Histamine H2 Antagonism as Adjuvant Therapy in Treatment Resistant Schizophrenia

Study Overview
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Brief Summary
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The purpose of the study is to investigate whether blockade of the histamine H2 receptors in the brain will have any beneficial effect on the symptoms of subjects with schizophrenia.

Detailed Description
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Histamine functions as a neurotransmitter in the brain. It has an important role as modulator of the release of other neurotransmitters, including dopamine. The histamine receptors are widely expressed in the brain, H1 and H2 receptors are post-synaptic, H3 a pre-synaptic autoreceptor. There is an abundance of neurobiologic data from animal and human studies supporting the role of histamine in the pathogenesis and treatment of psychoses. In 1990 a case report of a treatment resistant subject with schizophrenia whos symptoms improved markedly when he was prescribed a H2 antagonist because of peptic ulcer. Later, a open-label trial including 18 patients has been performed, reporting significant symptom reduction, especially on negative symptoms. Also the subjective comments both by the subjects and the investigators in that study were optimistic and suggested an effect primarily on negative symptoms. The present study will be the first double-blind, randomized, placebo controlled, parallel group study of the subject matter. The study focuses on treatment resistant schizophrenia cases in the stable phase.

Official Title
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Histamine H2 Antagonism as Adjuvant Therapy in Treatment Resistant Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: famotidine
* Drug: Placebo (Microcrystallized cellulose)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of schizophrenia assessed by SCID-I (DSM-IV) as well as RDC-criteria Patient record mention of schizophrenia (ICD-10) at least 5 years previously Disability pension due to psychiatric disorder At least 3 points on the CGI scale Exclusion Criteria: Epilepsy or a history of unclear seizures Stroke Parkinson's disease AIDS Substance addiction or abuse within 3 months prior to enrolment. Individuals who are deemed at risk for aggressive behavior or suicide by their clinician Pregnant and breast-feeding subjects Serious unstable physical illness Persons who have been deemed legally incapacitated according to Finnish law (Laki holhoustoimesta 1.4.1999/442, 3. luku, 18 §) Individuals who use H2-antagonists as prescribed by a physician Known allergy to famotidine or any other component of the Pepcidin® 40 mg tablet Glomerular Filtration Rate (GFR) according to the Cockcroft-Gault formula < 30 ml/min

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: famotidine<br> | Drug: famotidine<br>* Capsules containing 100 mg of famotidine p.o., twice daily for 4 weeks.<br>* Other names: Famotidin Hexal;|
| Placebo Comparator: Placebo<br> | Drug: Placebo (Microcrystallized cellulose)<br>* Placebo administered in identical capsules as the experimental drug.<br>* Other names: Microcrystallized cellulose;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Scale for the Assessment of Negative Symptoms (SANS) score |  | 5 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive and Negative Syndrome Scale (PANSS) score |  | 5 weeks | 
| Clinical Global Impression (CGI) score |  | 5 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treatment resistant, Chronic