The Nature of Depression and Antidepressants
The Nature of Depression and Antidepressants

Transitory sadness is a normal response to certain life events, and most people regain their psychological footing with time. In contrast, clinical depression—which affects some 19 million Americans—casts a persistent pall over a person's entire life. Sufferers of mild to moderate depression can function, but this often-chronic illness can have a negative impact on outlook and quality of life. Symptoms can include fatigue, insomnia, irritability and difficulty concentrating. In contrast, major depressive disorder is a severe, disabling, and often life-threatening condition that requires immediate medical intervention.

Depression is thought to be the result of a biochemical imbalance. Much of the current biochemical theories of the cause of depression focus on the biogenic amines, which is a group of chemical compounds important in neurotransmission—particularly norepinephrine, serotonin, and to a lesser extent dopamine, acetylcholine and epinephrine.

Antidepressant medications, which seek to restore the chemical balance in the brain, include monoamine oxidase (MAO) inhibitors, tricyclic antidepressants, and selective serotoin reuptake inhibitors (SSRIs). MAOs increase norepinephrine levels, while tricyclics enhance norepinephrine transmission. Serotonin has been the subject of much depression research; it has been found that a functional deficiency in this neurotransmitter results in depression.1 SSRIs prevent circulating serotonin from being reabsorbed by nerve endings. They are called selective SRIs because they affect only serotonin, whereas tricyclic antidepressants are designed to prevent reabsorption of several neurotransmitters, including serotonin.

An increasing number of studies support the efficacy of St. John's wort—an option with relatively few side effects—and have highlighted the complexity by which the herb works. Much attention has been given to hypericin, pseudohypericin and hyperforin—three of the herb's active ingredients thought to be responsible for its antiviral and antidepressive properties. But recent research indicates that its medicinal actions can be attributed to the complex interplay of many constituents.2

St. John's wort's ability to act as an antidepressant is not fully understood; previous literature points to its ability to inhibit MAOs. MAOs act by inhibiting MAO-A and MAO-B isozymes, thereby increasing synaptic levels of the biogenic amines, especially norepinephrine. Other research shows that St. John's wort not only inhibits MAO-A and MAO-B but also reduces the availability of serotonin receptors, resulting in additional serotonin in circulation, which alleviates depression.3


1. Rush AJ, et al. Neurobiological basis for psychiatric disorders. IN: Rosenberg RN, editor. Comprehensive neurology. New York: Raven Press; 1991. p. 563.

2. Holzl J, et al. Investigation about antidepressive and mood changing effects of Hypericum perforatum. Planta Med 1989;55:643.

3. Muller, WE, Rossel R. Effects of Hypericum extract on the expression of serotonin receptors. J Geriatr Psychiatry Neurol 1994;7(suppl 1):S63-4

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