A Review of Sensitivity and Tolerability of Antipsychotics in Patients With Bipolar Disorder or Schizophrenia: Focus on Somnolence
J Clin Psychiatry 2008;69:302-309
© Copyright 2014 Physicians Postgraduate Press, Inc.
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Objective: This study compared the sensitivity and
tolerability of antipsychotics in patients with bipolar disorder or
Data Sources: English-language literature from January 1966 to
December 2006 cited in MEDLINE was searched for the terms antipsychotics,
typical antipsychotics, atypical antipsychotic, generic and brand
names of antipsychotics, safety, tolerability, discontinuation
due to adverse events, somnolence, and bipolar mania,
bipolar depression, bipolar disorder, manic-depressive illness,
or schizophrenia, randomized, double blind, and
controlled clinical trial.
Study Selection: Randomized, double-blind, placebo-controlled,
monotherapy studies of antipsychotics in both bipolar disorder and
schizophrenia were prioritized.
Data Extraction: Absolute risk increase (ARI) or reduction (ARR)
and the numbers needed to treat to harm (NNTH) or benefit (NNTB) for the
discontinuation due to adverse events and somnolence relative to placebo were
Data Synthesis: Ten acute trials in mania, 3 in bipolar
depression, and 8 in schizophrenia were identified, along with 2 maintenance
studies in bipolar disorder and 2 in schizophrenia. In schizophrenia,
ziprasidone caused significantly more discontinuations due to adverse events
than placebo, with an NNTH of 19, while aripiprazole caused significantly fewer
discontinuations due to adverse events than placebo, with an NNTB of 12. In
mania, there was no statistically significant difference in discontinuation due
to adverse events between antipsychotics and placebo. However, in bipolar
depression, both quetiapine and olanzapine caused more discontinuations due to
adverse events than placebo, with NNTHs of 7 and 24, respectively. All atypical
antipsychotics caused a significantly greater incidence of somnolence than
placebo in mania and depression, with NNTHs from 5 to 8 for mania and 2 to 6
for depression. In schizophrenia, only olanzapine, ziprasidone, and
aripiprazole (NNTHs from 5 to 14) caused a significantly higher incidence of
somnolence. There was no significant difference between schizophrenia and mania
in the discontinuation due to adverse events or somnolence of all studied
antipsychotics. However, there was a significantly higher incidence of
discontinuation due to adverse events and somnolence caused by quetiapine in
bipolar depression than that in schizophrenia or mania.
Conclusion: Patients with bipolar disorder appear more
sensitive to antipsychotics, and depressed patients are less tolerant to
somnolence than those with either mania or schizophrenia.