Clozapine-associated extrapyramidal reaction.

OBJECTIVE: To report a case of extrapyramidal reaction associated with a dosage increase of clozapine. CASE SUMMARY: 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. DISCUSSION: 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. CONCLUSIONS: Regardless of anticipated safety associated with novel antipsychotics such as clozapine, reports of dystonic reactions must be taken into account and patients monitored appropriately.

Atypical antipsychotic agents: a critical review.

The pharmacology, efficacy, and adverse effects of atypical antipsychotic agents when used to treat schizophrenia and other disorders are reviewed. Atypical antipsychotic agents were developed in response to problems with typical agents, including lack of efficacy in some patients, lack of improvement in negative symptoms, and troublesome adverse effects, especially extrapyramidal symptoms (EPSs) and tardive dyskinesia CTD). Atypical antipsychotics differ from typical psychotics in their "limbic-specific" dopamine type 2 (D2)-receptor binding and high ratio of serotonin type 2 (5-HT2)-receptor binding to D2 binding. In clinical trials in patients with non-treatment-resistant schizophrenia, risperidone and olanzapine were superior to placebo for positive and negative symptoms. Risperidone and olanzapine were superior to haloperidol on some measures. Quetiapine was better than placebo but was not better than typical antipsychotics. Head-to-head comparisons of atypical antipsychotics in non-treatment-resistant schizophrenia have been inconclusive. Clozapine remains the standard agent for treatment-resistant schizophrenia. Atypical agents are substantially more expensive than their typical antipsychotic counterparts. To fully determine the overall efficiency of these drugs, other potential benefits, such as improved quality of life, need to be factored in. Atypical antipsychotics are associated with a decreased capacity to cause EPSs, TD, neuroleptic malignant syndrome, and hyperprolactinemia. Clozapine carries a risk of agranulocytosis; the white blood cell count must be monitored. Atypical antipsychotics are increasingly being used for indications other than schizophrenia, such as the management of aggression, mania, and depression. Atypical antipsychotics are often considered first-line agents for treating schizophrenia and are promising treatment alternatives for other psychiatric and neurologic conditions.

Risperidone and hyponatremia: a case report.

A 48 year-old white male not suffering from endocrine disease or polydipsia, not taking diuretics, and suffering from no renal disease was started on risperidone and discharged on no other drug from Western Missiouri Mental Health Center (WMMHC) after an 8-day hospitalization. Seven days later he was admitted to a university medical center with generalized seizures, hyponatremia, respiratory failure, and rhabdomyalysis. He eventually recovered, was transferred back to WMMHC, and stabilized on appropriate medication. A search of the literature indicates no case reports linking risperidone to hyponatremia. It is assumed that the mechanism of hyponatremia is similar to other psychotropic medication in that it is secondary to the syndrome of inappropriate antidiuretic hormone (SIADH).

Attenuation of antipsychotic-induced hyperprolactinemia with clozapine.

Hyperprolactinemia is a well-known consequence of conventional antipsychotic therapy. The atypical antipsychotic clozapine is reported to lack this effect. We describe a case of attenuated serum prolactin levels after conversion to clozapine therapy in an adolescent. A 13-year-old female patient developed hyperprolactinemia with galactorrhea and amenorrhea while receiving thioridazine 300 mg daily. These symptoms continued throughout 3 years of treatment with haloperidol 10 mg daily and then fluphenazine 10 mg daily. Subsequently, after an incomplete improvement in her psychiatric symptoms and hyperprolactinemia on thioridazine 150 mg and bromocriptine 15 mg daily, the patient was changed to clozapine at age 16. Clozapine 150 mg twice daily improved her psychiatric status and corrected her serum prolactin concentrations after 2 weeks; bromocriptine was able to be discontinued. We recommend systematic evaluation of atypical neuroleptics as alternative treatments for refractory hyperprolactinemia induced by conventional antipsychotics.