Plasma nortriptyline concentrations

Smith T, Riskin J. Effect of clozapine on plasma nortriptyline concentration. Pharmacopsychiatry 1994 27 41-42. 

JD Robinson, RA Braithwaite, S Dawling. Measurement of plasma nortriptyline concentrations radioimmunoassay and gas chromatography compared. Clin Chem 24 2023, 1978. 

Kahn DG. Increased plasma nortriptyline concentration in a patient cotreated witii fluoxetine. J Clin Psychiatry (1990) 51, 36. 

Measurement of Plasma Nortriptyline Concentration Radioimmunoassay and Gas Chromatography Compared Clin. Chem. 24(11) 2023-2025 (1978) CA 90 80590p... 

Routine monitoring of plasma concentrations of antidepressants, while technically feasible for most drugs, is of uncertain value (except for nortriptyline). However, studies suggest that at least 20% of patients become noncompliant at some time or other. Thus, a "poor response" in a patient for whom an adequate dosage of drug has been prescribed may be shown by measurement of the plasma drug concentration to be due merely to failure to take the drug. 

St John s wort can cause drug interactions by inducing hepatic microsomal drug-metabolizing enzymes or the drug transporter P-glycoprotein, which causes a net efflux of substrates, such as amitriptyline, from intestinal epithelial cells into the gut lumen (SEDA-24,12). In 12 patients (9 women, 3 men) the addition of St John s wort 900 mg/ day to amitriptyline 150 mg/day led to a 20% reduction in plasma amitriptyline concentrations, while nortriptyline concentrations were almost halved (210). 

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. 

A9. Asberg, M. B., Cronholm, F., and Sjoqvist, F., The correlation of subjective side-effects with plasma concentrations of nortriptyline. Brit. Med. J. Iv, 18-21... 

All. Asberg, M., Price Evans, D., and Sjoqvist, F., Genetic control of nortriptyline kinetics in man. A study of relatives of propositi with high plasma concentrations. J. Med. Genet. 8, 129-135 (1971). 

B34. Burrows, G. D., Davies, B., and Scoggins, B. A., Plasma concentration of nortriptyline and clinical response in depressive illness. ImticH ii, 619-623 (1972). 

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... 

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. 

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). 

The adverse effects of TCAs are also similar to those reported in adults (see Chapter 7). The secondary amine TCAs (e.g., desipramine, nortriptyline) are generally as well tolerated as newer antidepressants. Increased blood pressure may be more likely to occur in children than in adults but hypertension per se is rare ( 135). The most common cardiovascular effect is mild tachycardia. Despite their generally favorable adverse effect profile, secondary amine TCAs can cause serious toxicity in children and adolescents just as in adults when a taken in an overdose or when a high TCA plasma level occurs as a result of slow metabolism ( 136). For that reason, most clinicians reserve TCAs for the child or adolescent who has at least a moderate depressive disorder unresponsive to a trial of one or more newer antidepressants. In such instances, TDM should be done at least once to ensure plasma concentrations greater than 450 ng/mL do not develop ( 137). Such levels are associated with an increased risk of the following ... 

The usual daily dose ranges of antidepressants are shown in Table 30-4. Doses are almost always determined empirically the patient s acceptance of adverse effects is the usual limiting factor. Tolerance to some of the objectionable effects may develop, so that the usual pattern of treatment has been to start with small doses, increasing either to a predetermined daily dose, or to one that produces relief of depression, or to the maximum tolerated dose (except in the case of nortriptyline, which loses efficacy at plasma concentrations over 150 ng/mL). 

MAOIs TCAs-AMITRIPTYLINE CLOMIPRAMINE DESIPRAMINE IMIPRAMINE NORTRIPTYLINE t risk of stroke, hyperpyrexia and convulsions, t plasma concentrations of TCAs, with risk of toxic effects, t risk of serotonin syndrome and of adrenergic syndrome with older MAOIs. Clomipramine may trigger acute confusion in Parkinson s disease when used with selegiline TCAs are believed to also act by inhibiting the reuptake of serotonin and norepinephrine, increasing the risk of serotonin and adrenergic syndromes. The combination of TCAs and antidepressants can t risk of seizures Very hazardous interaction. Avoid concurrent use and consider the use of an alternative antidepressant. Be aware that seizures occur with overdose of TCAs just before cardiac arrest... 

TERBINAFINE ANTIDEPRESSANTS- IMIPRAMINE, NORTRIPTYLINE Possible T plasma concentrations ofTCAs Terbinafine strongly inhibits CYP2D6-mediated metabolism of nortriptyline Warn patients to report t side-effects of TCAs such as dry mouth, blurred vision and constipation, which may be an early sign of t TCA levels. In this case, consider i dose of TCA... 

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. 

Fluvoxamine, a CYP450 1A2 inhibitor, can decrease the conversion of amitriptyline to nortriptyline and increase amitriptyline plasma concentrations... 

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