Monica Vermani, Hon.BSc, MA Stress, Trauma, Anxiety, Rehabilitation Treatment (S.T.A.R.T.) Clinic for Mood & Anxiety Disorders, Toronto, Canada; Adler School of Professional Psychology, Chicago, Ill
Irena Milosevic, Hon.BSc University of Toronto, Toronto, Canada
Fraser Smith, BA, ND Canadian College of Naturopathic Medicine, Toronto, Canada
Martin A. Katzman, BSc, MD, FRCPC Stress, Trauma, Anxiety, Rehabilitation Treatment (S.T.A.R.T.) Clinic for Mood & Anxiety Disorders, Toronto, Canada; Department of Psychiatry, Faculty of Medicine, University of Toronto
Because many alternative options do not require the approval of the US Food and Drug Administration (FDA), products sold in health food stores can be purchased without a prescription or the provision of any clinical advice or professional review. The quality of many herbal preparations is thus unpredictable, with the content varying not only from brand to brand but also from batch to batch.5
A working knowledge of the pharmacologic data and clinical literature is necessary to properly counsel, diagnose, and treat patients who may be using herbal products. However, 1 study reported that only 5% of British doctors claimed more than a poor knowledge of herbal medicine,6 and another survey revealed that most psychiatrists who do not recommend herbal products avoid doing so because they feel uncomfortable with their current knowledge of alternative therapies.7 Alarmingly, the latter study reported that among psychiatrists who do not recommend herbal treatments, the safety of such treatments is not an issue in their decision-making process.
Mechanisms of action. The mechanisms for the antidepressant effects of St. John’s Wort are not fully understood, although monoamine oxidase (MAO) inhibition, inhibition of serotonin receptor expression, serotonin reuptake inhibition, and reduction of cytokine expression have all been suggested as means of its activity.9
Herb-drug interactions. Evidence suggests St. John’s Wort contains both inhibitory and inducing constituents for the cytochrome P-450 (CYP) system, resulting in both inhibition and induction on the CYP system.14 Consequently, it’s difficult to predict which drugs St. John’s Wort will interact with in a significant way.15 Best estimates of its activity suggest it has minimal short-term activity; when used for a longer period, it will inhibit the CytP450-3A4, 2C19, and 2D6 systems (TABLE 2). Therefore, St. John’s Wort may alter the blood levels of such medications as anticoagulants,16 oral contraceptives,18 and antiviral agents,19 possibly resulting in serious consequences.16,17 Exercise caution when initiating treatment for patients already taking St. John’s Wort.
The potential of St. John’s Wort to interact with standard prescribed antidepressants, possibly to produce a “serotonin syndrome,” is also a concern. Gordon20 reported a case in which a woman taking St. John’s Wort became groggy, weak, and lethargic shortly after taking a single 20-mg dose of paroxetine. This patient had tolerated St. John’s Wort and paroxetine separately, suggesting a drug-herb interaction.3 St. John’s Wort has also been implicated in reducing blood levels of digoxin when the two are taken together,21 and 1 study documented that 8% of psychiatrists treating patients who had used St. John’s Wort reported drug interactions between the herb and another agent.22
FAST TRACK
Reports of ginseng’s effectiveness for depression conflict dramatically
Adverse effects. In general, fewer adverse effects are seen with hypericum than with conventional antidepressants but they may include photodermatitis, delayed hypersensitivity, gastrointestinal tract upset, dizziness, dry mouth, sedation, restlessness, and constipation. Use of St. John’s Wort is contraindicated during pregnancy and lactation, for patients who experience intense exposure to strong sunlight, and for patients with a pheochromocytoma.23
There are several anecdotal reports of mania or hypomania associated with the herb. For example, O’Breasail and Argouarch24 reported 2 cases of persons with no history of bipolar disorder who developed hypomanic episodes after taking St. John’s Wort. Likewise, Moses and Mallinger25 reported 3 cases of possible mania induction associated with the herb.
TABLE 2 Effects of common herbs on cytochrome P-450 enzymes
Key: ++++ = very potent; ++ = potent (detectable); + = mildly potent; 0 = does not inhibit
Note: Caution should be undertaken when developing tables such as these, as the data came from a variety of in vivo and in vitro animal and human studies using simplified models (eg, cDNA-expressed CYP enzymes) of which there are significant interspecies variations in the activity of these systems. As well, in the presence of some pathological inflammatory states such as during an infection, the enzyme activity of the CYP can be modulated through cytokines and other mediators of inflammation.101
Ginseng
This herb is derived from the root of Panax ginseng and has been used as a cure-all in Eastern folk medicine for thousands of years.26 Today, both Chinese ginseng (P ginseng CA Meyer) and North American ginseng (P quinquefolius L) are associated with the treatment of mood and anxiety disorders and are used to reduce stress and fatigue and to improve endurance.
Efficacy. A systematic review of 16 double-blind randomized controlled trials found that ginseng did not improve cognitive function or psychomotor and physical performance.27 Another review reported conflicting results from several studies.28 For example, 1 double-blind randomized controlled trial of postmenopausal women who received either a placebo or ginseng for 16 weeks revealed the superiority of ginseng on measures of psychological well-being.29 Another double-blind randomized controlled trial, however, failed to find an effect of ginseng on positive affect, negative affect, or total mood disturbance in 83 healthy adults who took the herb for 8 weeks.30 Thus, at best, SOR=B for the evidence in support of ginseng, but only at best in relation to psychological well-being.
