L-theanine in the adjunctive treatment of generalized anxiety disorder: A double-blind, randomised, placebo-controlled trial.

Published on Mar 1, 2019in Journal of Psychiatric Research3.745
· DOI :10.1016/J.JPSYCHIRES.2018.12.014
Jerome Sarris37
Estimated H-index: 37
(USYD: University of Sydney),
Gerard J. Byrne35
Estimated H-index: 35
(UQ: University of Queensland)
+ 11 AuthorsChee H. Ng27
Estimated H-index: 27
(University of Melbourne)
Abstract Partial or non-response to antidepressants in Generalized Anxiety Disorder (GAD) is common in clinical settings, and adjunctive biological interventions may be required. Adjunctive herbal and nutraceutical treatments are a novel and promising treatment option. L-theanine is a non-protein amino acid derived most-commonly from tea (Camellia sinensis) leaves, which may be beneficial in the treatment of anxiety and sleep disturbance as suggested by preliminary evidence. We conducted a 10-week study (consisting of an 8-week double-blind placebo-controlled period, and 1-week pre-study and 2-week post-study single-blinded observational periods) involving 46 participants with a DSM-5 diagnosis of GAD. Participants received adjunctive L-theanine (450–900 mg) or matching placebo with their current stable antidepressant treatment, and were assessed on anxiety, sleep quality, and cognition outcomes. Results revealed that adjunctive L-theanine did not outperform placebo for anxiety reduction on the HAMA (p = 0.73) nor insomnia severity on the Insomnia Severity Index (ISI; p = 0.35). However, LT treated participants reported greater self-reported sleep satisfaction than placebo (ISI item 4; p = 0.015). Further, a separation in favour of L-theanine was noted on the ISI in those with non-clinical levels of insomnia symptoms (ISI ≤ 14; p = 0.007). No significant cognitive effects (trail making time and the modified emotional Stroop) were revealed. While this preliminary study did not support the efficacy of L-theanine in the treatment of anxiety symptoms in GAD, further studies to explore the application of L-theanine in sleep disturbance are warranted.
📖 Papers frequently viewed together
30 Citations
7 Authors (Shinsuke Hidese, ..., Hiroshi)
10 Citations
5 Citations
#1Joseph K. Carpenter (BU: Boston University)H-Index: 11
#2Leigh A. Andrews (BU: Boston University)H-Index: 4
Last. Stefan G. Hofmann (BU: Boston University)H-Index: 83
view all 6 authors...
: The purpose of this study was to examine the efficacy of cognitive behavioral therapy (CBT) for anxiety-related disorders based on randomized placebo-controlled trials. We included 41 studies that randomly assigned patients (N = 2,843) with acute stress disorder, generalized anxiety disorder (GAD), obsessive compulsive disorder (OCD), panic disorder (PD), posttraumatic stress disorder (PTSD), or social anxiety disorder (SAD) to CBT or a psychological or pill placebo condition. Findings demonst...
154 CitationsSource
#1Milan Latas (University of Belgrade)H-Index: 4
#2Goran Trajkovic (University of Belgrade)H-Index: 14
Last. Vladan Starcevic (USYD: University of Sydney)H-Index: 34
view all 7 authors...
OBJECTIVE: The objective of this study is to ascertain psychiatrists' treatment preferences for generalized anxiety disorder (GAD) and compare them to the same psychiatrists' treatment preferences in the hypothetical scenario that treatment is to be administered to themselves as patients. METHODS: A questionnaire was completed by 221 psychiatrists from 3 Balkan countries. They were asked to indicate their treatment preferences for patients with GAD and for themselves as patients. RESULTS: A larg...
3 CitationsSource
#1Shintaro OgawaH-Index: 15
#2Miho OtaH-Index: 24
Last. Hiroshi KunugiH-Index: 62
view all 5 authors...
Rationale and objectives The amino acid l-theanine (N-ethyl-l-glutamine) has historically been considered a relaxing agent. In the present study, we examined the effects of repeated l-theanine administration on behavior, levels of amino acids in the cerebrospinal fluid (CSF), and hippocampal activity in Wistar Kyoto (WKY) rats, an animal model of anxiety and depressive disorders.
11 CitationsSource
#1F. Ferre Navarrete (Hospital General Universitario Gregorio Marañón)H-Index: 1
#2M. Pérez Páramo (Pfizer)H-Index: 1
Last. V. López Gómez (Pfizer)H-Index: 1
view all 4 authors...
Sleep disturbance is one of the key diagnostic criteria for generalized anxiety disorder (GAD). In this cross-sectional, prospective, observational, and multicenter study, factors associated with the prevalence of insomnia and the impact of insomnia-associated factors on quality of life were evaluated. Using multivariate analyses, the factor most strongly associated with the presence of insomnia (ISI ≥ 8) was the severity of the disorder (Odds Ratio [OR]: 9.253 for severe GAD; 95% Confidence Int...
9 CitationsSource
#1Shinsuke HideseH-Index: 10
#2Miho OtaH-Index: 24
Last. Hiroshi KunugiH-Index: 62
view all 7 authors...
Objective l -theanine, an amino acid uniquely contained in green tea ( Camellia sinensis ), has been suggested to have various psychotropic effects. This study aimed to examine whether l -theanine is effective for patients with major depressive disorder (MDD) in an open-label clinical trial. Methods Subjects were 20 patients with MDD (four males; mean age: 41.0±14.1 years, 16 females; 42.9±12.0 years). l -theanine (250 mg/day) was added to the current medication of each participant for 8 weeks. ...
30 CitationsSource
#1Jerome SarrisH-Index: 37
#2Jenifer MurphyH-Index: 9
Last. Chee H. NgH-Index: 27
view all 7 authors...
Objective:There is burgeoning interest in augmentation strategies for improving inadequate response to antidepressants. The adjunctive use of standardized pharmaceutical-grade nutrients, known as nutraceuticals, has the potential to modulate several neurochemical pathways implicated in depression. While many studies have been conducted in this area, to date no specialized systematic review (or meta-analysis) has been conducted.Method:A systematic search of PubMed, CINAHL, Cochrane Library, and W...
208 CitationsSource
#1Rebecca C. Cox (Vandy: Vanderbilt University)H-Index: 9
#2Bunmi O. Olatunji (Vandy: Vanderbilt University)H-Index: 54
Last. Bunmi O. Olatunji (Vandy: Vanderbilt University)H-Index: 9
view all 2 authors...
Recent research suggests that sleep disturbance may be a transdiagnostic process, and there is increasing interest in examining how sleep disturbance may contribute to anxiety and related disorders. The current review summarizes and synthesizes the extant research assessing sleep in anxiety and related disorders. The findings suggest that sleep disturbance exacerbates symptom severity in the majority of anxiety and related disorders. However, the nature of sleep disturbance often varies as a fun...
114 CitationsSource
#1Miho OtaH-Index: 24
Last. Hiroshi KunugiH-Index: 62
view all 9 authors...
Objectives Glutamatergic dysfunction in the brain has been implicated in the pathophysiology of schizophrenia. Previous studies suggested that l -theanine affects the glutamatergic neurotransmission and ameliorates symptoms in patients with schizophrenia. The aims of the present study were twofold: to examine the possible effects of l -theanine on symptoms in chronic schizophrenia patients and to evaluate the changes in chemical mediators, including glutamate + glutamine (Glx), in the brain by u...
20 CitationsSource
#1Jennifer A Reinhold (University of the Sciences)H-Index: 5
#2Karl Rickels (UPenn: University of Pennsylvania)H-Index: 66
Introduction: Modest response and remission rates for the selective serotonin reuptake inhibitors and the serotonin-norepinephrine reuptake inhibitors, coupled with mounting evidence that the tolerability of the antidepressants (ADs) may have been overstated in the literature, has contributed to changes in prescribing patterns for generalized anxiety disorder (GAD). New interest in the absence of evidence that supports these standard therapies as superior to benzodiazepines stimulated a review o...
34 CitationsSource
AbstractTheanine (n-ethylglutamic acid), a non-proteinaceous amino acid component of green and black teas, has received growing attention in recent years due to its reported effects on the central nervous system. It readily crosses the blood–brain barrier where it exerts a variety of neurophysiological and pharmacological effects. Its most well-documented effect has been its apparent anxiolytic and calming effect due to its up-regulation of inhibitory neurotransmitters and possible modulation of...
41 CitationsSource
Cited By9
#1Genoveva Uzunova (Albert Einstein College of Medicine)H-Index: 3
#2Stefano PallantiH-Index: 46
Last. Eric Hollander (Albert Einstein College of Medicine)H-Index: 83
view all 3 authors...
COVID-19 is associated with neuropsychiatric complications, the most frequent one being anxiety. Multiple biological and psychosocial factors contribute to anxiety in COVID-19. Among the biological factors, stress, genetics, gender, immune system, resilience, anosmia, hypogeusia, and central nervous system infection with SARS-CoV-2 are key. Anxiety is a complication of COVID-19 that may exacerbate the infection course, and the infection may exacerbate anxiety. We present the mechanisms of anxiet...
#1Tharaka L. Dassanayake (University of Newcastle)H-Index: 7
#1Tharaka L. Dassanayake (University of Newcastle)H-Index: 2
Last. Vajira S. Weerasinghe (University of Peradeniya)H-Index: 11
view all 3 authors...
Objective: L-theanine, a non-proteinic amino acid found in tea, is known to enhance attention particularly in high doses, with no reported adverse effects. We aimed to determine whether oral administration of L-theanine acutely enhances neurophysiological measures of selective attention in a dose-dependent manner. Methods: In a double-blind, placebo-controlled, counterbalanced, 4-way crossover study in a group of 27 healthy young adults, we compared the effects of 3 doses of L-theanine (100, 200...
#1Xinru Pan (NU: Nanjing University)H-Index: 1
#2Yu Jinhai (NU: Nanjing University)H-Index: 2
Last. Hongjuan Zhang (Nanjing Medical University)H-Index: 2
view all 7 authors...
γ-Glutamyl compounds have unveiled their importance as active substances or precursors of pharmaceuticals. In this research, an approach for enzymatic synthesis of γ-glutamyl compounds was developed using γ-glutamylmethylamide synthetase (GMAS) from Methylovorus mays and polyphosphate kinase (PPK) from Corynebacterium glutamicum. GMAS and PPK were co-recombined in pETDuet-1 plasmid and co-expressed in E. coli BL21 (DE3), and the enzymatic properties of GMAS and PPK were investigated, respectivel...
#1Vittoria Borgonetti (UniFI: University of Florence)H-Index: 4
#2Paolo Governa (UNISI: University of Siena)H-Index: 1
Last. Nicoletta Galeotti (UniFI: University of Florence)H-Index: 33
view all 4 authors...
Mood disorders represent one of the most prevalent and costly psychiatric diseases worldwide. The current therapies are generally characterized by several well-known side effects which limit their prolonged use. The use of herbal medicine for the management of several psychiatric conditions is becoming more established, as it is considered a safer support to conventional pharmacotherapy. The aim of this study was to investigate the possible anxiolytic and antidepressant activity of a fixed combi...
1 CitationsSource
#1Jackson Williams (UC: University of Canberra)H-Index: 3
#2Julian M. Everett (UC: University of Canberra)H-Index: 1
Last. Nenad Naumovski (UC: University of Canberra)H-Index: 18
view all 10 authors...
The green tea amino acid, L-theanine (L-THE) is associated with several health benefits, including improvements in mood, cognition and a reduction of stress and anxiety-like symptoms. This systematic review evaluated the effect of pure L-THE intake, in the form of orally administered nutritional supplements, on stress responses and anxiety levels in human randomised controlled trials. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist, 9 peer-revi...
10 CitationsSource
#1Jing Xia (China Jiliang University)H-Index: 4
#2Dan Wang (China Jiliang University)H-Index: 6
Last. Zhi Yu (HAU: Huazhong Agricultural University)H-Index: 7
view all 7 authors...
Abstract Structural investigations, based on density functional theory (DFT) calculations, are performed on tea catechins, including 4-aminobutyric acid (GABA), L-theanine (Thea), caffeine (CAF), theobromine (TB), theophylline (TP), catechin (C), epicatechin (EC), gallocatechin (GC), epigallocatechin (EGC), catechin gallate (CG), epicatechin gallate (ECG), gallocatechin gallate (GCG) and epigallocatechin gallate (EGCG). With an identified lowest energy conformer of investigated molecules, FTIR a...
5 CitationsSource
#1Keiko Unno (University of Shizuoka)H-Index: 20
#2Yoriyuki Nakamura (University of Shizuoka)H-Index: 14
Abstract Epidemiological and animal studies have shown that the ingestion of green tea enhances a healthy life. However, caffeine in green tea can interfere with sleep. On the other hand, theanine, the major amino acid in green tea, blocks the effect of caffeine. We examined the interaction among tea components and sleep using green tea with a lowered caffeine content (LCGT). Sleep stages measured in participants, which consisted of elderly and middle-aged individuals, showed that early morning ...
#1Filipe Lopes Sakamoto (UWO: University of Western Ontario)H-Index: 1
#2Rodrigo Metzker Pereira Ribeiro (UWO: University of Western Ontario)H-Index: 1
Last. Heitor O. SantosH-Index: 9
view all 4 authors...
Abstract Anxiety disorders are highly prevalent in modern societies, and are ranked the sixth most important contributor of non-fatal negative health outcomes. L-theanine is an amino acid naturally found in green tea (Camellia sinensis) and some other plant extracts, and recent clinical studies have proposed promising adjuvant effects of L-theanine for the negative impact of anxiety and psychological stress on health. In this integrative narrative review, we aimed to appraise and further discuss...
4 CitationsSource
#1Toshiharu Ninomiya (Kyushu University)H-Index: 77
#2Noriyuki KanzakiH-Index: 1
Last. Takanari Kitazono (Kyushu University)H-Index: 49
view all 14 authors...
OBJECTIVE This study investigated the association between serum ethylamine levels as an indicator of l-theanine consumption and the development of type 2 diabetes in a Japanese community. RESEARCH DESIGN AND METHODS A total of 2,253 community-dwelling Japanese individuals aged 40–79 years without diabetes were monitored for 7 years. Serum ethylamine levels were divided into quartiles: ≤0.86, 0.87–2.10, 2.11–5.28, and ≥5.29 ng/mL. Kinetic analysis of serum ethylamine concentrations was performed ...
2 CitationsSource