title: Depression treatment by withdrawal of short-term low-dose antipsychotic, a proof-of-concept randomized double-blind study.
abstract: OBJECTIVE
  Because increased dopamine neurotransmission occurs with most antidepressants, and because antipsychotics cause behavioural supersensitivity to dopamine, short-term low-dose antipsychotic treatment was tested on depressed patients with an expectation of clinical improvement in the supersensitive phase following drug withdrawal.
  
  
  METHODS
  This was a randomized, double-blind, placebo-controlled study of 48 patients who met criteria for DSM-IV(®) Major Depressive Disorder, were in a Major Depressive Episode, and had a Hamilton Depression Rating Scale (HAMD) rating of ≥14. Half the participants received 0.25mg oral haloperidol each day for 7 days, after which they received placebo daily for 4 weeks. The other half received placebo throughout the trial.
  
  
  RESULTS
  One week after stopping the medication, the HAMD ratings of the drug-treated patients fell by 9.96 points, as compared to a reduction of 8.73 points in the placebo-treated patients, when comparing visits 1 and 4. There was no such difference when comparing visits 2 and 4. The differences were not significant, but indicated a trend. One week after the medication was stopped, the Clinical Global Index fell 1.64±0.18 units for the medication-treated patients, compared to 1.12±0.26 units for the placebo group (P=0.05). The regimen was well tolerated.
  
  
  CONCLUSIONS
  Seven days of an ultra-low dose of 0.25mg haloperidol, followed by withdrawal of haloperidol, resulted in clinical depression improvement greater than placebo and significantly decreased psychomotor retardation, consistent with haloperidol-induced behavioural supersensitivity to dopamine.
  
  
  CONCLUSIONS
  The sample was small. More patients are needed in a future study.
authors.affiliation: Department of Psychiatry, Toronto General Hospital, University Health Network, 200 Elizabeth Street, Toronto, ON, Canada M5G 2C4. Electronic address: Sidney.Kennedy@uhn.ca.
authors.forename: Sidney H
authors.initials: SH
authors.lastname: Kennedy
authors.affiliation: Department of Psychiatry, Toronto General Hospital, University Health Network, 200 Elizabeth Street, Toronto, ON, Canada M5G 2C4.
authors.forename: Peter
authors.initials: P
authors.lastname: Giacobbe
authors.affiliation: Department of Psychiatry, Toronto General Hospital, University Health Network, 200 Elizabeth Street, Toronto, ON, Canada M5G 2C4.
authors.forename: Franca
authors.initials: F
authors.lastname: Placenza
authors.affiliation: Department of Psychiatry, Alexandra Marine and General Hospital, 120 Napier Street, Goderich, ON, Canada N7A 1W5.
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Hudson
authors.affiliation: Clera Inc., 260 Heath Street West, Unit 605, Toronto, ON, Canada M5P 3L6.
authors.forename: Philip
authors.initials: P
authors.lastname: Seeman
authors.affiliation: Clera Inc., 260 Heath Street West, Unit 605, Toronto, ON, Canada M5P 3L6.
authors.forename: Mary V
authors.initials: MV
authors.lastname: Seeman
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004311:Double-Blind Method; D005260:Female; D006220:Haloperidol / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011597:Psychomotor Performance; D028761:Withholding Treatment
chemical_list: D014150:Antipsychotic Agents; D010919:Placebos; D006220:Haloperidol
keywords: Antidepressant; Antipsychotic; Depression; Dopamine D2High receptor; Dopamine supersensitivity