Dehydroepiandrosterone (DHEA) Treatment of Depression

Fluvoxamine enhances prefrontal dopaminergic neurotransmission in adrenalectomized/castrated mice via both 5-HT reuptake inhibition and σ1 receptor activation

“…This effect of fluvoxamine is mediated by both σ 1 receptor activation and 5-HT reuptake inhibition. In view of the previous studies suggesting a relationship between DHEA and/or progesterone concentrations and depressed mood (Berr et al 1996;Barrett-Connor et al 1999;Hardoy et al 2006;Michael et al 2000;Wolkowitz et al 1997Wolkowitz et al , 1999Yaffe et al 1998), the present study suggests that fluvoxamine may exert the beneficial effect via σ 1 receptor-mediated enhancement of prefrontal dopaminergic neurotransmission under steroid-deficient conditions such as depression.…”

“…There are clinical studies suggesting a link between the endogenous levels of these neuroactive steroids and the depressive state (George et al 1994;Hardoy et al 2006;Heinz et al 1999). Wolkowitz et al (1997Wolkowitz et al ( , 1999 reported that DHEA administered to depressive patients with low DHEA levels significantly reduced depression ratings. Moreover, recent studies show that venlafaxine and mitrazapine decrease plasma DHEA sulfate levels in depressive patients, and the decrease is related to their clinical efficacy (Paslakis et al 2010;Schüle et al 2009).…”

Neurosteroids in depression: a review

“…Some studies in depressed patients found significantly higher cortisol/DHEA(S) ratios compared to controls (Osran et al 1993;Scott et al 1999), while other studies failed to find abnormal ratios (Reus et al 1993;Fabian et al 2001). Reported values of plasma DHEA(S) levels differed between studies ranging from low (Ferguson et al 1964;Legrain et al 1995;Wolkowitz et al 1995Wolkowitz et al , 1997Goodyer et al 1996;Scott et al 1999;Barrett-Connor et al 1999;Morrison et al 2001) to normal (Osran et al 1993;Reus et al 1993;Goodyer et al 1996;Scott et al 1999;Fabian et al 2001) and high levels (Hansen et al 1982;Tollefson et al 1990;Takebayashi et al 1998;Heuser et al 1998;Maayan et al 2000;Weber et al 2000;Morrison et al 2001). These conflicting data on DHEA(S) levels in depressed patients could be explained by differences in age [as DHEA(S) concentration declines with increasing age (Orentreich et al 1992)], gender (Orentreich et al 1984), drug therapy, and concurrent somatic or psychiatric diseases (Berr et al 1996;Wolf and Kirschbaum 1999;Kroboth et al 1999;Salek et al 2002).…”

“…Open-label (Wolkowitz et al 1997) as well as doubleblind, randomized, placebo-controlled ) oral administration of DHEA decreases depressive symptoms in patients with major depression, reflected by a significant decrease in Hamilton Depression Rating Scale (HDRS) score. The same effect after oral administration of DHEA is achieved in patients with dysthymia (Bloch et al 1999).…”

“…Apart from the interaction with the sigma 1 receptor and its antiglucocorticoid effects, the interaction of DHEA with the GABA A and NMDA receptors has also been postulated as an underlying mechanism for the cognitive-enhancing effects of DHEA. Thus, the cognitive-enhancing properties of DHEA(S) may, at least in part, have contributed to the decrease in HDRS scores in depressive patients following DHEA treatment (Wolkowitz et al 1997Bloch et al 1999).…”