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Letter   |    
Clozapine in the Treatment of Mania
Detlef Degner, M.D.; Stefan Bleich, M.D.; Peter Müller, M.D.; Göran Hajak, M.D.; Lothar adler, M.D.; Eckart Rüther, M.D.
The Journal of Neuropsychiatry and Clinical Neurosciences 2000;12:283-283. 10.1176/appi.neuropsych.12.2.283
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.
Suppes T, Webb A, Paul B, et al: Clinical outcome in a randomized 1-year trial of clozapine versus treatment as usual for patients with treatment-resistant illness and a history of mania. Am J Psychiatry1999; 156:1164—  1169
 
Calabrese JR, Kimmel SE, Woyshville MJ, et al: Clozapine for treatment-refractory mania. Am J Psychiatry  1996; 153:759—764[PubMed]
 
Suppes T, McElroy SL, Gilbert J, et al: Clozapine in the treatment of dysphoric mania. Biol Psychiatry  1992; 32:270—280[PubMed][CrossRef]
 
Müller P, Heipertz R: Zur Behandlung manischer Psychosen mit Clozapin [On the treatment of manic psychoses with clozapine]. Fortschr Neurol Psychiatr  1977; 45:420—424
 
Adler L, Ulrich M, Lehmann K, et al: Acute medicamentous treatment of manic illness in in-patients. Nervenarzt  1996; 67:235—243[PubMed]
 
+
Suppes T, Webb A, Paul B, et al: Clinical outcome in a randomized 1-year trial of clozapine versus treatment as usual for patients with treatment-resistant illness and a history of mania. Am J Psychiatry1999; 156:1164—  1169
 
Calabrese JR, Kimmel SE, Woyshville MJ, et al: Clozapine for treatment-refractory mania. Am J Psychiatry  1996; 153:759—764[PubMed]
 
Suppes T, McElroy SL, Gilbert J, et al: Clozapine in the treatment of dysphoric mania. Biol Psychiatry  1992; 32:270—280[PubMed][CrossRef]
 
Müller P, Heipertz R: Zur Behandlung manischer Psychosen mit Clozapin [On the treatment of manic psychoses with clozapine]. Fortschr Neurol Psychiatr  1977; 45:420—424
 
Adler L, Ulrich M, Lehmann K, et al: Acute medicamentous treatment of manic illness in in-patients. Nervenarzt  1996; 67:235—243[PubMed]
 
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