High Dose Tertiary Amine Tricyclic Antidepressants in The Treatment of Severe Refractory Depression: The Central Role of Plasma Concentration Estimations.

Hodgkiss, A. D.; McCarthy, P. T.; Sulke, A. N.; Bridges, P. K.

The relationships between dosage, plasma concentration, antidepressant response and toxicity were investigated in 24 highly selected patients with severe, refractory major depression who were prescribed amitriptyline, clomipramine or dothiepin at high dosage (150- 525 mg/day), usually in combination with lithium or other psychotropic's. Of serious adverse effects 83 per cent were encountered when tricyclic antidepressant (TCA) plasma concentrations exceeded 400 meg/l. Therapeutic drug monitoring of high dose TCAs is useful in minimizing the risk of toxicity and in revealing poor compliance under treatment and pharmacokinetics interactions which can mitigate against drug efficacy. The value of carbamazepine in the management of refractory depression in the context of unipolar affective disorder is put into question.

DEPRESSED persons; ANTIDEPRESSANTS; CARBAMAZEPINE; PHARMACOKINETICS; AFFECTIVE disorders; DRUG dosage

Human Psychopharmacology: Clinical & Experimental, 1995, Vol 10, Issue 5, p407

0885-6222

Academic Journal

10.1002/hup.470100506