Potentiation strategies for treatment-resistant depression

Objective: To review the pharmacological basis of antidepressant potentiation in combination therapy and the clinical evidence for its efficacy. Method: Literature searches were undertaken and the results reviewed. Results: Treatment-resistant depression is common (15–30%). Various strategies exist for dealing with resistant depression, including pharmacological potentiation, i.e. adding a treatment that itself does not have antidepressant actions but that enhances the efficacy of the original treatment. Lithium, triiodothyronine (T3) and buspirone are the best studied potentiating drugs, although other options include pindolol, dopaminergic agents, second-generation antipsychotics, psychostimulants, hormones and anticonvulsants. Conclusion: Several pharmacological potentiation strategies exist. Whilst good evidence exists for lithium combined with antidepressants, although good results have also been reported with augmentation strategies involving T3 or buspirone.