Medicating mood with maintenance in mind: bipolar depression pharmacotherapy

Abstract

Objectives: Bipolar depression is a core feature of bipolar disorder, a phase in which many patients spend the majority of time and one that confers a significant degree of burden and risk. The purpose of this paper is to briefly review the evidence base for the pharmacotherapy of bipolar depression and to discuss the recommendations for its optimal management.Methods: A detailed literature review was undertaken with a particular emphasis on pharmacological treatment strategies for bipolar depression across the acute and maintenance phases of the illness. Electronic library and Web‐based searches were performed using recognised tools (MEDLINE, PubMED, EMBASE and PsychINFO) to identify the pertinent literature. A summary of the evidence base is outlined and then distilled into broad clinical recommendations to guide the pharmacological management of bipolar depression.Results: Partitioning treatment into acute and maintenance therapy is difficult based on the paucity of current evidence. The evidence from treatment trials favours the use of lithium and lamotrigine as first‐line treatment in preference to valproate, and indicates that, for acute episodes, quetiapine and olanzapine have perhaps achieved equivalence at least in terms of efficacy. However, the effectiveness of the atypical antipsychotics in maintenance therapy is constrained by the potential for significant side effects of individual agents and the lack of both long‐term research data and clinical experience in treating bipolar disorder as compared to other agents. Conversely, lithium and the anticonvulsants are generally slower to effect symptomatic change, and this limits their usefulness.Conclusions: There has been a tendency for research trials of bipolar depression to differentiate the illness cross‐sectionally into the acute and maintenance phases of bipolar depression; however, in clinical terms, bipolar depression invariably follows a longitudinal course in which the phases of illness are inextricably linked, and useful acute treatments are typically continued in maintenance. Therefore, when medicating mood in acute bipolar depression it is imperative to keep maintenance in mind as it is this aspect of treatment that determines long‐term success.

Increased ratio of anti-apoptotic to pro-apoptotic Bcl2 gene-family members in lithium-responders one month after treatment initiation

“…Interestingly, all of the significant differences between responders and non-responders occurred during the period from 4–6 weeks after initiation of treatment with lithium. This time period corresponds well with the typical 6–8-week delay in the acute antidepressant effect of lithium in the treatment of bipolar depression [34]. At week 4 there were 37 differentially expressed genes (22 up-regulated in responders vs. non-responders and 15 down-regulated) and at week 6 there were 90 differentially expressed genes (51 up-regulated and 39 down-regulated).…”

Balanced efficacy, safety, and tolerability recommendations for the clinical management of bipolar disorder

“…This choice has to be made on the basis of an array of factors unique to the individualÕs psychiatric history; specifically, the pattern and severity of symptoms, the course of illness, past treatments and tolerability profile, family history Table 3. In addition, because treatments that are successful in the short term tend to be continued in maintenance treatment, the long-term tolerability of pharmacological agents warrants particular consideration (26). In addition, because treatments that are successful in the short term tend to be continued in maintenance treatment, the long-term tolerability of pharmacological agents warrants particular consideration (26).…”

Aripiprazole in the Maintenance Treatment of Bipolar Disorder: A Critical Review of the Evidence and Its Dissemination into the Scientific Literature

“…Despite the need for robust evidence on the maintenance and/or long-term prophylactic treatment of bipolar disorder, to date very little has been supplied in this regard [4],[15],[22],[23]. There remains little consensus about recommended courses of maintenance or prophylactic treatment, and consequently overall psychopharmacological treatment patterns vary widely [24]–[28].…”