clozapine and Intellectual-Disability

This is a comprehensive review of antipsychotic (AP)-induced dysphagia and its complications: choking and pneumonia. Areas covered: Four PubMed searches were completed in 2018. The limited literature includes: 1) 45 case reports of AP-induced dysphagia with pharmacological mechanisms, 2) a systematic review of APs as a risk factor for dysphagia, 3) reviews suggesting adult patients with intellectual disability (ID) and dementia are prone to dysphagia (APs are a risk factor among multiple others), 4) studies of the increased risk of choking in patients with mental illness (APs are a contributing factor), 5) naturalistic pneumonia studies suggesting that pneumonia may contribute to AP-increased death in dementia, and 6) naturalistic studies suggesting that pneumonia may be a major cause of morbidity and mortality in clozapine patients. Expert commentary: The 2005 Food and Drug Administration requirement that package inserts warn of AP-induced dysphagia jumpstarted this area, but current studies are limited by: 1) its naturalistic nature, 2) the lack of dysphagia studies of patients with IDs and dementia on APs, and 3) the assumed indirect association between dysphagia with choking and pneumonia. Future clozapine studies on pneumonia, if they lead to a package insert warning, may have high potential to save lives.

Topics: Adult; Airway Obstruction; Antipsychotic Agents; Clozapine; Deglutition Disorders; Dementia; Drug Labeling; Humans; Intellectual Disability; Mental Disorders; Pneumonia; Risk Factors

Psychosis is three times more common in people with an intellectual disability than in those without an intellectual disability. A low intelligence quotient (IQ) is a defining characteristic for intellectual disability and a risk factor for poor outcome in psychosis. Clozapine is recommended for treatment-resistant psychosis. The effect of psychotropic medication can be different in people with intellectual disability; for example, they may be more prone to side effects. People with an intellectual disability and psychosis form a special subgroup and we wanted to examine if there is randomised controlled trial (RCT) data in this population to support the use of clozapine.. To determine the effects of clozapine for treating adults with a dual diagnosis of intellectual disability and psychosis.. We searched CENTRAL, Ovid MEDLINE, Embase and eight other databases up to December 2014. We also searched two trials registers, the Cochrane Schizophrenia Group's Register of Trials, and contacted the manufacturers of clozapine.. RCTs that assessed the effects of clozapine, at any dose, for treating adults (aged 18 years and over) with a dual diagnosis of intellectual disability and psychotic disorder, compared with placebo or another antipsychotic medication.. Three review authors independently screened all titles, abstracts and any relevant full-text reports against the inclusion criteria.. Of the 1224 titles and abstracts screened, we shortlisted 38 full-text articles, which we subsequently excluded as they did not meet the inclusion criteria. These studies were not RCTs. Consequently, no studies are included in this Cochrane review.. There are currently no RCTs that assess the efficacy and side effects of clozapine in people with intellectual disabilities and psychoses. Given the use of clozapine in this vulnerable population, there is an urgent need for a RCT of clozapine in people with a dual diagnosis of intellectual disability and psychosis to fill the evidence gap.

Topics: Adult; Antipsychotic Agents; Clozapine; Humans; Intellectual Disability; Psychotic Disorders

Topics: Adolescent; Adult; Age Factors; Aged; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Body Weight; Clinical Trials as Topic; Clozapine; Diabetes Mellitus; Diabetes Mellitus, Type 2; Dibenzothiazepines; Female; Glucose; Haloperidol; Humans; Intellectual Disability; Male; Mental Disorders; Metabolic Syndrome; Middle Aged; Olanzapine; Quetiapine Fumarate; Retrospective Studies; Risk Factors; Risperidone; Schizophrenia; Sex Factors; Time Factors; Weight Gain

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

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

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

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

Clozapine has proven efficacy in the management of treatment-resistant schizophrenia. Additional use in patients with mood and schizoaffective disorders, Parkinson's disease with psychosis, and brain injury has been reported. Preclinical data have suggested its possible utility in treating self-injurious behavior in patients with mental retardation.. The use of clozapine in six patients with moderate-to-profound mental retardation is described. The issue of diagnosing psychosis in such individuals and its impact on choice of pharmacotherapy is considered.. Clozapine in these individuals may have led to a significant reduction in aggression, self-injurious behavior, and psychotic symptoms. Side effects were minimal and similar to those seen in the schizophrenic population.. These case reports illustrate that clozapine may be useful and well tolerated in the treatment of aggression in patients with moderate-to-profound mental retardation.

Topics: Adult; Aggression; Clozapine; Female; Humans; Intellectual Disability; Male; Middle Aged; Self-Injurious Behavior; Severity of Illness Index

Young patients with intellectual disability (ID) have both diagnostic and therapeutic challenges. These include, inter alia, diagnostic overshadowing, diagnostic slippage and heightened vulnerability to adverse drug reactions. These would portent a generally poor prognostication.. This is a case-study of an adolescent with intellectual disability long-hospitalized for co-morbid treatment-resistant bipolar mood disorder that failed to respond to ECT. Patient partially responded to LAI risperidone with repeated ADRs. Top-up with low-dose clozapine (100 mg/d) was pursued.. Low-dose clozapine top-up complemented therapeutic response (mood lability and paranoia) and strikingly safeguarded effectively against risperidone-related extrapyramidal side effects.. Add-on clozapine remains a viable option, albeit off-label, in young patients with ID and treatment-resistant affective/schizophreniform psychoses. Clozapine has an edge over other agents in the setting of dyskinesias.

Topics: Adolescent; Antipsychotic Agents; Clozapine; Dystonia; Dystonic Disorders; Humans; Intellectual Disability; Risperidone

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

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

The management of challenging and refractory destructive behaviour in young patients with intellectual disability (ID) is a major issue faced by families, carers and healthcare professionals who support them. Often, paediatricians and psychiatrists use various behavioural and psychopharmacological approaches, including polypharmacy. We report on one such patient who benefitted greatly from a trial of clozapine, resulting in less aggression, improved quality of life and potentially huge cost savings. We conclude that clozapine may represent a beneficial though seldom-used option for severe, destructive behaviour in young people with ID.

Topics: Adolescent; Antipsychotic Agents; Clozapine; Humans; Intellectual Disability; Male; Quality of Life; Self-Injurious Behavior

There is paucity of empirical data regarding the use of either clozapine or electroconvulsive therapy (ECT) in the acute phase and maintenance treatment of schizophrenia in adults with intellectual disability. Herein we report the successful acute and long-term remission of psychotic symptoms and catatonia with the combination of clozapine and ECT in a 26-year-old female with moderate ID and treatment-resistant schizophrenia. To our knowledge, this is the first case example of the successful use of the combination of bilateral, standard-pulse ECT and clozapine in both acute and long-term treatment of treatment-resistant schizophrenia and catatonia in an adult with ID. Our report adds further support to the emerging evidence regarding the efficacy and safety of this combination in treatment-resistant schizophrenia.

Topics: Adult; Antipsychotic Agents; Clozapine; Electroconvulsive Therapy; Female; Humans; Intellectual Disability; Schizophrenia, Catatonic

Comorbid mental illness is common in patients with intellectual disability. Antipsychotics are widely used for these conditions, but the effect of clozapine remains largely unknown.. We aimed to investigate the effectiveness of clozapine on naturalistic outcomes in patients with intellectual disability.. By combining the national health registers, we identified all patients in Denmark with intellectual disability initiating clozapine treatment during the period 1996-2012. We used a mirror-image model to test whether initiation of clozapine treatment was associated with reduction in psychiatric admissions and inpatient days, reduction in the number of individuals performing intentional self-harm or overdose, and less frequent use of concomitant psychopharmacological treatment. Similar outcome measures were used in a reverse mirror-image model to investigate the effects of clozapine termination.. A total of 405 patients with intellectual disability redeemed clozapine. After initiation of clozapine the number of psychiatric admissions were reduced by 0.65 admissions (95% CI: 0.31-1.00) and the inpatient days were reduced by 67.2 days (95% CI: 51.2-83.3), with a similar decrease for patients with intellectual disability without psychiatric comorbidity. Clozapine treatment was not found to reduce the number of individuals with intentional self-harm, incidents of overdose, or the use of concomitant psychotropics. In cases where clozapine treatment was terminated, the number of psychiatric admissions increased by 0.57 admissions (95% CI: 0.01-1.12).. This nationwide study, which is the largest to date, suggests that treatment with clozapine is associated with a reduction in psychiatric admissions and inpatient days in patients with intellectual disability. Further studies evaluating the effects of clozapine in patients with intellectual disability are warranted.

Topics: Adult; Antipsychotic Agents; Clozapine; Denmark; Drug Overdose; Female; Follow-Up Studies; Hospitalization; Humans; Intellectual Disability; Male; Outcome Assessment, Health Care; Registries; Self-Injurious Behavior; Treatment Outcome

At least 11 rare copy number variants (CNVs) have been shown to be major risk factors for schizophrenia (SZ). These CNVs also increase the risk for other neurodevelopmental disorders, such as intellectual disability. It is possible that additional intellectual disability-associated CNVs increase the risk for SZ but have not yet been implicated in SZ because of previous studies being underpowered.. To examine whether additional CNVs implicated in intellectual disability represent novel SZ risk loci.. We used single-nucleotide polymorphism (SNP) array data to evaluate a set of 51 CNVs implicated in intellectual disability (excluding the known SZ loci) in a large data set of patients with SZ and healthy persons serving as controls recruited in a variety of settings. We analyzed a new sample of 6934 individuals with SZ and 8751 controls and combined those data with previously published large data sets for a total of 20 403 cases of SZ and 26 628 controls.. Burden analysis of CNVs implicated in intellectual disability (excluding known SZ CNVs) for association with SZ. Association of individual intellectual disability CNV loci with SZ.. Of data on the 20 403 cases (6151 [30.15%] female) and 26 628 controls (14 252 [53.52%] female), 51 intellectual disability CNVs were analyzed. Collectively, intellectual disability CNVs were significantly enriched for SZ (P = 1.0 × 10-6; odds ratio [OR], 1.9 [95% CI, 1.46-2.49]). Of the 51 CNVs tested, 19 (37%) were more common in SZ cases; only 4 (8%) were more common in controls (no observations were made for the remaining 28 [55%] loci). One novel locus, deletion at 16p12.1, was significantly associated with SZ after correction for multiple testing (rate in SZ, 33 [0.16%]; rate in controls, 12 [0.05%]; corrected P = .017; OR, 3.3; 95% CI, 1.61-7.05), and 2 loci reached nominal levels of significance (deletions at 2q11.2: 6 [0.03%] vs 1 [0.004%]; OR, 9.3; 95% CI, 1.03-447.76; corrected P > .99; and duplications at 10q11.21q11.23: 5 [0.2%] vs 0 [0.03%]; OR, infinity; 95% CI, 1.26-infinity; corrected P = .71). Our new data set also provided independent support for the 11 SZ risk loci previously reported to be associated with the disorder and for the protective effect of 22q11.2 duplication.. A large proportion of CNV loci implicated in intellectual disability are risk factors for SZ, but the available sample size precludes statistical confirmation for additional individual loci.

Topics: Adult; Case-Control Studies; Clozapine; Cohort Studies; Comorbidity; DNA Copy Number Variations; Drug Resistance; Female; Genetic Loci; Genetic Predisposition to Disease; Genotype; Humans; Intellectual Disability; Male; Polymorphism, Single Nucleotide; Reference Values; Risk; Schizophrenia; United Kingdom

Administration of second-generation antipsychotic drugs (SGAs) often leads to weight gain and consequent cardio-metabolic side effects. We observed that clozapine but not six other antipsychotic drugs reprogrammed the gene expression pattern of differentiating human adipocytes ex vivo, leading to an elevated expression of the browning marker gene UCP1, more and smaller lipid droplets and more mitochondrial DNA than in the untreated white adipocytes. Laser scanning cytometry showed that up to 40% of the differentiating single primary and Simpson-Golabi-Behmel syndrome (SGBS) adipocytes had the characteristic morphological features of browning cells. Furthermore, clozapine significantly upregulated ELOVL3, CIDEA, CYC1, PGC1A and TBX1 genes but not ZIC1 suggesting induction of the beige-like and not the classical brown phenotype. When we tested whether browning induced by clozapine can be explained by its known pharmacological effect of antagonizing serotonin (5HT) receptors, it was found that browning cells expressed 5HT receptors 2A, 1D, 7 and the upregulation of browning markers was diminished in the presence of exogenous 5HT. Undifferentiated progenitors or completely differentiated beige or white adipocytes did not respond to clozapine administration. The clozapine-induced beige cells displayed increased basal and oligomycin-inhibited (proton leak) oxygen consumption, but these cells showed a lower response to cAMP stimulus as compared with control beige adipocytes indicating that they are less capable to respond to natural thermogenic anti-obesity cues. Our data altogether suggest that novel pharmacological stimulation of these masked beige adipocytes can be a future therapeutic target for the treatment of SGA-induced weight gain.

Topics: Adipocytes, Beige; Adipocytes, Brown; Adipocytes, White; Adult; Aged; Antipsychotic Agents; Arrhythmias, Cardiac; Cell Differentiation; Cells, Cultured; Clozapine; Cyclic AMP; DNA, Mitochondrial; Female; Gene Expression; Genetic Diseases, X-Linked; Gigantism; Heart Defects, Congenital; Humans; Intellectual Disability; Lipid Droplets; Male; Middle Aged; Oxygen Consumption; Phenotype; Receptors, Serotonin; Thermogenesis; Uncoupling Protein 1; Up-Regulation; Weight Gain; Young Adult

Topics: Adolescent; Antipsychotic Agents; Clozapine; Combined Modality Therapy; Electroconvulsive Therapy; Female; Humans; Intellectual Disability; Schizophrenia

Tardive dyskinesia (TD) is still a severe side effect induced by old neuroleptic drugs as well as modern atypical ones. The treatment is inefficient and often experimental. Aim of this study was to examine the effect of pramipexole, a dopamine D3 receptor agonist, in a severe case of oro-facial TD.. The TD of a 21 year old male patient with severe oro-facial occurrence was assessed by the Simpson et al scale before starting pramipexole therapy. Reevaluation was made during therapy and when the maximum dose of 1.44 mg a day was reached. Standard therapy with clozapine, valproic acid, oxazepam, bornaprin hydrochlorid and tiapride was continued as before.. Oral dyskinesia decreased 20 % and no side effects were observed. Regarding psychopathology the patient was more interested in work and showed better concentration in therapies.. Pramipexole could be a new promising add-on therapy in severe TD. Additionally, the low plasma binding and mild side effect profile of pramipexole makes it safe in combination with antipsychotic therapy.

Topics: Adjustment Disorders; Aggression; Antipsychotic Agents; Benzothiazoles; Clozapine; Dopamine Agonists; Dose-Response Relationship, Drug; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Humans; Intellectual Disability; Male; Pramipexole; Receptors, Dopamine D3; Social Behavior Disorders; Young Adult

While clozapine is an effective treatment for refractory schizophrenia, its use is limited by haematological side effects. Treatment options that allow continued prescription of clozapine by tackling these side effects will greatly aid patients for whom this medication is all too often their only hope of recovery.. In this case report, we describe what we believe are two 'firsts' in the clozapine literature: the use of granulocyte-colony stimulating factor on a prophylactic basis in an intellectually disabled patient receiving clozapine for refractory schizophrenia.. Treatment with granulocyte-colony stimulating factor prevented discontinuation of clozapine, enabling our intellectually disabled patient's recovery from a schizophrenic illness.

Topics: Adult; Agranulocytosis; Clozapine; Comorbidity; Drug Therapy, Combination; Granulocyte Colony-Stimulating Factor; Humans; Injections, Subcutaneous; Intellectual Disability; Leukocyte Count; Leukopoiesis; Lithium Carbonate; Male; Schizophrenia, Paranoid

Topics: Aggression; Agranulocytosis; Antipsychotic Agents; Clozapine; Fatal Outcome; Humans; Intellectual Disability; Male; Middle Aged; Myelodysplastic Syndromes; Substance Withdrawal Syndrome; Time Factors

Topics: Adolescent; Antipsychotic Agents; Clozapine; Female; Humans; Intellectual Disability; Mental Disorders; Ocular Motility Disorders; Substance Withdrawal Syndrome

Clozapine is an atypical antipsychotic known to cause considerable weight gain. The extent to which genetic factors determine weight gain is unknown. Here we report on a pair of female monozygotic twins concordant for schizophrenia and mild mental retardation who were treated with clozapine over 5.5 years. One twin gained a total of 53.1 kg and had a weight of 107.5 kg (BMI=38.1 kg/m2) at the end of the observation period. The other twin gained a total of 48.2 kg and finally had a weight of 100.4 kg (BMI=33.8 kg/m2). Because both patients experienced considerable weight gain during treatment, our observation suggests that the antipsychotic-induced weight gain is under strong genetic control.

Topics: Adult; Antipsychotic Agents; Clozapine; Female; Humans; Intellectual Disability; Psychotic Disorders; Schizophrenia; Twins, Monozygotic; Weight Gain

Clozapine is licensed for the treatment of psychotic illnesses resistant to other antipsychotic medications. Velo-cardio-facial syndrome (VCFS) is associated with a vulnerability to psychotic illness that may be resistant to treatment with conventional typical and atypical antipsychotics.. A 32-year-old man with intellectual disability (ID) and a long history of treatment-resistant psychosis was found to have VCFS. Treatment with typical antipsychotic drugs and with one atypical olanzapine produced no improvement.. Treatment with clozapine produced an improvement in psychotic symptoms and associated behavioural abnormalities, but caused hypersalivation, constipation and a seizure disorder. The latter led to two fractures, one requiring surgery. The addition of sodium valproate stopped seizures.. Clozapine may improve psychotic symptoms for people with ID associated with VCFS, but clinicians should be alert for potential adverse effects.

Topics: Abnormalities, Multiple; Adult; Antipsychotic Agents; Cleft Palate; Clozapine; Face; Genetics, Behavioral; Heart Defects, Congenital; Humans; Intellectual Disability; Male; Psychotic Disorders; Syndrome

We conducted an analogue functional analysis contrasting motor tasks with varying types of social consequences for movements associated with tardive dyskinesia (TD) in 2 men who had been diagnosed with developmental disabilities and TD. Our findings suggest that TD-related movements were not a function of social reinforcement contingencies. However, motor-activation tasks decreased TD-related movements, suggesting a possible novel intervention.

Topics: Antipsychotic Agents; Clozapine; Dyskinesia, Drug-Induced; Humans; Intellectual Disability; Male; Middle Aged

Atypical antipsychotic medications for self-injurious behavior (SIB), aggression, and destruction among people with mental retardation and development disabilities are becoming increasingly accepted. Most studies are on risperidone and fewer have been conducted on clozapine. The present single-blind study reports marked reductions in SIB and aggression of two persons with profound mental retardation who were nonresponsive to all other behavioral and psychopharmacological interventions, including risperidone. The most effective dose was 200 mg/day. Side effects were mild and the drug was tolerated well.

Topics: Adult; Clozapine; Dose-Response Relationship, Drug; Humans; Intellectual Disability; Male; Middle Aged; Risperidone; Self-Injurious Behavior; Single-Blind Method; Treatment Failure; Treatment Outcome

A 17-year-old boy suffering from a severe schizophrenic disorder of the paranoid type and mental retardation did not respond to treatment with typical antipsychotics, whereas under clozapine treatment he showed a favourable response. Discontinuation of clozapine led to an acute psychotic relapse. During clozapine treatment the patient developed severe neutropenia.. Due to the history of unsatisfactory response to traditional antipsychotics, clozapine treatment was continued despite white blood cell (WBC) decline. Concomitant treatment with G-CSF was followed by a rapid normalisation of WBC.. This case report is not intended to challenge the clinical practice of discontinuing clozapine upon the development of neutropenia/agranulocytosis, but rather to stimulate further research in the pathophysiology and clinical consequences of a clozapine rechallenge after a WBC decline, especially in patients with a rather complex symptomatology where no sufficient therapeutic results can be achieved with any other pharmacological intervention than clozapine.

Topics: Adolescent; Antipsychotic Agents; Clozapine; Granulocyte Colony-Stimulating Factor; Humans; Intellectual Disability; Male; Neutropenia; Schizophrenia, Paranoid

Topics: Clomipramine; Clozapine; Compulsive Behavior; Drug Administration Schedule; Drug Therapy, Combination; Humans; Intellectual Disability; Male; Middle Aged; Self Mutilation; Treatment Outcome

Topics: Activities of Daily Living; Adolescent; Attention; Clozapine; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Intellectual Disability; Intelligence; Problem Solving; Schizophrenia, Disorganized

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

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

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

Bone-marrow chromosomes were examined from 38 mentally and physically retarded and two psychiatric patients who were being treated with a variety of neuropharmacologic drugs. Twenty of these patients used clozapine (Leponex). The clastogenic effects of clozapine in vitro were studied in the lymphocyte cultures of three patients--one free of hematologic disease and two who 6 months earlier had had agranulocytosis attributed to the use of clozapine. The mean frequency of cytogenetic abnormalities in the bone-marrow cells of patients who used clozapine was significantly increased (P less than 0.05). The two patients who had had agranulocytosis had a greater frequency of cytogenetic abnormalities in their cultured lymphocytes in vivo and in vitro than the patient free of hematologic disease. A clone with a 13/14 chromosome translocation was detected in one of the patients. As all patients received a number of drugs during the in vivo and in vitro studies no definite conclusions could be drawn regarding the role played by clozapine in the occurrence of chromosomal abnormalities.

Topics: Adolescent; Adult; Bone Marrow; Child; Child, Preschool; Chromosome Aberrations; Chromosome Disorders; Chromosomes, Human, 13-15; Clozapine; Dibenzazepines; Female; Humans; Intellectual Disability; Lymphocytes; Male; Middle Aged; Translocation, Genetic