These effects account for some therapeutic actions as well as for most side effects such as sedation, hypotension, anticholinergic effects, etc. Nortriptyline may also have a sleep-improving effect due to its affinity for 5HT2A and histaminergic receptors. In the short run however, nortriptyline may disturb sleep due to its activating effect.
Like other tricyclic antidepressants, nortriptyline also blockssodium channels, possibly accounting in part for its analgesic action.
In one study of long-term efficacy, nortriptyline showed a higher relapse rate in comparison with phenelzine in individuals being treated for depression, possibly due to the metabolite 10-hydroxynortriptyline being produced. The authors of a review noted that the nortriptyline group had more episodes prior to treatment.
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.
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. Blood levels of nortriptyline should be obtained during long term treatment to avoid toxicity and optimize response.
For depression low starting doses are used, increasing as necessary to 75–100 mg (0–50 mg for adolescents and the elderly). Maximum daily dosage is 150 mg.
For the management of nocturnal enuresis lower dosages are used with a maximum period of three months, followed by gradual withdrawal, and a full examination including electrocardiogram required before further courses.
For its off-label use for migraine and headache prophylaxis and treating chronic pain treatment is started at very low 10 mg once at night to minimize side-effects. The dose is then increased every two weeks if required to a maximum of 150 mg.
Dosage availability is 10 mg, 25 mg, 50 mg, and 75 mg capsules (Sandoz/Mallinckrodt Pharm).
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.
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.
The symptoms and the treatment of an overdose are largely the same as for the other tricyclic antidepressants, including serotonin syndrome and adverse cardiac effects. As tricyclic antidepressants have a relatively narrow therapeutic index, the likelihood of overdose (both accidental and intentional) is fairly high and should be considered carefully by the prescribing physician prior to patient use.
A nortriptyline overdose should always be considered a medical emergency and can result in death. In the event of a known or suspected overdose, poison control (1-800-222-1222 in the U.S.) or 911 (999 in the U.K.) should be contacted immediately. If no phone services are available the overdose victim should be brought to the nearest hospital as soon as possible.