Physiological Effects of Antidepressants Vary, Highlighting Need for Personalized Care
According to a recent systematic review and meta-analysis, the physiological effects of antidepressants vary, particularly for cardiometabolic parameters. The findings, published in The Lancet Psychiatry, underscore the need for updated treatment guidelines and individualized considerations when selecting an antidepressant.
To compare and rank antidepressants based on physiological side-effects, the researchers synthesized data from single- and double-blinded randomized controlled trials (RCTs) that compared antidepressants and placebo in acute monotherapy of any psychiatric disorder. The total sample included 58,534 participants from 151 studies and 17 US Food and Drug Administration (FDA) reports, comparing 30 antidepressants with placebo for a median treatment duration of 30 weeks. Researchers assessed treatment-induced changes in weight, total cholesterol, heart rate, glucose, systolic and diastolic blood pressure, corrected QT interval (QTc), sodium, potassium, and several other physiological parameters.
“We observed clinically significant differences between antidepressants in terms of metabolic and hemodynamic effects, including an approximate 4 kg difference in weight-change between agomelatine and maprotiline, over 21 beats-per-minute difference in heart rate change between fluvoxamine and nortriptyline, and over 11 mmHg difference in systolic blood pressure between nortriptyline and doxepin,” wrote Toby Pillinger, PhD, Institute of Psychiatry, Psychology and Neuroscience, Department of Psychosis Studies, King's College London, London, UK, and study coauthors.
Though paroxetine, duloxetine, desvenlafaxine, and venlafaxine reduced bodyweight, they were also associated with significant increases in total cholesterol, and duloxetine was associated with increases in glucose concentrations. There was no clinically significant evidence of any antidepressant affecting QTc, or concentrations of sodium, potassium, urea, and creatinine.
The researchers also did not observe a correlation between change in depressive symptom severity and metabolic outcomes.
Using meta-regressions to investigate study-level associations between physiological change and baseline weight, age, and sex, the researchers found that higher baseline bodyweight was associated with larger antidepressant-induced increases in systolic blood pressure, alanine transaminase (ALT), and aspartate transferase (AST). Higher baseline age was also associated with larger antidepressant-induced increases in glucose.
“Given the recognized co-morbid physical health burden in people with depression and resultant effects on morbidity and mortality, our findings can be used by clinicians and patients to guide choice of antidepressant,” the authors wrote.
To examine whether these physiological effects persist over time, the authors suggest a future meta-analysis evaluating maintenance-phase RCTs. They also emphasize the need for more data on metabolic outcomes to be routinely measured in future trials, as their findings were limited by the number of RCTs reporting these parameters.
