Bipolar disorder affects 5.7 million Americans every year, yet treating it remains an imperfect process. Lithium is one of the oldest medications known to treat the disorder, with records indicated it has been used since the 1870s, according to the World Health Organization. In the United States, however, the Food and Drug Administration didn’t approve it as a treatment until the 1970s. Since then, other drugs like antipsychotics and anticonvulsants have also been developed and used in its place, and altogether, this has complicated how doctors approach the mental health disorder.

In a new study published in JAMA Psychiatry, researchers sought to determine which bipolar medications could best treat the disorder’s harmful side effects, which include self-harm, unintentional injury, and death by suicide. Self-harm is a major cause of injury among bipolar patients, and the researchers noted that there is little evidence as to whether antipsychotics are effective in reducing it. Anticonvulsants also have a history of increasing self-harm.

To determine how these different medications fare, the researchers compared rates of self-harm, unintentional injury, and suicide deaths in nearly 7,000 bipolar patients using their electronic health records. The patients, who were from the United Kingdom, were actively taking either lithium (a mood stabilizer), valproate sodium (an anticonvulsant), olanzapine (an antipsychotic), or quetiapine (an antipsychotic). Compared to the patients who took lithium, the rest of the study’s subjects had increased rates of self-harm and unintentional injuries.

"This finding augments limited trial and smaller observational study results,” the study stated. “It supports the hypothesis that lithium use reduces impulsive aggression in addition to stabilizing mood.”

Across all of the study’s participants, the rate of suicide deaths was too low to show a significant difference between each drug. However, in 2013, another study found lithium was also able to reduce the occurrence of suicidal thoughts in people with bipolar disorder and depression. The researchers found that while other medications were still effective in managing the symptoms of bipolar disorder, they were not as effective as lithium at preventing thoughts of suicide.

Though lithium seems to be the most promising medicine for treating bipolar disorder — it is regarded as the best long-term treatment for the disorder to date — it is not flawless. In addition to having many side effects, such as weight gain, kidney failure, and thyroid issues, certain patients also fail to respond to the treatment.

In a 2015 study, researchers discovered that people with bipolar disorder have brain cells that are more sensitive and reactive to stimuli than those of the average person. But for unknown reasons, this sensitivity is more static for some bipolar patients than others, making lithium treatment unpredictable. In one experiment involving six cell samples collected from bipolar patients, the researchers found lithium reduced the sensitivity of three cells while the other three remained the same.

“Now that we have neurons that show differences in excitability, we can use them to screen for better drugs,” said Jerome Mertens, a postdoctoral research fellow and the lead author of the paper.

So while lithium may be best for reducing self-harm and potentially cases of suicide, further research into the treatment of bipolar disorder is still necessary.

Source: Hayes JF, et al. Self-harm, Unintentional Injury, and Suicide in Bipolar Disorder During Maintenance Mood Stabilizer Treatment: A UK Population-Based Electronic Health Records Study. Jama Psychiatry. 2016.