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Nortriptyline is a second-generation tricyclic antidepressant (TCA) marketed as the hydrochloride salt under the trade names Sensoval, Aventyl, Pamelor, Norpress, Allegron, Noritren and Nortrilen. It is used in the treatment of major depression and childhood nocturnal enuresis (bedwetting). In addition, it is sometimes used for chronic illnessessuch as chronic fatigue syndrome, chronic pain and migraine, and labile affect in some neurological conditions.

Although not approved by the FDA for neuropathic pain, a large number of randomized controlled trials have proven the efficacy of tricyclic antidepressants for the treatment of this condition in both depressed and non-depressed individuals. Recently, an evidence-based guideline sponsored by the International Association for the Study of Pain recommends nortriptyline as a first-line medication for neuropathic pain.[7]
Metabolism

Nortriptyline is metabolized in the liver by the hepatic enzyme CYP2D6. Approximately 7-10% of caucasians are poor metabolizers and might experience more adverse effects, so a lower dosage is often necessary in these individuals.[8] Blood levels of nortriptyline should be obtained during long term treatment to avoid toxicity and optimize response.

Side effects

The most common side effects include dry mouth, sedation, constipation, and increased appetite, mild blurred vision, tinnitus, often euphoria and mania. An occasional side effect is a rapid or irregular heartbeat. Alcohol may exacerbate some of its side effects and should be avoided.
However, the incidence of side effects with nortriptyline is lower than with the first-generation tricyclics (e.g., imipramine (Tofranil), amitriptyline (Elavil)). For this reason it is often used in elder patients instead of other TCAs to reduce side effects and improving patient's compliance.
A study with men has found that treatment with nortriptyline is associated with higher risk of suicidal ideation compared to escitalopram.[10]

Warnings

Closer monitoring is required for those with a history of cardiovascular disease, stroke, glaucoma, or seizures, as well as those that have hyperthyroidism or are receiving thyroid medication.
Excessive consumption of alcohol in combination with nortriptyline therapy may have a potentiating effect, which may lead to the danger of increased suicidal attempts or overdosage, especially in patients with histories of emotional disturbances or suicidal ideation.