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Depression treatment by withdrawal of short-term low-dose antipsychotic, a proof-of-concept randomized double-blind study
Journal of Affective Disorders, 06/17/14
Kennedy SH, et al. – Seven days of an ultra–low dose of 0.25 mg 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.
  • 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 0.25 mg oral haloperidol each day for 7 days, after which they received placebo daily for 4 weeks.
  • The other half received placebo throughout the trial.

  • 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.

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