Interestingly, there was no relationship between lithium blood level and outcome: depression and mania scales (Montgomery-Asberg Depression Rating Scale and Young Mania Rating Scale, respectively). Those patients whose levels were less than 0.4 mEq/L improved just as much as those whose levels were 0.4 to 0.9 mEq/L.
Unfortunately, only about one-quarter of all the patients in this study reached predefined “remission” after 6 months of treatment. These were not easy bipolar II disorder patients (eg, responsive to lamotrigine monotherapy).
But these harder patients are the very ones for whom I often turn to low-dose lithium, with what I’d thought were frequently very good results. How to reconcile the LiTMUS results and my experience?
First, I must consider the possibility that my belief in lithium has biased my observations (eg, over-recognizing improvement on lithium, overinclination to attribute improvement to lithium, or selectively remembering improving cases and forgetting those that didn’t).
Otherwise, I have to look for design features of the study that might account for the mismatch between their results and mine. In this study, there’s not much to quibble with. Perhaps they’d not have had 21% of patients bail out of lithium treatment if the dose was titrated to 600 mg rather than starting out with that dose.
Nevertheless, even though lithium plus OPT was not better than OPT alone, patients in the lithium arm were 23% less likely to receive a second-generation antipsychotic. As I noted in my recent article in Psychiatric Times, low-dose lithium (eg, blood levels below 0.8 mEq/L) has a much lower risk profile than full-dose lithium or second-generation antipsychotics. Is it worth adding lithium (and the oft-needed thyroxine) to lower the odds of needing an atypical?
Dr Phelps is Director of the Mood Disorders Program at Samaritan Mental Health in Corvallis, Ore. He is the Bipolar Disorder Section Editor for Psychiatric Times. Dr Phelps stopped accepting honoraria from pharmaceutical companies in 2008 but receives honoraria from McGraw-Hill and W.W. Norton & Co. for his books on bipolar disorders.
1. Nierenberg AA, Friedman ES, Bowden CL, et al. Lithium treatment moderate-dose use study (LiTMUS) for bipolar disorder: a randomized comparative effectiveness trial of optimized personalized treatment with and without lithium. Am J Psychiatry. 2013;170:102-110.
2. Suppes T, Dennehy EB, Hirschfeld RM, et al, for the Texas Consensus Conference Panel on Medication Treatment of Bipolar Disorder. The Texas implementation of medication algorithms: update to the algorithms for treatment of bipolar I disorder. J Clin Psychiatry. 2005;66:870-886.