Antidepressants vary widely in their physical side effects

Antidepressants vary widely in the side effects they cause – from weight gain to weight loss and changes in blood pressure. This may need to be taken into account when doctors decide which of many potentially life-saving drug options would be best for each individual.

About 1 in 10 people in Europe and the United States take antidepressants for problems such as depression and anxiety. Withdrawal symptoms may be less common than previously thought, but some studies suggest that there may also be physical side effects while taking these medications. It’s just not clear which specific medication causes which type of side effect.

Digging deeper into the data, Toby Pillinger of King’s College London and colleagues analyzed the results of 151 randomized controlled trials and 17 reports from the U.S. Food and Drug Administration. These involved 30 antidepressants whose effectiveness and side effects were compared to placebos over a treatment of approximately eight weeks for various psychiatric disorders.

“The beauty of these studies is that they were all placebo-controlled and randomized, so we can be confident that the differences we show are due to the drug,” says Pillinger.

Researchers found that some medications were linked to weight loss and others to weight gain. Maprotiline, for example, was associated with an average weight gain of around 1.8 kg, while agomelatine was associated with a loss of around 2.4 kg.

The study also showed that the drug fluvoxamine was linked to a slowing of heart rate by 8 beats per minute (bpm) on average, but nortriptyline increased it by 13 bpm. These also reduced systolic blood pressure – your blood pressure when your heart contracts – by 3 to 7 millimeters of mercury (mmHg), while doxepin increased it by almost 5 mmHG, which could have implications for overall health. “Every 1 mmHg increase in your blood pressure, if you have high blood pressure, increases your risk of stroke by 1 percent,” says team member Oliver Howes, also at King’s College London.

Other medications, such as paroxetine, duloxetine, desvenlafaxine, and venlafaxine, have been linked to increased cholesterol. It is not clear whether these side effects worsen, improve, or stabilize after eight weeks.

Although observational studies have raised concerns that antidepressants affect levels of electrolytes, like sodium, in the blood, which could impact heart rate, “our study showed that in reality there was no problem with sodium,” says Pillinger.

Of the more than 92 million doses of antidepressants prescribed in England last year, around 85 per cent were sertraline, mirtazapine, fluoxetine, amitriptyline, citalopram or venlafaxine. Four of them were found to have a relatively good profile for most of the factors examined, but amitriptyline increased weight, heart rate and blood pressure, while venlafaxine increased heart rate, blood pressure and cholesterol.

“It’s very informative for both doctors and patients,” says Mahyar Etminan of the epidemiology consulting group Epilytics in Vancouver, Canada. “This data can be integrated into an app. So, for example, if a person has high cholesterol or cardiovascular problems, the app can tell the doctor which ones to avoid. This will give doctors more leeway in choosing the antidepressant that is best for their patient.”

Pillinger says his team is developing a digital tool with a drop-down menu of common side effects of antidepressants, so doctors can evaluate which ones to avoid, or even which ones to choose, such as whether weight loss would be beneficial. “It’s about finding the right molecule for the right person and engaging in a personalized prescription,” says Pillinger.

But John Ioannidis of Stanford University in California says the results could be biased if the team only included studies showing side effects. Others may not have seen side effects or reported them, meaning these data were not included in the meta-analysis.

He also points out that people typically take antidepressants for more than 8 weeks; sometimes for years. “Very different, long-term studies would be needed to show the presence and relevance of such effects, if any, in the long term,” says Ioannidis.

In response, Pillinger says there is “always a risk of bias,” but “we can be relatively confident that we have gathered most of the available data.”

He admits that an analysis of longer-term studies is needed, which his team is working on, and points out that about 75 percent of participants in existing trials were white. But he thinks the trends the team spotted will show up in longer-term studies and likely apply to other groups.

Previous studies suggest that certain antidepressants, such as venlafaxine, are associated with long-term increases in blood pressure, he says. Rapid weight gain can also last, he says. “Once you gain weight, it’s hard to get rid of it.”

People on antidepressants who are concerned about side effects shouldn’t stop their treatment, however, Howes says, because these medications can be very effective. “It’s nuanced; it’s an individual decision, reflecting an individual’s risk profile and benefits. If they are concerned, we recommend they speak to their doctor.”