A large new study found that antidepressant side effects vary significantly by drug, with some medications causing weight loss and others weight gain, and notable differences in heart rate and blood pressure. People experiencing persistent, severe, or concerning side effects should speak with a healthcare professional.
Researchers published the study on October 21 in The Lancet, analyzing more than 58,000 participants within the first eight weeks of starting treatment. They reviewed 151 studies of 30 drugs commonly used to treat depression. While not everyone develops side effects, common findings included changes in weight, blood pressure, and metabolic markers.
Differences between medications were striking. An eight-week course of agomelatine was associated with average weight loss of around 2.4 kg (about 5.3 lbs), while maprotiline users gained nearly 2 kg in the same timeframe. Heart function changes were notable: fluvoxamine tended to slow heart rate, whereas nortriptyline increased it, creating a gap of about 21 beats per minute between the two drugs. Blood pressure also varied, with an 11 mmHg difference between nortriptyline and doxepin.
What to know about antidepressant side effects
Sharon Batista, MD, assistant clinical professor of psychiatry at Mount Sinai Hospital, noted that psychiatrists have long known different antidepressants affect weight, blood pressure, and metabolic measures differently. What this study adds is rigorous, comparative quantification across many physiological parameters using data from over 58,000 people.
Common antidepressant side effects may include:
– Gastrointestinal symptoms (nausea, diarrhea, constipation)
– Sexual dysfunction (decreased libido, anorgasmia)
– Weight changes (gain or loss, depending on the agent)
– Sleep disturbances (insomnia or sedation)
– Dry mouth, sweating, headache
Less common but clinically significant side effects can include:
– Increases in blood pressure or heart rate (notably with SNRIs and some tricyclics)
– Hyponatremia (especially in older adults with SSRIs and SNRIs)
– Liver enzyme elevations
– QTc prolongation (risk of arrhythmia, especially with citalopram and some tricyclics)
– Emotional blunting or apathy
Whitley Lassen, PsyD, MBA, clinical psychologist and head of operations at Willow Behavioral Health, emphasized that different classes of antidepressants produce different adverse effects and that individuals vary in response depending on drug, dose, metabolism, and co-occurring conditions. Some side effects like changes in sleep, appetite, or energy are common and may improve over time, while others may be less typical or more persistent.
When to consider changing medication
Side effects range in severity, and changes in medication may be warranted if side effects are persistent or intolerable and don’t improve with time or supportive measures. Switching may also be needed if new medical issues arise that could be worsened by the medication (for example, hypertension, arrhythmia, or significant weight gain).
Talk with your doctor if there’s no meaningful improvement in depressive or anxiety symptoms after an adequate trial—typically 4–8 weeks at a therapeutic dose. Patient preferences matter; some people may choose to avoid sexual dysfunction or weight gain.
Red-flag side effects that suggest urgent evaluation or medication change include:
– New or worsening suicidal thoughts, especially early in treatment or after dose changes
– Signs of serotonin syndrome (confusion, agitation, fever, muscle rigidity)
– Significant, unexplained weight gain or loss
– Marked increases in blood pressure or heart rate
– Severe allergic reactions (rash, swelling, difficulty breathing)
– Jaundice or dark urine (possible liver injury)
– Hyponatremia symptoms (confusion, seizures, severe headache)
If you experience thoughts of harming yourself or others or serious suicidal thoughts, seek immediate help.
Managing side effects
Side effects are expected with any medication. Strategies to manage them include adjusting dose timing—taking sedating antidepressants at night and activating ones in the morning—to help with sleep-related effects. Regular monitoring of weight, blood pressure, and metabolic labs is helpful. Maintaining a balanced diet, regular exercise, hydration, fiber-rich foods, and good sleep hygiene can mitigate weight and gastrointestinal effects. Reducing caffeine and screen time before bed can help with insomnia.
For psychological side effects such as emotional blunting or apathy, collaborative care with a therapist or counselor can support coping and adherence. Working with mental health professionals can help address symptoms and support treatment.
Shared decision-making
Switching antidepressants should be a collaborative decision with your clinician, weighing benefits against side effects to determine the best approach for recovery. Clinicians consider symptom targets, co-occurring medical conditions, family history of medication response, drug interactions, and side effect profiles. Patient input about goals, past medication experiences, and concerns helps ensure a tailored, acceptable treatment plan.
