Quick Read
- A large analysis compared side effects of 30 antidepressants across 58,000 patients.
- Weight change varied up to 4 kg between drugs—some caused gain, others loss.
- Heart rate and blood pressure shifts differed significantly by medication.
- SSRIs generally have fewer physical side effects than older drugs.
- Researchers call for personalized prescribing and updated guidelines.
How Physical Side Effects of Antidepressants Vary: The New Evidence
Antidepressants have become one of the most widely prescribed classes of medication worldwide, offering relief for millions struggling with depression and anxiety. But a new, comprehensive study led by researchers at King’s College London and the University of Oxford has brought fresh clarity to a question often overlooked in routine medical practice: how do side effects differ between the many types of antidepressants?
Drawing on data from 151 clinical trials and 17 FDA reports, covering more than 58,000 participants and 30 distinct antidepressants, the researchers uncovered a landscape marked by significant variation. The findings, published in The Lancet and highlighted by Pulse Today, The Guardian, and The Seattle Times, suggest that the physical impact of these drugs—particularly on weight, blood pressure, and heart rate—can be anything but uniform.
Weight Change: A Key Concern for Many Patients
Perhaps the most striking difference uncovered relates to body weight. Some antidepressants, such as maprotiline and amitriptyline, were associated with notable weight gain, affecting nearly half of those prescribed. On the other hand, drugs like agomelatine were linked to weight loss in over half of patients. The spread between these two extremes is substantial: up to a 4 kg (nearly 9 lbs) difference in average weight change over just eight weeks.
For patients and clinicians, this means the choice of medication can have a direct and immediate effect on physical health, beyond the intended mental health outcomes. While some may welcome weight loss, for others, unintended weight gain can become a significant concern, influencing self-esteem and overall wellbeing.
Cardiovascular Effects: Heart Rate and Blood Pressure Shifts
Beyond weight, the study found notable differences in cardiovascular side effects. Heart rate shifts ranged from an 8 BPM decrease with fluvoxamine to a 14 BPM increase with nortriptyline—a difference of 20 beats per minute. Blood pressure changes, too, varied: nortriptyline was linked to a 7 mmHg drop, while doxepin caused a 5 mmHg rise. Though not life-threatening for most, these changes are clinically relevant, particularly for patients with underlying cardiac or hypertensive conditions.
Dr. Toby Pillinger, lead researcher and consultant psychiatrist at South London and Maudsley NHS Foundation Trust, emphasized the importance of these findings: “While many people benefit from antidepressants, these drugs are not identical—some can lead to meaningful changes in weight, heart rate, and blood pressure in a relatively short period.”
SSRIs: A Reassuring Profile, but Not Free of Side Effects
Selective serotonin reuptake inhibitors (SSRIs) remain the most commonly prescribed type of antidepressant, both in the UK and the US. The good news for many is that SSRIs tend to have fewer pronounced physical side effects than older classes of drugs. As Dr. Pillinger noted, “Our findings show that SSRIs… tend to have fewer physical side effects, which is reassuring. But for others, closer physical health monitoring may be warranted.”
Nevertheless, the absence of major cardiovascular or metabolic effects does not mean SSRIs are free of side effects. Patients may still experience other issues, such as sexual dysfunction, sleep disturbances, or emotional blunting, which were outside the scope of the current analysis.
Personalized Prescribing: Why Individual Differences Matter
The study’s authors argue that their findings should prompt a shift toward more personalized prescribing. Rather than a one-size-fits-all approach, treatment decisions ought to be made collaboratively between doctor and patient, considering not only mental health needs but also physical health, lifestyle, and personal values.
Professor Andrea Cipriani, psychiatrist at the University of Oxford, put it plainly: “Our results emphasize the importance of shared decision making… bringing together [patients’] preferences, personal circumstances, goals, values, and beliefs. This should be the way forward in the NHS and globally.”
Regular medication reviews, as recommended by Professor Kamila Hawthorne of the Royal College of General Practitioners, are essential. These check-ins help determine whether the chosen treatment remains optimal, whether side effects are tolerable, and whether adjustments—like dose reduction or switching drugs—might be warranted. Lifestyle factors, too, can influence how antidepressants work over time.
Long-Term Effects: Still an Open Question
It’s important to note that the study focused on the first eight weeks of antidepressant use. Whether these physical side effects persist, diminish, or intensify over longer periods remains unclear. The researchers called for further investigation to better understand the long-term impact of these drugs on metabolic and cardiovascular health.
In the meantime, the advice is clear: decisions about antidepressant use should always be made on an individual basis, weighing potential benefits against risks and side effects, and guided by ongoing communication between patient and clinician.
Implications for Practice and Policy
With millions relying on antidepressants for mental health support, the study’s findings are likely to reverberate through clinical guidelines and patient care protocols. Calls have already been made to update treatment recommendations to reflect the varying physical side effects among different drugs.
Ultimately, these insights empower both patients and clinicians to make more informed choices, reducing the risk of unexpected health issues and supporting better overall outcomes. As Dr. Pillinger concluded, “The aim isn’t to deter use, but to empower patients and clinicians to make informed choices and to encourage personalized care.”
Assessment: This landmark analysis underscores a fundamental truth in medicine: not all antidepressants are created equal when it comes to physical side effects. By mapping out these differences in detail, the research gives patients and clinicians the tools they need for safer, more tailored treatment. The next step is clear—integrate these insights into everyday practice, ensuring that mental health care is both effective and holistic.