Antidepressants remain among the most prescribed psychotropics worldwide, yet their physiological side effects are often under-recognized. A recent meta-analysis pooled data from 151 randomized controlled trials and 17 FDA reports (n = 58,534 participants) comparing 30 antidepressants to determine their short-term effects on weight, cardiometabolic markers, liver enzymes, and renal function.

Antidepressants Differ Markedly in Physiological Impact

Weight: Ranged from loss with agomelatine (–2.4 kg) to gain with maprotiline (+1.8 kg).

• Agomelatine led to clinically relevant weight loss in ~55% of users.

Cardiovascular parameters:

• Heart rate: Varied by >20 bpm across agents — increased with nortriptyline, imipramine, and reboxetine; decreased with fluvoxamine and moclobemide.
• Blood pressure: SNRIs and TCAs (duloxetine, venlafaxine, desvenlafaxine, levomilnacipran, amitriptyline) caused measurable increases in systolic/diastolic BP.
• Nortriptyline uniquely reduced BP, contrary to others in its class.

Metabolic and Hepatic Findings

• Cholesterol: Raised by desvenlafaxine, venlafaxine, duloxetine, and paroxetine (~0.2–0.3 mmol/L).
• Glucose: Mild rise seen with duloxetine, particularly in older adults.
• Liver enzymes: Duloxetine, desvenlafaxine, and levomilnacipran slightly elevated AST/ALT/ALP — not clinically significant but noteworthy in hepatic disease.
• Renal and electrolyte measures: No clinically relevant effects observed.
• QTc: No meaningful prolongation in any agent over short-term treatment.

Risk modifiers observed in the study showed that individuals with higher baseline body weight experienced greater increases in blood pressure and liver enzymes during antidepressant treatment, while older adults demonstrated larger rises in glucose levels. Sex did not appear to significantly influence these physiological responses.

Clinically, these findings reinforce the importance of tailoring antidepressant selection not solely on efficacy but also on a patient’s cardiometabolic and hepatic profile. Early treatment should include monitoring of weight, blood pressure, and basic metabolic markers, particularly when prescribing SNRIs or TCAs, which tend to have stronger physiological effects. Clear patient education about possible bodily changes can improve adherence and support shared decision-making by aligning expectations and promoting proactive monitoring.

Reference:
Pillinger T et al. Lancet. 2025;406(10515):2063-2077. Abstract.