Effects of clozapine on sleep in bipolar and schizoaffective illness

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


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.

Download full-text


Available from: Mehmet Erkan Ozcan, Oct 30, 2015
  • Source
    • "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 "
    [Show abstract] [Hide abstract]
    ABSTRACT: Schizophrenia is associated with impaired sleep continuity. The second generation antipsychotics clozapine and olanzapine have been reported to improve sleep continuity but also to rarely induce restless legs syndrome (RLS). The aims of this randomized double-blind study were to compare the effects of clozapine and olanzapine on sleep and the occurrence of RLS. Therefore, polysomnographies were recorded and RLS symptoms were assessed in 30 patients with schizophrenia before and after 2, 4 and 6weeks of treatment with either clozapine or olanzapine. Treatment with both antipsychotics increased total sleep time, sleep period time and sleep efficiency and decreased sleep onset latency. These changes were similar in both groups, occurred during the first 2 treatment weeks and were sustained. For example, sleep efficiency increased from 83% (olanzapine) and 82% (clozapine) at baseline to 95% at week 2 and 97% at week 6 in both treatment groups. Sleep architecture was differently affected: clozapine caused a significantly stronger increase of stage 2 sleep (44%) than olanzapine (11%) but olanzapine a significantly stronger increase of REM-sleep. Olanzapine caused an 80% increase of slow wave sleep whereas clozapine caused a 6% decrease. No patient reported any of 4 RLS defining symptoms at baseline. During treatment, 1 patient of each group reported at one visit all 4 symptoms, i.e. met the diagnosis of an RLS. In conclusion, sleep continuity similarly improved and sleep architecture changed more physiologically with olanzapine. Neither of the antipsychotics induced RLS symptoms that were clinically relevant.
    Schizophrenia Research 12/2013; 152(1). DOI:10.1016/j.schres.2013.11.009 · 3.92 Impact Factor
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Sleep has been described as being of the brain, by the brain, and for the brain. This fundamental neurobiological behavior is controlled by homeostatic and circadian (24-hour) processes and is vital for normal brain function. This review will outline the normal sleep-wake cycle, the changes that occur during aging, and the specific patterns of sleep disturbance that occur in association with both mental health disorders and neurodegenerative disorders. The role of primary sleep disorders such as insomnia, obstructive sleep apnea, and REM sleep behavior disorder as potential causes or risk factors for particular mental health or neurodegenerative problems will also be discussed.
    Nature and Science of Sleep 05/2013; 5:61-75. DOI:10.2147/NSS.S34842
  • [Show abstract] [Hide abstract]
    ABSTRACT: Sleep disturbances are among the most common symptoms in patients who have acute episodes of mood disorders, and patients who have mood disorders exhibit higher rates of sleep disturbances than the general population, even during periods of remission. Insomnia and hypersomnia are associated with an increased risk for the development or recurrence of mood disorders and increased severity of psychiatric symptoms. Sleep electroencephalogram recordings have identified objective abnormalities associated with mood disorders, providing insight into the neurobiologic relationships between mood and sleep. Future studies will continue to investigate this association and potentially improve treatment of sleep and mood disorders.
    Psychiatric Clinics of North America 01/2007; 29(4):1009-32; abstract ix. DOI:10.1016/j.psc.2006.09.003 · 2.13 Impact Factor
Show more