Lithium's Role in Suicide Prevention Reinforced

Caroline Cassels

June 27, 2013

Lithium helps prevent suicide and is associated with a lower risk for all-cause mortality in patients with mood disorders, new research shows.

A large, systematic review showed that the drug reduced the risk for death and suicide by more than 60% compared with placebo, a finding investigators say reinforces lithium's role as an effective agent to reduce the risk for suicide in individuals with unipolar depression and bipolar disorder (BD).

"Lithium was associated with a reduced risk of suicide when compared with placebo, and also a reduced risk of deliberate self harm compared with carbamazepine. Our findings are in line with other previous observational studies, but they extend the applicability and the strength of the available information," the authors, led by Andrea Cipriani, MD, from University of Oxford in the United Kingdom and the University of Verona in Italy, write.

The study was published online June 27 in BMJ.

New Data

All psychiatric disorders are associated with an increased risk for suicide, but mood disorders carry the highest risk. The investigators note that individuals with a mood disorder have a 30-fold greater risk for suicide than the general population.

A previous meta-analysis by the same investigators published in 2005 in the American Journal of Psychiatry showed that compared with placebo or other drugs, long-term lithium use reduced the risk for suicide in individuals with mood disorders.

However, owing to the low numbers of events and consequent imprecise estimates of the treatment, the potential preventive effect of lithium for both suicide and self-harm remained uncertain.

In the meantime, 16 new randomized trials examining lithium's effect in suicide prevention have been published, increasing the number of events by 55% and the number of participants by 70%.

With this new data in hand, the researchers assessed lithium's impact on suicide prevention and self-harm in patients with depression and BD by reviewing and analyzing 48 randomized controlled trials involving 6674 participants.

The study's main outcomes were the number of individuals who completed suicide, engaged in deliberate self-harm, and died from any cause.

Potential Mechanisms

The updated systematic review revealed that lithium was more effective than placebo in reducing the number of suicides (odds ratio [OR], 0.13; 95% confidence interval [CI], 0.03 - 0.66) and deaths from any cause (OR, 0.38; 95% CI, 0.15 - 0.95).

The researchers found no clear benefits for lithium compared with placebo in preventing deliberate self-harm. When lithium was compared with each active individual treatment, the researchers found a statistically significant difference only with carbamazepine.

Although the underlying mechanism is not entirely clear, the investigators speculate that lithium may exert its antisuicidal effects by reducing relapse of mood disorder, but they add that there is some evidence to suggest the drug "decreases aggression and possibly impulsivity, which might be another mechanism mediating the antisuicidal effect."

More research to elucidate the drug's mechanism "could lead to a better understanding of the neurobiology of suicide."

Although lithium has several potential serious side effects, including reduced renal function, hypo- and hyperthyroidism, and weight gain, the researchers note that "a recent review indicated that the tolerability profile of lithium may be more favourable than previously thought."

The investigators add that adverse effects are likely to be dose related and that clinicians need to monitor plasma concentrations to ensure "optimum efficacy and adequate tolerability."

The authors report no relevant financial relationships.

BMJ. Published online June 27, 2013. Full article


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