An activating tricyclic antidepressant
Protriptyline
An older tricyclic antidepressant, more activating than most, used to treat depression.
What is Protriptyline?
Protriptyline is an older tricyclic antidepressant. It is more activating than most others in its class, so it is sometimes chosen when tiredness or low energy is a prominent part of depression. It is taken by mouth and works gradually over a few weeks. Like other tricyclics, it is dangerous in overdose, particularly because of dangerous effects on the heart's rhythm, and it causes antimuscarinic effects such as a dry mouth, constipation and blurred vision. It needs care in people with heart problems and is used under medical supervision.
Education and reference only. This is a plain-language guide to Protriptyline — it deliberately contains no doses. Doses depend on the person, the brand and the reason for treatment, and belong with your prescriber. Always check the BNF, the product labelling (SmPC) and follow medical advice.
What it is
Protriptyline is a tricyclic antidepressant, one of an older group of medicines used to treat depression. Compared with most tricyclics, which can be quite sedating, protriptyline tends to be activating, so it is sometimes preferred when a person's depression comes with marked tiredness or lack of energy. It is taken by mouth as a tablet. Tricyclics are effective but have more side effects and are more dangerous in overdose than newer antidepressants, so protriptyline is used thoughtfully and under medical supervision, with particular care around the heart.
How it works
Protriptyline increases the levels of the brain chemicals noradrenaline and serotonin by stopping nerve cells from reabsorbing them, which is thought to help lift mood over time. Its relatively strong effect on noradrenaline is part of why it tends to be activating rather than sedating. Like other tricyclics, it also blocks several other receptors in the body, which both causes its antimuscarinic side effects and contributes to its effects on the heart. It works gradually, so the full benefit on mood usually takes a few weeks to appear.
Company & origin
Originated / developed by: Generic (long-established).
An older tricyclic antidepressant, more activating than most, sometimes used when low energy or tiredness is a prominent feature.
What it treats
Conditions Protriptyline is used for
Practical use
How to take Protriptyline
General, dose-free guidance — always follow your prescriber's and the leaflet's specific instructions.
- Take it by mouth as prescribed, usually earlier in the day, as it can be activating and disturb sleep if taken late.
- Be patient; the effect on mood builds gradually over a few weeks rather than straight away.
- Do not stop it suddenly, as this can cause withdrawal effects; your prescriber will reduce it gradually if it is stopped.
- Tell your prescriber about any heart problems before starting, as tricyclics need particular care with the heart.
- Keep it well out of reach of others, as it is dangerous in overdose.
Weighing it up
Advantages & disadvantages of Protriptyline
Advantages
- An effective treatment for depression, with decades of experience behind its use.
- More activating than most tricyclics, which can suit depression with marked tiredness or low energy.
- Taken by mouth as a tablet.
Disadvantages
- Dangerous in overdose, particularly because of serious effects on the heart's rhythm.
- Commonly causes antimuscarinic effects such as dry mouth, constipation and blurred vision.
- Needs particular care in people with heart problems and works gradually rather than quickly.
Practical use
Good to know
The most important safety point with protriptyline, as with all tricyclics, is that it is dangerous in overdose, mainly because of serious effects on the heart's rhythm; this is a key reason for caution, especially when there is a risk of self-harm. Being an activating tricyclic, it is usually taken earlier in the day, as taking it late can disturb sleep, and it may not suit people who are already agitated or anxious. It commonly causes antimuscarinic effects such as a dry mouth, constipation, blurred vision and difficulty passing urine. It needs particular care in people with heart disease, and the heart may be checked. Like other antidepressants, it works gradually, should not be stopped suddenly, and mood and any thoughts of self-harm are watched, particularly early in treatment.
Who should not take it / use with caution
- People who have recently had a heart attack or who have certain serious heart-rhythm problems should not take it.
- People who have had a serious allergic reaction to protriptyline should not take it.
- It should not be taken with, or close to, medicines called MAOI antidepressants, and is used with caution in people with heart disease, glaucoma or difficulty passing urine.
Monitoring
- Reviewing mood and any thoughts of self-harm, particularly early in treatment.
- Checking the heart, including an ECG where appropriate, especially in people with heart problems.
- Watching for troublesome antimuscarinic effects and adjusting treatment as needed.
Side effects
- A dry mouth, constipation, blurred vision or difficulty passing urine (antimuscarinic effects).
- A fast or irregular heartbeat, dizziness on standing, or restlessness, given its activating nature.
- Rarely but seriously, dangerous heart-rhythm changes, especially in overdose.
Key interactions
- It must not be combined with MAOI antidepressants, and care is needed with other medicines that affect mood-related chemicals.
- Medicines that affect the heart's rhythm can add to its cardiac effects, so they are reviewed.
- Other medicines with antimuscarinic effects, and alcohol, can add to its side effects.
Available as: Tablets taken by mouth.
Answers
Protriptyline: frequently asked questions
What is protriptyline used for?
It is an older tricyclic antidepressant used to treat depression, and being more activating than most, it can suit depression with marked tiredness or low energy.
Why is it dangerous in overdose?
Like other tricyclics, it can seriously disturb the heart's rhythm in overdose, which is a key reason it is used carefully and kept out of reach of others.
Why do I have a dry mouth and constipation?
These are antimuscarinic side effects common to tricyclics, along with blurred vision and difficulty passing urine; tell your prescriber if they are troublesome.
Why should I take it earlier in the day?
Protriptyline tends to be activating, so taking it late can disturb sleep; your prescriber will usually advise taking it earlier in the day.
How quickly does it work?
It works gradually, so the full benefit on mood usually takes a few weeks; do not stop it suddenly if you do not feel better straight away.
The wider class
About Tricyclic antidepressant (activating)
Protriptyline belongs to the tricyclic antidepressant (activating) class. For how the class as a whole works, its shared safety principles and monitoring, see the full guide.
Browse by body system
Authoritative sources
- BNF
- NICE CKS
Building a medicines information resource?
We create evidence-led, dose-free drug and formulary references for teams.