“Our study is the first to quantify how much specific side effects — such as changes in weight, blood pressure, or heart rate — differ between each antidepressant,” says lead author Toby Pillinger, PhD, a psychiatrist and academic clinical lecturer at King’s College London. “This allows us to move from general assumptions to precise, drug-specific estimates.”
He adds that “no previous study had systematically compared individual antidepressants against one another.”
Overall, the research suggests that “not all antidepressants are built the same,” and have unique side effects, Pillinger says.
SSRIs Had Fewer Side Effects Compared With Older Drugs
The study analyzed data on 30 different antidepressants, using eight-week studies that included more 58,000 participants.
The results showed that physical side effects can differ substantially between antidepressants.
This is a “reassuring finding,” says Rehan Aziz, MD, a psychiatrist at Hackensack Meridian Jersey Shore University Medical Center in Neptune who was not involved with the research.
“SSRIs have long been the first-line treatment for depression because of their strong efficacy and generally mild side-effect profile, and this study reinforces that practice,” he says.
The analysis showed some older medications, such as those belonging to an antidepressant category called tricyclics, had more side effects:
- People taking the tricyclic antidepressant nortriptyline had a higher average resting heart rate (21 beats per minute higher) than people taking the SSRI Luvox (fluvoxamine).
- About half of people who took the tricyclic Amitid (amitriptyline) gained weight, while more than half lost weight taking Thymanax (agomelatine), which isn’t available in the United States.
Tricyclic antidepressants are used less widely today than SSRIs, Aziz says. These drugs, along with serotonin-norepinephrine reuptake inhibitors (SNRIs, sold under brand names including Effexor and Cybalta), are “typically reserved for patients who don’t respond to SSRIs, or who have co-occurring symptoms, like nerve pain, that those classes may better address.”
How the Study Can Help Patients and Doctors
Patients often try more than one antidepressant before finding the right fit, Dr. Aziz says.
This is often due to side effects and effectiveness, says Alex Dimitriu, MD, a psychiatrist, sleep medicine physician, and founder of Menlo Park Psychiatry and Sleep Medicine in California. Dr. Dimitriu was not involved with the study.
“Some people will benefit from some classes of antidepressants over others,” he says, adding that the new research provides “a single glance view of the clusters of side effects from various medications.”
Doctors typically start patients on lower doses, monitor side effects and effectiveness, and adjust the dose based on “response and tolerability,” says Owen Scott Muir, MD, a psychiatrist and chief medical officer at Radial, a psychiatric practice based in New York City, who was not involved with the research.
They may also switch patients to a different medication, if necessary, Aziz adds.
Pillinger says the new research will help doctors “move away from a one-size-fits-all approach to psychiatric prescribing; instead, we should be matching the antidepressant to the person, not the other way around.”
In conjunction with the study, Pillinger says his team developed a free digital tool for doctors and patients to use collaboratively. It offers personalized recommendations for patients based on the side effects they wish to avoid.
Having the capability to directly compare antidepressant side effects “lets patients have more control over their health and have a sense of what risks they might need to look out for in their treatment,” Dr. Muir says.
Researchers Continue to Study Side Effects
“We need to confirm that some of the side effects we observed in the short-term [after eight weeks] persist in the long term,” Pillinger explains. He says his team is working on this.
Ultimately, Aziz says patients should know that antidepressants are generally safe and effective. However, as with any medication, they can cause side effects that differ from person to person. While most side effects are mild, it’s vital to stay in regular contact with your healthcare team, who will make monitor your weight and blood pressure, evaluate the results of blood work, and take other steps to safeguard your health.
