Dual methylphenidate with SSRI use appears safe among adults with ADHD, depression

Key takeaways:

• Results showed no significant increase in adverse event risk with use of SSRI plus methylphenidate in adults with ADHD and depression.
• Risk of headache was lower with combined SSRI and methylphenidate use.

The combined use of selective serotonin reuptake inhibitors and methylphenidate did not significantly increase adverse event risk among adults with ADHD and comorbid depression, according to a study published in JAMA Network Open.

Previous studies have suggested that depression often coexists with ADHD among adults, leading researchers to question any potential interactions between stimulant medication and SSRIs and, because the former are known to increase the plasma concentration of the latter, according to researchers.

“There is a lack of large-scale safety research on the combined use of methylphenidate and SSRIs despite the high rate of comorbid depression in adult ADHD,” Dong Yun Lee, MD, PhD candidate in the department of biomedical informatics at Ajou University School of Medicine in Suwon, South Korea, and colleagues wrote.

This motivated the researchers to perform a retrospective observational cohort study to investigate the safety of concordant usage of SSRIs — including fluoxetine, escitalopram, sertraline and paroxetine — and methylphenidate among 17,234 adults aged 18 years or older (mean age at study entry, 29.4 years ± 10.8 years; 52.7% women) with a diagnosis of ADHD and depressive disorder.

The researchers obtained patient data from the Health Insurance Review and Assessment Service, a nationwide claims database in South Korea, from January 2016 to February 2021. They assessed 17 primary and secondary adverse outcomes with respiratory tract infection used as control.

Four study groups were created; first, the SSRI plus methylphenidate (SSRI; n = 9,873) group vs. methylphenidate-only group (n = 7,361). The SSRI group was then further categorized into the methylphenidate plus fluoxetine (fluoxetine; n = 2,791) group vs. methylphenidate plus escitalopram (escitalopram; n = 5,150) group.

Researchers then matched 5,181 pairs using propensity score analysis, with a median follow-up of 88 days for the SSRI group and 51 days for the methylphenidate-only group.

The researchers found that outcome risk did not significantly differ between the SSRI and methylphenidate-only group, except regarding the risk for headache. The SSRI group had a lower risk for headache compared with the methylphenidate-only group (14 vs. 19 cases; HR = 0.5; 95% CI, 0.24-0.99), which was confirmed by sensitivity analysis.

Further, there were no statistically significant differences in outcome risks between different SSRI types, including for tic disorder, which researchers said had been noted in previous trials of adolescents (fluoxetine, 22 cases vs. escitalopram, 25 cases; HR = 0.9; 95% CI, 0.5-1.6).

Lee and colleagues also found significant differences in hypertension and hyperlipidemia between the fluoxetine and escitalopram groups, according to sensitivity analyses that modified the PS methods to one to maximum matching. This analysis specifically showed the risk for hypertension (HR = 0.26; 95% CI, 0.08-0.67) and hyperlipidemia (HR = 0.23; 95% CI, 0.04-0.81) were lower in the fluoxetine group compared with the escitalopram group.

The researchers noted several limitations to this study, including limited availability of data on socioeconomic status and disease severity, small sample size and short follow-up period.

“The findings of this study suggest that combining SSRI and methylphenidate is not associated with increased risk of adverse events in adults with ADHD and comorbid depression,” Lee and colleagues wrote.

Additional research with larger datasets is necessary to verify these results, they added.