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Safety of SSRIs & Methylphenidate Combo in ADHD

Among 17,234 adults with ADHD and depression, adding SSRIs to methylphenidate not only proved safe but cut the risk of headaches by 50%, according to a recent study

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Among 17,234 adults with ADHD and depression, the combination of SSRIs and methylphenidate did not increase the risk of adverse events and may reduce the risk of headaches, particularly in females, according to a recent study.

Researchers evaluated adults in South Korea using nationwide data from 2016 to 2021 to assess the safety of combining selective serotonin reuptake inhibitors (SSRIs) with methylphenidate in those with comorbid ADHD and depression. The mean age of participants was 29.4 years (SD 10.8), and 52.7% were female. Participants were divided into four groups: methylphenidate only, SSRIs plus methylphenidate, methylphenidate plus fluoxetine, and methylphenidate plus escitalopram.

Seventeen primary and secondary outcomes were measured, including neuropsychiatric events like anxiety disorder and ADHD-related hospitalization, as well as cardiovascular outcomes such as hypertension. The study used propensity score matching to balance confounders and performed subgroup analyses based on sex.

The study, published in JAMA Network Open, found no significant increase in the risk of adverse events in the SSRI plus methylphenidate group compared to the methylphenidate-only group. Notably, females in the combination group experienced a significantly lower risk of headaches (hazard ratio [HR], 0.35; 95% confidence interval [CI], 0.14-0.83). Males showed a reduced risk of tremor (HR, 0.23; 95% CI, 0.05-0.77).

In a comparison between fluoxetine and escitalopram, fluoxetine was associated with a lower risk of hypertension (HR, 0.26; 95% CI, 0.08-0.67) and hyperlipidemia (HR, 0.23; 95% CI, 0.04-0.81), but no significant differences were found in the risk of neuropsychiatric events.

Sensitivity analyses further supported the reduced risk of headaches in the SSRI group, particularly among females. The study concluded that the combination of SSRIs and methylphenidate is safe in adults with ADHD and comorbid depression and may offer protective benefits against headaches and tremors, depending on sex.

Full disclosures can be found in the published study.