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Health Protocols


Complementary Therapies for Depression

Hormone Restoration Therapy

Although some physicians routinely screen for underlying hormonal disorders and/or imbalances as part of depression management, many use hormonal therapy in protocols for depression, most typically do not. Instead, they may consider hormonal imbalances a normal part of aging. Also, many ascribe to the philosophy of looking at studies of averages of population data as opposed to individual cases for potentially beneficial therapeutic programs, which can cause patients who may benefit from hormone restoration to go untreated.

Thyroid. Thyroid dysfunction may be a significantly underappreciated cause of depressive symptoms. In one study, thyroid disorders were associated with a 22% higher likelihood of depression in women.94

Studies have shown that treating subjects within so-called “normal” thyroid hormone levels may still be beneficial. In one such pilot study involving 17 female patients with depression, 11 (64.7%) saw significant improvement in response to a moderate dose of l-thyroxine.95 Similarly, in a study of 225 subjects with treatment-resistant depression, augmenting primary antidepressant therapy with thyroid hormone was found to be roughly as effective as adding a second antidepressant medication for providing relief of symptoms.96

Life Extension suggests maintaining a TSH (thyroid stimulating hormone) of 1–2 µIU/mL (typical lab normal range 0.45‒4.5 µIU/mL) to avoid the consequences of subclinical thyroid dysfunction, which may include depression. To learn more about sub-optimal thyroid function and how it may be impacting your life read our “Thyroid Regulation” protocol.

DHEA. DHEA is an important steroid hormone often referred to as a neurosteroid because it serves a variety of functions in the brain. DHEA levels decrease with age and stress, and people with depression often have low levels of DHEA. In one study, blood samples from women with a history of depression contained lower levels of select neurosteroids, including DHEA, than women with no depression history.97 Interestingly, experiments showed the women with a history of depression may metabolize progesterone differently than healthy women, reflecting an adaptive effort by the body to compensate for low neurosteroid levels.

A number of studies have examined the role of DHEA in depression, with very encouraging results. DHEA has been shown to modulate serotonin levels in the brains of laboratory animals.98,99 DHEA has also performed well in human trials. DHEA therapy significantly benefited patients with HIV/AIDS and depression.100 In a randomized, placebo-controlled, double-blind study, researchers studied the effects of 90 mg DHEA daily for three weeks and 450 mg daily for three weeks as a stand-alone treatment for both mild and severe depression. They found that DHEA therapy resulted in a significant improvement in symptoms compared with the placebo.101

Testosterone. Studies indicate that some depressed men have low levels of testosterone.102,103 In addition, several clinical trials have shown that testosterone replacement therapy, usually transdermal testosterone gel, can relieve depression in men with low testosterone, metabolic syndrome, and HIV/AIDS.50,104-106

Aging men should maintain their free testosterone level in the youthful range of 20–25 pg/mL to stabilize mood and avert other age-related diseases, such as cardiovascular disease and metabolic syndrome. Men interested in restoring their hormone levels should read Life Extension's “Male Hormone Restoration” protocol.

Estrogen. Estrogen is critically important for brain function and linked to depression, especially in perimenopausal or postmenopausal women.107 Women using estrogen replacement therapy to alleviate menopause symptoms appear to experience reduced depression.108 In some older women being treated for depression, estrogen replacement therapy may actually improve the effects of conventional antidepressants.109

Estrogen is thought to prevent depression through its association with serotonin regulation in the brain.110-112 Animal studies show that estrogen may facilitate the effects of antidepressants by modulating serotonin receptors. This suggests that an estrogen imbalance may dampen the efficacy of antidepressant medications.113,114

Further evidence suggests that estrogen promotes neuroplasticity, the process by which the brain adapts structurally and functionally to new stimuli.110,115 Disturbances in neuroplasticity may lead to recurrent depression.116

Women interested in learning more about the benefits of restoring their hormone levels should read Life Extension's “Female Hormone Restoration” protocol.

Melatonin. Melatonin is a hormone produced in the pineal gland in the brain; it is involved in sleep-wake function and other circadian rhythms. Melatonin decreases with age and some studies link low levels of melatonin with symptoms of depression.

A double-blind placebo-controlled pilot study of perimenopausal and post-menopausal women who took 3 mg of melatonin at bedtime for six months showed significant improvement in depressive symptoms.117 Recently, another well-controlled preliminary study looked at 33 participants with major depression and early morning waking who took 6 mg of melatonin for four weeks. The results suggested improvement in sleep and depressive symptoms.118

Studies of the medication agomelatine, which acts upon melatonin receptors in the brain, support melatonin's influences on depression.119 Some studies suggest that this drug may be as effective as venlafaxine, fluoxetine, and sertraline in relieving depression.120