Selective serotonin reuptake inhibitors (SSRIs) are associated with an increased risk of committing a violent crime, an effect that may linger up to 12 weeks after treatment discontinuation, new research suggests. However, investigators say the finding should be interpreted with caution.
A large population-based study of more than 800,000 individuals showed those taking these antidepressants had an overall 2.7% increased risk of committing a violent crime while on the medications compared with when they were not taking them.
The increased risk persisted up to 12 weeks after discontinuing SSRIs and then returned to pretreatment levels. The risk was highest in younger individuals and those with a history of a prior violent crime.
"Our findings should be interpreted with caution [because] we do not know how far the association between SSRI medication and violent crime reflect causation," lead author Tyra Lagerberg, MSc, a PhD candidate at Karolinska Institute, Sweden, told Medscape Medical News.
"Our findings should not be used as grounds for individuals to go off their [SSRI] medication or for clinicians to withhold medication from those who might benefit from it," Lagerberg said.
The study was published online May 29 in European Neuropsychopharmacology.
Previous Concerns
There has been "apprehension" about a possible association between SSRIs and elevated risk of aggression and violence, especially in young people, but it "remains unclear" if there is a similar risk in middle-aged and older adults, the authors note. Moreover, it is unclear whether the risk of violence varies with time after initiating and discontinuing SSRI treatment.
To assess how the risk of violent crime might vary by age and time after SSRI treatment initiation and discontinuation, the researchers calculated absolute rates of violent crime per 1000 person-years during on- and off-treatment periods and also conducted within-group analyses.
The cohort, which was derived from several Swedish national registers, included all individuals in Sweden prescribed an SSRI between January 1, 2006, and December 31, 2013 (n = 785,337, 64.2% female) over an average follow-up of 7.3 years.
Some of the covariates used in the analyses included age, recent or previous violent crime, use of non-SSRI medications, sex, family income, education, county of residence, birth country, and lifetime diagnoses.
"Rare" Effect
Almost the entire study cohort (99%) changed their SSRI treatment over the follow-up period. During this time, of the full study cohort, 2.7% committed violent crimes (21,203 crimes in 5,707,293 person-years).
More men than women were convicted of a violent crime (5.7% vs 1.0%, respectively).
Absolute rates of violent crime were lower in treated versus nontreated periods across all age categories (other than those between 15 and 24 years) when covariates were not taken into account.
However, when hazards during the on- and off-treatment periods were compared and adjusted for covariables, SSRI treatment was associated with a "modest increased" risk of violent crime (HR, 1.10) — particularly in those ages 15-25 years and ages 25–34 years (HR, 1.19 and 1.16, respectively).
Moreover, further analysis stratifying the cohort according to previous violent crime revealed that the elevated risk for violent crime convictions "seemed to be confined to the individuals with previous criminality," compared to those with no criminal history (HR, 1.13 vs 1.07).
The within-individual analysis included 2.6% of the overall cohort who experienced SSRI treatment switching as well as ≥ 1 violent event.
These individuals differed from the overall cohort in that they tended to be younger (close to half were aged 15-24 years compared with one quarter in the overall cohort) and predominantly male (77% vs 36%, respectively).
When the hazard of violent crime was compared between individuals' periods on and off medication, there was a significantly increased hazard during treatment in the whole cohort (HR, 1.26), but in particular, in those aged 25-34 years and 35-44 years (HR, 1.35 and 1.15, respectively).
The within-individual HRs remained elevated for up to 12 weeks post-discontinuation of the SSRI (HR 1.37 during the first 28 days, and HR 1.20 during days 29-84). Although women had a significantly elevated on-treatment hazard in the youngest age category, they had a lower incidence of crime across ages.
Treatment with benzodiazepines was associated with a significantly higher hazard of violent crime and treatment with non-SSRI antidepressants was associated with a "modest but nonsignificantly elevated" hazard.
By contrast, treatment with other psychotropic drugs was not associated with elevated risk.
Warn Patients
Commenting on the study for Medscape Medical News, Eduard Vieta, MD, PhD, professor of psychiatry, Institute of Neuroscience, University of Barcelona, Spain, and author of an accompanying editorial, said it's still not known if the mediating factor in the increased risk of violent crime was the SSRI or the underlying mental condition that prompted the prescription.
Vieta, who was not involved with the study, added that the results "raise a note of caution in terms of making a very accurate diagnosis and treatment in patients with a history of conviction, violence, or criminality, and opting ideally for psychosocial therapies whenever possible in this population."
Also commenting on the study for Medscape Medical News, Michael Thase, MD, professor of psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, said the findings are "not easy to brush away or explain away."
Thase, who was not involved with the study, continued, "although it is a small finding, it is also a serious problem."
He suggested the risk should be treated in a similar way to the risk for suicidal thoughts or behaviors.
"Just as you might caution patients [initiating treatment with SSRIs] regarding that risk, you might broaden your counsel to include other types of violent behavior because the same process that provokes the risk of self-harm for a given person may be externalized and provoke harm or violence toward others."
Lagerberg added that further research is needed to confirm their findings and "inform whether — and if so, how — clinical practice should change."
The study was supported by the Swedish Research Council, Horizon 2020 ACTION project, Stockholm County Council, and Thurings Foundation. Lagerberg has reported no relevant financial relationships. Other author disclosures are listed in the article. Vieta and coauthors have reported no relevant financial relationships. Thase has reported consulting with and receiving research funding from many of the companies that manufacture/sell antidepressants.
Eur Psychopharmacol. Published online May 29, 2020. Full text, Editorial
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