A new comprehensive analysis has highlighted how side effects of antidepressants vary widely, a finding that could help doctors make more personalized treatment decisions. The study, led by researchers at King’s College London, examined 30 different antidepressants, looking at their effects on weight, heart rate, blood pressure, and cholesterol.
According to the study, some antidepressants are linked to weight loss while others may cause weight gain. For instance, maprotiline users gained an average of 1.8 kilograms, while agomelatine users lost around 2.4 kilograms over an eight-week period.
Heart rate and blood pressure were also affected differently depending on the drug. Fluvoxamine slowed heart rate by about 8 beats per minute on average, whereas nortriptyline increased it by 13 bpm and lowered systolic blood pressure by 3 to 7 mmHg. Conversely, doxepin raised systolic blood pressure by nearly 5 mmHg — a potentially concerning change for people with hypertension. As Oliver Howes, one of the study’s authors, noted, “Each 1 mmHg increase in blood pressure increases stroke risk by 1 percent for people with high blood pressure.”
Other drugs such as paroxetine, duloxetine, desvenlafaxine, and venlafaxine were associated with increases in cholesterol. While these findings reflect short-term effects over about eight weeks, the long-term impacts remain unclear.
Interestingly, the study found no evidence that antidepressants caused problems with blood sodium levels — a concern raised in some previous observational studies that suggested a potential risk for heart rhythm disturbances.
The researchers analyzed data from 151 randomized controlled trials and 17 FDA reports. “The beauty of these studies is that they were all placebo-controlled and randomized, so we can be confident that the differences are due to the drug,” said Toby Pillinger of King’s College London.
In England alone, more than 92 million antidepressant doses were prescribed last year, with sertraline, mirtazapine, fluoxetine, amitriptyline, citalopram, and venlafaxine making up about 85 percent of prescriptions. While four of these drugs showed relatively favorable profiles, amitriptyline was linked to weight gain, higher heart rate, and increased blood pressure, while venlafaxine raised heart rate, blood pressure, and cholesterol.
The findings could have practical applications in personalized prescribing. “This data can be put into an app so physicians can avoid drugs for patients with high cholesterol or cardiovascular issues, helping them choose the antidepressant that best fits the patient,” said Mahyar Etminan, an epidemiology consultant in Vancouver, Canada.
Pillinger’s team is working on a digital tool that lists common side effects of each antidepressant, allowing doctors to select the most suitable medication based on a patient’s individual needs. “It’s about finding the right molecule for the right person and engaging in personalized prescribing,” he said.
However, not everyone is fully convinced. John Ioannidis of Stanford University cautioned that the study may be biased, as it relied on trials that reported side effects. Moreover, most antidepressants are taken for months or even years, making long-term studies necessary to fully understand their impact.
Still, Pillinger believes the patterns identified in short-term studies will likely persist in the long term and apply to broader populations, despite 75 percent of trial participants being white. “Some antidepressants, like venlafaxine, are known to increase long-term blood pressure. Rapid weight gain can also last,” he said.
For patients concerned about side effects, the experts emphasize that stopping antidepressants abruptly is not recommended. “It’s nuanced; patients should weigh risks and benefits with their doctors,” Howes said.