Role of Anti-Inflammatory Agents in Patients With Schizophrenia

Summary

There is some evidence that anti-inflammatory treatment may have beneficial effects in schizophrenia and major depression. Cox-2 inhibitors have been tested in preliminary clinical trials for schizophrenia and depression, showing favourable effects compared to placebo (Muller and Schwarz et al 2009).

Statins were introduced as cholesterol-lowering agents but have found much wider usage. They are anti-inflammatory agents and thus similar to the Cox-2 inhibitors, which have shown some ability as adjuncts to improve the symptoms of schizophrenia in preliminary studies. The statins are also known to decrease C-reactive protein (CRP), which has been shown in an SMRI-funded study to be elevated in a study of individuals with schizophrenia. Fan et al (2007) demonstrated in a small study in patients with schizophrenia that higher than normal levels of CRP (\>0.50 mg/dl) was associated with marked negative symptoms and higher total PANSS scores.

Ondansetron is a serotonin (5-HT3) receptor antagonist that is generic and widely used to prevent nausea and vomiting in patients receiving chemotherapy for cancer. GSK did a small study on it as an antipsychotic in the 1980s. Since then, several small studies have suggested that it is effective as an adjunct drug in improving the symptoms of schizophrenia.

Statins are widely used in schizophrenia sufferers, particularly those taking second generation antipsychotics, to treat hypercholesterolemia. Both drugs are well tolerated and their side effect profiles well understood.

We propose to conduct a feasibility study in patients with chronic schizophrenia to explore the adjunct use of simvastatin and ondansetron on positive, negative and general psychopathology in comparisons to treatment as usual (TAU) over a 12 week period.

Conditions

• Schizophrenia
• Schizoaffective Disorder
• Psychosis Not Otherwise Specified
• Schizophreniform Disorder

Interventions

DRUG

Ondansetron

ondansetron added to TAU Ondansetron will be administered in 8mg once daily dose

DRUG

Simvastatin

Simvastatin added to TAU Simvastatin 20mg taken as once daily dose

DRUG

Placebo

Placebo added to TAU

Sponsors & Collaborators

• Karwan e Hayat

  collaborator UNKNOWN

• Dow University of Health Sciences

  collaborator OTHER

• Pakistan Institute of Living and Learning

  lead OTHER

Principal Investigators

• Imran B Chaudhry, MD · University of Manchester

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2009-06-30

Primary Completion

2009-09-30

Completion

2010-09-30

Countries

• Pakistan

Study Locations