What did the study find?
Researchers have found that some antidepressants are more likely to cause weight gain and cardiovascular changes than others. For example, older drugs such as amitriptyline and mirtazapine were associated with higher risks of these side effects, while newer drugs such as sertraline and fluoxetine tended to have a more favorable profile.
This doesn’t mean that one drug is “better” than another—it means that side effects should be part of the discussion when choosing a treatment.
For some people, a drug that causes weight gain can be manageable. For others, especially those with heart disease or diabetes, it could be a serious concern.
| Medicine | Possible physical side effects |
| Amitriptyline | It can cause weight gain, dry mouth, drowsiness and constipation |
| Mirtazapine | Risk of weight gain, increased appetite and sedation |
| Venlafaxine | It can cause increased blood pressure, sweating and nausea |
| Duloxetine | Sweating, dry mouth and constipation |
| Sertraline | Mild weight gain, diarrhea and possible sexual dysfunction |
| Fluoxetine | Insomnia, nausea and sexual dysfunction |
| Paroxetine | Weight gain, sexual dysfunction and depression |
| Citalopram | Nausea, dry mouth and sexual dysfunction |
| Escitalopram | Similar to citalopram: nausea, headache and sexual dysfunction |
| Bupropion | Insomnia, dry mouth and possible risk of seizures when used in high doses. |
| Trazodone | Sedation, dizziness and orthostatic hypotension (drop in blood pressure when standing) |
| Nortriptyline | Dry mouth, constipation and weight gain |
| Imipramine | Weight gain, constipation and changes in heart rate |
What do these side effects mean?
- Weight gain: Can affect self-esteem and physical health, especially for people with diabetes or heart disease.
- Sexual dysfunction: Includes decreased libido or difficulty achieving orgasm, which can affect relationships.
- Sedation: Feeling excessively sleepy or lethargic, which may interfere with daily activities.
- Dry mouth and constipation: Often with older antidepressants, these can be uncomfortable and affect quality of life.
- Blood pressure changes: Important monitoring, especially for people with cardiovascular disease.
It is important to note that these side effects are only possible and will not affect everyone.
The study was welcomed by experts across the field.
Dr Lade Smith CBE, President of the Royal College of Psychiatrists, said:
“We know that more than 7 million adults have depression in England alone and that severe depression can ruin people’s lives if left untreated.
“Antidepressants play a key role in the treatment of more severe depression and are particularly effective when used in conjunction with talking therapies.
“As with all drugs, antidepressants have side effects, and we warmly welcome this study to help improve our understanding of some of the natural side effects that can be caused by different types of antidepressants. These findings will help patients and clinicians choose the drug that best suits their individual needs. It is vital that these decisions are informed by the best available evidence.”
What’s next?
The Petrushka trial is part of a growing movement in mental health research to make treatments more tailored and transparent. By understanding how different medications affect the body, doctors can help patients make informed choices and hopefully improve both mental and physical health outcomes.
The recently awarded PRADA study (funded by Wellcome and supported by MQ) is the next step after PETRUSHKA. This project aims to add genetic predictors to a multimodal online evidence-based tool to help patients and clinicians co-select the best pharmacological treatment for depression.
Andrea Cipriani also leads GALENO supporty, which is also supported by MQ, aims to review published evidence and data to answer specific questions about depression, anxiety and psychosis.
If you are currently taking antidepressants and have concerns about side effects, it is important to talk to your doctor. This study does not recommend stopping medication, but highlights the need for open conversations and individualized care.
