People suffering from a mood disorder are 30 times more likely to commit suicide than the general population. Finding an effective treatment that reduces the likelihood of suicide in individuals with mood disorders is therefore an important area of research. Previous studies have indicated that lithium may possess this effect, but concerns about its side effects have held the treatment back. A new systematic review of the evidence into the effectiveness of lithium for preventing suicide has revealed that the drug does appear to reduce the chances of suicide in people suffering from mood disorders. Combined with recent evidence, which indicates that the drug is better tolerated than originally assumed, lithium looks set to continue on as a core part of treatment for people with mood disorders. The Study The study was a systematic review, or in other words, combined results from numerous studies that had previously been conducted in order to determine the effectiveness of the treatment in a larger number of participants. The researchers looked at 48 randomized and controlled trials covering almost 6,700 participants. Randomized controlled trials are useful because neither the researchers nor the participants know who is taking the experimental medicine (in this case lithium) and who\u2019s taking the comparative (a known effective treatment) or placebo (inactive sugar pill), so the effects observed probably won\u2019t be due to the \u201cplacebo effect.\u201d The study was published in the British Medical Journal this summer. The researchers used several outcome measures to determine whether the treatment was effective. The main ones were the number of suicides in each group, the number of participants who died from any cause, and the number of participants who deliberately self-harmed. What They Found According to the systematic review of the evidence, lithium significantly outperformed the placebo when it came to reducing the numbers of suicides and deaths from any cause. The researchers calculated this to be over a 60 percent reduction in risk, although it\u2019s worth noting that this is only in comparison to an inactive medicine. There was no benefit when it came to cases of deliberate self-harm between those taking lithium and those on the placebo. In unipolar depression alone (which, unlike bipolar depression, doesn\u2019t involve episodes of mania interspersed with the depressive episodes), lithium helped to reduce cases of suicide and deaths from any cause when compared to the placebo. However, in comparison with other treatments, the difference was much less pronounced. On the whole, lithium was slightly more effective than the comparator drugs, but it only achieved a statistically significant benefit when compared to carbamazepine for reducing deliberate self-harm. The overall findings were positive, but the limited benefits when compared to other treatments may mean that the side effects must be considered before a decision is made in clinical practice. Possible Mechanisms The researchers suggested some potential explanations for the anti-suicidal effect observed from the studies of lithium. The main hypothesis is that lithium makes relapse into mood disorder less likely, which means people taking it will be less likely to hit the type of emotional low that may drive them to suicide. However, this is only an assumption, and the researchers also note that there is evidence that lithium reduces impulsivity and aggression in people taking it, thus providing another possible explanation for the reduced rates of suicide. Determining which of these two hypotheses is correct might give scientists a much deeper understanding of the neurology of suicide and thereby lead to new treatments. The interesting thing about the findings of this review is that the protective effect of lithium against suicide is larger than the positive impact on mood, meaning that the drug\u2019s effect may be specific to suicide. Side Effects and Use in Treatment The biggest problem with using lithium in practice is the side effects associated with the drug, which the researchers note are of concern to both clinicians and patients. However, another recent review of the drug indicated that lithium is actually better tolerated than previously thought, meaning that it may become more common in practice. Despite side effects possibly being less serious than originally assumed, there is still a risk of reduced kidney function, weight gain, hypothyroidism, hyperparathyroidism and a reduced ability to concentrate urine in patients taking lithium. The researchers note that this is probably related to dosage, and that doctors should make their decision based on the patient as an individual and the likelihood of positive or negative effects. In short, lithium appears to have some anti-suicidal properties, and if the side effects really aren\u2019t as severe as previously thought, it will continue to be used in cases of both unipolar and bipolar depression, particularly where there is an indication of risk of suicide. This is the least important implication of this research, though, because if the neurological mechanism by which lithium reduces suicide risk is determined, it could mean a revolution in the understanding and treatment of suicidal and self-harming patients.