Effects of clozapine on sleep in bipolar and schizoaffective disorders

Department of Psychiatry, Sleep Study Unit, The University of Texas Southwestern Medical Center, 2201 Inwood Road, Dallas, TX 75235, USA.
Progress in Neuro-Psychopharmacology and Biological Psychiatry (Impact Factor: 3.69). 12/2004; 28(7):1065-70. DOI: 10.1016/j.pnpbp.2004.05.048
Source: PubMed

ABSTRACT Sleep disturbances are strongly associated with mood disorders, although the majority of data have been obtained in patients with major depressive disorder. Studies reporting results in bipolar disorder are few, and results have not been consistent. Clozapine is a prototype of atypical antipsychotics, which is effective in improving symptoms of manic episodes in patients with bipolar disorder, or schizoaffective disorder, bipolar type and has been shown to influence sleep in other psychiatric disorders. The present study evaluated the sleep effects of clozapine in bipolar and schizoaffective disorders.
Participants were 11 women and 4 men (range:28-53 years of age, mean 40.9+/-8.6 years), all with a history of mania by DSM-IV criteria for either bipolar I disorder or schizoaffective disorder, bipolar type. They participated in a sleep study at baseline and again after 6 months initiation of clozapine add-on therapy.
Sleep latency was longer on clozapine and the number of awakenings were increased, whereas time in bed (TIB) and total sleep period (TSP) were increased (range: F=6.2-17.9; df=l,12; p<0.05). Although none of the individual sleep stage showed significant treatment changes, both Stage 2 and slow-wave sleep were increased and Stage 2 decreased on clozapine. Subjective sleep measures improved on clozapine with a small but significant improvement in how rested patients felt upon awakening (t=-2.1; df=26; p<0.05).
Clozapine prolonged sleep latency, improved restedness, and increased total sleep time. Although lack of a control group limits interpretation of these results, they are in general agreement with studies in other psychiatric populations, and support the view that clozapine is primarily a NREM sleep enhancer. The improvement in restedness may be of positive clinical consequence.

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    • "Salin-Pascual et al., 2004 schizophrenia 18 open, BL, Night 1, Night 2 TST↑, SE?, SOL↓, REML?, S1↓, S2=, SWS↑, REM↓/= Müller et al., 2004 schizophrenia 10 open, BL, Wk 4 TST↑, SE↑, SOL↓, REML=, S1=, S2=, SWS↑↑, REM↑ Lindberg et al., 2002 healthy subjects 13 open, single dose; BL, Night 1 TST↑, SE=, SOL↓, REML=, S1=, S2=, SWS↑↑, REM↑ Sharpley et al., 2000 healthy males 9 random., db, cross-over: pl., 5 mg, 10 mg TST↑, SE↑, SOL↓, REML↑, S1↓, S2=, SWS↑↑, REM↓ Salin-Pascual et al., 1999 schizophrenia 20 open, BL, Night 1, Night 2 TST↑, SE↑, SOL↓, REML=, S1↓, S2↑, SWS↑↑, REM= Clozapine Kluge, this study schizophrenia 14 random., db, parallel; BL, Wk 2, Wk 4, Wk 6 TST↑, SE↑, SOL↓, REML=, S1=, S2↑↑, SWS↓/=, REM↑ Armitage et al., 2004 "
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    • "In contrast, studies of the effects of the atypical antipsychotics (clozapine, olanzapine, quetiapine, risperidone, ziprasidone and paliperidone) in healthy controls and schizophrenia patients show a relatively consistent effect on measures of sleep continuity, with an increased total sleep time and/or sleep efficiency and individually varying effects on other sleep parameters, such as an increase in REM latency observed for olanzapine, quetiapine, and ziprasidone and an increase in SWS documented for olanzapine and ziprasidone.65,66 Additionally, clozapine and olanzapine demonstrate comparable influences on other sleep variables, such as SWS or REM density, in controls and schizophrenic patients.67,68 Therefore, it is possible that the effects of second generation antipsychotics observed on sleep in healthy subjects and schizophrenic patients might involve the action of these drugs on symptomatology, such as depression, cognitive impairment, and negative and positive symptoms. "
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