Psychiatry has provided primary care physicians with tools for recognising and labelling mild, moderate or severe 'depression'. General practitioners (GPs) in the UK have been guided to manage depression within primary care and to prescribe anti-depressants as a first-line treatment. The present study aimed to examine how GPs would construct 'depression' when asked to talk about those anomalous patients for whom the medical frontline treatment did not appear to be effective. Twenty purposively selected GPs were asked in an interview to talk about their experience and management of patients with depression who did not respond to anti-depressants. GPs initially struggled to identify a group, but then began to construct a category of person with a pre-medicalised status characterised by various deviant features such as unpleasant characters and personalities, manipulative tendencies, people with entrenched social problems unable to fit in with other people and relate to people normally. GPs also responded in non-medical ways including feeling unsympathetic, breaking confidentiality and prescribing social interventions. In effect, in the absence of an effective medical treatment, depression appeared to become demedicalised. The implications of this process are discussed in relation to patients' subsequent access or lack of access to services and the way in which these findings highlight the processes by which medicine frames disease.