Review of: Chen PH et al, Acta Psychiatr Scand 2023;147(3):234–247

Study type: Retrospective cohort study

The mortality rate in bipolar disorder is approximately double that of the general population. While suicide is one reason, bipolar disorder increases the risk of death from natural causes, too. Rates of suicide and all-cause mortality are lower with lithium, and this study compared those rates with anticonvulsant mood stabilizers (valproic acid, lamotrigine, and carbamazepine). Antipsychotics were not included.

Researchers analyzed records from 25,787 patients who were hospitalized for bipolar disorder (bipolar I, II, and not otherwise specified) in Taiwan using a national insurance database. Exposure to mood stabilizers was measured for five years following hospitalization. Sixteen percent of the patients died during the study period.

The primary outcome was the rates of suicide, all-cause mortality, and natural mortality. These rates were presented as standardized mortality ratios (SMRs). This is a comparison of the observed rate of death to that expected in the general population, where an SMR above 1 indicates a higher risk of death. SMRs were controlled for sex, age, employment status, comorbidities, and concomitant drugs.

For bipolar disorder, the SMRs were 26.0 for suicide, 5.3 for all-cause mortality, and 4.7 for natural mortality. The risk of suicide was highest in those age 45–65 years and in those with multiple psychiatric comorbidities.

Mood stabilizer use was associated with lower risks of suicide, all-cause mortality, and natural mortality, with adjusted hazard ratios (aHR) of 0.55–0.60. Lithium had the most profound effects, with an aHR for each outcome of 0.37–0.39. There was a strong association between higher cumulative lithium doses, longer lithium exposure, and a reduced risk of death from any cause.

Valproic acid also had an association with lower mortality, but it was not as impressive as that of lithium. Lamotrigine and carbamazepine had no significant association with either higher or lower mortality rates.

All of the study participants had at least one hospitalization, which may have led to an overestimation of the risks seen in this study.

Carlat Take

Patients who took lithium lived longer than those on anticonvulsants or no treatment, with a lower risk of death from suicide as well as natural causes. These data put lithium’s medical risks—including renal impairment, hypothyroidism, and toxicity—in perspective and argue against the trend toward decreased lithium utilization that we’ve seen since the introduction of branded options in the 1990s.