THE JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE Volume 0, Number 0, 2014, pp. 1–2 ª Mary Ann Liebert, Inc. DOI: 10.1089/acm.2013.0216
Commentary
Use of St. John’s Wort in Potentially Dangerous Combinations Scott A. Davis, MA,1 Steven R. Feldman, MD, PhD,1,2,3 and Sarah L. Taylor, MD1
Abstract
Objectives: The objective of this study was to assess how often St. John’s wort (SJW) is prescribed with medications that may interact dangerously with it. Design: The study design was a retrospective analysis of nationally representative data from the National Ambulatory Medical Care Survey. Settings: The study setting was U.S. nonfederal outpatient physician offices. Subjects: Those prescribed SJW between 1993 and 2010 were the subjects. Outcome Measures: The outcome measures were medications co-prescribed with SJW. Results: Twenty-eight percent (28%) of SJW visits involved a drug that has potentially dangerous interaction with SJW. These included selective serotonin reuptake inhibitors, benzodiazepines, warfarin, statins, verapamil, digoxin, and oral contraceptives. Conclusions: SJW is frequently used in potentially dangerous combinations. Physicians should be aware of these common interactions and warn patients appropriately.
cations co-prescribed with SJW were tabulated and their frequencies were assessed. All data analysis was performed using SAS 9.2 (SAS Institute, Cary, NC), and the study was declared exempt by the Wake Forest University Institutional Review Board.
Introduction
S
t. John’s wort (SJW) is the leading complementary and alternative medicine (CAM) treatment for depression and related psychiatric disorders in the United States. Like many other CAM treatments, SJW interacts dangerously with other common medications. Prescription of SJW with oral contraceptives, blood thinners, benzodiazepines, cancer chemotherapy medicines, digoxin, human immunodeficiency virus medicines, statins, immunosuppressants, selective serotonin reuptake inhibitors (SSRIs), or verapamil is not recommended due to potential interactions.1–3 SJW can reduce the concentration of most of these drugs in the body, resulting in impaired efficacy and treatment failure.2,3 However, with antidepressants such as SSRIs, serotonin syndrome (with possible mania) is the main concern.2 The purpose of this study is to assess how often SJW is being prescribed or taken with these other medications.
Results
SJW was mentioned in 2,230,000 visits (120,000 visits/ year). On average, visits mentioning SJW had 3.1 other drugs mentioned. Of the visits at which SJW was listed, 28% (620,000 visits over the 18-year study period) also listed a drug that is unsafe to use with SJW. Leading medications that could interact with SJW and that were listed at SJW visits included SSRIs (13.7%), benzodiazepines (9.8%), warfarin (4.2%), statins (3.3%), verapamil (1.0%), digoxin (1.0%), and oral contraceptives (0.6%, Table 1).
Materials and Methods
Discussion
The National Center for Health Statistics conducts the National Ambulatory Medical Care Survey (NAMCS) annually to characterize the provision of ambulatory medical care in the United States. We searched the 1993–2010 NAMCS for visits that mentioned SJW. Additional medi-
Frequent use of SJW in potentially harmful combinations was observed. These interactions are likely to lead to harmful consequences such as serotonin syndrome, heart disease due to impaired efficacy of antihypertensives, or unplanned pregnancy due to contraceptive failure. Patients
Center for Dermatology Research, Departments of 1Dermatology, 2Pathology, and 3Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC.
1
2
DAVIS ET AL.
Table 1. Leading Classes of Drugs that Interact Dangerously with SJW Were SSRIs and Benzodiazepines Medication or medication class SSRIs Benzodiazepines Warfarin Statins Verapamil Digoxin Oral contraceptives All medications that interact with SJW
Visits co-prescribed with SJW
Percentage of SJW visits in which drug co-prescribed
310,000 220,000 90,000 70,000 20,000 20,000 10,000 620,000
13.7 9.8 4.2 3.3 1.0 1.0 0.6 27.8
Totals may not add exactly because some patients received more than one of the medication classes. SJW, St. John’s wort; SSRIs, selective serotonin reuptake inhibitors.
may have a false sense of safety with so-called ‘‘natural’’ treatments like SJW. Particularly for patients who are taking many other medications, SJW may be no safer than standard allopathic treatments. Limitations of the study include the fact that only medications recorded by the physician could be analyzed. Patients who were using SJW or other therapies that interact with it, but did not inform their physician fully, would not be included, so this study may actually underestimate the rate of SJW interactions. It is crucial for physicians to know the dangers of ‘‘natural’’ treatments and to communicate the risks to patients effectively.4,5 In addition, labeling requirements for herbal supplements such as SJW need to provide appropriate cautions and risk information.4 Physicians also need to be trained to always ask, in a nonjudgmental and understanding manner, whether the patient is taking any supplements, vitamins, minerals, or herbs. Particularly before prescribing any of the common drugs that might interact with SJW, clinicians should be sure they have determined whether patients are using this very popular CAM treatment.
Disclosure Statement
The Center for Dermatology Research is supported by an unrestricted educational grant from Galderma Laboratories, L.P. Dr. Feldman is a consultant and speaker for Galderma, Connetics, Abbott Labs, Warner Chilcott, Centocor, Amgen, Photomedex, Genentech, BiogenIdec, and Bristol Myers Squibb. Dr. Feldman has received grants from Galderma, Astellas, Abbott Labs, Warner Chilcott, Janssen, Amgen, Photomedex, Genentech, BiogenIdec, Coria/Valeant, Pharmaderm, Ortho Pharmaceuticals, Aventis Pharmaceuticals, Roche Dermatology, 3M, Bristol Myers Squibb, Stiefel/ GlaxoSmithKline, Novartis, Medicis, Leo, HanAll Pharmaceuticals, Celgene, Basilea, and Anacor and has received stock options from Photomedex. Mr. Davis and Dr. Taylor have no conflicts to disclose. References
1. Shi S, Klotz U. Drug interactions with herbal medicines. Clin Pharmacokinet 2012;51:77–104. 2. Borrelli F, Izzo AA. Herb-drug interactions with St John’s wort (Hypericum perforatum): An update on clinical observations. AAPS J 2009;11:710–727. 3. Madabushi R, Frank B, Drewelow B, et al. Hyperforin in St. John’s wort drug interactions. Eur J Clin Pharmacol 2006;62:225–233. 4. Clauson KA, Santamarina ML, Rutledge JC. Clinically relevant safety issues associated with St. John’s wort product labels. BMC Complement Altern Med 2008;8:42. 5. Davidson JR, Rampes H, Eisen M, et al. Psychiatric disorders in primary care patients receiving complementary medical treatments. Compr Psychiatry 1998;39:16–20.
Address correspondence to: Scott A. Davis, MA Center for Dermatology Research Department of Dermatology Wake Forest School of Medicine Medical Center Boulevard Winston-Salem, NC 27157 E-mail: [email protected]
Commentary
Use of St. John’s Wort in Potentially Dangerous Combinations Scott A. Davis, MA,1 Steven R. Feldman, MD, PhD,1,2,3 and Sarah L. Taylor, MD1
Abstract
Objectives: The objective of this study was to assess how often St. John’s wort (SJW) is prescribed with medications that may interact dangerously with it. Design: The study design was a retrospective analysis of nationally representative data from the National Ambulatory Medical Care Survey. Settings: The study setting was U.S. nonfederal outpatient physician offices. Subjects: Those prescribed SJW between 1993 and 2010 were the subjects. Outcome Measures: The outcome measures were medications co-prescribed with SJW. Results: Twenty-eight percent (28%) of SJW visits involved a drug that has potentially dangerous interaction with SJW. These included selective serotonin reuptake inhibitors, benzodiazepines, warfarin, statins, verapamil, digoxin, and oral contraceptives. Conclusions: SJW is frequently used in potentially dangerous combinations. Physicians should be aware of these common interactions and warn patients appropriately.
cations co-prescribed with SJW were tabulated and their frequencies were assessed. All data analysis was performed using SAS 9.2 (SAS Institute, Cary, NC), and the study was declared exempt by the Wake Forest University Institutional Review Board.
Introduction
S
t. John’s wort (SJW) is the leading complementary and alternative medicine (CAM) treatment for depression and related psychiatric disorders in the United States. Like many other CAM treatments, SJW interacts dangerously with other common medications. Prescription of SJW with oral contraceptives, blood thinners, benzodiazepines, cancer chemotherapy medicines, digoxin, human immunodeficiency virus medicines, statins, immunosuppressants, selective serotonin reuptake inhibitors (SSRIs), or verapamil is not recommended due to potential interactions.1–3 SJW can reduce the concentration of most of these drugs in the body, resulting in impaired efficacy and treatment failure.2,3 However, with antidepressants such as SSRIs, serotonin syndrome (with possible mania) is the main concern.2 The purpose of this study is to assess how often SJW is being prescribed or taken with these other medications.
Results
SJW was mentioned in 2,230,000 visits (120,000 visits/ year). On average, visits mentioning SJW had 3.1 other drugs mentioned. Of the visits at which SJW was listed, 28% (620,000 visits over the 18-year study period) also listed a drug that is unsafe to use with SJW. Leading medications that could interact with SJW and that were listed at SJW visits included SSRIs (13.7%), benzodiazepines (9.8%), warfarin (4.2%), statins (3.3%), verapamil (1.0%), digoxin (1.0%), and oral contraceptives (0.6%, Table 1).
Materials and Methods
Discussion
The National Center for Health Statistics conducts the National Ambulatory Medical Care Survey (NAMCS) annually to characterize the provision of ambulatory medical care in the United States. We searched the 1993–2010 NAMCS for visits that mentioned SJW. Additional medi-
Frequent use of SJW in potentially harmful combinations was observed. These interactions are likely to lead to harmful consequences such as serotonin syndrome, heart disease due to impaired efficacy of antihypertensives, or unplanned pregnancy due to contraceptive failure. Patients
Center for Dermatology Research, Departments of 1Dermatology, 2Pathology, and 3Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC.
1
2
DAVIS ET AL.
Table 1. Leading Classes of Drugs that Interact Dangerously with SJW Were SSRIs and Benzodiazepines Medication or medication class SSRIs Benzodiazepines Warfarin Statins Verapamil Digoxin Oral contraceptives All medications that interact with SJW
Visits co-prescribed with SJW
Percentage of SJW visits in which drug co-prescribed
310,000 220,000 90,000 70,000 20,000 20,000 10,000 620,000
13.7 9.8 4.2 3.3 1.0 1.0 0.6 27.8
Totals may not add exactly because some patients received more than one of the medication classes. SJW, St. John’s wort; SSRIs, selective serotonin reuptake inhibitors.
may have a false sense of safety with so-called ‘‘natural’’ treatments like SJW. Particularly for patients who are taking many other medications, SJW may be no safer than standard allopathic treatments. Limitations of the study include the fact that only medications recorded by the physician could be analyzed. Patients who were using SJW or other therapies that interact with it, but did not inform their physician fully, would not be included, so this study may actually underestimate the rate of SJW interactions. It is crucial for physicians to know the dangers of ‘‘natural’’ treatments and to communicate the risks to patients effectively.4,5 In addition, labeling requirements for herbal supplements such as SJW need to provide appropriate cautions and risk information.4 Physicians also need to be trained to always ask, in a nonjudgmental and understanding manner, whether the patient is taking any supplements, vitamins, minerals, or herbs. Particularly before prescribing any of the common drugs that might interact with SJW, clinicians should be sure they have determined whether patients are using this very popular CAM treatment.
Disclosure Statement
The Center for Dermatology Research is supported by an unrestricted educational grant from Galderma Laboratories, L.P. Dr. Feldman is a consultant and speaker for Galderma, Connetics, Abbott Labs, Warner Chilcott, Centocor, Amgen, Photomedex, Genentech, BiogenIdec, and Bristol Myers Squibb. Dr. Feldman has received grants from Galderma, Astellas, Abbott Labs, Warner Chilcott, Janssen, Amgen, Photomedex, Genentech, BiogenIdec, Coria/Valeant, Pharmaderm, Ortho Pharmaceuticals, Aventis Pharmaceuticals, Roche Dermatology, 3M, Bristol Myers Squibb, Stiefel/ GlaxoSmithKline, Novartis, Medicis, Leo, HanAll Pharmaceuticals, Celgene, Basilea, and Anacor and has received stock options from Photomedex. Mr. Davis and Dr. Taylor have no conflicts to disclose. References
1. Shi S, Klotz U. Drug interactions with herbal medicines. Clin Pharmacokinet 2012;51:77–104. 2. Borrelli F, Izzo AA. Herb-drug interactions with St John’s wort (Hypericum perforatum): An update on clinical observations. AAPS J 2009;11:710–727. 3. Madabushi R, Frank B, Drewelow B, et al. Hyperforin in St. John’s wort drug interactions. Eur J Clin Pharmacol 2006;62:225–233. 4. Clauson KA, Santamarina ML, Rutledge JC. Clinically relevant safety issues associated with St. John’s wort product labels. BMC Complement Altern Med 2008;8:42. 5. Davidson JR, Rampes H, Eisen M, et al. Psychiatric disorders in primary care patients receiving complementary medical treatments. Compr Psychiatry 1998;39:16–20.
Address correspondence to: Scott A. Davis, MA Center for Dermatology Research Department of Dermatology Wake Forest School of Medicine Medical Center Boulevard Winston-Salem, NC 27157 E-mail: [email protected]
