H E R BA L S A N D N U T R I T I O N A L S U P P L E M E N T S
Psychophytomedicine An Overview of Clinical Efficacy and Phytopharmacology for Treatment of Depression, Anxiety and Insomnia ■
Stephanie Maxine Ross, MH, MS, HT, CNC, PDMT Holist Nurs Pract 2014;28(4):275–280
The World Health Organization low energy, and poor concentration, estimates that by the year 2020, to the more severe clinical major The role of depression will account for the depressive disorder that involves phytomedicines second greatest increase in morbidity feelings of deep despair that lead in the treatment following cardiovascular disease, to thoughts of suicide.3 The Centers of various for Disease Control and Prevention’s presenting a significant psychological 1 National Center for Health Statistics socioeconomic burden. disorders In the Global Burden of Disease reports that 11% of Americans continues to Study 2010, depressive disorders have 12 years or older take antidepressant demonstrate been identified as the second leading drugs, including many (>68%) who clinical evidence. cause of disability worldwide and that have not seen a mental health care major depressive disorder is a major professional in the past year. contributor to the burden of suicide Furthermore, this report indicates that antidepressant and ischemic heart disease.2 Investigators of the drug use in the United States has increased by an Global Burden of Disease Study concluded, astounding rate of 400% since 1988, a paradox in “The findings reinforce the importance of treating itself considering the medical literature continues to depressive disorders as a public-health priority and of document the limitations, adverse effects, and implementing cost-effective interventions to reduce withdrawal symptoms associated with antidepressant their ubiquitous burden.”2 medications, as well as their potential for precipitating Depression is not a singular entity but rather suicidal thoughts and feelings.4,5 Although psychopharmaceutical drugs appear to consists of a spectrum of clinical depression that have an important role in cases of very severe ranges from mild to moderate depression, which is depression, current research has shown that there is characterized by symptoms that include low selflittle evidence that conventional antidepressant drugs worth, depressed moods, disturbed sleep, anxiety, are effective in treating mild to moderate depression. According to a 2010 study that focused on a Author Affiliation: College of Nursing and Health Professions, Drexel, patient-level meta-analysis on antidepressant drug University, Philadelphia, Pennsylvania. effects and depression severity published in the The author has disclosed that she has no significant relationships with, or Journal of the American Medical Association, financial interest in, any commercial companies pertaining to this article. researchers concluded that antidepressant medication Correspondence: Stephanie Maxine Ross, MH, MS HT, CNC, PDMT, may be minimal or nonexistent, on average, in patients Director, Program in Complementary and Integrative Therapies, College 6 of Nursing and Health Professions, Drexel University, 1505 Race St, with mild to moderate depression. Philadelphia, PA19102 ([email protected]). Therefore, an important consideration in the treatment of mild to moderate depression is the DOI: 10.1097/HNP.0000000000000040 275 Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
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tolerability of pharmacological therapy and the benefit to risk factor. The common side effects associated with psychopharmaceutical drugs, including but not limited to dependence and mood alterations, are a realistic concern for patients, especially for those who are within the treatment spectrum of mild to moderate depression where drug treatment therapy offers minimal to zero effectiveness.7 In view of the complexity of mental health disorders, such as depression, anxiety, and insomnia, which are common comorbid psychiatric conditions, it would appear that a holistic treatment model that incorporates a complementary and integrative therapy approach within the framework of conventional health care would most effectively support optimal healing. This concept of an integrative healing model of treatment is evidenced by a growing body of practitioners who support the use of combinations of complementary and integrative therapy modalities such as neurofeedback, neuronutritional science, and psychophytomedicines to enhance the outcomes of treatment in mood disorders.8-10 The role of psychophytomedicines (psychotropic herbal medicines) in the treatment of various psychological disorders has become well established in both scientific and clinical trials, where phytotherapeutic standardized extracts of St John’s wort (SJW), kava, and valerian have demonstrated evidence of efficacy, with few or no adverse effects when used properly in accordance with expert recommendation.
use. Paracelsus (1540 AD), the Swedish physician, extolled Hypericum as a viable treatment option for mental disorders. Today, SJW proprietary, standardized preparations have been shown to be effective and well-tolerated in patients with mild to moderate depression, in well-designed studies for more than 2 decades. St John’s wort standardized extracts are the most frequently prescribed treatments of mild to moderate depression in Germany and are among the top-selling herbal medicines in the United States. Although practitioners predominately use SJW for the treatment of mild to moderate depressive disorders in accordance with modern diagnostic standards, traditional applications also include treatment of vegetative disorders, anxiety, and/or nervous agitation.
Phytochemistry Hypericum extracts are derived from dried aerial plant parts (flowers and stem) that are collected during the flowering season. Although the exact mechanism of action and key chemical constituents involved in SJW antidepressant activity have yet to be elucidated, studies indicate a synergistic effect in achieving clinical outcomes. The phytochemical ingredients known to play a role in antidepressant activity include phloroglucines (hyperforin), naphthodianthrones (hypericin), and flavonoids (quercitrin).12 High-quality SJW extracts are typically standardized to 0.3% hypercin or 2% to 4.5% hyperforin.
Phytopharmacology
PHYTOMEDICINE PROFILE St John’s wort11 Hypericum perforatum L. (Fam: Clusiacea) is a hardy perennial that grows to a height of approximately 2 ft, with erect, woody stems. The leaves are small and ovate and attach directly to the stem (sessile), with characteristic translucent oil glands stippling the leaf surface. The 5-petaled flowers are bright yellow in coloration, with small dark glands situated along the peripheral edges. The entire plant exudes a balsamic aroma. St John’s wort is one of oldest and most thoroughly researched medicinal herbs in Europe. It has been used as a medicine since antiquity, dating back to the ancient Greeks; the Greek physician Hippocrates (400 BC) is one of the first to describe its therapeutic
Antidepressant effects The primary pharmacological application of SJW is for the treatment of mild to moderate depression.13-15 The mechanism of action for SJW antidepressant effects has been observed in both in vitro and in vivo studies and is attributed to a range of mechanisms, including the inhibition of the synaptic uptake of serotonin, dopamine, and norepinephrine, and γ -aminobutyric acid (GABA) reuptake. It also exhibits a decreased degradation of neurochemicals and a sensitization of and increased binding to different receptors, including glutamate, adenosine, and GABA.12,16,17
Research overview The vast amount of clinical research on SJW has been performed on standardized hydroalcoholic extracts,
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Psychophytomedicine
obtained through dried plant parts (flowers or stems). The efficacy and safety of these preparations for mild to moderate depression have been assessed in more than 31 controlled, double-blind studies and 2 open clinical studies involving more than 3900 patients.18 St John’s wort has been shown to be clinically and statistically significant in reducing symptoms of mild to moderate depression and concomitant vegetative symptoms.19 Current research supports the efficacy of standardized SJW extract for the treatment of mild to moderate depression; meta-analysis of clinical trials suggest that SJW extract is significantly more effective than placebo, with at least similar efficacy and better tolerability than standard antidepressant drugs.20
Safety and tolerability In patients affected by mild to moderate depression, the absence of adverse effects is an important factor, since these patients are less likely to accept drugs with undesirable effects than patients with more severe forms of depression.21 Hypericum extracts have shown a favorable tolerability profile and are in general better tolerated than standard antidepressants.22 The efficacy, safety, and tolerability of SJW for the treatment of mild to moderate depression have been well studied. The safety profile of SJW has been shown in a systematic review detailing that the degree of adverse effects in (n = 35 562) pooled patients was 0% to 5.7%, which was comparable with placebo.23 In a 2006 review of 16 postmarketing surveillance studies (n = 34 834), SJW was found to be 10-fold safer than synthetic antidepressants (adverse effects 0.1%-2.4%).24 Adverse events with SJW are rare and involve reversible dermatological and gastrointestinal effects. Although several case studies have reported possible SJW-induced mania and serotonin syndrome, many of these cases detail concomitant use of other medications and/or recreational drugs.23 Therefore, caution should be exercised in patients with a personal or family history of bipolar disorder. Furthermore, SJW should not be used concomitantly with antidepressant drugs.
Potential drug interactions and contraindications The main concern in recommending SJW is its potential for drug interaction. As with synthetic antidepressants, pharmacokinetic interactions may occur on occasion as a result of activity changes of drug-metabolizing and drug-transporting proteins,
277
especially cytochrome P450 3A4 isozyme (CYP3A) pathways and P-glycoprotein drug efflux pump, resulting in reduced drug serum levels. According to researchers, the concerns surrounding herb-drug interactions with SJW focuses on extracts containing higher-dose amounts of hyperforin (>10 mg per day), which is responsible for inducting CYP3A and P-glycoprotein, in comparison with studies using low-dose hyperforin extracts (
Psychophytomedicine An Overview of Clinical Efficacy and Phytopharmacology for Treatment of Depression, Anxiety and Insomnia ■
Stephanie Maxine Ross, MH, MS, HT, CNC, PDMT Holist Nurs Pract 2014;28(4):275–280
The World Health Organization low energy, and poor concentration, estimates that by the year 2020, to the more severe clinical major The role of depression will account for the depressive disorder that involves phytomedicines second greatest increase in morbidity feelings of deep despair that lead in the treatment following cardiovascular disease, to thoughts of suicide.3 The Centers of various for Disease Control and Prevention’s presenting a significant psychological 1 National Center for Health Statistics socioeconomic burden. disorders In the Global Burden of Disease reports that 11% of Americans continues to Study 2010, depressive disorders have 12 years or older take antidepressant demonstrate been identified as the second leading drugs, including many (>68%) who clinical evidence. cause of disability worldwide and that have not seen a mental health care major depressive disorder is a major professional in the past year. contributor to the burden of suicide Furthermore, this report indicates that antidepressant and ischemic heart disease.2 Investigators of the drug use in the United States has increased by an Global Burden of Disease Study concluded, astounding rate of 400% since 1988, a paradox in “The findings reinforce the importance of treating itself considering the medical literature continues to depressive disorders as a public-health priority and of document the limitations, adverse effects, and implementing cost-effective interventions to reduce withdrawal symptoms associated with antidepressant their ubiquitous burden.”2 medications, as well as their potential for precipitating Depression is not a singular entity but rather suicidal thoughts and feelings.4,5 Although psychopharmaceutical drugs appear to consists of a spectrum of clinical depression that have an important role in cases of very severe ranges from mild to moderate depression, which is depression, current research has shown that there is characterized by symptoms that include low selflittle evidence that conventional antidepressant drugs worth, depressed moods, disturbed sleep, anxiety, are effective in treating mild to moderate depression. According to a 2010 study that focused on a Author Affiliation: College of Nursing and Health Professions, Drexel, patient-level meta-analysis on antidepressant drug University, Philadelphia, Pennsylvania. effects and depression severity published in the The author has disclosed that she has no significant relationships with, or Journal of the American Medical Association, financial interest in, any commercial companies pertaining to this article. researchers concluded that antidepressant medication Correspondence: Stephanie Maxine Ross, MH, MS HT, CNC, PDMT, may be minimal or nonexistent, on average, in patients Director, Program in Complementary and Integrative Therapies, College 6 of Nursing and Health Professions, Drexel University, 1505 Race St, with mild to moderate depression. Philadelphia, PA19102 ([email protected]). Therefore, an important consideration in the treatment of mild to moderate depression is the DOI: 10.1097/HNP.0000000000000040 275 Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
276
HOLISTIC NURSING PRACTICE • JULY/AUGUST 2014
tolerability of pharmacological therapy and the benefit to risk factor. The common side effects associated with psychopharmaceutical drugs, including but not limited to dependence and mood alterations, are a realistic concern for patients, especially for those who are within the treatment spectrum of mild to moderate depression where drug treatment therapy offers minimal to zero effectiveness.7 In view of the complexity of mental health disorders, such as depression, anxiety, and insomnia, which are common comorbid psychiatric conditions, it would appear that a holistic treatment model that incorporates a complementary and integrative therapy approach within the framework of conventional health care would most effectively support optimal healing. This concept of an integrative healing model of treatment is evidenced by a growing body of practitioners who support the use of combinations of complementary and integrative therapy modalities such as neurofeedback, neuronutritional science, and psychophytomedicines to enhance the outcomes of treatment in mood disorders.8-10 The role of psychophytomedicines (psychotropic herbal medicines) in the treatment of various psychological disorders has become well established in both scientific and clinical trials, where phytotherapeutic standardized extracts of St John’s wort (SJW), kava, and valerian have demonstrated evidence of efficacy, with few or no adverse effects when used properly in accordance with expert recommendation.
use. Paracelsus (1540 AD), the Swedish physician, extolled Hypericum as a viable treatment option for mental disorders. Today, SJW proprietary, standardized preparations have been shown to be effective and well-tolerated in patients with mild to moderate depression, in well-designed studies for more than 2 decades. St John’s wort standardized extracts are the most frequently prescribed treatments of mild to moderate depression in Germany and are among the top-selling herbal medicines in the United States. Although practitioners predominately use SJW for the treatment of mild to moderate depressive disorders in accordance with modern diagnostic standards, traditional applications also include treatment of vegetative disorders, anxiety, and/or nervous agitation.
Phytochemistry Hypericum extracts are derived from dried aerial plant parts (flowers and stem) that are collected during the flowering season. Although the exact mechanism of action and key chemical constituents involved in SJW antidepressant activity have yet to be elucidated, studies indicate a synergistic effect in achieving clinical outcomes. The phytochemical ingredients known to play a role in antidepressant activity include phloroglucines (hyperforin), naphthodianthrones (hypericin), and flavonoids (quercitrin).12 High-quality SJW extracts are typically standardized to 0.3% hypercin or 2% to 4.5% hyperforin.
Phytopharmacology
PHYTOMEDICINE PROFILE St John’s wort11 Hypericum perforatum L. (Fam: Clusiacea) is a hardy perennial that grows to a height of approximately 2 ft, with erect, woody stems. The leaves are small and ovate and attach directly to the stem (sessile), with characteristic translucent oil glands stippling the leaf surface. The 5-petaled flowers are bright yellow in coloration, with small dark glands situated along the peripheral edges. The entire plant exudes a balsamic aroma. St John’s wort is one of oldest and most thoroughly researched medicinal herbs in Europe. It has been used as a medicine since antiquity, dating back to the ancient Greeks; the Greek physician Hippocrates (400 BC) is one of the first to describe its therapeutic
Antidepressant effects The primary pharmacological application of SJW is for the treatment of mild to moderate depression.13-15 The mechanism of action for SJW antidepressant effects has been observed in both in vitro and in vivo studies and is attributed to a range of mechanisms, including the inhibition of the synaptic uptake of serotonin, dopamine, and norepinephrine, and γ -aminobutyric acid (GABA) reuptake. It also exhibits a decreased degradation of neurochemicals and a sensitization of and increased binding to different receptors, including glutamate, adenosine, and GABA.12,16,17
Research overview The vast amount of clinical research on SJW has been performed on standardized hydroalcoholic extracts,
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Psychophytomedicine
obtained through dried plant parts (flowers or stems). The efficacy and safety of these preparations for mild to moderate depression have been assessed in more than 31 controlled, double-blind studies and 2 open clinical studies involving more than 3900 patients.18 St John’s wort has been shown to be clinically and statistically significant in reducing symptoms of mild to moderate depression and concomitant vegetative symptoms.19 Current research supports the efficacy of standardized SJW extract for the treatment of mild to moderate depression; meta-analysis of clinical trials suggest that SJW extract is significantly more effective than placebo, with at least similar efficacy and better tolerability than standard antidepressant drugs.20
Safety and tolerability In patients affected by mild to moderate depression, the absence of adverse effects is an important factor, since these patients are less likely to accept drugs with undesirable effects than patients with more severe forms of depression.21 Hypericum extracts have shown a favorable tolerability profile and are in general better tolerated than standard antidepressants.22 The efficacy, safety, and tolerability of SJW for the treatment of mild to moderate depression have been well studied. The safety profile of SJW has been shown in a systematic review detailing that the degree of adverse effects in (n = 35 562) pooled patients was 0% to 5.7%, which was comparable with placebo.23 In a 2006 review of 16 postmarketing surveillance studies (n = 34 834), SJW was found to be 10-fold safer than synthetic antidepressants (adverse effects 0.1%-2.4%).24 Adverse events with SJW are rare and involve reversible dermatological and gastrointestinal effects. Although several case studies have reported possible SJW-induced mania and serotonin syndrome, many of these cases detail concomitant use of other medications and/or recreational drugs.23 Therefore, caution should be exercised in patients with a personal or family history of bipolar disorder. Furthermore, SJW should not be used concomitantly with antidepressant drugs.
Potential drug interactions and contraindications The main concern in recommending SJW is its potential for drug interaction. As with synthetic antidepressants, pharmacokinetic interactions may occur on occasion as a result of activity changes of drug-metabolizing and drug-transporting proteins,
277
especially cytochrome P450 3A4 isozyme (CYP3A) pathways and P-glycoprotein drug efflux pump, resulting in reduced drug serum levels. According to researchers, the concerns surrounding herb-drug interactions with SJW focuses on extracts containing higher-dose amounts of hyperforin (>10 mg per day), which is responsible for inducting CYP3A and P-glycoprotein, in comparison with studies using low-dose hyperforin extracts (
