Dehydroepiandrosterone Monotherapy in Midlife-Onset Major and Minor Depression

Schmidt, Peter J.; Daly, Robert C.; Bloch, Miki; Smith, M. J.; Danaceau, Merry A.; Clair, Linda Simpson St.; Murphy, Jean; Haq, Nowreen; Rubinow, David R.

doi:10.1001/archpsyc.62.2.154

Cited by 226 publications

(175 citation statements)

References 70 publications

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“…Two placebocontrolled clinical trials support the notion that DHEA treatment improves mood and alleviates depression (Morales et al, 1994;Schmidt et al, 2005). In the present study, peak levels of DHEA after smoking successive high-nicotine cigarettes averaged between 13 and 14.4 ng/ml or 46-50 nmol/l or 1328-1440 ng/dl.…”

Section: Tolerance To Nicotine's Biological and Subjective Effectssupporting

confidence: 77%

Effects of Smoking Successive Low- and High-Nicotine Cigarettes on Hypothalamic–Pituitary–Adrenal Axis Hormones and Mood in Men

Mendelson

Goletiani

Sholar

et al. 2007

Neuropsychopharmacol

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Smoking one cigarette produces rapid nicotine dose-related increases in hypothalamic-pituitary-adrenal (HPA) axis hormones, mood, and heart rate, but relatively little is known about the effects of smoking several cigarettes successively. Twenty-four healthy adult men who met Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria for nicotine dependence provided informed consent. After overnight abstinence from smoking, men smoked three low-or high-nicotine cigarettes for 4 min each at 60 min intervals. Samples for nicotine and hormone analysis, Visual Analog Scale (VAS) ratings of subjective effects and heart rate were collected at 4, 8, 12, 16, 20, 30, 40, and 50 min after each cigarette. After low-nicotine cigarettes, nicotine levels, adrenocorticotropin hormone, and heart rate did not increase significantly, cortisol and dehydroepiandrosterone decreased significantly, and positive VAS ratings were lower but parallel to ratings after high-nicotine cigarette smoking. After high-nicotine cigarettes, peak nicotine levels increased monotonically. HPA axis hormones increased after smoking, but peak levels did not differ significantly after successive high-nicotine cigarettes. Positive VAS ratings and heart rate increased after each high-nicotine cigarette, but peak levels were lower after smoking the second and third cigarette. 'Craving' decreased significantly after smoking both low-and high-nicotine cigarettes, then gradually increased during the 60 min interval between cigarettes. These data are consistent with clinical reports that the first cigarette after overnight nicotine abstinence is most salient. Tolerance to the subjective and cardiovascular effects of nicotine developed rapidly during repeated cigarette smoking, but nicotine-stimulated increases in HPA axis hormones did not change significantly.

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Section: Tolerance To Nicotine's Biological and Subjective Effectssupporting

confidence: 77%

Effects of Smoking Successive Low- and High-Nicotine Cigarettes on Hypothalamic–Pituitary–Adrenal Axis Hormones and Mood in Men

Mendelson

Goletiani

Sholar

et al. 2007

Neuropsychopharmacol

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“…By contrast, women with physiological menopause and intact adrenals did not show improvement in mood or self-perceived well-being following DHEA therapy (46). In general, the effects of DHEA replacement on mood may be more complex than those of testosterone replacement, as DHEA also potentially exerts direct neurosteroidal effects at gamma-aminobutyric acid and N-methyl-D-aspartate receptors, suggestive of a potential anti-depressive action (39), which has been demonstrated in women with midlife-onset dysthymia, significantly benefiting from DHEA replacement (47,48). In the largest study published on the use of DHEA in elderly women (60 to 79 years old), comparing 12 months of treatment with DHEA (n ¼ 70) vs placebo (n ¼ 70), modest increases in libido and bone mineral density were observed, but only in the subgroup of women older than 70 years of age (49).…”

Section: Weeksmentioning

confidence: 96%

Androgen therapy in women

Arlt

2006

eur j endocrinol

105

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Androgens in women either derive from direct ovarian production or from peripheral conversion of the adrenal sex steroid precursor, dehydroepiandrosterone, towards active androgens. Therefore, loss of adrenal or ovarian function, caused by Addison's disease or consequent to bilateral oophorectomy, results in severe androgen deficiency, clinically often associated with a loss of libido and energy. Importantly, physiological menopause does not necessarily lead to androgen deficiency, as androgen synthesis in the ovaries may persist despite the decline in estrogen production. However, the definition of female androgen deficiency, as recently provided by the Princeton consensus statement, is not precise enough and may lead to over-diagnosis due to the high prevalence of its diagnostic criteria: androgen levels below or within the lower quartile of the normal range and concurrent sexual dysfunction. Importantly, physiological menopause is not necessarily associated with androgen deficiency and therefore does not routinely require androgen therapy. Current replacement options include transdermal testosterone administration or dehydroepiandrosterone treatment, both of which have been shown to result in significant improvements, in particular in libido and mood, while effects on body composition and muscular function are not well documented. It is important to keep in mind that the number of randomized controlled trials is still limited and that currently none of the available preparations is officially approved for use in women. Currently, androgen replacement should be reserved for women with severe androgen deficiency due to an established cause and matching clinical signs and symptoms.

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“…In a 6-week, placebo-controlled cross-over trial in men and women with major or minor depression, DHEA administration (90 mg/ day for 3 weeks; 450 mg/day for 3 weeks) significantly improved mood and depression ratings in comparison to pretreatment baseline and placebo conditions (Schmidt et al, 2005). In the present study, peak levels of DHEA after smoking a high-nicotine cigarette (21.1372.55 ng/ml or 73.3278.84 nmol/l or 2113.0 ng/dl) were over four times higher than average DHEA levels achieved after 3 months of DHEA replacement in men (14.7271.4 nmol/l) (Morales et al, 1994) and over twice as high as average DHEA levels after 6 weeks of high-dose DHEA treatment (1047.27709.1 ng/dl) (Schmidt et al, 2005). Taken together, these data suggest that increases in DHEA levels may contribute to the mood-elevating effects reported after cigarette smoking.…”

Section: Subjective Responses To Smoking High-and Low-nicotine Cigarementioning

confidence: 98%

“…DHEA formulations are sold over the counter as dietary supplements, and DHEA is believed to improve a sense of well-being and sexuality in the elderly, and in persons with adrenal insufficiency. Although the evidence is conflicting (see for review Spark, 2002), two placebo-controlled clinical trials support the notion that DHEA treatment improves mood and alleviates depression (Morales et al, 1994;Schmidt et al, 2005). In a 6-month, placebo-controlled cross-over trial, DHEA administration at physiological levels (50 mg, p.o.)…”

Section: Subjective Responses To Smoking High-and Low-nicotine Cigarementioning

confidence: 99%

Effects of Low- and High-Nicotine Cigarette Smoking on Mood States and the HPA Axis in Men

Mendelson

Sholar

Goletiani

et al. 2005

Neuropsychopharmacol

125

106

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The acute effects of smoking a low-or high-nicotine cigarette on hypothalamic-pituitary-adrenal (HPA) hormones, subjective responses, and cardiovascular measures were studied in 20 healthy men who met American Psychiatric Association Diagnostic and Statistical Manual IV criteria for nicotine dependence. Within four puffs (or 2 min) after cigarette smoking began, plasma nicotine levels and heart rate increased significantly (Po0.01), and peak ratings of 'high' and 'rush' on a Visual Analogue Scale were reported. Reports of 'high,' 'rush,' and 'liking' and reduction of 'craving' were significantly greater after smoking a high-nicotine cigarette than a low-nicotine cigarette (Po0.05). Peak plasma nicotine levels after high-nicotine cigarette smoking (23.972.6 ng/ml) were significantly greater than after lownicotine cigarette smoking (3.6370.59 ng/ml) (Po0.001). After smoking a low-nicotine cigarette, adrenocorticotropin hormone (ACTH), cortisol, dehydroepiandrosterone (DHEA), and epinephrine did not change significantly from baseline. After high-nicotine cigarette smoking began, plasma ACTH levels increased significantly above baseline within 12 min and reached peak levels of 21.8875.34 pmol/l within 20 min. ACTH increases were significantly correlated with increases in plasma nicotine (r ¼ 0.85; Po0.0001), DHEA (r ¼ 0.66; P ¼ 0.002), and epinephrine (r ¼ 0.86; Po0.0001). Cortisol and DHEA increased significantly within 20 min (Po0.05) and reached peak levels of 424748 and 21.1372.55 ng/ml within 60 and 30 min, respectively. Thus cigarette smoking produced nicotine dose-related effects on HPA hormones and subjective and cardiovascular measures. These data suggest that activation of the HPA axis may contribute to the abuse-related effects of cigarette smoking.

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Dehydroepiandrosterone Monotherapy in Midlife-Onset Major and Minor Depression

Abstract: We find DHEA to be an effective treatment for midlife-onset major and minor depression.

Cited by 226 publications

References 70 publications

Effects of Smoking Successive Low- and High-Nicotine Cigarettes on Hypothalamic–Pituitary–Adrenal Axis Hormones and Mood in Men

Effects of Smoking Successive Low- and High-Nicotine Cigarettes on Hypothalamic–Pituitary–Adrenal Axis Hormones and Mood in Men

Androgen therapy in women

Effects of Low- and High-Nicotine Cigarette Smoking on Mood States and the HPA Axis in Men

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