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 (2015)

I haven’t yet seen the full text but here are the initial results from a trial I was keeping an eye on:

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 (2015)


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.


Double-blind, placebo-controlled trial of PREG – LT or placebo augmentation was conducted for 8 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), Hamilton Scale for Anxiety (HAM-A), and 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.


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.


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: Identifier: NCT01831986.

See also:

Effect of l-theanine on glutamatergic function in patients with schizophrenia (2015)

Neurosteroids as therapeutics

Sex hormones and oxytocin augmentation strategies in schizophrenia: A quantitative review (2015)

Dietary and nutritional therapies for schizophrenia

Clinical Management of Negative Symptoms of Schizophrenia: An update (2015)

My trials with supplements for schizophrenia

Augmentation with pregabalin in schizophrenia

Augmentation with pregabalin in schizophrenia.

Anxiety is a core symptom of schizophrenia that elicits significant subjective burden of disease and contributes to treatment resistance in schizophrenia. Anxious syndromes might be attributed to incompletely remitted delusions, the negative syndrome, depressive episodes, panic attacks, social phobia, avoidance after hospitalization, and down-tapering of benzodiazepine medication. Pregabalin, an antagonist at the alpha2delta subunit of voltage-gated Ca channels, modulates several neurotransmitter systems and was found to alleviate anxiety in different mental disorders. In schizophrenia, this treatment option has not been evaluated before.Here, we report a case series of 11 schizophrenic patients who had treatment-resistant anxiety and received augmentation with pregabalin. This observational analysis reveals that the strategy was able to significantly reduce scores on the Hamilton anxiety scale; furthermore, we observed improvements of psychotic positive and negative symptoms and mood as assessed by Positive and Negative Syndrome Scale, Scale for the Assessment of Negative Symptoms, and Calgary Depression Scale for Schizophrenia. After augmentation, both a complete discontinuation of concomitant benzodiazepine treatment as well as a dose reduction of antipsychotics could be achieved. We did not observe pharmacokinetic interactions or adverse events.These observations suggest that treating anxious syndromes in schizophrenia with pregabalin can be effective and tolerable. Further investigations should differentiate schizophrenic subsyndromes of anxiety and evaluate benefits and risks of pregabalin in comparison to placebo and active competitors.


panss pregabalin

Pregabalin was started with 75 mg/d and raised according to clinical necessity to a mean dose of 313.6 mg/d after a mean observation period of 6.7 weeks. Serum levels were assessed in a subgroup of 5 patients (mean dose, 375 mg/d; mean serum level, 1.7 mg/L). We observed improvements of anxiety (HAMA: P = 0.007, t16.9 = 3.041, effect size = 1.2) and mood (CDSS P = 0.002, t17.3 = 3.754, effect size = 1.6) (Fig. 1A). In addition, psychotic positive (PANSS positive: P = 0.009, t16.1 = 2.962, effect size = 1.3), negative (PANSS negative: P = 0.093, t17.7 = 1.773, effect size = 0.8; and SANS: P = 0.076, t19.1 = 1.875, effect size = 0.8), and global psychopathology (PANSS global psychopathology: P <= 0.000, t19.526 = 4.948, effect size = 2.1) responded, resulting in significantly decreased total PANSS scores (P <= 0.000, t16.6 = 4.326, effect size = 1.8) (Fig. 1B). In particular, partially remitted formerly treatment-resistant psychotic symptoms responded to the add-on of pregabalin.

Pregabalin may also be effective in treating alcohol dependence [1] Rarely, pregabalin-associated elevation of clozapine serum levels have been reported [2, 3]

I’d like to hear from anyone who has used pregabalin as an augmentation strategy in schizophrenia.