What Did the Study Find?
The researchers found that some antidepressants are more likely to cause weight gain and cardiovascular changes than others. For example, older drugs like amitriptyline and mirtazapine were linked to higher risks of these side effects, while newer medications like sertraline and fluoxetine tended to have a more favourable profile.
This doesn’t mean one drug is “better” than another—it means that side effects should be part of the conversation when choosing a treatment.
For some people, a medication that causes weight gain might be manageable. For others, especially those with heart conditions or diabetes, it could be a serious concern.
| Medication | Possible Physical Side Effects |
| Amitriptyline | Can cause weight gain, dry mouth, drowsiness, and constipation |
| Mirtazapine | Risk of weight gain, increased appetite, and sedation |
| Venlafaxine | Can cause increased blood pressure, sweating, and nausea |
| Duloxetine | Sweating, dry mouth, and constipation |
| Sertraline | Mild weight gain, diarrhoea, and possible sexual dysfunction |
| Fluoxetine | Insomnia, nausea, and sexual dysfunction |
| Paroxetine | Weight gain, sexual dysfunction, and sedation |
| 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 at 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 heart rhythm changes |
What Do These Side Effects Mean?
- Weight gain: Can affect self-esteem and physical health, especially for people with diabetes or heart conditions.
- Sexual dysfunction: Includes reduced libido or difficulty achieving orgasm, which can impact relationships.
- Sedation: Feeling overly sleepy or sluggish, which may interfere with daily activities.
- Dry mouth and constipation: Common with older antidepressants, these can be uncomfortable and affect quality of life.
- Blood pressure changes: Important to monitor, especially for people with cardiovascular conditions.
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 devastate 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 combination with talking therapies.
“As with all drugs, antidepressants have side effects, and we very much welcome this study which helps improve our understanding of some of the physical side effects that can be caused by different types of antidepressants. These findings will help patients and clinicians choose the medication that is best suited to their personal 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 drugs 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 an evidence-based multimodal web-tool, to help patients and clinicians choose the best pharmacological treatment for depression jointly.
Andrea Cipriani is also leading the GALENOS study, which is also supported by MQ, which aims to review the published evidence and data in order to answer specific questions about depression, anxiety and psychosis.
If you’re currently taking antidepressants and have concerns about side effects, it’s important to speak with your doctor. This study doesn’t suggest stopping medication, but it does highlight the need for open conversations and individualised care.