title: Allopurinol augmentation in the outpatient treatment of bipolar mania: a pilot study.
abstract: BACKGROUND
  Allopurinol promotes the salvage of purines, possibly increasing endogenous adenosine levels. Recent studies suggest that adenosine has neuroprotective and inhibitory effects. Two previous inpatient trials demonstrated that allopurinol has anti-manic activity. Our objective was to test allopurinol as an adjunct to standard medications in bipolar disorder manic outpatients.
  
  
  METHODS
  In this double-blind, placebo-controlled trial, 27 subjects who met DSM-IV criteria for bipolar disorder and scored ≥ 14 on the Young Mania Rating Scale (YMRS) were randomized to augmentation with allopurinol or placebo for six weeks. The primary efficacy measure was the YMRS. The primary safety measure was the Treatment Emergent Symptom Scale.
  
  
  RESULTS
  The effect of allopurinol augmentation in decreasing mean YMRS scores was modest, with an overall effect size of -0.25 (Cohen's d). Allopurinol-treated individuals who abstained from caffeine (n = 4) had a greater decrease in YMRS scores (-15.3 ± 1.8) than subjects using caffeine (n = 5) (-9.6 ± 3.4, p = 0.219), with an effect size of -0.86.
  
  
  CONCLUSIONS
  In this small outpatient pilot study, allopurinol augmentation did not show a statistically significant improvement over placebo in attenuating manic symptoms. Subjects with restricted caffeine use showed a greater effect size compared to caffeine users. This finding may be interpreted as corroborating the hypothesized mechanism of action of allopurinol's anti-manic effect in previous studies.
authors.affiliation: Department of Psychiatry and Behavioral Neurosciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. alexander.fan@cshs.org
authors.forename: Alexander
authors.initials: A
authors.lastname: Fan
authors.forename: Andrew
authors.initials: A
authors.lastname: Berg
authors.forename: Catherine
authors.initials: C
authors.lastname: Bresee
authors.forename: Lisa Hayley
authors.initials: LH
authors.lastname: Glassman
authors.forename: Mark Hyman
authors.initials: MH
authors.lastname: Rapaport
mesh_terms: D000328:Adult; D000493:Allopurinol / Q000009:adverse effects*; D001714:Bipolar Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D016166:Free Radical Scavengers / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010045:Outpatients; D010865:Pilot Projects; D011569:Psychiatric Status Rating Scales; D016896:Treatment Outcome
chemical_list: D016166:Free Radical Scavengers; D000493:Allopurinol