56 - Prophylaxis in bipolar disorder
Prophylaxis in bipolar disorder
326 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 2 Prophylaxis in bipolar disorder Any successful drug regimen used for an acute episode should be continued as prophylaxis. To a large extent, therefore, the choice of maintenance treatment for individual patients is dictated by the efficacy and tolerability of acute treatment. Possible exceptions include the consideration of withdrawing antipsychotic treatment from a mood-stabiliser combination after an episode of mania (recommended by some authorities1) and the withdrawal of antidepressants after the successful treatment of an acute episode of bipolar depression, assuming a mood stabiliser is continued (recommended by most authorities, at least implicitly2). Withdrawing antipsychotics from combination regimens with lithium or valproate may worsen the risk of relapse.3 Residual mood symptoms after an acute episode are a strong predictor of recurrence.4,5 In respect to monotherapy, most evidence supports the efficacy of lithium6,7 in preventing episodes of mania and depression.8 Carbamazepine is somewhat less effective6,9 and the long-term efficacy of valproate is uncertain,7,10–12 although it too may protect against relapse both into depression and mania.6,13 Lithium has the advantage of a proven anti-suicidal effect14–16 but perhaps, relative to other mood stabilisers, the disadvantage of a worsened outcome following abrupt discontinuation17–20 (although the effect of abrupt discontinuation of other drugs may be similar20). Early use of lithium might increase the likelihood of efficacy.21 The independent BALANCE study found that valproate as monotherapy was relatively less effective than lithium or the combination of lithium and valproate,11 casting doubt on its use as a first-line single treatment. Also, a large observational study has shown that lithium is much more effective than valproate in preventing relapse to any condition and in preventing rehospitalisation.22 Given this, valproate’s relative contraindication in women of child-bearing age and the fact that valproate is not licensed for prophylaxis, valproate should be considered a second- or third-line treatment. Conventional antipsychotics have traditionally been used and are perceived to be effective although the objective evidence base is rather weak.23,24 FGA depots probably protect against mania but may worsen depression25 (see ‘Antipsychotic long-acting injections in bipolar disorder’ earlier in this chapter). Evidence supports the efficacy of many SGAs particularly olanzapine,26,27 quetiapine,28 aripiprazole29 and risperidone.30 Most studies examine combinations with mood stabilisers and there are fewer supportive monotherapy trials, although asenapine, aripiprazole, olanzapine, quetiapine and risperidone monotherapy are all more effective than placebo. Olanzapine, quetiapine and aripiprazole are licensed for prophylaxis in many countries although only olanzapine and quetiapine offer protection against depression.7 Asenapine may also be effective,31 as may ziprasidone.32 There is some evidence to support maintenance treatment with lurasidone when added to valproate or lithium,33 but there are only acute data for lumateperone.34 Cariprazine may be ineffective as maintenance.35 All antipsychotic + mood stabiliser combinations were more effective than mood stabilisers alone in a meta-analysis of 41 studies and 9821 participants.36 Aripiprazole
- valproate was numerically the best maintenance treatment (in terms of risk of relapse to any episode) in this analysis. A later meta-analysis of 14 monotherapy studies found that monotherapy with aripiprazole, olanzapine, lurasidone, risperidone or quetiapine was more effective than placebo over 6 months or longer.37 A 2022 network meta- analysis found the order of effectiveness to be olanzapine (most effective), quetiapine, aripiprazole, risperidone, lurasidone and paliperidone (least effective).7 Long-acting aripiprazole has been shown to delay the time to, and reduced the rate of recurrence of, manic episodes and was generally safe and well tolerated.38 The use of