A systematic review and meta-analysis of clinical predictors of lithium response in bipolar disorder

Objective To determine clinical predictors of lithium response in bipolar disorder. Methods Systematic review of studies examining clinical predictors of lithium response was conducted. Meta-analyses were performed when >= 2 studies examined the same potential predictor. Results A total of 71 studies, including over 12 000 patients, identified six predictors of good response: mania-depression-interval sequence [odds ratio (OR): 4.27; 95% CI: 2.61, 6.97; P < 0.001], absence of rapid cycling (OR for rapid cycling: 0.30; 95% CI: 0.17, 0.53; P < 0.001), absence of psychotic symptoms (OR for psychotic symptoms: 0.52; 95% CI: 0.34, 0.79; P = 0.002), family history of bipolar disorder (OR: 1.61; 95% CI: 1.03, 2.52; P = 0.036), shorter prelithium illness duration [standardised mean difference (SMD): -0.26; 95% CI: -0.41, -0.12; P < 0.001] and later age of onset (SMD: 0.17; 95% CI: 0.02, 0.36; P = 0.029). Additionally, higher body mass index was associated with poor response in two studies (SMD: -0.61; 95% CI: -0.90, -0.32; P < 0.001). There was weak evidence for number of episodes prior to lithium treatment (SMD: -0.42; 95% CI: -0.84, -0.01; P = 0.046), number of hospitalisations before lithium (SMD: -0.40; 95% CI: -0.81, 0.01; P = 0.055) and family history of lithium response (OR: 10.28; 95% CI: 0.66, 161.26; P = 0.097). Conclusions The relative importance of these clinical characteristics should be interpreted with caution because of potential biases and confounding.