Efficacy of Allopurinol and Dypiridamole in Acute Mania
Condition: Mania
MeSH terms: Mania
Study type: Interventional
Phase: Phase 4

Summary: 
      This study aims to evaluate the potential antimanic efficacy, safety and tolorability of the
      purinergic agents allopurinol and dipyridamole as an add-on treatment to lithium in a sample
      of 180 drug-free manic patients enrolled in a double-blind, placebo-controlled design.
    

Detailed description: 
      Men and women ages 18 to 65 years, who were inpatients with a diagnosis of manic episode were
      recruited at the emergency room of Espirita Hospital of Porto Alegre (HEPA), Brazil (n=180)
      between September 2004 and 2006. The presence of manic episode was confirmed using SCID-I and
      the severity of episode was evaluated using the Young Mania Rating Scale (YMRS) and the
      Clinical Global Impression scale (CGI). Patients were required to present a score>22 on the
      YMRS at screening to be included. Subjects presenting rapid cycling, mixed episodes and
      comorbidities with axis I psychiatric disorders were not considered for inclusion. All
      subjects presented good physical health determined by physical exam, medical history, blood
      screening and electrocardiogram. Patients were randomly assigned to allopurinol 600 mg/day,
      dipyridamole 200mg or placebo as add-on medication lithium treatment for a 4-week,
      double-blind trial. The use of adjunctive antipsychotic agents (typical or second-generation
      drugs) was not allowed during the double-blind period. Adjunctive diazepam was used when
      necessary (maximum dose=20mg/day). Raters (psychiatrists) were trained together to establish
      reliability (YMRS =0.90). This study was approved by the Espirita Hospital Ethics
      Committee-IRB. Written informed consent was obtained from all patients and/or family member.
      Possible adverse events were monitored weekly during the follow-up period. Regarding primary
      outcome measures, we compared the percentage of responders according YMRS score decrease of
      at least 50% among allopurinol, dipyridamole and placebo groups, using fisher exact test.
      Also, the percentage of improvement from baseline to endpoint was obtained and compared among
      groups using analysis of variances (one-way ANOVA) with Duncan post-hoc test. Remission rates
      (YMRS scores < 12) were also analyzed. P values < 0.05 were considered statistically
      significant. Besides completers analysis, intention to treat and LOCF were employed to
      include data from drop-out patients who were evaluated at visit 3. Possible correlations were
      measured using Pearson test. Fischer exact test and X2 evaluated response and remission
      rates. Data are presented as mean ± standard deviation.
    

Intervention name(s): Allopurinol; Dipyridamole; Placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Allopurinol 600mg/day bid for 28 days; Dipyridamole 200mg/day bid for 28 days; Placebo
Intervention MeSH terms: Allopurinol; Dipyridamole
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment