1. Introduction
Anxiety, fear and worry are all completely natural human feelings. If these feelings occur and endure for an extended period, it affects both physical and mental health. This leads to clinical anxiety disorders. There are many types of treatment available to treat anxiety disorders. This article outlines more common herbal remedies to treat anxiety disorders.
Anxiety is an aversive emotional state, in which the feeling of fear is disproportionate to the threat (Weinberger, 2001). Anxiety is implicated in a number of psychiatric disorders, such as depression, panic attacks, phobias, generalized anxiety disorder, obsessive-compulsive disorder and post-traumatic stress disorder (Gross and Hen, 2004). Anxiety disorders are the most common class of neuropsychiatric disorders in USA (Kessler et al., 2005) and many other countries (Alonso and Lepine, 2007). The life time prevalence of panic attacks (a form of anxiety disorder) is around 7-9% in most countries and 1% alone in India with the prevalence of generalized anxiety disorder is very high i.e. 8.5% in the general population (WHO, 2001). Anxiety disorders affect 16.6% of population worldwide (Somers et al., 2006) and numerous efforts have been made to understand the pathophysiology of the disease and treatments.
According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR), anxiety is characterized by a feeling of persistent worry that hinders an individual’s ability to relax [Diagnostic and Statistical Manual of Mental Disorders Washington D.C.: American Psychiatric Association, 4 2000]. Anxiety disorders are described and classified in DSM and several anxiety disorders share common clinical symptoms such as widespread anxiety, physiological anxiety symptoms, and behavioral disturbances.
2. Common anxiety disorders
2.1. Generalized anxiety disorders (GAD)
Generalized anxiety disorder is a syndrome of ongoing anxiety and worry about many events or feelings that the patient generally recognizes as extreme and inappropriate (DSM-IV-TR). Individuals manifest both physical and psychological symptoms leading to significant distress or impairment.
2.2. Obsessive-compulsive disorder (OCD)
People suffering from OCD tend to have bothersome and intrusive thoughts that generate anxiety (obsession) and perform repetitive actions (compulsion). Obsessions include unwanted thoughts, impulses, or images that cause great anxiety. Compulsions include repetitive behaviors or mental acts that those affected feel driven to perform.
2.3. Panic disorder
People suffering from panic disorders often have panic attacks, defined as discrete periods of sudden symptom onset usually peaking in 10 minutes and can occur with most anxiety disorders.
2.4. Post-traumatic stress disorder (PTSD)
Individuals with PTSD avoid stimuli associated with the trauma and feel an extreme amount of fear and anxiety after presenting stimuli. Stress is a condition which affects physiological and psychological homeostasis. Evidence indicates that chronic repeated stress precipitates neuropsychiatric disorders like anxiety and depression (Holsboer, 1988; Mc Ewen and Stellar, 1993; Mc Ewen, 2000; Vyas et al., 2002; Veena et al., 2009b; 2011 ). Previous work in an animal model of stress revealed that chronic stress impairs learning in the T-maze (Sunanda et al., 2000a) and radial arm maze (Srikumar et al., 2006; 2007; Veena et al., 2009a) tasks in addition to inducing anxiety-like behavior (Adamec et al., 1999; Vyas et al., 2002; Govindarajan et al., 2006). Stress-induced behavioral impairments are associated with structural (Ramkumar et al., 2008; Shankaranarayana Rao et al., 2001; Shankaranarayana Rao & Raju, 2004; 2005; 2007), biochemical (Sunanda et al., 2000b), molecular (Bennur et al., 2007; Pawlak et al., 2005; Veena et al., 2011 ) and electrophysiological (Hegde et al., 2008) alterations in the hippocampus and amygdala regions. Recent studies have clearly demonstrated the abnormal synaptic plasticity is responsible for cognitive deficits including enhanced anxiety in fragile X mental retardation and autism (Dolen et al., 2007; Hayashi et al., 2007). Induction of progressive plasticity is known to be responsible for amelioration of stress-induced cognitive deficits and depression-like behavior by enriched environment and brain stimulation rewarding experience (Asha Devi et al., 2011; Ramkumar et al., 2008; Shankaranarayana Rao, 2009; 2010; Veena et al., 2009a).
Anxiety and other psychiatric conditions are one of the most frequent conditions seen by clinicians and often require long-term treatment with medications. Selective serotonin reuptake inhibitor (SSRI) and benzodiazepines are important class of drugs used to treat generalized anxiety disorders (Davidson, 2001; Davidson, 2009) and depression (Bhagya et al., 2008; Bhagya et al., 2011). With the increasing cost of anti-anxiety medications and their increased side effects like suicidal ideation, decreased alertness, sexual dysfunction and dependency (Hu et al., 2004; Gunnell et al., 2005; O'brien, 2005; Lader et al., 2009), drugs of natural origin are promising alternatives to treat neuropsychiatric disorders (Kienzle-Horn, 2002; Carlini, 2003).
3. Common herbal remedies for anxiety
Ayurveda, the Indian traditional system of medicine uses herbs and their preparations to treat various neuropsychiatric disorders. Numerous herbs have been used for centuries in folk and other traditional medicine to calm the mind and positively enhance mood. Herbal medicine which plays an important role in developing countries, are once again becoming popular throughout developing and developed countries. Study by Sparreboom et al. (2004) revealed that use of herbal medicine is increasing enormously in the Western world. In spite of the large number of animal studies evaluating the potential anxiolytic effects of plant extracts, very few controlled studies have been conducted in a clinical setup. The efficacy and safety of utilizing these natural drugs to treat anxiety, has only just begun to be exactly tested in clinical trials within the last 10 to 15 years (Saeed et al., 2007; Garcia-Garcia et al., 2008; Kinrys et al., 2009). For instance, both Kava-kava (
3.1. Passion flower
3.2. Kava kava (Piper methysticum )
There is substantial evidence that kava has a positive effect on the symptoms of anxiety disorders. Animal studies have demonstrated anti-anxiety activity of kava (Garrett et al., 2003; Bruner and Anderson, 2009). Several randomized double-blind clinical studies in GAD patients showed beneficial effect of kava-kava in reducing anxiety (Watkins et al., 2001; Connor and Davidson, 2002; Boerner et al., 2003; Sarris et al., 2009). Kava-kava was used in numerous controlled clinical studies to treat anxiety disorders, but the subjects included in these studies were heterogeneous i.e., they were diagnosed with agoraphobia, specific phobia, social phobia, adjustment disorder with anxiety (Volz and Kieser, 1997; Malsch and Kieser, 2001; Gastpar and Klimm, 2003; Lehrl, 2004). In the study by Connor & Davidson, kava extract was compared with placebo in GAD patients (2002). In another 8-week randomized, double-blind multi-center clinical trial, the efficacy of
3.3. St. John’s wort (Hypericum perforatum )
St. John’s wort is a popular supplement for treating depression but is much less popular for treating anxiety disorders. Studies conducted by Flausino et al. and Singewald et al. have shown that chronic administration of
Studies specifically testing the effects of St. John’s wort on patients with anxiety are extremely limited. The evidence of positive effects of St. John’s wort on anxiety disorders is weak. No placebo-controlled, randomized, double-blind trials have shown St. John’s wort to be effective in treating generalized anxiety disorder, post-traumatic stress disorder, obsessive-compulsive disorder (OCD), or phobias. Volz et al. (2002) showed that Hypericum extract to 149 out patients diagnosed with somatization disorder, undifferentiated somatoform disorder, or somatoform autonomic dysfunctions, significantly reduced anxiety scores in HAMA scale. Another open-label uncontrolled observation with 500 subjects showed beneficial effect of St. John’s wort extract in reducing anxiety disorder symptoms in patients diagnosed with depression comorbid with anxiety (Muller et al., 2003). However, stronger evidence is needed before St. John’s wort should be considered as a treatment option for patients with diagnosable anxiety disorders.
3.4. Valeriana officinalis
Valerian is one of the most popularly used herbal medicines for insomnia (Donath et al., 2000) and is also used to treat anxiety. Hydroalcoholic and aqueous extracts of valerian roots have shown affinity for the GABA-A receptor in the brains of rats (Benke et al., 2009). In humans, valerian has been successful in the treatment of insomnia and tension (Schmidt-Voigt, 1986; Vorbach, 1996; Leathwood, 1985; Donath et al., 2000; Stevinson and Ernst, 2000; Ziegler, 2002). Andreatini et al. (2002) compared the extract of
3.5. Ginkgo biloba
Extract of
3.6. Galphimia glauca
3.7. Matricaria recutita (chamomile)
Chamomile is one of the most popular single ingredient of herbal teas, or tisanes. Chamomile tea, brewed from dried flower heads is used traditionally for several medicinal purposes like gastrointestinal tract ailments. Other uses include allergic rhinitis, attention deficit-hyperactivity disorder (ADHD), restlessness, insomnia, dysmenorrhea, mastitis and varicose ulcers. Chamomile contains flavonoids, which exert benzodiazepine-like activity (Avallone et al., 2000) and also has a phosphodiesterase inhibitory action, which leads to increased cAMP levels (Kuppusamy and Das, 1992). A recent study evaluated the efficacy of a standardized extract of
3.8. Astragalus membranaceus
4. Indian traditional herbs
4.1. Centella asiatica (Mandookaparni or Gotu Kola)
4.2. Bacopa monnieri (Brahmi)
In Indian traditional medicine, several herbs have been used as nerve tonics. The most popular of these herbs is
Previous clinical study demonstrated that administration of
4.3. Withania somnifera (ashwagandha)
This has been an important herb in use within Ayurvedic and indigenous medical systems for over 3000 years. Both preclinical and clinical studies demonstrate the use of
5. Polyherbal formulations
In Ayurveda, compound formulations are generally used in the therapy as the combination of many drugs provides a synergistic therapeutic effect and also includes ingredients which help to minimize the adverse effects of few other major drugs. A recent study demonstrated adaptogenic potential of a compound natural health product which had
Mentat (BR-16A) is an herbal medication contains 20 different ingredients. The main herbs present in the mentat are
Agrawal et al. (1990a,b) reported that BR-16A improves memory parameters and decreases anxiety parameters in normal volunteers. Also, mentat (BR-16) brought about marked improvement in memory in all age groups and caused decrease in anxiety level and neuroticism index (Agrawal et al., 1991). Mentat in the form of syrup was given to patients of anxiety neurosis and depression in a placebo controlled study. Both anxiety and depressive patients showed memory impairment and also increased fatiguability. 3 month treatment with Mentat improved memory and decreased fatiguability in these patients (Sharma et al., 1990). Psychological problems like stress, anxiety and depression play an important role in the prognosis, quality of life as well as the survival rate of cancer patients. Treatment with mentat in cancer patients reduced stress, anxiety and depressive symptoms (Durgesh Kumar, 2000).
Another polyherbal formulation Geriforte showed significant anxiolytic effect in clinical studies. Geriforte contains Chyavanprash concentrate and the extracts of
Another common polyherbal formulation Euphytose, which is a combination of six extracts: Crataegus, Ballota, Passiflora and Valeriana, which have mild sedative effects, and Cola and Paullinia, which mainly act as mild stimulants. Euphytose reduced HAMA scores in outpatients with adjustment disorder with anxious mood in multicenter, double-blind, placebo-controlled study (Bourin et al., 1997).
Recent preclinical studies have shown anxiolytic activity of several herbal drugs.
Our own studies have demonstrated the role of different herbs and herbal formulations namely
6. Conclusion
Despite a large number of animal studies evaluating the potential anxiolytic effects of herbal drugs, very few controlled clinical studies have been conducted. These studies have methodological problems like small number of subjects, lack of placebo and control groups, and inclusion of heterogeneous subjects and short treatment duration, which hinders consistent conclusion about these herbal preparations. Some herbs like kava-kava, gingko showed promising results with substantial clinical significance when compared with benzodiazepines, buspirone and antidepressants. Although evidence of effectiveness of herbs and their preparations in treating neuropsychiatric disorders is increasing, translating these results to treat patients effectively is slowed down by the limited knowledge regarding chemical composition of the products, lack of standardization of these preparations and the paucity of well controlled studies. Preliminary evidence suggests that herbal medicines may have a role in the treatment of anxiety disorders and warrants further research. However, we would like to clearly warn that most of the remedies are not approved for clinical use and herbal remedies are not solely alternatives of clinical treatment regimens. Also some of the herbal remedies may interact with other medicines leading to drug-drug interactions, which may cause severe side effects and in some cases it may be fatal. Accordingly, it is advised to use herbal drugs under strict supervision of qualified ayurvedic physicians with periodic follow-ups.
Acknowledgments
We acknowledge the financial support from the Council of Scientific and Industrial Research (CSIR), New Delhi, India through a Senior Research Associate fellowship to BV, Research grants from Department of Biotechnology (DBT) and Department of Science and Technology (DST), Government of India to BSS, Fondation pour la recherche médicale (FRM) fellowship to BNS.
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