Tricyclic antidepressants for treatment-resistant depression

Tricyclic antidepressants (TCAs) are effective treatments for unipolar depressive syndromes, including major depressive disorder. However, despite decades of clinical use, the efficacy of TCAs for treatment-resistant depression (TRD) has received relatively little attention. In this chapter, we review the pharmacological properties (including their relative affinities for human cloned neuroreceptors, side effects, toxicological profiles, pharmacokinetic properties, and drug-drug interactions) and clinical evidence supporting the use of TCAs for a range of depressive disorders in adults, including those with TRD. We close by providing practical advice on the prescribing and monitoring of TCA treatment for patients with TRD, including strategies that may be effective for optimizing their clinical effectiveness, tolerability, and safety for depressed patients.