Abstract
Depression frequently fails to respond to initial treatment. Predominantly meta-analyses and RCTs but supplemented where necessary by additional data and the authors' clinical experience. A systematic assessment to identify remedial causes of poor response should be followed by planned sequential treatment trials. Joint decision making by the patient and clinician is essential. Strategies with the strongest support are antidepressant augmentation with lithium or second generation antipsychotics and adding cognitive behavioural treatment. Electroconvulsive therapy is highly effective in resistant depression but there is a high relapse rate when treatment ends. Some pharmacological strategies have inconsistent data (e.g. antidepressant combinations, T3 augmentation) or limited preliminary data (e.g. ketamine, antidepressant augmentation with pramipexole). The efficacy of vagus nerve stimulation, deep brain stimulation and repetitive transcranial magnetic stimulation is unclear. A greater understanding of the causes of depression may assist the development of more effective treatments. Role of glutamate antagonists and psychological treatments, other than cognitive behavioural therapy, as adjunctive treatments.
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