For years, the drug lithium has been widely regarded as a first-line treatment for adults with bipolar disorder. The scientific evidence of its advantages over other mood-stabilizing medicines has been persuasive to many doctors, with studies repeatedly indicating that lithium is effective for acute and maintenance treatment. Moreover, cumulative evidence by different investigators has shown that in comparison with other medications commonly used to treat bipolar disorder in adults, lithium significantly diminishes the risk of suicidal ideation and attempts.

There is evidence that lithium also is indicated for the management of mood symptoms in youths with bipolar disorder. But there are no studies regarding the effects of lithium on suicidal attempts or ideation in youths—symptoms frequently experienced in bipolar disorder. This gap in research has now been addressed by a team whose members include Boris Birmaher, M.D., a 2013 BBRF Colvin Prizewinner, and first author Danella Hafeman, M.D., Ph.D., both at the University of Pittsburgh.

Reporting online in the Journal of the American Academy of Child and Adolescent Psychiatry, the team reported findings “consistent with adult studies, showing that lithium is associated with decreased suicidality, less depression, and better psychosocial functioning” in a large sample of young people diagnosed with bipolar disorder.

The team took advantage of the ongoing Course and Outcome of Bipolar Youth (COBY) study that has been following 413 youths recruited in Pennsylvania, California, and Rhode Island for over 15 years. The participants had a diagnosis of bipolar disorder and were aged 7 to 17 when the study began. The study is longitudinal, meaning that researchers have been following the young people over a period of years, with assessments made on average every 8 months.

The Pittsburgh team analyzed data from 340 of the participants, with a total of 2,638 follow-ups for periods up to 10 years since the COBY study began. Of these follow-ups, 886 were in participants who were being maintained on lithium, while 1,752 were in participants who were taking other medications, including second-generation antipsychotics, stimulants, and to a lesser extent, valproate, lamotrigine, and antidepressants. Participants reported the medicine they were taking at the time of each assessment. The team only counted assessments in which participants were still under 18 years of age and were adhering to their mood-stabilizing prescription three-fourths of the time or more since the prior assessment.

The results were encouraging to the team: “We found that lithium use was associated with fewer suicide attempts, fewer depression symptoms, better psychosocial function, and less parent-reported aggression,” they said, as compared with other mood stabilizing medicines.

Importantly, the new Pittsburgh study was not a randomized control trial, the gold standard for shorter-term trials. Rather, it was an "observational" study, meaning, in this case, that the participants and those who assessed them were not "blind" to which mood stabilizer they were taking. Still, the sample used did provide a good opportunity to assess medication effects in a large sample of young people, and to follow them over a long period of time. Drs. Birmaher, Hafeman and colleagues in fact suggest that their sample, drawn from three communities, reflects "real-world information" and thus "arguably may be more applicable to our patient population," i.e., young people with bipolar disorder, than a hospital-based randomized trial would be.

They recommend that future research attempt to discover the mechanisms in the brain that enable lithium to improve outcomes in bipolar disorder, and in particular for suicidal behaviors. This might serve as a basis for making new medicines that would not have some of lithium’s side effects. In addition to being potentially lethal if taken in an overdose, lithium doses need to be calibrated through blood levels and carefully monitored.

The large research team also included Martin Keller, M.D., a member of the BBRF Scientific Council and winner of the 1998 Selo Prize; and Benjamin Goldstein, M.D., Ph.D., 2014 BBRF Independent Investigator, 2007 Young Investigator and 2018 Colvin Prizewinner.