Comparative efficacy, acceptability, and tolerability of adjunctive anti-inflammatory agents on bipolar disorder: A systemic review and network meta-analysis.

ABSTRACT

OBJECTIVES: We performed a network meta-analysis (NMA) with up-to-date evidence to compare different anti-inflammatory agents to improve the treatment of bipolar disorder (BD) patients. METHODS: Four databases (i.e., the Cochrane Library, Web of Science, PubMed, and Embase) were searched for randomized controlled trials (RCTs) published between 1995 and 2022 on the use of anti-inflammatory agents in the treatment of BD. A systematic review and NMA were conducted. RESULTS: Adjunctive N-acetylcysteine (NAC) was superior to placebo for the treatment of BD according to the endpoint scale score (SMD -0.65, 95% confidence interval (CI) - 0.99 to - 0.31), response rate (odds ratio (OR) 3.42, 95% CI 1.23-9.52), remission rate (OR 4.94, 95% CI 1.03-41.38) and surface under the cumulative ranking curve (SUCRA) value of the endpoint scale score (0.84). Adjunctive nonsteroidal anti-inflammatory drugs (NSAIDs) were more favorable than placebo based on the remission rate (OR 3.93, 95% CI 1.15-13.43) and were significantly more acceptable than other treatments (OR 0.60, 95% CI 0.36-0.99). Adjunctive coenzyme Q10 (CoQ10) was superior to other agents in terms of the response rate (OR 18.85, 95% CI 2.63-135.00), with a SUCRA value for the response rate of 0.90 and that for the remission rate of 0.71. CONCLUSION: Adjunctive NAC is recommended for the treatment of BD. Adjunctive NSAIDs and CoQ10 are still seen as effective, but more high-quality clinical studies are needed to verify their efficacy. Other anti-inflammatory agents may not be recommended for clinical use at present. All anti-inflammatory agents demonstrated a good safety profile. We call for further research on the combined treatment of BD with different anti-inflammatory agents to be included in future trials.