Amitriptyline INDEX

Those who fail to respond to an SSRI may respond to a TCA, and vice versa. Thus, these two broad-spectrum classes can be used in a sequential strategy to adequately treat the majority of cases. However, many physicians try another newer antidepressant (e.g, venlafaxine, bupropion, nefazodone) in such patients because of the safety and tolerability problems associated with TCAs. Of note, the tolerability profile of secondary amine TCAs such as desipramine is as favorable as any of the newer antidepressants and probably better than nefazodone. Nevertheless, the secondary amine TCAs have a therapeutic index as narrow as tertiary amine TCAs (e.g., amitriptyline, imipramine) in terms of lethality in overdoses resulting from cardiotoxicity. 

The majority of all deaths from antidepressant poisoning in Scotland, England, and Wales, during 1975-1984 and 1985-1989 were due to two tricyclic drugs, amitriptyline and dosulepin, and they, as well as the entire group of older tricyclic antidepressants, had a fatality index (deaths per million prescriptions) significantly higher than the mean (150). 

However, the use of antidepressants in completed suicide showed an upward trend, while the use of more violent methods (gassing, hanging) fell During this time prescription of moclobemide and two SSRIs (citalopram and fluoxetine) increased, while that of tricyclics (mainly doxepin and amitriptyline) remained steady. The mean annual fatal toxicity index was highest for tricyclics, such as doxepin, trimipramine, and amitripyline, and lowest for SSRIs. 

Very few fatalities have ever been reported (or studied), but it appears that the therapeutic index for ephedrine is very great. A 1997 case report described a 28-year-old woman with two prior suicide attempts, who died after ingesting amitriptyline and ephedrine. The blood ephedrine concentration was 11,000 ng/mL, and the liver concentration was twice that value (kidney, 14 mg/kg brain, 8.9 mg/kg). The amitriptyline concentration was 0.33 mg/kg in blood and 7.8 mg/kg in liver (131). Values in a second case report (where methylephedrine concentrations were nearly 6000 ng/mL) may or may not be relevant to the problem of ephedrine toxicity, as the individual in question took massive quantities of a calcium channel blocker, and it is not known whether methylephedrine exerts all the same effects as ephedrine (132). Baselt and Cravey mention the case of a young woman who died several hours after ingesting 2.1 g of ephedrine combined with 7.0 g of caffeine, but tissue findings were not described. Her blood ephedrine level was 5 mg/L, whereas the concentration in the liver was 15 mg/kg (133). 

Drug-Drug and Drug-Food Interactions. Since cinacalcet is metabolized by multiple hepatic enzymes there is potential for drug interactions. Cinacalcet is also a potent inhibitor of the enzyme CYP2D6. As a result, dose adjustments of concomitant medications that are predominantly metabolized by this enzyme and have a narrow therapeutic index such as flecainide, thioridazine, vinblastine, and most tricyclic antidepressants (i.e., amitriptyline) may be required. ... 

Very few fatalities have ever been reported (or studied), but it appears that the therapeutic index for ephedrine is very great indeed. A 1997 case report described a 28-yr-old woman with two prior suicide attempts, who died after ingesting amitriptyline and ephedrine. The blood ephedrine concentration was... 

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