Clinical effects of a randomized switch of patients from clozaril to generic clozapine.

INTRODUCTION: Clozapine was discovered in 1959 but withheld from the United States market after several deaths due to agranulocytosis. The medication was approved in the United States in 1989 on a compassionate-use basis and was first marketed in 1990 as Clozaril. In 1999, following approval by the U.S. Food and Drug Administration, Zenith Goldline Pharmaceuticals (ZGP) introduced a generic form of clozapine. METHOD: After 5 weeks of data collection (phase I), 24 patients were randomly assigned to group A and 21 patients to group B. Patients had DSM-IV diagnoses of schizophrenia, schizoaffective disorder, bipolar disorder with psychosis, or atypical psychosis with mood disorder. In phase II, group A received a mean daily dose of 630 mg of generic clozapine, and group B continued to receive Clozaril at a mean daily dose of 610 mg, each for 8 weeks. In phase III, group A was reassigned to Clozaril, and group B was switched to generic clozapine, each for 8 weeks. At the end of phase III, group B resumed Clozaril. Efficacy was measured with the Clinical Global Impressions-Improvement (CGI-I) scale, the Brief Psychiatric Rating Scale (BPRS), and the Beck Depression Inventory (BDI). RESULTS: Five patients experienced relapse when they were switched from Clozaril to generic clozapine. Eleven patients worsened short of full relapse, 9 while receiving ZGP generic clozapine and 2 while receiving Clozaril. CGI-I scores and BPRS scores favored patients receiving Clozaril significantly. Only BDI scores favored patients receiving generic clozapine significantly. CONCLUSION: Until more studies have been performed, clinicians and administrators should carefully monitor stable Clozaril-treated patients who are being switched to generic clozapine.

New uses of anticonvulsant drugs in psychosis.

Psychotic patients not adequately relieved by neuroleptic drugs often improve when anticonvulsants are added. In bipolar disorders and organic psychoses, anticonvulsants can sometimes be used to replace neuroleptics. No individual anticonvulsant is clearly, consistently superior. Patients who fail on one agent may improve on the next. Clonazepam is an excellent adjunct to neuroleptic therapy, but there is little evidence that it is effective as monotherapy. However, it is safe, sedates rapidly, and has an excellent patient tolerability profile. Carbamazepine is the best established drug for patients with bipolar disorders, particularly for rapid cyclers, and is often effective monotherapy. The therapeutic profile of valproic acid (sodium valproate) is similar to that of carbamazepine, but its side effects are quite different and are often preferred. Other anticonvulsants are little studied, but might be chosen to avoid certain side effects, or after better-studied drugs have failed. The pharmacological basis behind using anticonvulsants in psychoses is primarily empirical. In almost every case it has been clinicians who have first noted the beneficial effects of these drugs. Theories such as that of Post have followed.

Forty-year follow-up of United States prisoners of war.

The authors performed structured psychiatric examinations of 188 former prisoners of war (POWs). Sixty-seven percent had had posttraumatic stress disorder. Of those affected, 29% had fully recovered, 39% still reported mild symptoms, 24% had improved but had moderate residual symptoms, and 8% had had no recovery or had deteriorated. Presence of posttraumatic stress disorder was not significantly correlated with other mental disorders. Delayed onset was not seen. The findings confirm the DSM-III concept of and criteria for posttraumatic stress disorder.