A Review on Relevance of Herbal Medications for Psychiatric Patients

 

Aswathi T1, Venkateswaramurthy. N2*, Sambath Kumar. R3

1Pharm D Intern, J. K. K. Nattraja College of Pharmacy, Kumarapalayam, 638183, Erode, Tamil Nadu,

2Department of Pharmacy Practice, J. K. K. Nattraja College of Pharmacy, Kumarapalayam

638183, Erode, Tamil Nadu

3Department of Pharmaceutics, J. K. K. Nattraja College of Pharmacy, Kumarapalayam

638183, Erode, Tamil Nadu

*Corresponding Author E-mail: aswathit20@gmail.com, venkateswaramuhttps://mail.google.com/mail/u/1/images/cleardot.gifrthy.n@jkkn.org, https://mail.google.com/mail/u/1/images/cleardot.gifsambathkumar.r@jkkn.org

 

ABSTRACT:

Objective: This review illustrates on the use of herbal medication and its impact among psychiatric patients. Method: PubMed was searched for articles related to the herbal remedies used in the psychiatric patients. A secondary search was performed using references obtained from articles published from 2000 – 2017 identified by the PubMed search. Articles focusing on the experimental trails in adults and those patients who were not on medication was excluded during the selection process and those articles which aimed in accessing the incidence of drug interaction and possible negative effects due to co-administration of herbal medications with psychiatry drugs was included in this review. Result and Discussion: Effective studies have shown that additional alternative treatment with particularized herbal medicine increases antidepressant response and that reduces certain side effects associated with psychotropic medications. Herbal medicines used for the treatment of psychiatric problems was produced safe and effective towards severe depressive episodes, but usage of these herbal drugs in patients with mental illness led to unusual occurrence of side effects. This review also discusses the pharmacological mechanism of drug interaction of various herbal medications. Conclusion:  This review gives an insight of the importance in increasing the knowledge of the health care professionals of the safety and efficacy of psychiatric drug use with herbal medication, at the same time it is also important to provide information to the patients regarding the benefits and contraindications of these herbal remedies when accessed with the other psychiatric medications. 

 

KEYWORDS: Herbal remedies, Psychiatry, Gamma‐aminobutyric acid (GABA), Dopamine (DA), Noradrenalin (NA), Serotonin (5-HT), Central Nervous System (CNS).

 

 


INTRODUCTION:

Psychiatric disorders are one of the most common typical prevalent diseases in our society, and according to World Health Organization it may become a primary cause of affliction in the future even though there is a wide range of psychiatric medications being used, which was not effective with all patients pharmacologically and psychotherapeutically1.

 

 

 

In many countries of the world, natural medicine remains the most available and sometimes the only form of medical care when mental health is concerned. Herbs are concurrently used with prescribed medications by patients worldwide. Studies have shown that many natural herbs was effective as standard psychiatric drugs in clinical trials that was performed in laboratories, even though most clinicians are unaware of their pharmacological mechanisms2.

 

In order to treat and counter mental illness, there were many natural herbs containing vitamins, minerals and antioxidants. Many studies revealed that a range of plant medicines indicated to produce probable efficacy3. Herbal medication remedies may be encountered in order to treat psychiatric problems; that produce improvement in Side effect of the patients mood, thinking, behavior, or that may produce while interacting with psychiatric medications. A national survey conducted, shows that in the 14.5% of respondents who had used complementary and alternative medicine like herbal medications in the past year, 21% who was having one or more psychiatric disorders was compared to 12.8% of respondents or patients who did not acknowledge on herbal medication use4. The increasing engrossment in use of herbal remedies in psychiatric patients has highly demand for psychiatrists and other mental health professionals to become familiar with its influence and effects of more commonly used herbal medication, including their side effects, risks and contraindications5. The recently started neuroscience-based nomenclature (NbN) would be a regional application to herbal medicine in facilitating a better knowledge on the use of herbal medications in psychiatry2.

 

This review utilizes secured and more targeted studies in order to clearly express the evidence and to discuss any key developments in this field3.

 

METHOD:

PubMed was searched for articles related to the herbal remedies used in the psychiatric patients. A secondary search was performed using references obtained from articles published from 2000–2017 identified by the PubMed search, out of the case studies and observational studies so obtained from the PubMed, a total of 10- 15 articles were sorted according to the inclusion criteria. Use of keywords such as herbal medications, psychiatric disorder and drug interaction was found helpful during the PubMed search. Articles focusing on the experimental trails in adults and those patients who were not on medication was excluded during the selection process and those articles which aimed in accessing the incidence of drug interaction and possible negative effects due to co-administration of herbal medications with psychiatry drugs was included in this review.

 

REASON FOR THE NEED OF HERBAL MEDICATIONS:

Effective studies have shown that additional alternative treatment with particularized herbal medicine increases antidepressant response and that reduces certain side effects associated with psychotropic medications. Herbal medicines used for the treatment of psychiatric problems was produced safe and effective towards severe depressive episodes, but usage of these herbal drugs in patients with mental illness led to unusual occurrence of physical tiredness, headache, irregular heart rhythm, dry mouth, constipation, and higher prevalence of digestive discomfort in the patients6.


 

LIST OF HERBAL MEDICATIONS THAT WAS USED FOR PSYCHIATRIC CONDITONS:

Table 1: Common Herbal remedies with potential antidepressive effect:

Herbal Name

Herbal preparation -Active

Components

Mechanism of Action (Pre-Clinical Trials)

Antidepressive effect (Clinical Trials)

Hypericum (Hypericum L.)

Hyperforin

Hypericin

Exertion of modification in monoamine transmission –sodium channel get affected Non-selective inhibition of monoamine reuptake, Shows effect on functioning of 5HT1 receptor, Shows efficacy on dopaminergic activity, and Neuroendocrine modulation

In a randomized control trial conducted in >5000 samples showed antidepressive effect than the placebo - when compared to SSRIs

Lavender (Lavandula L.)

Linalool

Linalool acetate

GABA modulation

Unconfirmed (not enough data)

Borage (Borago officinalis, Echium amoenum)

Rosmarinic acid

γ-linoleic acid

impede the 5HT reuptake and Immunomodulation

Unconfirmed (not enough data)

Roseroot (Rhodiola rosea L.)

Salidroside

Tyrosol

Rosavin

Inhibition of monoamine oxidase, Changes in monoamine transmission, Transmission of serotonin get normalised

Unconfirmed (not enough data)

Chamomile (Matricaria chamomilla)

Apigenine

Bisabolol

Variation in GABA acton, Changes in monoamine transmission Neuroendocrine modulation

Unconfirmed (not enough data)

Saffron (Crocus sativus)

Crocin

Crocetin

Safranal

Inhibition of monoamine NA, DA (crocin), Inhibiting the reuptake of 5HT, (safranal) NMDA antagonism, GABAα agonism, activation of BDNF (neurotrophic influence)

In a 2 randomized control trial conducted in 80 samples (placebo) and other 4 Randomised control trial in 154 samples with fluoxetine 20mg or imipramine 100mg – in that case, Saffron shows its effectiveness for mild – moderate depression symptoms

Ginseng (Panax ginseng)

Ginsenosides

Changes in the action of hypothalamic-pituitary axis, variation in action of monoamine (DA and 5HT) transmission, Shows Antioxidant and anti-inflammatory effect, Inhibition of nitric oxide synthase 5HT2A agonist BDNF activation and increase the response to neurogenesis in the hippocampus

Unconfirmed (not enough data)

RCT – randomized controlled clinical trial, DA – dopamine, NA – noradrenalin, 5HT – serotonin, 5HT2A – type 2A serotonin receptor, 5HT1 – type 1 serotonin receptor, NMDA – receptor for glutamate, activated by N-methyl-D-aspartic acid, GABAα – type A GABA receptor, BDNF Brain Derived Neurotrophic Factor SSRI – serotonin reuptake inhibitors, TLPD – tricyclic antidepressants

 


VARIETY OF HERBAL REMEDIES IN THE TREATMENT OF OTHER PSYCHIATRIC DISORDERS:

Hypericum (St John's Wort):

Hypericum is the investigated herbal, that was best recommended for treating depression, by producing antidepressive properties. The hypericum mechanism for antidepressant action was nonselective inhibition of neuronal reuptake of serotonin, dopamine, Gamma‐aminobutyric acid (GABA), norepinephrine and L‐glutamate, decreased loss of neurochemicals and increased binding to various receptors (e.g., GABA, glutamate, and adenosine). Also Hypericum has a less noticeable adverse reactions.

 

An important oblige of hypericum is about its action, hypercium at high doses may activate CYP3A and p-glycoprotein induction. In case of using more than 1 medication, it mainly produce a decrease in serum levels of innumerable agents, such as oral contraceptives, digoxin or warfarin. And regarding xenobiotics, the metabolism and elimination may get increased. Hypericum preparations interact with countless psychotropic drugs like: clomipramine, citalopram, alprazolam, clozapine, diazepam sertindole, aripiprazole, zopiclone. For patients with mild-moderate depression, hypericum extracts of dose 900-1800 mg/daily was used as second line or third-line therapy7.

 

Saffron:

Saffron is a substance procured from saffron crocus (Crocus sativus). Over the last decade there were number of clinical trials in which standardized water-alcohol extract of saffron (saffron 30 mg were contained about 0.6-0.7 mg of safranal) was used in mild-moderate depression subjects.

 

In the initial trials of 6 week on saffron, the extract was obtained from the stigma of the saffron flowers. Nevertheless, it is the petals which are more available and profitable on industrial scale. Preparations that was obtained from stigma and petals of saffron were used in therapies of 2 groups, but it doesn’t shown any differences even after treatment of 6 weeks. In both groups, 18% of subjects were reported under remission, whereas remaining 50% shows significant decrease in psychiatric symptom intensity, and HDRS was observed in 68% of one group (saffron petals) and 77% of the other group (stigmas).

And the results of many recently conducted randomized, double-blinded, clinical trial that comparing the safety and efficacy of saffron 30 mg/day with other antidepressant like fluoxetine 40mg/d for improving depressive symptoms in post percutaneous coronary intervention patients. Saffron extract capsules of 15 mg were standardized to 0.13–0.15 mg of safranal and 1.65–1.75 mg of crocin. and that preparations was used in studies. The efficacy and tolerance of antidepressant were similar in short term therapy. These study results are useful with regard to saffron’s potential effect, greatest approval and its cardioprotective properties8.

 

All the above trials were of good quality, with a score of 4 or 5 on the 5-point Jadad scale. Modabbernia etal, conducted a study on use of saffron extract, in male patients with sexual dysfunctions developed due to the use of fluoxetine. In that case saffron shows a great advancement in decreased sexual dysfunction that caused by fluoxetine9.

 

Curcuma Longa (Turmeric):

The main active integral component of turmeric is curcumin, which have many actions like anti inflammatory, antioxidant, neuroprotective, and monoaminergic modulatory activities (He etal., Kunnumakkara etal)10 Berk et al11 conducted a study states that turmeric has an potential anti‐inflammatory effect, and there by it produces effectiveness against inflammation as being increased causative factor in many people suffering from depression. Yu, Pei et al12 conducted a 6week randomized control trials including 108 adults (males) in China, they were tested with 1,000 mg of curcumin daily versus placebo as an augmentation to escitalopram. And the study result shows, a significant depletion of depression on the Hamilton Depression Rating Scale (HAM‐D) and the Montgomery–Asberg Depression Rating Scale (MADRS) to be replaced by turmeric outperforming placebo. The fact that curcumin reduced inflammatory cytokines (interleukin‐1β and tumour necrosis factor‐α) and salivary cortisol concentrations remains interesting, while increasing plasma brain‐derived neurotrophic factor levels, compared with placebo.

 

Lavender:

Many recently conducted clinical trials were evaluated the antidepressive effect of lavender alcohol solution, which uses lavender tincture and imipramine as single therapy or lavender tincture combined with imipramine. The suggested synergistic effect may depend on the hypothesized effect of lavender on the GAGAergic system and its anxiolytic effect. And the study imprints no specific drug interactions13.

 

Borage:

In the pre-clinical trials conducted, were shown that the borage extract has a similar effect to that of serotonin reuptake inhibitors. In a small (n=35) randomized placebo-controlled trial of 4 weeks using borage as treatment option, there were a notable improvement in patients with depressive symptoms.

 

Borage oil is a source of gamma-linolenic acid and it was used in the treatment of atopic dermatitis and rheumatic disease. A case report on female subjects with staticus epilepticus, who were recommended to receive high doses of borage oil for a week, was shown a greater response to the borage treatment. But, the use of borage as treatment option for depression would require further more studies, but according to some study researchers it was shown that, in its high dose it was not recommendable due to its potential issues like toxicity14.

 

Roseroot (Arctic Root):

It was derived from Rhodiola rosea. In comparison with placebo, the effectiveness of two doses like 340 mg and 680 mg of roseroot extract was evaluated. Eighty nine patients exhibiting with depression symptoms were included in this six-week randomized trial, and when assessed by using Hamilton scale, there were only a slight effect on depression symptoms. And the tolerance of the treatment was good.

 

Roseroot has no addictive potential effects, but have good tolerance. And there were no serious adverse reactions reported in any of the studies. The possible adverse effects of Rhodiola rosea at its high dose include insomnia, irritability, vivid dreams, headaches, and a decrease in platelet aggregation.

 

In the in vivo studies conducted, Rose root were not shown any influence on CYP enzymes. The doses used in the trials were ranged from 50 mg to 1500mg daily. In clinical trials showing positive results, incase of mental fatigue, the doses of 100-600mg were used and for physical fatigue they used dose 200-700 mg daily. The roseroot extract should be taken on empty stomach, due to its one of the adverse effect like insomnia, it should not be taken late in the evenings. Also it was revealed that the roseroot extract may binds to estrogen receptor in the body. Thus, it should not be used by women with a family history of breast cancer15,16.

 

 

Chamomile:

Chamomile extract of 220mg-1100mg (standardised to 1.2% apigenine) in comparison to placebo after 8 weeks of treatment, Chamomile exhibits an anxiolytic effect. And It is a promising plant-derived medicine.

 

Many trials revealed that, not only an anxiolytic effect of the chamomile extract, but also it has an antidepressive effect. In most cases, chamomile is well tolerable in many conditons. The possible interaction of chamomile was with warfarin, statins and oral contraceptives. Due to chamomile anxiolytic effect, that may escalates the activity of benzodiazepines17.

 

Ginseng:

Many conventional medicines of ginseng preparations exhibits a stimulating effect. In an 8-week clinical trial conducted by Reay et al, including both young and healthy subjects found that, ginseng of 400mg/day when compared with placebo, it has a significant influence on the its reaction time. And the most possible adverse reactions include insomnia, anxiety, agitation, gastro-intestinal disorders.

 

Also, the decreased platelet aggregation was reported in the above study, which produces a higher risk of bleeding in subjects administered with anticoagulants. The other reported problem of ginseng was reduction in glycemic level, and at its high doses it may affect CYP3A4 activity and also inhibit p-glycoprotein activity. It was also reported that ginseng reduces the analgesic effect of morphine18.

 

Kava:

The kava shrub (Piper methysticum) is native to Polynesia and the Pacific Islands. According to Kava, its medicinal properties were more seen either in ethanol-water or acetone-water extracts, and it was one of the main herbal preparation with pharmacologically active ingredient.

 

One of the study, manifest that the medicinal effects of kava are due to the kavapyrones, mostly in animal models it exhibits its action like muscle relaxants and anticonvulsants, protection against strychnine poisoning and also reduces limbic system excitability. Also it includes variety of actions involving inhibition of voltage-dependent sodium channels, increasing GABA-A receptor densities, blocking norepinephrine reuptake, and suppressing the release of glutamate19.

 

And in many studies they has selected small sample sizes and were of short duration. In addition to kava extracts anxiolytic properties, when kava extract ranging from 100 to 210 mg dosages, It has been associated with few adverse effects. In studies, effectiveness of kava along with oxazepam, kava appears not to show any adverse effect on cognitive functioning, mental acuity, or coordination, although slight morning tiredness and reduced reactivity while driving have been reported, as has ataxia.

 

In rare cases, treatment on kava may lead to some allergic reactions, yellowing or scaling of the skin, gastrointestinal complaints, pupil dilation, and blurred vision. Treatment on Kava extract during pregnancy and lactation time may contraindicated. Kava elevates the effects of alcohol, benzodiazepines, and other sedative-hypnotic agents through additive effects. Patients taking benzodiazepines should be advised not to take kava20,21.

 

Ginkgo:

Ginkgo trees (Ginkgo biloba) are native to East Asia and are grown ornamentally in Europe and North America. A standardized commercial preparation of Ginkgo contains, the active components flavone glycosides (24%) and terpenoids (6%). The extracts most commonly used therapeutically are designated as EGb 761(Extract of Ginkgo Biloba) and LI 1370.

 

A review by Kleijnen and Knipschild of more than 40 controlled trials of gingko showed that all but one found clinically significant improvement in symptoms such as memory loss, concentration difficulties, fatigue, anxiety, and depressed mood22.

 

Ginkgo extracts contain a huge number of substances that have been found to have a variety of pharmacological effects. The ginkgo flavonoids are thought to be antioxidants, and the ginkgolides, especially ginkgolide B, inhibit platelet-activating factor. There is also evidence that ginkgo extracts can improve vascular perfusion by modulating vessel wall tone. Side effects from ginkgo are relatively uncommon but include headache, gastrointestinal upset, and allergic skin reactions. Rarely, ginkgo preparations have been associated with cerebral hemorrhage. The safety of ginkgo in pregnancy or lactation has not been established. Because ginkgolide B is a potent inhibitor of platelet-activating factor, ginkgo extracts have the potential to interact with platelet-antiaggregating and antithrombolytic therapies. In addition, patients who consume alcohol or who have other risk factors for hemorrhagic stroke should be used with caution23.

 

Valerian:

Around 250 different species of valerian were existing. The one used most commonly for medicinal purposes (Valeriana officinalis) is a eternal and it was seen in areas of Europe and Asia. Also the valerian root has differently utilized to make tea, by adding 3 to 5 g of dried valerian root to boiling water and made to strain after 10 to 15 minutes. In addition, a variety of extracts and tinctures have been prepared, with considerable differences in composition between the aqueous and ethanol extracts. Valerenic acids have sedative and anticonvulsant effects, and valerian extracts have been demonstrated to have a variety of effects on GABAergic neurons, including increased release of GABA, decreased GABA reuptake, and decreased GABA degradation.

 

Adverse effects of valerian preparations are rare but may include GI upset, contact allergies or dermatitis, headache, restlessness, sleep deprivaton and mydriasis. Incase of overdosing of valerian extract, it appears to be safe. Currently, there were only less information on safety of valerian extract during pregnancy and lactation. The major drug interactions of valerian are with other sedative-hypnotics. The sedative effects of valerian may synergize the effects of other CNS depressants24.

 

Bacopa monniera (Brahmi):

Usually, Brahmi was used for cognitive enhancing activity, and already it has its own traditional medicinal use in treating anxiety and insomnia and even it has been put forth in past years for the outdated diagnosis of “insanity.” Preclinical research has signified that various CNS actions including antidepressant, anxiolytic, and antioxidant effects. Neurologically enrapt preclinical studies has shown that Brahmi regulate acetylcholine, dopamine, serotonin, and noradrenalin pathways (Charles et al)25 and in the hippocampus, it increases the activity of protein kinase (Singh et al)26. And the key chemical constituent is considered as bacoside A. And in the other Double‐Blind Randomized control trial conducted by Stough et al, after 12 weeks of treatment they assessed Brahmi’s effect on anxiety, by taking 300mg of brahmi, it shows great effect against anxiety symptoms when compared with placebo27.

 

Melissa officinalis (Lemon Balm):

Lemon balm (Melissa officinalis) has been used as a enhancement and refreshment in mood and control in cognitive function, with anxiolytic. Also it has an traditional medicinal effect like mild sedative and as spasmolytic agent. In many vitro studies it has been revealed that anxiolytic activity is due to its effects on GABA receptor, by inhibiting GABA transaminase, elevation of GABA levels was achieved. Andrew S et al 28 conducted a study on 17 female and 8 male patients, and the study shows that Lemon balm delivered in foodstuffs shows positive behavioural effects like enhancement in mood and cognitive performance which may be used in applied health settings.

 

Withania somnifera (Ashwagandha):

Ashwagandha is used for many kinds of diseases processes and specially it act as an nervine tonic. It has GABA mimetic effect and also useful in promoting formation of dendrites. It has an anxiolytic effect, anti-inflammatory and anti-arthritic agent. Besides that it enhance or boost energy levels and mitochondrial health and also promote memory. Chandrasekhar K et al29 conducted a study on 64 subjects (41 male, and 23 female) who were under severe stress and anxiety. And the study endorse to use high-concentrated Ashwagandha root extract inorder to improves an individual's stressful mind and as a result it improves self-evaluated quality of life.

 

Passion Flower:

Passiflora incarnata (Purple Passion flower) is originated naturally in areas of American vine with white and blue or purple flowers and an edible fruit. It has its medicinal effect for insomnia and anxiety.

 

Elsasa M et al30 conducted a randomized control trial, in this study they produced five different extracts from fresh or dried Passiflora herb. Extract PAS 1, whereas extracts PAS 4, 5, 7 and 8 were extracted. Two of the extracts, PAS4 and PAS5, reduced the frequency and severity of pentylenetetrazol (PTZ) induced seizures. Unexpectedly, all of the Passiflora extracts increased anxiety levels when compared to control.

 

CONCLUSION:

In spite of the fact that, authentication in the safe and efficacy of herbal remedy preparations in treating psychiatric diseases is been progressing day by day, sufficient information’s regarding the negative reactions of these herbal medication is being lacking. The extent of utilization of herbal medications for mental disorders shows that psychiatrists should become more aware about developments in this area and increase their knowledge on the herbal remedies commonly used in the psychiatric patients.

 

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Received on 27.01.2019           Modified on 28.02.2019

Accepted on 29.03.2019         © RJPT All right reserved

Research J. Pharm. and Tech. 2019; 12(7):3151-3156.

DOI: 10.5958/0974-360X.2019.00531.6