|Systematic (IUPAC) name|
|Legal status||℞ Prescription only|
|Half-life||16 and 90 hours|
|Mol. mass||263.38 g/mol|
| (what is this?)
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.
Nortriptyline is an 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. Nortriptyline also has antagonistic effects at a variety of receptors:
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.2 In the short run however, nortriptyline may disturb sleep due to its activating effect.
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.3 The authors of a review noted that the nortriptyline group had more episodes prior to treatment.3
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 temporomandibular joint 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 also reduce symptoms of ADHD.6
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
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.
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.9
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.9
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.
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.
Nortriptyline should not be used 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 crisis caused by serotonin syndrome or severe convulsions.
The symptoms and the treatment of an overdose are largely the same as for the other tricyclic antidepressants. 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.
- Gillman PK (2007). "Tricyclic antidepressant pharmacology and therapeutic drug interactions updated". Br J Pharmacol 151 (6): 737–48. doi:10.1038/sj.bjp.0707253. PMC 2014120. PMID 17471183.
- Thase ME (2006). "Depression and sleep: pathophysiology and treatment". Dialogues Clin Neurosci 8 (2): 217–26. PMC 3181772. PMID 16889107.
- Kennedy SH (March 1997). "Continuation and maintenance treatments in major depression: the neglected role of monoamine oxidase inhibitors". J Psychiatry Neurosci 22 (2): 127–31. PMC 1188835. PMID 9074307.
- Sweetman SC, ed. (2002). Martindale. The complete drug reference (33 ed.). Pharmaceutical Press. ISBN 0-85369-499-0.
- Prochazka A, Weaver M, Keller R, Fryer G, Licari P, Lofaso D (1998). "A randomized trial of nortriptyline for smoking cessation". Arch Intern Med 158 (18): 2035–9. doi:10.1001/archinte.158.18.2035. PMID 9778204.
- Wilens, Timothy E.; Biederman, Joseph M.D.; Geist, David E.; Steingard, Ronald M.D.; Spencer, Thomas M.D. (1993). "Nortriptyline in the Treatment of ADHD: A Chart Review of 58 Cases". J. Am. Acad. Child Adolesc. Psychiatry (American Academy of Child and Adolescent Psychiatry) 32 (2): 343–349. doi:10.1097/00004583-199303000-00015. PMID 8444763.
- Robert H. Dworkin et al. (2010). "Recommendations for the Pharmacological Management of Neuropathic Pain: An Overview and Literature Update". Mayo Clinic Proceedings 85 (3): S3–S14. doi:10.4065/mcp.2009.0649. PMC 2844007. PMID 20194146.
- "Pamelor (nortriptyline HCl) drug information". Retrieved 15 February 2010.
- British National Formulary 45 March 2003
- Perroud, N.; Uher, R.; Marusic, A.; Rietschel, M.; Mors, O.; Henigsberg, N.; Hauser, J.; Maier, W. et al. (2009). "Suicidal ideation during treatment of depression with escitalopram and nortriptyline in Genome-Based Therapeutic Drugs for Depression (GENDEP): a clinical trial". BMC medicine 7: 60. doi:10.1186/1741-7015-7-60. PMC 2768737. PMID 19832967. More than one of
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