Allopurinol in Schizophrenia: A Randomized Trial Administering Allopurinol vs Placebo as add-on Antipsychotics in Patients With Schizophrenia

Sheba Medical Center

Status and phase

Completed

Phase 4

Conditions

Schizophrenia

Schizoaffective Disorder

Treatments

Drug: Allopurinol

Study type

Interventional

Funder types

Other

Identifiers

NCT00864825

SHEBA-09-6893-MW-CTIL

Details and patient eligibility

About

The objective of the study is to evaluate the efficacy of allopurinol, compared to placebo, as add-on to anti-psychotics in the treatment of patients with schizophrenia.

Full description

An emerging body of evidence supports a purinergic hypothesis for schizophrenia. Adenosine agonists have been shown to have properties similar to those of dopamine antagonists and there is a well characterized antagonistic interaction between adenosine and dopamine receptors in the ventral striatum1. Increased adenosinergic transmission has been demonstrated to reduce the affinity of dopamine agonists for dopamine receptors. It has been theorized that adenosine may exert some of its antipsychotic effects through modulation of glutamatergic transmission.

Three double-blind, randomized, placebo-controlled trials have showed statistically significant greater improvements in PANSS scores in the allopurinol groups vs. placebo groups. These empiric data, together with the theoretical and basic science background cited, provide the impetus for this proposed study.

Enrollment

248 patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Male or female, 18-65 years of age, inclusive
Because gout is relatively rare in women of childbearing age, there are few reports describing the use of allopurinol during pregnancy; in those there were no adverse fetal outcomes attributable to allopurinol. Therefore, only females who are abstinent or practicing an established method of birth control (oral contraceptive tablets, hormonal implant device, hormone patch, injectable contraceptive, intrauterine device [IUD]) can be included in the trial.
Willing and able to provide informed consent, after the nature of the study has been fully explained
Current DSM-IV-TR diagnosis of schizophrenia as confirmed by SCID
Symptoms: 4 (moderate) or above on CGI-S AND >= 4 (moderate) score on two of the following four PANSS items: delusions, hallucinatory behaviors, conceptual disorganization or suspiciousness/ persecution.
Must be on any antipsychotic drug for at least 2 weeks prior to the baseline visit, at doses within the PORT criteria. Patients receiving higher doses will have their records reviewed to insure that dose is required. Patients receiving two anti-psychotics, or IM depot antipsychotics can also be included.
Inpatients or outpatients.

Exclusion criteria

Unwilling or unable, in the opinion of the Investigator, to comply with study instructions
Pregnant or breast-feeding
Unstable medical disease (malignancy, poorly controlled diabetes, active ischemic cardiac disease, or cardiomyopathy, serious pulmonary disease, , kidney disease, impaired liver functioning
Likely allergy or sensitivity to allopurinol
At significant risk of committing suicide, or in the opinion of the Investigator, currently is at imminent risk of suicide or harming others.
Suffers from a significant Substance Dependence disorder based on DSM-IV criteria within the 3 months prior to Screening, or is deemed by the Investigator to have a high risk of substance use during the study. Patients with a history of recreational use of cannabinoids or alcohol, and/or patients who smoke cigarettes can be included.
Concurrent delirium, mental retardation, drug-induced psychosis, or history of brain trauma.