Molero, 2015 Selective Serotonin Reuptake Inhibitors and Violent Crime: A Cohort Study

[Vonnegutjunky]

PLoS Med 12(9): e1001875. doi:10.1371/journal.pmed.1001875

Selective Serotonin Reuptake Inhibitors and Violent Crime: A Cohort Study.

Molero Y, Lichtenstein P, Zetterqvist J, Gumpert CH, Fazel S (2015)

 

Abstract and free full text at http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1001875

Background

Although selective serotonin reuptake inhibitors (SSRIs) are widely prescribed, associations with violence are uncertain.

Methods and Findings

From Swedish national registers we extracted information on 856,493 individuals who were prescribed SSRIs, and subsequent violent crimes during 2006 through 2009. We used stratified Cox regression analyses to compare the rate of violent crime while individuals were prescribed these medications with the rate in the same individuals while not receiving medication. Adjustments were made for other psychotropic medications. Information on all medications was extracted from the Swedish Prescribed Drug Register, with complete national data on all dispensed medications. Information on violent crime convictions was extracted from the Swedish national crime register. Using within-individual models, there was an overall association between SSRIs and violent crime convictions (hazard ratio

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= 1.19, 95% CI 1.08–1.32, p < 0.001, absolute risk = 1.0%). With age stratification, there was a significant association between SSRIs and violent crime convictions for individuals aged 15 to 24 y (HR = 1.43, 95% CI 1.19–1.73, p < 0.001, absolute risk = 3.0%). However, there were no significant associations in those aged 25–34 y (HR = 1.20, 95% CI 0.95–1.52, p = 0.125, absolute risk = 1.6%), in those aged 35–44 y (HR = 1.06, 95% CI 0.83–1.35, p = 0.666, absolute risk = 1.2%), or in those aged 45 y or older (HR = 1.07, 95% CI 0.84–1.35, p = 0.594, absolute risk = 0.3%). Associations in those aged 15 to 24 y were also found for violent crime arrests with preliminary investigations (HR = 1.28, 95% CI 1.16–1.41, p < 0.001), non-violent crime convictions (HR = 1.22, 95% CI 1.10–1.34, p < 0.001), non-violent crime arrests (HR = 1.13, 95% CI 1.07–1.20, p < 0.001), non-fatal injuries from accidents (HR = 1.29, 95% CI 1.22–1.36, p < 0.001), and emergency inpatient or outpatient treatment for alcohol intoxication or misuse (HR = 1.98, 95% CI 1.76–2.21, p < 0.001). With age and sex stratification, there was a significant association between SSRIs and violent crime convictions for males aged 15 to 24 y (HR = 1.40, 95% CI 1.13–1.73, p = 0.002) and females aged 15 to 24 y (HR = 1.75, 95% CI 1.08–2.84, p = 0.023). However, there were no significant associations in those aged 25 y or older. One important limitation is that we were unable to fully account for time-varying factors.

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Conclusions

The association between SSRIs and violent crime convictions and violent crime arrests varied by age group. The increased risk we found in young people needs validation in other studies.

Editors' Summary

Background

Antidepressants—drugs that treat depression (unbearable feelings of sadness and despair caused by changes in brain chemistry)—are widely prescribed in many countries. In the US, for example, about one in ten people over 12 years old take antidepressants. The first antidepressants—monoamine oxidase inhibitors and tricyclic antidepressants—were developed in the 1950s. Experts think that both these classes of drugs treat depression by increasing serotonin levels in the brain. Serotonin, which is thought to improve mood, emotion, and sleep, is a neurotransmitter, a chemical that carries messages between nerve cells. However, monoamine oxidase inhibitors and tricyclic antidepressants had many adverse side effects unrelated to their effects on serotonin levels. So, in the late 1980s, a new class of antidepressant drugs was launched known as selective serotonin reuptake inhibitors (SSRIs). After serotonin delivers a message between nerve cells, it is usually reabsorbed by the nerve cells. Fluoxetine (Prozac), paroxetine (Seroxat), and other SSRIs block this “reuptake,” thereby increasing serotonin levels in the brain.

Why Was This Study Done?

SSRIs (which are also used to treat several other mental health conditions) have fewer side effects than the older antidepressants, although they can cause headache, nausea, sleep problems, restlessness, and sexual problems. However, SSRIs are not recommended for use in people under the age of 18 years because there is some evidence that SSRIs increase the risk of self-harm and suicidal thoughts in this age group. Moreover, there is limited and inconclusive evidence linking SSRI use with violent behavior. Because SSRIs are widely prescribed, it is important to clarify this latter issue. In this cohort study—an observational study that follows a group of individuals who are identical with the exception of exposure to a specific factor to determine whether exposure to that factor increases the likelihood of a specific outcome—the researchers investigate the association between violent crime and SSRIs in Sweden.

What Did the Researchers Do and Find?

The researchers extracted information on SSRIs prescribed in Sweden between 2006 and 2009 from the Swedish Prescribed Drug Register and information on convictions for violent crimes for the same period from the Swedish national crime register. They then compared the rate of violent crime while individuals were prescribed SSRIs with the rate of violent crime in the same individuals while not receiving medication. This “within-individual” design accounts for time-invariant factors such as genetic and early environmental factors that might otherwise lead to confounding. In observational studies, participants exposed to a specific factor can also share another unknown characteristic (confounder) that is actually responsible for the outcome of interest. During the study period, about 850,000 individuals (10.8% of the Swedish population) were prescribed SSRIs, and 1% of these individuals were convicted of a violent crime. Using within-individual statistical models, there was a significant but modest overall association (an association unlikely to have occurred by chance) between SSRIs and convictions for violent crime. After adjustment for age, the association between SSRIs and convictions for violent crimes remained significant for individuals (males and females combined or males and females considered separately) aged 15 to 24 years but became non-significant among older individuals.

What Do These Findings Mean?

These findings show an association between SSRIs and violent crime that varies by age group. They cannot, however, prove that taking SSRIs actually causes an increase in violent crime among young people because the analytical approach used does not fully account for time-varying risk factors such as symptom severity or alcohol misuse that might affect an individual’s risk of committing a violent crime (residual confounding). In addition, some people who committed a violent crime might have subsequently taken SSRIs to cope with the anxiety and stress of arrest (reverse causation). The lack of a significant association between SSRIs and violent crime among most people taking SSRIs is reassuring; the association between violent crimes and SSRIs among individuals younger than 25 years is worrying. However, this finding needs confirming in studies with other designs undertaken in other settings. If confirmed, warnings about the increased risk of violent behavior among young people when being treated with SSRIs might be needed. But, note the researchers, it might be inappropriate to restrict the use of SSRIs in this age group because increases in adverse outcomes associated with poorly treated depression, such as suicide, might outweigh the public health benefit accruing from decreases in violence.

Additional Information.

This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1​001875.

The UK National Health Service Choices website provides information about depression (including personal stories) and about SSRIs; a “behind the headlines” article discusses a research article on recent increases in the use of SSRIs across Europe
The UK Royal College of Psychiatrists provides leaflets on depression and on antidepressants
Mind, a UK noMind, a UK not-for-profit organization, also provides information about depression (including personal stories) and about antidepressants
The US National Institute of Mental Health provides information about depression and about antidepressant medications for children and adolescents
MedlinePlus provides links to additional resources about depression and antidepressants
Citation: Molero Y, Lichtenstein P, Zetterqvist J, Gumpert CH, Fazel S (2015) Selective Serotonin Reuptake Inhibitors and Violent Crime: A Cohort Study. PLoS Med 12(9): e1001875. doi:10.1371/journal.pmed.1001875

Academic Editor: Alexander C. Tsai, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America

Received: March 31, 2015; Accepted: August 5, 2015; Published: September 15, 2015

Copyright: © 2015 Molero et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Data Availability: All relevant data are within the paper and its Supporting Information files.

Funding: SF is supported by the Wellcome Trust [095806]. YM and CHG are supported by Karolinska Institutet. JZ and PL are supported by grants from the Swedish Research Council. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: SF has received travelling expenses from Janssen to attend a Janssen-organized conference on the effectiveness of antipsychotics where he presented a Wellcome-funded study on antipsychotics that had been published in the Lancet (Janssen do not currently produce an antidepressant). The speaker's fee was donated to charity. None of the other authors report competing interests.

Abbreviations: DDD, defined daily dose;HR, hazard ratio;SSRI, selective serotonin reuptake inhibitor

Edited September 20, 2015 by Altostrata
formatted for Journals

[Laura1981]

Background

 

Antidepressants—drugs that treat depression (unbearable feelings of sadness and despair caused by changes in brain chemistry)—are widely prescribed in many countries. 

 

Ouch... even the critical studies are clinging to the chemical imbalance theory?

[Altostrata]

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