Antidepressants and Violence: Problems at the Interface of Medicine and Law

Healy, David; Herxheimer, Andrew; Menkes, David B.

doi:10.1371/journal.pmed.0030372

Cited by 69 publications

(60 citation statements)

References 25 publications

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“…14 Given the FDA's statement about the rate of suicide attempts, 14 we wanted to determine whether duloxetine increased the risk of suicidality, violence or their possible precursors (drug-induced akathisia, an extreme type of restlessness; activation, which consists of stimulating effects such as insomnia, anxiety and agitation; emotional disturbance, such as depersonalization and derealization; or psychotic events, such as delusions and hallucinations) in the randomized phases of the trials. 15,16 We therefore assessed the benefits and harms of duloxetine in stress urinary incontinence using clinical study reports, including individual patient data, of the 4 main trials submitted to the EMA.…”

Section: Resultsmentioning

confidence: 99%

Considering benefits and harms of duloxetine for treatment of stress urinary incontinence: a meta-analysis of clinical study reports

Maund

Guski

Gøtzsche

2016

CMAJ

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The European Medicines Agency makes clinical study reports publicly available and publishes reasons for not approving applications for marketing authorization. Duloxe tine has been approved in Europe for the treatment of stress urinary incontinence in women. The reported adverse effects of duloxe tine include mental health problems and suicidality. We obtained clinical study reports from the European Medicines Agency concerning use of this drug for stress urinary incontinence.

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Section: Resultsmentioning

confidence: 99%

Considering benefits and harms of duloxetine for treatment of stress urinary incontinence: a meta-analysis of clinical study reports

Maund

Guski

Gøtzsche

2016

CMAJ

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“…It included events both during treatment and in the subsequent withdrawal phase and found a doubling in hostility events (odds ratio 2.10, 95% confidence interval 1.27 to 3.48). 23 While it is now generally accepted that antidepressants increase the risk of suicide and violence in children and adolescents 5,12 (although many psychiatrists still deny this 10 ), most people believe that these drugs are not dangerous for adults. This is a potentially lethal misconception.…”

Section: Discussionmentioning

confidence: 99%

“…The authors, several of whom were employees of Eli Lilly or owned stock in the company, judged her suicide 'to be unrelated to study drug treatment', A15 although it is well known that the suicide risk is high when an antidepressant is stopped abruptly. 10,23 There was no more information about the suicide in the articles, and it was not included in the listing of adverse events we acquired from Eli Lilly, which only mentioned a woman who reported suicidal ideation twice while on placebo. As we do not know if this was the same patient, we asked Eli Lilly for access to anonymised data for the volunteer who committed suicide and the detailed person narrative, as we also wanted to know how it could be possible to state that the suicide was not related to duloxetine, but the company refused to give us the data.…”

Section: Discussionmentioning

confidence: 99%

Precursors to suicidality and violence on antidepressants: systematic review of trials in adult healthy volunteers

2016

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Objective: To quantify the risk of suicidality and violence when selective serotonin and serotonin-norepinephrine reuptake inhibitors are given to adult healthy volunteers with no signs of a mental disorder. Design: Systematic review and meta-analysis. Main outcome measure: Harms related to suicidality, hostility, activation events, psychotic events and mood disturbances. Setting: Published trials identified by searching PubMed and Embase and clinical study reports obtained from the European and UK drug regulators. Participants: Double-blind, placebo-controlled trials in adult healthy volunteers that reported on suicidality or violence or precursor events to suicidality or violence. Results: A total of 5787 publications were screened and 130 trials fulfilled our inclusion criteria. The trials were generally uninformative; 97 trials did not report the randomisation method, 75 trials did not report any discontinuations and 63 trials did not report any adverse events or lack thereof. Eleven of the 130 published trials and two of 29 clinical study reports we received from the regulatory agencies presented data for our meta-analysis. Treatment of adult healthy volunteers with antidepressants doubled their risk of harms related to suicidality and violence, odds ratio 1.85 (95% confidence interval 1.11 to 3.08, p ¼ 0.02, I2 ¼ 18%). The number needed to treat to harm one healthy person was 16 (95% confidence interval 8 to 100; Mantel-Haenszel risk difference 0.06). There can be little doubt that we underestimated the harms of antidepressants, as we only had access to the published articles for 11 of our 13 trials. Conclusions: Antidepressants double the occurrence of events in adult healthy volunteers that can lead to suicide and violence.

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“…Cotherapy might be considered at the start of fluoxetine treatment, especially for those with insomnia, and when a dose increase of fluoxetine is anticipated (Smith et al, 2002). SSRIs are reported to increase the risk of the suicidality (Walia, 2016c) and the main reason behind this is the development of the akathisia; that occurs frequently with the SSRIs treatment (Healy et al, 2006) and it may be one of the main causes of suicidality associate with the SSRIs therapy (Rothschild and Locke, 1991). Therefore to minimize the incidence of akathisisa, agitation and anxiety, benzodiazepines had been co-prescribed with SSRIs (Healy, 1999).…”

Section: Fstmentioning

confidence: 99%

GABAergic Influence in the Antidepressant Effect of Fluoxetine in Unstressed and Stressed Mice

2017

J App Pharma Sci

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Objective:To determine the influence of GABA in the antidepressant effect of fluoxetine in unstressed and stressed mice. Materials and methods: Male swiss albino mice were used in the present study. Mice were stressed by immobilization for 2h. Mice subjected to immobilization were considered as stressed mice and mice not subjected to immobilization were considered as unstressed mice. Depression like behavioral alterations in unstressed and stressed mice was measured by tail suspension test (TST) followed by forced swim test (FST). Results:The present study showed that the immobilization stress of 2h significantly enhanced the immobility period of mice in both TST and FST. Fluoxetine (FLX) (20 mg/kg, i.p.) significantly reduced the immobility period of both unstressed and stressed mice significantly as compared to their respective controls. Diazepam (DZP) (2 and 4 mg/kg, i.p.) significantly increased the immobility period of the unstressed mice whereas significantly reduced the immobility period of stressed mice in both TST and FST as compared to their respective controls. The combine treatment of DZP (2 mg/kg, i.p.) and FLX (20 mg/kg, i.p.) to the unstressed mice reduced the immobility period of unstressed mice in both TST and FST significantly as compared to the vehicle and DZP (2 mg/kg, i.p.) treated unstressed mice in TST. The co-administration of DZP (2 mg/kg, i.p.) and FLX (20 mg/kg, i.p.) before the immobilization of 2h significantly reduced the immobility period of stressed mice significantly as compared to the vehicle treated stressed mice in both TST and FST; whereas significantly as compared to the FLX (20 mg/kg, i.p.) treated stressed mice in TST only. Conclusion: It has been concluded that the GABAergic influence is involved in the compromised antidepressant effect of the fluoxetine in stressed mice.

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Antidepressants and Violence: Problems at the Interface of Medicine and Law

Abstract: David Healy and colleagues review several sources of data which suggest an association in a small number of cases between antidepressant treatment and aggression and violence.

Cited by 69 publications

References 25 publications

Considering benefits and harms of duloxetine for treatment of stress urinary incontinence: a meta-analysis of clinical study reports

Considering benefits and harms of duloxetine for treatment of stress urinary incontinence: a meta-analysis of clinical study reports

Precursors to suicidality and violence on antidepressants: systematic review of trials in adult healthy volunteers

GABAergic Influence in the Antidepressant Effect of Fluoxetine in Unstressed and Stressed Mice

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