Nortriptyline

Nortriptyline is a second generation tricyclic antidepressant marketed as the hydrochloride under the tradenames Aventyl®, Pamelor® and Nortrilen®. It is used in the treatment of depression and childhood nocturnal enuresis (bedwetting). In addition it is sometimes used for chronic pain modification and labile affect in some neurological conditions.

Clinical pharmacology
Nortriptyline inhibits the reuptake of serotonin, and, to a lesser extent, norepinephrine (noradrenalin) (Basic & Clinical Pharmacology, 10th Edition, Bertram G. Katzung, MD, PhD). Operant conditioning techniques in rats and pigeons suggest that nortriptyline has a combination of stimulant and depressant properties.

Indications
FDA-approved for treatment of depressive disorders. In the United Kingdom also may be used for treating nocturnal enuresis with courses of treatment lasting no more than three months. Also used off-label for the treatment of panic disorder, irritable bowel disease, prevention of migraine headaches and chronic pain or neuralgia modification (particularly Temporomandibular joint disorder). It can also aid in quitting smoking with one study showing a six-month abstinence rate of 14% for subjects receiving nortriptyline compared to 3% for subjects not undergoing pharmacological treatment.

Metabolism
Nortriptyline is metabolised in the liver by hepatic enzyme CYP2D6. Approximately 7 to 10 percent of Caucasians are poor metabolisers 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 optimise response.

Dosage
For depression: low starting doses are used, increasing as necessary to 75–100mg (0–50mg for adolescents and the elderly). Maximum daily dosage is 150mg.

For the management of noctiral enuresis: lower dosages are used with the maximum period of treatment, including gradual withdrawal, being three months and a full examination including electrocardiogram (ECG or EKG) required before further courses.

For its off-label use for migraine and headache prophylaxis and treating chronic pain: treatment is started at very low 10mg once at night to minimise side-effects. The dose is then increased every two weeks if required to a maximum of 50mg.

Side effects
Dry mouth, drowsiness, orthostatic hypotension, urinary retention, constipation, and rapid or irregular heartbeat. Some sexual side effects may be a problem as well. Less commonly, seizures and ECG/EKG changes have been reported, especially in overdose.

Alcohol may exacerbate some of its side effects and should be avoided.

However, the incidence of side effects with nortriptyline is somewhat lower than with the first generation tricyclics (e.g. imipramine (Tofranil®), amitriptyline (Elavil®)).

Warnings
Closer monitoring is required for those with a history of cardiovascular disease, stroke, glaucoma and/or seizures as well as those who have hyperthyroidism or are receiving thyroid medication.

Contraindications
In the acute recovery phase after myocardial infarction (e.g. heart attack). As for all tricyclic antidepressants concurrent use, or failure to allow a two week gap, with monoamine oxidase inhibitors (MAO inhibitors, e.g. phenelzine, tranylcypromine, etc.) may precipitate hyperpyretic crises and/or severe convulsions; fatalities have occurred.

Overdose
The symptoms and the treatment of an overdose are largely the same as for the other tricyclic antidepressants.