Nortriptyline

Also Known As: Nortriptyline, Sensoval, Aventyl, Pamelor, Norpress, Allegron, Noritren, Nortrilen

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 illnesses such as chronic fatigue syndrome, chronic pain and migraine, and labile affect in some neurological conditions. It is inferior to other antidepressants due to it having a high relapse rate in the treatment of major depression; this is believed to be due to the adverse effects of a metabolite of nortriptyline called 10-hydroxynortriptyline.

Nortriptyline is the active metabolite of amitriptyline that is demethylated in the liver. It inhibits the reuptake of norepinephrine (noradrenaline) and, to a lesser extent, serotonin with negligible effects on dopamine reuptake.

These effects account for some therapeutic actions as well as for most side effects (sedation, hypotension, anticholinergic effects, etc.). Nortriptyline may also have a sleep-improving effect due to its affinity for 5HT2A and histaminergic receptors.[2] In the short run however, nortriptyline may disturb sleep due to its activating effect.

Like other tricyclic antidepressants, nortriptyline also blocks sodium channels, possibly accounting in part for its analgesic action.

Nortriptyline has poor long-term efficacy with a high relapse rate in individuals being treated for depression, possibly due to a toxic metabolite 10-hydroxynortriptyline, being produced. Thus it is significantly inferior to other antidepressants such as moclobemide and other older antidepressants.[3](The authors of this review did note that the nortriptyline group had more prior episodes.)

Indications

Nortriptyline is FDA-approved for the treatment of major depression. In the United Kingdom, it may also be used for treating nocturnal enuresis, with courses of treatment lasting no more than three months. It is also used off-label for the treatment of panic disorder, irritable bowel syndrome, migraine prophylaxis and chronic pain or neuralgia modification (particularly TMJ disorder).[4] 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.[5] Research has been done suggesting it can reduce symptoms of ADHD.[6]

Neuropathic pain

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].

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