To Örebro University

BACKGROUND AND AIMS: Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed medications for patients with anxiety/depression. These patients often have problems with substance use, but it remains unclear whether the risk of substance misuse is influenced by SSRI treatment. We aimed to determine whether SSRI treatment is associated with a decreased risk of acute substance misuse-related outcomes.

DESIGN: Cohort study following individuals through Swedish nationwide registers between July 2005 and December 2013 and comparing the risk of substance misuse outcomes during periods on- versus off-treatment within the same individual.

SETTING: Swedish general population.

PARTICIPANTS: Individuals with a new dispensed prescription of SSRIs between July 2006 and December 2013, and an ICD-10 diagnosis of anxiety/depressive disorder before the first treatment initiation. The cohort included 146,114 individuals (60.7% women).

MEASUREMENTS: Substance misuse outcomes included ICD-10 diagnoses of acute intoxications (F10.0-F19.0), accidental poisonings by alcohol or drugs (X41-X42, X45-X46), and substance-related criminal offenses.

FINDINGS: The absolute rate of substance misuse increased sharply before the onset of SSRI treatment and decreased after treatment initiation. Stratified Cox regression models showed an elevated risk (hazard ratio (HR)=1.70, 95% confidence interval (CI): 1.62-1.78) of substance misuse outcomes during a 1-month period preceding treatment initiation, compared with the reference period of more than 1 month before treatment start. The on-treatment estimates (1-30 days [HR=1.29, 95% CI: 1.23-1.37], 31-120 days [HR=1.30, 95% CI: 1.24-1.35], and >120 days [HR=1.24, 95% CI: 1.18-1.30] after treatment initiation) were consistently lower than the 1-month pre-treatment estimate, but still elevated compared with the reference period.

CONCLUSIONS: For people with anxiety/depression, the risk of substance misuse appears to be particularly elevated right before initiating selective serotonin reuptake inhibitor (SSRI) treatment, which may reflect the emergence or worsening of substance use problems concurrently with anxiety/depression. SSRI treatment appears to be associated with a lower risk of substance misuse compared with the 1-month period preceding treatment initiation, but causality remains uncertain.