Millions of people worldwide take antidepressants. While these drugs can be very effective in treating mental health conditions such as depression and anxiety, they can also cause a range of physical side-effects - including weight gain, heart rate changes and altered blood pressure.
Author
- Toby Pillinger
Doctor and Clinical Researcher, King's College London
But not all antidepressants are equal when it comes to the physical effects they can have on the body, a new analysis published by myself and my colleagues has revealed. We found clear and meaningful differences between the drugs, with some causing greater effects on weight, heart rate, cholesterol levels and blood pressure. For the millions of people who take these prescription drugs, these differences matter.
Our study brought together 151 randomised trials which contained data on 58,534 people and looked at 30 different antidepressants. Each study had recorded routine physical measures you'd see in a clinic such as blood pressure, body weight and heart rate. Most of the studies lasted about eight weeks.
We then used a method called network meta-analysis that lets you compare multiple treatments against each other simultaneously. This approach gives a sort of "league table" of treatments, ranking them from best to worst for each physical health outcome.
We found that even after only eight weeks of treatments, the physical effects of the various different antidepressants were not subtle.
Weight effects varied markedly between drugs. For example, people taking the antidepressant agomelatine lost around 2.5kg on average, whereas those on maprotiline gained nearly 2kg.
Heart rate effects also varied widely. The antidepressant fluvoxamine actually lowered heart rate by about eight beats per minute, while nortriptyline raised it by around 14 - a difference of more than 20 beats per minute between drugs.
Systolic blood pressure saw a more than 11mmHg spread between the antidepressant doxepin and nortriptyline.
And for cholesterol and blood sugar levels, several antidepressants - including paroxetine, venlafaxine, desvenlafaxine and duloxetine - were associated with higher total cholesterol. Duloxetine was also associated with higher blood sugar levels.
It's important to note that the analysis only focused on antidepressant treatment that lasted for around eight weeks. Since many people take antidepressants for a longer period than this, real-world, long-term physical effects could be greater. This is one reason why routinely monitoring patients taking antidepressants is essential.
We also only included objective outcomes that are consistently collected in trials. Some important physical problems, such as sexual side-effects, are not routinely measured in research so were not included in the analysis due to a lack of data - not a lack of importance. It will be important for future studies to investigate such outcomes.
The results also should not be read as a list of "good" and "bad" antidepressants. Rather, they illustrate how different drugs can have different physical effects. The aim with our research is to show why it's important to tailor prescribing to each patient.
Peronalised prescribing
For years, debates about antidepressants have been framed as "do they work?" or "are side-effects real?" Our findings suggest a more useful question: which drug suits which person, given their physical health and priorities?
The data shows that antidepressants are not interchangeable. For someone with obesity, diabetes or hypertension, choosing an antidepressant that has a more neutral effect on weight, blood sugar and blood pressure is sensible. But for an underweight person with low blood pressure, the trade-off may be different. The right answer will depend on the patient.
In light of our recent findings, it's more important than ever that doctors work closely with patients to understand their priorities and match them with the correct antidepressant.
Of course, this is a challenge in and of itself for doctors, who would need to consider two dozen different antidepressants and their many potential side-effects. So alongside the analysis we performed, we also previously developed a freely-available tool that doctors and patients can use together to decide on the right antidepressant.
The tool allows doctors and patients to select the side-effects the patient most wants to avoid and set how important each one is. The tool then integrates those preferences with side-effect databases, then produces a personalised table of options which ranks antidepressants based on which best fits the patient's preferences.
Antidepressants are effective for many people. Our study does not change that. But what it does show is that not all antidepressants are the same. We now have high-quality evidence that their effects on weight, blood pressure, heart rate and blood sugar differ in clinically meaningful ways.
Rather than argue for or against antidepressants as a group, we should focus on matching the medicine to the person, with shared decisions being made between doctor and patient.
Tools such as the one we've built make this possible, so that patients can be prescribed antidepressants that are safer for them and better-tolerated.
Toby Pillinger has received speaker or consultancy fees from Boehringer Ingelheim, Bristol Myers Squibb, Recordati, Lundbeck, Otsuka, Janssen, CNX Therapeutics, Sunovion, ROVI Biotech, Schwabe Pharma, and Lecturing Minds Stockholm AB; he receives book royalties from Wiley Blackwell; and he co-directs a company that designs digital resources to support treatment of mental illness.
