Alternative Therapies In Health And Medicine

can be replaced where warranted); lifestyle adjustments such as
dietary improvement and reduction of alcohol and caffeine; adequate
relaxation and regular exercise; appropriate psychological
interventions; and improved social dynamics.
Individual Interventions: Overview of Evidence
A literature review was required to determine which nonpharmaceutical
options have sufficient evidence of efficacy in the
treatment of depressed mood. These evidence-based treatments
were then applied as components to form a working clinical
model. As detailed in Table 1, superior efficacy over controls was
found for several interventions. Specifically, evidentiary support
in varying degrees was found for herbal medicines (Hypericum
perforatum, Rhodiola rosea, Crocus sativus); nutrients
(L-tryptophan and 5-hydroxytryptamine [5-HTP], omega-3 fatty
acids, S-adenosyl methionine [SAMe]; dehydroepiandrosterone
[DHEA] was omitted as it is a hormone and a pharmacological
drug); psychological techniques (eg, cognitive behavioral therapy,
interpersonal therapy, mindfulness); physical exercise (aerobic,
anaerobic, yoga); and social interventions (eg, group therapy,
social skill development).
Evidence-based Interventions to Treat Depression
Antidepressants. In addition to synthetic antidepressants,
several natural products have evidence as thymoleptics. Among
them, Hypericum perforatum (St John’s wort: SJW), a traditional
phytomedicine used to treat nervous system disorders, has level-A
evidence (Table 1). Enough human clinical trials have been conducted
for several meta-analyses to be conducted. 34 All meta-analyses
have revealed that SJW provides a significant antidepressant effect
compared to placebo and an equivalent efficacy compared to synthetic
antidepressants. In vivo and in vitro studies have revealed
antidepressant activity via modulation of serotonin, dopamine,
norepinephrine pathways (involving neurotransmitter transport
systems, increased binding to various receptors, and decreased
neurotransmitter degradation). 35 Aside from SJW, the herbal
medicines Rhodiola rosea (rosenroot) and Crocus sativus (saffron)
currently possess the most evidence as monoamine and neuroendocrine
modulators, and have preliminary human clinical evidence
of efficacy in treating MDD. 36, 37 Rhodiola rosea is a
stimulating adaptogen, which possesses antidepressant, antifatigue,
and tonic activity. 36,38 In animal models, Rhodiola rosea has
been documented to increase noradrenaline, dopamine, and
serotonin in the brainstem and hypothalamus and to increase
the blood brain permeability to neurotransmitter precursors. 39
As detailed in Table 1, one randomized controlled trial (RCT) has
documented efficacy against placebo in the treatment of depression;
however, further studies need to be conducted to confirm
efficacy. Saffron is developing clinical evidence as an effective
antidepressant with several studies displaying positive results vs
placebo and comparable efficacy vs a positive pharmaceutical
control. 37 The mechanisms responsible for the antidepressant
actions are posited to be mediated via reuptake inhibition of
dopamine, norepinephrine, serotonin, and n-methyl-D-aspartate
(NMDA) receptor antagonism. 37 Safranal, a constituent from saffron,
is posited to exert selective GABA-α agonism and possible
opioid receptor modulation, as demonstrated via intracerebroventricular
administration in an animal model. 37,40
SAMe is an endogenous compound produced from methionine
and various methylators (eg, B 6
, B 12
, folate) in the body. 41,42
SAMe serves as a necessary methyl donor of methyl groups
involved with the metabolism and synthesis of neurotransmitters.
42 In vivo studies have consistently shown that SAMe possesses
antidepressant properties, and many human clinical trials
using SAMe in MDD have revealed beneficial antidepressant
effects comparable to synthetic antidepressants. L-tryptophan is
an essential monoamine precursor required for the synthesis of
serotonin and has been studied extensively in the latter half of
the 20th century as an antidepressant. 43 Although many positive
studies exist, only one RCT of sufficient methodological rigor
using the nutrient as a monotherapy in the treatment of MDD
was found to exist. Eight controlled adjuvancy studies using
L-tryptophan with antidepressants, however, provide encouraging
evidence, with L-tryptophan augmentation being effective in
increasing the antidepressant response with phenezine sulphate,
clomipramine, tranylcypromine, and fluoxetine. 44 Other clinical
studies using tricyclics discovered no additional benefit compared
placebo, however.
Omega-3 fatty acids may also have a role in reducing depression,
especially if an inflammatory causation is present (a link
between inflammation and depression has been documented). 8
Epidemiological studies have demonstrated that increased risk of
depressive symptoms may be correlated with lower dietary omega-3
fish oil (eicosapentaenoic acid [EPA] and docosahexaenoic
acid [DHA]). 45 Studies also have demonstrated that people with
depressed mood have a tendency towards a higher ratio of serum
arachidonic acid to essential fatty acids and an overall lower
serum level of omega-3 compared to healthy controls. 46 Several
human clinical trials have been conducted assessing the efficacy
of EPA, DHA, or a combination of both. 47 Clinical evidence
regarding the use of essential fatty acids as a monotherapy for
unipolar or bipolar depression is equivocal, with a mixture of
positive and negative trials. This may be due in part to many
studies using olive oil as an “inert” control and some studies
using higher DHA to EPA ratio or DHA alone. Preparations higher
in EPA vs DHA in the treatment of depression may be advised,
as is the use of a higher initial dosage to correct any relative
imbalance to greater ratio of arachidonic acid to essential fatty
acids. 44,48,49 Clinical trials using essential fatty acids adjuvantly
with antidepressants have provided evidence of a greater reduction
of depression level. 44 Adjuvant prescription of essential fatty
acids with antidepressants can be advised in cases of deficiency
or if comorbid cardiovascular or inflammatory disorders are
present. Evidence currently suggests that omega-3 fatty acids
exert antidepressant activity via beneficial effects on neurotransmission.
This may occur via modulation of neurotransmitter
(norepinephrine, dopamine, and serotonin) reuptake, degradation,
synthesis and receptor binding, antiinflammatory effect,
An Evidence-based Integrative CAM Model for Depression
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