Intro

Antidepressants can meaningfully affect weight, blood pressure (BP), heart rate (HR), lipids, glucose, and liver enzymes. These effects vary by drug and class, and matter most for people with obesity, hypertension, diabetes risk, dyslipidemia, or cardiovascular disease.

Short-term randomized trials show wide physiological spreads between agents, even when antidepressant efficacy is similar.

Key Points

Short-term trials show about 4 kg spread in weight change, ~20 bpm spread in heart rate, and ~11 mmHg spread in systolic BP across antidepressants.
SNRIs (venlafaxine, desvenlafaxine, duloxetine, levomilnacipran): tend to raise BP and cholesterol; duloxetine also shows small increases in glucose and AST/ALT.
TCAs (amitriptyline, imipramine, maprotiline): tend to raise HR, BP, and weight.
Agomelatine, fluoxetine, and bupropion: generally more favorable short-term weight profiles.
QTc prolongation and hyponatremia are uncommon in short RCTs, but real-world risk rises in older, multimorbid populations.

Evidence Summary (Network Meta-Analysis)

Source: Pillinger et al., The Lancet (2025)
Data: 151 RCTs · ~58,500 participants · 30 antidepressants

Key findings

SNRIs increase BP and cholesterol; duloxetine shows small increases in glucose and liver enzymes.
TCAs increase heart rate, blood pressure, and weight.
Agomelatine, fluoxetine, and bupropion are associated with less weight gain or modest short-term weight loss.
Short-term trials show minimal QTc and sodium signal, which may underestimate real-world risk.

Options by Clinical Profile

Metabolic risk (obesity, type 2 diabetes, dyslipidemia)

Prefer

Agomelatine
Fluoxetine
Bupropion

Avoid when possible

Mirtazapine
TCAs
High-dose SNRIs

Hypertension or cardiovascular disease

Avoid or monitor closely:

Venlafaxine
Desvenlafaxine
Duloxetine
Levomilnacipran
TCAs

Weight-gain sensitivity

Higher risk:

Mirtazapine
Amitriptyline
Maprotiline

Lower risk:

Bupropion
Fluoxetine
Agomelatine

Older adults / polypharmacy

Start low, titrate slowly.
Consider baseline and follow-up sodium and QTc when risk factors exist.

Monitoring (First 8–12 Weeks)

Baseline → Week 4 → Week 8: weight, waist circumference, BP, HR.
Labs (if risk present):
- Fasting lipids and glucose (especially with SNRIs or metabolic risk).
- Liver enzymes (especially duloxetine / desvenlafaxine / levomilnacipran or hepatic history).
Electrolytes (Na⁺) and ECG (QTc) for older adults or those on diuretics / QT-prolonging drugs.

Generic → Trade Names (Quick Map)

SSRIs:
Fluoxetine (Prozac), Sertraline (Zoloft), Paroxetine (Paxil), Citalopram (Celexa), Escitalopram (Lexapro), Fluvoxamine (Luvox)

SNRIs:
Venlafaxine (Effexor), Desvenlafaxine (Pristiq), Duloxetine (Cymbalta), Levomilnacipran (Fetzima)

Atypical:
Bupropion (Wellbutrin), Agomelatine (Valdoxan), Mirtazapine (Remeron)

TCAs:
Amitriptyline (Elavil), Nortriptyline (Pamelor), Imipramine (Tofranil), Doxepin (Sinequan), Maprotiline (Ludiomil)

FAQ

Do SSRIs behave the same physiologically?
No. Paroxetine tends to have more lipid/weight effects; fluoxetine, sertraline, and escitalopram are more neutral short-term.

If weight falls early, will it stay down?
Not reliably. Longer observational cohorts often show net weight gain with chronic use.

Are QTc or sodium problems common?
Not in short-term RCTs, but registry data in older or multimorbid patients shows increased risk — monitor when indicated.

Antidepressant Side-Effects: Cardiometabolic & Physiological Guide