St. John's Wort for Depression: Uses, Effects & Evidence

Overview of Depression in Adults

An estimated 9.5% of the American population — approximately 20.9 million American adults — suffer from depression. Major depression is a severe mental illness that inhibits a patient's daily functioning, making it difficult or impossible to work, study, sleep, eat, or feel pleasure. Dysthymia is a less debilitating but still pervasive form of depression that, while chronic, does not interfere with daily functioning to the same degree. ("Depression," 2000, National Institute of Health)

Current research indicates that people suffering from depression have imbalances in their brain chemistry, specifically regarding the neurotransmitters serotonin and norepinephrine. A deficiency in serotonin may cause sleep problems, irritability, and anxiety. A decreased level of norepinephrine, which regulates alertness and arousal, may contribute to fatigue and depressed mood. Cortisol — a hormone the body produces in response to stress, anger, or fear — is also frequently implicated in depression. In healthy individuals, cortisol levels typically peak in the morning and decrease as the day progresses. In depressed individuals, cortisol peaks earlier in the morning and does not level off or decrease in the afternoon or evening. ("Depression," 2006, Healthy Place) This elevated cortisol level is likely a physiological response to the increased environmental stress perceived by the patient because of their depressed mood.

Signs, Symptoms, and Complications

Signs of depression vary from person to person and with the severity of the illness. Not every depressed person experiences all symptoms, although most experience a persistent sad, anxious, or empty feeling. Other common symptoms include feelings of hopelessness, pessimism, guilt, worthlessness, and helplessness; loss of interest or pleasure in hobbies and activities once enjoyed; decreased energy, fatigue, and reduced sexual desire; and difficulty concentrating, remembering, and making decisions. Some persons — especially younger adults — may feel more restless and irritable than sad. Some people with depression experience insomnia, while others are persistently fatigued and compensate by oversleeping. Weight loss or gain may arise from disordered appetite. ("Depression," 2000, National Institute of Health)

Depression may also be characterized by thoughts of suicide or actual suicide attempts. Restlessness and irritability can lead to increased risk-taking behaviors, such as careless driving. Additionally, patients may experience persistent physical symptoms that do not respond to treatment, including headaches, digestive disorders, and chronic pain. ("Depression," 2000, National Institute of Health)

Because of elevated cortisol levels, the bodies of depressed individuals often exhibit signs similar to those seen in people under considerable physical or emotional stress. Unhealthy eating or sleeping habits worsen these symptoms. Physical changes or medical conditions — such as stroke, heart attack, cancer, Parkinson's disease, and hormonal disorders — can also exacerbate depression or, in some cases, trigger it. ("Depression," 2000, National Institute of Health)

Causes and Theoretical Frameworks

Most current theories hold that a combination of genetic, psychological, and environmental factors contribute to depression. There appears to be a strong genetic component, as depression often runs in families. As one source notes, "if one identical twin suffers from depression, the other twin has a 70% chance of also having the illness." ("Depression," 2006, Healthy Place) There is also a hormonal component: women are more likely to develop depression than men. External physical or psychological stressors — such as pregnancy, aging, a heart attack, or puberty — may trigger the onset of depression in vulnerable individuals. ("Depression," 2000, National Institute of Health)

Because a deficit of the neurotransmitter serotonin has been identified in patients with depression, the development of selective serotonin reuptake inhibitors (SSRIs) such as Prozac is considered an effective pharmacological approach to treatment. ("Depression," 2000, National Institute of Health) Depression is a mood disorder that can affect daily life broadly, making effective self-care difficult; in untreated cases, suicide remains a serious risk.

St. John's Wort: Mechanism of Action and Clinical Evidence

According to the National Institutes of Health, there has been widespread interest in St. John's Wort as an alternative treatment for depression. The herb has been used for many years as a folk remedy for depression, and it is speculated that it may work by increasing serotonin levels, though the precise mechanism of action remains uncertain. ("St. John's Wort," 2006, NCCAM)

Clinical research on its efficacy is, at present, inconclusive. The National Institutes of Health conducted a three-year study of 336 patients with major depression of moderate severity. Patients were randomly assigned to an eight-week trial in which one-third received a uniform dose of St. John's Wort, one-third received an SSRI commonly prescribed for depression, and the final third received a placebo. Participants who responded positively were followed for an additional 18 weeks. At the end of the first phase, participants were evaluated on two scales: one measuring depression and one measuring overall functioning. There was no significant difference in the rate of response for depression across the three groups; however, the overall functioning scale showed better outcomes for the antidepressant than for either St. John's Wort or placebo. ("Depression," 2000, National Institute of Health)

A second study, published in the Journal of the American Medical Association, also enrolled adult outpatients with major depression who were randomly assigned to receive St. John's Wort, an SSRI, or a placebo. The authors concluded: "On the 2 primary outcome measures, neither sertraline [the antidepressant] nor H. perforatum [St. John's Wort] was significantly different from placebo." (JAMA, 2002, p. 1814) However, a separate study published in the British medical journal BMC Medicine found that significantly more patients taking St. John's Wort — compared with either a placebo group or an SSRI group — "showed treatment response and remission." (Kasper et al., 2006) A recognized challenge in all such studies is the difficulty of objectively quantifying "depressed mood," though all comparative studies cited here use the same standardized mood inventory to measure depression levels in participants.

The method by which St. John's Wort interacts with the brain and body chemistry of depressed patients remains uncertain, in part because even the herb's clinical efficacy is not yet established. The herb has been found to unpleasantly exacerbate the side effects of other SSRIs when taken concurrently with other antidepressants. ("St. John's Wort," 2006, NCCAM)

Works Cited

"Depression." (2006). Healthy Place. Retrieved 23 Oct 2006 from

"Depression." (2000). National Institute of Health. Retrieved 23 Oct 2006 from http://www.nimh.nih.gov/publicat/depression.cfm

Hypericum Depression Trial Study Group. (2002). Journal of the American Medical Association, 287(14): 1807–1814. Retrieved 23 Oct 2006 from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11939866&query_hl=2

Kasper, S., Anghelescu, I. G., Szegedi, A., Dienel, A., & Kieser, M. "Superior efficacy of St. John's Wort extract WS 5570 compared to placebo in patients with major depression: a randomized, double-blind, placebo-controlled, multi-center trial." (2006). BMC Medicine, 4(14). Retrieved 23 Oct 2006 from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?itool=abstractplus&db=pubmed&cmd=Retrieve&dopt=abstractplus&list_uids=16796730

"St. John's Wort." (2006). NCCAM: National Center for Complementary and Alternative Medicine. Retrieved 23 Oct 2006 from http://nccam.nih.gov/health/stjohnswort/