Correlation of Subjective Side Effects with Plasma Concentrations of Nortriptyline

Abstract

Summary: Plasma levels of tricyclic antidepressant drugs vary considerably between individuals receiving the same amount of drug. The bearing of this variation on the occurrence of subjective side effects was investigated in 40 psychiatric inpatients with depressive disorders. Plasma levels were determined before and during four weeks of treatment with nortriptyline 50 mg. three times a day and patients were rated for subjective side effects, the assessors being unaware of the plasma levels of the drug.Plasma levels varied widely between individual patients, but in any given patient the plasma level tended to be constant over a period of time. The side effects of nortriptyline diminished significantly with time and were in most cases absent during the fourth week of treatment. There was a significant positive correlation between plasma level of nortriptyline and subjective side effects. The steady-state plasma level of a drug which is metabolized is usually a more important determinant for its effect than dosage, since it reflects the amount of drug available for biological action. Very high plasma levels of nortriptyline should presumably be avoided, since there is no evidence that they are needed for therapeutic effect and they are potentially harmful.

Symptoms of Major Depression and Tricyclic Side Effects in Primary Care Patients

“…It extends our understanding of the course of these somatic symptoms beyond the time frame previously reported for depressed psychiatric, 13,15 geriatric, 16 or primary care patients. 18 Our findings clearly support the concept that treatment of the underlying depressive episode can reduce the number and severity of depression-associated somatic symptoms experienced by primary care patients.…”

“…Nevertheless, our findings resemble those in previous studies of somatic symptoms among depressed patients. [13][14][15]36,46 The presence of symptoms resembling tricyclic side effects in depressed primary care patients does not appear to contraindicate the initiation of tricyclic pharmacotherapy. Clinicians should consider their patients' somatic complaints within the clinical context in which they occur before attributing them to their medications.…”

“…Symptoms resembling the side effects of tricyclic antidepressants have been found among depressed psychiatric, [13][14][15] geriatric, 16 and primary care [17][18][19] patients even before these medications were provided them. Given these earlier reports, more information is needed about the relation between subjective symptoms resembling tricyclic side effects and the severity of the depressive episode along with the influence of a comorbid anxiety disorder on these symptoms.…”

CSF and plasma levels of nortriptyline and its 10‐hydroxy metabolite.

“…High plasma levels of NT have also been shown to be associated with side effects (Asberg et al, 1970). Plasma levels of NT are determined by the rate of 10-hydroxylation in the liver (Alexanderson & Borg'a 1973;Mellstrom et al, 1981).…”

The Assessment of Potential Drug Interactions With a New Tricyclic Antidepressant Drug

“…Individual variability in metabolism of tricyclics, or interaction with these drugs, leads to difficulty in choosing optimal dosage for many patients (Alexanderson, (Asberg, Cronholm, Sjoqvist & Tuck, 1970). Some tricyclic antidepressants inhibit microsomal drug oxidizing enzymes and may alter the metabolism of drugs such as propranolol (Shand & Oates, 1971) and antipyrine (O'Malley, Sawyer, Stevenson & Turnbull, 1972) when administered simultaneously.…”