Nortriptyline

Is nortriptyline safe?

At the low doses used for nerve pain, where the NHS starts at 10 mg a day, nortriptyline is usually well tolerated, and many find it easier than amitriptyline. The serious risk is the same as for every tricyclic: a modest overdose can stop the heart. It is not addictive.

Nortriptyline is the main active product of amitriptyline in the body, sold as a medicine in its own right since 1964. The UK label calls it less anticholinergic than amitriptyline, though more antihistaminic, so dry mouth and constipation may be milder while drowsiness still occurs. Its heart effects and its toxicity in overdose are much the same.

We score it 54, just above amitriptyline (52) and well below duloxetine (66), which is also used for nerve pain. For someone on 10 mg with a healthy heart and no history of self-harm, the everyday risk is lower than that number suggests.

Nerve pain doses vs depression doses

In the UK, nortriptyline is licensed only for depression, but the NHS says it can also be used for nerve pain, at much lower doses.

Nortriptyline is unusual among antidepressants in having a known blood level range. The labels say levels should be checked above 100 mg a day and kept between 50 and 150 ng/ml, because higher levels bring more side effects without more benefit. People who break it down slowly can reach high levels on ordinary doses.

Side effects and the heart

The UK label lists these as very common (more than 1 in 10): dry mouth, constipation, blurred near vision, palpitations and a fast heart rate, dizziness on standing, sweating, flushing and headache. Common ones include tiredness, tremor, confusion, erection problems and low libido. Most ease after the first weeks, and at 10 to 25 mg many people have few.

The heart effects matter most. Changes on the ECG, a longer QT and QRS and some kinds of heart block, are listed as common. The label rules nortriptyline out after a recent heart attack and in any degree of heart block or arrhythmia, and warns that it has unmasked Brugada syndrome, an inherited rhythm disorder that can cause sudden death. Older people are more prone to confusion and falls. It lowers the seizure threshold and can worsen glaucoma and urinary retention.

Overdose

Tricyclics are the most dangerous common antidepressants in overdose. The UK label says 50 mg can be an overdose in a child, that 0 to 15% of people who reach hospital alive have died, and that symptoms such as seizures, coma and dangerous arrhythmias can begin within hours. In a study of England and Wales from 2000 to 2006, tricyclics as a class had a case fatality ratio of 13.8, against 0.5 for SSRIs.

The ONS does not count nortriptyline separately. In 2024, 201 drug-poisoning deaths in England and Wales mentioned any tricyclic and 171 mentioned amitriptyline. That leaves 30 that named a tricyclic but not amitriptyline, a group that covers nortriptyline, dosulepin and the other tricyclics together. The US label asks for prescriptions in the smallest practical quantity for this reason. Treat any overdose as an emergency even if the person seems well: call 911 and Poison Help on 1-800-222-1222 in the US, or 999 in the UK.

Interactions

Nortriptyline is cleared mainly by CYP2D6CYP450 enzymesA family of liver enzymes that break down many medicines. When another drug or supplement speeds them up or slows them down, drug levels change.More in the glossary, an enzyme that works poorly in 7 to 10% of white people, according to the US label. In them, or in anyone taking a CYP2D6 blocker, tricyclic exposure can rise up to eightfold and a stable dose can suddenly become toxic. The UK label reports nortriptyline levels more than doubling when fluoxetine was added; paroxetine, bupropion, quinidine and cimetidine can raise levels too.

It is contraindicatedContraindicationA situation in which a medicine should not be used, because the risk clearly outweighs any benefit, such as a known allergy to it.More in the glossary with MAOIs and should not be combined with linezolid or IV methylene blue because of serotonin syndromeSerotonin syndromeA reaction caused by too much serotonin in the body, usually from combining medicines that raise it. Symptoms range from shivering to high fever.More in the glossary. The UK label also warns about other QT-prolongingQT prolongationA delay in the heart's electrical recovery between beats, seen on an ECG. Some medicines cause it, and in rare cases it leads to a serious heart rhythm problem.More in the glossary drugs, fluconazole and terbinafine, decongestants such as phenylephrine, tramadol, which raises seizure risk, anticholinergic medicines, thyroid hormone and alcohol.

Who should be careful

Talk to your doctor or pharmacist before starting nortriptyline, or adding anything to it, if you:

• have heart disease, heart block, a long QT intervalQT prolongationA delay in the heart's electrical recovery between beats, seen on an ECG. Some medicines cause it, and in rare cases it leads to a serious heart rhythm problem.More in the glossary, or a family history of sudden cardiac death
• are over 65 or have had falls or confusion
• have epilepsy, glaucoma or an enlarged prostate
• take another antidepressant, tramadol, an antipsychotic or a QT-prolonging drug
• have had thoughts of self-harm, or live with children (store it locked away)
• are pregnant or planning a pregnancy

How we scored it

Track record (92) and dependence (82) are strong. Overdose marginOverdose marginHow far a normal dose is from a harmful one. A wide margin means an accidental extra dose is unlikely to cause serious harm.More in the glossary (30) is the weakest factor and the main reason for the low score, followed by interactions (40) and heart side effects (52), which are slightly milder than amitriptyline's. A low score is not a reason to stop a medicine that is helping; plan any change with your prescriber.