It can be tried for depression as a second-line therapy, after the failure of other treatments. For treatment-resistant adolescent depression or for cancer-related depression amitriptyline is no better than placebo. It is sometimes used for the treatment of depression in Parkinsons disease, but supporting evidence for that is lacking. Pain
Amitriptyline alleviates painful diabetic neuropathy. It is recommended by a variety of guidelines as a first or second line treatment. It is as effective for this indication as gabapentin or pregabalin but less well tolerated.Low doses of amitriptyline moderately improve sleep disturbances and reduce pain and fatigue associated with fibromyalgia. It is recommended for fibromyalgia accompanied by depression by Association of the Scientific Medical Societies in Germany and as a second-line option for fibromyalgia, with exercise being the first line option, by European League Against Rheumatism. Combinations of amitriptyline and fluoxetine or melatonin may reduce fibromyalgia pain better than either medication alone.There is some (low-quality) evidence that amitriptyline may reduce pain in cancer patients. It is recommended only as a second line therapy for non-chemotherapy-induced neuropathic or mixed neuropathic pain, if opioids did not provide the desired effect.Moderate evidence exists in favor of amitriptyline use for atypical facial pain. Amitriptyline is ineffective for HIV-associated neuropathy. Headache
Amitriptyline is probably effective for the prevention of periodic migraine in adults. Amitriptyline is similar in efficacy to venlafaxine and topiramate but carries a higher burden of adverse effects than topiramate. For many patients, even very small doses of amitriptyline are helpful, which may allow for minimization of side effects.
Benzodiazepines are recommended to control seizures. Dialysis is of no use due to the high degree of protein binding with amitriptyline. Interactions
Since amitriptyline and its active metabolite nortriptyline are primarily metabolized by cytochromes CYP2D6 and CYP2C19 (see Amitriptyline#Pharmacology), the inhibitors of these enzymes are expected to exhibit pharmacokinetic interactions with amitriptyline. According to the prescribing information, the interaction with CYP2D6 inhibitors may increase the plasma level of amitriptyline. However, the results in the other literature are inconsistent: the co-administration of amitriptyline with a potent CYP2D6 inhibitor paroxetine does increase the plasma levels of amitriptyline two-fold and of the main active metabolite nortriptyline 1.5-fold, but combination with less potent CYP2D6 inhibitors thioridazine or levomepromazine does not affect the levels of amitriptyline and increases nortriptyline by about 1.5-fold; a moderate CYP2D6 inhibitor fluoxetine does not seem to have a significant effect on the levels of amitriptyline or nortriptyline. A case of clinically significant interaction with potent CYP2D6 inhibitor terbinafine has been reported.A potent inhibitor of CYP2C19 and other cytochromes fluvoxamine increases the level of amitriptyline two-fold while slightly decreasing the level of nortriptyline. Similar changes occur with a moderate inhibitor of CYP2C19 and other cytochromes cimetidine: amitriptyline level increases by about 70%, while nortriptyline decreases by 50%. CYP3A4 inhibitor ketoconazole elevates amitriptyline level by about a quarter. On the other hand, cytochrome P450 inducers such as carbamazepine and St. Johns Wort decrease the levels of both amitriptyline and nortriptylineOral contraceptives may increase the blood level of amitriptyline by as high as 90%.