High dose tertiary amine tricyclic antidepressants in the treatment of severe refractory depression: The central role of plasma concentration estimations

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, clompramine or dothiepin at high dosage (150–525 mg/day), usually in combination with lithium or other psychotropics. of serious adverse effects 83 per cent were encountered when tricyclic antidepressant (TCA) plasma concentrations exceeded 400 mcg/1. Therapeutic drug monitoring of high dose TCAs is useful in minimizing the risk of toxicity and in revealing poor compliance, undertreatment and pharmacokinetic 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.