Atypical antipsychotics in bipolar disorder: systematic review of randomised trials.
BACKGROUND
Atypical antipsychotics are increasingly used for treatment of mental illnesses like schizophrenia and bipolar disorder, and considered to have fewer extrapyramidal effects than older antipsychotics.


METHODS
We examined efficacy in randomised trials of bipolar disorder where the presenting episode was either depression, or manic/mixed, comparing atypical antipsychotic with placebo or active comparator, examined withdrawals for any cause, or due to lack of efficacy or adverse events, and combined all phases for adverse event analysis. Studies were found through systematic search (PubMed, EMBASE, Cochrane Library), and data combined for analysis where there was clinical homogeneity, with a special reference to trial duration.


RESULTS
In five trials (2,206 patients) participants presented with a depressive episode, and in 25 trials (6,174 patients) the presenting episode was manic or mixed. In 8-week studies presenting with depression, quetiapine and olanzapine produced significantly better rates of response and symptomatic remission than placebo, with NNTs of 5-6, but more adverse event withdrawals (NNH 12). With mania or mixed presentation atypical antipsychotics produced significantly better rates of response and symptomatic remission than placebo, with NNTs of about 5 up to six weeks, and 4 at 6-12 weeks, but more adverse event withdrawals (NNH of about 22) in studies of 6-12 weeks. In comparisons with established treatments, atypical antipsychotics had similar efficacy, but significantly fewer adverse event withdrawals (NNT to prevent one withdrawal about 10). In maintenance trials atypical antipsychotics had significantly fewer relapses to depression or mania than placebo or active comparator. In placebo-controlled trials, atypical antipsychotics were associated with higher rates of weight gain of >or=7% (mainly olanzapine trials), somnolence, and extrapyramidal symptoms. In active controlled trials, atypical antipsychotics were associated with lower rates of extrapyramidal symptoms, but higher rates of weight gain and somnolence.


CONCLUSIONS
Atypical antipsychotics are effective in treating both phases of bipolar disorder compared with placebo, and as effective as established drug therapies. Atypical antipsychotics produce fewer extrapyramidal symptoms, but weight gain is more common (with olanzapine). There is insufficient data confidently to distinguish between different atypical antipsychotics.
Derry
Sheena
S
Pain Research and Nuffield Department of Anaesthetics, University of Oxford, Oxford Radcliffe Hospitals, The Churchill, Headington, Oxford, OX3 7LJ, UK. sheena.derry@pru.ox.ac.uk
Moore
R Andrew
RA
D014150:Antipsychotic Agents / Q000009:adverse effects / Q000145:classification* / Q000627:therapeutic use*; D001480:Basal Ganglia Diseases / Q000139:chemically induced / Q000453:epidemiology; D001569:Benzodiazepines / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000453:epidemiology; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000453:epidemiology; D003987:Dibenzothiazepines / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D000077213:Lamotrigine; D000077152:Olanzapine; D015995:Prevalence; D000069348:Quetiapine Fumarate; D016032:Randomized Controlled Trials as Topic; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D014227:Triazines / Q000627:therapeutic use
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D014227:Triazines; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; D000077152:Olanzapine; D000077213:Lamotrigine
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