Add-On Pregnenolone with L-Theanine to Antipsychotic Therapy Relieves Negative and Anxiety Symptoms of Schizophrenia: An 8-Week, Randomized, Double-Blind, Placebo-Controlled Trial.

AIMS: Pregnenolone (PREG) and L-theanine (LT) have shown ameliorative effects on various schizophrenia symptoms. This is the first study to evaluate the efficacy and safety of augmentation of antipsychotic treatment among patients with chronic schizophrenia or schizoaffective disorder with PREG-LT.

METHODS: Double-blind, placebo-controlled trial of PREG-LT or placebo augmentation was conducted for eight weeks with 40 chronic DSM-IV schizophrenia and schizoaffective disorder patients with suboptimal response to antipsychotics. Oral PREG (50 mg/day) with LT (400 mg/day) or placebo were added to a stable regimen of antipsychotic medication from March 2011 to October 2013. The participants were rated using the Scale for the Assessment of Negative Symptoms (SANS), the Hamilton Scale for Anxiety (HAM-A), and the Positive and Negative Syndrome Scale (PANSS) scales bi-weekly. The decrease of SANS and HAM-A scores were the co-primary outcomes. Secondary outcomes included assessments of general functioning and side effects.

RESULTS: Negative symptoms such as blunted affect, alogia, and anhedonia (SANS) were found to be significantly improved with moderate effect sizes among patients who received PREG-LT, in comparison with the placebo group. Add-on PREG-LT also significantly associated with a reduction of anxiety scores such as anxious mood, tension, and cardiovascular symptoms (HAM-A), and elevation of general functioning (GAF). Positive symptoms, antipsychotic agents, concomitant drugs, and illness duration did not associate significantly with effect of PREG-LT augmentation. PREG-LT was well-tolerated.

CONCLUSIONS: Pregnenolone with L-theanine augmentation may offer a new therapeutic strategy for treatment of negative and anxiety symptoms in schizophrenia and schizoaffective disorder. Further studies are warranted.

TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01831986.