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 uptake equally, whereas nortriptyline is a more potent inhibitor of noradrenaline than of serotonin uptake38. Nortriptyline has a longer half-life.
Nortriptyline is unique among the antidepressants in that its blood level exhibits the classical therapeutic window effect37. Bood 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.
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. The outcome 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 outcomes.
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 Gabapentin (Neurontin)
Diabetic peripheral neuropathy pain
In the study comparing
the efficacy of gabapentin with amitriptyline on diabetic peripheral
neuropathy pain, moderate or greater pain relief was experienced in
52% of patients with gabapentin and 67% of patients with amitriptyline.
Gabapentin does not appear to offer considerable advantage over amitriptyline
and is more expensive 4.
Another study have shown that gabapentin produces greater improvements
than amitriptyline in pain and paresthesia associated with diabetic
Chronic pelvic pain
Gabapentin alone or in combination with
amitriptyline is superior to amitriptyline alone in the treatment
of female chronic pelvic pain 5.
Peripheral neuropathic pain
Both gabapentin and amitriptyline
provided effective pain control in peripheral neuropathic pain. However,
improvement in shooting pain and patient satisfaction is significantly
higher with gabapentin treatment. Additionally gabapentin was more
effective especially in paroxysmal shooting pain than other pain qualities 13.
Safety & Side effects
Gabapentin is better tolerated than
amitriptyline and is associated with lower rate of side effects 5, 6, 13.
Gabapentin has no significant interactions while amitriptyline has several clinically significant drug interactions (e.g. MAOI, cisapride, thyroid agents).
Gabapentin is more costly than amitriptyline and requires frequent dosing regimen.
Amitriptyline vs Desipramine (Norpramin)
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 Topical 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 the pain of diabetic
neuropathy and, unlike amitriptyline, is not assosiated with systemic
side effects 8.
Amitriptyline vs Fluoxetine
Major depressive disorder
Both are effective in relieving
the symptoms of depression 23. Recent memory can be improved significantly
with the fluoxetine treatment 24.
Fluoxetine and amitriptyline have comparable
efficacy in the treatment of major depression with associated anxiety 21.
Fluoxetine and amitriptyline are similarly effective
treatments for FM, and they work better in combination than either
antidepressant alone 9.
In the study moderate or good pain
relief was reported by 82% patients with amitriptyline, and by 77%
patients with fluoxetine. Fluoxetine relieved low back pain and whiplash
associated cervical pain with efficacy similar to that of amitriptyline 22.
Adverse effects are more frequent and
more severe with the amitriptyline 21. The most frequent side effects
with fluoxetine are nausea, nervousness, sleep disturbances, and headaches;
and dry mouth, dizziness, and drowsiness with amitriptyline 23, 24, 26.
Weight gain is associated more with amitriptyline 25.
Amitriptyline vs Venlafaxine
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.
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
Venlafaxine is associated with the lower
rate of adverse effects than amitriptyline 10, 14.
Amitriptyline vs Citalopram
Comorbidity of depression, migraine, and tension-type headache
Amitriptyline and citalopram are equally efficacious in relieving
depressive symptoms. However, amitriptyline appears to be more efficacious
than citalopram in reducing migraine and tension-type headache attacks
Combined therapy with amitriptyline and citalopram may be particularly
beneficial for individuals with tension-type headache, migraine and
comorbid depression that do not respond to monotherapy.
Chronic tension-type headache
Amitriptyline can significantly
reduce the duration of headache, headache frequency, and intake of
analgesics, whereas citalopram has no significant effect 12.
Both are effective, and citalopram is probably
as efficacious as amitriptyline. However, amitriptyline may have
a better effect on sleep disturbances due to its more hypnotic effect 19, 20.
Amitriptyline produces more frequent
side effects and is less well tolerated than citalopram 19, 20.
Amitriptyline vs Paroxetine
Major depressive disorder
Amitriptyline and paroxetine appear
to have similar antidepressive efficacy. However, in clinical study
amitriptyline showed a greater degree of retardation reduction 27, 28, 29.
Amitriptyline is associated with a significantly
higher incidence of anticholinergic effects, whereas nausea, agitation
and insomnia occur more often with paroxetine 27, 28.
Amitriptyline vs Sertraline
Major depressive disorder
Both sertraline and amitriptyline
are effective and have comparable efficacy in major
depression 30, 31.
Sertraline has significant advantages
over amitriptyline in regard to safety. Sertraline produces higher
proportion of gastrointestinal and male sexual dysfunction complaints
than the amitriptyline. Amitriptyline produces a higher proportion
of anticholinergic, sedative, autonomic and circulatory side effects
and dizziness compared with sertraline. Sertraline has a considerably
less detrimental effect on psychomotor performance and may have a
slight activating effect not found with amitriptyline 30, 31, 32.
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.
is less effective in the treatment of neurotic depression 18.
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
The study demonstrated that information processing, attention, and
visual-motor skills are more adversely affected by amitriptyline 17.
Amitriptyline vs Divalproate
Divalproate ER is more effective during first 3 months than amitriptyline in migraine33. However after 6 months, both are equally effective in migraine prophylaxis.
Hair fall, menstrual irregularity, polycystic ovary, and weight gain occur more frequently with Divalproate ER33.
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Published: March 31, 2008
Last updated: December 03, 2013