Lithium lowers suicide risk – study finds

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Lithium reduces the risk of suicide in people with mood disorder, a large analysis of randomized controlled trials has confirmed.

Patients with mood disorders, also called effective disorders, suffer from depression. In contrast to “the blues” that we all go through, a depressive episode is a true illness, often referred to as clinical depression. Some patients also experience episodes of mania-intense excitement and mental disorganization that usually require immediate hospitalization. Although mania is popularly thought of as a state of excess euphoria, patients report that a depressive mood is as frequent as euphoria during a manic episode, and irritability is the most common symptom.

Some people may experience both depression and mania at the same time; these are the mixed states that doctors sometimes refer to. Some patients cycle rapidly from one state to the other, sometimes within the course of a day. Some people have episodes of clinical depression alternating with hypomania that never progresses to mania; this form is usually called bipolar-II illness. Severe depression that occurs without mania is usually referred to as unipolar depression, clinical depression, major depression or, sometimes, the classic term, melancholia.

John Cade, an Australian physician, introduced lithium into psychiatry in 1949 when he reported that lithium carbonate was an effective treatment for manic excitement. Unfortunately, Dr. Cade’s discovery coincided with reports of several deaths from the unrestricted use of lithium chloride as a salt substitute for cardiac patients. Four patients died, and several developed toxic reactions. It was not known at that time that lithium can accumulate to dangerous levels in the body or that lithium has to be used with special caution in patients with cardiac disorders. As a result of these experiences, lithium was virtually neglected in this country until the early 1960s. Research by European psychiatrists, especially Dr. Mogens Schou in Denmark, hastened acceptance of lithium in the United States. Renewed interest in the compound led to numerous clinical trials, including pivotal studies conducted by NIMH. These studies showed how lithium could be used safely and effectively to treat psychiatric disorders. In addition, research-both in animals and humans-showed that lithium influences several functions in the body, including the distribution of sodium and potassium, which regulate impulses along the nerve cells. Lithium can affect the activity of neurotransmitter and biological systems because it alters the way in which a variety of messages are transmitted after they reach their target.

Psychiatrists use lithium in two ways: to treat episodes of mania and depression and to prevent their recurrence. Lithium can often subdue symptoms when a patient is in the midst of a manic episode, and it may also ameliorate the symptoms of a depressive episode. The single most important use for lithium, though, is in preventing new episodes of mania and depression. Lithium is also being used experimentally to treat other disorders.

Unlike other psychoactive drugs, Li+ typically produces no obvious psychotropic effects (such as euphoria) in normal individuals at therapeutic concentrations. Li+ possibly produces its effects by interacting with the transport of monovalent or divalent cations in neurons.

Recent research suggests three different mechanisms which may or may not act together to deliver the mood-stabilizing effect of this ion. The excitatory neurotransmitter glutamate could be involved in the effect of lithium as other mood stabilizers, such as valproate and lamotrigine, exert influence over glutamate, suggesting a possible biological explanation for mania. The other mechanisms by which lithium might help to regulate mood include the alteration of gene expression.

Researchers from the Universities of Verona and Oxford found 48 published and unpublished studies, with a total of 6675 participants of either sex and any age, that had compared the effects of lithium with those of other drugs, or with placebo. They looked at three outcomes: completed suicide, deliberate self-harm and death from any cause.

Overall, lithium was considerably more effective than placebo in reducing risk of completed suicide and deaths from any cause, but any benefit in reducing the risk of self-harm was not statistically significant. In people with unipolar depression, the risks of suicide and of any-cause death were lower with lithium than with placebo.

Generally, lithium was better than other active treatments, but not significantly so. The exception to this was a statistically significant reduction in risk of deliberate self-harm with lithium compared with carbamazepine.

The study’s authors said that adverse events associated with lithium are likely to be dose-related, so dose and plasma concentrations of the drug should be monitored, but added that recent evidence showed it might be better tolerated than was thought. “Clinical decision making will need to take a balanced view of the likely benefits and harm of lithium in the individual patient,” they said.

They concluded: “Lithium seems to reduce the risk of death and suicide by more than 60% compared with placebo …

“People treated for an affective disorder have a 30 times greater risk of suicide than the general population, and the evidence that lithium reduces the risk of suicide and possibly deliberate self-harm in people with bipolar disorder and recurrent unipolar depression indicates that lithium should continue to have an important clinical role.”

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