Complementary and Alternative Medicine Treatments for Generalized Anxiety Disorder: Systematic Review and Meta-analysis of Randomized Controlled Trials

Abstract

Introduction

The objective was to evaluate efficacy/safety of complementary and alternative medicine (CAM) methods for generalized anxiety disorder (GAD) based on randomized controlled trials in adults.

Methods

Data sources. Six electronic databases (“generalized anxiety (disorder)” and “randomized trial”) and reference lists of identified publications were searched to March 2017. Study selection. Eligibility: full-text publications (English, German language); CAM versus conventional treatment, placebo/sham or no treatment; GAD diagnosed according to standard criteria; and a validated scale for disease severity. Of the 6693 screened records, 32 were included (18 on biologically-based therapies, exclusively herbal preparations; eight on manipulative and body-based therapies; and three on alternative medical systems and three on mind–body therapies). Data extraction. Cochrane Collaboration methodology was used for quality assessment and data extraction.

Results

Direct comparisons of Kava Kava (Piper methysticum) extracts to placebo (4 quality trials, n = 233) were highly heterogeneous. Network meta-regression reduced heterogeneity and suggested a modest Kava effect [end-of-treatment Hamilton Anxiety scale score difference adjusted for baseline scores and trial duration: − 3.24 (95% CI − 6.65, 0.17; P = 0.059), Kava Kava 4 arms, n = 139; placebo 5 arms, n = 359]. Lavender (Lavandula angustifolia) extract (1 quality trial, 10 weeks, n = 523) and a combination of extracts of C. oxycantha, E. californica and magnesium (1 quality trial, 12 weeks, n = 264) were superior to placebo and balneotherapy was superior to paroxetine (1 quality trial, 8 weeks, n = 237) indicating efficacy. All other trials were small and/or of modest/low quality and/or lacked assay sensitivity. Safety reporting was poor.

Conclusion

Evidence about efficacy/safety of most CAM methods in GAD is limited. Apparent efficacy of certain herbal preparations and body-based therapies requires further confirmation.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2

References

  1. 1.

    Kessler RC, McGonagle KA, Zhao S, et al. Lifetime and 12-month prevalence of dsm-iii-r psychiatric disorders in the united states. Results from the national comorbidity survey. Arch Gen Psychiatry. 1994;51:8–19.

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Nutt DJ, Kessler RC, Alonso J, et al. Consensus statement on the benefit to the community of ESEMeD (European study of the epidemiology of mental disorders) survey data on depression and anxiety. J Clin Psychiatry. 2007;68:42–8.

    PubMed  Google Scholar 

  3. 3.

    Stein M, Sherbourne C, Craske M, et al. Quality of care for primary care patients with anxiety disorders. Am J Psychiatry. 2004;161:2230–7.

    Article  PubMed  Google Scholar 

  4. 4.

    Kessler RC, Chiu WT, Demler O, Walters EE. Prevalence, severity, and comorbidity of 12-month dsm-iv disorders in the national comorbidity survey replication. Arch Gen Psychiatry. 2005;62:617–27.

    Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Alonso J, Angermeyer M, Bernert S, et al. Prevalence of mental disorders in Europe: results from the European Study of the epidemiology of mental disorders (ESEMeD) project. Acta Psychiatr Scand. 2004;109:21–7.

    Article  Google Scholar 

  6. 6.

    Hidalgo RB, Tupler LA, Davidson JR. An effect-size analysis of pharmacologic treatments for generalized anxiety disorder. J Psychopharmacol. 2007;21:864–72.

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Schweitzer I, Maguire K, Ng C. Sexual side-effects of contemporary antidepressants: review. Aust N Z J Psychiatry. 2009;43:795–808.

    Article  PubMed  Google Scholar 

  8. 8.

    Baldwin DS, Montgomery SA, Nil R, et al. Discontinuation symptoms in depression and anxiety disorders. Int J Neuropsychopharmacol. 2007;10:73–84.

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Foa EB, Franklin ME, Moser J. Context in the clinic: How well do cognitive-behavioral therapies and medications work in combination. Biol Psychiatry. 2002;10:987–97.

    Article  Google Scholar 

  10. 10.

    Baldwin DS, Polkinghorn C. Evidence-based pharmacotherapy of generalized anxiety disorder. Int J Neuropsychoph. 2005;8:293–302.

    CAS  Article  Google Scholar 

  11. 11.

    Liu L, Liu C, Wang Y, et al. Herbal medicine for anxiety, depression and insomnia. Curr Neuropharmacol. 2015;13:481–93.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Kinrys G, Coleman E, Rothstein E. Natural remedies for anxiety disorders: potential use and clinical applications. Depress Anxiety. 2009;26:259–65.

    Article  PubMed  Google Scholar 

  13. 13.

    Garcia-Garcia P, Lopez-Munoz F, Rubio G, et al. Phytotherapy and psychiatry: bibliometric study of the scientific literature from the last 20 years. Phytomedicine. 2008;15:566–76.

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Williams J, Gierisch J, McDuffie J, et al. An overview of complementary and alternative medicine therapies for anxiety and depressive disorders: supplement to efficacy of complementary and alternative medicine therapies for posttraumatic stress disorder. Evidence-based synthesis program. Washington: Department of Veterans Affairs; 2011:1–23.

  15. 15.

    Sarris J, Moylan S, Camfield DA, et al. Complementary medicine, exercise, meditation, diet, and lifestyle modification for anxiety disorders: a review of current evidence. Evid Based Complement Alternat Med. 2012;2012:809653.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Jorm AF, Christensen H, Griffiths KM, et al. Effectiveness of complementary and self-help treatments for anxiety disorders. Med J Aust. 2004;181:S29–46.

    PubMed  Google Scholar 

  17. 17.

    Sarris J, Goncalves D, Robins-Wahlins T, et al. Complementary medicine use by middle-aged and older women: personality, mood and anxiety factors. J Health Psychol. 2010;16:314–21.

    Article  PubMed  Google Scholar 

  18. 18.

    Eisenberg D, Davis R, Ettner S, et al. Trends in alternative medicine use in the United States, 1990–1997: results of a follow-up national survey. JAMA. 1998;280:1569–75.

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Unutzer J, Klap R, Sturm R, et al. Mental disorders and the use of alternative medicine: results from a national survey. Am J Psychiatry. 2000;157:1851–7.

    CAS  Article  PubMed  Google Scholar 

  20. 20.

    Kessler R, Soukup J, Davis R, et al. The use of complementary and alternative therapies to treat anxiety and depression in the United States. Am J Psychiatry. 2001;158:289–94.

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Bazzan A, Zabrecky G, Monti D, et al. Current evidence regarding the management of mood and anxiety disorders using complementary and alternative medicine. Expert Rev Neurother. 2014;14:411–23.

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Generalised anxiety disorder and panic disorder in adults: management | Guidance and guidelines | NICE. Niceorguk. 2017. Available at: https://www.nice.org.uk/guidance/cg113/chapter/1-Guidance#principles-of-care-for-people-with-generalised-anxiety-disorder-gad. Accessed April 25, 2017.

  23. 23.

    Higgins JPT, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomized trials. BMJ. 2011;343:d5928.

    Article  PubMed  PubMed Central  Google Scholar 

  24. 24.

    IntHout J, Ioannidis JPA, Borm GF. The Hartung–Knapp–Sidik–Jonkman method for random effects meta-analysis is straightforward and considerably outperforms the standard DerSimonian-Laird method. BMC Med Res Method. 2014;14:25.

    Article  Google Scholar 

  25. 25.

    Riley R, Higgins JPT, Deeks JJ. Interpretation of random effects meta-analyses. BMJ. 2011;342:d549.

    Article  PubMed  Google Scholar 

  26. 26.

    Kessels AGH, terRiet G, Puhan MA, et al. A simple regression model for network meta-analysis. OA Epidemol. 2013;1:7.

    Google Scholar 

  27. 27.

    Brown H, Prescott R. Applied mixed models in medicine, 3rd ed, Wiley 2013:197-230.

  28. 28.

    Whitehead A. Meta-analysis of controlled clinical trials. New Jersey: Wiley; 2002. p. 131–6.

    Google Scholar 

  29. 29.

    Volz H, Kieser M. Kava-kava extract WS 1490 versus placebo in anxiety disorders—a randomized placebo-controlled 25-week outpatient trial. Pharmacopsychiatry. 1997;30:1–5.

    CAS  Article  PubMed  Google Scholar 

  30. 30.

    Malsch U, Kieser M. Efficacy of kava-kava in the treatment of non-psychotic anxiety, following pretreatment with benzodiazepines. Psychopharmacology. 2001;157:277–83.

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    Connor K, Davidson J. A placebo-controlled study of Kava kava in generalized anxiety disorder. Int Clin Psychopharmacol. 2002;17:185–8.

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Sarris J, Stough C, Bousman C, et al. Kava in the treatment of generalized anxiety disorder. J Clin Psychopharmacol. 2013;33:643–8.

    Article  PubMed  Google Scholar 

  33. 33.

    Wheatley D. Kava-kava (LI 150) in the treatment of generalized anxiety disorder. Primary Care Psychia. 2001;7:97–100.

    Article  Google Scholar 

  34. 34.

    Boerner R, Sommer H, Berger W, Kuhn U, Schmidt U, Mannel M. Kava-Kava extract LI 150 is as effective as opipramol and buspirone in generalised anxiety disorder—an 8-week randomized, double-blind multi-centre clinical trial in 129 out-patients. Phytomedicine. 2003;10:38–49.

    Article  PubMed  Google Scholar 

  35. 35.

    Woelk H, Schläfke S. A multi-center, double-blind, randomized study of the Lavender oil preparation Silexan in comparison to lorazepam for generalized anxiety disorder. Phytomedicine. 2010;17:94–9.

    CAS  Article  PubMed  Google Scholar 

  36. 36.

    Kasper S, Gastpar M, Müller W, et al. Lavender oil preparation Silexan is effective in generalized anxiety disorder—a randomized, double-blind comparison to placebo and paroxetine. Int J Neuropsychopharmacol. 2014;17:859–69.

    CAS  Article  PubMed  Google Scholar 

  37. 37.

    Herrera-Arellano A, Jiménez-Ferrer E, Zamilpa A, Morales-Valdéz M, García-Valencia C, Tortoriello J. Efficacy and tolerability of a standardized herbal product from Galphimiaglauca on generalized anxiety disorder. A randomized, double-blind clinical trial controlled with Lorazepam. Planta Med. 2007;73:713–7.

    CAS  Article  PubMed  Google Scholar 

  38. 38.

    Herrera-Arellano A, Jiménez-Ferrer J, Zamilpa A, García-Alonso G, Herrera-Alvarez S, Tortoriello J. Therapeutic effectiveness of Galphimiaglauca vs. lorazepam in generalized anxiety disorder. A controlled 15-week clinical trial. Planta Med. 2012;78:1529–35.

    CAS  Article  PubMed  Google Scholar 

  39. 39.

    Amsterdam J, Li Y, Soeller I, Rockwell K, Mao J, Shults J. A randomized, double-blind, placebo-controlled trial of oral Matricaria recutita (Chamomile) extract therapy for generalized anxiety disorder. J Clin Psychopharmacol. 2009;29:378–82.

    Article  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Mao J, Xie S, Keefe J, Soeller I, Li Q, Amsterdam J. Long-term chamomile (Matricaria chamomilla L.) treatment for generalized anxiety disorder: a randomized clinical trial. Phytomedicine. 2016;23:1735–42.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  41. 41.

    Hanus M, Lafon J, Mathieu M. Double-blind, randomized, placebo-controlled study to evaluate the efficacy and safety of a fixed combination containing two plant extracts (Crataegus oxyacantha and Eschscholtzia californica) and magnesium in mild-to-moderate anxiety disorders. Curr Med Res Opin. 2004;20:63–71.

    Article  PubMed  Google Scholar 

  42. 42.

    Sayyah M, Siahpoosh A, Khalili H, Malayeri A, Samaee H. A double-blind, placebo-controlled study of the aqueous extract of Echium amoenum for patients with general anxiety disorder. Iran J Pharm Res. 2012;11:697–701.

    PubMed  PubMed Central  Google Scholar 

  43. 43.

    Park D, Kim S, Park Y, Kang W, Lee S, Jung I. The comparative clinical study of efficacy of Gamisoyo-San (Jiaweixiaoyaosan) on generalized anxiety disorder according to differently manufactured preparations: Multicenter, randomized, double blind, placebo controlled trial. J Ethnopharmacol. 2014;158:11–7.

    Article  PubMed  Google Scholar 

  44. 44.

    Akhondzadeh S, Naghavi H, Vazirian M, Shayeganpour A, Rashidi H, Khani M. Passionflower in the treatment of generalized anxiety: a pilot double-blind randomized controlled trial with oxazepam. J Clin Pharm Ther. 2001;26:363–7.

    CAS  Article  PubMed  Google Scholar 

  45. 45.

    Andreatini R, Sartori V, Seabra M, Leite J. Effect of valepotriates (valerian extract) in generalized anxiety disorder: a randomized placebo-controlled pilot study. Phytother Res. 2002;16:650–4.

    CAS  Article  PubMed  Google Scholar 

  46. 46.

    Wang T, Ding J, Xu G, Zeng Y, Xiao S. Efficacy of Yiqiyangxin Chinese medicine compound combined with cognitive therapy in the treatment of generalized anxiety disorders. Asian Pac J Trop Med. 2012;5:818–22.

    Article  PubMed  Google Scholar 

  47. 47.

    Eich H, Agelink M, Lehmann E, Lemmer W, Klieser E. AkupunkturbeileichtenbismittelschwerendepressivenEpisoden und Angststörungen–Ergebnisseeiner experimentellen Untersuchung. Fortschr Neurol Psychiatr. 2000;68:137–44.

    CAS  Article  PubMed  Google Scholar 

  48. 48.

    Merom D, Phongsavan P, Wagner R, et al. Promoting walking as an adjunct intervention to group cognitive behavioral therapy for anxiety disorders— a pilot group randomized trial. J Anxiety Disord. 2008;22:959–68.

    Article  PubMed  Google Scholar 

  49. 49.

    Dubois O, Salamon R, Germain C, et al. Balneotherapy versus paroxetine in the treatment of generalized anxiety disorder. Complement Ther Med. 2010;18:1–7.

    Article  PubMed  Google Scholar 

  50. 50.

    Sherman K, Ludman E, Cook A, et al. Effectiveness of therapeutic massage for generalized anxiety disorder: a randomized controlled trial. Depress Anxiety. 2010;27:441–50.

    Article  PubMed  PubMed Central  Google Scholar 

  51. 51.

    Herring M, Jacob M, Suveg C, Dishman R, O’Connor P. Feasibility of exercise training for the short-term treatment of generalized anxiety disorder: a randomized controlled trial. Psychother Psychosom. 2012;81:21–8.

    Article  PubMed  Google Scholar 

  52. 52.

    Ma H, Kui Y, Li Y, Huang B, Li S, Chen X. Bloodletting therapy combined with paroxetine hydrochloride for generalized anxiety disorder: A randomized controlled trial. 2013 IEEE International Conference on Bioinformatics and Biomedicine. 2013.

  53. 53.

    Jonsson K, Kjellgren A. Promising effects of treatment with flotation-REST (restricted environmental stimulation technique) as an intervention for generalized anxiety disorder (GAD): a randomized controlled pilot trial. BMC Complement Altern Med. 2016;16:108.

    Article  PubMed  PubMed Central  Google Scholar 

  54. 54.

    Rapaport M, Schettler P, Larson E et al. Acute Swedish massage monotherapy successfully remediates symptoms of generalized anxiety disorder. J Clin Psychiatry 2016:e883–e891.

  55. 55.

    Bonne O, Shemer Y, Gorali Y, Katz M, Shalev A. A randomized, double-blind, placebo-controlled study of classical homeopathy in generalized anxiety disorder. J Clin Psychiatry. 2003;64:282–7.

    Article  PubMed  Google Scholar 

  56. 56.

    Tubaki B, Chandrashekar C, Sudhakar D, Prabha T, Lavekar G, Kutty B. Clinical efficacy of Manasamitra Vataka (an ayurveda medication) on generalized anxiety disorder with comorbid generalized social phobia: a randomized controlled study. J Altern Complement Med. 2012;18:612–21.

    Article  PubMed  Google Scholar 

  57. 57.

    Gupta K, Mamidi P, Thakar A. Randomized placebo controlled study on Sarasvata choorna in generalised anxiety disorder. Int J Green Pharm. 2014;8:231–6.

    Article  Google Scholar 

  58. 58.

    Zhang Y, Young D, Lee S, et al. Chinese Taoist cognitive psychotherapy in the treatment of generalized anxiety disorder in contemporary China. Transcult Psychiatry. 2002;39:115–29.

    Article  Google Scholar 

  59. 59.

    Koszycki D, Raab K, Aldosary F, Bradwejn J. A multifaith spiritually based intervention for generalized anxiety disorder: a pilot randomized trial. J Clin Psychol. 2010;66:430–41.

    PubMed  Google Scholar 

  60. 60.

    Koszycki D, Bilodeau C, Raab-Mayo K, Bradwejn J. A multifaith spiritually based intervention versus supportive therapy for generalized anxiety disorder: a pilot randomized controlled Trial. J Clin Psychol. 2013;70:489–509.

    Article  PubMed  PubMed Central  Google Scholar 

  61. 61.

    Bandelow B, Zohar J, Hollander E, et al. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of anxiety, obsessive-compulsive and posttraumatic stress disorders. World J Biol Psychiatry. 2002;3:171–99.

    Article  PubMed  Google Scholar 

  62. 62.

    Bereza BG, Machado M, Ravindran AV, Einarson TR. Evidence-based review of clinical outcomes of guideline-recommended pharmacotherapies for generalized anxiety disorder. Can J Psychiatry. 2012;57:470–8.

    Article  PubMed  Google Scholar 

  63. 63.

    Baldwin D, Anderson I, Nutt D, et al. Evidence-based pharmacological treatment of anxiety disorders, post-traumatic stress disorder and obsessive-compulsive disorder: a revision of the 2005 guidelines from the British Association for Psychopharmacology. J Psychopharmacol. 2014;28:403–39.

    Article  PubMed  Google Scholar 

  64. 64.

    Mochcovitch M, da Rocha Freire R, Garcia R, Nardi A. Can long-term pharmacotherapy prevent relapses in generalized anxiety disorder? A Systematic Review. Clin Drug Investig. 2017;37:737–43.

    CAS  Article  PubMed  Google Scholar 

  65. 65.

    Bandelow B, Seidler-Brandler U, Becker A, Wedekind D, Rüther E. Meta-analysis of randomized controlled comparisons of psychopharmacological and psychological treatments for anxiety disorders. World J Biol Psychiatry. 2007;8:175–87.

    Article  PubMed  Google Scholar 

  66. 66.

    Bandelow B, Reitt M, Röver C, Michaelis S, Görlich Y, Wedekind D. Efficacy of treatments for anxiety disorders. Int Clin Psychopharmacol. 2015;30:183–92.

    Article  PubMed  Google Scholar 

  67. 67.

    Otto MW, Smits JA, Reese HE. Combined psychotherapy and pharmacotherapy for mood and anxiety disorders in adults: review and analysis. Clin Psychol Sci Pract. 2005;27:572–81.

    Google Scholar 

  68. 68.

    Kessler RC, Davis RB, Foster DF, et al. Long-term trends in the use of complementary and alternative medical therapies in the United States. Ann Intern Med. 2001;135:262–8.

    CAS  Article  PubMed  Google Scholar 

  69. 69.

    Barnes PM, Bloom B, Nahin RL. Complementary and alternative medicine use among adults and children: United States, 2007, National health statistics reports; no 12.Hyattsville, MD: National Center for Health Statistics; 2008.

  70. 70.

    Fontenelle L, Santana. A review of studies concerning treatment adherence of patients with anxiety disorders. Patient Prefer Adherence. 2011;5:427–39.

  71. 71.

    Jonas WB. Policy, the public, and priorities in alternative medicine research. Ann Am Acad Polit Soc Sci. 2002;583:29–43.

    Article  Google Scholar 

  72. 72.

    Complementary and alternative medicine in the United States. 1st ed. Washington, DC: The National Academies Press; 2005.

  73. 73.

    Sarris J, Stough C, Teschke R, et al. Kava for the treatment of generalized anxiety disorder RCT: analysis of adverse reactions, liver function, addiction, and sexual effects. Phytother Res. 2013;27:1723–8.

    CAS  Article  PubMed  Google Scholar 

  74. 74.

    Plint AC, Moher D, Morrison A, Schulz K, Altman DG, Hill C, Gaboury I. Does the CONSORT checklist improve the quality of reports of randomized controlled trials? A systematic review. Med J Aust. 2006;185:263–7.

    PubMed  Google Scholar 

  75. 75.

    Nutt D, Allgulander C, Lecrubier Y, Peters T, Wittchen H. Establishing non-inferiority in treatment trials in psychiatry—guidelines from an Expert Consensus Meeting. J Psychopharmacol. 2008;22:409–16.

    CAS  Article  PubMed  Google Scholar 

Download references

Acknowledgements

Funding

No funding or sponsorship was received for this study or publication of this article.

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Disclosures

Hrvoje Barić, Veljko Đorđević, Ivan Cerovečki, and Vladimir Trkulja have nothing to disclose.

Compliance with Ethics Guidelines

This article is based on previously conducted studies and does not involve any new studies of humans or animals performed by any of the authors.

Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Vladimir Trkulja.

Additional information

Enhanced content

To view enhanced content for this article go to https://doi.org/10.6084/m9.figshare.5896606.

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 1039 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Barić, H., Đorđević, V., Cerovečki, I. et al. Complementary and Alternative Medicine Treatments for Generalized Anxiety Disorder: Systematic Review and Meta-analysis of Randomized Controlled Trials. Adv Ther 35, 261–288 (2018). https://doi.org/10.1007/s12325-018-0680-6

Download citation

Keywords

  • Complementary and alternative medicine
  • Generalized anxiety disorder
  • Meta-analysis
  • Systematic review
  • Psychiatry