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 patient s with severe, refractory major depression who were prescribed amitrip tyline, clomipramine or dothiepin at high dosage (150-525 mg/day), usu ally in combination with lithium or other psychotropics. Of serious ad verse effects 83 per cent were encountered when tricyclic antidepressa nt (TCA) plasma concentrations exceeded 400 mcg/l. Therapeutic drug mo nitoring of high dose TCAs is useful in minimizing the risk of toxicit y and in revealing poor compliance, undertreatment and pharmacokinetic interactions which can mitigate against drug efficacy, The value of c arbamazepine in the management of refractory depression in the context of unipolar affective disorder is put into question.