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Effects of chronic l-theanine administration in patients with major depressive disorder: an open-label study

  • Shinsuke Hidese (a1) (a2), Miho Ota (a1), Chisato Wakabayashi (a1), Takamasa Noda (a3), Hayato Ozawa (a4), Tsutomu Okubo (a4) and Hiroshi Kunugi (a1) (a2)...
Abstract
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. Symptoms and cognitive functions were assessed at baseline, 4, and 8 weeks after l-theanine administration by the 21-item version of the Hamilton Depression Rating Scale (HAMD-21), State-Trait Anxiety Inventory (STAI), Pittsburgh Sleep Quality Index (PSQI), Stroop test, and Brief Assessment of Cognition in Schizophrenia (BACS).

Results

HAMD-21 score was reduced after l-theanine administration (p=0.007). This reduction was observed in unremitted patients (HAMD-21>7; p=0.004) at baseline. Anxiety-trait scores decreased after l-theanine administration (p=0.012) in the STAI test. PSQI scores also decreased after l-theanine administration (p=0.030) in the unremitted patients at baseline. Regarding cognitive functions, response latency (p=0.001) and error rate (p=0.036) decreased in the Stroop test, and verbal memory (p=0.005) and executive function (p=0.016) were enhanced in the BACS test after l-theanine administration.

Conclusion

Our study suggests that chronic (8-week) l-theanine administration is safe and has multiple beneficial effects on depressive symptoms, anxiety, sleep disturbance and cognitive impairments in patients with MDD. However, since this is an open-label study, placebo-controlled studies are required to consolidate the effects.

Copyright
Corresponding author
Dr. Hiroshi Kunugi, Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan. Tel: +81 42 346 1714; Fax: +81 42 346 2094; E-mail: hkunugi@ncnp.go.jp
References
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1. Kennedy, SH. Core symptoms of major depressive disorder: relevance to diagnosis and treatment. Dialogues Clin Neurosci 2008;10:271277.
2. Rock, PL, Roiser, JP, Riedel, WJ, Blackwell, AD. Cognitive impairment in depression: a systematic review and meta-analysis. Psychol Med 2014;44:20292040.
3. Hamon, M & Blier, P. Monoamine neurocircuitry in depression and strategies for new treatments. Progress in Neuro-Psychopharmacology and Biological Psychiatry 2013;45:5463.
4. Rush, AJ, Trivedi, MH, Wisniewski, SR et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry 2006;163:19051917.
5. Freeman, MP, Mischoulon, D, Tedeschini, E et al. Complementary and alternative medicine for major depressive disorder: a meta-analysis of patient characteristics, placebo-response rates, and treatment outcomes relative to standard antidepressants. J Clin Psychiatry 2010;71:682688.
6. Nahas, R, Sheikh, O. Complementary and alternative medicine for the treatment of major depressive disorder. Can Fam Physician 2011;57:659663.
7. Yokogoshi, H, Kobayashi, M, Mochizuki, M, Terashima, T. Effect of theanine, r-glutamylethylamide, on brain monoamines and striatal dopamine release in conscious rats. Neurochem Res 1998;23:667673.
8. Kakuda, T, Nozawa, A, Sugimoto, A, Niino, H. Inhibition by theanine of binding of [3H]AMPA, [3H]kainate, and [3H]MDL 105,519 to glutamate receptors. Biosci Biotechnol Biochem 2002;66:26832686.
9. Tamano, H, Fukura, K, Suzuki, M, Sakamoto, K, Yokogoshi, H, Takeda, A. Preventive effect of theanine intake on stress-induced impairments of hippocamapal long-term potentiation and recognition memory. Brain Res Bull 2013;95:16.
10. Tamano, H, Fukura, K, Suzuki, M, Sakamoto, K, Yokogoshi, H, Takeda, A. Advantageous effect of theanine intake on cognition. Nutr Neurosci 2014;17:279283.
11. Lardner, AL. Neurobiological effects of the green tea constituent theanine and its potential role in the treatment of psychiatric and neurodegenerative disorders. Nutr Neurosci 2014;17:145155.
12. Unno, K, Fujitani, K, Takamori, N et al. Theanine intake improves the shortened lifespan, cognitive dysfunction and behavioural depression that are induced by chronic psychosocial stress in mice. Free Radic Res 2011;45:966974.
13. Wakabayashi, C, Numakawa, T, Ninomiya, M, Chiba, S, Kunugi, H. Behavioral and molecular evidence for psychotropic effects in L-theanine. Psychopharmacology 2012;219:10991109.
14. Wise, LE, Premaratne, ID, Gamage, TF et al. L-theanine attenuates abstinence signs in morphine-dependent rhesus monkeys and elicits anxiolytic-like activity in mice. Pharmacol Biochem Behav 2012;103:245252.
15. Tian, X, Sun, L, Gou, L et al. Protective effect of L-theanine on chronic restraint stress-induced cognitive impairments in mice. Brain Res 2013;1503:2432.
16. Kimura, K, Ozeki, M, Juneja, LR, Ohira, H. L-Theanine reduces psychological and physiological stress responses. Biol Psychol 2007;74:3945.
17. Nobre, AC, Rao, A, Owen, GN. L-theanine, a natural constituent in tea, and its effect on mental state. Asia Pac J Clin Nutr 2008;17(Suppl. 1):167168.
18. Gomez-Ramirez, M, Kelly, SP, Montesi, JL, Foxe, JJ. The effects of L-theanine on alpha-band oscillatory brain activity during a visuo-spatial attention task. Brain Topogr 2009;22:4451.
19. Gomez-Ramirez, M, Higgins, BA, Rycroft, JA et al. The deployment of intersensory selective attention: a high-density electrical mapping study of the effects of theanine. Clin Neuropharmacol 2007;30:2538.
20. Knyazev, GG. Motivation, emotion, and their inhibitory control mirrored in brain oscillations. Neurosci Biobehav Rev 2007;31:377395.
21. Foxe, JJ, Morie, KP, Laud, PJ, Rowson, MJ, de Bruin, EA, Kelly, SP. Assessing the effects of caffeine and theanine on the maintenance of vigilance during a sustained attention task. Neuropharmacology 2012;62:23202327.
22. Park, SK, Jung, IC, Lee, WK et al. A combination of green tea extract and L-theanine improves memory and attention in subjects with mild cognitive impairment: a double-blind placebo-controlled study. J Med Food 2011;14:334343.
23. Ritsner, MS, Miodownik, C, Ratner, Y et al. L-theanine relieves positive, activation, and anxiety symptoms in patients with schizophrenia and schizoaffective disorder: an 8-week, randomized, double-blind, placebo-controlled, 2-center study. J Clin Psychiatry 2011;72:3442.
24. Ota, M, Wakabayashi, C, Sato, N et al. Effect of L-theanine on glutamatergic function in patients with schizophrenia. Acta Neuropsychiatr 2015;27:291296.
25. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th edn. Arlington, VA: American Psychiatric Association, 2013.
26. Sheehan, DV, Lecrubier, Y, Sheehan, KH et al. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 1998;59(Suppl. 20):2233.
27. Inada, T, Inagaki, A. Psychotropic dose equivalence in Japan. Psychiatry Clin Neurosci 2015;69:440447.
28. Williams, JB, Kobak, KA, Bech, P et al. The GRID-HAMD: standardization of the Hamilton Depression Rating Scale. Int Clin Psychopharmacol 2008;23:120129.
29. Hamilton, M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960;23:5662.
30. Spielberg, CD. GRLaLRE. STAI Manual. Palo Alto, CA: Consulting Psychologists Press, 1970.
31. Buysse, DJ, Reynolds, CF 3rd, Monk, TH, Berman, SR, Kupfer, DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res 1989;28:193213.
32. Lingjaerde, O, Ahlfors, UG, Bech, P, Dencker, SJ, Elgen, K. The UKU side effect rating scale. A new comprehensive rating scale for psychotropic drugs and a cross-sectional study of side effects in neuroleptic-treated patients. Acta Psychiatr Scand Suppl 1987;334:1100.
33. Stroop, JR. Studies of interference in serial verbal reactions. J Exp Psychol 1935;18:643662.
34. Keefe, RS, Goldberg, TE, Harvey, PD, Gold, JM, Poe, MP, Coughenour, L. The Brief Assessment of Cognition in Schizophrenia: reliability, sensitivity, and comparison with a standard neurocognitive battery. Schizophr Res 2004;68:283297.
35. MacLeod, CM, MacDonald, PA. Interdimensional interference in the Stroop effect: uncovering the cognitive and neural anatomy of attention. Trends Cogn Sci 2000;4:383391.
36. Gardener, MC, Gillman, MP. Analyzing variability in nectar amino acids: composition is less variable than concentration. J Chem Ecol 2001;27:25452558.
37. Seretti, A, Cusin, C, Lattuada, E, Di Bella, D, Catalano, M, Smeraldi, E. Serotonin transporter gene (5-HTTLPR) is not associated with depressive symptomatology in mood disorders. Mol Psychiatry 1999;4:280283.
38. Riedel, M, Moller, HJ, Obermeier, M et al. Response and remission criteria in major depression – a validation of current practice. J Psychiatr Res 2010;44:10631068.
39. Skolnick, P, Popik, P, Trullas, R. Glutamate-based antidepressants: 20 years on. Trends Pharmacol Sci 2009;30:563569.
40. Hashimoto, K. Emerging role of glutamate in the pathophysiology of major depressive disorder. Brain Res Rev 2009;61:105123.
41. Newport, DJ, Carpenter, LL, McDonald, WM, Potash, JB, Tohen, M, Nemeroff, CB, Biomarkers APACoRTFoN, & Treatments. Ketamine and other NMDA antagonists: early clinical trials and possible mechanisms in depression. Am J Psychiatry 2015;172:950966.
42. Caddy, C, Giaroli, G, White, TP, Shergill, SS, Tracy, DK. Ketamine as the prototype glutamatergic antidepressant: pharmacodynamic actions, and a systematic review and meta-analysis of efficacy. Ther Adv Psychopharmacol 2014;4:7599.
43. Miller, OH, Moran, JT, Hall, BJ. Two cellular hypotheses explaining the initiation of ketamine’s antidepressant actions: direct inhibition and disinhibition. Neuropharmacology 2016;100:1726.
44. Bergink, V, van Megen, HJ, Westenberg, HG. Glutamate and anxiety. Eur Neuropsychopharmacol 2004;14:175183.
45. Yamada, T, Terashima, T, Okubo, T, Juneja, LR, Yokogoshi, H. Effects of theanine, r-glutamylethylamide, on neurotransmitter release and its relationship with glutamic acid neurotransmission. Nutr Neurosci 2005;8:219226.
46. Kimura, R, Murata, T. Influence of alkylamides of glutamic acid and related compounds on the central nervous system. I. Central depressant effect of theanine. Chem Pharm Bull 1971;19:12571261.
47. Lyon, MR, Kapoor, MP, Juneja, LR. The effects of L-theanine (Suntheanine(R)) on objective sleep quality in boys with attention deficit hyperactivity disorder (ADHD): a randomized, double-blind, placebo-controlled clinical trial. Altern Med Rev 2011;16:348354.
48. Dodd, FL, Kennedy, DO, Riby, LM, Haskell-Ramsay, CF. A double-blind, placebo-controlled study evaluating the effects of caffeine and L-theanine both alone and in combination on cerebral blood flow, cognition and mood. Psychopharmacology 2015;232:25632576.
49. Roberts, KL, Hall, DA. Examining a supramodal network for conflict processing: a systematic review and novel functional magnetic resonance imaging data for related visual and auditory stroop tasks. J Cogn Neurosci 2008;20:10631078.
50. Godsil, BP, Kiss, JP, Spedding, M, Jay, TM. The hippocampal-prefrontal pathway: the weak link in psychiatric disorders? Eur Neuropsychopharmacol 2013;23:11651181.
51. Marsden, WN. Synaptic plasticity in depression: molecular, cellular and functional correlates. Prog Neuropsychopharmacol Biol Psychiatry 2013;43:168184.
52. Zhang, G, Miura, Y, Yagasaki, K. Effects of dietary powdered green tea and theanine on tumor growth and endogenous hyperlipidemia in hepatoma-bearing rats. Biosci Biotechnol Biochem 2002;66:711716.
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