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REVIEW Focus on Alternative and Complementary Therapies Volume () 2016 © 2016 Royal Pharmaceutical Society DOI 10.1111/fct.12255 ISSN 1465-3753

Complementary and alternative medicine for addiction: an overview of systematic reviews

Pawel Posadzki, Mohamed MK Khalil, Abdullah MN AlBedah, Olena Zhabenko, Josip Car

Abstract Background Complementary and alternative medicine (CAM) is popular among individuals with a variety of addictions. Objective To critically evaluate the evidence from systematic reviews (SRs) of the effectiveness of CAM for addictions. Methods Ten electronic databases were searched from their inception to January 2015. Systematic reviews (SRs) of any type of CAM with any type of addiction-related outcome were considered eligible. The Oxman criteria for assessing the methodological quality of the included SRs were used. Results Twenty-seven SRs met the inclusion criteria. Most of them were of high methodological quality (mean=4.66, SD=5.20). Twelve SRs arrived at equivocal conclusions (of these, seven were of high quality), four drew positive conclusions (three of which were of high quality), and 11 arrived at negative conclusions (of which six were of high quality). A wide variety of addictions were examined, including alcohol, amphetamine, cannabis, cocaine, methamphetamine, opiates (heroin, morphine, opium), tobacco and various (unspecified) drugs. A diversity of CAM modalities was also used such as acupuncture (and related techniques), herbal medicine, hypnotherapy, meditative/ mindfulness techniques, music therapy, spirituality and yoga. Conclusion A large number of SRs exist in the area of addiction. The evidence from SRs examining the effectiveness of various CAM interventions for myriad addictions is highly ambiguous or negative. Keywords Addictions complementary and alternative medicine effectiveness systematic reviews

Introduction Addiction can be defined as a primary, chronic disease of brain reward, motivation, memory and related circuitry.1 According to the Diagnostic and Statistical Manual of Mental Disorders, 5th edn (DSM–5), addiction from alcohol, caffeine, illicit or prescription drugs or tobacco constitutes a substance-related disorder.2 The World Health Organization (WHO) has estimated that in 2010, between 153 and 300 million people worldwide aged 15– 64 years had used an illicit substance (excluding alcohol) at least once in the preceding year.3 The

burden of addiction for individuals and societies around the globe is significant. Complementary and alternative medicine (CAM) can be defined as ‘diagnosis, treatment and/or prevention which complements mainstream medicine by contributing to a common whole, satisfying a demand not met by orthodoxy, or diversifying the conceptual framework of medicine’.4 The National Center for Complementary and Integrative Health (NCCIH) (formerly National Center for Complementary and Alternative Medicine, NCCAM) operationally divides CAM into five categories: alternative medical systems, mind–body interventions,

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Focus on Alternative and Complementary Therapies 2016 ()

biologically based therapies, manipulative and bodybased methods and energy therapies.5 The prevalence of CAM use among patients with addiction/substance use disorders is high, ranging from 34%6 to 45%.7 There might be several explanations for this high level of popularity; one reason is that various CAM modalities are being promoted as effective treatment strategies for addictions/substance use disorders. Some patients might also feel that their needs are not being met by mainstream psychiatry, and, as a result, seek alternatives. Whatever the reasons are for this high level of popularity, it is essential to identify the forms of CAM that are safe and effective for addictions. Many published RCTs have examined the effectiveness of CAM modalities for various addictions, and their results have been evaluated in systematic reviews (SRs). Some of these SRs have arrived at conflicting conclusions, which may be confusing. To the best of our knowledge, no attempt has been made to summarise and rigorously evaluate the evidence from these SRs. The aim of this article is therefore to review and critically appraise the data from SRs of CAM for any type of addiction. Methods Data sources The Google Scholar search engine and the following nine databases were searched from their respective inceptions to January 2015: AMED, CINAHL, The Cochrane Library, EMBASE, ISI Web of Knowledge, ISI Web of Science, MEDLINE, PsycINFO, and Scopus. A detailed search strategy for MEDLINE is presented in Box 1. In addition to the electronic

Concept 1 (Alternative adj3 (heal$ or medic$ or remed$ or therap$ or treatment$)).ti,ab. OR (Complementary adj3 (heal$ or medic$ or remed$ or therap$ or treatment$)).ti,ab. OR (integrat$ adj3 (heal$ or medic$ or remed$ or therap$ or treatment$)).ti,ab. OR CAM.ti,ab. OR exp Complementary Therapies/

Concept 2 Substance-Related Disorders. sh OR addict*.ti,ab. OR overdos*.ti,ab. OR intoxicat*.ti,ab. OR abstin*.ti,ab. OR abstain*.ti,ab. OR withdrawal*.ti,ab. OR abuse*.ti,ab. OR use*.ti,ab. OR misuse.ti,ab. OR disorder*.ti,ab. OR dependen*.ti,ab.

Concept 3 review.ti Box 1 Detailed search strategy for MEDLINE

searches, the reference lists of all identified papers were reviewed for further potentially relevant SRs. Study selection The data screening and selection process were performed by two independent reviewers (PP and MMKK) and verified and validated by a third reviewer (AMNA). Eligibility The present overview of SRs included all articles evaluating the effects of CAM for any type of drug addiction, including alcohol, amphetamine, cannabis, cocaine, methamphetamine, opiates (heroin, morphine, opium), tobacco, or other unspecified drugs. Papers published in English were considered eligible. Systematic reviews were defined as articles that include replicable eligibility criteria for primary studies and a comprehensive and repeatable literature search method. Systematic reviews with overlapping RCTs, or updated SRs were also included. Non-systematic reviews were excluded. The following CAM modalities were considered eligible: acupuncture (AT) and associated techniques, Alexander Technique, Ayurvedic medicine, aromatherapy, (Bach) flower remedies, biofeedback, chiropractic, herbal medicine, homeopathy, hypnosis, massage, music therapy, meditation, mindfulness techniques, naturopathy, osteopathy, qigong, spirituality/spiritual healing, tai chi, TCM and yoga. Dietary supplements, physical exercises or psychotherapeutic approaches were not considered a part of CAM and were therefore excluded from the analyses. Any type of addiction-related outcome measures were considered eligible. Data extraction Data extraction and quality assessments were performed by the two selection reviewers (PP and MK) independently of each other, using a predefined data extraction form. The following information was extracted from the included reviews: first authors’ names and publication date, type of addiction, total number of primary studies, quality of primary studies (poor, moderate or high as determined by the present authors), whether meta-analysis had been conducted, quality of SR (Oxman score8), overall result (quote), direction of conclusion (judged by the present authors (positive, negative or equivocal), whether SR had mentioned adverse effects (AEs) (yes or no), authors’ conflicts of interest (declared or not mentioned), source of funding (mentioned or not mentioned) and any additional comments. The direction of conclusions of each SR was evaluated in the following way: statements such as ‘no

Review evidence of benefit’ were categorised as ‘negative’, or lack of effectiveness ( ); statements such as ‘a significant effect of acupuncture was found in smoking cessation rates’ were categorised as ‘positive’ (+) or existence of effectiveness; and statements that were neither explicitly positive nor clearly negative were categorised as ‘unclear’ (+/ ) or existence of ambiguity. Any disagreements regarding these categorisations were resolved by discussion between the authors. Risk of bias assessment The methodological quality of the included SRs was independently evaluated by two reviewers using the Oxman score.8 This validated tool evaluates the quality of review articles in nine domains, including: reporting of search strategy, comprehensiveness of searches, repeatable eligibility criteria, avoidance of selection bias, presence of a validity assessment tool, use of the validity assessment tool, robustness of data analysis, appropriateness of data analysis and supportiveness of conclusions. Each question can be scored as 1 (domain fulfilled), 0 (domain partially fulfilled) or 1 (domain not fulfilled). The final score ranges from 9 to 9. A result of 1 or below means the Total number of hits for electronic search (n = 4032)

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review has extensive flaws; 2–3 indicates the presence of major flaws; 4–5 means minor flaws, and 6–9 indicates minimal or no flaws. Data synthesis The results are presented in a narrative fashion using tables. Descriptive statistics were used to analyse and synthesise the data. Sensitivity analyses were conducted to explore the impact of the methodological quality of each SR on the outcomes of the review. Sensitivity analyses were conducted according to the following criteria: (a) direction of conclusion as a function of the quality of the SR and primary trials; (b) quality of the SR (Oxman score) as a function of addiction type; (c) quality of the SR as a function of the quality of primary data; and (d) direction of conclusion as a function of the CAM modality. Results Study description Our searches generated a total of 4035 records; 27 SRs met the inclusion criteria9–35 (Figure 1). The Additional records identified through manual search (n = 3)

Duplicates removed (n = 1981)

Records screened (n = 2054)

Excluded: not SR (n = 1856)

Full-text articles assessed for eligibility (n = 198)

Excluded: not CAM (n = 171)

Total number of articles included (n = 27)

Figure 1 Flow diagram for included studies. CAM, complementary and alternative medicine; SR, systematic review.

Intervention(s)

Cocaine

Cocaine, opiates

Opiates (heroin)

Cocaine

Opiates 10 (heroin, morphine, opium) Amphetamine, 8 cannabis, cocaine, opiates (heroin) and various drugs

AA

AT

TCM

AT

AA, AT, EA

AA

Gates (2006)17

Jordan (2006)18

Jordan (2008)19

Kim (2005)20

Lin (2012)21

Lua (2012)22

7

6

n.m.

7

6

AA

D’Alberto (2004)16

Cocaine

11

AA, AEA, AT, Alcohol ALA, EA, LA,

Cho (2009)15

N*

20

Type of addiction

Tobacco

I: Alternative medical systems AA, AP, AT, Cheng EA, LA (2012)13

First author (year)

No

Yes

No

Yes

No

No

Low

Low

Low to No moderate

Low to No moderate

Low

Low

Moderate

Low

3

5

7

2

2

9

4

9

7

‘There is currently no evidence that AA is effective for the treatment of cocaine dependence.’ ‘[T]here was no significant evidence for AT being a more effective treatment than controls’ ‘The majority of clinical evidence. . . demonstrates good evidence for TCM patent medicines in heroin addiction treatment’ ‘AT is not effective for treating cocaine addiction as the sole mode of treatment’ ‘This review cannot be used to establish the efficacy of acupuncture in the treatment of opiate addiction’ ‘The overall effectiveness of AA in treating drug addiction remains inconclusive’

‘A significant effect of acupoint stimulation was found in smoking cessation rates and cigarette consumption at immediate, 3- and 6-month follow-ups’ ‘[T]he poor methodological quality and the limited number of the trials do not allow any conclusion about the efficacy of acupuncture for treatment of alcohol dependence.’ ‘This review could not confirm that AT was an effective treatment for cocaine abuse.’

MetaQuality Overall result analysis of SR (quote) (Oxman 8 score)

Low to Yes moderate

Quality of RCTs

Table 1 Systematic reviews of CAMs for addictions

Yes

Yes

(+/ )

No

Yes

Yes

Yes

Yes

Yes

No

(+/ )

( )

(+)

( )

( )

( )

(+/ )

(+)

No statistically significant differences between AT and sham treatments were found for one of the POMs

Combined all types of acupoint stimulation thus significant heterogeneity of the analyses; no funnel plots provided

Comment

Unknown number of primary trials; lack of validity assessments; poor overall quality Poor quality review; its findings and conclusions difficult to interpret

A wide variety of drugs were included; some of the addicts were on methadone

No eligibility criteria, only one database used for searches; highly biased Mentioned Biased search strategy; primary data missing

n.m.

n.m.

n.m.

None n.m. declared

n.m.

n.m.

n.m.

n.m.

n.m.

n.m.

n.m.

Source of funding

Of the six primary studies, two reported a positive outcomes whereas four were negative None Mentioned The majority of the primary declared trials used sham AA

n.m.

n.m.

n.m.

Direction of Mention Conflict conclusion of adverse of interest effects

4 Focus on Alternative and Complementary Therapies 2016 ()

Alcohol, opiates (heroin), tobacco

Tobacco

Tobacco

Tobacco

Tobacco

Tobacco

AT

AA,AT,EA

AA, AP, AT, EA, LA

AA

AA, AP, AT, EA, LA

AA, AP, AT, EA, LA

AA, AP, AT, EA, LA

AA, AT, EA

Ter Riet (1990)26

White (1999)28

White (2002)29

White (2006)30

White (2006)31

White (2011)32

White (2014)33

Zhang (2014)35

Opioids

Tobacco

Cocaine

Type of addiction

AA

Intervention(s)

Mills (2005)24

First author (year)

Table 1 (Continued)

16

38

33

24

13

22

14

22

9

N*

Yes

Yes

Yes

Yes

No

Low

Moderate

Yes

Yes

LowYes moderate

Low

Low to high

Low

Low

Low

8

9

9

9

9

9

7

3

5

‘This systematic review and meta-analysis does not support the use of AT for the treatment of cocaine dependence’ ‘Claims that AT is efficacious as a therapy for these addictions are thus not supported by results from sound clinical research.’ ‘Acupuncture was not superior to sham acupuncture for smoking cessation’ ‘There is no clear evidence that AT, AP, LA or EA are effective for smoking cessation.’ ‘AA appears to be effective for smoking cessation, but the effect may not depend on point location’ ‘There is no consistent evidence whether the effectiveness of AT, AP, LA or EA for smoking cessation is any different from a placebo effect’ ‘There is no bias-free, consistent evidence that AT, AP, LA or EA are effective interventions for smoking cessation. Acupuncture is less effective than nicotine chewing gum.’ ‘Although pooled estimates suggest possible short-term effects there is no consistent, bias-free evidence that AT, AP or LA have a sustained benefit on smoking cessation for 6 months or more.’ ‘This review and meta-analysis could not confirm that acupuncture was an effective treatment for psychological symptoms associated with opioid addiction’


Low to Yes moderate

Quality of RCTs

No

Yes

(+/ )

( )

Yes

No

No

No

No

No

Yes

(+/ )

( )

(+)

( )

( )

( )

( )

Source of funding

n.m.

n.m.

Low internal validity of the included trials

The worse the quality of the primary studies were, the more positive outcomes were reported

Lack of standardised sessions of AA, disparate endpoints and outcomes

Comment

n.m.

There were no effects of AT compared with sham AT in both the short term and long term

Mentioned There was a considerable heterogeneity of all three meta-analyses

None Mentioned Low quality of declared RCTs; meta-analysis of one RCT only is being reported (for depression associated with opioid addiction)

None Mentioned Continuous AA declared was more effective in the short term than sham stimulation

None Mentioned There was a declared reduced risk ratio for the short-term effect of AT compared to sham AT

n.m.

n.m.

None Mentioned Acupuncture was more declared effective in short term compared to no treatment

n.m.

n.m.

None n.m. declared

Conflict Direction of Mention conclusion of adverse of interest effects

Review 5

Intervention(s)

Low

3b

Meditation

Zgierska (2009)34

Low

Alcohol, tobacco, various drugs Alcohol, cocaine, opiates (heroin)

Yoga

Posadzki (2014)25

8

Low

5a

Alcohol, various drugs

Music therapy

Mays (2008)23

Moderate

Low

14

Moderate

No

No

No

No

No

Yes

6

8

3

7

7

9

9

‘There is not enough evidence to show whether hypnotherapy could be as effective as counselling treatment.’ ‘The small number of studies available and associated methodological problems require more clinical trials with larger sample sizes and carefully monitored interventions to determine rigorously if yoga and meditation are effective treatments’ ‘[C]urrent evidence suggests that mindfulness based interventions can reduce the consumption of several substances. . .to a significantly higher extent than several types of active and inactive control groups’ ‘In the literature, no consensus exists regarding of the efficacy of music therapy as treatment for patients with addictions’ ‘The evidence in support of the effectiveness of yoga for addiction is encouraging but inconclusive.’ ‘Conclusive data for MM [mindfulness meditationbased Interventions] as a treatment for addictive disorders are lacking.’

‘There is insufficient evidence to recommend hypnotherapy as a specific treatment for smoking cessation.’


LowYes moderate

Quality of RCTs

24 Meditation, Alcohol, mindfulness, cannabis, cocaine, spirituality methamphetamine, opiates, tobacco

Tobacco

Carim-Todd Yoga, (2013)12 meditation and mindfulness

11

9

N*

Chiesa (2014)14

Tobacco

Tobacco

Type of addiction

Hypnotherapy

Barnes (2010)10

II: Mind–body interventions Abbot Hypnotherapy (2000)9

First author (year)

Table 1 (Continued)

(+/ )

(+/ )

Yes

Yes

No

Yes

(+)

(+/ )

Yes

Yes

No

(+/ )

(+/ )

( )

Source of funding

Comment

Mentioned Review based on a small number of pilot studies

Of the primary studies, 14 pertained to CAM; most of them suffered from major methodological limitations

n.m.

Mentioned Review also included non-RCTs, case series, case report and qualitative studies. A mixture of psychotherapeutic approaches had been included

None Mentioned Small number of poor quality declared RCTs; a variety of addictions

n.m.

None n.m. declared

None Mentioned Review also declared included non-controlled trials; 11 of the primary studies pertained to CAM

None Mentioned Studies that favoured declared hypnotherapy were small and methodologically flawed None Mentioned Wide confidence declared intervals of the primary data; difficult to infer equivalence

Conflict Direction of Mention conclusion of adverse of interest effects


Intervention(s)

Type of addiction

16

Low to No moderate

None

e

None None

No

7

None

None

2

‘More systematic studies are required before these systems of medicine can be widely recommended in the treatment of substance use disorders’

None

None

‘Systematic clinical trials are needed to test promising substances’


None

Low

Quality of RCTs

None None

4c

N*

(+/ )

None

None

(+/ )

No

None

None

Yes

Source of funding

n.m.

None

None

n.m.

None

None

None n.m. declared

Direction of Mention Conflict conclusion of adverse of interest effects

Review also included animal studies and SRs

None

None

Of the four studies included, two were RCTs and two were open-label trials

Comment

AA, auricular acupuncture; AEA, auricular electro-acupuncture; ALA, auricular laser acupuncture; AP, acupressure; AT, acupuncture; EA, electro-acupuncture; LA, laseracupuncture; MBM, mind–body medicine; N*, total number of primary studies; n.m., not mentioned; POMs, primary outcome measures; SR, systematic review; +, positive; , negative; +/ , equivocal. a All of the primary data referred to as ‘studies’-unclear whether the number pertained to RCTs. b Number reflects RCTs of meditative techniques. c Number pertains to two trials on addictions only. d The review also included dietary supplements. e Pertains to the number of RCTs.

III: Biologically-based therapies Herbal Alcohol, Werneke medicine cocaine, (2006)27 opiates (heroin) IV: Manipulative and body-based methods None None None V: Energy therapies None None None VI: Miscellaneous CAM in Alcohol, Behere generald cocaine, (2009)11 opiates, tobacco

First author (year)

Table 1 (Continued)

Review 7

1 1 0 1 1 1 1 1 1 1 1 0 0 1 1 0 1 1 0 1 1 1 1 1 1 1 1

Abbot (2000)9 Barnes (2010)10 Behere (2009)11 Carim-Todd (2013)12 Cheng (2012)13 Chiesa (2014)14 Cho (2009)15 D’Alberto (2004)16 Gates (2006)17 Jordan (2006)18 Jordan (2008)19 Kim (2005)20 Lin (2012)21 Lua (2012)22 Mays (2008)23 Mills (2005)24 Posadzki (2014)25 Ter Riet (1990)26 Werneke (2006)27 White (1999)28 White (2002)29 White (2006)30 White (2006)31 White (2011)32 White (2014)33 Zgierska (2009)34 Zhang (2014)35 1 1 1 1 1 1 1 1 1 1 1 1 0 0 1 1 1 1 1 1 1 1 1 1 1 1 1

Search comprehensive? (b) 1 1 1 1 1 1 1 1 1 1 0 1 1 1 1 1 1 1 1 0 1 1 1 1 1 1 1

Inclusion criteria? (c) 1 1 1 1 1 1 1 1 1 1 0 1 1 1 0 1 1 0 1 0 1 1 1 1 1 1 1

Bias avoided? (d) 1 1 1 0 1 1 1 1 1 1 1 1 1 1 1 0 1 1 1 1 1 1 1 1 1 1 1

Validity criteria? (e) 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 0 1 1 1 1 1 1 1 1 1 1 1

Validity assessed? (f) 1 1 1 1 1 0 1 0 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1

Methods for combining studies? (g) 1 1 1 0 0 0 1 0 1 1 1 1 0 1 1 1 0 1 1 1 1 1 1 1 1 1 1

Appropriately combined? (h) 1 1 0 1 0 1 1 0 1 0 0 0 0 0 0 0 1 0 1 1 1 1 1 1 1 0 1

Conclusions supported? (i)

9 9 7 7 7 7 9 4 9 2 2 7 5 3 3 5 8 3 2 7 9 9 9 9 9 6 8

Sum

Scoring: each question is scored as 1, 0, or 1. The column headings denoting scoring are identified by the letters (a)–(i) in the explanatory notes below. One means that: (a) the review states the databases used, date of most recent searches, and some mention of search terms; (b) the review searches at least two databases and looks at other sources; (c) the review states the criteria used for deciding which studies to include in the overview; (d) the review reports how many studies were identified by searches, numbers excluded and appropriate reasons for excluding them; (e) the review states the criteria used for assessing the validity of the included studies; (f) the review reports validity assessment and did some type of analysis with it; (g) the report mentions that quantitative analysis was not possible and reasons that it could not be done; (h) the review performs a test for heterogeneity before pooling or does appropriate subgroup testing, appropriate sensitivity analysis, or other such analysis; (i) the conclusions made by the author(s) are supported by the data and/or analysis reported in the review. Zero means that the above-mentioned criteria were partially fulfilled. 1 means that none of the above-mentioned criteria were fulfilled. This is operationalisation of the Oxman criteria,8 adapted from Posadzki and Ernst (2011).36

Search methods? (a)

First author (year)

Table 2 Quality ratings for included systematic reviews of CAMs for addictions


Review key data from the included SRs are summarised in Table 1. Table 28–36 presents the methodological quality/risk of bias of the included SRs. Characteristics of included studies A wide variety of CAM modalities were evaluated such as acupuncture (AT), acupressure (AP), auricular acupuncture (AA), auricular electro-acupuncture (AEA), auricular laser acupuncture (ALA), CAM in general, electro-acupuncture (EA) or laser-acupuncture (LA), herbal medicine, hypnotherapy, meditation, mindfulness techniques, music therapy, spirituality, TCM and yoga. One SR included evidence from animal studies alongside human trials,11 and one failed to mention the total number of included studies.18 Addictions included alcohol (n=8), amphetamine (n=1), cannabis (n=2), cocaine (n=10), methamphetamine (n=1), opiates (n=10), tobacco (n=14) and various drugs (n=3). Sixteen SRs evaluated single addictions; the remaining 11 SRs evaluated more than one type of addiction. Overall, 11 (40.7%) SRs did not mention AEs and 16 (59.3%) did. Thirteen (48.2%) SRs mentioned the authors’ conflict of interest, and 13 (48.2%) reported the source of funding. Effectiveness of CAM modalities in addictions (NCCIH classification) Overall, 18 SRs fell under the alternative medical systems category; these reviews evaluated the following addictions: alcohol (n=2), amphetamine (n=1), cannabis (n=1), cocaine (n=6), opiates (n=6), tobacco (n=8) and other drugs (n=1). Of these, three SRs showed positive results for tobacco and opiate addiction; 10 SRs showed negative results for alcohol, cocaine, opiate and tobacco addiction; and five SRs showed equivocal results for alcohol, amphetamine, cannabis, cocaine, opiate, tobacco and other drug addictions. Seven reviews were classified as mind–body interventions; these reviews evaluated the following addictions: alcohol (n=4), cannabis (n=1), cocaine (n=2), methamphetamine (n=1), opiates (n=2), tobacco (n=5) and other drugs (n=2). Of these, one SR showed positive results for alcohol, cannabis, cocaine, methamphetamine, opiate or tobacco addiction; one SR showed negative results for tobacco addiction; and five SRs showed equivocal results for alcohol, cocaine, opiate, tobacco or other drug addictions. One review was classified as a biologically based therapy (herbal medicine); the review jointly evaluated alcohol, cocaine and opiates, and showed equivocal results. None of the included reviews were classified as manipulative/ body-based methods or energy therapies. One was classified as miscellaneous as it included a plethora of CAM modalities (as well as dietary supplements) in the management of alcohol, cocaine, opiate and tobacco addiction, which showed equivocal results.

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Table 3 The direction of conclusion as a function of quality of systematic reviews and primary trials Quality of systematic review (Oxman score)8

The direction of conclusion (n)

Extensive flaws (≤1) Major flaws (2–3) Minor flaws (4–5) Minimal or no flaws (6–9) Quality of primary trials Low Moderate High

1

2

3

0

1

1

0 3

2 6

1 7

4 3 1

10 4 0

9 5 0

Positive (+)

Negative ( )

Equivocal (+/ )

n, number of systematic reviews.

Risk of bias of primary and secondary studies In the included SRs, the number of primary studies (RCTs) ranged from three to 38 (mean=13.3; SD=9.15). Thirteen high-quality SRs (Oxman score 6–9) were based on poor-quality RCTs; seven were based on moderate-quality RCTs; and only one was based on high-quality RCTs. Thirteen SRs (48.1%) used meta-analysis and 14 (51.9%) did not. The methodological quality of the included SRs ranged from Oxman score 9 (poor) to 9 (excellent) (mean=4.66, SD=5.20). Table 3 summarises the direction of conclusions as a function of the quality of the SRs as well as that of the primary RCTs. The largest number of high-quality SRs arrived at equivocal conclusions (n=7). The largest number of SRs that arrived at equivocal or negative conclusions were based on poor-quality RCTs (n=10). There were no methodologically flawed SRs (Oxman score 2–3 or 4–5) that would draw unanimously positive conclusions. Table 4 summarises the quality of the SRs as a function of addiction type. The highest number of methodologically sound SRs focused on tobacco addiction, followed by alcohol, cocaine, opiate, cannabis and other drug addictions. Discussion This overview of systematic reviews aimed to summarise and critically evaluate the evidence from SRs of various CAMs for various addictions. Twenty-seven SRs were included. Only two SRs (7.4%) had been published before the year 2000 with the remainder (92.6%) published after that date. The majority of SRs (44.4%) arrived at equivocal conclusions; 40.7% of them drew negative conclusions; and only 14.8% arrived at positive conclusions.

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Table 4 The quality of systematic review as a function of addiction type Quality of systematic review (Oxman score)8

Type of addiction

Alcohol Amphetamine Cannabis Cocaine Methamphetamine Opiates (including heroin, morphine and opium) Tobacco Various/unspecified drugs

Extensive flaws (≤1)

Major flaws (2–3)

Minor flaws (4–5)

2 1 1 4 0 4

2 0 0 1 0 2

0 0 0 2 0 1

4 0 1 3 1 3

1 2

1 0

0 0

12 1

There was contradictory evidence to support the effectiveness of CAM in all addictions. For instance, three SRs concluded that AT and associated techniques, such as AA, mindfulness, meditation and spirituality are effective in the management of tobacco addiction; whereas five SRs drew negative conclusions for the effectiveness of hypnotherapy, AA, AP, AT, EA and LA in tobacco addiction. Six SRs drew equivocal conclusions for AA, AP, AT, CAM in general, EA, hypnotherapy, LA, meditation, mindfulness and yoga in tobacco addiction. The most conflicting evidence was for AA, which is in line with the previous review.37 For alcohol and opiate addiction, the evidence available so far is predominately equivocal. For cocaine dependence, it is negative. Overall, the largest number of the included SRs focused on tobacco addition (n=14); 12 (86%) of those reviews were determined to be of the highest methodological quality, with the direction of conclusions predominantly equivocal or negative. Various CAM modalities have been investigated in SRs. Using the NCCIH classifications, alternative medical systems were the most frequently tested types of CAM, including AA (n=14), AT (n=12), EA (n=9), LA (n=6), AP (n=5), AEA (n=1), ALA (n=1) and TCM (n=1); followed by mind–body interventions such as meditation (n=3), hypnotherapy (n=2), mindfulness (n=2), yoga (n=2), music therapy (n=1)

Minimal or no flaws (6–9)

and spirituality (n=1). The remaining SR evaluated biologically based herbal medicine (n=1). We used Oxman criteria8 to evaluate the methodological quality of the 27 SRs; 16 were of high methodological quality, three had minor flaws, two had major flaws and six had extensive flaws. Overall, 59.2% of the included SRs were of high methodological quality (Table 2). Of these, all but one drew their conclusions on low- to moderatequality RCTs. It may sound counterintuitive but even the highest-quality SRs are subject to question and a reader’s confidence in the conclusions can be significantly undermined if SRs are based on poorquality primary RCTs (Table 5). Some self-regulatory techniques/mind–body medicines (MBM) such as meditation, mindfulness or yoga have been suggested as being effective for the treatment of addictions; and there might be several plausible mechanisms of action involved.25,38,39 For instance, studies have shown that mindfulness meditation limits experiential avoidance by interrupting the tendency to respond using maladaptive behaviours (i.e. substance use).40 Yoga, for example, might serve as a direct substitute for the reduced arousal that follows the consumption of addictive substances; it may also minimise the reinforcement of addictive behaviours, increase the sense of control and cognitive flexibility, improve well-being and self-esteem and decrease negative emotions.25

Table 5 The quality of systematic review (Oxman score)8 as a function of quality of primary data Quality of primary trials

Low Moderate High

Quality of systematic review (Oxman score) Extensive flaws (≤1)

Major flaws (2–3)

Minor flaws (4–5)

Minimal or no flaws (6–9)

6 3 0

2 0 0

2 2 0

13 7 1

Review The beneficial effects of MBM might also involve self-efficacy beliefs related to the patient’s feelings of personal empowerment that they can effectively manage the stressful situation. It is also worth mentioning that other CAM modalities, for which no SRs exist, show promise for various types of addictions. For instance, preliminary evidence supports the effectiveness of massage as an adjunct to traditional medical detoxification for alcohol, psychoactive drugs and nicotine.41–43 In light of these analyses, it is important to mention the risk–benefit balance of CAM. The majority of therapies in question have a good safety profile.44–47 Given the paucity of adverse effects from MBM and its benefits, the risk–benefit ratio for meditation, mindfulness and yoga would seem to be positive for some addictions. A cost–benefit ratio of CAM for addictions is largely unknown, and more research is needed in this area. Considerable challenges exist for addiction research. The studies included in this overview highlight the inherent difficulties of conducting RCTs of behavioural interventions, such as the lack of blinding, standardisation of treatment packages and control for placebo effects. Furthermore, comparator groups in the RCTs were heterogeneous and included placebo/sham treatments (e.g. sham AT), no treatment, pharmacological or non-pharmacological treatments (e.g. cognitive–behavioural interventions), as well as usual care, leading to indirect comparisons and lower quality of evidence.48 In order to advance this area, there needs to be appropriately funded, high-quality trials with sufficiently powered samples, allocation concealment, ITT analysis, validated and objective outcome measures, sufficiently long follow-ups and cost-effectiveness analyses. The findings of such RCTs should then be quantitatively pooled in meta-analyses to guide policy makers and clinicians. This overview of SRs has several limitations that should be kept in mind when interpreting its outcomes. The principal limitation is that many of these SRs often analysed the same primary studies but, confusingly, arrived at different conclusions (Table 6). Considering this overlap between SRs is critical when interpreting results of this overview. One such example is AT, for which different authors drew contradictory conclusions for similar datasets; and there was an overlap (double-counting) in terms of primary studies. For instance, 14 SRs focused on AA and the majority of those relied on the same RCTs. The problem of double-counting in overviews of SRs is, however, methodologically unavoidable (i.e. non-Cochrane SRs including large proportions of the same RCTs already included in Cochrane reviews and vice versa). Our searches were limited to the English language, so there is a

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Table 6 Types of addictions with multiple systematic reviews Condition

Alcohol Cannabis Cocaine Opiates Tobacco

Conclusion (n) Positive (+)

Negative ( )

Equivocal (+/ )

1 1 1 2 3

1 0 5 3 5

6 1 4 5 6

n, number of systematic reviews. Table 7 The direction of conclusion as a function of CAM modality Type of CAM

Auricular acupuncture Auricular electro-acupuncture Auricular laser-acupuncture Acupressure Acupuncture CAM in general Electro-acupuncture Herbal medicine Hypnotherapy Meditation Mindfulness Music therapy Spirituality Traditional Chinese medicine Yoga

Conclusion (n) Positive (+)

Negative ( )

Equivocal (+/ )

2 0 0 1 1 0 1 0 0 1 1 0 1 1 0

7 0 0 2 7 0 4 0 1 0 0 0 0 0 0

5 1 1 2 4 1 4 1 1 2 1 1 0 0 2

n, number of systematic reviews.

possibility that relevant non-English articles were omitted. Some SRs had methodological weaknesses and were based on poor-quality primary data (Table 7). In addition, reviewing SRs might neglect the nuances that may be hidden in the original data. Furthermore, all SRs are susceptible to publication bias within the primary data that they include, and, therefore, any such bias has been inherited in our study. Collectively, these limitations render our findings open to criticism. Conclusion To conclude, a large number of SRs of CAM exists in the area of addiction. Our review suggests that the evidence of the effectiveness of CAM for addiction is confusing; or negative. Several limitations of the current evidence have been emphasised. Also highlighted is the need for more quality primary RCTs to determine the therapeutic usefulness of CAM.

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Pawel Posadzki, PhD, MSc, BSc, Senior Research Fellow, Centre for Population Health Sciences, Lee Kong Chian School of Medicine, Nanyang Technological University, 3 Fusionopolis Link, #06–13 Nexus@One-North, South Tower, Singapore 138543. E-mail: [email protected] Mohamed MK Khalil, MBBS, MD, MPH, Consultant Public Health, National Center for Complementary and Alternative Medicine (NCCAM), Riyadh, Saudi Arabia. E-mail: [email protected] Abdullah MN AlBedah, MBBS, FFCM, Executive Director, National Center for Complementary and Alternative Medicine (NCCAM), Riyadh, Saudi Arabia. E-mail: [email protected] Olena Zhabenko, MD, PhD, Research Fellow, Centre for Population Health Sciences, Lee Kong Chian School of Medicine, Nanyang Technological University, 3 Fusionopolis Link, #06–13 Nexus@One-North, South Tower, Singapore 138543. E-mail: [email protected] Josip Car, MD, PhD, DIC, MSc, Associate Professor and Director, Centre for Population Health Sciences, Lee Kong Chian School of Medicine, Nanyang Technological University, 3 Fusionopolis Link, #06–13 Nexus@One-North, South Tower, Singapore 138543. E-mail: [email protected]