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Nortriptyline is a second generation tricyclic antidepressant
marketed as the hydrochloride under the trade names
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, Migraine, and labile
affect in some neurological conditions.
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.
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.
Research has been done suggesting it can reduce symptoms
of ADHD.
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 150mg.
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®)).
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.
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