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Psychopharmacological Treatment to Reduce Suicide Risk

Psychopharmacological Treatment to Reduce Suicide Risk

Suicide may be the culmination of a complex combination of psychological, biological, social, and cultural factors, and it is particularly likely to occur during periods of individual, family, and socioeconomic crises associated with loss and shame. Psychiatric disorders, especially depression, bipolar disorder, and substance abuse, are most often associated with suicide.1,2In bipolar disorder, mixed manic-depressive states are often associated with increased suicide risk.3 Suicide rates are also surprisingly high among persons who have anxiety disorders, and severe anxiety may accompany suicidal behavior. However, evidence of the efficacy of antianxiety medications in lowering suicide risk is limited.4

The effect of treatment on suicide risk has been a topic of growing research interest in recent years. There is limited evidence that psychiatric treatments reduce suicide risk, although a decrease in the long-term suicide rate for patients with mood disorders treated with lithium, neuroleptics, and antidepressants has been reported in more recent studies.5 Psychiatric treatments as diverse as psychotherapy, rapid hospitalization, and ECT can be lifesaving in acute emergencies, but there are limited data to suggest that any of them decrease suicide risk.4

In this article, we review psychopharmacological interventions that have been associated with suicide prevention in patients with major psychiatric illnesses.

Clozapine and other novel antipsychotics

The first FDA-approved medication with an antisuicide indication was clozapine for schizophrenia. The regulatory approval in 2003 was largely based on the International Suicide Prevention Trial (InterSePT), a remarkable randomized trial that compared clozapine with olanzapine in patients with schizophrenia and schizoaffective disorder who were at high risk for suicide.6 In that trial, suicidal behavior (measured by suicide attempts, hospitalizations, and rescue interventions) was significantly decreased in patients treated with clozapine.

The efficacy of other antipsychotic drugs in reducing suicide risk has not been adequately tested. However, some evidence suggests that olanzapine may reduce suicidal ideation when given in combination with a mood-stabilizing agent in patients with bipolar I disorder mixed-episode.7

Quetiapine (300 to 600 mg) may help prevent suicide in patients with bipolar depression.8,9 When compared with lithium and paroxetine, quetiapine (600 mg) was associated with a statistically significant reduction in suicidal ideation (as measured by the Montgomery-Asberg Depression Rating Scale [MADRS]).10,11 Quetiapine may reduce suicidal ideation and may be considered for patients with other diagnoses for which clozapine cannot or should not be used.


In 1986, Jamison12 prophetically stated:

One of the most interesting questions in preventive medicine today is the impact of lithium on suicide rates. There are no systematic data available at this time [about its efficacy], although it can be hoped that a well-documented answer will be possible within the next 10 years. Until then, we must rely upon preliminary speculations and clinical observations.

Just a decade later, the first scientific evidence convincingly supported a suicide risk–reducing effect of long-term treatment of bipolar and other manic-depressive disorders with lithium.13,14

A recent meta-analysis of data on long-term lithium treatment in bipolar disorder or a mix of major mood disorders supported a marked reduction (5-fold, or approximately 80%) in risk of suicide attempts and of completed suicides.15 Interestingly, the researchers also found that the proportion of suicide attempts relative to completed suicides during treatment with lithium was more than 2-fold higher, which suggests reduced lethality of suicidal behavior. The evident beneficial effects of lithium in reducing mortality from suicide are all the more remarkable in light of its potentially lethal toxicity in acute overdoses.

What is already known about pharmacotherapy interventions for reducing suicidality?

? Robust treatment of the underlying psychiatric illness has been the most effective antisuicide approach.

What new information does this article provide?

? Clozapine appears to be useful in decreasing suicide risk in persons with schizophrenia; lithium appears effective for suicidal bipolar patients.

What are the implications for psychiatric practice?

? SSRIs are useful in the treatment of suicidal depressed patients. However, patients should be carefully monitored, especially adolescents who receive these agents.



Evidence that antidepressant treatment decreases suicide risk or suicide attempts is mixed. It is often based on data from correlative or “ecological,” pharmacoepidemiological studies that compare suicide rates by regions or years with concurrent rates of prescriptions for antidepressant drugs.16 There have been moderate decreases in overall suicide rates, varying by sex and age-groups, in some Nordic countries and in the US since the 1990s; these decreases are possibly associated with the emergence of the modern, less toxic antidepressants that now dominate current clinical practice.17,18 Data from observational studies indicate that SSRIs may be associated with a reduced risk of suicide in adults with depression, while their use may increase suicidality in adolescents.19


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