A cohort study following over 17,000 South Koreans living with Attention Deficit Hyperactivity Disorder (ADHD) has found that selective serotonin reuptake inhibitors (SSRIs) widely prescribed for anxiety and or depression are safe for people taking methylphenidate.
Methylphenidate is the active ingredient in Ritalin and Concerta. Until now, little safety data regarding mixing the two drugs has been available, leaving some professionals reluctant to prescribe SSRIs to ADHD patients suffering with depression.
ADHD and Depression
A 2009 survey of the data in the British journal of Psychiatry, estimated that around 2.5% of adults live with ADHD. This developmental condition has wide-reaching effects on a patient’s quality of life as day-to-day activities can be difficult to navigate.
It’s not surprising then, that depression is a pretty commonly reported comorbidity. In fact, US researchers revealed in 2006 that adults living with ADHD are three times more likely to suffer from major depressive disorder than the general population. Certain types of antidepressants such as tricyclic antidepressants (for example Elavil, or Amitriptyline), and monoamine oxidase inhibitors (MAOIs) should not be prescribed alongside common ADHD medications containing methylphenidate.
Some data has also shown that stimulants, such as methylphenidate, can slow down metabolism of SSRIs resulting in higher levels of the antidepressant than intended in a patient’s blood stream. This has led to, perhaps reasonable, hesitation by doctors when it comes to prescribing SSRIs alongside methylphenidate.
Safety Testing SSRIs
The study, published October 9th this year in JAMA Network Open gives the green light to psychiatrists to prescribe SSRI based antidepressants to adults using methylphenidate to manage their ADHD.
Doctors found that taking the two drugs together did not cause any more negative outcomes than using methylphenidate based drugs alone, with the pleasant surprise that people who took both seemed to suffer less from head aches.
Searching the Record
The Ajou University Medical Center, South Korea, based research team collected South Korea – wide insurance data for 17, 234 adults with ADHD, between January 2016 and February 2021.
After identifying all the records of patients suffering both ADHD and depression, they excluded individuals who had been prescribed non-methylphenidate based ADHD medications or had been using stimulant based ADHD drugs for less than a year. This left the researchers with four subgroups.
Patients who had never used antidepressants, patients who were taking an SSRI (fluoxetine, escitalopram, sertraline, and paroxetine) and methylphenidate, methylphenidate plus fluoxetine, and methylphenidate plus escitalopram.
Searching for Side Effects
The team hunted through the records of each patient checking to see whether they had experienced any one of seventeen negative neuropsychiatric outcomes including: Abnormal gait, ADHD, agitation, anorexia, anxiety, appetite loss, delirium, dizziness, dystonia, eating disorder epilepsy, extrapyramidal symptoms, Gambling, Insomnia, Mania, Parkinsonism, Schizophrenia related hospitalization, seizures, sleep disorder, substance abuse, Suicidal event, tremor, psychosis.
They also checked for other safety-related events including: Abdominal pain, Accident, Acute respiratory failure, Anemia, Arrhythmia, Asthma, Atrial fibrillation, Bleeding, Cardiomyopathy, Cerebrovascular disease, Chronic kidney disease, Diarrhoea, Essential hypertension, Fatigue, Fever, Gynaecomastia, Headache, Heart failure, Hyperlipidaemia, Hyperprolactinemia, Hypo/hyperthyroidism, Hyponatraemia, Hypotension Ischaemic heart disease, Liver disease, Myocardial infarction, Myocarditis, Nasopharyngitis,
Nausea and vomiting, Obesity, Osteoporosis, Thrombocytopenia, Traumatic injury, Type II diabetes mellitus, Upper respiratory tract infection or pneumonia.
Researchers carefully matched 9873 patients prescribed both SSRIs and methylphenidate and 7361 people using methylphenidate only, based on shared characteristics such as age, sex, ethnicity, comorbidities and other medications they consumed. This allowed them to limit the differences between the two groups as much as possible, leaving whether or not they used an SSRI based drug the most important difference.
Headaches and high blood pressure
The researchers found few statistically significant differences in the likelihood that a person would experience any of the negative outcomes, other than the headache measure. In this case, they found a small reduction in the number of headaches reported in patients who took SSRIs with their ADHD meds versus just ADHD meds. They found a very small decrease in the incidence of tremors in men who added SSRIs to their stimulants and women were slightly more likely to have hypertension if they used escitalopram vs. fluoxetine with their ADHD meds.
Overall this data indicates that there is very little difference in negative outcomes between taking a methylphenidate based medicine alone and taking an SSRI along with it. With SSRIs bringing a small risk of increasing hypertension or increasing blood lipid levels, doctors might recommend patients monitor their blood pressure.
Safety First
The authors themselves remark that they were surprised by the result as they had expected there to be quite large differences. They do acknowledge that their study design didn’t allow them to distinguish severity of symptoms experienced, or their underlying ADHD and depressive symptoms. As with all studies, follow-ups will be needed to validate these results and it’s always wise to monitor for adverse outcomes when prescribing two drugs that may interact.
Powell V, Agha SS, Jones RB, et al. ADHD in adults with recurrent depression. Journal of Affective Disorders. 2021;295:1153. doi:10.1016/j.jad.2021.09.010
Simon V, Czobor P, Bálint S, Mészáros A, Bitter I. Prevalence and correlates of adult attention-deficit hyperactivity disorder: meta-analysis. Br J Psychiatry. 2009;194(3):204-211. doi:10.1192/bjp.bp.107.048827
Kessler RC, Adler L, Barkley R, et al. The prevalence and correlates of adult ADHD in the United States: Results from the National Comorbidity Survey Replication. The American journal of psychiatry. 2006;163(4):716. doi:10.1176/appi.ajp.163.4.716
Lee DY, Kim C, Shin Y, Park RW. Combined Methylphenidate and Selective Serotonin Reuptake Inhibitors in Adults With Attention-Deficit/Hyperactivity Disorder. JAMA Network Open. 2024;7(10):e2438398. doi:10.1001/jamanetworkopen.2024.38398
