Efficacy of Allopurinol and Dypiridamole in Acute Mania

NCT ID: NCT00560079

Last Updated: 2016-08-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 180 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-11-30
• Study Completion Date: 2006-04-30

Brief 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.

Conditions

Mania

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1

Lithium 900mg/day plus allopurinol 600mg/day

Group Type: EXPERIMENTAL

Allopurinol

Intervention Type: DRUG

Allopurinol 600mg/day bid for 28 days

2

Group Type: ACTIVE_COMPARATOR

Dipyridamole

Intervention Type: DRUG

Dipyridamole 200mg/day bid for 28 days

3

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

Interventions

Allopurinol

Allopurinol 600mg/day bid for 28 days

Intervention Type: DRUG

Dipyridamole

Dipyridamole 200mg/day bid for 28 days

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.All subjects presented good physical health determined by physical exam, medical history, blood screening and electrocardiogram

Exclusion Criteria

• Subjects presenting rapid cycling, mixed episodes and comorbidities with axis I psychiatric disorders were not considered for inclusion. .

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stanley Medical Research Institute

OTHER

Sponsor Role: collaborator

Hospital Espirita de Porto Alegre

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rodrigo Machado-Vieira, MD, MSc, PhD

Role: PRINCIPAL_INVESTIGATOR

Staff Member

Locations

Hospital Espirita de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Countries

Brazil

References

Machado-Vieira R, Soares JC, Lara DR, Luckenbaugh DA, Busnello JV, Marca G, Cunha A, Souza DO, Zarate CA Jr, Kapczinski F. A double-blind, randomized, placebo-controlled 4-week study on the efficacy and safety of the purinergic agents allopurinol and dipyridamole adjunctive to lithium in acute bipolar mania. J Clin Psychiatry. 2008 Aug;69(8):1237-45. doi: 10.4088/jcp.v69n0806.

Reference Type: DERIVED

PMID: 18681754 (View on PubMed)

Other Identifiers

03T-356

Identifier Type: -

Identifier Source: org_study_id