Substitution therapy in patients with major depression

Antidepressants are one of the most effective treatments for major depressi ve disorder. However, despite optimal treatment, a substantial number of pa tients, up to 50%, may have a partial or no response to the first antidepre ssant used. In such cases, several options are available. These include sub stitution of the first antidepressant with a second antidepressant, often o f a different class, or various combination or augmentation strategies. In general, substitution is a well tolerated and effective way of managing treatment-resistant depression. Switching to an alternative class of antide pressants usually increases the chances of treatment response, although wit h the selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors ( SSRIs) a second trial may be attempted with the same class of drug. In gene ral, a washout period between trials of different compounds is not necessar y, except when first generation monoamine oxidase inhibitors are used. In t hat situation, an appropriate washout period is required when switching to or from this class of compound, particularly when switching to or from the SSRIs. Further studies are required to determine the relative benefits of augmenta tion/combination versus substitution treatment of refractory depression.