Antisuicide Properties of Psychotropic Drugs: A Critical Review

Abstract

The authors consider the extent to which psychotropic medications demonstrate benefits in the prevention of suicidal behavior in psychiatric patients. Results of a MedLine search are critically reviewed for lithium, divalproex and other anticonvulsants, conventional and atypical antipsychotics, and antidepressants. The existing literature is almost entirely limited to noncontrolled, often retrospective studies that do not control for potential biases in treatment selection, the use of multiple medications, the impact of medication nonadherence, and nonrandomized treatment discontinuations. Nevertheless, an extensive literature has arisen regarding observed reductions in suicidal behavior with lithium for mood disorders and, to a lesser extent, with clozapine for schizophrenia. A substantially smaller literature suggests more negative than positive data with divalproex or carbamazepine in bipolar disorder, while minimal information exists regarding suicidality with atypical antipsychotics other than clozapine. Studies of antidepressants have mostly been short-term and have focused more on whether they induce (rather than ameliorate) suicidal thoughts or behaviors. The sum of existing studies is generally inconclusive about whether antidepressants appreciably reduce risk for suicide completions. Relatively little is known about pharmacotherapy effects on suicidal ideation as distinct from behaviors. Possible mechanistic considerations for understanding antisuicide properties include a therapeutic impact on depression, impulsivity, or aggression, potentially mediated through serotonergic or other neuromodulatory systems. Recommendations are provided to guide future research as well as clinical practice.

Do Atypical Antipsychotics Have Antisuicidal Effects? A Hypothesis-Generating Overview

“…Risk of suicide appears to be greater among psychotic disorder patients who are younger, male, never married, with evidence of current or previous depression or substance abuse, as well as previous suicide attempts, and who have had relatively good premorbid functioning [8,10,11]. Evidence that older, typical neuroleptic drugs, alone or with antidepressants added, alter suicidal risks in schizophrenia patients, either favorably or unfavorably, is limited and inconsistent [8,12,13,14]. Risk of mortality due to natural causes, including sudden death presumably related to cardiac dysfunction, may be increased with older neuroleptics as well as with modern atypical or second-generation antipsychotics (SGAs) [15,16].…”

Lithium in the prevention of suicide in mood disorders: updated systematic review and meta-analysis

“…32 The antisuicidal effect estimated here is larger than the effect on mood episodes, 27 28 raising the possibility of a specific effect. 33 Possible mechanisms include an effect on aggression or impulsivity, both of which are associated with an increased risk of suicide. 32 34 Lithium may decrease aggression and possibly impulsivity, 35 which might mediate its antisuicidal effect.…”

Suicidal Behavior in the Older Patient with Schizophrenia

“…One review investigating the effects of first-generation antipsychotics on suicide rates demonstrated a modest advantage in patients with schizophrenia [102]. However, in considering this in the elderly, there is a concern of a higher rate of extrapyramidal, anticholinergic and sedating side effects which could arise with these agents in this population [103]. In studies examining individuals of all ages, extrapyramidal side effects have been associated with dysphoria, worsening subjective distress, agitation and suicidal behavior [104,105].…”

“…Ernst and Goldberg point out many of the methodological limitations of the investigations utilizing first-generation antipsychotic medications [103]. They state that many results appear to be confounded by retrospective study design, treatment assignments lacking randomization, recall bias, varying medication regimens and lack of control for comorbid psychiatric diagnoses.…”

“…Data on clozapine use in the elderly is limited. Furthermore the ‘Consensus Guidelines for the use of Antipsychotic Medication in the Elderly’ recommend caution when using clozapine in the elderly [103]. …”