Gabapentin in Patients at Clinical Risk for Psychosis

Phase 1

Terminated

Brief Summary: The purpose of this study is to test the effects of the drug gabapentin on brain function thought to be important in the development of schizophrenia. Researchers think that treating a brain region with gabapentin (the hippocampus) may reduce the risk for developing schizophrenia.

Detailed Description: Six week, single site, proof-of concept, randomized double-blind placebo-controlled pilot study to examine the effects of moderate dose gabapentin (3600mg) in n= 100 putatively prodromal patients on hippocampal activity.

Recruitment & Eligibility

Inclusion Criteria

COPE patient between age of 18-30
Capacity to give informed consent
Currently using a reliable method of birth control (female) (condom plus spermicide, diaphragm plus spermicide, IUD, birth control pills, norplant, vasectomy in partner)

Exclusion Criteria

Metal implants in body or a history of metal working, or more than one past MRI scan with gadolinium
Lifetime diagnosis of asthmatic symptoms within the past 3 years or known sensitivity to contrast agents
Lifetime diagnosis of renal failure/disease
Acute neurological, neuroendocrine,or medical disorder including renal insufficiency
Lifetime diagnosis of hypertension or diabetes
Intelligence Quotient (IQ) < 70
Acute risk for suicide and/or violence
Pregnant, lactating
Current abuse of substances (alcohol, cocaine, stimulants, cannabis, opiates, sedative hypnotics)
Current use or anticipated need for antipsychotics or mood stabilizers (all antipsychotics, also Depakote, lithium, lamotrigine, pregabalin or any med with a mechanism of action like gabapentin)
The Clinical Global Impressions Scale (CGI)-improvement score during study equal to or greater than 6

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Matching placebo PO daily
Gabapentin	Gabapentin	Gabapentin 3600mg PO daily

Primary Outcome Measures

Name	Time	Method
Change in Left CA1 Cerebral Blood Volume (CBV) (MRI Measure)	6 weeks	Change from 6 week follow up minus baseline of left CA1 CBV (MRI measure) in patients who receive active drug vs. placebo, after 6 weeks of treatment.

Secondary Outcome Measures

Name	Time	Method
Change in Positive, Negative, Disorganization, and General Symptoms Over Time as Measured by the Structured Interview for Psychosis-Risk Syndromes (SIPS)/the Scale of Psychosis-Risk Symptoms (SOPS)	6 weeks	Exploratory analyses will be conducted examining the effects of gabapentin on changes in Positive symptoms (P scores), negative symptoms (N scores) and general symptoms (G scores) and disorganization symptoms (D scores) compared to placebo. There are 19 items on the SIPS. Each item is scored 0-6. There are 5 positive symptom items (range=0-30), 6 negative symptom items (range=0-36), 4 disorganization symptom items (range=0-24), and 4 general symptom items (range=0-24). The range of scores is 0-114. A lower score at baseline indicates less symptoms, and therefore a negative change over the 6 week period indicates an improvement, and a positive change indicates worsening of symptoms.
Change in Cognitive Function (Hippocampal-dependent Verbal Memory) as Measured by the California Verbal Learning Test-Second Edition (CLVT-II)	6 weeks	Exploratory analyses will be conducted on changes between gabapentin and placebo groups on the California Verbal Learning Test-Second Edition (CLVT-II) measures. The unit measured was 'learning slope', where higher slope indicates better memory and a lower slope indicates poorer memory.