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

Walsh, Marie Therese; Dinan, Timothy G.

doi:10.1034/j.1600-0447.2001.00357.x

Cited by 92 publications

(33 citation statements)

References 28 publications

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“…This conclusion was supported by mouse knockout studies of the 5-HT transporter (3), and by other studies in which mice received selective 5-HT reuptake inhibitors (SSRIs), which mitigate aggression in psychiatric patients (13,14) and reduce SI-induced aggression in mice (5,6). …”

mentioning

confidence: 83%

In socially isolated mice, the reversal of brain allopregnanolone down-regulation mediates the anti-aggressive action of fluoxetine

Pinna¹,

Dong²,

Matsumoto³

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

205

236

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Social isolation (SI) of male mice lasting >4 weeks is associated with aggression toward intruders and a down-regulation of brain allopregnanolone (Allo) content. SI of female mice fails to downregulate brain Allo content or to induce aggressiveness. Fluoxetine (Prozac in clinical use) is an S-and R-fluoxetine (FLX) mixture, which in mammals is metabolized into S-and R-norfluoxetine (NFLX). The S isomers of FLX and NFLX are more active than their respective R isomers in normalizing brain Allo down-regulation and in reducing the aggressiveness induced by SI. Thus, FLX stereospecifically reduces brain Allo down-regulation and the aggressiveness induced by SI, whereas serotonin (5-HT) uptake inhibition lacks stereospecificity. The doses of S-FLX and S-NFLX that reduce aggressiveness and Allo brain content down-regulation induced by SI are at least one order of magnitude lower than the doses that block 5-HT reuptake. Doses of imipramine that inhibit 5-HT uptake neither reduce aggressiveness nor normalize brain Allo downregulation. We conclude that Allo brain content normalization is a better candidate than 5-HT reuptake inhibition to explain the reduction of aggressiveness elicited by S-FLX and S-NFLX.A ggressive behavior and violence are included in the phenotypic expression of several central nervous system disorders (i.e., schizophrenia, premenstrual dysphoria, major manicdepressive illness, posttraumatic stress disorder, and epilepsy).Human and animal studies suggest that often a genetic component contributes to aggressive behavior. For example, the altered transcription of genes encoding for various serotonin (5-HT) receptor subtypes or for the 5-HT transporter has been implicated in the pathophysiology of violence and aggression in humans and other mammals (1-3). However, a Mendelian inheritance of these 5-HT neurotransmission dysregulations could not be demonstrated (4). Probably, epigenetic factors contribute to aggressive behavior.Social isolation (SI) of male mice for Ͼ4 weeks causes a syndrome characterized by anxiety, decreased susceptibility to barbiturates and other ␥-aminobutyric acid (GABA)mimetic drugs, and frequent severe attacks against an intruder mouse (5, 6). Socially isolated (SI) male mice also show a marked decrease of Allo brain content (5, 7) and a down-regulation of serotonergic neurotransmission (8-10).Valzelli and his coinvestigators (11) pioneered studies of SI-induced aggression in mice and concluded that this aggressiveness involves an impairment of 5-HT neurotransmission (11,12). This conclusion was supported by mouse knockout studies of the 5-HT transporter (3), and by other studies in which mice received selective 5-HT reuptake inhibitors (SSRIs), which mitigate aggression in psychiatric patients (13,14) and reduce SI-induced aggression in mice (5, 6).In patients with major depression, the allopregnanolone (Allo) content of cerebrospinal fluid (CSF) is reduced, and this reduction is reversed by appropriate treatment with fluoxetine (FLX) or fluvoxamine (15). Interestingly, in depr...

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mentioning

confidence: 83%

In socially isolated mice, the reversal of brain allopregnanolone down-regulation mediates the anti-aggressive action of fluoxetine

Pinna¹,

Dong²,

Matsumoto³

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

205

236

View full text Add to dashboard Cite

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“…In spite of these reports the chance of violence (suicide, homicide) being brought about by the use of anti-depressants must be considered to be extremely small [11][12][13][14]. But this does not necessarily mean that this relationship is negligibly small in individual cases.…”

Section: Ssris and Violencementioning

confidence: 99%

Aspects of Causality: A Verdict Inquiry of a Case with SSRI Use

Brouwers¹,

Loonen²,

Nielen³

et al. 2014

JHS

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Sometimes more than one expert advises the court. They use different notional frameworks in doing so, and may report different opinions about the case they examined. In this case, the authors discuss the relation between the use of a SSRI (serotonin reuptake inhibitor) and a fatal tragedy in a family where the mother was accused of killing her husband and daughter a few days after use of the SSRI. No fewer than seven experts were heard (four behavioral experts, one behavioral toxicologist, one pharmacist and one pharmacologist) at the ensuing trial, and various possible diagnoses were dealt with in the experts' reports and at trial. More attention must be paid to the mentally debilitating influence of SSRI medication on certain psychological functions shortly after its intake. Although a mono-causal relationship between that influence and the accused's intention is necessary to exculpate the accused from guilt, the authors believe that a singular connection is never happened in the case.

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“…For example, impulsive violence has been linked to seratonergic abnormalities in patient 24 , criminal 25 and healthy community populations 26 . Accordingly, SSRIs have been tried as a treatment for aggressive behavior, and found to be helpful 27 . For example, in three double-blind studies, fluoxetine (compared against placebo) reduced aggression in patients with personality disorder 25,28,29 .…”

Section: Court-ordered Cns Interventionmentioning

confidence: 99%