INTRODUCTION:

Complementary therapies have become hugely popular. Herbal medicine is among the most popular complementary therapy ^[1].Depression is one of the top five most prevalent diseases worldwide. By 2020 it is expected to be the second-leading cause of disability globally. Depression typically presents as lowered mood, difficulty in thinking, loss of interest, and physical complaints such as headache, disturbed sleep, loss of energy, and change in sex drive. While there are many potential precipitating factors, it is currently believed that depression is primarily the result of biochemical alterations in the brain. Pharmaceutical treatments, including selective serotonin reuptake inhibitors (SSRI), Tricyclic antidepressants (TCA), and monoamine oxidase inhibitors (MAOI), cause alterations in brain chemistry through neurotransmitter amplification and regulation and have been shown to be effective in the treatment of depression ^{[2] .}The use of herbal and dietary supplements appears to be twice as great in persons reporting anxiety and depression than in those reporting any other problem, except for back and neck pain. Currently, the preferred treatment for anxiety disorders is cognitive behavior therapy and pharmacologic agents ^[3].The use of a neurophysiologic theory of the effects of Sudarshan Kriya Yoga (SKY) is also effective in the treatment of stress, anxiety, and depression ^[4]. It is not surprising that there is universal interest in finding effective natural anxiolytic (anti-anxiety) treatments with a lower risk of adverse effects or withdrawal ^[5-7].

METHODS

SEARCH STRATEGY

PubMed/Medline databases were searched without the regard for date of publication, using the search terms ‘’alternative therapies’’, ‘’herbal supplements’’ and individual herb supplement names. An electronic and manual search was done.

DEPRESSION

INEFFECTIVE REMEDIES

Ginkgo biloba (maidenhair tree) was tested in a small trial involving people with ‘winter depression’. The results did not suggest that this approach was superior to placebo. It has, however, been shown to be effective for conditions such as dementia ^[6-7].

PROMISING REMEDIES

Lavandula angustifolia (common lavender) was compared with imipramine in a small randomized controlled trial (RCT) including individuals with moderate depression. Both treatments seemed similarly effective but the study had significant methodological shortfalls. Another trial designed along the same lines suggested that Crocus sativus (saffron crocus) and imipramine were similarly effective. Unfortunately, the same limitations applied ^[8].

EFFECTIVE REMEDIES

The only herbal remedy that has been shown beyond reasonable doubt to be effective as a treatment for mild to moderate depression is Hypericum perforatum (St John’s wort). The active ingredients of this herbal medicine are probably hypericin and/or hyperforin. Its antidepressive activity seems to be due to inhibition of both serotonin reuptake and monoamine oxidase. An authoritative systematic review and metaanalysis included 30 RCTs involving individuals mostly (but not exclusively) with mild to moderate depression . compared St John’s wort with placebo. The results strongly favoured the former over the latter ^[8-9].

Though herbal remedies are not better than conventional drugs , still many patients prefer ‘natural’ treatments. A perhaps more convincing reason is that its adverse effects profile is preferable. In fact, St John’s wort is associated with similar frequency and severity of adverse effects as placebo. There are, however, two caveats. Extracts of St John’s wort powerfully interact with the cytochrome P450 enzyme system and thus increase the plasma level of a wide range of other drugs. It seems to follow that it is safe only for people who use no other medication. The second caveat is the suspicion that St John’s wort can trigger psychoses, particularly in patients who concomitantly take SSRIs ^[10].

ANXIETY

INEFFECTIVE REMEDIES

No anxiolytic effects of valerian (Valeriana officinalis) extract were noted in an RCT involving people with generalised anxiety disorder ^[10-11].

PROMISING REMEDIES

A large RCT found that a combination of Crataegus oxyacantha (hawthorn), Eschscholzia californica (Californian poppy) and magnesium was more effective than placebo in reducing anxiety in individuals with generalised anxiety disorder. There is some evidence for the efficacy of Matricaria recutita (German chamomile) in the treatment of anxiety but the study was methodologically weak. Short-term anxiolytic effects were noted after administration of Melissa officinalis (lemon balm) to healthy volunteers. Passiflora incarnata (passion flower) generated encouraging anxiolysis in an RCT with people who had generalised anxiety disorder. Even though these results are encouraging they do require independent replication before firm recommendations can be made ^[12].

EFFECTIVE REMEDIES

The only herbal remedy that is demonstrably effective in reducing anxiety is Piper methysticum (kava). Without exception, these trials showed anxiolytic effects of kava that were superior to placebo. Despite these clearly positive efficacy data, kava cannot currently be recommended for clinical use. This is because it has been associated with (sometimes severe) hepatotoxicity. Recently there has been much debate about whether this association is causal or not. At present, however, this herbal remedy remains banned from the UK market ^[13-14].

Major safety issues with herbal medicine

1. Inherent toxicity (e.g. liver damage after kava intake)

2. Contamination (e.g. heavy metals in Ayurvedic preparations)

3. Adulterations (e.g. sildenafil in herbal aphrodisiacs)

4. Interactions (e.g. St John’s wort lowers the plasma level of about half of prescription drugs)

Examples of interactions between herbal and synthetic medicines

1. St John’s wort can increase the effects of conventional SSRIs

2. Kava can interact with levodopa and alprazolam, causing extrapyramidal symptoms or lethargy

3. Valerian can interact with loperamide and fluoxetine, causing delirium

4. Evening primrose oil can interact with phenothiazide, causing epileptic seizures

RESULTS:

HERBAL ANTIDEPRESSANTS ^[6-11]

1. Borage (Echium amoenum) has its mechanism of action by anxiolysis shown in an animal model (elevated plus maze test) and its Antidepressant mechanism currently unknown and it is widely used in treating depression and anxiety.

2. Lavender (Lavandula spp. ) has its action by GABA modulation and Anxiolysis shown in animal models and used for the treatment of anxiety, depression and somatic tension.

3. Korean ginseng (Panax ginseng) exhibits its action by HPA-axis modulation, Monoamine modulation (dopamine, serotonin), Nitric oxide synthase inhibition and Anti-inflammatory and antioxidant effects and used in the treatment of fatigue, depression and poor cognition.

4. Mimosa (Albizia julibrissin) has its action by 5-HT1A receptor binding , 5-HT2c receptor binding affinity, Antidepressant, anxiolytic effects in animal models (elevated plus maze and tail suspension tests) and Significantly decreased sleep latency and increased sleep duration in pentobarbital-induced sleep and used for treating depression, anxiety and insomnia.

5. Roseroot (Rhodiola rosea) executes its action by neuroendocrine modulation (inhibition of cortisol, stress-induced protein kinases, nitric oxide), Monoamine oxidase A inhibition ,Monoamine modulation and Normalisation of 5-HT and anti-stress effects in animal depression models and used in treating fatigue, depression and anxiety.

6. Saffron (Crocus sativus) executes its action mechanism by the increased Re-uptake inhibition of monoamines (dopamine, norepinephrine, serotonin) NMDA receptor antagonism ,GABA-α agonism and Anxiolytic effects in animal models (elevated plus maze and open field test) and used in the treatment of depression and anxiety.

7. St John Wort (Hypercium perforatum) shows its action by the modulation of monoamine transmission via Na+ channel , Nonselective inhibition of re-uptake of serotonin, dopamine, norepinephrine , Decreased degradation of neurochemicals , Increased binding/sensitivity/density to 5-HT1A,B , Inhibited neuronal release of glutamate, Neuroendocrine modulation and Anti-depressant and anxiolytic activity in animal models and used to treat depression and bipolar depression

HERBAL ANXIOLYTICS [6-13]

1. Brahmi (Bacopa monniera) executes its action by Metal chelation/ β-amyloid protection, Cholinesterase inhibition, 5HT2c modulation, Antioxidant effects, Antidepressant effects in forced swim and learned helplessness animal models used to treat depression, anxiety, nervous exhaustion and cognitive impairment.

2. California poppy (Eschscholzia californica) has its mechanism of action by binding affinity with GABA receptor (flumazenil antagonist), anxiolysis in animal models (familiar environment and anti-conflict tests) used to treat anxiety, insomnia and pain.

3. Charmomile (Matricaria recutita) exhibits its action by binding to GABA receptors , Modulates monoamine neurotransmission and Neuroendocrine modulation and used to treat anxiety, insomnia and stress.

4. Ginkgo (Ginkgo biloba) executes its action by the modulation of cholinergic and monoamine pathways ,antioxidant, anti-PAF, anti-nflammatory effects, GABAergic effects and Nitric oxide activity and used to treat cognitive impairment depression and anxiety .

5. Gotu cola (Centella asiatica) exhibits its action by GABA transaminase inhibition , Animal models have shown anxiolytic effects (elevated plus maze, open field, social interaction tests) and inhibition of acoustic startle response in human RCT and used for the treatment of cognitive impairment stress and anxiety.

6. Kava (Piper methysticum) executes its action by GABA channel modulation (lipid membrane structure and sodium channel function), Weak GABA binding, β-adrenergic downregulation, MAO-B inhibition and Re-uptake inhibition of norepinephrine in the prefrontal cortex and used to treat comorbid depression, anxious insomnia, anxiety, ADHD and pain.

7. Lemonbalm (Melissa officinalis) has its action by potent in vitro inhibitor of rat brain GABA transaminase (GABA-T), MAO-A inhibition, acute dosing caused a significant increase in self-rated calmness on a human stress tests and used in the treatment of acute stress and anxiety.

8. Passionflower (Passionflora spp.) has its action by GABA-system mediated anxiolysis ,Benzodiazepine receptor partial agonist animal behavioural models have shown non-sedative anxiolytic effects (elevated-plus maze, light/dark box choice tests) used to treat anxiety, depression and insomnia.

9. Scullcap (Scutellaria lateriflora) increases its action by posited GABA-α binding affinity(Anxiolysis in animal maze-test model) and used to treat anxiety, nervous exhaustion and insomnia.

10. Withania (Withania somnifera) executes its action by GABA-mimetic activity (enhanced flunitrazepam binding), anxiolytic effect comparable to that produced by lorazepam in animal models (elevated plusmaze, social interaction and feeding latency in an unfamiliar environment tests) and used to treat nervous exhaustion, anxiety, insomnia and fatigue.

CONCLUSION:

Based on the available evidence, it appears that nutritional and herbal supplementation is an effective method for treating anxiety and anxiety-related conditions including depression without the risk of serious side effects. There is the possibility that any positive effects seen could be due to a placebo effect, which may have a significant psychological impact on participants with mental disorders. However, based on this systematic review, strong evidence exists for the use of herbal supplements containing extracts of passionflower or kava. St. John’s wort monotherapy has insufficient evidence for use as an effective antidepressant treatment.

As there is now sufficient evidence to consider Sudarshan kriya Yoga as a potentially beneficial, low-risk adjunct for the treatment of stress, anxiety, depression, stress-related medical illnesses, and substance abuse, and for the rehabilitation of criminal offenders. Including exercise in treatment programs for people with affective disorders has a number of advantagesas as there are no side effects compared with drug treatment and it is potentially useful as a prophylactic prevention of future affective episodes.

ABBREVATIONS

SSRI- Selective Serotonin Reuptake Inhibitors

TCA- Tricyclic Antidepressants

MAOI- Monoamine Oxidase Inhibitors

SKY- Sudarshan Kriya Yoga

RCT- Randomized Controlled Trial

GABA- Gamma Aminobutyric Acid

5-HT- 5-hydroxytryptamine receptors

NMDA- N-methyl-D-aspartate receptor

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Received on 23.05.2016 Modified on 02.06.2016

Research J. Pharm. and Tech 2016; 9(8):1253-1256.

DOI: 10.5958/0974-360X.2016.00237.7