clozapine and Dystonia

Patients with chronic psychosis on prolonged antipsychotic therapy may present with paroxysmal dystonia along with an exacerbation of their psychotic symptoms: paroxysmal dystonia and psychotic exacerbations (PDPE). The interindividual variability in the clinical presentations of PDPE can pose challenges in its diagnosis and treatment. The objectives of this work are to (i) discuss this rare phenomenon through a series of 10 patients and a relevant literature review, (ii) conceptualize its neurobiological underpinnings, and (iii) explore the preliminary treatment approaches for its management. Acute stress and/or a dysfunctional gamma-aminobutyric acid (GABA) ergic or dopaminergic system may be implicated in the pathogenesis of PDPE. The episodes respond acutely to parenteral benzodiazepines, while long-term management can be achieved by reducing antipsychotic doses, switching to clozapine or using central GABA enhancers. This article is the first attempt at conceptualizing and exploring treatment options for the rare condition PDPE and intends to guide future research in this regard.

Topics: Antipsychotic Agents; Clozapine; Dystonia; gamma-Aminobutyric Acid; Humans; Psychotic Disorders

The enthusiasm produced by the introduction of antipsychotic medication in the 1950s gave way to a certain frustration in the 1970s and 1980s. Despite the development of a large number of new drugs, little progress was made in treatment because these new agents were, in essence, therapeutically equivalent. This lack of progress was perhaps also related to an emphasis on tardive dyskinesia in the 1970s, i.e., the preoccupation with a negative effect of treatment. The reverse is taking place today. Clozapine and the other atypical antipsychotics are associated in people's minds with fewer or absent extrapyramidal symptoms and less tardive dyskinesia than the older typical agents. As a result, a certain amount of complacency exists. Tardive dyskinesia not only may be painful and disfiguring, but it also predicts poor outcome in patients with schizophrenia. Although many treatments have been tried, none have proven completely efficacious. The best treatment for tardive dyskinesia and dystonia is prevention, which is a function of medication choice. Pharmacologic interventions for tardive dyskinesia include clozapine and the other atypical antipsychotics. If typical antipsychotics must be used, they should be started at the lowest possible levels. Studies of risperidone suggest that it, too, should be used at very low doses to minimize the risk of tardive dyskinesia. It is also possible that schizophrenic patients taking atypical antipsychotics may experience fewer spontaneous dyskinesias, although further study is warranted.

Topics: Adult; Akathisia, Drug-Induced; Algorithms; Antipsychotic Agents; Benzodiazepines; Clozapine; Decision Trees; Drug Administration Schedule; Dyskinesia, Drug-Induced; Dystonia; Female; Humans; Male; Olanzapine; Pirenzepine; Probability; Reserpine; Risperidone; Schizophrenia; Substance Withdrawal Syndrome; Tetrabenazine; Treatment Outcome; Vitamin E

The incidence of acute extrapyramidal symptoms (EPS)--akathisia, dystonia, and parkinsonism--associated with traditional antipsychotics varies, but most researchers agree that neuroleptic-induced EPS occur in 50% to 75% of patients who take conventional antipsychotics. Atypical antipsychotics were developed to widen the therapeutic index and to reduce EPS. Although the mechanisms are unclear, the risk of EPS is less with the novel antipsychotics than with conventional drugs, and agents that produce low levels of acute EPS are likely to produce less tardive dyskinesia. Nevertheless, clinicians should exercise caution when comparing data from investigations of the novel antipsychotics and, until long-term data become available, should administer the new drugs at doses below the EPS-producing level.

Topics: Akathisia, Drug-Induced; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clinical Trials as Topic; Clozapine; Dibenzothiazepines; Drug Administration Schedule; Dyskinesia, Drug-Induced; Dystonia; Humans; Olanzapine; Parkinson Disease, Secondary; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Substance Withdrawal Syndrome

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

Although antipsychotic drugs are the mainstay of treatment in older patients with schizophrenia, much of the theoretical work underpinning their use is based on evidence gained from younger patients. With respect to dosages, there has been little work comparing plasma concentrations of antipsychotics in older patients with those of younger patients. However, there are well documented changes in the pharmacokinetics of these drugs in the elderly, particularly in their hepatic metabolism and renal excretion. There is also evidence that older patients experience more adverse effects from antipsychotics than younger patients. Such effects include extrapyramidal symptoms, postural hypotension and falls. For these reasons it is recommended that starting doses of antipsychotic drugs in older patients should be in the region of 25 to 50% of that recommended for younger patients, and should be slowly increased. Selection of a particular antipsychotic agent is best made on the basis of individual patient characteristics and the adverse effect profiles of particular drugs.

Topics: Aged; Aging; Akathisia, Drug-Induced; Antipsychotic Agents; Clozapine; Drug Prescriptions; Dyskinesia, Drug-Induced; Dystonia; Humans; Parkinson Disease, Secondary; Schizophrenia

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

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

Topics: Antipsychotic Agents; Biomechanical Phenomena; Clozapine; Drug Tolerance; Dystonia; Humans; Neurology; Psychoses, Substance-Induced

Pharmacologic treatment of severe dystonia is often unsatisfactory. The atypical antipsychotic medication clozapine appears to improve tardive dystonia associated with conventional neuroleptic use. We studied the efficacy of clozapine for severe dystonia in five patients in an open trial. The patient cohort included four with generalized dystonia and one with Meige syndrome. All patients were evaluated at baseline and at least weekly while on medication with subjective assessment of response by the patient and physician rating using the Burke-Fahn-Marsden Evaluation Scale for Dystonia. All five subjects had significant improvement detected by the Burke-Fahn-Marsden Evaluation Scale as well as subjective improvement while on clozapine. Side effects, such as sedation and orthostatic hypotension, developed in all patients but was only treatment-limiting in one subject who developed persistent symptomatic orthostatic hypotension and tachycardia. Two of the four remaining patients continued clozapine after completion of the study; an additional patient was uncertain if the benefit outweighed the side effects. One patient discontinued treatment because of difficulty obtaining the FDA-required weekly white blood cell counts for patients on clozapine. We conclude that clozapine appears to be effective for generalized and refractory focal dystonia although its use may be limited by the side effects and need for hematologic monitoring.

Topics: Adult; Aged; Analysis of Variance; Clozapine; Dystonia; Female; GABA Antagonists; Humans; Male; Middle Aged; Treatment Outcome

1. This open clinical trial (N = 7) measured the course of severe tardive dystonia in chronic psychiatric patients after discontinuation of neuroleptics and subsequent use of clozapine. 2. The dystonia was regularly assessed using the Fahn-Marsden Rating Scale. The eventual concomitant tardive dyskinesia was assessed using the Abnormal Involuntary Movement Scale. The mean follow up was 103 weeks. 3. The results for the tardive dystonia: four patients recovered totally, two improved considerably and one did not recover. 4. The results for the concomitant tardive dyskinesia: five of the seven patients had also dyskinesia, one patient had a total, two a partly remission, one had a very fluctuating course, and one patient worsened. Another patient developed dyskinesia. 5. It is suggested to consider clozapine for patients with tardive dystonia who have to continue antipsychotic treatment.

Topics: Adult; Clozapine; Dystonia; Female; Humans; Male; Middle Aged; Piperidines; Triazoles

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

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

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

Topics: Antipsychotic Agents; Clozapine; Drug Interactions; Drug Therapy, Combination; Dystonia; Female; Humans; Hypoglycemic Agents; Metabolic Syndrome; Metformin; Middle Aged; Schizophrenia; Sulpiride

Topics: Adult; Antipsychotic Agents; Aripiprazole; Clozapine; Dyskinesia, Drug-Induced; Dystonia; Female; Humans; Piperazines; Quinolones; Schizophrenia

Topics: Adult; Amisulpride; Antipsychotic Agents; Clozapine; Dyskinesia, Drug-Induced; Dystonia; Humans; Male; Schizophrenia, Paranoid; Sulpiride

Topics: Antipsychotic Agents; Cholinergic Antagonists; Clozapine; Dyskinesia, Drug-Induced; Dystonia; Electroconvulsive Therapy; Female; Humans; Middle Aged; Schizophrenia

To report a case of olanzapine-induced Pisa syndrome that improved after treatment with clozapine.. A 22-year-old male with paranoid schizophrenia presented with insidious onset tonic truncal flexion with axial rotation and difficulty in walking after exposure to olanzapine in doses up to 15 mg/day for 9 months. An objective causality assessment suggested that Pisa syndrome was probably related to olanzapine. There was improvement in his symptoms after 6 weeks of treatment with clozapine in doses gradually titrated to 350 mg/day.. Pisa syndrome is a type of dystonia that has been associated with both typical and atypical antipsychotics. Both acute and insidious onset cases have been described in the literature, which have different course and treatment response. Clozapine was found to be effective in reducing the severity of olanzapine-induced Pisa syndrome.. Clozapine may be a useful treatment option for Pisa syndrome that has been caused by olanzapine.

Topics: Adult; Benzodiazepines; Clozapine; Dyskinesia, Drug-Induced; Dystonia; Humans; Male; Olanzapine; Schizophrenia, Paranoid; Syndrome

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Drug Administration Schedule; Dystonia; Female; Humans; Olanzapine; Recurrence; Schizophrenia, Paranoid

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Basal Ganglia Diseases; Clozapine; Depressive Disorder, Major; Dystonia; Female; Humans; Syndrome

Topics: Clozapine; Diagnostic and Statistical Manual of Mental Disorders; Dose-Response Relationship, Drug; Drug Interactions; Dyskinesia, Drug-Induced; Dystonia; Female; Humans; Piperazines; Schizophrenia; Serotonin Antagonists; Thiazoles

Topics: Adult; Benzodiazepines; Clozapine; Dyskinesia, Drug-Induced; Dystonia; Female; Humans; Olanzapine; Pirenzepine; Tongue Diseases

Topics: Adult; Antipsychotic Agents; Clozapine; Dose-Response Relationship, Drug; Drug Administration Schedule; Dystonia; Female; Humans; Laryngeal Diseases; Neurologic Examination; Schizophrenia; Treatment Outcome; Voice Disorders

To report a case of extrapyramidal reaction associated with a dosage increase of clozapine.. A 44-year-old white man with a 20-year history of chronic paranoid schizophrenia was admitted to an inpatient psychiatric facility. His prior medications restarted on admission were clozapine 650 mg at bedtime, haloperidol 10 mg at bedtime, clonazepam 2 mg/d, and aspirin 325 mg/d. Two days after admission (hospital day 3), clozapine and clonazepam were discontinued, and he was prescribed haloperidol 5 mg every morning and 10 mg every evening. Stabilization occurred over the following 24 days, with progressively lower dosages of haloperidol and increasing dosages of clozapine. Haloperidol was discontinued on day 24. On day 47, the patient was agitated and making bizarre statements; thus, the morning dose of clozapine was increased by 50 mg (total 450 mg/d). On day 48 at 2200, a dystonic reaction was diagnosed; he received intramuscular diphenhydramine 50 mg, which caused the reaction to subside. At the time of the adverse reaction, he was prescribed clozapine 450 mg/d, vitamin E 400 IU three times daily, aspirin 325 mg/d, and acetaminophen, milk of magnesia, and Maalox as needed.. Although the risk of extrapyramidal symptoms (EPS) is significantly lower with clozapine than with conventional agents, elevated clozapine blood concentrations have been reported to cause EPS; other reports have cited severe dystonias and dyskinesias on abrupt clozapine withdrawal. Considering the medications prescribed at the time and the discontinuation of haloperidol 24 days before the event, clozapine was the most likely cause of the extrapyramidal reaction.. Regardless of anticipated safety associated with novel antipsychotics such as clozapine, reports of dystonic reactions must be taken into account and patients monitored appropriately.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Clozapine; Dyskinesias; Dystonia; Humans; Male; Schizophrenia

Neuroleptic primed Cebus apella monkeys have proven reliable in screening antipsychotics for extrapyramidal side effect (EPS) potential in humans, and the ratio EPS liability/antiamphetamine efficacy ["therapeutic index" (TI)] has fit well with clinical results.. 1) To find the TIs of one new (quetiapine), three potential [NNC 756 (dopamine (DA) D1 antagonist), NNC 22-0031 (alpha-1 adrenergic/5-HT2 serotonergic/DA D1 and D2 antagonist) and DOD 647 (DA D1 and D2 antagonist)] and three old antipsychotics (haloperidol, melperone and clozapine), 2) to test the model further and 3) to gain more insight as to clozapine's neuropharmacology.. Seven monkeys received haloperidol daily for 2 years; all were sensitized to dystonia. All drugs were given SC, in increasing doses until two animals had dystonia/other adverse effects (AE), and in decreasing doses with a fixed dose of dextroamphetamine producing motor unrest and stereotypies, to find the minimum significant antiamphetamine dose (AA). The ratio AE/AA = TI.. Excepting clozapine and DOD 647, all drugs induced dystonia. At 2-4 mg/kg, clozapine caused uncoordinated movements, myoclonic jerks and rough tremor; unlike dystonia, the syndrome was not alleviated but worsened by the anticholinergic, biperiden. DOD 647 up to 2 mg/kg had no adverse effects. The TIs of the new and potential antipsychotics were 3-5 versus 4 for clozapine and 1 for haloperidol and melperone, suggesting that like clozapine, these new drugs will not produce EPS at antipsychotic doses.

Topics: Amphetamine; Animals; Antipsychotic Agents; Cebus; Clozapine; Dextroamphetamine; Disease Models, Animal; Dopamine Agents; Dystonia; Female; Male; Motor Activity; Movement Disorders

Topics: Adult; Clozapine; Dose-Response Relationship, Drug; Dystonia; Humans; Male; Serotonin Antagonists

Topics: Clozapine; Dominance, Cerebral; Dose-Response Relationship, Drug; Dystonia; Epilepsies, Partial; Female; Humans; Middle Aged; Treatment Outcome

Antipsychotic-induced extrapyramidal adverse effects continue to be a serious problem in the treatment of psychotic disorders. While the pathophysiology of these adverse effects is not well understood, much recent research has focused on improving our ability to use available pharmacotherapy in the most effective and least toxic manner. Acute dystonic reactions only occur within the first days of antipsychotic treatment. They are often distressing and frightening for the patient and may even be dangerous. However, they can be effectively prevented or reversed with anticholinergics. Furthermore, the growing use of the new atypical antipsychotics will lead to a significant decrease in the rate of acute dystonic reactions. In contrast, tardive dystonia is a long-lasting menace in the course of antipsychotic treatment, for which there is no established therapy. Tardive dystonia is sometimes disabling or disfiguring and, like other tardive disorders, is potentially irreversible. Because, in most cases, patients need to continue taking the antipsychotic that has caused the adverse effect to prevent relapse of the mental illness, preventive measures are crucial. Antipsychotics should be prescribed only for patients affected by psychotic disorders, when definitely indicated and at the lowest effective dosage. The use of clozapine and other novel antipsychotic agents is also likely to represent an important step in the prevention and treatment of tardive dystonia. Compared with traditional antipsychotics, most of the new antipsychotics are characterised by a low acute extrapyramidal adverse effects liability and they also bring the hope of reducing the risk of tardive disorders. If tardive dystonia has occurred, switching to clozapine or another atypical antipsychotic and treatment with tetrabenazine, reserpine and botulinum toxin are possible options.

Topics: Antipsychotic Agents; Cholinergic Antagonists; Clozapine; Dyskinesia, Drug-Induced; Dystonia; Humans; Prevalence; Risk Factors; Risperidone

The interaction of nigrostriatal dopamine and corticostriatal glutamate plays a critical role in motor output. Recent studies in mutant dystonic hamsters (dt[sz]), an animal model of idiopathic generalized dystonia, revealed antidystonic effects of both N-methyl-D-aspartate (NMDA) receptor antagonists, such as dizocilpine (MK-801), and of neuroleptics, such as haloperidol and clozapine. Whereas the neuroleptics reduced spontaneous locomotion at antidystonic effective doses, MK-801 caused hyperactivity in mutant hamsters. Therefore, the combination of neuroleptics and MK-801 may exhibit synergistic antidystonic effects, while the side effects may be counteracted. In order to prove this assumption, the neuroleptics haloperidol and clozapine were coadministered with MK-801 in dt(sz) hamsters in the present study. The antidystonic effects were potentiated by coadministration of MK-801 and clozapine, but not by the combination of MK-801 and haloperidol. The coadministration of MK-801 and clozapine did not cause severe side effects, such as catalepsy in dystonic hamsters. In contrast to the well-documented reverse of haloperidol-induced catalepsy by MK-801 in rats, in mutant hamsters, catalepsy was increased by coadministration of haloperidol and MK-801. This unexpected finding could be due to pathophysiological brain alterations in dt(sz) hamsters, because in non-dystonic control hamsters, combined treatment with MK-801 and haloperidol did not cause cataleptogenic effects.

Topics: Animals; Anti-Dyskinesia Agents; Catalepsy; Clozapine; Cricetinae; Dizocilpine Maleate; Drug Synergism; Dystonia; Female; Haloperidol; Male; Mutation; Neuroprotective Agents

Topics: Adult; Antipsychotic Agents; Bromocriptine; Clozapine; Dancing; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Dystonia; Humans; Male; Psychotic Disorders; Trihexyphenidyl; Vitamin E

Tardive dystonia is an uncommon complication of neuroleptic treatment which is frequently disabling and poorly responsive to treatment.. The case is reported of a 28-year-old patient with schizophrenia who developed severe, generalised tardive dystonia after five years of neuroleptic treatment. Stopping neuroleptic medication and treatment with tetrabenazine, an anticholinergic and a benzodiazepine were ineffective. Treatment with clozapine and then the novel combination of clozapine plus clonazepam was instituted.. Treatment with clozapine alone brought about limited improvement. Addition of clonazepam resulted in virtually complete disappearance of all abnormal movements. This remission has been sustained for nearly two years.. This report adds to two other cases suggesting that the combination of clozapine and clonazepam may be an effective treatment for tardive dystonia.

Topics: Adult; Anticonvulsants; Antipsychotic Agents; Clonazepam; Clozapine; Drug Therapy, Combination; Dystonia; Female; Humans; Neurologic Examination; Schizophrenia; Schizophrenic Psychology

Topics: Antipsychotic Agents; Clozapine; Drug Interactions; Dystonia; Humans; Risperidone

Topics: Adult; Antipsychotic Agents; Clozapine; Dystonia; Haloperidol; Humans; Male; Schizophrenia; Tongue

Topics: Adult; Antipsychotic Agents; Clozapine; Dystonia; Humans; Isoxazoles; Male; Piperidines; Risperidone; Schizophrenia

Topics: Adult; Chemical and Drug Induced Liver Injury; Clozapine; Dose-Response Relationship, Drug; Dystonia; Female; Humans; Schizophrenia, Paranoid

Topics: Adult; Antipsychotic Agents; Clozapine; Dose-Response Relationship, Drug; Drug Administration Schedule; Dystonia; Humans; Isoxazoles; Male; Neurologic Examination; Piperidines; Risperidone; Schizophrenia; Schizophrenic Psychology; Substance Withdrawal Syndrome

A 45-year-old white male with a positive family history for various neurological disorders (not including dystonias), and a long history of neuroleptic exposure on account of a chronic schizoaffective illness, developed severe torsion trunkal movement to the left which were accompanied by inversion of the left arm and outward extension of the right arm, as well as left torticollis. The axial dystonia, which was refractory to treatment, was disabling interfering with the activities of daily living, posture and gait. Radiological studies revealed marked dextroscoliosis. The administration of clozapine in dosages of 200 mg p.o. in the morning and 250 mg p.o. at bedtime, resulted in a significant improvement of the neck and trunk dystonia. After the discontinuation of the clozapine, an exacerbation of the movement disorder back to baseline levels prior to the use of this agent, was observed. Subsequent therapy with thioridazine in a dosage of 600 mg/day did not mask or treat the dystonia. The clinical implications of these findings are discussed.

Topics: Clozapine; Dystonia; Humans; Male; Middle Aged; Psychotic Disorders

Long-term experience with clozapine has shown that the agent has a motor and mental side effect profile that is distinct in many ways from classical neuroleptics. It can produce a parkinsonian-like bradykinesia and mild akathisia, but no rigidity and rarely tremor. In patients with tardive dyskinesia induced by other neuroleptics, clozapine permits the dyskinesia to disappear in about half the cases. That clozapine may induce tardive dyskinesia in extremely rare cases cannot be excluded, but it seems more likely that this tardive dyskinesia in clozapine-treated patients is due to previous treatment with classical neuroleptics. The earlier clozapine is started, the less chance for development of tardive dyskinesia. As do other neuroleptics, clozapine can elicit sedation and asthenia, but corresponding to the motoric extrapyramidal syndrome, clozapine causes emotional indifference ("mental parkinsonism"), depression, and restlessness to a significantly lesser degree, which may be of importance in the higher compliance seen with this drug.

Topics: Affective Symptoms; Akathisia, Drug-Induced; Antipsychotic Agents; Asthenia; Basal Ganglia Diseases; Clozapine; Dyskinesia, Drug-Induced; Dystonia; Humans; Parkinson Disease, Secondary; Schizophrenia; Schizophrenic Psychology

We report a patient with severe axial tardive dystonia who has had dramatic improvement for 4 years after treatment with the atypical antipsychotic drug clozapine (625 mg/day). Clozapine differs from conventional neuroleptics in that it has higher affinity for D1 and lower affinity for D2 dopamine receptors than do conventional antipsychotics, which are relatively selective D2 antagonists. We propose that repetitive stimulation of the D1 receptor by endogenous dopamine, resulting in sensitization of the D1-mediated striatal output in the presence of D2 receptor blockade, is a fundamental mechanism mediating tardive dyskinesia, including the dystonic type. According to this hypothesis, it is primarily the D1 antagonist action of clozapine that accounts for its inability to cause tardive dyskinesia as well as its therapeutic effect in tardive dystonia. Regardless of its mechanism of action, the sustained improvement observed in this case suggests that clozapine should be tried in cases of severe refractory tardive dystonia.

Topics: Adult; Antipsychotic Agents; Clozapine; Corpus Striatum; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Dystonia; Follow-Up Studies; Humans; Long-Term Care; Male; Neurologic Examination; Psychotic Disorders; Receptors, Dopamine D1; Receptors, Dopamine D2

Topics: Adult; Clozapine; Dystonia; Female; Humans; Kindling, Neurologic; Schizophrenia, Paranoid; Seizures; Stuttering

The development of severe tardive dystonia after short-term use of low-dose Fluspirilen is described. A 39-year-old woman was treated with Fluspirilen IM by her family doctor for reactive depression. She did received no other neuroleptic agents and no risk factors for the development of tardive dyskinesia (e.g. old age or organic brain damage) were present. For the first time a relation between short-term monotherapy with Fluspirilen and tardive dyskinesia appears highly probable. The use of Fluspirilen for the treatment of psychogenic disturbances should therefore be considered carefully.

Topics: Adjustment Disorders; Adult; Clozapine; Dose-Response Relationship, Drug; Drug Administration Schedule; Dyskinesia, Drug-Induced; Dystonia; Female; Fluspirilene; Humans; Neurologic Examination

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

Topics: Adult; Antipsychotic Agents; Clozapine; Dyskinesia, Drug-Induced; Dystonia; Humans; Male; Psychotic Disorders

The effects of the atypical neuroleptic clozapine were studied in an inbred line of Syrian golden hamsters with generalized dystonia, i.e. a frequent movement disorder in humans. The effects of clozapine were compared with those of the classical neuroleptic, haloperidol. Clozapine, 7.5-20 mg/kg i.p., potently reduced the severity of dystonic attacks in the mutant hamster model, but induced marked sedation at these doses. Lower doses were ineffective. Haloperidol, 0.5 mg/kg i.p., significantly reduced the severity of dystonia without marked sedation. The finding that clozapine possesses antidystonic potency similar to that of haloperidol in a genetic model of dystonia might suggest that this atypical neuroleptic is an effective alternative in the treatment of dystonic patients who respond to neuroleptics, particularly because of the clinical evidence that clozapine is almost devoid of extrapyramidal adverse effects.

Topics: Animals; Clozapine; Cricetinae; Disease Models, Animal; Dystonia; Female; Haloperidol; Male; Mesocricetus; Mutation

Topics: Adult; Antipsychotic Agents; Clonazepam; Clozapine; Dystonia; Female; Humans; Schizophrenia