clozapine and Acute-Disease

The dose-response relationships of antipsychotic drugs for schizophrenia are not well defined, but such information would be important for decision making by clinicians. The authors sought to fill this gap by conducting dose-response meta-analyses.. A search of multiple electronic databases (through November 2018) was conducted for all placebo-controlled dose-finding studies for 20 second-generation antipsychotic drugs and haloperidol (oral and long-acting injectable, LAI) in people with acute schizophrenia symptoms. Dose-response curves were constructed with random-effects dose-response meta-analyses and a spline model. The outcome measure was total score reduction from baseline on the Positive and Negative Syndrome Scale or the Brief Psychiatric Rating Scale. The authors identified 95% effective doses, explored whether higher or lower doses than the currently licensed ones might be more appropriate, and derived dose equivalencies from the 95% effective doses.. Sixty-eight studies met the inclusion criteria. The 95% effective doses and the doses equivalent to 1 mg of oral risperidone, respectively, were as follows: amisulpride for patients with positive symptoms, 537 mg/day and 85.8 mg; aripiprazole, 11.5 mg/day and 1.8 mg; aripiprazole LAI (lauroxil), 463 mg every 4 weeks and 264 mg; asenapine, 15.0 mg/day and 2.4 mg; brexpiprazole, 3.36 mg/day and 0.54 mg; haloperidol, 6.3 mg/day and 1.01 mg; iloperidone, 20.13 mg/day and 3.2 mg; lurasidone, 147 mg/day and 23.5 mg; olanzapine, 15.2 mg/day and 2.4 mg; olanzapine LAI, 277 mg every 2 weeks and 3.2 mg; paliperidone, 13.4 mg/day and 2.1 mg; paliperidone LAI, 120 mg every 4 weeks and 1.53 mg; quetiapine, 482 mg/day and 77 mg; risperidone, 6.3 mg/day and 1 mg; risperidone LAI, 36.6 mg every 2 weeks and 0.42 mg; sertindole, 22.5 mg/day and 3.6 mg; and ziprasidone, 186 mg/day and 30 mg. For amisulpride and olanzapine, specific data for patients with predominant negative symptoms were available. The authors have made available on their web site a spreadsheet with this method and other updated methods that can be used to estimate dose equivalencies in practice.. In chronic schizophrenia patients with acute exacerbations, doses higher than the identified 95% effective doses may on average not provide more efficacy. For some drugs, higher than currently licensed doses might be tested in further trials, because their dose-response curves did not plateau.

Topics: Acute Disease; Administration, Oral; Antipsychotic Agents; Aripiprazole; Clozapine; Delayed-Action Preparations; Dose-Response Relationship, Drug; Haloperidol; Humans; Imidazoles; Indoles; Isoxazoles; Lurasidone Hydrochloride; Olanzapine; Paliperidone Palmitate; Piperazines; Piperidines; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Schizophrenic Psychology; Thiazoles; Thiophenes

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

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

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

The frequency and severity of extrapyramidal syndrome (EPS) were evaluated in patients with DSM-III or DSM-IV schizophrenia in the acute phase (- 8 weeks) of randomized, double-blind, controlled trials from the integrated olanzapine clinical trial database.. This retrospective analysis included 23 clinical trials and 4611 patients from November 11, 1991, through July 31, 2001. Incidences of dystonic, parkinsonian, and akathisia events were compared using treatment-emergent adverse-event data. Categorical analyses of Simpson-Angus Scale and Barnes Akathisia Scale (BAS) scores, use of anticholinergic medications, and baseline-to-endpoint changes in Simpson-Angus Scale and BAS scores were compared.. A significantly smaller percentage of olanzapine-treated patients experienced dystonic events than did haloperidol- (p <.001) or risperidone-treated patients (p =.047). A significantly greater percentage of haloperidol-treated patients experienced parkinsonian (p <.001) and akathisia (p <.001) events than did olanzapine-treated patients. Categorical analysis of Simpson-Angus Scale scores showed significantly more haloperidol- (p <.001) or risperidone-treated patients (p =.004) developed parkinsonism than did olanzapine-treated patients. Olanzapine-treated patients experienced significantly greater reductions in Simpson-Angus Scale scores than did haloperidol- (p <.001), risperidone- (p <.001), or clozapine-treated (p =.032) patients. Categorical analysis of BAS scores showed significantly more haloperidol-treated patients experienced treatment-emergent akathisia versus olanzapine-treated patients (p <.001). Significantly greater reductions in BAS scores were experienced during olanzapine treatment versus placebo (p =.007), haloperidol (p <.001), and risperidone (p =.004) treatments. A significantly smaller percentage of olanzapine-treated patients received anticholinergic medications compared with that of haloperidol- (p <.001) or risperidone-treated patients (p =.018). Compared with that in olanzapine-treated patients, the duration of anticholinergic cotreatment was significantly longer among haloperidol- (p <.001) or risperidone-treated patients (p =.040) and significantly shorter among clozapine-treated patients (p =.021).. This analysis of available data from olanzapine clinical trials lends additional support to olanzapine's favorable EPS profile.

Topics: Acute Disease; Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Cholinergic Antagonists; Clozapine; Double-Blind Method; Female; Haloperidol; Humans; Male; Olanzapine; Pirenzepine; Placebos; Randomized Controlled Trials as Topic; Retrospective Studies; Risperidone; Schizophrenia

A 40-year-old schizophrenic man was found unconscious, with constricted pupils, sinus tachycardia, and twitching of the limbs. There were signs of lung infection, which was treated with antibiotics, and mild rhabdomyolysis. He regained consciousness over 8 hours, and reported taking 3-4 g clozapine. Recovery was uneventful. Measured peak clozapine and norclozapine concentrations were 3.53 mg/L and 0.70 mg/L, respectively. The concentration-time curves were biphasic, with secondary peaks at approximately 36 hours postadmission. Terminal elimination half-lives were 16.9 hours and 22.5 hours for clozapine and norclozapine, respectively.. Clozapine and its metabolite norclozapine can show biphasic plasma concentration-time curves after overdosage.

Topics: Acute Disease; Adult; Antipsychotic Agents; Chromatography, High Pressure Liquid; Clozapine; Drug Overdose; Half-Life; Humans; Male

For patients hospitalized with acute episodes of psychosis, rapid stabilization of intense positive symptoms, hostility, and agitation is typically a preeminent therapeutic goal. These goals often differ from those of the nonhospitalized patient with psychosis for whom long-term treatment goals such as improvement of negative symptoms, cognitive function, compliance, and reduction in side effect burden may be paramount. Therefore, when selecting an antipsychotic treatment for hospitalized patients, efficacy against positive symptoms and hostility as well as speed of therapeutic onset should strongly be considered. At the same time, selection of antipsychotic treatment in the inpatient setting should establish a definitive treatment that will address long-term goals effectively after discharge. This article presents the rationale and practical guidelines for selection of treatment regimens for patients hospitalized due to acute psychosis.

Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Clozapine; Drug Administration Schedule; Drug Therapy, Combination; Haloperidol; Hospitalization; Hostility; Humans; Olanzapine; Pirenzepine; Practice Guidelines as Topic; Psychomotor Agitation; Psychotic Disorders; Risperidone; Treatment Outcome

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

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

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

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

The author reviews the evolution of emergency psychiatric practice over the past 20 years--from the concept of high-dose antipsychotic medication to the more rational treatment approach for acute psychosis made possible by modern pharmacodynamic insight and the availability of new pharmacotherapeutic agents. A decision tree for current practice in the rapid tranquilization of agitated, apparently psychotic patients is described.

Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Clozapine; Decision Trees; Drug Administration Schedule; Emergency Services, Psychiatric; Emergency Treatment; Haloperidol; History, 20th Century; Humans; Lorazepam; Olanzapine; Pirenzepine; Psychotic Disorders; Risperidone

Severe psychotic decompensation during clozapine withdrawal has been reported previously. Less attention has been paid to movement disorders following abrupt clozapine withdrawal. This report describes 4 subjects who experienced severe dystonias and dyskinesias upon abrupt clozapine withdrawal.. Current and past medical records of 4 subjects with DSM-IV schizophrenia or schizo-affective disorder were reviewed.. All subjects had a history of neuroleptic-induced extrapyramidal symptoms, 1 had a history of severe dystonias, and 1 had neuroleptic malignant syndrome. All had mild orolingual tardive dyskinesia prior to clozapine treatment. All subjects had received clozapine for several months, and 3 of the 4 subjects stopped clozapine abruptly. Two subjects experienced cholinergic rebound symptoms within hours, which resolved quickly. These subjects had severe limb-axial and neck dystonias and dyskinesias 5 to 14 days after clozapine withdrawal. Two subjects were unable to ambulate, and 1 had a lurching gait. Two gagged while eating or drinking. Two subjects were returned to clozapine, 1 was started on low-dose risperidone treatment, and 1 was started on olanzapine treatment. All experienced significant improvements in their mental state and movement disorders.. Severe movement disorders, which may be worse than the movements prior to clozapine treatment, and cholinergic rebound symptoms may occur upon abrupt clozapine withdrawal and must be recognized in addition to the severe psychotic decompensation noted in some patients. Patients, families, and caregivers must be alerted to this possibility. Where possible, a slow clozapine taper, the use of anticholinergic agents, and symptomatic treatment may help minimize these withdrawal symptoms, and reintroduction of clozapine or treatment with the newer atypical agents can help in the clinical management of these symptoms.

Topics: Acute Disease; Adolescent; Adult; Antipsychotic Agents; Clozapine; Drug Administration Schedule; Dyskinesia, Drug-Induced; Dystonia; Female; Humans; Male; Middle Aged; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Substance Withdrawal Syndrome

Determining the optimal dose of antipsychotic for an acute schizophrenic episode has been an elusive goal. Empirical dose adjustment with conventional neuroleptics has generally led to excessive drug exposure, in part due to the lag time between initiation of therapy and response and in part due to the indefinite nature of the response. Data from dose- and plasma concentration-response studies and from imaging studies have provided some guidance. In particular, newer antipsychotic drugs such as risperidone and sertindole have been evaluated in multiple fixed-dose designs to determine the optimal dose or dose range. To devise an overall treatment strategy for an acute psychotic episode, we reviewed and incorporated data from a number of controlled studies.

Topics: Acute Disease; Antipsychotic Agents; Clozapine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Delivery Systems; Haloperidol; Humans; Risperidone; Schizophrenia

To assess the effectiveness of aripiprazole in the treatment of patients with psychotic symptoms in the emergency psychiatric setting.. We considered all patients admitted to a psychiatric intensive care unit of a general hospital in a two year-period, treated with at least one dose of aripiprazole. We measured 1) the rate of cases starting aripiprazole who did not change antipsychotic in the course of hospitalization; 2) the rate of cases who were concurrently treated with another antipsychotic; 3) the CGI Improvement score.. In 63 cases, aripiprazole was started on admission. Forty-nine (77.7%) of these cases were treated with aripiprazole also on discharge. Among the 63 cases who started aripiprazole on admission, 22 (34.9%) were concurrently treated with another antipsychotic. Among the 53 cases discharged with aripiprazole, 15 (28.3%) were concurrently treated with another antipsychotic. Of the 49 cases treated with aripiprazole both on admission and on discharge, 24 cases were much improved, 11 cases moderately improved, 10 cases mildly improved, and 4 cases were not improved at the CGI Improvement Score.. Aripiprazole should be considered as first line treatment in some patients affected by psychotic disorders visited in the emergency psychiatric setting.

Topics: Acute Disease; Adult; Antipsychotic Agents; Aripiprazole; Clozapine; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Drug Therapy, Combination; Emergency Services, Psychiatric; Female; Humans; Intensive Care Units; Male; Middle Aged; Piperazines; Psychiatric Department, Hospital; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Severity of Illness Index; Treatment Outcome

Acute extrapyramidal side effects (EPS) are a common phenomenon of treatment with conventional antipsychotics. Previous studies found that clozapine has little propensity to cause EPS, while risperidone produces some EPS, but at levels lower than those of conventional antipsychotics.. We compared the prevalence and severity of EPS in patients treated with clozapine, risperidone, or conventional antipsychotics for at least 3 months. Our main hypothesis was that there would be differences between the three treatment groups with regard to akathisia, measured with the Barnes Akathisia Scale, and extrapyramidal motor side effects (rigidity, rigidity factor, tremor, salivation), measured with the Simpson-Angus scale. Secondarily, we were interested in possible differences between the three groups with respect to the anticholinergic comedication and the subjective impression of the patients, measured with the van Putten scale.. We studied 106 patients (41 patients treated with clozapine, 23 patients with risperidone, and 42 patients treated with conventional antipsychotics). The sample was 57.5% male and had a mean +/- SD age of 36.6 +/- 9.3 years. The mean dose of antipsychotics calculated in chlorpromazine equivalents was 425.6 +/- 197.1 mg/day in the clozapine group, 4.7 +/- 2.1 mg/day in the risperidone group, and 476.5 +/- 476.9 mg/day in the group treated with conventional antipsychotics. The point-prevalence of akathisia was 7.3% in the clozapine group, 13% in the risperidone group, and 23.8% in the group treated with conventional antipsychotics. The point-prevalence of rigidity and cogwheeling respectively was 4.9% and 2.4% in the clozapine group, 17.4% and 17.4% in the risperidone group, and 35.7% and 26.2% in the group treated with conventional antipsychotics.. Our results indicate that risperidone is superior to conventional neuroleptics in that it causes fewer EPS. In comparison to clozapine, risperidone produces EPS levels that are intermediate between clozapine and conventional antipsychotic drugs.

Topics: Acute Disease; Adolescent; Adult; Akathisia, Drug-Induced; Ambulatory Care; Antipsychotic Agents; Basal Ganglia Diseases; Clozapine; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Prevalence; Product Surveillance, Postmarketing; Psychotic Disorders; Risperidone; Schizophrenia; Severity of Illness Index

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

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

To establish the effect of the atypical neuroleptic clozapine on chorea, voluntary motor performance, and functional disability in patients with Huntington's disease.. Thirty three patients with Huntington's disease participated in a double blind randomised trial. A maximum of 150 mg/day clozapine or placebo equivalent was given for a period of 31 days. Assessments were performed in the week before and at the last day of the trial. Chorea was scored using the abnormal involuntary movement scale (AIMS), the chorea score of the unified Huntington's disease rating scale (UHDRS), and judgement of video recordings. Voluntary motor performance was assessed using the UHDRS motor scale. Patients and their partners completed a questionnaire regarding functional disability. Twelve patients already used other neuroleptic medication, which was kept unchanged during the trial period. Results of neuroleptic naive and neuroleptic treated patients were analysed separately.. Clozapine tended to reduce chorea in neuroleptic naive patients only (AIMS); improvement seemed more pronounced in patients receiving higher doses of clozapine. Other measures of chorea (UHDRS chorea score, video ratings) showed no improvement. Clozapine had no beneficial effect on chorea in patients already receiving neuroleptic medication. Voluntary motor performance did not improve with clozapine. Neuroleptic naive patients reported aggravation of functional disability, possibly reflecting the frequent occurrence of side effects. Adverse reactions forced trial termination in six patients and dose reduction in another eight, and consisted mainly of drowsiness, fatigue, anticholinergic symptoms, and walking difficulties.. Clozapine has little beneficial effect in patients with Huntington's disease, although individual patients may tolerate doses high enough to reduce chorea. Because adverse reactions are often encountered, clozapine should be used with restraint in this patient group.

Topics: Acute Disease; Adult; Aged; Antipsychotic Agents; Clozapine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Fatigue; Female; Humans; Huntington Disease; Male; Middle Aged; Placebos; Severity of Illness Index; Sleep Stages; Treatment Outcome

1. In order to verify the hypothesis that risperidone is a useful therapeutic alternative to clozapine the authors carried out a randomized double blind trial in 59 patients with paranoid hallucinatory psychoses. 2. In a treatment lasting 28 days three groups of patients received either 4 mg risperidone (N = 20), 8 mg risperidone (N = 19), or 400 mg clozapine (N = 20) daily. 3. The tolerance of 4 mg risperidone was globally assessed as being better than that of 400 mg clozapine. Drop-outs under clozapine were mostly caused by side effects, whereas under risperidone they tended to occur for therapeutic inefficacy. 4. The antipsychotic effect was highly significant and clinically relevant under both risperidone and clozapine.

Topics: Acute Disease; Adult; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Clozapine; Double-Blind Method; Electrocardiography; Electroencephalography; Female; Humans; Infant, Newborn; Isoxazoles; Male; Middle Aged; Piperidines; Psychiatric Status Rating Scales; Risperidone; Schizophrenia, Paranoid

Clozapine is a unique compound belonging to a relatively new group of antipsychotic agents, the dibenzazepines. To our knowledge, the present study represents the first double-blind, controlled comparison recorded in the United States. The data suggest that clozapine in the present population of newly admitted, acutely psychotic schizophrenic individuals, and in the doses employed, was more effective in overall improvement response, discharge rate, and ameliorating discrete symptoms across the different objective rating scales used than was chlorpromazine (Thorazine) hydrochloride. Placebo was ineffective. Unlike chlorpromazine, no extrapyramidal reactions occurred in those patients ingesting clozapine. Clozapine was also beneficial in reversing abnormal involuntary motor movements. It is an excellent anxiolytic and hypnotic agent. Sedation, hypotension, and hypersalivation are among the more common side effects observed.

Topics: Acute Disease; Adult; Chlorpromazine; Clinical Trials as Topic; Clozapine; Dibenzazepines; Double-Blind Method; Female; Hospitals, Psychiatric; Humans; Male; Middle Aged; Placebos; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Social Adjustment; United States

Topics: Acute Disease; Adult; Clinical Trials as Topic; Clozapine; Dibenzazepines; Double-Blind Method; Female; Humans; Male; Middle Aged; Schizophrenia

Double Blind comparative trial of a new dibenzodiazepine derivative Clozapine (Leponex) with Chlorpromazine was conducted in the treatment of acute schizophrenic illness over a 6 week period. Factor Analysis of ratings in 9 matched pairs indicates that Clozapine, at 300 mg. per day, is comparable in efficacy to Chlorpromazine in all factors except "Irritability" for which Clozapine appears to be superior. Illness severity and Global Change ratings in all patients showed that Clozapine is more effective in producting a shift towards improvement at the end of 6 weeks. Major side effects reported in Clozapine confirmed sedation and hypersalivation as consistent problems and presence of rigidity and tremor (extra-pyramidal) being at variance with other studies.

Topics: Acute Disease; Adolescent; Adult; Chlorpromazine; Clinical Trials as Topic; Clozapine; Dibenzazepines; Female; Humans; Male; Middle Aged; Schizophrenia

Topics: Acute Disease; Clozapine; Dangerous Behavior; Female; Humans; Male; Nephritis, Interstitial

Acute pancreatitis is a rare but recognised complication of clozapine leading to termination of treatment.. We present the case of a 39-year-old man with treatment-resistant schizoaffective disorder and a history of recurrent acute pancreatitis attributed to clozapine. After 15 years of unremitting symptoms with disruptive and aggressive behaviour, he was admitted for a clozapine rechallenge. Despite experiencing two further episodes of acute pancreatitis during clozapine treatment that led to its temporary withdrawal, clozapine was successfully re-established under gastroenterology consultation with close monitoring which resulted in progressively marked improvement of his mental state.. This case demonstrates that patients who develop pancreatitis during clozapine treatment may be cautiously rechallenged with specialist gastroenterology support.

Topics: Acute Disease; Adult; Antipsychotic Agents; Clozapine; Humans; Male; Pancreatitis; 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

Clozapine is a second-generation antipsychotic typically reserved for refractory psychotic disorders due to its high-risk side effect profile to include agranulocytosis, with its attendant need for regular blood draws. While reports of extrapyramidal symptoms (EPS), including acute dystonic reactions, are exceedingly rare, we present the case of a 44-year-old male with a long-standing history of treatment-resistant schizoaffective disorder and no history of EPS who experienced an acute buccal dystonic reaction in the setting of clozapine initiation and discontinuation of depot and oral risperidone. This case report presents one of the few documented episodes of acute dystonic reactions occurring in the setting of clozapine administration. Based upon the patient's history and the dosing time line of the medications, we propose that an interaction between the clozapine and residual risperidone was responsible for the development of the acute buccal dystonia.

Topics: Acute Disease; Adult; Antipsychotic Agents; Clozapine; Drug Interactions; Dystonia; Humans; Male; Psychotic Disorders; Risperidone

Upregulation of selenium binding protein 1 (SELENBP1) mRNA expression has been reported in schizophrenia, primarily in the dorsolateral prefrontal cortex. However, peripheral blood studies are limited and results are inconsistent. In this study, we examined SELENBP1 mRNA expression in whole blood and protein expression in plasma from patients with recent-onset schizophrenia (n = 30), treatment-resistant schizophrenia (n = 71) and healthy controls (n = 57). We also examined the effects of SELENBP1 genetic variation on gene and protein expression. We found lower SELENBP1 plasma protein levels in patients with recent-onset schizophrenia (p = 0.042) but not in treatment-resistant schizophrenia (p = 0.81). Measurement of peripheral mRNA levels showed no difference between treatment-resistant schizophrenia and healthy controls (p = 0.234) but clozapine plasma levels (p = 0.036) and duration of illness (p = 0.028) were positively correlated with mRNA levels. Genetic variation was not associated with mRNA or protein expression. Our data represent the first peripheral proteomic study of SELENBP1 in schizophrenia and suggest that plasma SELENBP1 protein is downregulated in patients with recent-onset schizophrenia.

Topics: Acute Disease; Adult; Antipsychotic Agents; Biomarkers; Chronic Disease; Clozapine; Down-Regulation; Drug Resistance; Female; Haplotypes; Humans; Male; Polymorphism, Single Nucleotide; Proteome; Proteomics; RNA, Messenger; Schizophrenia; Selenium-Binding Proteins; Time Factors; Young Adult

Treatment of patients with Treatment-resistant Schizophrenia (TRS), who fail to respond to multiple antipsychotic trials, including clozapine (CLZ), is challenging. Several alternative strategies are reported in studies, one of which includes augmenting antipsychotics (AP) with Electroconvulsive therapy (ECT). We discuss a case of an acutely psychotic patient with TRS who responded effectively and sustained remission to this strategy which was ECT combined with two AP, CLZ and aripiprazole. Notable improvement in clinical and cognitive outcomes was seen with just five right unilateral ECT sessions, CLZ titrated up to 62.5 mg/d and aripiprazole 20 mg/d with no adverse effects. Nine days into the psychiatric hospitalization, patient had decreased total scores on the Positive and Negative Syndrome Scale by 44% and an improved score on the St. Louis University Mental Status Exam by increasing from 3 to 22. This case report suggests that a subgroup of patients with TRS could benefit from a trial of adjunct ECT combined with AP to achieve a rapid alleviation of positive and negative symptoms which allows patients to have greater functional stability.

Topics: Acute Disease; Adult; Antipsychotic Agents; Aripiprazole; Clozapine; Combined Modality Therapy; Drug Therapy, Combination; Electroconvulsive Therapy; Female; Hospitalization; Humans; Psychiatric Status Rating Scales; Schizophrenia; Treatment Outcome

Focal epilepsy is commonly pharmacoresistant, and resective surgery is often contraindicated by proximity to eloquent cortex. Many patients have no effective treatment options. Gene therapy allows cell-type specific inhibition of neuronal excitability, but on-demand seizure suppression has only been achieved with optogenetics, which requires invasive light delivery. Here we test a combined chemical-genetic approach to achieve localized suppression of neuronal excitability in a seizure focus, using viral expression of the modified muscarinic receptor hM4Di. hM4Di has no effect in the absence of its selective, normally inactive and orally bioavailable agonist clozapine-N-oxide (CNO). Systemic administration of CNO suppresses focal seizures evoked by two different chemoconvulsants, pilocarpine and picrotoxin. CNO also has a robust anti-seizure effect in a chronic model of focal neocortical epilepsy. Chemical-genetic seizure attenuation holds promise as a novel approach to treat intractable focal epilepsy while minimizing disruption of normal circuit function in untransduced brain regions or in the absence of the specific ligand.

Topics: Acute Disease; Animals; Clozapine; Epilepsies, Partial; Gene Silencing; Genetic Therapy; Humans; Male; Motor Activity; Neocortex; Picrotoxin; Pilocarpine; Rats, Sprague-Dawley; Receptor, Muscarinic M4; Synaptic Transmission

We studied the development of metabolic disorders related to tissue hypoxia in 54 patients with acute severe asaleptin intoxication complicated by acute respiratory insfficiency of mixed genesis. We also estimated the role of a substrate antihypoxant cytoflavin in the correction of these disorders and clinical features of acute intoxication. Cyroflavin was shown to accelerate normalization of metabolic disorders which in turn improves clinical symptoms of severe forms of acute asaleptin intoxication.

Topics: Acute Disease; Adult; Antipsychotic Agents; Clozapine; Drug Combinations; Female; Flavin Mononucleotide; Humans; Hypoxia; Inosine Diphosphate; Male; Metabolic Diseases; Middle Aged; Niacinamide; Respiratory Insufficiency; Severity of Illness Index; Succinates; Young Adult

This is the case of a young man suffering from schizophrenia and treated with clozapine. He developed acute heart failure associated with pericardial effusion and midventricular dyskinesia with severe systolic dysfunction and left ventricular dilatation at echocardiogram, readily resolved after the suspension of clozapine therapy. The segmental wall motion abnormalities observed at echocardiogram in this case are peculiar and have never been described before. The possible cardiotoxic effects of clozapine have been reported previously in the literature. Because of its serious potential side effects this drug is not considered the first choice for treatment of schizophrenia. Before beginning treatment, patients should undergo a cardiac evaluation, and they should also be periodically followed up with echocardiograms.

Topics: Acute Disease; Antipsychotic Agents; Clozapine; Heart Failure; Humans; Male; Myocardial Contraction; Myocarditis; Pericardial Effusion; Schizophrenia; Ultrasonography; Ventricular Dysfunction; Ventricular Function, Left; Ventricular Function, Right; Young Adult

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Chemical and Drug Induced Liver Injury; Clozapine; Hepatitis C, Chronic; Humans; Male; Olanzapine; Schizophrenia, Paranoid; Time Factors

Topics: Abdomen; Abdominal Pain; Acute Disease; Adult; Blood Coagulation Disorders; Clozapine; Colon; Diagnosis, Differential; Dilatation, Pathologic; Gastrointestinal Motility; Humans; Male; Megacolon, Toxic; Radiography; Schizophrenia, Paranoid; Serotonin Antagonists; Shock, Septic

The study of depressions in 183 schizophrenic patients after the management of acute psychosis included evaluation of depressive symptoms, their relation to other psychopathologic syndromes, and the efficiency of drug therapy. The Calgary scale (CDSS) was used to assess severity of depression in schizophrenia along with other standardized psychometric scales to characterize general psychopathologic, positive, and negative symptoms, locomotor disturbances, other concomitant disorders, and general clinical picture. The predominance of depressive conditions with adynamic symptoms was documented. The majority of depressions occurred after the first attack. Those developing in the early post-attack period differed from depressions within a few months after the reduction of psychosis. Syndromic nature of depressions was evident from the number of psychotic episodes experienced by the patients. Depressive symptoms that developed after the management of the acute psychotic state could be efficiently and safely relieved by additional differential treatment with antidepressants. Depressive symptoms in schizophrenia are not predictors of poor prognosis provided the patient receives adequate therapy. More attention is needed to identification and adequate treatment of depression in schizophrenia. Optimized therapy of affective disorders in schizophrenic patients permits to improve prognosis of the disease.

Topics: Acute Disease; Adult; Antipsychotic Agents; Clozapine; Depressive Disorder, Major; Drug Administration Schedule; Female; Humans; International Classification of Diseases; Male; Patient Compliance; Psychotic Disorders; Schizophrenia; Severity of Illness Index; Time Factors

Although it is generally accepted that atypical antipsychotics differ in their risk for diabetic side effects, the underlying pharmacological mechanisms are unknown. Studies on the mechanisms of antipsychotic-induced hyperglycemia or insulin resistance are often confounded by the concomitant weight gain and dyslipidemia, known diabetic risk factors. To investigate whether antipsychotics can acutely cause metabolic effects before any change in body composition, we studied the effects of four atypical antipsychotics on whole-body insulin resistance. Using the hyperinsulinemic, euglycemic clamp technique in conscious rats, insulin and somatostatin were infused at a constant rate to provide constant hyperinsulinemia and to suppress pancreatic insulin secretion. Glucose was infused at a variable rate, adjusted to maintain euglycemia. At steady state, animals were administered vehicle (V) or antipsychotic and the glucose infusion rate was monitored as an index of insulin sensitivity. Clamp experiments using radiotracers and studies on glucose uptake into isolated skeletal muscle were conducted to differentiate between effects on hepatic glucose production (HGP) and on peripheral glucose uptake. Olanzapine (OLAN) and clozapine (CLOZ) acutely impaired whole-body insulin sensitivity in a dose-dependent manner (P<0.001 vs V), whereas ziprasidone and risperidone had no effect. CLOZ also induced profound insulin resistance after dosing 10 mg/kg/day for 5 days (P<0.05 vs V). Tracer studies indicated that acute changes mainly reflect increased HGP, consistent with the lack of effect on glucose uptake. OLAN and CLOZ can thus rapidly induce marked insulin resistance, which could contribute to the hyperglycemia and ketoacidosis reported for patients receiving those therapies.

Topics: Acute Disease; Animals; Antipsychotic Agents; Benzodiazepines; Clozapine; Disease Models, Animal; Dose-Response Relationship, Drug; Energy Metabolism; Glucose; Hyperglycemia; Insulin; Insulin Resistance; Liver; Male; Metabolic Syndrome; Muscle, Skeletal; Olanzapine; Rats; Rats, Wistar; Somatostatin

Topics: Acute Disease; Adult; Antipsychotic Agents; Ascites; Chemical and Drug Induced Liver Injury; Clozapine; Female; Humans; Pleurisy; Psychotic Disorders; Serositis

Recent volumetric magnetic resonance imaging (MRI) studies have suggested brain volume changes in schizophrenia to be progressive in nature. Whether this is a global process or some brain areas are more affected than others is not known. In a 5-year longitudinal study, MRI whole brain scans were obtained from 96 patients with schizophrenia and 113 matched healthy comparison subjects. Changes over time in focal gray and white matter were measured with voxel-based morphometry throughout the brain. Over the 5-year interval, excessive decreases in gray matter density were found in patients in the left superior frontal area (Brodmann areas 9/10), left superior temporal gyrus (Brodmann area 42), right caudate nucleus, and right thalamus as compared to healthy individuals. Excessive gray matter density decrease in the superior frontal gray matter was related to increased number of hospitalizations, whereas a higher cumulative dose of clozapine and olanzapine during the scan interval was related to lesser decreases in this area. In conclusion, gray matter density loss occurs across the course of the illness in schizophrenia, predominantly in left frontal and temporal cortices. Moreover, the progression in left frontal density loss appears to be related to an increased number of psychotic episodes, with atypical antipsychotic medication attenuating these changes.

Topics: Acute Disease; Adolescent; Adult; Antipsychotic Agents; Atrophy; Benzodiazepines; Brain; Caudate Nucleus; Clozapine; Disease Progression; Female; Follow-Up Studies; Frontal Lobe; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Middle Aged; Olanzapine; Schizophrenia; Temporal Lobe; Thalamus; Time Factors

Topics: Acute Disease; Adrenergic beta-Antagonists; Adult; Akathisia, Drug-Induced; Antipsychotic Agents; Circadian Rhythm; Clozapine; Humans; Male; Propranolol; Schizophrenia

A case of acute myocarditis associated with the commencement of clozapine is described, highlighting the onset, course and possible contributing factors. There is an urgent need to raise awareness about this potentially fatal complication of clozapine use.. A 20-year-old male with schizophrenia developed a sudden onset of myocarditis after commencement of clozapine. The patient recovered with intensive medical support. The symptoms occurred around 2 weeks after starting clozapine in an inpatient setting. Possible contributing factors may have been concomitant antidepressant use and unaccustomed physical activity.. Myocarditis is an increasingly recognized complication associated with the use of clozapine. It can be fatal if not recognized and treated early. Considering that clozapine remains the gold standard in treatment of resistant psychosis, there is an urgent need to raise awareness among medical and paramedical staff involved in the care of these patients. There are also implications for recommendations and regulations regarding the use of clozapine.

Topics: Acute Disease; Adult; Antidepressive Agents; Antipsychotic Agents; Clozapine; Drug Interactions; Drug Therapy, Combination; Fluoxetine; Humans; Lithium Compounds; Male; Myocarditis; Psychotic Disorders; Risk Factors

No systematic study has focused on the characteristics and outcome of acute clozapine intoxication, although clozapine is the most widely used antipsychotic agent in China. The study reported herein examined the features of clozapine intoxication and the therapeutic effect of hemoperfusion (HP).. In a retrospective chart review, the notes of 47 patients who attempted suicide by ingesting large amounts of clozapine and were treated at the only psychiatric emergency service in Beijing were analyzed. Of the 20 unconscious patients with plasma clozapine concentrations of more than 2000 ng/mL, 14 received a combination of HP and symptomatic treatment, whereas the other 6 and the remaining 27 patients received only symptomatic treatment. Patients' psychiatric conditions and both plasma clozapine and norclozapine concentrations were closely monitored and registered.. One patient died of pulmonary edema and subsequent heart failure, but the rest of the patients recovered without any sequelae. Patients who received HP regained consciousness significantly faster than their counterparts with the same level of clozapine plasma concentration (>2000 ng/mL) who did not receive HP.. A combination of HP and symptomatic treatment is the best therapeutic option when plasma clozapine concentration is high.

Topics: Acute Disease; Adult; Alprazolam; Antipsychotic Agents; China; Clonazepam; Clozapine; Depressive Disorder; Dose-Response Relationship, Drug; Drug Overdose; Emergency Service, Hospital; Hemoperfusion; Humans; Medical History Taking; Middle Aged; Pulmonary Edema; Retrospective Studies; Schizophrenia; Stress Disorders, Post-Traumatic; Suicide, Attempted; Sulpiride; Unconsciousness; Wine

Topics: Acute Disease; Adult; Antipsychotic Agents; Clozapine; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Myocarditis; Psychotic Disorders

Topics: Acute Disease; Aged; Clozapine; Drugs, Generic; Humans; Loxapine; Male; Medication Errors; Schizophrenia, Paranoid; Therapeutic Equivalency; Treatment Outcome

The aims of our study were (1) to compare the dose of clozapine needed to achieve remission in patients who stopped their treatment (study group) versus patients who continued taking this medication (control group) and (2) to compare the clinical characteristics of remission between these 2 groups.. We retrospectively reviewed the medical records of all treatment-resistant schizophrenic and schizoaffective patients (according to DSM-IV criteria) who were treated with clozapine over a period of 9 years, from January 1995 through December 2003. The study group consisted of 43 patients and the control group of 12 patients. All patients' files from both groups were examined, and each patient's remission was scored twice--initially on discharge from the hospital and subsequently after final discharge for the study group, or at the end of the study for the control group.. The change of clozapine dose from the first to the last remission expressed by percentage shows a significant difference between the 43% increase in clozapine dose in the study group and the 12.5% decrease in clozapine dose in the control group (p < .001). Quality of remission assessment showed deterioration in the global remission score in the study group, while the quality of remission assessment in the control group did not show any change.. Our findings suggest that the discontinuation of clozapine treatment leads to a deterioration in the quality of remission, with a need for an increased dose of clozapine. Further prospective studies on larger samples are needed to confirm these findings.

Topics: Acute Disease; Adult; Antipsychotic Agents; Clozapine; Diagnostic and Statistical Manual of Mental Disorders; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Patient Dropouts; Prognosis; Psychiatric Status Rating Scales; Psychotic Disorders; Retrospective Studies; Schizophrenia; Schizophrenic Psychology; Substance Withdrawal Syndrome; Treatment Outcome

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

Acute poisonings by medical, narcotic substances and alcohol are actual in Russia in the recent years. Comparison of analytic facilities of modern analytical techniques: chromatographic (HPLC, GC, GC-MS) and immuno-chemical (FPIA) in clinical toxicology for urgent diagnostics, assessment of the severity of acute poisoning and the efficacy of the treatment in patients with acute poisonings by psychotropic drugs, narcotics and alcohol have been done. The object of the study were serum, blood, urine of 611 patients with acute poisonings by amitriptyline, clozapine, carbamazepine, opiates and also alcohol. Threshold concentrations (threshold, critical and lethal) of the toxicants and their active metabolites which corresponded to different degrees of poisoning severity have been determined. The most comfortable and informative screening method for express diagnostics and assessment of severity of acute poisonings by psychotropic drugs and narcotics showed the HPLC with using automatic analyzers. FPIA using the automatic analyzer could be applied for screening studies, if group identification is enough. GC-FID method is advisable in case of poisoning by medical substances and narcotics in view of repeated investigation for assessment of the efficacy of the therapy. GC-MS could be advisable for confirming the results of other methods. GC-TCD possess high sensitivity and specificity and is optimal for express differential diagnostics and quantitative assessment of acute poisoning by ethanol and other alcohols.

Topics: Acute Disease; Amitriptyline; Carbamazepine; Central Nervous System Agents; Clozapine; Ethanol; Female; Humans; Immunoenzyme Techniques; Male; Mass Spectrometry; Narcotics; Poisoning; Reproducibility of Results; Russia; Severity of Illness Index; Substance Abuse Detection; Substance-Related Disorders; Toxicology

Topics: Acute Disease; Adult; Antipsychotic Agents; Clozapine; Humans; Male; Nephritis, Interstitial; Schizophrenia, Paranoid

Topics: Acute Disease; Aged; Antipsychotic Agents; Clozapine; Humans; Male; Pericardial Effusion; Pleural Effusion; Psychotic Disorders; Serositis

Topics: Acute Disease; Adolescent; Catatonia; Clozapine; Humans; Male; N-Methyl-3,4-methylenedioxyamphetamine

Case series suggest that some antipsychotics may induce or exacerbate type 2 diabetes. This study measured the association of antipsychotic treatments with diabetes at a population level.. Claims data for psychosis patients (ICD-CM-9 290.xx-299.xx) within health plans encompassing 2.5 million individuals were analyzed. Patients reporting preexisting type 2 diabetes up to 8 months prior to observation were excluded. The frequency of newly reported type 2 diabetes in untreated patients and among patients treated with antipsychotics from 5 categories (risperidone, olanzapine, clozapine, and high-potency and low-potency conventionals) was compared. Logistic regression models compared the odds of diabetes based on exposure to each of the antipsychotic categories.. Based on 12 months of exposure, the odds of type 2 diabetes for risperidone-treated patients (odds ratio = 0.88, 95% CI = 0.372 to 2.070) was not significantly different from that for untreated patients, whereas patients receiving other antipsychotics had a significantly greater risk of diabetes than untreated patients (p < .05): olanzapine, 3.10 (95% CI = 1.620 to 5.934); clozapine, 7.44 (95% CI = 0.603 to 34.751); high-potency conventionals, 2.13 (95% CI = 1.097 to 4.134); and low-potency conventionals, 3.46 (95% CI = 1.522 to 7.785). Older age and greater use of non-antipsychotic psychotropic medications also contributed to risk of type 2 diabetes. Olanzapine also showed significantly higher (p < .01) odds of diabetes associated with increasing dose.. Consistent with previously published literature, these data suggest that olanzapine, clozapine, and some conventional antipsychotics appear to increase the risk of acquiring or exacerbating type 2 diabetes and that the effect may vary by drug. In contrast to these agents, risperidone was not associated with an increased risk of type 2 diabetes.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Comorbidity; Confidence Intervals; Databases as Topic; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Insurance Claim Review; Logistic Models; Male; Middle Aged; Odds Ratio; Olanzapine; Pirenzepine; Psychotic Disorders; Risk Factors; Risperidone; United States

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Eosinophilia; Humans; Male; Olanzapine; Pirenzepine; Psychotic Disorders; Selective Serotonin Reuptake Inhibitors

Topographic quantitative electroencephalographic (EEG) power and frequency indices were collected in 17 treatment refractory, DSM-III diagnosed schizophrenic patients, before and after acute (single dose) and chronic (six weeks) clozapine treatment, as well as in 17 healthy volunteers. Prior to treatment, patients exhibited greater overall absolute theta power, slower mean alpha frequency and elevated absolute delta and total power in anterior regions. Acute dosing increased total spectrum power globally, slow wave power posteriorally, mean alpha frequency and beta power anteriorally and decreased alpha power posteriorally. Six weeks of clozapine treatment significantly reduced clinical ratings of positive and negative symptoms as well as symptoms of global psychopathology. Chronic treatment resulted in EEG slowing as shown by decreases in relative alpha power, mean beta/total spectrum frequency and by widespread increases in absolute total and delta/theta power. The preliminary findings suggest that brain electric profiling may be a promising tool for assessing and understanding the central impact of pharmacotherapeutic interventions in schizophrenia.

Topics: Acute Disease; Adolescent; Adult; Antipsychotic Agents; Brain Mapping; Clozapine; Drug Administration Schedule; Electroencephalography; Female; Humans; Male; Middle Aged; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Time Factors

A 45-year-old woman of Moroccan origin developed a dilated cardiomyopathy during clozapine treatment for a psychosis that did not respond to conventional antipsychotics. The onset of her illness was acute with chest pain. She subsequently developed shortness of breath and oedema of the face and legs. The cardiomyopathy appeared to be partially reversible after the clozapine was halted. Cardiomyopathy during the use of clozapine is rarely described in the literature, although myocarditis is a known complication. The cause of cardiomyopathy during the use of clozapine is not known. Myocarditis might evolve into cardiomyopathy. There are indications that myocarditis is caused by an allergic reaction to clozapine. It is advised that clozapine treatment should only be initiated under the close supervision of a psychiatrist, and that during the use of clozapine one should be alert to the risk of cardiac complications.

Topics: Acute Disease; Antipsychotic Agents; Cardiomyopathy, Dilated; Chest Pain; Clozapine; Edema; Female; Humans; Middle Aged; Remission Induction

Topics: Acute Disease; Amisulpride; Antipsychotic Agents; Benzodiazepines; Clozapine; Cost-Benefit Analysis; Dibenzothiazepines; Dibenzothiepins; Dyskinesia, Drug-Induced; Germany; Humans; Neurotransmitter Agents; Olanzapine; Patient Compliance; Pirenzepine; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Sulpiride

With the advent of atypical antipsychotics, quality of life for patients with schizophrenia has improved significantly. The positive effects are based not only on the compliance-enhancing reduction of extrapyramidal side effects but also due to improved cognitive function and social integration, shorter duration, and overall reduction of hospital treatment. Numerous controlled studies have addressed the issue of switching patients from typical to atypical antipsychotics. However, published data on substituting one atypical antipsychotic for another are preliminary and very limited. This case report describes acute side effects which occurred when switching from clozapine to amisulpride and discusses mechanisms on the receptor level. Regarding these two agents, the clinical relevance of the knowledge of receptor profiles is outlined.

Topics: Acute Disease; Adult; Amisulpride; Antipsychotic Agents; Clozapine; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Pharyngeal Diseases; Psychotic Disorders; Receptors, Dopamine; Spasm; Sulpiride; Tongue Diseases

The atypical antipsychotic, clozapine, has been reported to reduce smoking in schizophrenic patients. We sought to determine whether other atypical antipsychotics would also be associated with a decreased prevalence of smoking in this population. Data were obtained from three groups of chronic, hospitalized, schizophrenic patients, receiving either a typical antipsychotic (n=15), clozapine (n=6), or another atypical antipsychotic (n=18). In addition to smoking prevalence, the groups were compared with regard to demographics (age, education), medication (doses, duration of treatment, side-effects), clinical (diagnosis, duration of illness) and behavioral (Wide-Range Achievement Test, Wechsler Adult Intelligence Scale) variables. Smoking prevalence differed significantly among the three groups (P<0.001). Clozapine was associated with a significantly lower incidence of smoking than either typical drugs (P<0.003) or other atypical antipsychotics (P=0. 042). The groups did not differ on demographic or other medication variables or on any of several behavioral measures. However, a diagnosis of paranoid schizophrenia was also significantly correlated with smoking (P<0.01), but not with medication class. Although the cause is still unknown, these results are consistent with reports that clozapine reduces smoking and provide new data on smoking prevalence associated with other atypical agents.

Topics: Acute Disease; Adult; Brief Psychiatric Rating Scale; Chronic Disease; Clozapine; Female; Hospitalization; Hospitals, Psychiatric; Humans; Male; Prevalence; Schizophrenia; Serotonin Antagonists; Smoking; Wechsler Scales

Drug hypersensitivity reactions commonly cause acute interstitial nephritis (AIN). Clozapine, a new antipsychotic, can cause fatal bone-marrow toxicity. We report clozapine-induced AIN as another serious adverse drug reaction.

Topics: Acute Disease; Adult; Antipsychotic Agents; Clozapine; Creatinine; Female; Humans; Nephritis, Interstitial; Renal Dialysis

Topics: Acute Disease; Antipsychotic Agents; Clozapine; Drug Administration Schedule; Drug Interactions; Drug Therapy, Combination; Humans; Male; Middle Aged; Perphenazine; Psychoses, Substance-Induced; Psychotic Disorders

110 patients (52 men, 58 women) in a state of acute intoxication were examined in emergency department of psychoneurologic hospital. Neuroleptics of different groups were used to commit a suicide (91.3% of the cases), to obtain a toxicomanic effect (6.3%) and accidentally (1.8%). The patients suffered from borderline mental disorders (39.2%), schizophrenia (40.9%), manic-depressive psychosis in depressive phase (10.9%), chronic alcoholism (4.5%) and organic damages of CNS (4.5%). The patients with borderline states used various drugs and had more light disorders of consciousness (deafness). Meanwhile, the patients with endogenic mental disorders used strong neuroleptics, as a rule, that resulted in coma. In residual period there were different syndromes from asthenic to psychoorganic ones. They were more severe after poisoning with aminazinum, haloperidol, leponex.

Topics: Acute Disease; Adult; Age Distribution; Antipsychotic Agents; Chlorpromazine; Clozapine; Female; Haloperidol; Humans; Male; Mental Disorders; Middle Aged; Suicide, Attempted

Clozapine-induced hepatotoxicity is not well known and is usually of no clinical significance. This report describes fatal acute fulminant liver failure caused by clozapine in a 39-year-old man with chronic paranoid schizophrenia. The hepatotoxicity of clozapine is reviewed. Asymptomatic elevation of transaminase levels is observed most commonly, affecting between 30% and 50% of patients. Icteric hepatitis is uncommon, noted in 84 of 136,000 patients (0.06%). Fatal acute fulminant hepatitis has been documented in 2 patients (0.001%). The mechanism of clozapine hepatotoxicity is unknown. Although serious toxicity is rare, prescribers of clozapine should be aware of the hepatotoxic potential.

Topics: Acute Disease; Adult; Clozapine; Fatal Outcome; Hepatic Encephalopathy; Humans; Liver; Male; Schizophrenia, Paranoid

Acute generalized exanthematic pustulosis is a severe adverse drug reaction which occurs after taking antibiotics. Rare cases implicating psychotrops have been observed.. A 71-year old women with schizophrenia was given closapine for six weeks when she developed an erythematopustular skin reaction and fever typical of acute generalized exanthematic pustulosis. The skin disease regressed one week after withdrawing clozapine.. This is the first case of acute generalized exanthematic pustulosis observed after taking the neuroleptic drug, clozapine, used in severe schizophrenia.

Topics: Acute Disease; Aged; Antipsychotic Agents; Clozapine; Exanthema; Female; Humans; Schizophrenia; Skin Diseases, Vesiculobullous

Topics: Acute Disease; Biperiden; Clozapine; Dystonia; Haloperidol; Humans; Male; Middle Aged; Schizophrenia

Eosinophilia associated with clozapine treatment has been reported in some studies and limited case reports. Because little is known regarding incidence, course, and relevance of this finding, clozapine therapy has been terminated prematurely in some patients with elevated eosinophil counts.. Records were reviewed on 118 consecutively hospitalized, acutely psychotic patients treated over a 1-year period with clozapine for at least 3 weeks. Demographic data were obtained on those patients, and white blood cell counts were analyzed. We reviewed the data for predisposing factors, associated medical findings, or clinical sequelae, and performed a two-sided Fisher's exact test to determine if sex or diagnosis was associated with a higher risk of developing eosinophilia. The literature pertaining to this blood dyscrasia and its relationship to clozapine was reviewed.. In our population, the cumulative incidence of eosinophilia among women was 23% (13/57), a statistically significant higher risk (p < .01) than that in men (7% [4/61]). In all cases, the eosinophilia was noted between Weeks 3 and 5 of treatment and resolved without medical or psychiatric complications.. Eosinophilia should be added to the list of commonly observed side effects of clozapine treatment. Women appear to be at significant risk. Eosinophilia usually occurs early in therapy, spontaneously resolves, and is not associated with any known complications. An otherwise healthy person with this blood dyscrasia may continue with treatment but should be monitored closely. Further investigation into this finding may provide insight into the mechanism of neutropenia and other adverse reactions to clozapine.

Topics: Acute Disease; Adult; Clozapine; Depressive Disorder; Eosinophilia; Female; Hospitalization; Humans; Incidence; Leukocyte Count; Male; Middle Aged; Psychotic Disorders; Risk Factors; Schizophrenia; Sex Factors

Topics: Acute Disease; Adult; Bulimia; Clozapine; Dyskinesia, Drug-Induced; Female; Fluoxetine; Humans; Recurrence; Schizophrenia; Thiothixene

Topics: Acute Disease; Adult; Clozapine; Humans; Male; Pancreatitis; Psychotic Disorders

Haloperidol and clozapine were rapidly withdrawn from a schizophrenic patient on separate occasions several months apart. Mental status changes and fluctuations in involuntary movements were carefully observed under both conditions. Although little change in either mental status or involuntary movements was observed within the 3 weeks following the withdrawal of haloperidol, marked deterioration in mental status and involuntary movements occurred within 1 week of withdrawal of clozapine. Implications of this differential response to withdrawal of antipsychotic medications are discussed.

Topics: Acute Disease; Adult; Ambulatory Care; Clozapine; Haloperidol; Hospitalization; Humans; Male; Psychiatric Status Rating Scales; Psychoses, Substance-Induced; Schizophrenia; Schizophrenic Psychology; Substance Withdrawal Syndrome

Topics: Acute Disease; Adult; Agranulocytosis; Bone Marrow; Chemical and Drug Induced Liver Injury; Clozapine; Dibenzazepines; Humans; Male; Schizophrenia

Topics: Acute Disease; Adult; Clozapine; Death, Sudden; Dibenzazepines; Humans; Male; Myocarditis

Topics: Acute Disease; Agranulocytosis; Clozapine; Female; Humans; Middle Aged

Fifty-two mental hospital cases of acute and chronic schizophrenia and gross behaviour disorders were investigated and observed for 6-12 months during treatment with clozapine. Three-quarters of the acute cases recovered with full occupation capacity. Two-thirds of the chronic cases improved markedly. Antisocial behaviour was controlled in 12 out of the 13 behaviour-disordered group. The improvement in initiative and social capacity was striking and appeared to be due to improved awareness of the environment and the acquisition and handling of useful knowledge. The response to clozapine appears to be specific and relapses occurred when maintenance medication was stopped. It is of value in treating temper states in epilepsy and has the advantage of not causing extrapyramidal symptoms and side-effects are slight after the first week. Maximum improvement may not be reached before 8 weeks. Thereafter the maintenance dose can be small and fluctuations in the illness do not seem to occur. The dosage, side-effects and precautions are discussed. A rating system to display the effect of clozapine on individual parameters as well as on the over-all state was devised for this study.

Topics: Acute Disease; Adolescent; Adult; Aged; Chronic Disease; Clozapine; Dibenzazepines; Epilepsy; Female; Humans; Male; Middle Aged; Recurrence; Schizophrenia; Social Behavior Disorders

The treatment of acute schizophrenic disorders with large doses of droperidol was compared to clozapine and clopenthixol in a special study. Apart from the clinical protocol, psychometric test for the assessment of social behaviour and thought disorders were used. The advantages of the treatment with droperidol, especially in highly disturbed acute schizophrenic patients, are shown and discussed by means of the results of psychological tests and clinical experience.

Topics: Acute Disease; Biperiden; Blood Pressure; Clopenthixol; Clozapine; Droperidol; Drug Administration Schedule; Drug Evaluation; Humans; Male; Psychological Tests; Remission, Spontaneous; Salivation; Schizophrenia; Schizophrenic Psychology