Antidepressant drugs and the emergence of suicidal tendencies

Drug Saf. 1993 Mar;8(3):186-212. doi: 10.2165/00002018-199308030-00002.


Although antidepressant medications represent the cornerstone of treatment for patients with moderate to severe clinical depression, they also carry serious risks. There is evidence which suggests that antidepressants can, in rare instances, induce or exacerbate suicidal tendencies. Nine clinical mechanisms have been proposed through which this may occur. These are: (a) energizing depressed patients to act on pre-existing suicidal ideation; (b) paradoxically worsening depression; (c) inducing akathisia with associated self-destructive or aggressive impulses; (d) inducing panic attacks; (e) switching patients into manic or mixed states; (f) producing severe insomnia or interfering with sleep architecture; (g) inducing an organic obsessional state; (h) producing an organic personality disorder with borderline features; and (i) exacerbating or inducing electroencephalogram (EEG) or other neurological disturbances. Epidemiological and controlled studies also provide data on the association between antidepressant drugs and suicidal ideation, attempts and fatalities. These include studies which: (a) suggest that electroconvulsive therapy may be more effective than antidepressant drugs in reducing the frequency of suicide attempts; (b) indicate that antidepressants may differ in their capacity to reduce the frequency of suicide attempts; (c) find that more overdose attempts were made by patients receiving maprotiline than placebo; and (d) suggest that fluoxetine may be associated with a greater risk of inducing de novo suicidal ideation. Evidence suggests that antidepressants may vary by at least 15-fold in the number of fatal overdoses per million prescriptions. Estimated overdose proclivity rates were derived after adjusting the fatal toxicity data by the therapeutic index of the drug. These rates were very consistent between agents with the same pharmacological properties, and correlated well with known overdose risk rates for amitriptyline, mianserin and maprotiline. Estimated overdose proclivity rates suggest that the highly selective noradrenaline (norepinephrine) uptake inhibitors (desipramine, nortriptyline, maprotiline) may be associated with a greater risk for overdose than more mixed uptake inhibitors and monoamine oxidase inhibitors (MAOIs). Antidepressants are not uniformly neutral in regard to suicidal ideation and attempts. Data clearly demonstrate that antidepressants ameliorate suicidal ideation more effectively than placebo in patients with depression. Although antidepressants diminish suicidal ideation in many recipients, about as many patients experience worsening suicidal ideation on active medication as they do on placebo. Furthermore, at least as many patients attempted suicide on fluoxetine and tricyclic antidepressants as on placebo, and more patients attempted to overdose on maprotiline than placebo. These observations suggest that antidepressants may redistribute suicide risk, attenuating risk in some patients who respond well, while possible enhancing risk in others who respond more poorly.(ABSTRACT TRUNCATED AT 400 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Antidepressive Agents / adverse effects*
  • Depressive Disorder / complications
  • Depressive Disorder / drug therapy*
  • Drug Overdose
  • Electroencephalography / drug effects
  • Humans
  • Suicide / psychology*
  • Suicide / statistics & numerical data


  • Antidepressive Agents