Randomised controlled trials investigating pharmacological and psychological interventions for treatment-refractory depression

Background About 30% of people with depression do not respond to an antidepressant at the recommended dose and can be described as having treatment-refractory depression. Aims To summarise the findings from all randomised controlled trials (RCTs) that have assessed the efficacy of a pharmacological or psychological intervention for treatment-refractory depression. Method We used a systematic search strategy to identify RCTs that included adults aged 18–75 years with a diagnosis of unipolar depression that had not responded to a 4-week course of a recommended dose of an antidepressant. Results We identified 16 RCTs. None of the included trials assessed the efficacy of psychotherapy. All the trials were too small to detect an important clinical response. We found only two trials on lithium augmentation, which randomised 50 subjects in total. Conclusions There is little evidence to guide the management of depression that has not responded to a course of antidepressants. Treatment-refractory depression is an important public health problem and large pragmatic trials are needed to inform clinical practice.