorders

Sedation is a common adverse effect of clozapine treatment, which may be partly related to clozapine binding to histamine receptors in the central nervous system. The objective of this study was to investigate whether single nucleotide polymorphisms (SNPs) in the histaminergic system are associated with sedation in clozapine-treated patients. The study population comprised 237 clozapine-treated, Finnish, Caucasian patients that were diagnosed with schizophrenia and 176 were genotyped using Illumina HumanCoreExome-12 BeadChip. Sedation levels were assessed using self-rating questions from the Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS). The relationships between 55 different SNPs in the histaminergic system and adverse sedation effects were examined. SNPs were analyzed separately, and in groups, to formulate a genetic risk score (GRS). A permutation test was performed to avoid type I errors. Eight linked SNPs (r

Topics: Adult; Amine Oxidase (Copper-Containing); Antipsychotic Agents; Chi-Square Distribution; Clozapine; Conscious Sedation; Female; Finland; Genotype; Histamine N-Methyltransferase; Humans; Male; Middle Aged; Neuroleptic Malignant Syndrome; Polymorphism, Single Nucleotide; Receptors, Histamine; Regression Analysis; Schizophrenia; Severity of Illness Index

Neuroleptic malignant syndrome (NMS) is a rare but severe adverse effect of antipsychotic drugs.. We report two cases of NMS highlighted by clinical pharmacists in an emergency unit during summer. One of them was fatal. Medication reconciliation processes performed at admission identified treatment with loxapine for one of them and with loxapine and clozapine for the other. Interview of the patients highlighted clinical symptoms suggesting NMS, allowing the pharmacists to alert the medical team.. Adverse drug events may be severe and clinical pharmacists in emergency departments can help to detect them.

Topics: Aged; Antipsychotic Agents; Clozapine; Emergency Service, Hospital; Fatal Outcome; Humans; Loxapine; Male; Middle Aged; Neuroleptic Malignant Syndrome; Pharmacists; Pharmacy Service, Hospital; Professional Role

Topics: Adult; Antipsychotic Agents; Catatonia; Clozapine; Diagnosis, Differential; Humans; Male; Neuroleptic Malignant Syndrome; Psychoses, Substance-Induced; Schizophrenia; Substance Withdrawal Syndrome

Topics: Antipsychotic Agents; Clozapine; Humans; Neuroleptic Malignant Syndrome

Neuroleptics are a group of drugs widely used in the treatment of psychotic symptoms. Among their adverse effects is the ability to trigger a neuroleptic malignant syndrome (NMS). The diagnosis of NMS is determined by exclusion, and its initial therapeutic management should be the withdrawal of neuroleptics, the administration of benzodiazepines, and electroconvulsive therapy (ECT). ECT is an effective treatment in these patients, and in those cases with a poor response to treatment with antipsychotic drugs. A review is presented on the treatment options and anaesthetic implications of ECT used to handle a patient diagnosed with paranoid schizophrenia in the context of NMS.

Topics: Androstanols; Anesthetics, Intravenous; Antipsychotic Agents; Clozapine; Electroconvulsive Therapy; gamma-Cyclodextrins; Humans; Male; Middle Aged; Neuroleptic Malignant Syndrome; Neuromuscular Monitoring; Neuromuscular Nondepolarizing Agents; Propofol; Rocuronium; Schizophrenia, Paranoid; Sugammadex

Topics: Adult; Antipsychotic Agents; Catatonia; Clozapine; Humans; Male; Neuroleptic Malignant Syndrome

Clozapine is the gold-standard antipsychotic medication for treatment-refractory schizophrenia (TRS). However, one potentially lethal side effect of clozapine, as with other antipsychotics, is neuroleptic malignant syndrome (NMS) which could present differently in clozapine therapy. 'Atypical NMS' is a recognised variant of NMS with less rigidity and delayed elevation of creatine kinase; this variant is associated with clozapine.. A case from the author's clinical practice was reviewed.. A 67-year-old man with TRS was treated with clozapine. Unfortunately, his physical condition deteriorated and he presented with atypical NMS, which initially was treated as presumable urinary tract infection.. Atypical NMS is associated with clozapine. This case exposes the potential difficulties in diagnosis, and highlights the importance of considering less common diagnoses in acutely unwell psychiatric patients.

Topics: Acute Kidney Injury; Aged; Antipsychotic Agents; Clozapine; Confusion; Fever; Humans; Male; Neuroleptic Malignant Syndrome; Polypharmacy; Risperidone; Schizophrenia

We present the case of a middle-aged man with a chronic history of schizoaffective disorder, depressed type, stable on a second-generation antipsychotic. Psychotic symptoms recurred contingent to medication noncompliance necessitating hospitalization. Treatment was complicated by the development of neuroleptic malignant syndrome (NMS). In addition, subsequent medication rechallenges failed because of recurrent rhabdomyolysis and atypical NMS. Electroconvulsive therapy (ECT) treatment was initiated, affording remission of psychotic symptoms and nonrecurrence of NMS and rhabdomyolysis. Our experience confirmed the efficacy of ECT treatment in providing symptom relief of psychosis complicated by recurrent episodes of NMS and atypical NMS. Likewise, it illustrated the efficacy of ECT treatment for rhabdomyolysis.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Electroconvulsive Therapy; Humans; Male; Neuroleptic Malignant Syndrome; Olanzapine; Patient Compliance; Rhabdomyolysis; Schizophrenia; Treatment Outcome

Topics: Amisulpride; Antipsychotic Agents; Clozapine; Humans; Male; Middle Aged; Neuroleptic Malignant Syndrome; Pancreatitis; Schizophrenia; Seizures

Topics: Antipsychotic Agents; Clozapine; Diagnosis, Differential; Female; Humans; Middle Aged; Neuroleptic Malignant Syndrome; Schizophrenia

Topics: Aged, 80 and over; Antipsychotic Agents; Clozapine; Fatal Outcome; Female; Humans; Neuroleptic Malignant Syndrome; Parkinson Disease

Neuroleptic malignant syndrome (NMS) is a potentially fatal manifestation of antipsychotic use associated with symptoms that include mental status changes, muscle rigidity, fever and autonomic dysfunction. An occurrence of NMS with clozapine has been reported in the past but there are very few reports of successfully rechallenging the drug in individuals who have developed the syndrome. This case report discusses one of the few instances in literature where clozapine has been re-administered successfully to a patient without a reoccurrence of NMS. In conclusion, a rechallenge of clozapine after neuroleptic malignant syndrome can be done if care is taken to avoid concurrent use of lithium and other psychotropics, monitoring for NMS symptoms and titrating the dose upward slowly after a reasonable period of time.

Topics: Adult; Antipsychotic Agents; Clozapine; Female; Humans; Neuroleptic Malignant Syndrome; Psychotic Disorders; Young Adult

Although many patients with schizophrenia fail to respond adequately to trials of 2 or more antipsychotics, utilization of clozapine for these patients remains low, despite recommendations for its use by accepted treatment guidelines. Some experts estimate that 5-10 times more patients could benefit from clozapine than who are now receiving it. Learning how to manage the unique side effect profile of clozapine can potentially remove barriers to prescribing this agent and thus unlock its unique therapeutic efficacy for more patients.

Topics: Agranulocytosis; Antipsychotic Agents; Clozapine; Constipation; Diabetes Mellitus; Eosinophilia; Humans; Myocarditis; Neuroleptic Malignant Syndrome; Neutropenia; Practice Guidelines as Topic; Practice Patterns, Physicians'; Schizophrenia; Sialorrhea; Tachycardia; Weight Gain

Neuroleptic malignant syndrome (NMS) is a rare life-threatening condition associated with the use of antipsychotics and other drugs that influence dopaminergic transmission. Although NMS is typically associated with classical antipsychotics, it can also be induced by atypical antipsychotics. In this paper, we report a case of NMS associated with clozapine use.. A 27-year-old male was diagnosed as schizophrenia in 2006 and zuclopenthixol depot was administered parenterally. Following the second injection, NMS was diagnosed and he was switched to clozapine. After 4 years of clozapine use, one day, he suddenly stopped eating, stayed in bed all day, and had incontinence. Upon examination at our hospital the patient had muscle rigidity, high fever, leukocytosis, and a high creatine phosphokinase level, and NMS was diagnosed. He was put on bromocriptine. NMS resolved, but psychotic relapse and catatonia developed. 10 sessions of electro convulsive treatment (ECT) were administered. Quetiapine 25 mg/day was introduced and titrated up to 600 mg/day afterwards. He has been using quetiapine 600 mg/day for 18 months and at the time this manuscript was written has not had any signs of psychosis or NMS.. NMS is usually induced by the use of agents with high dopaminergic affinity. Incomplete or extraordinary NMS cases have been reported due to clozapine and atypical antipsychotics. The presented case is noteworthy due to the complete and typical presentation of NMS. It should always be kept in mind that all atypical antipsychotics including clozapine have the probability to induce NMS although not common.

Topics: Adult; Antipsychotic Agents; Catatonia; Clozapine; Creatine Kinase; Diagnosis, Differential; Humans; Male; Neuroleptic Malignant Syndrome; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Serotonin Antagonists

Topics: Antipsychotic Agents; Clozapine; Consciousness; Diagnosis, Differential; Fever; Humans; Male; Middle Aged; Muscle Rigidity; Neuroleptic Malignant Syndrome; Schizophrenia, Paranoid; Substance Withdrawal Syndrome

Topics: Antipsychotic Agents; Clozapine; Humans; Male; Middle Aged; Neuroleptic Malignant Syndrome

Topics: Adult; Antipsychotic Agents; Clozapine; Electroconvulsive Therapy; Haloperidol; Humans; Male; Neuroleptic Malignant Syndrome

Topics: Adolescent; Antipsychotic Agents; Clozapine; Humans; Male; Neuroleptic Malignant Syndrome; Psychotic Disorders

Topics: Antipsychotic Agents; Clozapine; Humans; Male; Neuroleptic Malignant Syndrome

Atypical antipsychotic drugs (AADs) are the standard treatment for both the acute and long-term management of schizophrenia and an augmentation to mood stabilizers for bipolar disorder (BD). Yet many individuals who take AADs do not fully respond to them, while others experience side effects that include weight gain and metabolic disorder. This in vitro pharmacogenetic study examined whether allelic variants in the 5-hydroxytryptamine (HT)(2A) receptor alter the in vitro pharmacology of six AADs (clozapine, olanzapine, risperidone, quetiapine, ziprasidone, and aripiprazole). We selected 4 functional single-nucleotide polymorphisms (SNPs) for investigation (Thr25Asn, Ile197Val, Ala447Val, and His452Tyr), conducted site-directed mutagenesis studies to induce variants into human HEK-293 cell lines, and screened allelic variants for their effects on 5-HT( 2A) receptors in the cell lines. We conducted numerous binding assays and fluorescence-based assay system (FLEX station) experiments using the six AADs. Our results indicated that three polymorphic 5-HT(2A) receptors (Ile197Val, Ala447Val, and His452Tyr) exhibited statistically significant, though modest, changes in atypical antipsychotic affinity. In addition, three polymorphic receptors (Thr25Asn, Ile197Val, and His452Try) altered AAD potency. Our findings support in vivo evidence that functional SNPs in genes encoding neuroreceptor drug targets could explain interindividual differences in AAD drug response and tolerability. We suggest that more in vivo pharmacogenetic studies of well-characterized patients who are prescribed AADs be indicated. Future pharmacogenetic studies of well-characterized patients will likely involve tagging SNPs and the use of haplotypes related to other genes encoding neuroreceptor drug targets.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Dibenzothiazepines; Drug Resistance; HEK293 Cells; Humans; Mutagenesis, Site-Directed; Neuroleptic Malignant Syndrome; Nursing Research; Olanzapine; Pharmacogenetics; Piperazines; Polymorphism, Single Nucleotide; Quetiapine Fumarate; Quinolones; Receptor, Serotonin, 5-HT2A; Risperidone; Thiazoles

Topics: Adult; Antipsychotic Agents; Aripiprazole; Clozapine; Drug Synergism; Humans; Male; Neuroleptic Malignant Syndrome; Piperazines; Quinolones

Topics: Adult; Antipsychotic Agents; Clopenthixol; Clozapine; Dibenzothiazepines; Humans; Male; Neuroleptic Malignant Syndrome; Quetiapine Fumarate; Treatment Outcome

Topics: Antiparkinson Agents; Clozapine; Delusions; Drug Therapy, Combination; Humans; Levodopa; Lewy Body Disease; Movement Disorders; Neuroleptic Malignant Syndrome; Severity of Illness Index

We report on the treatment of a patient suffering from dementia with Lewy bodies who initially presented with severe neurological and psychopathological symptoms. After treating the patient with levodopa and clozapine, these symptoms remitted.

Topics: Aged; Antiparkinson Agents; Antipsychotic Agents; Clozapine; Delusions; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Levodopa; Lewy Body Disease; Neuroleptic Malignant Syndrome; Quetiapine Fumarate; Severity of Illness Index

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

A case of neuroleptic malignant syndrome (NMS) secondary to aripiprazole in a schizophrenic patient previously managed with clozapine is reported.. A 42-year-old Caucasian woman with a history of schizophrenia (chronic paranoid type) arrived at the emergency department (ED) with a chief complaint of altered mental status and oliguria. The patient was previously managed with clozapine for 14 years, which was well tolerated until the patient developed urinary retention. As a result, clozapine was gradually discontinued over several weeks. Aripiprazole 30 mg orally once daily was initiated four days before her arrival at the ED. Approximately four days after starting aripiprazole therapy, the patient began experiencing tremors, confusion, and rigidity. Physical examination revealed poor inspiratory effort, diffuse abdominal tenderness, and decreased muscle strength. Initial blood work confirmed acute renal failure and leukocytosis. The patient developed both hypokalemia and hypomagnesemia; her urine myoglobin level was suggestive of rhabdomyolysis. In light of her fever, encephalopathy, autonomic instability, elevated creatine kinase levels, and muscle rigidity, a diagnosis of NMS was made. Supportive care in the form of cooling blankets, electrolyte management, and blood pressure control was provided to the patient. Bromocriptine was also initiated to restore her dopamine balance. Twenty days after the initial presentation, the patient was initiated on paliperidone 3 mg orally at bedtime, which was slowly increased to 9 mg over several weeks. Follow-up evaluation demonstrated no signs or symptoms of NMS. Laboratory test values were also within normal limits.. A 42-year-old Caucasian woman with schizophrenia who could no longer tolerate therapy with clozapine developed NMS secondary to the initiation of aripiprazole.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Clozapine; Female; Humans; Isoxazoles; Neuroleptic Malignant Syndrome; Paliperidone Palmitate; Piperazines; Pyrimidines; Quinolones; Schizophrenia

Neuroleptic malignant syndrome (NMS) is a physiologic phenomenon that has been associated with the use of both first- and second-generation antipsychotics resultant to their ability to block dopamine blockade in the basal ganglia and hypothalamic regions of the brain. The typical reaction involves the presentation of muscle rigidity, changes in mental status, temperature elevation, labile blood pressure, and elevations in creatinine kinase and white blood cell counts. The reaction is most often reported early in the course of therapy but is well documented to have the potential to occur at any point in time. Untreated NMS can be fatal, often from secondary causes such as deep venous thrombosis and pulmonary embolism. Treatment involves immediate discontinuation of the offending agent, supportive therapy of clinical symptoms, and may include the use of the skeletal muscle relaxant, dantrolene sodium, or the dopaminergic agents bromocriptine or amantadine. In this case, we present a patient who developed symptoms of NMS during the cross-taper and conversion from quetiapine to clozapine. The patient was treated for NMS; however, his clinical diagnosis was never able to be definitively determined as he was initially evaluated for septicemia and later treated for suspected bacterial infection with antibiotics, and clozapine-associated side effects cannot be ruled-out as a contributing source to the clinical presentation. The estimated Naranjo Scale score for this case report is 3.

Topics: Antipsychotic Agents; Clozapine; Dibenzothiazepines; Drug Therapy, Combination; Humans; Male; Middle Aged; Neuroleptic Malignant Syndrome; Quetiapine Fumarate

Topics: Adult; Antipsychotic Agents; Aripiprazole; Clozapine; Creatine Kinase; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Humans; Male; Myocardial Infarction; Neuroleptic Malignant Syndrome; Piperazines; Quinolones; Risperidone; Schizophrenia; Valproic Acid

Tolerability of haloperidol, clozapine and risperidone has been studied in 60 women with different psychiatric disorders including schizophrenia (83,2%) and neurotic disorders (16,7%). A spectrum of neurological, mental and somatic side-effects was different in the treatment with typical (haloperidol) and atypical (clozapine and risperidone) antipsychotics. The treatment with haloperidol more often results in movement disorders, sleepiness, inhibition, sexual dysfunction and cholinolytic effects. Sedative effects, reduced sexual drive, somatic-autonomic symptoms (hypersalivation, constipations, dry mouth, orthostatic symptoms, tachycardia), and metabolic endocrine effects (weight gain) were the most characteristic side-effects for clozapine. Risperidone caused less intensive extrapyramidal and somatic-autonomous symptoms but more expressed metabolic endocrine disturbances (weight gain, galactorrhea, menstrual cycle dysfunction). Comparing to clozapine, side effects of risperidone were represented by the less intensive somatic-autonomous symptoms but more intensive weight gain, menstrual dysfunction and galactorrhea. Based on the previous results of the study of men, the authors conclude that frequency and intensity of neuroleptic side-effects are sex-related that should be taken into account in the choice of antipsychotics.

Topics: Adult; Antipsychotic Agents; Clozapine; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Haloperidol; Humans; Neuroleptic Malignant Syndrome; Risperidone; Sexuality; Treatment Outcome

Catatonia is characterized by the predominance of psychomotor abnormalities and shares many clinical, biological and treatment response features with the neuroleptic malignant syndrome (NMS), a rare adverse reaction to psychoactive medications. It has been advocated that the two conditions should be placed along the same spectrum of disorders. A case of a 49-year-old woman, who developed NMS while on low dose clozapine soon after recovering from catatonia, is presented. The potential relationship between catatonia and NMS is discussed in the light of the existing literature, and attention is drawn to the risk for clozapine-induced NMS in catatonic patients.

Topics: Antipsychotic Agents; Catatonia; Clozapine; Dose-Response Relationship, Drug; Female; Humans; Middle Aged; Neuroleptic Malignant Syndrome; Psychotic Disorders; Risk Factors; Schizophrenia, Catatonic

Topics: Antipsychotic Agents; Catatonia; Clozapine; Humans; Neuroleptic Malignant Syndrome; Risperidone

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Clozapine; Humans; Mood Disorders; Neuroleptic Malignant Syndrome; Randomized Controlled Trials as Topic; Schizophrenia; Treatment Outcome

Clozapine-induced neuroleptic malignant syndrome (NMS) may present differently from NMS associated with traditional antipsychotic agents, with fewer clinical features, particularly fewer extrapyramidal manifestations. The risk of developing NMS with clozapine does not appear dose-related. In half of cases, it occurs within 2 weeks of beginning clozapine therapy, but it can develop at any stage, especially with long-term use. We describe a patient who presented with atypical NMS after more than 10 years of clozapine treatment, and who was safely re-challenged with the same drug.

Topics: Antipsychotic Agents; Clozapine; Creatinine; Humans; Male; Middle Aged; Neuroleptic Malignant Syndrome; Time Factors

The neuroleptic malignant syndrome (NMS) is a rare, but potentially lethal side effect of conventional and atypical antipsychotic drugs. We present a 62 years old male patient who was admitted to our institution because of sudden onset of mild hyperthermia, muscle rigidity, stupor, leucocytosis and massive rhabdomyolysis after 30 years uneventful treatment with clozapine. The medication with clozapine was suspended because of the suspicion of NMS. When the acute symptoms were abated, the treatment with clozapine was resumed again after 14 days. The very next day, the patient suffered again from raised body core temperature, leucocytosis, elevated serum creatine kinase and new catatonia. The therapy with clozapine was stopped definitively and benzodiazepines were administered assuming a relapse of an alleviated, probably reconvening NMS. Under the treatment with benzodiazepines the patient was free of symptoms even after 1 month. To our knowledge, the latency of 30 years between the beginning of the treatment with clozapine and the onset of NMS is the longest period in the literature. According to our case, the differential diagnosis of NMS is not always trivial and is therefore discussed.

Topics: Antipsychotic Agents; Body Temperature; Clozapine; Diagnosis, Differential; Humans; Male; Middle Aged; Neuroleptic Malignant Syndrome; Rhabdomyolysis; Schizophrenia

A 77-year-old patient with initial behavioral and psychological symptoms of dementia was treated with clozapine (50 mg/daily). Since no clinical benefit was apparent, clozapine was discontinued after six weeks and the patient started on paroxetine (20 mg/daily). After three weeks on paroxetine, he was given another trial of clozapine at a starting dosage of 25 mg/daily. While clozapine had previously been well tolerated, this time he rapidly developed fever, mental confusion, lethargy, muscle spasms and rigidity. The diagnosis of neuroleptic malignant syndrome was delayed, because there was no leukocytosis and serum creatine phosphokinase was initially not elevated. Subcutaneous apomorphine was then given but, after an initial improvement, the patient developed a multiple organ failure syndrome and died.

Topics: Aged; Antipsychotic Agents; Clozapine; Drug Therapy, Combination; Fatal Outcome; Humans; Male; Neuroleptic Malignant Syndrome; Paroxetine; Selective Serotonin Reuptake Inhibitors

The authors report a case of a patient, who in a few days after an abrupt discontinuation of clozapine and haloperidol developed agitated and confused state resembling neuroleptic malignant syndrome (NMS) and clozapine withdrawal symptoms at the same time. Data obtained from family members led to gradual reintroduction of clozapine and to subsequent recovery. The case illustrates the importance for clinicians to be familiar with the variety of discontinuation symptoms, so they can recognize them and offer effective treatment.

Topics: Adult; Antipsychotic Agents; Clozapine; Haloperidol; Humans; Male; Neuroleptic Malignant Syndrome; Psychomotor Agitation; Substance Withdrawal Syndrome; Treatment Refusal

A 54-year-old woman with schizophrenia presented to hospital with unconsciousness, fever and marked muscle rigidity. She had been given fluphenazine decanoete 20 mg intramuscularly 15 days before the admission and she had continued taking haloperidol 20 mg daily and oral biperiden 2-4 mg. She was extremely rigid and unresponsive. On laboratory investigations revealed: serum sodium 120 mEq/l, creatinine phosphokinase 12,980 IU/l (normal up to 170), lactate dehydrogenase 1544 IU/l (150-500), free trioidothyronine < 1.00 pg/ml (1.5-4.5), free throxyine 0.76 ng/dl (0.8-1.9), thyroid stimulating hormone 1.14 microU/ml (0.4-4), cortisol (at 8.00 a.m.) 9 microg/dl (5-25). Antipsychotic drugs were withdrawn after admission. A diagnosis of secondary adrenal insufficiency and secondary hypothyroidism was made. Hormonal substitution with hydrocortisone and levothyroxine and correction of hyponatremia with intravenous hypertonic saline solution resulted in rapid improvement of symptoms and signs. It seems that the symptoms and signs of hypothyroidism and hyponatremia were attributed to acute psychosis in this patient. As a conclusion failure to recognize the endocrinopathy may not only produce recovery difficulties but also psychiatric and endocrine repercussions if psychotropic medications are given in such masked cases.

Topics: Adrenal Insufficiency; Antipsychotic Agents; Body Temperature; Clozapine; Female; Haloperidol; Humans; Hyponatremia; Hypothyroidism; Middle Aged; Muscle Rigidity; Neuroleptic Malignant Syndrome; Schizophrenia

Topics: Adult; Anti-Anxiety Agents; Antiparkinson Agents; Antipsychotic Agents; Bromocriptine; Clozapine; Creatine Kinase; Dose-Response Relationship, Drug; Electroconvulsive Therapy; Haloperidol; Humans; Lorazepam; Male; Neuroleptic Malignant Syndrome; Psychotic Disorders; Schizophrenia; Substance Withdrawal Syndrome

Topics: Administration, Oral; Adolescent; Antipsychotic Agents; Benzodiazepines; Child; Child Development Disorders, Pervasive; Clozapine; Creatine Kinase; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Humans; Injections, Intramuscular; Male; Neuroleptic Malignant Syndrome; Olanzapine; Schizophrenia

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: Administration, Oral; Adolescent; Antipsychotic Agents; Clozapine; Combined Modality Therapy; Electroconvulsive Therapy; Humans; Injections, Intramuscular; Male; Methotrimeprazine; Neuroleptic Malignant Syndrome; Recurrence; Risperidone; Schizophrenia

Topics: Antipsychotic Agents; Clozapine; Hematoma, Subdural; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neuroleptic Malignant Syndrome; Psychiatric Status Rating Scales; Psychotic Disorders

Serious adverse events and even sudden death have been reported during administration of the combination of clozapine and benzodiazepines. However, this combination does not necessarily result in increased frequency of serious adverse events. Thus it is not regarded as an absolute contraindication and might be useful in distinct clinical situations, e.g., during the occurrence of a malignant neuroleptic syndrome, "catatonic dilemma," or severe agitation during clozapine treatment. In the following report, certain suggestions on how to deal with this combination therapy are provided which may provide a basis for discussion that ultimately may lead to the formulation of guidelines for this combination therapy. Such guidelines may help psychiatrists in dealing with this combination in clinical situations. Moreover, the formulation of such guidelines would help with forensic issues in case of serious adverse events occurring during this combination therapy.

Topics: Adverse Drug Reaction Reporting Systems; Anti-Anxiety Agents; Antipsychotic Agents; Benzodiazepines; Catatonia; Clozapine; Death, Sudden; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Humans; Neuroleptic Malignant Syndrome; Practice Guidelines as Topic; Risk Factors

The incidence of neuroleptic malignant syndrome (NMS) is not known, but the frequency of its occurrence with conventional antipsychotic agents has been reported to vary from 0.02% to 2.44%.. MEDLINE search conducted in January 2003 and review of references within the retrieved articles.. Our MEDLINE research yielded 68 cases (21 females and 47 males) of NMS associated with atypical antipsychotic drugs (clozapine, N = 21; risperidone, N = 23; olanzapine, N = 19; and quetiapine, N = 5). The fact that 21 cases of NMS with clozapine were found indicates that low occurrence of extrapyramidal symptoms (EPS) and low EPS-inducing potential do not prevent the occurrence of NMS and D(2) dopamine receptor blocking potential does not have direct correlation with the occurrence of NMS. One of the cardinal features of NMS is an increasing manifestation of EPS, and the conventional antipsychotic drugs are known to produce EPS in 95% or more of NMS cases. With atypical antipsychotic drugs, the incidence of EPS during NMS is of a similar magnitude.. For NMS associated with atypical antipsychotic drugs, the mortality rate was lower than that with conventional antipsychotic drugs. However, the mortality rate may simply be a reflection of physicians' awareness and ensuing early treatment.

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Bromocriptine; Clozapine; Dantrolene; Dibenzothiazepines; Dopamine Agonists; Female; Humans; Intubation; Male; MEDLINE; Mental Disorders; Middle Aged; Muscle Relaxants, Central; Neuroleptic Malignant Syndrome; Olanzapine; Quetiapine Fumarate; Respiration, Artificial; Risperidone; Treatment Outcome

Topics: Adult; Clozapine; Cyclohexanols; Dantrolene; GABA Antagonists; Humans; Male; Muscle Relaxants, Central; Neuroleptic Malignant Syndrome; Selective Serotonin Reuptake Inhibitors; Time Factors; Venlafaxine Hydrochloride

A 17-year-old African-American male developed neuroleptic malignant syndrome (NMS) with hyperthermia, autonomic instability, increased muscle tone, rhabdomyolysis, and obtundation after a maximum of 2 days of treatment with olanzapine and 1 day of treatment with divalproex sodium. Intensive care unit (ICU)-level care was required. Paranoid psychosis with catatonia was present after recovery from the NMS. Because of his continued psychotic symptoms following resolution of the NMS, the alternate atypical antipsychotic, clozapine, was started under close observation. Reports of NMS resulting from atypical antipsychotic agents are generally uncommon, and much more so in the child and adolescent population. However, these agents are frequently prescribed in this population and require due caution.

Topics: Adolescent; Benzodiazepines; Clozapine; Humans; Male; Neuroleptic Malignant Syndrome; Olanzapine

Topics: Adult; Antipsychotic Agents; Clozapine; Haloperidol; Humans; Male; Neuroleptic Malignant Syndrome; Schizophrenia

Topics: Antipsychotic Agents; Choice Behavior; Clozapine; Humans; Neuroleptic Malignant Syndrome; Psychotic Disorders; Weight Gain

Topics: Adult; Antipsychotic Agents; Clozapine; Dose-Response Relationship, Drug; Humans; Male; Neuroleptic Malignant Syndrome

Topics: Adult; Antipsychotic Agents; Clozapine; Humans; Male; Neuroleptic Malignant Syndrome; Risperidone; Schizophrenia, Paranoid

Although atypical antipsychotics have generally a decreased risk of neurotoxicity, there are reports regarding various neurotoxic or idiosyncratic reactions including neuroleptic malignant syndrome (NMS). The authors present here the toxic interaction between risperidone (RIS) and clozapine (CLZ) in a first-episode schizophrenic patient. A 20-year-old man suffering from first-episode schizophrenia--catatonic subtype, developed a neurotoxic syndrome, which has been characterized as a mild form of NMS, after CLZ (100 mg/day) was added to a regimen of RIS (16 mg/day). The NMS symptomatology subsided only by drug discontinuation and supportive care. Later, CLZ monotherapy restarted without further complications. This case report shows that neurotoxic syndromes, even NMS, may occur during combination therapy with RIS and CLZ.

Topics: Adult; Antipsychotic Agents; Clozapine; Diagnosis, Differential; Drug Interactions; Humans; Male; Neuroleptic Malignant Syndrome; Neurotoxicity Syndromes; Risperidone; Schizophrenia

Neuroleptic malignant syndrome (NMS) is a rare, but potentially lethal complication of antipsychotic medication. The risk of developing NMS under atypical neuroleptics seems lower than under typical neuroleptics. However, the use of atypical neuroleptics in modern psychopharmacotherapy is increasing, so the incidence of NMS under these drugs may also increase. Here, we will describe three episodes of NMS that fulfilled the DSM-IV criteria for NMS (APA, 1994). The epivodes of NMS occured under treatment with clozapine, risperidone, and amisulpride. These episodes had some atypical features that will be discussed with regard to the pathophysiological mechanisms leading to NMS.

Topics: Amisulpride; Antipsychotic Agents; Clozapine; Female; Humans; Middle Aged; Neuroleptic Malignant Syndrome; Risperidone; Schizophrenia; Sulpiride

Topics: Aged; Antidepressive Agents; Antipsychotic Agents; Clozapine; Drug Combinations; Haloperidol; Humans; Male; Neuroleptic Malignant Syndrome

Topics: Aged; Antiparkinson Agents; Antipsychotic Agents; Benzophenones; Chemical and Drug Induced Liver Injury; Clozapine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Liver Function Tests; Neuroleptic Malignant Syndrome; Neurologic Examination; Nitrophenols; Tolcapone

Topics: Antipsychotic Agents; Catatonia; Clozapine; Humans; Neuroleptic Malignant Syndrome; Receptors, Dopamine D2; Risk Factors

Side effects of antipsychotic medications are particularly problematic in elderly patients, who experience many age-related changes that may exacerbate medication side effects. Side effects of particular concern in the elderly include anticholinergic reactions, parkinsonian events, tardive dyskinesia, orthostatic hypotension, cardiac conduction disturbances, reduced bone mineral density, sedation, and cognitive slowing. In addition, elderly patients with schizophrenia often have comorbid medical illnesses-such as cardiovascular disease and dementia of the Alzheimer's type-and are thus likely to be taking multiple medications. The effects of polypharmacy must be carefully considered. Patients, caregivers, and family often have different perspectives on side effects. This article addresses the side effects of the currently available antipsychotic medications in light of these concerns.

Topics: Age Factors; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Clinical Trials as Topic; Clozapine; Comorbidity; Dementia; Dibenzothiazepines; Humans; Movement Disorders; Neuroleptic Malignant Syndrome; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia

Topics: Adult; Antipsychotic Agents; Clozapine; Female; Humans; Neuroleptic Malignant Syndrome; Psychotic Disorders

A case of neuroleptic malignant syndrome (NMS) in a 23 year old male patient is reported. The symptoms were hyperthermia, muscle rigidity, change in mental status, sinus tachycardia, creatinine phosphokinase elevation and myoglobinuria. The patient suffered from severe muscle pain and compromised respiratory function. Treatment was cessation of neuroleptic medication and institution of intensive medical care focusing on symptomatic treatment. One week after admission clinical status and laboratory findings were normalized and the patient was readmitted to a psychiatric hospital. The neuroleptic medication of the reported patient had been olanzapine during seven months at a dose of 25 mg daily. The day before onset of NMS the pharmacological treatment was supplemented by 100 mg of clozapine. The cause of onset of NMS in this case is discussed. Clozapine, an atypical neuroleptic, is known to have reduced potential to cause NMS and in such cases without extrapyramidal symptoms. Olanzapine, however, has not yet been reported to cause NMS. Alternatively the cause of onset of NMS in this patient could be explained by the combination treatment and possible synergistic effect of the two antipsychotic drugs. Further research in this field is needed.

Topics: Adult; Antipsychotic Agents; Autistic Disorder; Benzodiazepines; Clozapine; Drug Synergism; Humans; Male; Neuroleptic Malignant Syndrome; Olanzapine; Pirenzepine

The neuroleptic malignant syndrome (NMS) is a side-effect of treatment with neuroleptic drugs. It is infrequent, but underdiagnosed. The diagnosis can be especially difficult to verify, in older patients with dementia because they often have symptoms of NMS, as a consequence of age and dementia. The importance of monitoring serum-creatine-kinase is discussed and proposals for treatment are suggested.

Topics: Aged; Antipsychotic Agents; Clozapine; Creatine Kinase; Dementia; Diagnosis, Differential; Humans; Male; Neuroleptic Malignant Syndrome

Neuroleptic malignant syndrome (NMS) is a rare but potentially fatal side-effect of antipsychotic drug therapy, especially of dopamine receptor antagonists. As a dose relationship has been postulated, low dose neuroleptization would be expected to help to avoid this side-effect. In contrast, we report on a 21-year-old female following low dose fluphenazine treatment with 2.5 mg/day. The patient recovered from NMS after 3 days of dantrolene administration. Eventually, remission from psychotic symptoms was achieved with clozapine. At 8-month follow-up, psychopathology remained stable and there were no more signs of NMS.

Topics: Adult; Antipsychotic Agents; Clozapine; Dantrolene; Female; Fluphenazine; Humans; Muscle Relaxants, Central; Neuroleptic Malignant Syndrome; Psychotic Disorders

Topics: Antiparkinson Agents; Antipsychotic Agents; Clozapine; Humans; Neuroleptic Malignant Syndrome; Parkinson Disease; Psychoses, Substance-Induced

Topics: Adult; Antipsychotic Agents; Clozapine; Dopamine D2 Receptor Antagonists; Female; Humans; Neuroleptic Malignant Syndrome; Receptors, Purinergic

We report four cases of neuroleptic malignant syndrome occurring after administration of a typical antipsychotic haloperidol and a newer atypical antipsychotic clozapine. The management of these patients is discussed.

Topics: Adolescent; Adult; Antipsychotic Agents; Clozapine; Female; Haloperidol; Humans; Neuroleptic Malignant Syndrome

A 19-year-old man presented to a community hospital with a sudden change in level of consciousness, fever, and muscle rigidity. The patient had a history of schizophrenia and was being treated with clozapine. Despite a high index of suspicion for neuroleptic malignant syndrome, definitive care was delayed for more than 24 hours after the patient was transferred to a tertiary care center. This case illustrates the importance of primary care physicians being able to recognize and diagnose this syndrome, particularly as the use of atypical antipsychotic agents increases.

Topics: Adult; Antipsychotic Agents; Clozapine; Humans; Male; Neuroleptic Malignant Syndrome; Schizophrenia

We are reporting on a patient with a schizoaffective disorder (ICD 10:F25.1), whose catatonic symptoms deteriorated while receiving high-potency neuroleptic drugs in combination with anticholinergic medication. Initially there was a "catatonic dilemma", i.e. it was not possible to differentiate between the morbigenous and pharmacogenic (malignant neuroleptic syndrome) etiology of the catatonic symptoms. Catatonic symptoms were successfully treated with a combination of lorazepam and clozapine. The severe catatonic syndrome was found to be a neuroleptic-induced deterioration of a primary morbogenous catatonic syndrome. Thus, this case also suggests that the malignant neuroleptic syndrome and neuroleptic non-responsive catatonia may not be two different disease entities but that catatonia under neuroleptic medication is caused by the interaction of individual disposition, morbigenous and pharmacogenic factors.

Topics: Adult; Anti-Anxiety Agents; Antipsychotic Agents; Clozapine; Diagnosis, Differential; Drug Therapy, Combination; Humans; Lorazepam; Male; Neuroleptic Malignant Syndrome; Schizophrenia, Catatonic

Topics: Antipsychotic Agents; Clozapine; Creatine Kinase; Creatinine; Drug Therapy, Combination; Humans; Male; Middle Aged; Neuroleptic Malignant Syndrome; Schizophrenia, Paranoid

Topics: Antipsychotic Agents; Clozapine; Humans; Neuroleptic Malignant Syndrome

Topics: Clozapine; Humans; Neuroleptic Malignant Syndrome; Schizophrenia

Clozapine is an atypical neuroleptic drug that was initially thought not to cause neuroleptic malignant syndrome (NMS). The authors report a case of NMS associated with clozapine use, developed in a patient without previous history of NMS. Considering that 13 such cases (including ours) have been reported so far, NMS should be considered in the differential diagnosis of a febrile patient treated with clozapine.

Topics: Aged; Clozapine; Female; Humans; Neuroleptic Malignant Syndrome

Catatonia as a clozapine withdrawal syndrome has not been documented. We report a case of excited catatonia with fever, autonomic instability, and delirium--a picture of malignant catatonia (lethal catatonia) after abrupt clozapine withdrawal. The use of conventional neuroleptics transformed the excited malignant catatonia into a stuporous state resembling neuroleptic malignant syndrome (NMS). Such a transformation of excited lethal catatonia into NMS has been described in the literature, providing support for the hypothesis that NMS is a variant of catatonia. Opinions, however, have been conflicting whether lethal catatonia and NMS are indistinguishable. We argue that NMS may be regarded as a neuroleptic-induced retarded (stuporous) subtype of malignant catatonia, clinically indistinguishable from nonneuroleptic retarded malignant catatonia but different from the excited form. To differentiate between the two subtypes of malignant catatonia would help resolve the controversy. The nosological status of excited catatonia, a poorly studied condition, remains unclear. The two subtypes of catatonia may differ in pathophysiology and responses to treatment. Clinicians should be alert to catatonia as a possible clozapine withdrawal phenomenon, and excited catatonia deserves more research attention.

Topics: Adult; Antipsychotic Agents; Catatonia; Clozapine; Humans; Male; Neuroleptic Malignant Syndrome; Schizophrenia; Substance Withdrawal Syndrome

Topics: Aged; Antipsychotic Agents; Clozapine; Humans; Male; Neuroleptic Malignant Syndrome; Schizophrenia, Paranoid

Topics: Antipsychotic Agents; Clozapine; Humans; Neuroleptic Malignant Syndrome

To report a case of suspected neuroleptic malignant syndrome (NMS) associated with clozapine therapy.. A 42-year-old schizophrenic man treated with clozapine developed a temperature of 39.5 degrees C, diaphoresis, tachycardia, rigidity, and leukocytosis. His serum creatine kinase concentration was 25 000 U/L. A diagnosis of NMS was made. He was treated with bromocriptine and supportive therapy, and recovered within a week.. Despite earlier expectations that clozapine, with a pharmacologic profile differing from that of other antipsychotic medications, might not cause NMS, NMS remains the most likely diagnosis in this case.. NMS may be a possible complication of clozapine therapy.

Topics: Adult; Antipsychotic Agents; Bromocriptine; Clozapine; Dopamine Agonists; Humans; Male; Neuroleptic Malignant Syndrome

This report identifies neuroleptic malignant syndrome (NMS) occurring on a steady state dosage of clozapine monotherapy.. An outpatient presented with a recent history of stiffness and soreness of his legs, dizziness, polydipsia, polyuria, abdominal and chest pains. After admission to a general hospital, further symptomatology was identified including: pallor, diaphoresis, nausea, confusion, agitation, decrease in normal reflexes, minimally reactive pupils and rigid limbs.. Intravenous (I/V) diazepam was administered but failed to decrease the agitation and confusion. He was sedated with the administered of I/V droperadol, intubated and placed on a ventilator with circulatory supports for 4 days.. On day five he was extubated and transfered to a medical ward. All laboratory values had returned to normal values by this time. The patient was subsequently discharged.. Neuroleptic malignant syndrome can occur at any stage of clozapine treatment, and the patient can be rechallenged after such an episode. This person was rechallenged and after 6 months of treatment has suffered no further recurrence of NMS.

Topics: Antipsychotic Agents; Clozapine; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Male; Middle Aged; Neuroleptic Malignant Syndrome; Neurologic Examination; Schizophrenia; Schizophrenic Psychology

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Clozapine; Diagnosis, Differential; Female; Fever; Humans; Male; Middle Aged; Neuroleptic Malignant Syndrome

Topics: Adult; Antipsychotic Agents; Clozapine; Disseminated Intravascular Coagulation; Humans; Male; Neuroleptic Malignant Syndrome; Thrombocytopenia

Although not universally accepted, evidence exists that clozapine treatment may be associated with neuroleptic malignant syndrome (NMS). To date, 10 cases of NMS associated with the use of clozapine have been reported in the literature. We report two more cases of NMS in patients on clozapine treatment and review the clinical presentations, biochemical features, risk factors, treatment, and rechallenge with neuroleptics in all reported patients who developed NMS while receiving clozapine treatment. An update and critical review of clozapine-induced NMS are also presented. Clozapine treatment can cause NMS similar to that induced by conventional neuroleptics. A history of NMS, existing brain insults, low serum iron concentrations, and being a young male may be risk factors for the development of NMS associated with clozapine treatment. NMS most commonly occurs when clozapine is being used along with other psychotropics. Early recognition of the syndrome and cessation of clozapine when NMS occurs are advised. Supportive care and use of dopamine agonists and dantrolene may be helpful in treating clozapine-associated NMS. These results support the notion that clozapine can cause NMS. However, NMS associated with clozapine treatment is a rare event. When it happens, the clinical presentation, risk factors, and management appear to be similar to those of NMS associated with conventional neuroleptics.

Topics: Adult; Antipsychotic Agents; Clozapine; Female; Humans; Male; Neuroleptic Malignant Syndrome; Psychotic Disorders; Schizophrenia

We describe a patient with marked elevations of creatine kinase following institution of clozapine treatment. The enzyme levels promptly subsided with discontinuation of clozapine. The clinical features did not meet any of the published criteria for neuroleptic malignant syndrome.

Topics: Adult; Clozapine; Creatine Kinase; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Male; Neuroleptic Malignant Syndrome; Schizophrenia, Paranoid

Topics: Antipsychotic Agents; Clozapine; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Lithium; Middle Aged; Neuroleptic Malignant Syndrome; Schizophrenia

Topics: Adult; Clozapine; Delirium; Humans; Male; Neuroleptic Malignant Syndrome; Schizophrenia

Clozapine is an atypical neuroleptic drug that was initially thought not to cause neuroleptic malignant syndrome (NMS). We report a case of NMS associated with clozapine as a single agent that developed in a patient with no prior history of NMS. In contrast to other reported cases of NMS with clozapine monotherapy in which rigidity was reported to be absent, our patient had classic NMS with lead-pipe rigidity. NMS should be included in the differential diagnosis of a febrile patient with a history of any neuroleptic treatment, including clozapine.

Topics: Adult; Antipsychotic Agents; Bromocriptine; Clozapine; Dantrolene; Diagnosis, Differential; Fever; Humans; Male; Muscle Rigidity; Neuroleptic Malignant Syndrome; Schizophrenia

Topics: Antipsychotic Agents; Clozapine; Humans; Neuroleptic Malignant Syndrome; Neurologic Examination; Psychotic Disorders; Recurrence; Risk Factors

Topics: Clozapine; Diagnosis, Differential; Humans; Neuroleptic Malignant Syndrome; Risk Factors; Schizophrenia; Schizophrenic Psychology

Topics: Adult; Atropine; Autonomic Nervous System Diseases; Clozapine; Humans; Male; Neuroleptic Malignant Syndrome; Parasympathetic Nervous System; Schizophrenia

Topics: Adult; Aged; Clozapine; Diagnosis, Differential; Female; Fever; Humans; Male; Middle Aged; Neuroleptic Malignant Syndrome; Research Design

Clozapine is an atypical antipsychotic drug which must only be prescribed for the treatment resistant schizophrenic patients. Contra-indications and precautionary measures (F.e no use of a drug that can enhance the potential for a granulocytoxic reaction) have to be well known and respected. There is an increased risk of granulocytopenia, and 1 or 2% of granulocytopenia may induce an agranulocytosis. This risk is compared with what is observed with other psychotropic drugs, phenothiazines particularly. Beyond clozapine adverse effects, three cases of severe cardio-vascular and respiratory dysregulation, one case of sudden death, and one case of induced coma are presented in detail from the literature: possible interactions between clozapine and adjunctive medications are discussed. Appropriate patients should be proposed a treatment by clozapine, in principle without association to any other psychotropic drug and in all the necessary precautions.

Topics: Agranulocytosis; Clozapine; Drug Synergism; Hematologic Diseases; Humans; Neuroleptic Malignant Syndrome; Schizophrenia

Nine out of 4044 patients admitted to our institution between 1987 and 1990 suffered an episode of NMS. Neuroleptic rechallenge using clozapine for persisting psychiatric illness was tolerated by eight patients. Clozapine was discontinued in one older, high-risk patient because recurrence of NMS was anticipated. Clozapine should be considered a drug of choice for psychotic patients with a history of NMS.

Topics: Adult; Antipsychotic Agents; Clozapine; Female; Humans; Male; Middle Aged; Neuroleptic Malignant Syndrome; Psychotic Disorders

Topics: Catatonia; Clozapine; Diagnosis, Differential; Humans; Lorazepam; Neuroleptic Malignant Syndrome

Topics: Adult; Clozapine; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Male; Neuroleptic Malignant Syndrome; Neurologic Examination; Schizophrenia; Schizophrenic Psychology

The treatment of psychotic symptoms in patients with a previous history of neuroleptic malignant syndrome (NMS) remains a dilemma. The authors describe a case in which clozapine caused NMS in a schizophrenic man who had previously experienced NMS during treatment with various antipsychotics. To their knowledge, this is the first report of "classical" NMS caused by clozapine alone.

Topics: Antipsychotic Agents; Clozapine; Dantrolene; Humans; Male; Middle Aged; Neuroleptic Malignant Syndrome; Schizophrenia, Catatonic

Topics: Clozapine; Humans; Neuroleptic Malignant Syndrome; Psychiatric Status Rating Scales; Regression Analysis; Schizophrenia; Schizophrenic Psychology

Topics: Clozapine; Humans; Neuroleptic Malignant Syndrome; Risk Factors

Clozapine, an atypical antipsychotic drug, is indicated for severely ill schizophrenic patients refractory to treatment with conventional neuroleptics. One advertised advantage of clozapine is the absence of associated neuroleptic malignant syndrome (NMS). On the basis of a clinical case, the authors question this claim. They are concerned that this potentially fatal condition may be misdiagnosed if physicians are not aware of possible NMS associated with the use of clozapine.

Topics: Adult; Clozapine; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Neuroleptic Malignant Syndrome; Schizophrenia, Paranoid

Neuroleptic malignant syndrome (NMS), a rare but serious side effect of psychotropic drugs, is usually attributed to blockade of striatal and hypothalamic dopaminergic tracts. Clozapine is an atypical antipsychotic that has minimal extrapyramidal effects and might not be expected to cause NMS. The authors report the development of NMS in a 30-year-old white man after three 25-mg clozapine doses. To their knowledge, this is the first case of NMS linked with clozapine in which concurrent psychotropic medications cannot be implicated.

Topics: Adult; Catatonia; Clozapine; Dose-Response Relationship, Drug; Humans; Male; Neuroleptic Malignant Syndrome; Psychotic Disorders

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

Topics: Adult; Chlorpromazine; Clopenthixol; Clozapine; Drug Therapy, Combination; Humans; Male; Neuroleptic Malignant Syndrome; Procyclidine; Recurrence; Schizophrenia; Schizophrenic Psychology

Topics: Adult; Clozapine; Dibenzazepines; Drug Therapy, Combination; Female; Humans; Neuroleptic Malignant Syndrome; Puerperal Disorders; Referral and Consultation; Respiratory Insufficiency; Schizophrenia, Catatonic

Topics: Adolescent; Carbamazepine; Clozapine; Diagnosis, Differential; Dose-Response Relationship, Drug; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Female; Follow-Up Studies; Haloperidol; Humans; Meclofenoxate; Neuroleptic Malignant Syndrome; Schizophrenia; Schizophrenic Psychology; Tiapamil Hydrochloride

Reinstitution of antipsychotic medication is problematic in patients with a history of neuroleptic malignant syndrome (NMS). In this case, a patient with a history of probable neuroleptic malignant syndrome caused by administration, as single agents, of haloperidol, molindone, and lithium was later treated successfully with the novel antipsychotic clozapine. The propensity of various antipsychotic agents to cause NMS is discussed.

Topics: Activities of Daily Living; Antipsychotic Agents; Clozapine; Humans; Male; Middle Aged; Neurocognitive Disorders; Neuroleptic Malignant Syndrome; Recurrence; Schizophrenia, Catatonic

Topics: Aged; Carbamazepine; Clozapine; Drug Therapy, Combination; Humans; Lithium; Male; Neuroleptic Malignant 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