MJA
MJA

Effectiveness of complementary and self-help treatments for depression

Anthony F Jorm, Helen Christensen, Kathleen M Griffiths and Bryan Rodgers
Med J Aust 2002; 176 (10): 84. || doi: 10.5694/j.1326-5377.2002.tb04508.x
Published online: 20 May 2002

Abstract

Objectives: To review the evidence for the effectiveness of complementary and self-help treatments for depression.

Data sources: Systematic literature search using PubMed, PsycLit, the Cochrane Library and previous review papers.

Data synthesis: Thirty-seven treatments were identified and grouped under the categories of medicines, physical treatments, lifestyle, and dietary changes. We give a description of each treatment, the rationale behind the treatment, a review of studies on effectiveness, and the level of evidence for the effectiveness studies.

Results: The treatments with the best evidence of effectiveness are St John's wort, exercise, bibliotherapy involving cognitive behaviour therapy and light therapy (for winter depression). There is some limited evidence to support the effectiveness of acupuncture, light therapy (for non-seasonal depression), massage therapy, negative air ionisation (for winter depression), relaxation therapy, S-adenosylmethionine, folate and yoga breathing exercises.

Conclusion: Although none of the treatments reviewed is as well supported by evidence as standard treatments such as antidepressants and cognitive behaviour therapy, many warrant further research.

Every year, 5.8% of Australian adults experience a depressive disorder,1 and such disorders are the biggest source of non-fatal disease burden in Australia, accounting for 8% of disability.2 Depressive symptoms that fall short of a diagnosis of a depressive disorder are also very common and are an additional contributor to disability.3

A number of treatments for depressive disorders are supported as effective by evidence-based systematic reviews, and these have been incorporated in clinical practice guidelines. However, it is estimated that only 50% of Australians who are depressed receive an evidence-based professional intervention.4 One possible reason for this is that many Australians state a preference for self-help and complementary therapies for depression.5,6 For example, in a national sample, 57% regarded vitamins, minerals, tonics or herbal medicines as likely to be helpful for treating depression, compared with 29% who regarded antidepressants as likely to be helpful.5 People in the community have also been found to use self-help interventions more commonly than professional treatments when they have anxiety and depressive symptoms. In one survey, the most commonly used self-help interventions over a six-month period were taking alcohol to relax (55% of respondents), taking pain relievers (55%) or becoming involved in physical activity (50%), compared with 35% who consulted a general practitioner, 20% who took antidepressants, and 4% who received psychotherapy.6 Australians also commonly use complementary therapies. It has been estimated that almost half of Australian adults used complementary medicines in the past year and a fifth consulted complementary practitioners.7 Although we do not know how much of this use is attributable to mental health problems, results from surveys in the United States indicate that people who are depressed have a higher use of complementary treatments.8,9

Given their frequent use, complementary and self-help treatments warrant the same degree of evaluation as conventional treatments. The community needs information about which treatments are likely to be effective, which are not, and which have not been adequately evaluated. General practitioners can play an important role in providing guidance.

The purpose of this review is to provide an overview of the evidence on complementary and self-help treatments. We define:

  • a complementary treatment as one that involves practices and beliefs that are not generally upheld by the dominant health system in Western countries; and

  • a self-help treatment as one that can be used by a person without necessarily consulting a healthcare professional.

Although some self-help treatments are complementary, others are not (eg, bibliotherapy, exercise). Our review focuses on depressive disorders and depressive symptoms, but excludes bipolar disorder.

Methods

Treatments were identified by searching the 21 most popular websites on depression,10 amazon.com's list of the top 25 books on stress management, and treatments mentioned in pamphlets gathered from pharmacists and health food shops. Once the treatments had been identified, PubMed, PsycLit and the Cochrane Library were searched using the following terms: Name-of-Treatment AND (Depressi* OR Dysthym* OR Affective OR Mood). Searches were carried out of literature up to August 2001. Three recent review articles and a book on complementary therapies for mental disorders were also consulted.11-14 Articles were included only if they reported studies of individuals selected to have a depressive disorder or a high level of depressive symptoms. Occasionally, articles on depressive symptoms in non-clinical samples not selected for depression or depressive symptoms are mentioned in the reviews below if they form an important part of the literature. However, they were not used in rating the effectiveness of treatments. Articles on bipolar disorder were excluded.

The evidence was evaluated using the levels of evidence shown in Box 1.15 It should be noted that these levels relate to the quality of the evidence, not the effectiveness of the intervention. A treatment could have been evaluated by rigorous methodologies and found to be ineffective, or, conversely, evaluated by weaker methodologies but found to be highly effective.

Results

For convenience, treatments have been grouped under the categories of medicines, physical treatments, lifestyle, and dietary changes. For some treatments, no evidence regarding effects on depression was available. These treatments are briefly summarised in Box 2.

Medicines
Natural progesterone
Review of effectiveness:

There have been two recent systematic reviews of the effectiveness of progesterone in treating postnatal depression. The first, a Cochrane review, failed to find any studies of acceptable methodological quality.21 The only study of the effectiveness of natural progesterone in postnatal depression22 was excluded on the grounds of insufficient quality. The excluded study found no effect of natural progesterone on postnatal depression. The second systematic review also concluded that there is little evidence to suggest that the hormone was effective, and that the available evidence is of low quality.23 There are no studies of the effectiveness of natural progesterone for perimenopausal, menopausal or premenstrual depression. However, a systematic review of double-blind prospective studies found that natural progesterone does not improve mood in women diagnosed with premenstrual syndrome in general.24

S-Adenosylmethionine
Rationale:

SAMe plays a role in many biological reactions by transferring its methyl group to DNA, proteins, phospholipids and biogenic amines.27 This could result in SAMe indirectly influencing neurotransmitter metabolism and receptor function.

Review of effectiveness:

A meta-analysis of six randomised controlled trials found that 70% of subjects showed some response to SAMe, compared with 30% for placebo. Furthermore, pooling of data from seven trials comparing SAMe with tricyclics found no difference.28 Although these results are encouraging, the studies all had small sample sizes and were short term, and there have been no comparisons with the newer antidepressants.

An advantage of SAMe is that it seldom has side effects. However, the Therapeutic Goods Administration has warned that individuals who are using prescription antidepressants for bipolar depression should not use SAMe unless under the supervision of a healthcare practitioner.29

St John's wort
Review of effectiveness:

A meta-analysis of 27 randomised controlled trials concluded that this treatment is superior to placebo and not different from tricyclic antidepressants in the treatment of mild to moderate depression.31 A meta-analysis of six studies that met stringent methodological criteria concluded that St John's wort is 50% more likely to produce an antidepressant effect than placebo and is equivalent to standard antidepressants.32 The side effects and drop-out rate are lower with St John's wort than with tricyclic antidepressants. Fewer trials have compared St John's wort with the newer antidepressants, but results to date indicate that it is as effective as selective serotonin re-uptake inhibitors.33-35 Although most of the evidence on St John's wort is positive, the largest trial so far found no difference between St John's wort and placebo.36 This study was too recent to be included in the meta-analyses cited above.

Although St John's wort is generally reported to have fewer side effects than antidepressants, the Therapeutic Goods Administration has warned that it can interact with a number of prescription medicines, leading to a loss of therapeutic effect of these medicines. Medicines affected include HIV protease inhibitors, HIV non-nucleoside reverse transcriptase inhibitors, cyclosporin, tacrolimus, warfarin, digoxin, theophylline, anticonvulsants, oral contraceptives, SSRIs and related drugs, and triptans. An information sheet is available for healthcare professionals.37

Vitamins
Rationale:

It has been suggested that folate and vitamin B12 might facilitate monoamine neurotransmitter synthesis by promoting synthesis of tetrahydrobiopterin, a cofactor involved in converting amino acids to serotonin, dopamine and norepinephrine.40 Folate and vitamin B12 might also facilitate the production of S-adenosylmethionine, leading to an increase in serotonin levels.40 There is less detailed discussion of the proposed mechanisms by which other B vitamins might work. Several B vitamins are involved in amino acid metabolism, and vitamin B6 is involved in the synthesis of serotonin from tryptophan. It is thought some vitamins (eg, the antioxidants) might improve mood by decreasing oxygen free radicals in the brain.41 Vitamin D might affect mood through activational effects on the brain.42 Vitamin D levels decrease during winter, leading to the suggestion that a deficiency in vitamin D might play a role in winter depression.43

Review of effectiveness:

Folate. There have been four published, double-blind, randomised-controlled studies of the effectiveness of folate.44-47 Three of these trials (two using intent-to-treat analyses44,45) found that methylfolate/folic acid combined with an antidepressant was more effective than an antidepressant alone,44-46 although in one study the effect was confined to women.44 In another, the effect was observed for clinical outcome scores but not depression scores and included only patients with low folate levels.45 The fourth study (intent-to-treat design) reported that methylfolate is at least as effective as trazadone for patients with a combined diagnosis of Alzheimer's disease and depression, with both groups showing an improvement in depression scores, and 45% of the folate group and 29% of the trazadone group showing a partial or complete response to treatment.47 Positive effects of folate have also been reported for depressed alcoholics and depressed (but otherwise healthy) older people, although in less well controlled studies. In an open pre–post trial (one week placebo washout) of methylfolate with older patients with depressive disorder there was an 81% response rate among completers and a marked decrease in depression scores.48 Similarly, a study using a double-blind, pre–post design with one-week placebo washout reported an improvement in depression among alcoholics with depressive disorder.49

Other B vitamins. There have been three randomised trials of the effectiveness of B vitamins other than folate for depression50-52 and two less well controlled trials. The results of these studies are summarised below.

  • Vitamin B1. There are no reported controlled trials of the effect of thiamine alone for depressed patients. However, according to one recent review, there is evidence from several double-blind, placebo-controlled studies that thiamine improves mood among people who are not selected for depression.53

  • Vitamin B6. A randomised controlled trial comparing the effect of vitamin B6 with placebo on the mood of women who reported significant premenstrual mood changes found no effect of B6 on self-reported mood change.52 By contrast, a meta-analysis of 10 studies involving patients with premenstrual syndrome did conclude that vitamin B6 improves mood (odds ratio, 2.12).54 However, the review was not restricted to patients complaining of mood problems, nor was it confined to randomised controlled trials. Two other trials of the effectiveness of B6 for depression did not use a randomised controlled trial design. One used parallel groups and reported that adding B6 to an antidepressant did not confer any additional benefit compared with antidepressants alone.55 Arguably, this two-week trial was too short to permit meaningful conclusions to be drawn. The other study used a placebo-controlled cross-over design and found B6 to be more effective than placebo in women who were B6 deficient and suffering from depression due to the contraceptive pill.56

  • Vitamin B12. No significant difference between placebo and vitamin B12 was found in a small, short (two-week) randomised controlled trial of the vitamin in people with winter depression.51

  • Combined B1, B2 and B6. It has been suggested that B vitamins are most effective when taken together. There has been one small, short, randomised controlled trial comparing a combination of B vitamins (B1, B6 and B12) and tricyclic antidepressants with placebo and tricylic antidepressants.50 Although the results were described as containing "promising" trends, the effects on mood were not significant.

Vitamin C. Although it has been suggested that vitamin C may be effective for depression,57 there are no reports of group trials on the effectiveness of ascorbic acid in treating depression.

Vitamin D. In a small, short, single-blind, randomised-controlled trial involving patients with winter depression, depression was alleviated in patients receiving vitamin D but not in those receiving light therapy.43

Vitamin E. There are no reported randomised controlled trials of the effectiveness of vitamin E for depression. In a very small, uncontrolled trial, vitamin E was administered to nine subjects with prolonged major depressive disorder who had responded partially to antidepressants.41 All but one patient had tried at least two antidepressants and there had been no change in the patients' clinical states in the six months preceding the trial. Following the addition of vitamin E, there was a significant improvement in depressive symptoms in the group, and six of the nine patients showed more than 80% improvement in their depression scores.

Physical treatments
Acupuncture
Review of effectiveness:

A small, randomised controlled trial compared acupuncture for symptoms of depression, acupuncture for other symptoms (placebo group) and a wait-list control group.59 The specific acupuncture group improved more than the placebo group, but only marginally more than the wait-list group. A larger trial examined the benefits of adding acupuncture to antidepressant medication. Both specific acupuncture and placebo acupuncture added a therapeutic benefit, but did not differ from each other.60 Three controlled trials carried out in China have shown that electroacupuncture is as effective as tricyclic antidepressants.58,61 While two of these studies were double-blind, it is not clear if the third was. The double-blind studies included patients with both unipolar and bipolar depression, complicating the interpretation of the results.

Lifestyle
Bibliotherapy
Review of effectiveness:

A meta-analysis of six studies evaluating a range of books found that bibliotherapy is superior to no treatment for depression.75 On measures of depressive symptoms, treated individuals averaged 0.82 standard deviation units above wait-list controls (individuals placed on a treatment waiting list). Bibliotherapy was as effective as individual or group therapy in the four studies that examined this comparison. Most studies used small samples. Participants were recruited usually by media announcements, and therapists maintained minimal contact. Two more recent studies76,77 support the findings of the meta-analysis. In the first, people from the community with depressive symptoms and who met criteria for major depressive disorder were compared with a wait-list control group. There were significant improvements in depressive symptoms and dysfunctional thoughts. A follow-up study reported that the effects were maintained over a three-year period. The second study77 examined the efficacy of bibliotherapy in 30 adolescents using a cross-over design. The intervention was found to significantly reduce symptoms and lead to clinically significant levels of change. Bibliotherapy does not lead to a greater dropout rate compared with other interventions.78

Exercise
Review of effectiveness:

Three meta-analyses of the effects of exercise on mood are available. The first two do not address specifically whether exercise is effective in clinically depressed individuals, nor do they provide clear outcomes separately for randomised controlled trials in depressed subjects.82,83 A more recent review specifically examined the effectiveness of exercise in depression.84 This review identified 11 studies which compared exercise with "no treatment". Two of these reports were conference abstracts and two were doctoral dissertation studies. The mean difference in effect size for the studies was – 1.1 standard deviation units (95% CI, – 1.5 to – 0.6). However, three of these studies85-87 evaluated exercise as an adjunct to standard treatment or permitted the continuation of antidepressant medication/psychotherapy. As a result, the effects of exercise may have been underestimated. Our search of published reports where antidepressant or adjunctive treatment was not permitted identified seven studies using randomised controlled trials to evaluate exercise that used clinically depressed groups.87-93 Six of these were included in the earlier review, but one study92 is additional. Two studies included in the earlier review were excluded from our analysis because they included adjunctive treatments.85,86 Five of the seven randomised controlled trials88-92 compared exercise with a no-treatment control, and all found exercise (jogging, running, walking, progressive resistance training, bicycling) to be superior. Exercise was more effective than relaxation88 in one study, but not in another.87 In other studies, exercise was more effective than light therapy (for non-seasonal depression),92 and as effective as social contact90 and antidepressants.93 Follow-up findings from the latter study indicate that individuals who benefited from exercise at four months had significantly lower relapse rates than individuals who took antidepressant medication.94 One study that directly compared two types of exercise found no difference between weightlifting and running.89

Conclusion:

The authors of the earlier review84 concluded that the effects of exercise might be overestimated, as many individuals who were not motivated to exercise may have been screened out, people with depression were recruited from the community rather than from clinics, and outcomes were expressed in terms of change in symptoms rather than shifts in diagnosis. They concluded "it is not possible to determine from the available evidence the effectiveness of exercise in the management of depression". In our view, this is a conservative interpretation. Further randomised controlled trials, particularly in younger people and using intent-to-treat analyses, are needed, as three of the seven articles we reviewed used older people.90,91,93 However, given the large effect sizes reported in these trials, the recent evidence that the effects of exercise persist at follow-up94,95 and the consistency of positive findings in studies excluding potentially effective treatments as "control treatments" we conclude that the use of exercise for depression is supported by the available evidence.

Music
Review of effectiveness:

Randomised controlled trials of the acute effect of music on mood in depressed patients have found no effects.97,98 However, a controlled trial of music therapy which incorporated elements of cognitive behaviour therapy (a known effective treatment) did find a beneficial effect on depressive symptoms. There is also a Chinese study reporting a more rapid response in depressed patients exposed to music combined with antidepressants compared with patients receiving antidepressants alone, but the details of the method are not available in English.99

Pets
Review of effectiveness:

Few randomised controlled trials have been carried out with depressed people and all have had methodological weaknesses. One trial with psychogeriatric inpatients found no therapeutic benefit, but it gave exercise (a possibly active treatment) to the control group and did not specifically analyse the results for the depressed subgroup.100 Another negative study involved hospitalised psychiatric patients, but evaluated anxiety symptoms rather than depression as the outcome.101 A third trial with depressed students did find benefits, but did not use random assignment and the control group had lower depression initially.102 All studies have looked only at the short-term benefits of pet therapy rather than at the long-term benefits of pet ownership. There have been cross-sectional studies of the association between pet ownership and depressive symptoms in the general population, but these studies cannot determine cause and effect.

Yoga
Review of effectiveness.

Two randomised controlled trials have been carried out on the use of yogic breathing exercises in depression. One compared yogic breathing with no treatment in students who had a high level of depressive symptoms.111 After training, the students were instructed to practise for 30 minutes each morning for 30 days. The treated group was found to improve significantly more than the control group. In the second study, hospitalised patients with melancholic depression were randomly assigned to receive training in yogic breathing, electroconvulsive therapy (ECT) or imipramine.112 All groups were found to improve, with the greatest improvement after ECT. Yogic breathing did not differ from imipramine. This study did not have a placebo or no treatment control group.

Dietary changes
Caffeine avoidance
Rationale:

It has been proposed that some individuals have a sensitivity to caffeine which leads to depression.122 These people tend to have a particular constellation of symptoms (see Sugar avoidance). There is also some evidence that caffeine can increase anxiety in individuals who experience panic attacks.123 Because anxiety disorders often co-occur with depression, caffeine avoidance may confer an indirect benefit by relieving anxiety.

Review of effectiveness:

One small, randomised controlled trial has been carried out on patients whose depression was thought to be due to dietary factors.122 Patients were randomly assigned either to avoid sugar and caffeine or (as a control) to avoid red meat and artificial sweeteners. Patients assigned to avoid sugar and caffeine showed significantly greater improvement in depressive symptoms. Ten patients were assigned to sugar and caffeine avoidance, and subsequent testing indicated that three were sensitive to caffeine. There is no evidence on whether caffeine avoidance helps most people with depression.

Sugar avoidance
Rationale:

It has been proposed that some individuals have a sensitivity to sucrose which leads to depression.122 These individuals are said to have symptoms such as feeling fatigued, moody and depressed, with many having headaches, sleeping more than usual, and feeling tense and irritable. Some of these symptoms (eg, sleeping more) are atypical for depression.

Review of effectiveness:

One small, randomised controlled trial has been carried out on patients whose depression was thought to be due to dietary factors.122 Patients were randomly assigned either to avoid sugar and caffeine or (as a control) to avoid red meat and artificial sweeteners. Patients assigned to avoid sugar or caffeine showed significantly greater improvement in depressive symptoms. Ten patients were assigned to sugar and caffeine avoidance, and subsequent testing indicated that four were sensitive to sugar. There is no evidence on whether sugar avoidance helps most people with depression. On the contrary, there is some evidence that carbohydrate intake has a short-term effect of improving mood.53

Discussion

The complementary and self-help treatments with the best evidence of effectiveness are St John's wort, physical exercise, self-help books involving cognitive behaviour therapy, and light therapy for winter depression. However, none of these has as much support as antidepressants or face-to-face cognitive behaviour therapy, both of which are standard treatments recommended in clinical practice guidelines.127 For example, according to recent meta-analyses, newer antidepressants have been tested on more than 30 000 participants in 315 trials128 and cognitive behaviour therapy on 2765 participants in 48 trials.129 By contrast, St John's wort has been tested on 2291 participants in 27 trials,31 exercise on 724 participants in 14 trials,84 and self-help books involving cognitive behaviour therapy on 273 participants in six trials.75 Furthermore, while there are some well-designed studies on these complementary and self-help treatments, in general the reported studies are of poorer quality, with common deficiencies being small sample sizes, short follow-up periods, lack of blinding, and failure to use intent-to-treat analysis. We also know little about how some of these self-help treatments perform in special populations such as children and adolescents, the elderly, and perinatal women.

There are a number of other complementary and self-help treatments which have limited evidence to support their effectiveness: acupuncture, light therapy (for non-seasonal depression), massage therapy, negative air ionisation (for winter depression), relaxation therapy, SAMe, folate and yoga breathing exercises. Some of these treatments might be effective, but they have received very little research attention. Research on the effectiveness of treatments for depression has tended to focus on a small number of standard treatments and needs to be broadened, particularly in view of the public's more favourable attitudes to some non-standard treatments.

Although some complementary and self-help treatments may be useful, the available evidence is almost entirely confined to patients with mild to moderate depression. However, mild to moderate depression is more prevalent in the community than severe depression. According to data from the National Survey of Mental Health and Wellbeing,1 the prevalences are 4.4% for mild to moderate and 2.3% for severe depression. For severely depressed people, only conventional medical treatment is supported by evidence.

Given the frequent use of complementary and self-help treatments, it would be prudent for GPs and others treating depressed patients to routinely inquire about the use of these other treatments. An important reason is to prevent potentially harmful interactions with conventional treatments. The Therapeutic Goods Administration has already issued warnings about the use of St John's wort and SAMe in conjunction with some prescribed medications, and there might be unknown interactions with other complementary medicines.

Another reason to inquire about use of complementary and self-help treatments is to educate patients to make better choices. If patients wish to use such treatments, it is preferable that they use those best supported by evidence. To assist the education of the public about evidence-based treatments, a consumer guide to treatments for depression is available as a companion to this review.130

1: National Health and Medical Research Council (NHMRC) levels of evidence15

Level

Description


I

Evidence obtained from a systematic review of all relevant randomised controlled trials

II

Evidence obtained from at least one properly designed randomised controlled trial

III-1

Evidence obtained from well-designed pseudorandomised controlled trials (alternate allocation or some other method)

III-2

Evidence obtained from comparative studies (including systematic reviews of such studies) with concurrent controls and allocation not randomised, cohort studies, case-control studies, or interrupted time series with a parallel control group

III-3

Evidence obtained from comparative studies with historical control, two or more single-arm studies, or interrupted time series without a parallel control group

IV

Evidence obtained from case-series, either post-test, or pretest/post-test

V*

No evidence or minimal evidence such as testimonials


* We have added Level V to the NHMRC scheme to allow for even weaker types of evidence

2: Treatments for which there is no evidence evaluating effects on depression

Treatment

Description and rationale


Medicines

Ginseng

The roots of ginseng plants, or preparations of them, are used to improve energy levels and vigour. Ginseng is held to help the body cope with stress through its effects on the adrenal gland.

Lemon balm

This member of the mint family has been used traditionally for a number of medicinal purposes, including sedative and antidepressant effects.

Painkillers

Although there is no sound rationale for expecting painkillers to be helpful, many people report taking them when they feel depressed. Codeine (a narcotic), in higher doses, does have some mood-enhancing properties, and there has been speculation that aspirin could have beneficial mood-modulating effects.

Vervain

The aerial parts of this flowering plant are a traditional herbal remedy and have been used for treating depression.

Lifestyle

Colour therapy

It has been proposed that colours in the environment can affect the mood of someone who is depressed.

Prayer

Prayer is a traditional way of relieving illness and is often used by the public for mental health problems.

Dietary changes

Chocolate

Chocolate has several properties that could affect mood. It has a high carbohydrate content (hypothesised to increase serotonin production), contains several psychoactive substances (phenylethylamine, caffeine and theobromine, anandamide analogues), and has pleasant sensory characteristics (hypothesised to stimulate the release of endorphins).

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