Amitriptyline (Elavil) versus ...

Amitriptyline vs Nortriptyline (Pamelor)

Both amitriptyline and nortriptyline are tricyclic antidepressants. Nortriptyline, a major metabolite of amitriptyline, is a secondary amine. It is less sedating and better tolerated than amitriptyline. But both have similar side effects, toxicities, and pharmacologic activity.

Amitriptyline and nortriptyline are FDA-approved for the treatment of depression. Amitriptyline has been better studied and its various off-label uses are better established.

Amitriptyline inhibits serotonin and noradrenaline reuptake equally, whereas nortriptyline is a more potent inhibitor of noradrenaline than of serotonin reuptake38. Nortriptyline has a longer half-life.

Nortriptyline is unique among the antidepressants in that its blood level demonstrates the classical therapeutic window effect37. Blood concentrations above or below the therapeutic window (60-200 ng/ml) correlate with poor clinical response. Thus, therapeutic monitoring to ensure the drug level within the therapeutic window is critical for successful treatment with nortriptyline.

Postherpetic neuralgia
Both amitriptyline and nortriptyline have a similar analgesic action in postherpetic neuralgia34. Nortriptyline causes fewer side effects and may be better tolerated than amitriptyline.


Which antidepressant is more effective? Amitriptyline may be more effective in the treatment of endogenous depressive illness.

Nortriptyline was compared with amitriptyline in the treatment of 50 patients suffering from primary depression and classified as reactive and endogenous depressions35. All patients received promazine hydrochloride in addition to specific antidepressant. Comparison without diagnostic classification showed no significant difference in outcome between the two drugs, although amitriptyline was consistently more effective. Improvement of symptoms of endogenous depressions treated with amitriptyline was significantly better than all other diagnostic groups. Reactive depressions on amitriptyline showed the least improvement but not significantly inferior to reactive and endogenous cases on nortriptyline, the latter two groups having almost identical results.

Which antidepressant work faster? Nortriptyline provides more rapid antidepressant effect36.

In a double-blind trial37 after 1 week patients treated with nortriptyline had a significantly greater mean reduction in Hamilton depression score (55% compared to 25% for amitriptyline patients).

Amitriptyline vs Desipramine (Norpramin)

Postherpetic neuralgia
Desipramine appears to produce the greater reduction in pain intensity. Clinically meaningful pain relief (moderate or better) is significantly more likely with desipramine than with amitriptyline 7.

Amitriptyline vs Capsaicin

Painful diabetic neuropathy
Topical capsaicin and oral amitriptyline produce equal and significant improvements in pain. However, topically applied capsaicin is considerably safer alternative to amitriptyline for relief of diabetic neuropathy pain and, unlike amitriptyline, does not cause systemic side effects 8.

Amitriptyline vs Venlafaxine

Migraine prophylaxis
Both have significant beneficial effect on pain parameters 10. Venlafaxine prevents headaches in much the same way as the amitriptyline but with a much more tolerable side effect profile. Venlafaxine may be preferred for migraine prophylaxis in patients involved in intense daily activities at work.

Major depression
Both are effective in the treatment of depression. There are no significant differences in efficacy 14.
Venlafaxine can improve social functioning more than amitriptyline. This effect may be linked to the higher rate of side effects with amitriptyline 15.

Side effects
Venlafaxine is associated with the lower rate of adverse effects than amitriptyline 10, 14.

Amitriptyline vs Trazodone

Major depressive disorder
Amitriptyline and trazodone are both effective but not statistically different from each other in terms of antidepressant action 2.

Neurotic depression
Amitriptyline is less effective than trazodone in the treatment of neurotic depression 18. Significant improvement may be noted with trazodone within the first 7 days of treatment.

Side effects
Amitriptyline produces significantly higher weight gains than Trazodone 1.
Amitriptyline has the effects on the electrocardiograph and on systolic time intervals consistent with its proven anticholinergic and quinidine-like properties. Trazodone, in contrast, has no quinidine-like effects and minor effects on systolic time intervals 3.
Both produce impairments on memory tasks. However, the effect of amitriptyline is significantly greater and may reflect its anticholinergic action over and above global sedative effects 16.
The study demonstrated that information processing, attention, and visual-motor skills are more adversely affected by amitriptyline 17.

Amitriptyline vs Divalproate

Migraine prophylaxis
Divalproate ER is more effective during first 3 months than amitriptyline in migraine33. However after 6 months, both are equally effective in migraine prophylaxis.

Side effects
Hair fall, menstrual irregularity, polycystic ovary, and weight gain occur more frequently with Divalproate ER33.


Further reading
  • 1. Hecht Orzack M, Cole JO, Friedman L, Bird M, McEachern J. Weight changes in antidepressants: a comparison of amitriptyline and trazodone. Neuropsychobiology. 1986;15 Suppl 1:28-30. PubMed
  • 2. Kerr TA, McClelland HA, Stephens DA, Ankier SI. A comparative clinical and predictive study. Acta Psychiatr Scand. 1984 Dec;70(6):573-7. PubMed
  • 3. van de Merwe TJ, Silverstone T, Ankier SI, Warrington SJ, Turner P. A double-blind non-crossover placebo-controlled study between group comparison of trazodone and amitriptyline on cardiovascular function in major depressive disorder. Psychopathology. 1984;17 Suppl 2:64-76. PubMed
  • 7. Rowbotham MC, Reisner LA, Davies PS, Fields HL. Treatment response in antidepressant-nai"ve postherpetic neuralgia patients: double-blind, randomized trial. J Pain. 2005 Nov;6(11):741-6. PubMed
  • 8. Biesbroeck R, Bril V, Hollander P, Kabadi U, Schwartz S, Singh SP, Ward WK, Bernstein JE. A double-blind comparison of topical capsaicin and oral amitriptyline in painful diabetic neuropathy. Adv Ther. 1995 Mar-Apr;12(2):111-20. PubMed
  • 10. Bulut S, Berilgen MS, Baran A, Tekatas A, Atmaca M, Mungen B. Venlafaxine versus amitriptyline in the prophylactic treatment of migraine: randomized, double-blind, crossover study. Clin Neurol Neurosurg. 2004 Dec;107(1):44-8. PubMed
  • 14. Benedictis E. Double-blind comparison of venlafaxine and amitriptyline in outpatients with major depression with or without melancholia. J Psychopharmacol. 2000 Mar;14(1):61-6. PubMed
  • 15. Gorenstein C, Andrade L, Moreno RA, Artes R. Social adjustment in depressed patients treated with venlafaxine and amitriptyline. Int Clin Psychopharmacol. 2002 Jul;17(4):171-5.
  • 16. Sakulsripong M, Curran HV, Lader M. Does tolerance develop to the sedative and amnesic effects of antidepressants? A comparison of amitriptyline, trazodone and placebo. Eur J Clin Pharmacol. 1991;40(1):43-8.
  • 17. Burns M, Moskowitz H, Jaffe J. A comparison of the effects of trazodone and amitriptyline on skills performance by geriatric subjects. J Clin Psychiatry. 1986 May;47(5):252-4. PubMed
  • 18. Goldberg HL, Finnerty RJ. Trazodone in the treatment of neurotic depression. J Clin Psychiatry. 1980 Dec;41(12 Pt 1):430-4. PubMed
  • 33. Kalita J, Bhoi SK, Misra UK. Amitriptyline vs divalproate in migraine prophylaxis: a randomized controlled trial. Acta Neurol Scand. 2013 Jul;128(1):65-72.
  • 34. Watson CP, Vernich L, Chipman M, Reed K. Nortriptyline versus amitriptyline in postherpetic neuralgia: a randomized trial. Neurology. 1998 Oct;51(4):1166-71. PubMed
  • 35. Rose JT, Leahy MR, Martin IC, Westhead TT. A comparison of nortriptyline and amitriptyline in depression. Br J Psychiatry. 1965 Nov
  • 36. Mendels J. Comparative Trial of Nortriptyline and Amitriptyline in 100 Depressed Patients. Am J Psychiatry. 1968 Feb
  • 37. Lehmann LS, Bowden CL, Redmond FC, Stanton BC. Amitriptyline and nortriptyline response profiles in unipolar depressed patients. Psychopharmacology (Berl). 1982
  • 38. Hyttel J, Christensen AV, Fjalland B. Neuropharmacological properties of amitriptyline, nortriptyline and their metabolites. Acta Pharmacol Toxicol (Copenh). 1980

Published: March 31, 2008
Last reviewed: May 14, 2017


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