The aim of the present study was to critically appraise current conceptual approaches; demographic, neurobiological and clinical correlates; and management strategies of treatment-resistant depression (TRD), especially in light of recent research findings. To this end, a review of the relevant English-language literature was undertaken using Medline, Embase and Psychinfo. TRD has been defined in conceptually restrictive terms as symptomatic non-response to physical therapies alone, with little systematic study of aetiology made. It is likely that a range of sociodemographic (such as higher socioeconomic status), genetic (such as variation in functional monoamine polymorphisms) and clinical variables (such as signal hyperintensities seen on structural neuroimaging scans) are responsible for non-response in individuals. There is insufficient evidence to suggest that TRD is associated with specific subtypes of depression, physical comorbidity, personality or chronicity. The large-scale Sequenced Treatment Alternatives to Relieve Depression (STAR*D) and other studies have suggested that a structured psychotherapy such as cognitive behaviour therapy may be as effective as medication in initial drug non-responders. Also conventional alternatives such as the use of older antidepressant classes, pharmacological augmentation or electroconvulsive therapy in established cases of TRD are not as effective as traditionally thought. There is insufficient preliminary evidence to make formal recommendations about the use of novel brain stimulation techniques in TRD. TRD should be re-defined as the failure to reach symptomatic and functional remission after adequate treatment with physical and psychological therapies. Treatment resistance may be more usefully conceived within the context of well-defined cohorts such as patients with specific subtypes of depression. Although neurobiological markers such as gene polymorphisms, which are potentially predictive of medication tolerance and efficacy, may be used in the future, it is likely that sociocultural variables such as beliefs about depression, and evidence-based treatments for it, will also determine treatment resistance.

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Background Medical practitioners experience high levels of mental disorders but may be reluctant to seek care. Aims To determine medical practitioner attitudes towards other doctors with anxiety/depression, barriers to seeking mental healthcare, treatments received for depression and the effects of age. Methods Data from the National Mental Health Survey of Doctors and Medical Students, conducted in Australia, were analysed (N = 10 038 medical practitioners). Attitudes to anxiety/depression were assessed with 12 statements (total stigma score, range 12–60). Barriers to seeking professional help, and coping strategies used, for anxiety/depression were measured. Practitioners with a history of depression were asked what personal supports and treatments were received. Practitioners were compared by age—younger (40 years and younger), middle-aged (41–60) and older (61+). Results Attitudes and help-seeking behaviours varied with age. Older doctors had a more positive outlook and less total stigma, with the exception that they believed a doctor with anxiety/depression was less reliable. Younger practitioners were most likely to report barriers, such as confidentiality, impact on career progression and registration, to seeking help. For practitioners with depression, counselling and counselling plus medication were most likely to be received by the younger and middle-aged groups, whereas medication alone was most likely to be received by the middle-aged and older groups. Conclusions Stigmatizing attitudes towards mental disorder and barriers to help-seeking remain prevalent within the medical profession. Our results suggest doctors’ health programs should address mental health stigma in younger practitioners and facilitate education about psychological treatments in older practitioners.