Bipolar disorder, with mood swings between depression and mania, may affect up to 1.5% of adults, and increases the risk of suicide and disability. Most people improve over time, but two thirds may have residual dysfunction, and at least 40% may have recurrent episodes.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments in people with mania associated with bipolar disorder? What are the effects of treatments in bipolar depression? What are the effects of interventions to prevent relapse of mania or bipolar depression? We searched: Medline, Embase, The Cochrane Library and other important databases up to July 2006 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
We found 60 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antidepressants, carbamazepine, chlorpromazine, clonazepam, cognitive therapy, education, family-focused psychoeducation, gabapentin, haloperidol, lamotrigine, lithium, olanzapine, psychological treatments, quetiapine, risperidone, topiramate, valproate, and ziprasidone.
Bipolar disorder, with mood swings between depression and mania, may affect up to 1.5% of adults, and increases the risk of suicide and disability.
Most people improve over time, but two thirds may have residual dysfunction, and at least 40% may have recurrent episodes.
Lithium reduces symptoms of mania compared with placebo, and seems as effective as haloperidol, carbamazepine, and clonazepam, but can cause adverse effects including hypothyroidism.
Older antipsychotic drugs such as chlorpromazine and haloperidol are widely used to treat mania, but few studies have been done to confirm their efficacy.
Olanzapine, valproate, carbamazepine, and risperidone increase the likelihood of response in people with mania compared with placebo, and seem to have similar efficacy as each other, with different adverse-effect profiles.
Ziprasidone, quetiapine, and clonazepam may also be beneficial, but few studies have been done to assess the effects of lamotrigine or gabapentin in mania.
Topiramate is unlikely to be beneficial in mania.
Antidepressants increase treatment response compared with placebo in people with bipolar depression. It is possible that selective serotonin reuptake inhibitors are more effective, and less likely to induce mania, compared with tricyclic antidepressants.
Lamotrigine may increase response rates in people with depression compared with placebo, but can cause headache.
Quetiapine may also improve depression compared with placebo.We don't know whether lithium,
carbamazepine, valproate, or topiramate improve depression in people with bipolar disorder.We don't know whether psychological treatments are effective for people with bipolar depression, as we found no studies.
Lithium reduces relapse in bipolar disorder compared with placebo.
Valproate, carbamazepine, and lamotrigine seem as effective as lithium in reducing relapse.
Cognitive therapy and patient or family education may reduce the risk of relapse, but studies have given conflicting results.We don't know whether antidepressants can prevent relapse, and they may induce mood instability or manic episodes.
Olanzapine may reduce relapse, but long-term use may be associated with weight gain.