cadth rapid response report: summary of abstracts ... · anxiety disorders were examined in seven...

Service Line: Rapid Response Service

Version: 1.0

Publication Date: April 25, 2018

Report Length: 21 Pages

CADTH RAPID RESPONSE REPORT: SUMMARY OF ABSTRACTS

Alternative Practitioners and Treatments for Mental Health Conditions: Clinical and Cost-Effectiveness and Guidelines

SUMMARY OF ABSTRACTS Alternativ e Practitioners and Treatments f or Mental Health Conditions 2

Authors: Charlotte Wells, Lorna Adcock

Cite As: Alternativ e practitioners and treatments f or mental health conditions: clinical and cost-ef f ectiveness and guidelines Ottawa: CADTH; 2018 Apr.

(CADTH rapid response report: summary of abstracts).

Acknowledgments:

Disclaimer: The inf ormation in this document is intended to help Canadian health care decision-makers, health care prof essionals, health sy stems leaders,

and policy -makers make well-inf ormed decisions and thereby improv e the quality of health care serv ices. While patients and others may access this document,

the document is made av ailable f or inf ormational purposes only and no representations or warranties are made with respect to its f itness f or any particular

purpose. The inf ormation in this document should not be used as a substitute f or prof essional medical adv ice or as a substitute f or the application of clinical

judgment in respect of the care of a particular patient or other prof essional judgment in any decision-making process. The Canadian Agency f or Drugs and

Technologies in Health (CADTH) does not endorse any inf ormation, drugs, therapies, treatments, products, processes, or serv ic es.

While care has been taken to ensure that the inf ormation prepared by CADTH in this document is accurate, complete, and up-to-date as at the applicable date

the material was f irst published by CADTH, CADTH does not make any guarantees to that ef f ect. CADTH does not guarantee and is not responsible f or the

quality , currency , propriety , accuracy, or reasonableness of any statements, information, or conclusions contained in any third-party materials used in preparing

this document. The v iews and opinions of third parties published in this document do not necessarily state or ref lect t hose of CADTH.

CADTH is not responsible f or any errors, omissions, injury , loss, or damage arising f rom or relating to the use (or misuse) of any inf ormation, statements, or

conclusions contained in or implied by the contents of this document or any of the source materials.

This document may contain links to third-party websites. CADTH does not hav e control ov er the content of such sites. Use of third-party sites is gov erned by

the third-party website owners’ own terms and conditions set out f or such sites. CADTH does not make any guarantee with respect to any inf ormation

contained on such third-party sites and CADTH is not responsible f or any injury , loss, or damage suf f ered as a result of using such third-party sites. CADTH

has no responsibility f or the collection, use, and disclosure of personal inf ormation by third-party sites.

Subject to the af orementioned limitations, the v iews expressed herein are those of CADTH and do not necessarily represent the v iews of Canada’s f ederal,

prov incial, or territorial gov ernments or any third party supplier of inf ormation.

This document is prepared and intended f or use in the context of the Canadian health care sy stem. The use of this document outside of Canada is done so at

the user’s own risk.

This disclaimer and any questions or matters of any nature arising f rom or relating to the content or use (or misuse) of this document will be gov erned by and

interpreted in accordance with the laws of the Prov ince of Ontario and the laws of Canada applicable therein, and all proceedings shall be subject to the

exclusiv e jurisdiction of the courts of the Prov ince of Ontario, Canada.

The copy right and other intellectual property rights in this document are owned by CADTH and its licensors. These rights are protected by the Canadian

Copyright Act and other national and international laws and agreements. Users are permitted to make copies of this document f or non-commercial purposes

only , prov ided it is not modif ied when reproduced and appropriate credit is giv en to CADTH and its licensors.

About CADTH: CADTH is an independent, not-f or-prof it organization responsible f or prov iding Canada’s health care decision-makers with objectiv e ev idence

to help make inf ormed decisions about the optimal use of drugs, medical dev ices, diagnostics, and procedures in our health care sy stem.

Funding: CADTH receiv es f unding f rom Canada’s f ederal, prov incial, and territorial gov ernments, with the exception of Quebec.


Research Questions

1. What is the clinical effectiveness of alternative healthcare providers for the management

or treatment of mental health conditions?

2. What is the clinical effectiveness of natural health products for the management or

treatment of mental health conditions?

3. What is the cost-effectiveness of alternative healthcare providers for the management

or treatment of mental health conditions?

4. What is the cost-effectiveness of natural health products for the management or

treatment of mental health conditions?

5. What are the evidence-based guidelines regarding the use of alternative healthcare

providers or natural health products for the management or treatment of mental health

conditions?

Key Findings

Forty-two systematic reviews (SRs), three economic evaluations, and six evidence based

guidelines were identified regarding the use of alternative healthcare providers or natural

health products for the management or treatment of mental health conditions.

Methods

A limited literature search, with main concepts appearing in title or major subject heading,

was conducted on key resources including Ovid Medline, PubMed, The Cochrane Library,

University of York Centre for Reviews and Dissemination (CRD) databases , Canadian and

major international health technology agencies, as well as a focused Internet search. No

methodological filters were applied to limit retrieval by publication type. The search was

limited to English language documents published between January 1, 2013 and April 11,

2018. Internet links were provided, where available.

Selection Criteria

One reviewer screened citations and selected studies based on the inclusion criteria

presented in Table 1.


Table 1: Selection Criteria

Population Individuals of any age with any mental health condition

Interventions Alternative healthcare providers (e.g., naturopath) Natural health products (e.g., kava extract, St. John’s wort, lavender extract)

Comparators Q1-4: Any other treatment; No treatment Q5: No comparator

Outcomes Q1-2: Clinical effectiveness (e.g., improvement or change in mental health symptoms or quality of life) Q3-4: Cost-effectiveness Q5: Guidelines

Study Designs Health technology assessments, systematic reviews, meta-analyses, randomized controlled trials, non-randomized studies, economic evaluations, evidence-based guidelines

Results

Rapid Response reports are organized so that the higher quality evidence is presented first.

Therefore, health technology assessment reports, systematic reviews, and meta-analyses

are presented first. These are normally followed by randomized controlled trials and non-

randomized studies; however, these were not included in the report due to the volume of

identified literature. Economic evaluations and evidence-based guidelines follow the

systematic reviews and meta-analyses.

Forty-two systematic reviews (SRs), three economic evaluations, and six evidence based

guidelines were identified regarding the use of alternative healthcare providers or natural

health products for the management or treatment of mental health conditions. No relevant

health technology assessments were identified.

Additional references of potential interest are provided in the appendix.

Overall Summary of Findings

Forty-two systematic reviews (SRs)1-42 (fourteen of which had meta-

analyses1,2,4,6,8,16,19,25,27,31,33,38- 40 and one of which was an overviews of reviews21), three

economic evaluations,43-45 and six evidence based guidelines46-51 were identified regarding

the use of alternative healthcare providers or natural health products for the management

or treatment of mental health conditions. Detailed study characteristics are provided in

Table 2.

The majority of SRs identified commented on the limitations of the evidence and high levels

of bias in their included reports.1,2,4,5,8,10-13,15,18,22-28,30-32,35- 37,41 This makes firm conclusions

about the clinical effectiveness of natural health products or treatments difficult and many of

the conclusions should be interpreted with caution.

Five SRs focused on St. John’s Wort,4,8-10,21 six SRs focused on acupuncture,2,6,15,32,37,39

and sixteen SRs focused on herbal medicines or herbal

supplements.1,3,4,14,18,20,24,26,27,29,30,33-36,38 Additionally, fifteen SRs focused on mineral and

vitamin supplements,21,40-42 including vitamin D,7,19,28,31 omega-3 polyunsaturated fatty

acids,4,7,11,16,21,37 and magnesium.5 The remaining SRs focused on S-adenosyl

methionine,4,12,21 probiotics,17 reiki,22 melatonin,23 and morita therapy.25


The majority of SRs focused on individuals with depression, major depressive disorders

(MDDs), or depressive symptoms.2-4,6,8-13,16-22,24,26-29,31,33,34335,38 Four SRs focused on

postpartum depression7,14,37,41 and one focused on seasonal affective disorders (SAD).23

Anxiety disorders were examined in seven SRs,1,3,5,17,22,25,30 and post-traumatic stress

disorder (PTSD) was examined in three SRs.15,32,39

Three economic evaluations (EEs) were identified.43-45 Two EEs examined depression,44,45

and one EE examined anxiety.43 The EEs examined St. John’s wort,45 acupuncture,44 and

complementary and alternative therapies as interventions.43

Seven evidence based guidelines were identified.46-51 For depression and MDDs, three

guidelines47-49 were identified. One guideline, produced by Department of Veterans Affairs

and Department of Defense (VA/DoD), states that there is insufficient evidence to

recommend acupuncture as a primary treatment or adjunctive therapy to pharmacotherapy

for depression.47 Another guideline, also by VA/DoD, states that there is also insufficient

evidence to recommend acupuncture as a primary treatment for PTSD.46 For other

alternative therapies, the guideline for treatment of depression by VA/DoD has a weak

recommendation for the use of St. John’s wort as a monotherapy in mild MDD for

individuals who are not pregnant or breastfeeding.47 Omega-3 fatty acids and vitamin D are

not recommended as treatment for MDD.47 The Canadian Network for Mood and Anxiety

Treatments (CANMAT) also created guidelines for adults with MDD.48 For mild to moderate

MDD, St. John's wort, omega-3 fatty acids, and S-adenosyl-L-methionine are

recommended as first- or second-line treatments.48 For moderate to severe MDD, CANMAT

recommends adjunctive St. John's wort as a second-line therapy.48

For children with depression, one guideline produced by the National Institute for Health

and Care Excellence (NICE) recommends that St. John’s wort not to be used in children or

adolescents due to an unknown side effect profile and interaction with other medications.49

They also recommend that a child or young person currently using St. John’s wort be

advised to discontinue use.49

For anxiety and mood disorders, including obsessive compulsive disorder (OCD) and

PTSD, a guideline by the Canadian Anxiety Guidelines Initiative Group on behalf of the

Anxiety Disorders Association of Canada recommends that St. John’s wort not be used for

the treatment of SAD.50 They also do not widely recommend the use of herbal supplements

for the treatment of generalized anxiety disorder, as preparations are poorly standardized

and vary in medicinal content.50 Due to this poor standardization, they also do not

recommend the use of St. John’s wort or herbal therapies in the treatment of OCD.50

Table 2: Summary of Included Studies on The Use of Alternative Healthcare Providers or Natural Health Products for the Management or Treatment of Mental Health Conditions

First Author, Year

Study Characteristi

cs

Disorder

Therapy/Treatment

Comparator Conclusions

Systematic Reviews and Meta-Analyses

Baric, 20181 N = 32 MA performed Network MA

GAD

CAM

Kava Kava Lavender

Placebo

“Network meta-regression reduced heterogeneity and suggested a modest Kava effect.



First Author, Year

Study Characteristi

cs

Disorder

Therapy/Treatment


performed C. oxycantha, E. californica and magnesium

Lavender extract…and a combination of extracts of C. oxycantha, E. californica and magnesium…were superior to placebo.”1 “Evidence about efficacy/safety of most CAM methods in GAD is limited.”1

Smith, 20182 N = 64 MA performed

Depression

Acupuncture Acupuncture plus pharmacological therapy

Treatment as usual No treatment Wait list control Control acupuncture Pharmacological therapies Psychological therapies

“The reduction in severity of depression was less when acupuncture was compared with control acupuncture than when acupuncture was compared with no treatment control, although in both cases, results were rated as providing low-quality evidence. The reduction in severity of depression with acupuncture given alone or in conjunction with medication versus medication alone is uncertain owing to the very low quality of evidence. The effect of acupuncture compared with psychological therapy is unclear. The risk of adverse events with acupuncture is also unclear”2

Yeung, 20183 N =100 Depression Anxiety

Single-herb medicines

Lavender Passionflower

Saffron

Black cohosh Chamomile

Chasteberry

Conventional medicines Standard treatments

“…lavender, passionflower, and saffron produced benefits comparable to standard anxiolytics and antidepressants.”3 “Based on availab le data, b lack cohosh, chamomile, chasteberry, lavender, passionflower, and saffron appear useful in mitigating anxiety or depression with favorable risk-benefit profiles compared to standard treatments.”3

Asher, 20174 N = 22 for direct trials

N = 127 for indirect trials

MA

MDD CAM

Acupuncture Omega-3 fatty

acids

SAME

SGAs “Although we found little difference in the comparative efficacy of most CAM therapies or exercise and SGAs, the overall poor quality of the



First Author, Year

Study Characteristi

cs

Disorder

Therapy/Treatment


performed

Network MA performed

St. John's wort

availab le evidence base tempers any conclusions that we might draw from those trials”4

Boyle, 20175 N = 18 Anxiety Mg supplementation

NR “Four/eight studies in anxious samples reported positive effects of Mg on subjective anxiety outcomes. Mg had no effect on postpartum anxiety”5

Dong, 20176 N = 18 MA performed

Depression Depression related insomnia

Acupuncture Western medicine “There was no statistical difference … between acupuncture treatment and Western medicine towards improving the HAMD score. Acupuncture combined with Western medicine…had more effect on improving depression degree compared with the Western medicine alone.”6

Gould, 20177 N = 13 PPD Perinatal nutrition interventions

Long chain PUFA

Vitamin D

Overall diet

NR “… prenatal fish oil supplementation RCT's show null and positive effects on PPD symptoms… no relevant RCT's were identified, however seven observational studies of maternal vitamin D levels with PPD outcomes showed inconsistent associations… dietary advice interventions in pregnancy had a positive and null result on PPD”7

Hansen, 20178 N = 27 MA performed

Depression St. John’s wort SSRI “For patients with mild-to-moderate depression, St. John’s wort has comparable efficacy and safety when compared to SSRIs”8

Ng, 20179 N = 35 MDD St. John’s wort Placebo Active comparator

“SJW monotherapy for mild and moderate depression is superior to placebo in improving depression symptoms and not significantly different from antidepressant medication. However, evidence of heterogeneity and a lack of



First Author, Year

Study Characteristi

cs

Disorder

Therapy/Treatment


research on severe depression reduce the quality of the evidence”9

Apaydin, 201610

N = 35 MDD St. John’s wort Placebo Active comparator

“SJW monotherapy for mild and

moderate depression is superior to placebo in improving depression symptoms and not significantly different from antidepressant medication”10

Appleton, 201611

N = 26 MDD PUFA Placebo Anti-depressant

treatment

Standard care

No treatment Wait-list control

“At present, we do not have sufficient high quality evidence to determine the effects of n-3PUFAs as a treatment for MDD.”11

Galizia, 201612 N = 8 MDD SAME Placebo Imipramine Desipramine

Escitalopram

“Given the absence of high quality evidence and the inability to draw firm conclusions based on that evidence, the use of SAME for the treatment of depression in adults should be investigated further”12

Gartlehner, 201613

N = 45 Acute MDD CAM Antidepressants “The evidence was too limited to make firm conclusions about differences in the benefits and harms of antidepressants compared with other treatment options as first-step therapies for acute MDD”13

Li, 201614 N = 47 PPD CHM Routine treatment “This review suggested that CHM was safe and effective in the treatment of PPD. However, this could not be proven conclusively.”14

Metcalf, 201615 N = 19 PTSD Acupuncture NR “The majority of emerging interventions for the treatment of PTSD currently have an insufficient level of evidence supporting their efficacy, despite their increasing popularity”15

Mocking, 201616

N = 13 MA performed

MDD PUFA Placebo “In conclusion, present meta-analysis suggested a beneficial overall effect of omega-3 PUFA supplementation in MDD patients, especially for higher



First Author, Year

Study Characteristi

cs

Disorder

Therapy/Treatment


doses of EPA and in participants taking antidepressants”16

Pirbaglou, 201617

N = 10 Anxiety Depression

Probiotic supplementation

Placebo “…provided limited support for the use of some probiotics in

reducing human anxiety and depression. Despite methodological limitations of the included trials and the complex nature of gut-brain interactions, results suggest the detection of apparent psychological benefits from probiotic supplementation.”17

Wang, 201618 N = 13 CHD complicated with depression

CHM Control “CHMs showed potentially benefits on patients with CHD complicated with depression. Moreover, the effect of CHMs may be similar to or better than antidepressant in certain fields but with less side effects. However, because of small sample size and potential b ias of most trials, this result should be interpreted with caution”18

Gowda, 201519 N = 9 MA performed

Depression Vitamin D supplementation

NR “No significant reduction in depression was seen after vitamin D supplementation … however, most of the studies focused on individuals with low levels of depression and sufficient serum vitamin D at baseline.”19

Hausenblas, 201520

N = 12 (6 on MDD)

MDD Saffron Placebo

Anti-depressants

“The data from these studies support the efficacy of saffron as compared to placebo in improving the following

conditions: depressive symptoms (compared to anti-depressants and placebo)…”20

Hazell, 201521 N = 43 Children and adolescents Overview of reviews

Depression

Complementary therapies PUFA

SAME

St. John’s wort

Vitamin C

NR NR



First Author, Year

Study Characteristi

cs

Disorder

Therapy/Treatment


Joyce, 201522 N = 3 Anxiety Depression

Reiki delivered by a trained Reiki practitioner

NR “There is insufficient evidence to say whether or not Reiki is useful for people over 16 years of age with anxiety or depression or both”22

Kaminski, 201523

N = 0 SAD Melatonin Aglamelatine

Control “No availab le methodologically sound evidence indicates that melatonin or agomelatine is or is not an effective intervention for prevention of SAD and improvement of patient-centred outcomes among adults with a history of SAD.”23

Ren, 201524 N = 26 Depression CHM Fluoxetine “Due to the poor quality of included trials and the potential publication bias of this review, no confirmed conclusion could be draw to evaluate the effectiveness and safety of CHM for depression compared with fluoxetine.”24

Wu, 201525 N = 7 MA performed

Anxiety Social phobia

Morita therapy Pharmacological therapy

Other psychological therapy

No intervention Wait list

“Therefore, we graded the evidence as very low quality and were unable to draw conclusions on the effectiveness of Morita therapy in the treatment of anxiety disorders.”25

Yeung, 201526 N = 61 Depression TCM Xiaoyao

decoction

Chaihu Shugan decoction

Bai Shao

Chai Hu

NR “Due to the limited number of studies on TCM pattern-based

treatment of depression and their low methodological quality, we are unable to draw any conclusion regarding which herbal formulas have higher

efficacy and which TCM patterns respond better to CHM.”26

Jun, 201427 N = 13 MA performed

Depression GMDZ Anti-depressants

“In summary, our systematic review and meta-analysis failed to provide evidence of the superiority of GMDZ decoction over anti-depressant therapies for major depression, post-surgical depression, or depression in the elderly, although there was evidence of



First Author, Year

Study Characteristi

cs

Disorder

Therapy/Treatment


an effect in post-stroke depression”27

Li, 201428 N = 6 Depression Vitamin D supplementation

Placebo “There is insufficient evidence to support the efficacy of Vit D

supplementation in depression symptoms, and more RCTs using depressed patients are warranted.”28

Lopresti, 201429

N = 6 Mild-to-moderate depression

Saffron Placebo “In the placebo-comparison trials, saffron had large treatment effects and, when compared with antidepressant medications, had similar antidepressant efficacy”29

Pratte, 201430 N = 5 Anxiety Withania somnifera (ashwagandha)

Placebo Psychotherapy

“All five studies concluded that WS intervention resulted in greater score improvements (significantly in most cases) than placebo in outcomes on anxiety or stress scales”30

Shaffer, 201431 N = 7 MA performed

Depressive symptoms

Vitamin D supplementation

NR “Vitamin D supplementation may be effective for reducing depressive symptoms in patients with clinically significant depression; however, further high-quality research is needed.”31

Wahbeh, 201432

N = 33

PTSD CAM

Acupuncture

Natural products

NR “Scientific evidence of benefit for posttraumatic stress disorder was …good for acupuncture … Evidence was unclear or conflicting for … natural products”32

Yeung, 201433 N = 10 MA performed

Depression GMDZ Antidepressants “The overall results suggest that GMDZ has few side effects and the potential as an

antidepressant. Adding GMDZ to antidepressants reduces side effects and enhances efficacy of antidepressants”33

Zhang, 201434 N = 7 MDD Shuganjieyu Placebo Venlafaxine

“Shuganjieyu capsule was superior than placebo in terms of response rate … remission rate … the scores of the mean change from baseline of the HAM-D17 …and from baseline of



First Author, Year

Study Characteristi

cs

Disorder

Therapy/Treatment


traditional Chinese medicine (TCM) syndrome score scale scores … In addition, Shuganjieyu plus venlafaxine had a significantly higher response rate … and was superior in terms of the scores of the mean change from baseline of the treatment emergent symptoms scale scores… than venlafaxine alone.34

Zhang, 201435 N = 10 Depression in Parkinson’s disease

TCM Placebo

Venlafaxine

“Shuganjieyu capsule is superior to placebo in terms of overall treatment effectiveness and safety. Both response rate and remission rate among patients treated with the combination of Shuganjieyu plus venlafaxine were significantly higher than those treated with venlafaxine alone.”35

Butler, 201336 N = 13 (5 SRs, 8 trials from supplementary review)

Depression Chinese herbs

Chaihu-Shugan-San

Xiao Yao San

Free and Easy Wanderer Plus

Placebo Medication

“Despite promising results, particularly for Xiao Yao San and its modifications, the effectiveness of Chinese herbal medicine in depression could not be fully substantiated based on current evidence.”36

Dennis, 201337 N = 6 PPD Non-specific acupuncture

Depression specific acupuncture

PUFA

Usual antepartum care

Massage

Non-specific acupuncture

Placebo

“The evidence is inconclusive to allow us to make any recommendations for depression-specific acupuncture… and omega-3 fatty acids for the treatment of antenatal depression. “37

Hausenblas, 201338

N = 5 MA performed

MDD Saffron Placebo Antidepressants

“Findings from clinical trials conducted to date indicate that saffron supplementation can improve symptoms of depression in adults with MDD”38

Kim, 201339 N = 6 MA performed

PTSD Acupuncture Waitlist control

Cognitive-behavioral therapy

SSRIs

“This systematic review and meta-analysis suggest that the evidence of effectiveness of acupuncture for PTSD is encouraging but not cogent.”39



First Author, Year

Study Characteristi

cs

Disorder

Therapy/Treatment


Long, 201340 N = NR MA performed

Mild psychiatric symptoms Mood issues

Vitamin supplements

Mineral supplements

Placebo “Micronutrient supplementation has a beneficial effect on perceived stress, mild psychiatric

symptoms, and aspects of everyday mood in apparently healthy individuals.”40

Miller, 201341 N = 2 PPD Dietary supplements

Selenium yeast tablets

EPA-rich fish oil

DHA-rich fish oil

Placebo

“There is insufficient evidence to conclude that selenium, DHA or EPA prevent postnatal depression. There is currently no evidence to recommend any other dietary supplement for prevention of postnatal depression.”41

Sylvia, 201342 N = NR Bipolar disorder

Nutritional supplements

n-3

Chromium Inositol

Choline

Magnesium Folate

Tryptophan

No comparator Control

“Preliminary data yields conflicting but mainly positive evidence for the use of n-3 fatty acids and chromium in the treatment of b ipolar depression. Limited evidence found that inositol may be helpful for b ipolar depression, but larger sample sizes are needed. Preliminary randomized, controlled trials suggest that choline, magnesium, folate and tryptophan may be beneficial for reducing symptoms of mania.”42

Economic Evaluations

Kutch, 201643 Survey data (Medical Expenditure Panel Survey)

Anxiety CAM combined with traditional therapy

Nonusers of treatment

“Complementary and alternative medicine users with an anxiety disorder showed a statistically insignificant decrease in costs compared to nonusers ($458.95

versus $467.03; p-value 0.920). Complementary and alternative medicine expenditures were offset by a statistically significant decrease in office-based and pharmaceutical costs… The evidence suggests a high probability that complementary and alternative medicine is cost-effective for large values of effect for anxiety disorders (p-value



First Author, Year

Study Characteristi

cs

Disorder

Therapy/Treatment


0.080 for WTP of $5000).”43

Spackman, 201444

Based on the Acupuncture, Counselling or Usual care for Depression (ACUDep) trial results

Depression Acupuncture Counselling Usual care

“Acupuncture is cost-effective compared with counselling or usual care alone, although the

ranking of counselling and acupuncture depends on the relative cost of delivering these interventions. For patients in whom acupuncture is unavailable or perhaps inappropriate, counselling has an ICER less than most cost-effectiveness thresholds”44

Soloman, 201345

Markov model Mild to moderate depression

St. John’s wort Antidepressants “In this model, St. John's wort was shown to be a cost-effective alternative to generic antidepressants. Patients are more likely to receive treatment for a duration consistent with professional guidelines for treatment of major depression due to reduced incidence of adverse effects, improving outcomes.”45

CAM = complementary and alternativ e medicine; CHD = coronary heart disease; CHM = Chinese herbal medicine; GAD = generalized anxiety disorder; GMDZ = ganmai

dazao decoction; HAS = Hamilton anxiety scale; HAMD = Hamilton depression scale score; ICER = incremental cost-ef fectiveness ratio; MA = meta-analy sis; MDD =

major depressiv e disorder; Mg = magnesium; NMB = net monetary benef its; NR = not reported; PUFA = omega-3 poly unsaturated f atty acid; PPD = postpartum

depression/post-natal depression; PTSD = post-traumatic stress disorder; RCT = randomized controlled trial; QALY = quality adjusted lif e y ears; SAD = seasonal

af f ective disorder; SAME = S-adenosy l methionine; SGA = second-generation antidepressant; SR = sy stematic rev iew; SSRI = selectiv e serotonin reuptake inhibitor; TCM

= traditional Chinese medicine; WTP = willingness-to-pay

References Summarized

Health Technology Assessments

No literature identified.

Systematic Reviews and Meta-analyses

1. Baric H, Dordevic V, Cerovecki I, Trkulja V. Complementary and alternative medicine

treatments for generalized anxiety disorder: systematic review and meta-analysis of

randomized controlled trials. Adv Ther. 2018 Mar;35(3):261-288.

PubMed: PM29508154

http://www.ncbi.nlm.nih.gov/pubmed/29508154


2. Smith CA, Armour M, Lee SM, Wang L-Q, Hay PJ. Acupuncture for depression.

Cochrane Database of Syst Rev. 2018 Mar 4;3:CD004046.

PubMed: PM29502347

3. Yeung KS, Hernandez M, Mao JJ, Haviland I, Gubili J. Herbal medicine for depression

and anxiety: A systematic review with assessment of potential psycho-oncologic

relevance. Phytother Res. 2018 Feb 21.

PubMed: PM29464801

4. Asher GN, Gartlehner G, Gaynes BN, Amick HR, Forneris C, Morgan LC, et al.

Comparative benefits and harms of complementary and alternative medicine therapies

for initial treatment of major depressive disorder: systematic review and meta-analysis.

J Altern Complement Med. 2017 Dec;23(12):907-919.

PubMed: PM28700248

5. Boyle NB, Lawton C, Dye L. The effects of magnesium supplementation on subjective

anxiety and stress-a systematic review. Nutrients. 2017 Apr 26;9(5):26.

PubMed: PM28445426

6. Dong B, Chen Z, Yin X, Li D, Ma J, Yin P, et al. The efficacy of acupuncture for treating

depression-related insomnia compared with a control group: a systematic review and

meta-analysis. BioMed Res Int. 2017;2017:9614810.

PubMed: PM28286776

7. Gould JF, Best K, Makrides M. Perinatal nutrition interventions and post-partum

depressive symptoms. J Affect Disord. 2017 Dec 15;224:2-9.

PubMed: PM28012571

8. Hansen MV, Halladin NL, Rosenberg J, Gogenur I, Moller MA. Melatonin for pre - and

postoperative anxiety in adults. Cochrane Database of Syst Rev. 2015 Apr

9;(4):CD009861.

PubMed: PM2585665

9. Ng QX, Venkatanarayanan N, Ho CY. Clinical use of hypericum perforatum (St. John’s

wort) in depression: A meta-analysis. J Affect Disord. 2017 Mar 01;210:211-221.

PubMed: P M28064110

10. Apaydin EA, Maher AR, Shanman R, Booth MS, Miles JN, Sorbero ME, et al. A

systematic review of St. John's wort for major depressive disorder. Syst Rev. 2016 09

02;5(1):148.

PubMed: PM27589952

11. Appleton KM, Sallis HM, Perry R, Ness AR, Churchill R. Omega-3 fatty acids for

depression in adults. Cochrane Database of Syst. Rev2015 Nov 5;(11):CD004692. PubMed: PM26537796

12. Galizia I, Oldani L, Macritchie K, Amari E, Dougall D, Jones TN, et al. S-adenosyl

methionine (SAMe) for depression in adults. Cochrane Database of Syst Rev. 2016

(10).

PubMed: PM27727432

https://www.ncbi.nlm.nih.gov/pubmed/?term=29502347http://www.ncbi.nlm.nih.gov/pubmed/29464801http://www.ncbi.nlm.nih.gov/pubmed/28700248http://www.ncbi.nlm.nih.gov/pubmed/28445426http://www.ncbi.nlm.nih.gov/pubmed/28286776http://www.ncbi.nlm.nih.gov/pubmed/28012571https://www.ncbi.nlm.nih.gov/pubmed/?term=25856551https://www.ncbi.nlm.nih.gov/pubmed/?term=25856551http://www.ncbi.nlm.nih.gov/pubmed/28064110http://www.ncbi.nlm.nih.gov/pubmed/27589952https://www.ncbi.nlm.nih.gov/pubmed/?term=26537796https://www.ncbi.nlm.nih.gov/pubmed/?term=27727432


13. Gartlehner G, Gaynes BN, Amick HR, Asher GN, Morgan LC, Coker-Schwimmer E, et

al. Comparative benefits and harms of antidepressant, psychological, complementary,

and exercise treatments for major depression: an evidence report for a clinical practice

guideline from the American College of Physicians. Ann Intern Med. 2016 Mar

01;164(5):331-41.

PubMed: PM26857743

14. Li Y, Chen Z, Yu N, Yao K, Che Y, Xi Y, et al. Chinese herbal medicine for postpartum

depression: a systematic review of randomized controlled trials. Evid Based

Complement Alternat Med. 2016;2016:5284234.

PubMed: PM27774110

15. Metcalf O, Varker T, Forbes D, Phelps A, Dell L, DiBattista A, et al. Efficacy of fifteen

emerging interventions for the treatment of posttraumatic stress disorder: a systematic

review. J Trauma Stress. 2016 Feb;29(1):88-92.

PubMed: PM26749196

16. Mocking RJ, Harmsen I, Assies J, Koeter MW, Ruhe HG, Schene AH. Meta-analysis

and meta-regression of omega-3 polyunsaturated fatty acid supplementation for major

depressive disorder. Transl Psychiatry. 2016 Mar 15;6:e756.

PubMed: PM26978738

17. Pirbaglou M, Katz J, de Souza RJ, Stearns JC, Motamed M, Ritvo P. Probiotic

supplementation can positively affect anxiety and depressive symptoms: A systematic

review of randomized controlled trials. Nutr Res. 2016 Sep;36(9):889-898.

PubMed: PM27632908

18. Wang AL, Chen Z, Luo J, Shang QH, Xu H. Systematic review on randomized

controlled trials of coronary heart disease complicated with depression treated with

Chinese herbal medicines. Chin J of Integr Med. 2016 Jan;22(1):56-66.

PubMed: PM26085199

19. Gowda U, Mutowo MP, Smith BJ, Wluka AE, Renzaho AM. Vitamin D supplementation

to reduce depression in adults: meta-analysis of randomized controlled trials. Nutrition.

2015 Mar;31(3):421-9.

PubMed: PM25701329

20. Hausenblas HA, Heekin K, Mutchie HL, Anton S. A systematic review of randomized

controlled trials examining the effectiveness of saffron (Crocus sativus l.) on

psychological and behavioral outcomes. J Integr Med. 2015 Jul;13(4):231-40.

PubMed: PM26165367

21. Hazell P. Depression in children and adolescents: complementary therapies. BMJ Clin

Evid. 2015 Dec 08;pii:1008.

PubMed: PM26649557

22. Joyce J, Herbison PG. Reiki for depression and anxiety. Cochrane Database of Syst

Rev. 2015 Apr 3;(4):CD006833.

PubMed: PM25835541

http://www.ncbi.nlm.nih.gov/pubmed/26857743http://www.ncbi.nlm.nih.gov/pubmed/27774110http://www.ncbi.nlm.nih.gov/pubmed/26749196http://www.ncbi.nlm.nih.gov/pubmed/26978738http://www.ncbi.nlm.nih.gov/pubmed/27632908http://www.ncbi.nlm.nih.gov/pubmed/26085199http://www.ncbi.nlm.nih.gov/pubmed/25701329http://www.ncbi.nlm.nih.gov/pubmed/26165367http://www.ncbi.nlm.nih.gov/pubmed/26649557https://www.ncbi.nlm.nih.gov/pubmed/25835541


23. KaminskiHartenthaler A, Nussbaumer B, Forneris CA, Morgan LC, Gaynes BN, Sonis

JH, et al. Melatonin and agomelatine for preventing seasonal affective disorder.

Cochrane Database of Syst Rev. 2015 Nov 11;(11):CD01127111)

PubMed: PM26560173

24. Ren Y, Zhu C, Wu J, Zheng R, Cao H. Comparison between herbal medicine and

fluoxetine for depression: A systematic review of randomized controlled trials.

Complement Ther Med. 2015 Oct;23(5):674-84.

PubMed: PM26365447

25. Wu H, Yu D, He Y, Wang J, Xiao Z, Li C. Morita therapy for anxiety disorders in adults.

Cochrane Database Syst Rev 2015 Feb 19;(2):CD008619.

PubMed: PM25695214

26. Yeung WF, Chung KF, Ng KY, Yu YM, Zhang SP, Ng BF, et al. Prescription of Chinese

herbal medicine in pattern-based traditional Chinese medicine treatment for depression:

a systematic review. Evid Based Complement Alternat Med. 2015;2015:160189.

PubMed: PM26180532

27. Jun JH, Choi TY, Lee JA, Yun KJ, Lee MS. Herbal medicine (Gan Mai Da Zao

decoction) for depression: a systematic review and meta-analysis of randomized

controlled trials. Maturitas. 2014 Dec;79(4):370-80.

PubMed: PM25262476

28. Li G, Mbuagbaw L, Samaan Z, Falavigna M, Zhang S, Adachi JD, et al. Efficacy of

vitamin D supplementation in depression in adults: a systematic review. J Clin

Endocrinol Metab. 2014 Mar;99(3):757-67.

PubMed: PM24423304

29. Lopresti AL, Drummond PD. Saffron (crocus sativus) for depression: A systematic

review of clinical studies and examination of underlying antidepressant mechanisms of

action. Human Psychopharmol. 2014 Nov;29(6):517-27.

PubMed: PM25384672

30. Pratte MA, Nanavati KB, Young V, Morley CP. An alternative treatment for anxiety: A

systematic review of human trial results reported for the Ayurvedic herb shwagandha

(Withania somnifera). J Altern Complement Med. 2014 Dec;20(12):901-8.

PubMed: PM25405876

31. Shaffer JA, Edmondson D, Wasson LT, Falzon L, Homma K, Ezeokoli N, et al. Vitamin

D supplementation for depressive symptoms: a systematic review and meta-analysis of

randomized controlled trials. Psychosom Med. 2014 Apr;76(3):190-6.

PubMed: PM24632894

32. Wahbeh H, Senders A, Neuendorf R, Cayton J. Complementary and alternative

medicine for posttraumatic stress disorder symptoms: a systematic review. J Evid

Based Complement Altern Med. 2014 Jul;19(3):161-175.

PubMed: PM24676593

33. Yeung WF, Chung KF, Ng KY, Yu YM, Ziea ET, Ng BF. A meta-analysis of the efficacy

and safety of traditional Chinese medicine formula Ganmai Dazao decoction for

depression. J Ethnopharmacol. 2014 Apr 28;153(2):309-17.

PubMed: PM24632021

https://www.ncbi.nlm.nih.gov/pubmed/26560173http://www.ncbi.nlm.nih.gov/pubmed/26365447https://www.ncbi.nlm.nih.gov/pubmed/25695214http://www.ncbi.nlm.nih.gov/pubmed/25695214http://www.ncbi.nlm.nih.gov/pubmed/26180532http://www.ncbi.nlm.nih.gov/pubmed/25262476http://www.ncbi.nlm.nih.gov/pubmed/24423304http://www.ncbi.nlm.nih.gov/pubmed/25384672http://www.ncbi.nlm.nih.gov/pubmed/25405876http://www.ncbi.nlm.nih.gov/pubmed/24632894http://www.ncbi.nlm.nih.gov/pubmed/24676593http://www.ncbi.nlm.nih.gov/pubmed/24632021


34. Zhang X, Kang D, Zhang L, Peng L. Shuganjieyu capsule for major depressive disorder

(MDD) in adults: a systematic review. Aging Ment Health. 2014;18(8):941-53.

PubMed: PM24697344

35. Zhang Y, Wang ZZ, Sun HM, Li P, Li YF, Chen NH. Systematic review of traditional

Chinese medicine for depression in Parkinson's disease. Am J Chin Med.

2014;42(5):1035-51.

PubMed: PM25183301

36. Butler L, Pilkington K. Chinese herbal medicine and depression: the research evidence.

Evid Based Complement Alternat Med. 2013;2013:739716.

PubMed: PM23476701

37. Dennis CL, Dowswell T. Interventions (other than pharmacological, psychosocial or

psychological) for treating antenatal depression. Cochrane Database of Syst Rev. 2013

Jul 31(7):CD006795.

PubMed: PM23904069

38. Hausenblas HA, Saha D, Dubyak PJ, Anton SD. Saffron (Crocus sativus l.) and major

depressive disorder: a meta-analysis of randomized clinical trials. J Integr Med. 2013

Nov;11(6):377-83.

PubMed: PM24299602

39. Kim YD, Heo I, Shin BC, Crawford C, Kang HW, Lim JH. Acupuncture for posttraumatic

stress disorder: a systematic review of randomized controlled trials and prospective

clinical trials. Evid Based Complement Alternat Medicine 2013; 2013: 615857

PubMed: PM23476697

40. Long SJ, Benton D. Effects of vitamin and mineral supplementation on stress, mild

psychiatric symptoms, and mood in nonclinical samples: a meta-analysis. Psychosom

Med 2013; 75(2): 144-153

PubMed: PM23362497

41. Miller BJ, Murray L, Beckmann MM, Kent T, Macfarlane B. Dietary supplements for

preventing postnatal depression. Cochrane Database of Syst Rev. 2013 Oct

24(10):CD009104.

PubMed: PM24158923

42. Sylvia LG, Peters AT, Deckersbach T, Nierenberg AA. Nutrient-based therapies for

bipolar disorder: a systematic review. Psychother Psychosom. 2013;82(1):10-9.

PubMed: PM23147067

Economic Evaluations

43. Kutch M. Cost-effectiveness analysis of complementary and alternative medicine in

treating anxiety disorders. Altern Integr Med [Internet] 2016 [cited 2018 Apr 23];5:3.

Available from:

https://www.omicsonline.org/open-access/costeffectiveness-analysis-of-complementary-

and-alternative-medicine-intreating-anxiety-disorders-2327-5162-

1000218.php?aid=79415

http://www.ncbi.nlm.nih.gov/pubmed/24697344http://www.ncbi.nlm.nih.gov/pubmed/25183301http://www.ncbi.nlm.nih.gov/pubmed/23476701http://www.ncbi.nlm.nih.gov/pubmed/23904069http://www.ncbi.nlm.nih.gov/pubmed/24299602https://www.ncbi.nlm.nih.gov/pubmed?term=23476697https://www.ncbi.nlm.nih.gov/pubmed?term=23362497http://www.ncbi.nlm.nih.gov/pubmed/24158923http://www.ncbi.nlm.nih.gov/pubmed/23147067https://www.omicsonline.org/open-access/costeffectiveness-analysis-of-complementary-and-alternative-medicine-intreating-anxiety-disorders-2327-5162-1000218.pdfhttps://www.omicsonline.org/open-access/costeffectiveness-analysis-of-complementary-and-alternative-medicine-intreating-anxiety-disorders-2327-5162-1000218.pdfhttps://www.omicsonline.org/open-access/costeffectiveness-analysis-of-complementary-and-alternative-medicine-intreating-anxiety-disorders-2327-5162-1000218.pdfhttps://www.omicsonline.org/open-access/costeffectiveness-analysis-of-complementary-and-alternative-medicine-intreating-anxiety-disorders-2327-5162-1000218.pdf


44. Spackman E, Richmond S, Sculpher M, Bland M, Brealey S, Gabe R, et al. Cost-

effectiveness analysis of acupuncture, counselling and usual care in treating patients

with depression: the results of the ACUDep trial. PLoS ONE. 2014;9(11):e113726.

PubMed: PM25426637

45. Solomon D, Adams J, Graves N. Economic evaluation of St. John's Wort (hypericum

perforatum) for the treatment of mild to moderate depression. J Affect Disord. 2013

Jun;148(2-3):228-34.

PubMed: PM23291009

Guidelines and Recommendations

46. VA/DoD clinical practice guidelines: management of posttraumatic stress disorder and

acute stress reaction [Internet]. Washington: Dept. of Veteran Affairs; 2017 [cited 2018

Apr 23]. Available from: https://www.healthquality.va.gov/guidelines/MH/ptsd/

See: h. Complementary and Integrative Treatments

47. National Guideline Clearinghouse. Guideline summary: VA/DoD clinical practice

guideline for the management of major depressive disorder. In: National Guideline

Clearinghouse [Internet]. Rockville (MD): Agency for Healthcare Research and Quality;

2016 [cited 2018 Apr 23]. Available from:

https://www.guideline.gov/summaries/summary/50325/vadod-clinical-practice-guideline-

for-the-management-of-major-depressive-disorder?q=complementary+therapy

See: Self-help and Complementary and Alternative Treatments

48. Ravindran AV, Balneaves LG, Faulkner G, Ortiz A, McIntosh D, Morehouse RL, et al.

Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical

guidelines for the management of adults with major depressive disorder: Section 5.

Complementary and alternative medicine treatments. Cdn J Psychiatry. 2016

Sep;61(9):576-87.

PubMed: PM27486153

49. National Guideline Clearinghouse. Guideline summary: depression in children and

young people: identification and management in primary, community and secondary

care. In: National Guideline Clearinghouse [Internet]. Rockville (MD): Agency for

Healthcare Research and Quality; 2015 [cited 2018 Apr 24]. Available from:

https://www.guideline.gov/summaries/summary/49118/depression-in-children-and-

young-people-identification-and-management-in-primary-community-and-secondary-

care?q=complementary+therapy

See: How to Use Antidepressants in Children and Young People

50. Katzman MA, Bleau P, Blier P, Chokka P, Kjernisted K et al. Canadian clinical practice

guidelines for the management of anxiety, posttraumatic stress and obsessive-

compulsive disorders, BMC Psychiatry [Internet]. 2014[cited 2018 Apr 24];14(Suppl 1)

S1. Available from:

https://bmcpsychiatry.biomedcentral.com/track/pdf/10.1186/1471-244X-14-S1-S1

See: Biological and alternative therapies, various pages

51. Social anxiety disorder: recognition, assessment and treatment [Internet]. London:

National Institute for Health and Care Excellence; 2013 [cited 2018 Apr 23]. Available

from:

https://www.nice.org.uk/guidance/cg159/

See: 1.6 Interventions that are not recommended to treat social anxiety disorder

http://www.ncbi.nlm.nih.gov/pubmed/25426637http://www.ncbi.nlm.nih.gov/pubmed/23291009https://www.healthquality.va.gov/guidelines/MH/ptsd/https://www.guideline.gov/summaries/summary/50325/vadod-clinical-practice-guideline-for-the-management-of-major-depressive-disorder?q=complementary+therapyhttps://www.guideline.gov/summaries/summary/50325/vadod-clinical-practice-guideline-for-the-management-of-major-depressive-disorder?q=complementary+therapyhttp://www.ncbi.nlm.nih.gov/pubmed/27486153https://www.guideline.gov/summaries/summary/49118/depression-in-children-and-young-people-identification-and-management-in-primary-community-and-secondary-care?q=complementary+therapyhttps://www.guideline.gov/summaries/summary/49118/depression-in-children-and-young-people-identification-and-management-in-primary-community-and-secondary-care?q=complementary+therapyhttps://www.guideline.gov/summaries/summary/49118/depression-in-children-and-young-people-identification-and-management-in-primary-community-and-secondary-care?q=complementary+therapyhttps://bmcpsychiatry.biomedcentral.com/track/pdf/10.1186/1471-244X-14-S1-S1https://www.nice.org.uk/guidance/cg159/


Appendix — Further Information

Previous CADTH Reports

52. Treatment for post-traumatic stress disorder, operational stress injury, or critical incident

stress: a summary of clinical practice guidelines [Internet]. Ottawa: CADTH; 2016 [cited

2018 Apr 23]. Available from:

https://www.cadth.ca/treatment-post-traumatic-stress-disorder-operational-stress-injury-

or-critical-incident-stress-0

Systematic Reviews and Meta-Analyses – Alternative Intervention

Alternative Therapy as Adjunct to Conventional Therapy

53. Schefft C, Kilarski LL, Bschor T, Kohler S. Efficacy of adding nutritional supplements in

unipolar depression: a systematic review and meta-analysis. Eur

Neuropsychopharmacol. 2017 11;27(11):1090-1109.

PubMed: PM28988944

54. Zeng LF, Cao Y, Wang L, Dai YK, Hu L, Wang Q, et al. Role of medicinal plants for

liver-qi regulation adjuvant therapy in post-stroke depression: a systematic review of

literature. Phytother Res. 2017 Jan;31(1):40-52.

PubMed: PM27762458

55. Bosch P, van den Noort M, Staudte H, Lim S. Schizophrenia and depression: a

systematic review of the effectiveness and the working mechanisms behind

acupuncture. Explore (NY). 2015 Jul-Aug;11(4):281-91.

PubMed: PM26007331

56. Chan YY, Lo WY, Yang SN, Chen YH, Lin JG. The benefit of combined acupuncture

and antidepressant medication for depression: a systematic review and meta-analysis. J

Affect Disord. 2015 May 01;176:106-17.

PubMed: PM25704563

57. Ravindran AV, da Silva TL. Complementary and alternative therapies as add-on to

pharmacotherapy for mood and anxiety disorders: a systematic review. J Affect Disord.

2013 Sep 25;150(3):707-19.

PubMed: PM23769610

Economic Evaluations – Unknown Provider of Intervention

58. Beil H, Beeber LS, Schwartz TA, Lewis G. Cost-effectiveness of alternative treatments

for depression in low-income women. J Ment Health Policy Econ. 2013 Jun;16(2):55-

65.

PubMed: PM23999203

https://www.cadth.ca/treatment-post-traumatic-stress-disorder-operational-stress-injury-or-critical-incident-stress-0https://www.cadth.ca/treatment-post-traumatic-stress-disorder-operational-stress-injury-or-critical-incident-stress-0https://www.ncbi.nlm.nih.gov/pubmed/?term=28988944http://www.ncbi.nlm.nih.gov/pubmed/27762458http://www.ncbi.nlm.nih.gov/pubmed/26007331http://www.ncbi.nlm.nih.gov/pubmed/25704563http://www.ncbi.nlm.nih.gov/pubmed/23769610http://www.ncbi.nlm.nih.gov/pubmed/23999203


Review Articles – Uncertain if Systematic

59. Ciappolino V, Delvecchio G, Agostoni C, Mazzocchi A, Altamura AC, Brambilla P. The

role of n-3 polyunsaturated fatty acids (n-3pufas) in affective disorders. J Affect Disord.

2017 Dec 15;224:32-47.

PubMed: PM28089169

60. Rakofsky JJ, Dunlop BW. Review of nutritional supplements for the treatment of bipolar

depression. Depress Anxiety. 2014 May;31(5):379-90.

PubMed: PM24353094

61. Ralevski E, Olivera-Figueroa LA, Petrakis I. PTSD and comorbid AUD:a review of

pharmacological and alternative treatment options. Subst Abuse Rehab. 2014;5:25-36.

PubMed: PM24648794

62. Qureshi NA, Al-Bedah AM. Mood disorders and complementary and alternative

medicine: a literature review. Neuropsychiat Dis Treat. 2013;9:639-58.

PubMed: PM23700366

63. Sarris J, McIntyre E, Camfield DA. Plant-based medicines for anxiety disorders, part 2:

a review of clinical studies with supporting preclinical evidence. CNS Drugs. 2013

Apr;27(4):301-19.

PubMed: PM23653088
http://www.ncbi.nlm.nih.gov/pubmed/28089169http://www.ncbi.nlm.nih.gov/pubmed/24353094http://www.ncbi.nlm.nih.gov/pubmed/24648794http://www.ncbi.nlm.nih.gov/pubmed/23700366http://www.ncbi.nlm.nih.gov/pubmed/23653088

cadth rapid response report: summary of abstracts ... · anxiety disorders were examined in seven...

Documents