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

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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.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Abbreviations

DSM-V:

Diagnostic and Statistical Manual of Mental Disorders, fifth edition

PANSS:

Positive and Negative Syndrome Scale

SD:

Standard deviation

HDRS:

Hamilton Depression Rating Scale

ESRS:

Extrapyramidal Symptom Rating Scale

MD:

Mean difference

CI:

Confidence interval

GLM:

General linear model

ANOVA:

Analysis of variance

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Acknowledgements

This study was performed in support of Dr. Setareh Fattollahzadeh-Noor’s postgraduate thesis toward the Iranian Board of Psychiatry.

Funding

This study was supported by a grant from the Tehran University of Medical Sciences (TUMS) to Professor Shahin Akhondzadeh (grant number 49661). TUMS had no role in the design, conduct, data collection, analysis, data interpretation, manuscript preparation, review, final approval, and the decision to submit the paper for publication.

Author information

Author notes

  1. Ahmad Shamabadi and Setareh Fattollahzadeh-Noor contributed equally to this study.

Authors and Affiliations

  1. Psychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Ahmad Shamabadi, Setareh Fattollahzadeh-Noor & Shahin Akhondzadeh

  2. Department of Psychiatry, Razi Hospital, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran

    Bita Fallahpour & Mohammad-Reza Khodaei Ardakani

  3. Tehran Medical Branch, Islamic Azad University, Tehran, Iran

    Fatemeh A. Basti

Authors
  1. Ahmad Shamabadi
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  4. Fatemeh A. Basti
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  5. Mohammad-Reza Khodaei Ardakani
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Contributions

SA and MK: conceptualization, project administration, supervision, funding acquisition, methodology, and software; AS, SF, BF, and FAB: writing—original draft, formal analysis, editing, data curation, and investigation. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Shahin Akhondzadeh.

Ethics declarations

Ethics approval

The protocol followed the ethical principles of the seventh revision of the Declaration of Helsinki, as revised in Brazil in 2013, and was approved by the institutional research ethics committee on 2020–09-22 (approval code: IR.TUMS.DDRI.REC.1399.034).

Consent to participate

Informed consent was obtained from all patients or their legally authorized representatives while being aware of the possibility of withdrawing from the study at any time without affecting their therapy and relationship with healthcare providers.

Competing interests

The authors declare no competing interests.

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Shamabadi, A., Fattollahzadeh-Noor, S., Fallahpour, B. et al. L-Theanine adjunct to risperidone in the treatment of chronic schizophrenia inpatients: a randomized, double-blind, placebo-controlled clinical trial. Psychopharmacology 240, 2631–2640 (2023). https://doi.org/10.1007/s00213-023-06458-9

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  • DOI: https://doi.org/10.1007/s00213-023-06458-9

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