Nortriptyline therapeutic plasma concentration

In acutely depressed patients, there is a correlation between antidepressant effect and plasma concentrations for some TCAs. Table 70-3 shows suggested therapeutic plasma concentration ranges. The best-established therapeutic range is for nortriptyline, and data suggest a therapeutic window. 

In healthy elderly patients, cautious use of a secondary amine TCA (desi pramine or nortriptyline) may be appropriate because of their defined therapeutic plasma concentration ranges, well-established efficacy, and well-known adverse-effect profiles. 

Therapeutic plasma concentrations of TCAs have clinically significant antiarrhythmic activity (420). Imipramine and nortriptyline (and probably other TCAs) share electrophysiological properties characteristic of type I (A, B) compounds (e.g., quinidine, procainamide, disopyramide) and can even be used in cardiac patients free from depression, exclusively for the control of arrhythmia (421). 

Fig. 9. Relationship between amelioration scores in depressed patients and steady-state plasma concentrations of the antidepressant nortriptyline. Both low and high concentrations are associated with minimum therapeutic effect. (From Asherg M, Cronholm B, Sjoqvist F, Tuck D. Relationship between plasma level and therapeutic effect of nortriptyline. Br Med J 1971 3 331-4, with permission from the BMJ Publishing Group.)...

Determination of nortriptyline plasma concentrations is not routinely recommended but may be useful in identifying toxicity, drug interactions, or noncompliance (adjustments in dosage should be made according to clinical response, not plasma concentrations) therapeutic range is 50-150 ng/ml... 

Large genetic differences in rate of metabolism concentrations of drug and metabolite (nortriptyline) cannot be predicted from dosage. Evidence for correlation between plasma concentrations and therapeutic response is mainly negative. 

Doses of tricyclic antidepressants are generally lower for pain than therapeutic ranges for depression. Most tricychcs can be started at 10-25 mg and titrated 25 mg at weekly intervals to therapeutic level (typically 75 mg for pain, maximum 150 mg) [1]. Nortriptyline is typically effective at about half the dose of am itriptyl-ine. Although not routinely recommended, plasma concentration may be measured to ensure nontoxic levels. 

Clinically meaningful plasma levels are available for imipramine, desipramine, and nortriptyline. For imipramine, the sum of the plasma levels of imipramine and the desmethyl metabolite (desipramine) should be greater than 200-250 ng/mL. Desipramine levels should be greater than 125 ng/mL. A therapeutic window has been noted for nortriptyline, with optimal response between 50 and 150 ng/mL. These therapeutic levels are based on steady-state concentrations, which are reached after 5-7 days of administration of these medications. Blood should be drawn approximately 10-14 hours after the last dose of medication. 

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