Use of Central Nervous System Drugs in Combination with Selective Serotonin Reuptake Treatment: A Bayesian Screening Study for Risk of Suicidal Behavior

Sunday, August 28, 2022

8:45 AM – 9:00 AM CEST

Location: C1M0

Publication Number: 225

Background: Concurrent use of selective serotonin reuptake inhibitors (SSRIs) and other central nervous system (CNS) medications is common. However, evidence regarding the efficacy and risk of such co-medication is limited, especially for suicidal outcomes.

Objectives: We sought to evaluate the impact of adding another non-SSRI CNS drug during SSRI treatment on the risk of suicidal behavior, in a data-driven screening approach.

Methods: We used data from linkage of Swedish national registers and identified a national cohort of SSRI users aged 6-59 years residing in Sweden during 2006-2013. We used a two-stage Bayesian Poisson model to estimate the incidence rate ratio (IRR) of suicidal behavior in periods up to 90 days before and after another non-SSRI CNS drug initiation during SSRI treatment, while accounting for multiple testing. For comparison, and to assess whether there were interactions between SSRIs and other CNS drugs, we also estimated the IRR of initiating the CNS drug without SSRI treatment.

Results: We identified 53 common non-SSRI CNS drugs initiated during SSRI treatment, dispensed to 262,721 individuals. We found 20 CNS drugs with statistically significant IRRs during any SSRI treatment. Of these, only two showed a greater risk of suicidal behavior after versus before initiating a CNS drug (alprazolam, IRR=1.39, 95% CrI=1.13, 1.71; flunitrazepam, IRR=1.83, 95% CrI=1.11, 3.07). Those with the greatest reduction in risk after initiation were disulfiram, naltrexone, and acamprosate (IRR range 0.49-0.52). We did not find evidence of harmful interactions between SSRIs and the selected CNS drugs.

Conclusions: Several of the detected signals for reduced risk correspond to drugs where there is previous evidence of benefit for antidepressant augmentation (e.g. olanzapine, quetiapine, lithium, buspirone, and mirtazapine). Novel signals of reduced suicidal behavior risk, including lamotrigine, valproic acid, risperidone, and melatonin, when using in addition to SSRIs, warrant further investigation.

Presenting Author(s)

Zheng Chang

Principal researcher
Karolinska Institutet
Solna, Stockholms l�n, Sweden

Slides

Co-Author(s)

TL

Tyra Lagerberg

Karolinska Institutet, Sweden
AS

Arvid Sjölander

Karolinska Institutet, Sweden
RG

Robert Gibbons

University of Chicago, United States
PQ

Patrick Quinn

Indiana University, United States
BD

Brian D'Onofrio

Indiana University, United States
CH

Clara Hellner

Karolinska Institutet, Sweden
PL

Paul Lichtenstein

Karolinska Institutet, Sweden
SF

Seena Fazel

University of Oxford, United Kingdom