Download Is there good evidence for alternative therapies in depression?

Is there good evidence for alternative therapies in depression?
Ralf Ilchef, Consultant Psychiatrist, Northside Macarthur Clinic
The short answer is no, not really. As a common disorder with a high placebo response rate but
relatively low full remission rate with conventional therapy, depression is a magnet for dubious and
overstated claims of effectiveness for a wide array of interventions. Let’s look at the evidence
base for some of these:
St John’s wort (hypericum). There is reasonable evidence, in a meta-analysis of 29 trials, for the
effectiveness of St John’s Wort as monotherapy in mild- moderate depression using 500 –
1200mg daily. Rosenroot (Rhodiola rosea) and saffron (Crocus sativus) are other herbal
preparations with claimed antidepressant activity. Two small RCTs support the effectiveness of
saffron.
S-adenylmethionine (SAM-e). This is a naturally occurring molecule involved in the methylation
of a number of entities of many neurotransmitters, phospholipids and cellular receptors. There is
some evidence for the effectiveness of SAM-e, using 1600mg daily, as monotherapy in mild to
moderate depression, and reasonable evidence for its effectiveness as an augmenting agent with
SSRIs. Expense is a significant barrier, with therapeutic doses costing up to $160.00 per month.
Omega-3 fatty acids. In a systematic review of 35 RCTs using doses of 0.5 to 9.6 grams per day,
O3FAs showed a modest benefit, more evident in patients with more severe depression.
L-tryptophan. This is a monoamine precursor of serotonin that has been studied extensively, but
has failed to clearly distinguish itself from placebo in the treatment of depression.
Folate. A precursor of SAM-e, folate has been shown to increase treatment response to
fluoxetine, especially in women. It is of demonstrated value in depressed patients with folate
deficiency, women contemplating pregnancy, and people taking valproate, but the evidence for
more widespread use is insufficient.
Acupuncture. Meta-analysis of 30 studies, and a review of 5 further studies, has failed to find
evidence of significant benefit.
Exercise. Regular exercise has a host of physiological and psychological benefits, but what is the
evidence for it’s effectiveness in major depression? A Cochrane review of 25 studies showed a
large clinical effect when compared to inactive control groups, and equivalence when compared to
CBT and antidepressant medication. There did not seem to be any difference in effectiveness
between aerobic (e.g. running), resistance (e.g. weights) or mindfulness-based (e.g. yoga). There
was however, evidence of publication and observer bias in these studies. Doctors can be reluctant
to prescribe exercise to depressed patients but one study showed 30% of depressed subjects
exercised for the duration of a 26-month study period.
Bright light therapy. Bright light therapy has been used since the 1980s for the treatment of
seasonal mood disorders, but some RCT evidence exists for effectiveness as monotherapy in
nonseasonal mood disorders (three studies). It has not been shown to be effective as an adjunct
to antidepressant medication (five studies).
Homeopathy. A recent review of homeopathic treatments for psychiatric conditions found no
placebo-controlled trials in depression. Given this and the lack of a plausible mechanism of action,
homeopathy cannot be recommended unless compelling trial data emerges.
Traditional Chinese medicine. A meta-analysis of ten RCTs comparing the use of ChaihuShugan-San (CSS), a traditional Chinese medicine formulation combined with antidepressant
medication, with a control arm of antidepressant alone, showed a significant benefit to the CSStreated group in terms of improved depressive symptoms, effectiveness and recovery. As
monotherapy it was at least equivalent to antidepressant therapy in remission rates, and superior
in improving depressive symptoms. While very interesting, this finding needs to be duplicated and
more known about the safety and tolerability of CSS before it can be recommended as a
treatment. Promising results have also been reported in systematic reviews in the Chinese
literature for another formulation, Xiao Yao San, charmingly also known as Free and Easy
Wanderer. Peony (Paeonia lactiflora) root, used in Chinese traditional medicine, has been
demonstrated to show antidepressant-like effects in laboratory animal studies.
Other therapies. There are no published RCTs for iridology, kinesiology or a host of other claimed
interventions for depression.
Conclusion. The field of complementary and alternative medicines (CAM) is bedevilled by a lack
of good-quality studies, which typically have small sample size, short duration and poor monitoring
of adverse events.
There is level I evidence (meta-analysis or systematic review of RCTs) regarding St John's wort
(Hypericum perforatum), Tryptophan and 5-hydroxy-tryptophan, S-adenosyl methionine (SAMe),
folate, inositol, acupuncture and exercise.
Of these interventions there is clear evidence of effectiveness for St John’s wort, SAM-e and
exercise, and these can be confidently recommended as treatment options in mild to moderate
depression, although St John’s wort should not be prescribed in combination with another
antidepressant because of the risk of serotonin syndrome. SAM-e can be used as an augmenting
agent in depression, but patients should be warned of the cost. The evidence strongly supports
assertive encouragement of regular exercise.
The evidence base for other interventions is not yet strong enough to support their regular use
although there are some interesting prospects in herbal and Chinese traditional medicine that
merit further research.
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