Prophylaxis of bipolar disorder: how and who should we treat in the long term?

Bipolar disorder is a devastating and chronic mood disorder, which can require life-long treatment. The vast majority of patients will suffer relapse of symptoms in the absence of effective therapy. Of those patients receiving treatment, compliance to medication regimens is poor. Non-compliance, when associated with lithium treatment in particular, increases the risk of recurrence of illness. Problems associated with withdrawal serve as powerful stimuli to develop alternatives to lithium monotherapy. Conventional placebo-controlled studies of treatments are difficult in patients with bipolar disorder. Large-scale, pragmatic and clinically relevant trials should be employed to assess existing and novel treatments for bipolar disorder. These can only develop out of genuine clinician and patient uncertainty and the creation of a trial culture in everyday practice.