Commonly used antidepressants can differ by as much as 4 kg in their short-term effects on patient weight, revealing unexpectedly wide variation in cardiometabolic impact, according to a recent study.
Antidepressants demonstrated distinct physiologic effects, with the greatest variability observed in weight, heart rate, and blood pressure. Agomelatine was associated with a mean weight reduction of 2.44 kg compared with placebo, whereas maprotiline increased weight by 1.82 kg. An estimated 48% of patients receiving maprotiline and 46% receiving amitriptyline gained at least 2 kg. Further, nortriptyline increased the heart rate by 13.77 bpm, whereas fluvoxamine lowered the heart rate by 8.18 bpm. Systolic blood pressure increased with amitriptyline, levomilnacipran, fluoxetine, venlafaxine, imipramine, desvenlafaxine, and duloxetine, with mean changes ranging from 1.59 to 4.86 mmHg. Nortriptyline produced a reduction of 6.68 mmHg.
Diastolic pressure increased with several tricyclic antidepressants and serotonin–noradrenaline reuptake inhibitors. In addition, total cholesterol increased with desvenlafaxine, venlafaxine, duloxetine, and paroxetine despite accompanying weight reductions. Duloxetine increased glucose by 0.30 mmol/L, and several agents—most prominently duloxetine, desvenlafaxine, and levomilnacipran—raised hepatic enzyme concentrations, although these changes weren't considered clinically significant. No clinically important alterations were observed in corrected QT interval, potassium, urea, or creatinine. Sodium concentrations decreased modestly with duloxetine and venlafaxine.
The findings were derived from a systematic review and network meta-analysis of 151 randomized controlled trials and 17 US Food and Drug Administration reports, encompassing 58,534 adults treated with 30 antidepressants as monotherapy for acute psychiatric disorders over a median of 8 weeks. Frequentist random-effects network meta-analyses were used to compare drug effects across cardiometabolic, hepatic, renal, and electrolyte parameters. Meta-regression analyses showed that higher baseline weight predicted larger increases in systolic blood pressure and hepatic enzymes, while older age predicted greater increases in glucose.
The investigators reported that several network models showed inconsistency, potential small-study effects, and limited reporting of key metabolic outcomes, which constrained the robustness of some comparisons. They also noted that unavailable trial data, reliance on study-level meta-regression, and the absence of sex-stratified results restricted interpretation and highlighted the need for more comprehensive future trials.
“[W]e found strong evidence that antidepressants differ markedly in their physiological effects, particularly for cardiometabolic parameters,” noted lead study author Toby Pillinger, PhD, of the Institute of Psychiatry, Psychology and Neuroscience in the Department of Psychosis Studies at King's College London as well as the South London and Maudsley National Health Service Foundation Trust at Maudsley Hospital, and colleagues.
The study was funded by the National Institute for Health Research, Maudsley Charity, Wellcome Trust, and the Medical Research Council; several investigators reported consulting fees, speaker honoraria, or research support from multiple pharmaceutical companies.
Source: The Lancet
