Mental Health

Antidepressant Side-Effects: Cardiometabolic & Physiological Guide

2025-10-23

Intro

Antidepressants can shift weight, blood pressure (BP), heart rate (HR), lipids/glucose, and liver enzymes — and the pattern differs by drug/class. Short-term RCTs show meaningful spreads in these parameters across agents, which matters for people with obesity, hypertension, diabetes risk, or dyslipidemia.

Key Points

• Expect ≈4 kg spread in short-term weight change, ~20 bpm spread in HR, ~11 mmHg spread in systolic BP across agents.
• SNRIs (venlafaxine, desvenlafaxine, duloxetine, levomilnacipran): ↑ BP and cholesterol; duloxetine → ↑ glucose and small ↑ AST/ALT.
• TCAs (amitriptyline, imipramine, maprotiline): ↑ HR/BP and weight.
• Agomelatine, fluoxetine, bupropion: more favorable weight profiles short-term.
• Minimal QTc/sodium signal in RCTs; real-world risk rises in older, multimorbid adults.

Options by Clinical Profile

• Metabolic risk (obesity, T2D, dyslipidemia): prefer Agomelatine, Fluoxetine, Bupropion.
• Hypertension/CVD: avoid agents with BP/HR rises (Venlafaxine / Desvenlafaxine / Duloxetine, Levomilnacipran, many TCAs).
• Weight gain concern: avoid Mirtazapine, Amitriptyline, Maprotiline.
• Older adults/polypharmacy: start low, go slow; consider Na⁺ and QTc monitoring even if RCT signal is minimal.

Monitoring (first 8–12 weeks)

• Baseline → week 4 → week 8: weight/waist, BP, HR.
• Labs: fasting lipids & glucose (SNRIs or metabolic risk); LFTs (duloxetine/desvenlafaxine/levomilnacipran or hepatic history).
• Electrolytes (Na⁺) and ECG (QTc) for older adults or those on QT-prolongers/diuretics.

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?
No. Paroxetine shows more lipid impact; fluoxetine/sertraline/escitalopram look more neutral short-term.

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

Any big QTc/sodium issues?
Not in these RCTs; registry data in older, sicker patients still flags hyponatremia and QT concerns, so monitor when indicated.

Further Reading

• Pillinger T, Arumuham A, McCutcheon RA, et al. Lancet (2025). doi:10.1016/S0140-6736(25)01293-0
• NICE. Depression in adults: treatment and management.

• #antidepressants
• #side-effects
• #cardiometabolic
• #metabolic-health