Behavioural outcomes of antidepressant treatment

Mood and anxiety disorders are some of the biggest contributors to morbidity worldwide, and may be lethal. Appropriate treatment is therefore paramount and antidepressants is the first choice of pharmacological treatment for these disorders, with selective serotonin reuptake inhibitors (SSRIs) as the most common type in the Western world.

There is concern that SSRI treatment may increase the risk for severe behavioral outcomes, such as violence and suicide, especially among young people. However, mood and anxiety disorders are in themselves risk factors for these outcomes.

The aim of a new thesis by Tyra Lagerberg, Ph.D. student at the Department of Medical Epidemiology and Biostatistics, is therefore to contribute to the understanding of the risks and benefits of treatment with SSRIs in relation to severe behavioral outcomes in different age groups, including when SSRIs are combined with other central nervous system (CNS) drugs.

Tyra has also documented antidepressant prescription patterns in young individuals—the age group where the balance between benefits and risks of antidepressant treatment is least clear. The studies show an increasing prevalence of antidepressant use and polypharmacy of antidepressants with other CNS drugs in young individuals resident in Sweden. The studies also show associations between SSRI use and violent crime and suicidal behavior. The findings will hopefully help guide future research and clinical decision-making.

What are the most important result in your thesis?

We confirmed that the risk for violent crime and suicidal behavior outcomes is elevated during SSRI treatment across age groups (up to 60 years). However, it is unclear how far confounding by indication explains these results (that is, how far the disorders that SSRIs are prescribed for cause the association). This was highlighted by one of our studies, which found that the risk of suicidal behavior was highest in the month immediately prior to SSRI initiation, and then declined over treatment time.

We also documented the increasing prevalence of co-medication of other CNS drug classes with antidepressants in children, adolescents, and young adults. This is important to investigate further, given the lack of guidelines on the appropriateness of combining SSRIs with other drugs. In a screening study, we identified several drugs which were associated with reduced risk of suicidal behavior when initiated during SSRI treatment, and which could be investigated further to assess whether—and if so under what circumstances—they are appropriate to add to SSRI treatment.

Why did you choose to study this particular area?

Antidepressants in general and SSRIs in particular are common prescription drugs, meaning it is important to study their risks and benefits. They are, in turn, developed to treat common and sometimes hugely debilitating diseases. However, debate remains about how safe and efficacious SSRIs are, and I hoped to be able to contribute to the knowledge base with this Ph.D. It should be emphasized that we have not found definitive answers, and the debate around these medications will continue.