Lithium response in families can inform the selection of long-term treatment of bipolar disorder

Lithium, recommended as the first-line choice for recurrence prevention in bipolar disorder, is fully effective in only about one-third of patients. It is therefore important to identify early those patients likely to benefit in the long-term. Earlier studies suggested that the response to lithium stabilization runs in families and that family history is an important predictor of treatment outcome. To overcome the limitations of the earlier studies - small sample size in particular - we carried out a multicenter study and used a standardized assessment of treatment response. Collaborating centers in Canada, Italy, and Poland recruited 92 biological relatives of 78 probands assessed for response to long term lithium monotherapy. We compared their data with those from 78 unrelated persons with bipolar disorder. The response to treatment has been quantified on a scale previously described and validated. Among the relatives of lithium responders, 69% were also good responders; in relatives of non-responders, only 22% responded to treatment (p < 0.0001). The odds of responding were 7.8 times higher in families of responders compared to non-responders (95% CI 3.0 to 20.1). The response rate in the comparison group was 31%, lower than in the responders' relatives (p < 0.0001), but not significantly different from the rate in families of non-responders (p = 0.31). Our findings support the familial nature of the response to lithium. When information about the response in relatives is available, family history of lithium response is a crucial factor to consider when selecting long term treatment.