Polypharmacy is combined pharmaceutical treatment that is used for patients who are unresponsive or partially responsive to single therapies.

What is the evidence for polypharmacy?

Moderate quality evidence finds fewer relapses with any combination therapy than with any monotherapy or placebo. The following combination therapies reduced overall relapse rates more than placebo for over 6 months (in descending order of effectiveness); aripiprazole + valproate, lithium + oxcarbazepine, lithium + valproate, and aripiprazole + lamotrigine.

Moderate to high quality evidence finds greater improvement in depression symptoms with combined olanzapine + fluoxetine therapy than with placebo, olanzapine or lamotrigine alone. Overall, adjunctive second-generation antidepressants were associated with a small improvement in depression in the short-term (< 12 weeks), however there was an increased risk of switching to mania/hypomania in the longer term (~52 weeks).

Moderate quality evidence finds a medium-sized reduction in relapses to any mood episode after 6 months of treatment with antipsychotics plus mood stabilisers (mostly lithium and valproate) compared to placebo plus mood stabilisers. Aripiprazole plus mood stabilisers and quetiapine plus mood stabilisers prevented both depression and mania relapses, while lurasidone plus mood stabilisers was more effective for preventing relapse to depression, and ziprasidone plus mood stabilisers was more effective for preventing relapse to mania.

Adding antipsychotics to mood stabilisers also resulted in greater response and remission compared to mood stabilisers alone, but was associated with more sleepiness, somnolence, weakness, faintness, dizzyness, appetite, weight gain, tremor, use of antiparkinsonian drugs, dry mouth and thirst, and changes in triglycerides, fasting glucose, and HbA1c levels. Compared to antipsychotics alone, adding mood stabilisers to antipsychotics improved mania but not depression and resulted in more tremor, sleepiness, and vomiting.

November 2021

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