Abstract
ABSTRACTObjectivesPolypharmacy is common in maintenance treatment of bipolar illness, but proof of greater efficacy compared to monotherapy is assumed rather than well known. We systematically reviewed the evidence from the literature to provide recommendations for clinical management and future research.MethodA systematic review was conducted on the use of polypharmacy in bipolar prophylaxis. Relevant papers published in English through 31 December 2019 were identified searching the electronic databases MEDLINE, Embase, PsycINFO, and the Cochrane Library.ResultsTwelve studies matched inclusion criteria, including 10 randomized controlled trials (RCTs). The best drug combination in prevention is represented by lithium + valproic acid which showed a significant effect on time to mood relapses (HR = 0.57) compared to valproic acid monotherapy, especially for manic episodes (HR = 0.51). The effect was significant in terms of time to new drug treatment (HR = 0.51) and time to hospitalization (HR = 0.57). A significant reduction in the frequency of mood relapses was also reported for lithium + valproic acid vs. lithium monotherapy (RR=0.12); however, the trial had a small sample size. Lamotrigine + valproic acid reported significant efficacy in prevention of depressive episodes compared to lamotrigine alone.ConclusionsThe literature to support a generally greater efficacy with polypharmacy in bipolar illness is scant and heterogeneous. Within that limited evidence base, the best drug combination in bipolar prevention is represented by lithium + valproic acid for manic, but not depressive episodes. Clinical practice should focus more on adequate monotherapy before considering polypharmacy.
Highlights
Bipolar illness is a disabling mental illness with a high risk of relapse and recurrence affecting about 45 million people worldwide.[1]
Within that limited evidence base, the best drug combination in bipolar prevention is represented by lithium + valproic acid for manic, but not depressive episodes
| 3 the possible combinations of couples of first-line maintenance drugs reported by the Canadian Network for Mood and Anxiety Treatments (CANMAT) and ISBD 2018 guidelines, we systematically reviewed the evidence from the literature on bipolar illness maintenance polypharmacy to provide recommendations for clinical management and future research
Summary
Bipolar illness is a disabling mental illness with a high risk of relapse and recurrence affecting about 45 million people worldwide.[1] In most patients, it is a chronic condition, associated with clinical, psychosocial, and cognitive decline.[2]. Sustained remission of mood episodes has been associated with better outcomes on cognitive performances and brain morphology, while affective recurrences have been shown to have an impact in terms of treatment resistance and disability.[3,4] an effective maintenance treatment is needed to prevent relapses, minimize illness progression, reduce residual symptoms, restore functioning and quality of life. Experts and clinicians feel comfortable with this approach, assuming that this disease is too severe to respond to monotherapy in most cases.[6]
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