L-Theanine adjunct to risperidone in the treatment of chronic schizophrenia inpatients: a randomized, double-blind, placebo-controlled clinical trial

Psychopharmacology (Berl). 2023 Dec;240(12):2631-2640. doi: 10.1007/s00213-023-06458-9. Epub 2023 Sep 12.

Abstract

Rationale: Inadequate responses to current schizophrenia treatments have accelerated research into novel therapeutic approaches.

Objectives: This study investigated the efficacy and tolerability of adjunctive L-theanine, an ingredient with neuroimmunomodulatory and neuroprotective properties, for chronic schizophrenia.

Methods: Eighty chronic schizophrenia inpatients were equally assigned to receive risperidone (6 mg/day) plus either L-theanine (400 mg/day) or matched placebo in this 8-week, randomized, parallel-group, double-blind, placebo-controlled trial. The participants were assessed using the Positive and Negative Syndrome Scale (PANSS) by recording the results of subscales at baseline and weeks 4 and 8 to measure treatment efficacy. Additionally, the participants were assessed for the Hamilton Depression Rating Scale (HDRS) and adverse events, including the Extrapyramidal Symptom Rating Scale (ESRS).

Results: Sixty patients, 30 in each group, were included in the analyses. All baseline demographic and clinical characteristics were comparable between the groups (p-values > 0.05). The reduction rates from baseline to endpoint in negative, general psychopathology, and total scores of PANSS were greater in the L-theanine group (p-values = 0.03, 0.01, and 0.04, respectively). Regarding general psychopathology scores, the reduction in the L-theanine group was also greater until week 4 (p-value < 0.01). The time × treatment interaction effect was significant on negative (p-value = 0.03), general psychopathology (p-value < 0.01), and total (p-value = 0.04) scores of PANSS, indicating additional improvements in the L-theanine group. The HDRS and side effects were comparable between the groups (p-values > 0.05).

Conclusions: L-Theanine adjunct to risperidone safely and tolerably outperformed adjunctive placebo for schizophrenia, and promising evidence indicated its effects on primary negative symptoms, which need to be scrutinized in further studies.

Trial registration: The study protocol was registered and published prospectively in the Iranian Registry of Clinical Trials ( http://www.irct.ir ; registration number: IRCT20090117001556N133) on 2020-12-12.

Keywords: Camellia sinensis; Combination drug therapy; Glutamate; Green tea; Inflammation; Psychosis; Psychotic disorder; Randomized controlled trial; Refractory schizophrenia.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Antipsychotic Agents* / adverse effects
  • Double-Blind Method
  • Drug Therapy, Combination
  • Humans
  • Inpatients
  • Iran
  • Psychiatric Status Rating Scales
  • Risperidone / adverse effects
  • Risperidone / therapeutic use
  • Schizophrenia* / chemically induced
  • Schizophrenia* / drug therapy
  • Treatment Outcome

Substances

  • Risperidone
  • Antipsychotic Agents
  • theanine