ADHD and Depression: Is it Safe to Combine Methylphenidate and SSRIs?

Co-use of methylphenidate and selective serotonin reuptake inhibitors (SSRIs) for the treatment of attention-deficit/hyperactivity disorder (ADHD) and depression has a similar safety profile as methylphenidate monotherapy, according to study results published in JAMA Network Open.

Although comorbid depression is highly prevalent among individuals with ADHD, there are limited data about the interaction between stimulant medications and SSRIs to guide patient care for adults with comorbid ADHD and depression.

Investigators from Ajou University School of Medicine conducted this retrospective observational study using data from the Health Insurance Review and Assessment Service (HIRA) database which houses nationwide medical claims from South Korea. Patients (N=17,234) with ADHD and depression who initiated methylphenidate between 2016 and 2021 were evaluated for adverse events on the basis of SSRI concomitant use. Patients who used methylphenidate alone (n=5181) were matched with those who used methylphenidate and SSRIs (n=5181). The SSRI group was further stratified, and those who used methylphenidate with fluoxetine (n=2577) were matched with those who used methylphenidate and escitalopram (n=2577).

The methylphenidate alone, SSRI, fluoxetine, and escitalopram groups comprised 50.8%, 51.1%, 60.3%, and 60.3% women; 85.8%, 86.1%, 87.3%, and 87.2% were aged 18 to 39 years; and the average initial dose of methylphenidate was 17.7, 17.8, 17.6, and 16.3 mg, respectively.

Patients who took methylphenidate alone or in combination with SSRIs had similar risk for all adverse outcomes, with the exception that patients who took SSRIs were at lower risk for headache (hazard ratio [HR], 0.50; 95% CI, 0.24-0.99).

No risk differences for any outcomes were observed between the fluoxetine and escitalopram cohorts.

When stratified by patient gender, men with concomitant SSRI use were at lower risk for tremor compared with men who took methylphenidate alone (HR, 0.23; 95% CI, 0.05-0.77), whereas women with concomitant SSRI use were at lower risk for headache (HR, 0.35; 95% CI, 0.14-0.83) and higher risk for hypertension (HR, 3.24; 95% CI, 1.31-9.73) than women who took methylphenidate alone. Further, women who took fluoxetine were at lower risk for hypertension than women who took escitalopram (HR, 0.31; 95% CI, 0.09-0.88).

In sensitivity analyses, the reduced risk for headache with concomitant SSRI use was replicated in most analyses. In the fluoxetine and escitalopram comparisons, significant group differences in hypertension and hyperlipidemia were observed in analyses that used different matching approaches.

“In this cohort study of adults with ADHD, there was no significant increase in risks of adverse events associated with use of the combination of SSRI plus methylphenidate vs methylphenidate alone in adults with ADHD and comorbid depression,” the investigators concluded.

This study may have been limited by the lack of data regarding disease severity.

Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

This article originally appeared on Psychiatry Advisor