Lithium May Reduce Self-Harm, Unintentional Injury in Patients With Bipolar Disorder

Patients with bipolar disorder have increased risks of self-harm and suicide, but determining the medications that might best mitigate this risk has been difficult, due to the fact most trials exclude those with a history of suicidal behavior. A study published this month in JAMA Psychiatry now suggests lithium may help to lower rates of self-harm and unintentional injury in patients with bipolar disorder compared with those prescribed other common maintenance treatments for the disorder.

Olimpik/Shutterstock

A team of researchers at University College London (UCL) and the University of Oxford analyzed electronic health record (EHR) data from 6,671 patients with bipolar disorder who were prescribed either lithium, the anticonvulsant valproate, or the antipsychotics olanzapine or quetiapine—the four most common medications given for bipolar maintenance therapy in the United Kingdom. They then compared the rates of suicide, self-harm, and unintentional harm (for example, falls or car accidents) among this population.

Lead author Joseph Hayes, M.B.Ch.B., a clinical research fellow in the Division of Psychiatry at UCL, told Psychiatric News that it was important to examine unintentional harm because it is a common yet understudied outcome of bipolar disorder; studies have shown that deaths from accidental injury are around six times higher in people with bipolar disorder.

“In addition, unintentional injuries are believed to arise from manic as opposed to depressive symptoms,” Hayes said. “So the best medication to treat deliberate harm may not be the best at reducing unintentional harm.”

The results of the analysis by Hayes and colleagues suggest that lithium may, in fact, be most appropriate for both.

The authors found that self-harm rates in patients prescribed lithium were about 205 incidents per 10,000 person-years at risk (PYAR) compared with 392 for valproate, 409 for olanzapine, and 582 for quetiapine. Lithium also resulted in fewer cases of unintentional harm (583 per 10,000 PYAR) than valproate (669) or quetiapine (705), but was similar to olanzapine (569 per 10,000 PYAR). The number of suicides was too low to uncover differences among these four medications.

The observed superiority of lithium in reducing self-harm and unintentional injury suggests that the medication may reduce impulsive behaviors in addition to stabilizing mood, suggested Hayes. While he noted it is possible that clinician monitoring of lithium (due to the medication’s potential toxicity) may improve adherence, the analysis found that lithium patients had the same amount of physician contact as patients taking other medications.

While Hayes and colleagues attempted to adjust the results for all possible factors that might also affect patient outcomes, such as demographics or clinical history, subtle but important elements of clinician decision-making could not be analyzed, Michael Ostacher, M.D., M.P.H., an associate professor of psychiatry at Stanford University School of Medicine, told Psychiatric News.

“You can account for a lot of confounding variables, but you can’t adjust for a clinician’s gut feeling,” Ostacher, who was not involved with this study, said. For instance, because lithium has a narrow dosage window between being therapeutic and toxic, a clinician may be less likely to prescribe the medication to those at greatest risk of self-harm, he said. As a result, “the population that received lithium might be less prone to commit harm to begin with,” he explained.

“Still, I believe lithium is an effective but underutilized medication and am not opposed to any data that suggests we should use lithium more,” he continued. (Ostacher is part of a multi-center prospective study examining the effects of add-on lithium in veterans with major depression or bipolar disorder and suicidal behaviors.)

Hayes acknowledged that while his study could not take every possible variable into account, he believes the findings of the trial are an important step forward.

“There is growing evidence that lithium works better than other drugs for mood stabilization, and little evidence that these other drugs have a positive impact on self-harm,” he said. “So I believe the case for use of lithium as a first-line therapy is getting stronger. Of course, we always need to be mindful of the potential side effects of all bipolar drugs and work to mitigate or minimize these, and I think further research on how to do this is necessary.”

This work was supported by a Medical Research Council Population Health Scientist Fellowship. ■