Thought Archive

The Hidden Weight of Antidepressants

23 Oct 2025

The Hidden Weight of Antidepressants

Hook

“Four kilos, eleven millimetres, twenty beats per minute.”
That’s the physiological distance separating the “lightest” and “heaviest” antidepressants — not in emotion, but in metabolic load.

A Lancet network meta-analysis (~58,500 participants; 151 RCTs) compared 30 antidepressants for physiological side-effects. The results make one thing clear: these drugs do more than change how we feel — they change how our bodies function.

Note

At a glance
Up to 4 kg spread in weight change (8 weeks), ~20 bpm spread in heart rate, and ~11 mmHg spread in systolic BP across agents.

Key Figures

Key Figures

Key Figures

Lancet Network Meta-Analysis — 30 antidepressants, physiological outcomes

Pillinger et al. — 2025-10-21

  • SNRIs (venlafaxine, desvenlafaxine, duloxetine, levomilnacipran) increased cholesterol/BP; duloxetine also nudged glucose.
  • TCAs (amitriptyline, imipramine, maprotiline) increased HR/BP and weight.
  • Agomelatine, fluoxetine, and bupropion showed more favorable weight profiles.
  • Minimal QTc/sodium signals in short-term RCTs.

Comparative Highlights

Weight

  • Lower / neutral: Agomelatine (Valdoxan) Low risk , Fluoxetine (Prozac) Low risk , Bupropion (Wellbutrin) Low risk
  • Higher: Mirtazapine (Remeron) High risk , Amitriptyline (Elavil) High risk , Maprotiline (Ludiomil) High risk

Heart Rate (HR)

  • ↓ HR: Fluvoxamine (Luvox) ≈ –8 bpm
  • ↑ HR: Nortriptyline (Pamelor) ≈ +13 bpm; Imipramine (Tofranil), Amitriptyline (Elavil)

Blood Pressure (BP)

  • Systolic BP ↑: Levomilnacipran (Fetzima), Venlafaxine (Effexor), Desvenlafaxine (Pristiq), Duloxetine (Cymbalta); TCAs like Amitriptyline
  • Systolic BP ↓: Nortriptyline showed a small decrease in trials

Lipids & Glucose

  • Cholesterol ↑: Paroxetine (Paxil), Duloxetine (Cymbalta), Venlafaxine (Effexor), Desvenlafaxine (Pristiq)
  • Glucose ↑: signal with Duloxetine

    Note

    Some lipid/glucose increases occurred even when bodyweight fell — suggesting weight-independent metabolic effects.

Quick Compare

Agomelatine

Low risk

Valdoxan

  • Weight: ↓ ~2.4 kg
  • HR/BP: Neutral
  • Metabolic: Neutral

Fluoxetine

Low risk

Prozac

  • Weight: ↓ ~0.8 kg
  • HR/BP: Neutral
  • Metabolic: Neutral

Bupropion

Low risk

Wellbutrin

  • Weight: ↓ / neutral
  • HR/BP: Neutral
  • Metabolic: Neutral

Venlafaxine

Moderate risk

Effexor

  • Weight: neutral
  • HR/BP: ↑ BP
  • Metabolic: ↑ Cholesterol

Duloxetine

Moderate risk

Cymbalta

  • Weight: ↓ (small)
  • HR/BP: ↑ BP
  • Metabolic: ↑ Chol/Glucose

Amitriptyline

High risk

Elavil

  • Weight: ↑ ~1.5–1.6 kg
  • HR/BP: ↑ HR/BP
  • Metabolic: ↑ Lipids

Mirtazapine

High risk

Remeron

  • Weight: ↑
  • HR/BP: Neutral/↑ HR
  • Metabolic: ↑ Lipids (some data)

Figure

Heatmap of antidepressant physiological effects (blue=decrease/neutral, red=increase)

Blue = lower or neutral effect; Red = increased physiological parameter. Data: Pillinger et al., Lancet (2025).

Why this matters

Small average shifts over weeks can compound if sustained:

  • Each 1 kg weight increase raises long-term CVD risk.
  • Higher resting HR and BP correlate with elevated all-cause and cardiovascular mortality.

Bottom line: when choosing an antidepressant for someone with obesity, hypertension, dyslipidemia, or diabetes risk, consider the metabolic profile alongside efficacy and tolerability.

FAQ

Which look most “metabolically gentle”?
Agomelatine, Fluoxetine, Bupropion.

Which raise flags?
For weight: Mirtazapine, Amitriptyline, Maprotiline.
For lipids/BP: Venlafaxine, Desvenlafaxine, Duloxetine; Levomilnacipran for BP.

Any big QTc or sodium signals in RCTs?
Not in these short-term monotherapy trials; registry data in older, multimorbid populations may differ.

Further Reading