CLOZAPINE IN THE TREATMENT OF REFRACTORY BIPOLAR AND SCHIZOAFFECTIVE DISORDERS S. Khaldi MD, C. Kornreich MD Phd Service de Psychiatrie. CHU Brugmann. Bruxelles, Belgium Table II: CLZ in the treatment of resistant depression BACKGROUND AND AIM: Clozapine (CLZ) is a dibenzodiazepine antipsychotic. CLZ is more effective than standard neuroleptic drugs to treat refractory schizophrenic patients. However its use may be restricted by other adverse reactions, such as agranulocytosis, which occurs in 0.5 to 2% of patients, and seizures, especially at high dosage (Stahl, 2000). Studies examining efficacy of CLZ in affective disorders are rare but many authors suggest that clozapine may have mood-stabilizing properties (Green et al, 2000). To evaluate the efficacy of clozapine monotherapy in the treatment of refractory depression and refractory psychotic mania in both bipolar (BD) and schizoaffective disorders (SCD). To review data about eventual CLZ’s mood stabilizing properties. METHODS: The MEDLINE was searched with a combination of each one of the following key words ^ refractory mania, bipolar disorder, schizoaffective disorder, refractory depression and clozapine. ^ RESULTS: Many case reports, open label, prospective and retrospective study reporting a follow-up of one to ten years confirm the efficiency of CLZ in BD and SCD especially in refractory depression and refractory psychotic mania. Some authors are also in favour of a mood-stabilizing properties of this molecule. Studies concerning acute mania consist of prospective studies or case reports. CLZ’s Mood stabilizing properties was pointed out through retrospective studies interested in patient stabilized for a period between 1 and 10 years. Antidepresif effect of CLZ was found in 2 studies:a non randomized clinical trial and a case report. Table I: CLZ’s Antimanic properties Authors Study Design Diagnosis Critetria Cases and Dg Study’s Duation: Months Conclusion Rajan (9) 1995 case reports DSM III R HDRS BPRS N=3 MDD 12 à 48 Favourable evolution* Loza (7) 2004 Non randomised Clinical trial DSM IV CGI PANSS N=16 MDD 1,5 favorable in 34% cases (5) Table III: CLZ’s Mood Stabilizing Properties Authors Study’s design Diagnosis Criteria Cases and Study’s Duration: months Conclusion Banov (1) 1994 Retrospective Comparative Unipolar vs bipolar DSM III R CGI EGF N=193 52 BD 81 SCD 19,4 Better efficiency of CLZ in BD then in UNID Meynard (8) 1995 CIM 10 PANSS, CGI MADRS N=19 11BD 4 à 38 Efficacy CLZ in 70% BD (7cases/11) Frannburg (3) Prospective comparative BPRS N=75 16 BD 25 SCD 48 favorable without significant differences between BD, SCD and schizophrenic Ciapparelli (2) 2003 N=101 37BD 30 SCD Favourable course of illness: 83% in BD et 90% in SCD Le Voyer (6) 2004 Retrospective descriptive DSM IV N=170 4 BD 17 SCD 120 Significant ameliortion of social insertion and less frequent Hospitalization CONCLUSION: Studies concerning use of CLZ in BD and SCD confirmed: Acute antimanic properties of CLZ, in particular those with psychotics features in wich CLZ is effective in 60% of cases (Suppes et al, 1999) Efficiency in the treatment of refractory depression. (Lorza et al, 2004) Mood-stabilizing properties seems to be an interesting way for research, we found 3 retrospective and 2 prospective studies wich confirm the benefit of CLZ BD and SCD after a treatment of 10 years. CLZ should come to play an increasingly important role in the acute and long-term management of bipolar disorder and schizoaffective disorders, but there is a clear need for further controlled randomized double blind trials in this indication. Authors Study’s Design Diagnosis Criteria Cases and Dg study’s Duration: weeks Conclusion Kimmel (5) 1994 Prospective comparative DSM III R EMY BPRS EGF N=25 10 TB 15 TSA 13 favorable course in 72% of cases (18). Suppes (10) 1999 Randomised Clinical Trial CLZ vs Classical treatment DSM IV PANSS, CGI N=38 26 TB 12 TSA 54 Significant efficacy of CLZ compared to other treatment Green (4) 2000 Non Randomized Clinical Trial EMY, CGI N=22 22 TB 12 Efficiency CLZ in 56% of cases (12). Volavk (11) 2002 Randomized clinical Trial Typical Antipsychotics vs Halopéridol PANSS N=157 22 SCD 14 Significant efficacy CLZ and Olanzapine in SCD versus Halopéridol and Risperidone REFERENCES: Banov M, Zarate C, Tohen M. et al: Clozapine therapy in refractory affective disorders: polarity predicts response in long-term follow-up. J Clin Psychiatry July 1994; 55(7): 295-300. Volavka J, Czobor P, Sheitman B et al: Clozapine, olanzapine, risperidone and haloperidol in the treatment of patients with chronic schizophrenia and schizoaffective disorder. Am J Psychiatry February 2002; 159: 255-262.