Complementary and alternative therapies as add-on to pharmacotherapy for mood and anxiety disorders: A systematic review
Abstract
Background Depressed and anxious patients often combine complementary and alternative medicine (CAM) therapies with conventional pharmacotherapy to self-treat symptoms. The benefits and risks of such combination strategies have not been fully evaluated. This paper evaluates the risk-benefit profile of CAM augmentation to antidepressants in affective conditions.Methods PubMed was searched for all available clinical reports published in English up to December 2012. Data were evaluated based on graded levels of evidence for efficacy and safety.Results Generally, the evidence base is significantly larger for depression than for anxiety disorder. In unipolar depression, there is Level 2 evidence for adjunctive sleep deprivation (SD) and Free and Easy Wanderer Plus (FEWP), and Level 3 for exercise, yoga, light therapy (LT), omega-3 fatty acids, S-adenosylmethionine and tryptophan. In bipolar depression, there is Level 1 evidence for adjunctive omega-3s, Level 2 for SD, and Level 3 for LT and FEWP. In anxiety conditions, exercise augmentation has Level 3 support in generalized anxiety disorder and panic disorder. Though mostly well-tolerated, these therapies can only be recommended as third-line interventions due to the quality of available evidence.Limitations Overall, the literature is limited. Studies often had methodological weaknesses, with little information on long-term use and on potential drug-CAM interactions. Many CAM studies were not published in English.Conclusions While several CAM therapies show some evidence of benefit as augmentation in depressive disorders, such evidence is largely lacking in anxiety disorders. The general dearth of adequate safety and tolerability data encourages caution in clinical use.
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The finding that Seduction of Spirit participants experienced a greater reduction in depressed mood compared to other courses supports previous data on the beneficial effects of meditation specifically on depression.
“We found that participants in the Seduction of Spirit meditation course experienced a greater reduction in depressed mood scores compared to the other courses, which supports previous data on the beneficial effects of meditation specifically on depression.34”
From Psychosocial Effects of a Holistic Ayurvedic Approach to Well-being in Health and Wellness Courses (2019) · cites this paper as [34]
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BackgroundSelf-citationNutrition and behavioral health disorders: depression and anxiety
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BackgroundHerbal Medicine for Anxiety, Depression and Insomnia
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Health benefits and phenolic compounds of Moringa oleifera leaves: A comprehensive review
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Complementary therapies for clinical depression: an overview of systematic reviews
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“While some complementary therapies have become a promising adjunct in the standard treatment of depression,(29) 30 others are known for their possible side effects or interactions with standard drugs.(30) Recent clinical practice guidelines, in addition, vary widely in their search strategies and resulting recommendat…”
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Nutrients Turned into Toxins: Microbiota Modulation of Nutrient Properties in Chronic Kidney Disease
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“However, this use of tryptophan is not supported by scientific evidence [120].”
BackgroundLight therapy in the treatment of patients with bipolar depression: A meta-analytic study
Tseng, P.-T., Chen, Y.-W., Tu, K.-Y., Chung, W., Wang, H.-Y., Wu, C.-K., & Lin, P.-Y. (2016) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2016.03.001 · Cited by 100 · see citing works
The American Psychiatric Association Practice Guidelines for the Psychiatric Evaluation of Adults
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“[1] Ravindran and da Silva[2] have”
BackgroundTreatment-resistant panic disorder: clinical significance, concept and management
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de Jonge, P., Wardenaar, K. J., Hoenders, R. H. J., Evans-Lacko, S. E., Kovess–Masféty, V., Aguilar‐Gaxiola, S., Al-Hamzawi, A., Alonso, J., Andrade, L. H., Benjet, C. L., et al. (2017) · Epidemiology and Psychiatric Sciences · doi:10.1017/s2045796017000774 · Cited by 74 · see citing works
“Standardised translation, back-translation, harmonization and quality control procedures were applied in all of the participating survey sites (Pennell et al. 2008).”
MethodLopresti, A. L., Drummond, P. D., Inarejos-García, A. M., & Pródanov, M. (2018) · Journal of Affective Disorders · doi:10.1016/j.jad.2018.02.070 · Cited by 68 · see citing works
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Ravindran, A., Balneaves, L., Faulkner, G., Ortiz, A., Mcintosh, D., Morehouse, R., Ravindran, L. N., Yatham, L., Kennedy, S., Lam, R. W., et al. (2018) · Focus · doi:10.1176/appi.focus.16106 · Cited by 348 · see citing works
“It involves keeping patients awake for extended periods, with total SD lasting up to 40 hours and partial SD allowing 3 to 4 hours of sleep per night.(29) Sleep deprivation is typically employed 2 to 4 times over the course of 1 week, with total SD often interspersed with partial SD or normal (recovery) sleep.”
BackgroundSelf-citationMoslemi, F., Alijaniha, F., Naseri, M., Kazemnejad, A., Charkhkar, M., & Heidari, M. R. (2019) · The Journal of Alternative and Complementary Medicine · doi:10.1089/acm.2019.0061 · Cited by 58 · see citing works
“12 13–15 Furthermore, in traditional Persian medicine (TPM), there is a considerable emphasis on using aromatic herbal drugs to relieve emotional disorders, including anxiety.”
Koga, N., Ogura, J., Yoshida, F., Hattori, K., Hori, H., Aizawa, E., Ishida, I., & Kunugi, H. (2019) · Translational Psychiatry · doi:10.1038/s41398-019-0536-0 · Cited by 54 · see citing works
Current status of yoga in mental health services
Varambally, S. S., & Gangadhar, B. N. (2016) · International Review of Psychiatry · doi:10.3109/09540261.2016.1159950 · Cited by 54 · see citing works
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Guidelines for the diagnosis and treatment of depressive disorders in China: The second edition
Feng, Y., Xiao, L., Wang, W., Ungvari, G. S., Ng, C. H., Wang, G., & Xiang, Y. (2019) · Journal of Affective Disorders · doi:10.1016/j.jad.2019.04.104 · Cited by 46 · see citing works
Prader–Willi syndrome: From genetics to behaviour, with special focus on appetite treatments
Griggs, J. L., Sinnayah, P., & Mathai, M. L. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.10.003 · Cited by 45 · see citing works
Biofeedback to treat anxiety in young people at clinical high risk for developing psychosis
McAusland, L., & Addington, J. (2018) · Early Intervention in Psychiatry · doi:10.1111/eip.12368 · Cited by 37 · see citing works
Schuch, F. B., da Silveira, L. E., de Zeni, T. C., da Silva, D. P., Wollenhaupt-Aguiar, B., Ferrari, P., Reischak-Oliveira, Á., & Kapczinski, F. P. (2015) · Psychiatry Research · doi:10.1016/j.psychres.2015.07.072 · Cited by 32 · see citing works
“The Schmidt-Kassow et al. (2012) study used an exercise protocol based on sustained exercise during 30 min.”
MethodCorreale, C., Borgi, M., Collacchi, B., Falamesca, C., Gentile, S., Vigevano, F., Cappelletti, S., & Cirulli, F. (2022) · Frontiers in Psychology · doi:10.3389/fpsyg.2022.840107 · Cited by 31 · see citing works
Animal-Assisted Therapy in Pediatric Palliative Care
Gilmer, M. J., Baudino, M. N., Goddard, A., Vickers, D. C., & Akard, T. F. (2016) · Nursing Clinics of North America · doi:10.1016/j.cnur.2016.05.007 · Cited by 30 · see citing works
Psychosocial Effects of a Holistic Ayurvedic Approach to Well-being in Health and Wellness Courses
Patel, S., Klagholz, S., Peterson, C. T., Weiss, L., Chopra, D., & Mills, P. J. (2019) · Global Advances In Health and Medicine · doi:10.1177/2164956119843814 · Cited by 29 · see citing works
“We found that participants in the Seduction of Spirit meditation course experienced a greater reduction in depressed mood scores compared to the other courses, which supports previous data on the beneficial effects of meditation specifically on depression.(34) Participants in the Seduction of Spirit course also spent…”
ResultThe role of n-3 polyunsaturated fatty acids (n-3PUFAs) in affective disorders
Ciappolino, V., Delvecchio, G., Agostoni, C. V., Mazzocchi, A., Altamura, A. C., & Brambilla, P. (2016) · Journal of Affective Disorders · doi:10.1016/j.jad.2016.12.034 · Cited by 29 · see citing works
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Panic Disorder: A Review of Treatment Options
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“TABLE 3 lists supplements considered to have possible anti-anxiety effects that have been studied for that purpose.(115-126) While some of these supplements have modest evidence validating their use for other problems (for example, St.”
Insight in psychosis: An independent predictor of outcome or an explanatory model of illness?
Jacob, K. S. (2014) · Asian Journal of Psychiatry · doi:10.1016/j.ajp.2014.06.001 · Cited by 26 · see citing works
Kishore, R. K., Abhishekh, H. A., Udupa, K., Thirthalli, J., Lavekar, G. S., Gangadhar, B. N., Raju, T. R., & Sathyaprabha, T. N. (2014) · Asian Journal of Psychiatry · doi:10.1016/j.ajp.2014.07.002 · Cited by 26 · see citing works
Jacob, K. (2016) · Indian Journal of Psychological Medicine · doi:10.4103/0253-7176.183078 · Cited by 24 · see citing works
“[15] People with mental illness commonly combine modern medicine with complementary and alternative therapies for relief of symptoms and distress.[41] Patients and their families seem to be comfortable with compartmentalizing their contradictory EMs and seek diverse forms of cure and healing.”
BackgroundPain in Mucopolysaccharidoses: Analysis of the Problem and Possible Treatments
Congedi, S., ORZALESI, M. M., Pede, C. D., & Benini, F. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19103063 · Cited by 23 · see citing works
“Non-pharmacological therapies should be taken into consideration in addition to the pharmacological ones mostly for illness associated emotional, social, and spiritual disturbances and in the case of chronic pain [96].”
BackgroundRavindran, A. V., McKay, M. S., Silva, T. D., Tindall, C., Garfinkel, T., Paric, A., & Ravindran, L. (2021) · The Canadian Journal of Psychiatry · doi:10.1177/0706743720940535 · Cited by 22 · see citing works
“Depressed patients are often seeking these options, partly due to poor access to conventional treatments, but in addition, they often perceive CAMs as safer, accessible, more tolerable, and easily acceptable compared to pharmaceuticals.(15) It has been estimated that 10% to 30% of depressed patients use CAM therapies,…”
BackgroundSelf-citationBanaschewski, T., Belsham, B., Bloch, M. H., Ferrín, M., Johnson, M., Kustow, J., Robinson, S., & Zuddas, A. (2018) · Nutrition and Health · doi:10.1177/0260106018772170 · Cited by 22 · see citing works
“Data from autism (van Elst et al., 2014), anxiety disorders (Ravindran and da Silva, 2013) and obsessive–compulsive disorder studies (Fux et al., 2004) are too sparse from which to draw conclusions.”
BackgroundVoluntary exercise enables stress resistance in females
Tanner, M. K., Fallon, I. P., Baratta, M. V., & Greenwood, B. N. (2019) · Behavioural Brain Research · doi:10.1016/j.bbr.2019.111923 · Cited by 20 · see citing works
Effect of Osteopathic Manipulative Therapy on Generalized Anxiety Disorder
Dixon, L., Fotinos, K., Sherifi, E., Lokuge, S., Fine, A., Furtado, M., Anand, L., Liberatore, K., & Katzman, M. A. (2020) · Journal of Osteopathic Medicine · doi:10.7556/jaoa.2020.026 · Cited by 20 · see citing works
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“, insomnia, mood alteration, and pain control) (18), despite the mixed evidence for its effectiveness for these conditions.”
BackgroundTsai, C.-Y., Yang, H.-C., Islam, M., Hsieh, W.-S., Juan, S.-H., Chen, J.-C., Khan, H. A., & Jian, W.-S. (2017) · International Journal for Quality in Health Care · doi:10.1093/intqhc/mzx123 · Cited by 14 · see citing works
“We found that psychotropic medication prescription has increased in adolescents over the study period, although the percentage of adolescents treated with psychotropic medications was still lower than in the USA (6%), [11], Italy (2.”
BackgroundStreeter, C. C., Gerbarg, P. L., Nielsen, G. H., Brown, R. P., Jensen, J. E., & Silveri, M. M. (2018) · PubMed · doi:10.4172/neuropsychiatry.1000535 · Cited by 18 · see citing works
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Tennis enhances well-being in university students
Yazıcı, A. B., Gul, M. O., Yazıcı, E., & Gül, G. K. (2016) · Mental Illness · doi:10.4081/mi.2016.6510 · Cited by 21 · see citing works
Integrating yoga in mental health services
Gangadhar, B. N., & Varambally, S. S. (2015) · The Indian Journal of Medical Research · doi:10.4103/0971-5916.160685 · Cited by 13 · see citing works
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Non-pharmacological strategies to decrease anxiety in cardiac catheterization: integrative review
Ferreira, N. D. C., Ramalho, E. D. S., & Lopes, J. D. L. (2015) · Revista Brasileira de Enfermagem · doi:10.1590/0034-7167.2015680614i · Cited by 12 · see citing works
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Acupuncture for Major Depressive Disorder: A Systematic Review.
Sorbero, M., Reynolds, K., Colaiaco, B., Lovejoy, S. L., Farris, C. A., Vaughan, C., Sloan, J., Kandrack, R., Apaydin, E. A., & Herman, P. M. (2016) · Rand health quarterly · doi:10.7249/rhq-05-04-07 · Cited by 13 · see citing works
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Practice Guidelines for the Psychiatric Evaluation of Adults, Third Edition
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Yoga-based interventions for the management of psychiatric disorders
Varambally, S. S., & Gangadhar, B. N. (2016) · Cambridge University Press eBooks · doi:10.1017/cbo9781316157565.010 · Cited by 9 · see citing works
Yoga in Psychiatry: An Examination of Concept, Efficacy, and Safety
Reddy, M. S. S., & Vijay, M. S. (2016) · Indian Journal of Psychological Medicine · doi:10.4103/0253-7176.185948 · Cited by 9 · see citing works
“Anxiety and depression There are many studies[4‐6] showing improvement in anxiety and depressive symptoms (level 3 evidence[7]) Editorial”
Gnasso, R., Corrado, B. M., Iommazzo, I., Migliore, F., Magliulo, G., Giardulli, B., & Ruosi, C. (2022) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-022-02402-w · Cited by 8 · see citing works
“in 2018, instead, in their systematic review have summarised the effects of complementary and alternative medicine (CAM) on depression, panic and anxiety disorders [49].”
BackgroundOlatunji, T. L., Siebert, F., Adetunji, A. E., Harvey, B. H., Gericke, J., Hamman, J. H., & van der Kooy, F. (2021) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2021.114711 · Cited by 8 · see citing works
On Gelsemium and Complementary and Alternative Medicine (CAM) in Anxiety and Experimental Neurology
Chirumbolo, S. (2014) · Neurology and Therapy · doi:10.1007/s40120-014-0025-6 · Cited by 8 · see citing works
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“on termination, however, can be major deterrents to compliance, and affect over 50% of users in the longer-term (20, 22, 23).”
BackgroundPráticas corporais no Centro de Atenção Psicossocial de Álcool e Drogas: a percepção dos usuários
da Silva, P. P. C., dos Santos, A. R. M., dos Santos, P. D. J. C., Rodrigues, E. A. P. C., & de Freitas, C. M. S. M. (2018) · Revista Brasileira de Ciências do Esporte · doi:10.1016/j.rbce.2018.08.004 · Cited by 8 · see citing works
Use of Recorded Poetic Audios to Manage Levels of Anxiety and Sleep Disorders
dos Reis, A. C., Vidal, C. L., Caetano, K. A. D. S., & Dias, H. D. (2019) · Journal of Religion and Health · doi:10.1007/s10943-019-00947-y · Cited by 7 · see citing works
Neurotrophic paths in the treatment of depression
Hayley, S. P., & Anisman, H. (2013) · Journal of Psychiatry and Neuroscience · doi:10.1503/jpn.130146 · Cited by 7 · see citing works
Lipids in the Treatment of Mental Disorders
Lange, K. W. (2020) · Bailey's Industrial Oil and Fat Products · doi:10.1002/047167849x.bio120 · Cited by 7 · see citing works
Pasten, C. S., & Caneo, C. (2022) · Medwave · doi:10.5867/medwave.2022.01.002146 · Cited by 6 · see citing works
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Chronobiology and Treatment in Depression
Geoffroy, P. A., & Yeim, S. (2017) · Springer eBooks · doi:10.1007/978-981-10-6577-4_9 · Cited by 5 · see citing works
MATSUURA, Y., Watanabe, Y., Taniguchi, H., Koga, Y., Yasuno, F., & SAKAI, T. (2020) · Clinical Medicine Insights Case Reports · doi:10.1177/1179547620967379 · Cited by 5 · see citing works
Aktaş, Y. Y., & Karabulut, N. (2017) · European Journal of Integrative Medicine · doi:10.1016/j.eujim.2017.10.004 · Cited by 4 · see citing works
Adjunctive Docosahexaenoic Acid in Residual Symptoms of Depression and Anxiety
Piperoglou, M., Hopwood, M., & Norman, T. R. (2023) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000001767 · Cited by 4 · see citing works
Morbid Anxiety: Identification and Treatment
Goddard, A. W. (2017) · FOCUS The Journal of Lifelong Learning in Psychiatry · doi:10.1176/appi.focus.20160046 · Cited by 4 · see citing works
Treatment-Resistant Panic Disorder
Chen, M., & Tsai, S. (2018) · Springer eBooks · doi:10.1007/978-981-10-4358-1_13 · Cited by 5 · see citing works
Thomas, S. R. (2015) · Advances in Integrative Medicine · doi:10.1016/j.aimed.2015.03.001 · Cited by 4 · see citing works
“In a review of complementary antidepressant augmentation agents, Ravindran notes that serotonin syndrome resulting from augmentation of antidepressants with L-tryptophan is ‘‘rare’’ [19].”
BackgroundEyre, H. A. (2014) · Journal of Yoga & Physical Therapy · doi:10.4172/2157-7595.1000165 · Cited by 4 · see citing works
“A number of primary research, meta-analyses and systematic reviews have examined the efficacy of various subtypes of PA in depression [26,34,29-32,48-54].”
BackgroundRådmark, L., Hanson, L. L. M., Horwitz, E. B., & Osika, W. (2017) · PLoS ONE · doi:10.1371/journal.pone.0184635 · Cited by 4 · see citing works
Castelli, L., Galasso, L., Borrelli, M., Esposito, F., Caumo, A., Michielon, G., Roveda, E., & Montaruli, A. (2025) · BMC Public Health · doi:10.1186/s12889-025-25951-8 · Cited by 3 · see citing works
“Notably, physical activity has been shown to be as effective as pharmacological or psychological treatments in alleviating symptoms of anxiety, psychological distress, and depression, primarily through activation of the serotonergic and noradrenergic systems [49–52].”
Plantas utilizadas en la medicina popular paraguaya para tratar afecciones relacionadas al estrés
Ebenhoch, R., Saenger, K., Crosa, F., González, Y. P., & de Arrúa, R. D. (2021) · Revista de la Sociedad Científica del Paraguay · doi:10.32480/rscp.2021.26.1.82 · Cited by 3 · see citing works
Palmieri, M. A., Agosti, L. P., Bové, M., Sikora, V., Santoro, M., Tucci, P., Schiavone, S., Trabace, L., & Morgese, M. G. (2025) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2025.111362 · Cited by 3 · see citing works
“Research indicates that n-3 PUFA may have antidepressant effects through their ability to modulate neuroinflammation, influence neurotransmitters and improve neuro-plasticity (Ravindran and da Silva, 2013).”
Yoga and Traditional Healing Methods in Mental Health
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Exploring on the comparative merit of allopathy medicine and yoga therapy for PCOD condition
Devi, C. R., & Rani, N. J. (2022) · International Journal of Health Sciences · doi:10.53730/ijhs.v6ns3.5187 · Cited by 2 · see citing works
Kim, R. W., & Kim, M. (2024) · Journal of Integrative and Complementary Medicine · doi:10.1089/jicm.2023.0577 · Cited by 4 · see citing works
“16 Particularly, aromatherapy is widely utilized as one of the various complementary and alternative therapies for alleviating anxiety.”
Nimri, L., Zohar, L., & Horovitz, O. (2024) · Food and Humanity · doi:10.1016/j.foohum.2024.100407 · Cited by 2 · see citing works
S-Adenosyl-L-Methionine for Major Depressive Disorder
Berardis, D. D., Orsolini, L., Iasevoli, F., Tomasetti, C., Mazza, M., Valchera, A., Fornaro, M., Perna, G., Piersanti, M., Nicola, M. D., et al. (2016) · Springer eBooks · doi:10.1007/978-81-322-2803-5_49 · Cited by 2 · see citing works
Body practices in rehabilitation alcohol and drugs users: a lifestyle setting
da Silva, P. P. C., dos Santos, A. R. M., dos Santos, P. D. J. C., & de Freitas, C. M. S. M. (2017) · Motricidade · doi:10.6063/motricidade.12945 · Cited by 2 · see citing works
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“Interestingly, one commonly cited reason for the use of complementary medicines, such as dietary supplements, in the general population is to help manage chronic diseases (5) , including mental health issues such as disordered mood (6,7) .”
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Komplementärmedizin im Krankenhaus: Strategien, Konzepte, Umsetzung
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Treatment of Adolescent Mental Disorders: Cross‐Cultural Issues
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- Authors
- Ravindran, A. V., & da Silva, T. L.
- Affiliations
- Centre for Addiction and Mental Health (CA)
- Corresponding author
- Ravindran, Arun V.
- ORCID
- Ravindran, Arun V.
- Venue
- Journal of Affective Disorders
- Publisher
- Elsevier BV
- Published
- 2013-09
- Volume
- 150
- Issue
- 3
- Pages
- 707-719
- ISSN
- 0165-0327 (ISSN-L)
- OpenAlex
- W1977854880
- Cited by
- 121
- References
- 201
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 7 · 2023: 3 · 2022: 5 · 2021: 9 · 2020: 12 · 2019: 10 · 2018: 9 · 2017: 14 · 2016: 18 · 2015: 18 · 2014: 7 · 2013: 4
- FWCI
- 3.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Affective Disorders (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Complementary and Alternative Medicine Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plant Extracts Effects
- Keywords
- complementary and alternative medicine, adjunctive therapy, antidepressants, depression, anxiety disorders, bipolar depression, sleep deprivation, physical activity, yoga, phototherapy, omega-3 fatty acids, S-adenosylmethionine, tryptophan, generalized anxiety disorder, panic disorder, safety and tolerability
- MeSH terms
- Complementary Therapies, Anxiety Disorders, Combined Modality Therapy, Female, Humans, Male, Phototherapy, S-Adenosylmethionine, Tryptophan, Yoga, Fatty Acids, Omega-3, Meditation, Mood Disorders
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