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DATE: September 8, 2026 at 11:00AM
SOURCE: PSYPOST.ORG

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TITLE: Antidepressants show wide variation in physical side effects

URL: https://www.psypost.org/antidepressants-show-wide-variation-in-physical-side-effects/

Different antidepressants can have drastically different effects on a patient’s physical health, according to a recent review of medical research. Some medications cause substantial weight gain and increased blood pressure, while others lead to weight loss and lowered heart rates. The findings were published in The Lancet.

Millions of people rely on prescription medications to manage mental health conditions. Up to 17 percent of adults in Europe and North America currently take antidepressants. While these drugs are effective at treating mood disorders, they can also cause unintended bodily changes. These physical side effects are a common reason why people stop taking their prescribed treatments.

Medical guidelines recommend that doctors discuss potential physical changes with patients before starting a prescription. However, it can be difficult for physicians to provide precise comparisons between specific drugs.

Toby Pillinger and Atheeshaan Arumuham of King’s College London led the research team to address this knowledge gap. They worked alongside other international experts, including Orestis Efthimiou of the University of Bern, Oliver D. Howes of King’s College London, and Andrea Cipriani of the University of Oxford. The team wanted to determine exactly how different medications compare in terms of physical side effects. They also wanted to see if factors like age or starting weight influenced these bodily reactions.

To answer these questions, the researchers conducted a network meta-analysis. This type of statistical study pools data from multiple independent trials. It allows researchers to compare treatments that might never have been tested directly against each other in the same room. By linking trials through a common comparator, researchers can estimate how two different drugs would perform head-to-head.

The team gathered data from 151 randomized controlled trials and 17 government regulatory reports. The resulting large study included 58,534 participants. The researchers evaluated 30 different antidepressants prescribed for acute psychiatric treatment, which typically lasted about eight weeks.

The analysis revealed major differences in how these drugs affect body weight. People taking agomelatine experienced the most weight loss, losing an average of about 2.4 kilograms compared to those taking a placebo, an inactive control pill. On the other end of the spectrum, maprotiline and amitriptyline caused the most weight gain, adding up to 1.8 kilograms on average. This created a roughly four-kilogram gap between the highest and lowest weight-altering medications.

The researchers estimated that almost half of the people taking maprotiline or amitriptyline would gain a noticeable amount of weight. Medications that caused the most weight gain were generally those known to block specific histamine and serotonin receptors, which act as chemical docking stations in the brain. Over time, extra weight can elevate a person’s risk for metabolic issues and joint stress.

Cardiovascular changes also varied widely depending on the specific medication. Nortriptyline increased patients’ heart rates by an average of nearly 14 beats per minute. By contrast, fluvoxamine lowered heart rates by about eight beats per minute. This difference amounts to a 21-beat-per-minute gap between the two drugs.

Blood pressure effects showed a similar split among the evaluated medications. Amitriptyline raised systolic blood pressure, which measures the pressure in your arteries when your heart beats, by almost five millimeters of mercury. Nortriptyline lowered the same metric by over six millimeters of mercury. The researchers noted that these cardiovascular shifts could influence a patient’s long-term risk for heart disease, especially if the changes persist over several years.

The medications that increased blood pressure were largely serotonin-noradrenaline reuptake inhibitors, or tricyclic antidepressants. These drug classes share a mechanism that affects the neurotransmitter noradrenaline. This chemical messenger plays a well-documented role in blood pressure regulation.

The researchers also tracked metabolic markers like cholesterol and blood sugar. Paroxetine, duloxetine, desvenlafaxine, and venlafaxine were associated with measurable increases in total cholesterol. Duloxetine was also linked to increased blood glucose levels. These metabolic increases occurred even though the medications themselves generally caused patients to lose body weight.

Some medications also affected liver function tests. Duloxetine, desvenlafaxine, and levomilnacipran caused increases in the concentration of certain liver enzymes. These enzymes are proteins that help the organ filter blood and break down medications. While these enzyme elevations were substantial enough to measure, the researchers noted that the amounts were not high enough to pose an immediate medical threat to most patients.

The team did not find that any of the evaluated antidepressants altered heart rhythm intervals to a problematic degree. The medications also did not have a strong effect on sodium levels, potassium levels, or kidney function markers during the trial periods.

In a separate analysis, the researchers examined how patient characteristics influenced these side effects. They used a statistical technique called meta-regression to look for trends across the different study populations. They found that groups of patients with higher starting body weights experienced larger medication-induced increases in blood pressure and liver enzymes. Populations with a higher average age saw larger medication-induced increases in blood sugar.

Finally, the team wanted to know if experiencing physical side effects was linked to mental health improvements. In patients with severe psychiatric conditions like schizophrenia, past research has shown a correlation between metabolic disturbances and improved symptoms. To test this concept in depression, the researchers looked specifically at trials involving patients with major depressive disorder.

The researchers compared the change in depressive symptoms against changes in weight, cholesterol, and blood sugar across the studies. They did not find a correlation between improved mental health and metabolic side effects. This suggests that patients do not need to experience physical changes to get the mental health benefits of the medication.

A primary limitation of this research is the short duration of the included trials. Most studies lasted only eight weeks, meaning the long-term physical effects of these medications remain unconfirmed by this specific analysis. Some cardiovascular shifts might fade over time, while other metabolic changes could worsen over a period of years.

The trials also mostly included younger, relatively healthy individuals taking only one medication. This focus might obscure side effects that occur more frequently in older adults or people taking multiple drugs at once. Real-world observational data suggests that certain antidepressants might increase the risk of low sodium or heart rhythm problems in older populations. The researchers suggest that doctors should consider both clinical trial data and real-world observations when prescribing medications to older or medically vulnerable patients.

The study, “The effects of antidepressants on cardiometabolic and other physiological parameters: a systematic review and network meta-analysis,” was authored by Toby Pillinger, Atheeshaan Arumuham, Robert A McCutcheon, Enrico D’Ambrosio, Georgios Basdanis, Marco Branco, Richard Carr, Valeria Finelli, Toshi A Furukawa, Siobhan Gee, Adrian Heald, Sameer Jauhar, Zihan Ma, Valentina Mancini, Calum Moulton, Georgia Salanti, David M Taylor, Anneka Tomlinson, Allan H Young, Orestis Efthimiou, Oliver D Howes, and Andrea Cipriani.

URL: https://www.psypost.org/antidepressants-show-wide-variation-in-physical-side-effects/

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