Nortriptyline
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Nortriptyline
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| Systematic (IUPAC) name | |
| 3-(10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5-ylidene)- N-methyl-1-propanamine | |
| Identifiers | |
| CAS number | 894-71-3 (hydrochloride) |
| ATC code | N06 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C19H21N |
| Mol. mass | 263.377 g/mol |
| Pharmacokinetic data | |
| Bioavailability | well absorbed |
| Metabolism | Hepatic |
| Half life | 16 and 90 hours |
| Excretion | Renal |
| Therapeutic considerations | |
| Pregnancy cat. |
C |
| Legal status |
℞ Prescription only |
| Routes | oral |
Nortriptyline is a second generation tricyclic antidepressant marketed as the hydrochloride under the trade names Sensoval, Aventyl, Pamelor, Allegron and Nortrilen. It is used in the treatment of depression and childhood nocturnal enuresis (bedwetting). In addition it is sometimes used for chronic illnesses such as chronic fatigue syndrome, chronic pain and migraines, and labile affect in some neurological conditions.
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[edit] Clinical pharmacology
Nortriptyline inhibits the reuptake of norepinephrine (noradrenaline), and, to a lesser extent, serotonin. Nortryptiline also presents clinicically relevant post-synaptic antagonism of muscarinergic and 5HT2A receptors [1]. The former is responsible for anticholinergic side effects whereas the affinity for 5HT2A may be responsible for its sleep improving effect[2]. In the short run however, nortryptiline may disturb sleep due to its activating effect.
[edit] Indications
Nortriptyline is FDA approved for the treatment of depressive disorders. 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, prevention of migraine headaches and chronic pain or neuralgia modification (particularly TMJ disorder).[3] 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.[4] Research has been done suggesting it can reduce symptoms of ADHD.[citation needed] It should however be noted, that the co-administration of Tricyclic Antidepressants and stimulant ADD medications is highly inadvisable. Due to the blocking effect such medications have on both norepinephrine and serotonin, the stimulant properties of ADD medications can be severely potentiated, resulting in a risk of hypertension, tachycardia and central overstimulation.
[edit] 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.[citation needed] Blood levels of nortriptyline should be obtained during long term treatment to avoid toxicity and optimise response.
[edit] 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.[5]
For the management of nocturnal 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.[5]
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.
[edit] 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)).
[edit] 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.
[edit] 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 crisis and/or severe convulsions; fatalities have occurred.
[edit] Overdose
The symptoms and the treatment of an overdose are largely the same as for the other tricyclic antidepressants.
[edit] References
- ^ Gillman PK (2007). "Tricyclic antidepressant pharmacology and therapeutic drug interactions updated.". Br J Pharmacol 151 (6): 737-48. doi:. PMID 17471183.
- ^ Thase ME (2006). "Depression and sleep: pathophysiology and treatment.". Dialogues Clin Neurosci 8 (2): 217-26. PMID 16889107.
- ^ (2002) in Sweetman SC: Martindale. The complete drug reference, 33, 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:. PMID 9778204.
- ^ a b British National Formulary 45 March 2003
[edit] External links
- Internet Mental Health - Nortriptyline
- Drugs.com - Nortriptyline
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