title: Managing inadequate antidepressant response in depressive illness.
abstract: BACKGROUND
  Depression frequently fails to respond to initial treatment.
  
  
  METHODS
  Predominantly meta-analyses and RCTs but supplemented where necessary by additional data and the authors' clinical experience.
  
  
  RESULTS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  A greater understanding of the causes of depression may assist the development of more effective treatments.
  
  
  CONCLUSIONS
  Role of glutamate antagonists and psychological treatments, other than cognitive behavioural therapy, as adjunctive treatments.
authors: Neuroscience and Psychiatry Unit, University of Manchester, Stopford Building, Oxford Rd, Manchester M13 9PT, UK Greater Manchester West Mental Health NHS Foundation Trust, Cromwell House, Eccles, Salford M30 0GT, UK peter.haddad@manchester.ac.uk.
authors: Peter M
authors: PM
authors: Haddad
authors: Wolfson Molecular Imaging Centre, University of Manchester, 27 Palatine Road, Manchester M20 3LJ, UK peter.haddad@manchester.ac.uk.
authors: Peter S
authors: PS
authors: Talbot
authors: Neuroscience and Psychiatry Unit, University of Manchester, Stopford Building, Oxford Rd, Manchester M13 9PT, UK.
authors: Ian M
authors: IM
authors: Anderson
authors: Institute of Neuroscience, Newcastle University, Wolfson Research Centre, Campus for Ageing and Vitality, Westgate Road, Newcastle upon Tyne NE4 5PL, UK Northumberland, Tyne and Wear NHS Foundation Trust, Regional Affective Disorders Service, Campus for Ageing and Vitality, Westgate Road, Newcastle upon Tyne NE4 5PR, UK.
authors: R Hamish
authors: RH
authors: McAllister-Williams
mesh_terms: D000928:Antidepressive Agents / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000627:therapeutic use; D003131:Combined Modality Therapy; D015897:Comorbidity; D003866:Depressive Disorder / Q000188:drug therapy* / Q000628:therapy; D004351:Drug Resistance; D057915:Drug Substitution; D004359:Drug Therapy, Combination; D004565:Electroconvulsive Therapy; D006801:Humans; D055118:Medication Adherence; D011613:Psychotherapy / Q000379:methods; D012307:Risk Factors; D050781:Transcranial Magnetic Stimulation
chemical_list: D000928:Antidepressive Agents; D014150:Antipsychotic Agents
keywords: ECT; antidepressants; antipsychotics; depression; lithium; neurostimulation therapies; treatment resistance