Abstract
Below the toxic plasma level of nortriptyline (NT) an upper therapeutic limit has been postulated in patients with endogenous depression. If so the clinical significance is obvious and a double-blind, randomized study was performed in order to solve this problem. Two groups of patients were controlled at different plasma levels (< 150 ng/ml and > 180 ng/ml). The degree of depression was rated weekly. Only about one third (n=24) of the patients originally included, were carried through the full protocol, the most prominent reason for drop out beeing spontaneous remission during an initial placebo period. After 4 weeks of NT treatment the majority in the high level group was still depressed, but the difference barely significant (P=5.5%). However, a randomized reduction of the plasma level among the patients at the high level resulted in a significant correlation to remission. Evaluation of the total material after 6 weeks of NT treatment demonstrated a strong correlation of high plasma level to poor antidepressive effect of NT. No correlation could be obtained between side-effects, which were few, and plasma level. The non-proteinbound fraction in plasma was found to 7% (SD 1.83) by simultaneous determinations of NT in plasma and CSF in 13 patients. The variation in the proteinbinding was not likely to invalidate the over all results based on total NT determination. A therapeutic plasma range of 50–150 ng/ml is recommended.
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Supported by Grants from The Danish State Medical Research Council.
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Kragh-SØrensen, P., Eggert Hansen, C., Baastrup, P.C. et al. Self-inhibiting action of nortriptylin's antidepressive effect at high plasma levels. Psychopharmacologia 45, 305–312 (1976). https://doi.org/10.1007/BF00421145
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DOI: https://doi.org/10.1007/BF00421145