1. 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):
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: