SSRIs Linked to Violent Crime in Young People

Liam Davenport

September 24, 2015

The use of selective serotonin reuptake inhibitors (SSRIs) is associated with a significantly increased risk for violent crime among adolescents and young adults, new research shows.

Swedish researchers examined data from more than 850,000 individuals and found that SSRI use was linked to a 43% increased risk for violent crime among people aged 15 to 24 years. The association was not significant in older individuals.

"If our findings related to young people are validated in other designs, samples, and settings, warnings about an increased risk of violent behaviours while being treated with SSRIs may be needed," say the investigators, led by Seena Fazel, MD, professor, Department of Psychiatry, Warneford Hospital, University of Oxford, United Kingdom.

"Any such changes to the advice given to young persons prescribed SSRIs will need to be carefully considered, as the public health benefit from decreases in violence following restrictions in SSRI use may be countered by increases in other adverse outcomes (such as more disability, rehospitalisation, or suicides)."

However, the authors highlight the fact that a number of factors may explain the increased risk for violent crime with SSRI use in younger people, aside from any connection with the medication itself.

The study was published online September 15 in PLOS Medicine.

Uncertain Link

Dr Fazel explained that the study was undertaken because there was "quite a bit of uncertainty" over possible associations between SSRI use and violence.

"You have observational studies and also some syntheses of randomized controlled trial [RCT] data that pointed in different directions. The RCT data really reported outcomes such as hostility and aggression, and it's not clear whether that would translate into harder outcomes, such as violence," said Dr Fazel.

The team examined data on 856,493 individuals from the Swedish Prescribed Drug Register who had been prescribed SSRIs between 2006 and 2009. Data were also extracted from the Swedish national crime register and was matched to the prescription information.

Of the individuals studied, 9.9% were aged 15-24 years, 12.7% were aged 25-34 years, 16.5% were aged 35-44 years, 15.6% were aged 45-54 years, 15.5% were aged 55-64 years, and 29.7% were aged 65 years or older at baseline. The most commonly prescribed SSRI was citalopram (multiple brands), followed by sertraline (Zoloft, Pfizer Inc), escitalopram (Lexapro, Forest Laboratories, Inc), fluoxetine (multiple brands), paroxetine (multiple brands), and fluvoxamine (Luvox, Solvay/ANI Pharmaceuticals/Jazz).

During the study period, 8377 (1.0%) individuals were convicted of a violent crime. This compared with 40,384 (0.6%) convictions among 7,061,361 individuals from the general Swedish population aged 15 years or older in 2006.

Analysis revealed that there was an overall association between SSRI use and violent crime conviction, at a hazard ratio (HR) of 1.19 (P < .001; absolute risk, 1.0%).

On stratifying the individuals by age, a significant association was seen between use of SSRIs and convictions for violent crimes among those aged 15-24 years (HR, 1.43; P < .001; absolute risk, 3.0%).

The relationship between SSRI use and violent crime was not significant in individuals aged 24 years or older.

Among those aged 15-24 years, there were significant associations between SSRI use and arrests for violent crimes with preliminary investigations (HR = 1.28; P < .001), nonviolent crime convictions (HR = 1.22; P < .001), nonviolent crime arrests (HR = 1.13; P < .001), nonfatal injuries from accidents (HR = 1.29; P < .001), and emergency inpatient or outpatient treatment for alcohol intoxication or misuse (HR = 1.98; P < .001).

The researchers also found that the association between violent crime and SSRIs remained significant among individuals aged 15-24 years after analyzing the results with regard to sex (among males: HR, 1.40; P = .002; among females: HR, 1.75; P = .023).

Important Signal

Discussing the findings, Dr Fazel said that it is not possible from this study to pinpoint the mechanism underlying the link between SSRI use and violent crime in young people and adolescents.

"Ours was based on registry data, so we had the advantage of being able to study 850,000 people taking SSRIs, but it means the disadvantage is that we can't look in any detail and interview people face to face, which is obviously important to unpack some of these associations," he said.

Nevertheless, he added, looking at the wider body of literature, it could be that the same mechanism that leads to suicidal ideation and suicidal acts in young people could be linked to irritability and anxiety. Another factor could be young people withdrawing from medication.

"Our own view is that some evidence suggests that it's a bit more complicated than that, because we found a link with subtherapeutic doses of SSRIs, and that would suggest to us that it may be that it's actually a lack of treatment [and] it could be residual symptoms that are driving this link.

"We know that people present to their doctors and primary care with a range of symptoms, including hostility and irritability, and it may well be that those are not being fully treated.

"The third thing that we found in our data was that there was an increased association of alcohol intoxication and misuse. What could be happening is that particularly younger people, when they're taking these medications, feel a bit better, and maybe they start misusing alcohol, and it's the alcohol which is the problem and not the medication per se," he said.

The results also pointed to a connection between accidents and violent crime.

Although Dr Fazel does not think that the current results are enough to change clinical practice, he noted that a substantial proportion of young people are prescribed SSRIs for indications other than depression, including substance use, anxiety, and personality problems.

"It may well be that what's also important to examine is the pattern of prescribing of these medications in primary care."

Another issue is that of adherence, inasmuch as young people may not be using the medications correctly. "It may just be a case of people, if they followed the recommended dose and the recommended length of time that they take the medication, that this association would not be there."

"My view is that [the study] shouldn't, on its own, change practice. I think it needs to be triangulated with other forms of evidence, but it's an important signal that needs further work," said Dr Fazel.

A Good First Step

Georgia Hodes, PhD, assistant professor (pending) in neuroscience, Icahn School of Medicine at Mount Sinai, New York City, told Medscape Medical News that the findings are "really interesting."

She noted that a number of studies have indicated that antidepressants may have different effects in adolescents than in adults.

"When you're talking about adolescents, you're talking about a period when the brain is still developing, and none of these drugs were really tested on kids.

"We don't know that their brains really respond to them in the same way that the adult brain does, and certainly in the animal literature, there are studies going back to an early age, looking more in early development, that show that antidepressant treatment at those ages actually induces anxiety and depressionlike behavior in later life," said Dr Hodes.

"That said, this particular study is a good beginning, but it doesn't really prove that it's the antidepressants. In fact, there are a couple of different reasons that this might be occurring, and the authors are very good at talking about potential mechanisms of this and also the limitations of the present study."

She added that there is a "pretty strong body of literature" showing that low serotonin levels are linked to aggression, in particular, the serotonin metabolite 5-HIAA.

"There's been really interesting work done by J. D. Higley and others that have looked in nonhuman primates and have also shown a relationship between low levels of serotonin and impulsive behavior, violent behavior and aggression, and risk-taking behavior," she said.

This finding appears to be linked to alcohol intake, which the authors of the current study found to be correlated with antidepressant treatment.

"I think that that might really be the connection, especially since they mention that the people who were at greatest risk were taking SSRIs that had a very short half-life," said Dr Hodes.

She also observed that long-term use of SSRIs can reduce levels of 5-HIAA.

"I think that if you're going to look a biological reason as to why this particular group might be more prone towards violent behavior, I think probably they're right that it's likely that the faster metabolism of the adolescents, combined with these effects in the adolescent brain and the shorter half-life of the drug, [possibly] ended up triggering these violent responses," she said.

Dr Hodes believes that, taken together, the findings of the current and previous studies reinforce the idea that a different approach should be taken when managing adolescents with depression from that used in adults.

"We need to stop thinking of the brain as being the same at all ages, and this true for older people too," she said.

"We need to consider things like metabolism and development of the brain for children, obviously, and for adolescents. This is not an adult brain. It's still changing, and we need to think about how these chemicals are going to affect it."

Dr Hodes suggested that adolescent patients should be started on psychotherapy "and then move from there into treatment.

"Clearly the kids who are on these treatments need to be watched a little bit more closely than maybe adults are."

Dr Fazel and Dr Hodes report no relevant financial relationships.

PLoS Med. Published online September 15, 2015. Full text


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.