Clozapine in the Treatment of Mania

SIR: Recently it has been shown that clozapine use for patients with treatment-resistant illness and a history of mania was associated with significant clinical improvement relative to usual treatment.¹ Furthermore, it has been shown that clozapine has an independent mood-stabilizing property; however, the pharmacological treatment of mania with clozapine is still a matter of debate.^2,3

We would like to draw the readers' attention to our studies on clozapine in mania, which were undertaken in the years 1974 to 1997. We present here an analysis of a total of 117 retrospectively investigated patients (67 male, 50 female; mean age±SD=42.2±19.8 years) suffering from acute mania (according to ICD-9 and ICD-10 classification in the respective studies) who were treated with clozapine given as monotherapy.^4,5 A mean dosage of clozapine of 353.4±76.4 mg/day over the whole treatment period in all studies had excellent antimanic properties. These were characterized by an early onset of clinical improvement (decreased activity, sedation, sleep improvement, decreased flight of ideas) between the 2nd and 3rd day of treatment. The mean Clinical Global Impression score improved from 6.0±1.0 at admission to 4.3±1.2 at demission, and the mean score on the Global Assessment of Functioning scale increased from 37.8±12.6 to 68.9±14.7. In 28 patients who were treated additionally with conventional antipsychotics (e.g., haloperidol), clozapine significantly reduced extrapyramidal side effects. We did not observe any severe side effects such as agranulocytosis, seizures, or malignant neuroleptic syndrome.

We believe that the presented data significantly support worldwide attempts to test clozapine for the treatment of acute manic episodes. In addition, clozapine appears to be a safe drug with proven efficacy and practicability (e.g., measuring of plasma levels). Furthermore, clozapine seems to be a reasonable treatment alternative considering the cost-benefit analysis.