Selective serotonin reuptake inhibitors and violence: a review of the available evidence

OBJECTIVE To provide a clinically useful analysis of the relationship between selective serotonin reuptake inhibitors (SSRIs), in particular fluoxetine and violent or suicidal behaviour. METHOD All published papers on Medline and other databases linking serotonin, SSRIs and aggression were reviewed. RESULTS A small proportion of patients treated with SSRIs may become akathisic and others may show increases in anxiety in the initial phase of treatment, but no increased susceptibility to aggression or suicidality can be connected with fluoxetine or any other SSRI. In fact SSRI treatment may reduce aggression, probably due to positive effects on the serotonergic dysfunction that is implicated in aggressive behaviour directed towards oneself or others. CONCLUSION In the absence of convincing evidence to link SSRIs causally to violence and suicide, the recent lay media reports are potentially dangerous, unnecessarily increasing the concerns of depressed patients who are prescribed antidepressants.

[1]  J. Korf,et al.  5-Hydroxyindoleacetic Acid Levels in the Cerebrospinal Fluid of Depressive Patients treated with Probenecid , 1970, Nature.

[2]  M. Åsberg,et al.  5-HIAA in the cerebrospinal fluid. A biochemical suicide predictor? , 1976, Archives of general psychiatry.

[3]  M. Dubocovich,et al.  High-affinity [3H]imipramine binding in rat hypothalamus: association with uptake of serotonin but not of norepinephrine. , 1980, Science.

[4]  M. Briley,et al.  High-affinity binding of 3H-imipramine in brain and platelets and its relevance to the biochemistry of affective disorders. , 1981, Life sciences.

[5]  M. Åsberg,et al.  Monoamine metabolites in CSF and suicidal behavior. , 1981, Archives of general psychiatry.

[6]  J. Mann,et al.  INCREASED SEROTONIN-2 BINDING SITES IN FRONTAL CORTEX OF SUICIDE VICTIMS , 1983, The Lancet.

[7]  G. Tedeschi,et al.  Prolactin secretion in man: a useful tool to evaluate the activity of drugs on central 5-hydroxytryptaminergic neurones. Studies with fenfluramine. , 1983, British journal of clinical pharmacology.

[8]  H. Meltzer,et al.  Effect of 5-hydroxytryptophan on serum cortisol levels in major affective disorders. III. Effect of antidepressants and lithium carbonate. , 1984, Archives of general psychiatry.

[9]  Postmortem serotonergic and adrenergic receptor binding to frontal cortex: correlations with suicide. , 1986, Psychopharmacology bulletin.

[10]  M. Linnoila,et al.  Suicidal behavior, impulsiveness and serotonin , 1988, Acta psychiatrica Scandinavica.

[11]  The benefits and risks of 5-HT uptake inhibitors in depression. , 1988, The British journal of psychiatry. Supplement.

[12]  L. Siever,et al.  Serotonergic studies in patients with affective and personality disorders. Correlates with suicidal and impulsive aggressive behavior. , 1989, Archives of general psychiatry.

[13]  N. K. Popova,et al.  Behavior, adrenocortical activity, and brain monoamines in Norway rats selected for reduced aggressiveness towards man , 1989, Pharmacology Biochemistry and Behavior.

[14]  E. Coccaro,et al.  Fluoxetine treatment of impulsive aggression in DSM-III-R personality disorder patients. , 1990, Journal of clinical psychopharmacology.

[15]  N. K. Popova,et al.  Evidence for the involvement of central serotonin in mechanism of domestication of silver foxes , 1991, Pharmacology Biochemistry and Behavior.

[16]  C. Beasley,et al.  Fluoxetine and suicide: a meta-analysis of controlled trials of treatment for depression. , 1991, BMJ.

[17]  E. Coccaro,et al.  Fluoxetine Not Associated With Increased Violence or Aggression in Controlled Clinical Trials , 1992 .

[18]  C. Beasley,et al.  Fluoxetine and suicide : a meta-analysis of controlled trials of treatment for depression , 1992 .

[19]  R. Kahn,et al.  Functional interrelationship of serotonin and norepinephrine: Cortisol response to MCPP and DMI in patients with panic disorder, patients with depression, and normal control subjects , 1992, Psychiatry Research.

[20]  Marc Laruelle,et al.  SPECT imaging of dopamine and serotonin transporters with [123I]β‐CIT: Pharmacological characterization of brain uptake in nonhuman primates , 1993, Synapse.

[21]  M. Fava,et al.  Anger attacks in unipolar depression, Part 1: Clinical correlates and response to fluoxetine treatment. , 1993, The American journal of psychiatry.

[22]  J. Fawcett,et al.  Evaluation of suicidality during pharmacologic treatment of mood and nonmood disorders. , 1993, Annals of clinical psychiatry : official journal of the American Academy of Clinical Psychiatrists.

[23]  G. Enas,et al.  Absence of a relationship between adverse events and suicidality during pharmacotherapy for depression. , 1994, Journal of clinical psychopharmacology.

[24]  L. Siever,et al.  Familial correlates of reduced central serotonergic system function in patients with personality disorders. , 1994, Archives of general psychiatry.

[25]  C. Sánchez,et al.  Isolation-induced aggression in mice: effects of 5-hydroxytryptamine uptake inhibitors and involvement of postsynaptic 5-HT1A receptors. , 1994, European journal of pharmacology.

[26]  M. Linnoila,et al.  Low CSF 5-HIAA concentrations and severe aggression and impaired impulse control in nonhuman primates. , 1994, The American journal of psychiatry.

[27]  R. Pies,et al.  Self-injurious behavior: pathophysiology and implications for treatment. , 1995, The Journal of clinical psychiatry.

[28]  R. Hen,et al.  Serotonin receptors and animal models of aggressive behavior. , 1995, Pharmacopsychiatry.

[29]  H. Jick,et al.  Antidepressants and suicide , 1995, BMJ.

[30]  M. Keller,et al.  The relationship between fluoxetine use and suicidal behavior in 654 subjects with anxiety disorders. , 1996, The Journal of clinical psychiatry.

[31]  L. Siever,et al.  Impulsivity and serotonergic function in compulsive personality disorder. , 1996, The Journal of neuropsychiatry and clinical neurosciences.

[32]  M. Fava,et al.  Fluoxetine treatment of anger attacks: a replication study. , 1996, Annals of clinical psychiatry : official journal of the American Academy of Clinical Psychiatrists.

[33]  Fluoxetine in the treatment of anger: an open clinical trial. , 1996, The Journal of clinical psychiatry.

[34]  S. Kasper,et al.  Risk of suicide in depression and its implication for psychopharmacological treatment , 1996, International clinical psychopharmacology.

[35]  M. Fava,et al.  Hostility changes following antidepressant treatment: relationship to stress and negative thinking. , 1996, Journal of psychiatric research.

[36]  C. McDougle,et al.  Neurobiology of Tryptophan Depletion in Depression: Effects of m-Chlorophenylpiperazine (mCPP) , 1997, Neuropsychopharmacology.

[37]  L. Siever,et al.  Serotonin function in human subjects: intercorrelations among central 5-HT indices and aggressiveness , 1997, Psychiatry Research.

[38]  E. Coccaro,et al.  Fluoxetine and impulsive aggressive behavior in personality-disordered subjects. , 1997, Archives of general psychiatry.

[39]  M. Linnoila,et al.  Low Central Nervous System Serotonergic Activity Is Traitlike and Correlates with Impulsive Behavior , 1997, Annals of the New York Academy of Sciences.

[40]  R. Mann,et al.  A comparison of fluvoxamine, fluoxetine, sertraline and paroxetine examined by observational cohort studies , 1997, Pharmacoepidemiology and drug safety.

[41]  C. Caley,et al.  Extrapyramidal Reactions and the Selective Serotonin-Reuptake Inhibitors , 1997, The Annals of pharmacotherapy.

[42]  R. Saunders,et al.  In vivo association between alcohol intoxication, aggression, and serotonin transporter availability in nonhuman primates. , 1998, The American journal of psychiatry.

[43]  A. Papassotiropoulos,et al.  Upregulation of the Platelet Serotonin2A Receptor and Low Blood Serotonin in Suicidal Psychiatric Patients , 1998, Neuropsychobiology.

[44]  H. V. van Praag Anxiety and increased aggression as pacemakers of depression. , 1998, Acta psychiatrica Scandinavica. Supplementum.

[45]  L. Lynd,et al.  Selective Serotonin-Reuptake Inhibitor–Induced Movement Disorders , 1998, The Annals of pharmacotherapy.

[46]  M. Fava,et al.  Anger attacks in depressed outpatients and their response to fluoxetine , 1998, European Psychiatry.

[47]  L. Siever,et al.  Hostility is associated with a heightened prolactin response to meta-chlorophenylpiperazine in abstinent cocaine addicts , 1998, Psychiatry Research.

[48]  N. K. Popova,et al.  Specific [3H]8-OH-DPAT Binding in Brain Regions of Rats Genetically Predisposed to Various Defense Behavior Strategies , 1998, Pharmacology Biochemistry and Behavior.

[49]  D. Healy,et al.  Suicide in the course of the treatment of depression , 1999, Journal of psychopharmacology.

[50]  W. Coryell,et al.  Prospective study of fluoxetine treatment and suicidal behavior in affectively ill subjects. , 1999, The American journal of psychiatry.

[51]  R. Hen,et al.  Altered Emotional States in Knockout Mice Lacking 5-HT1A or 5-HT1B Receptors , 1999, Neuropsychopharmacology.

[52]  J. Mann,et al.  Association of aggressive behavior with altered serotonergic function in patients who are not suicidal. , 2000, The American journal of psychiatry.