Antidepressant Treatment and Dehydroepiandrosterone Sulfate: Different Effects of Amitriptyline and Paroxetine

Deuschle, Michael; Luppa, Peter B.; Gilles, Maria; Hamann, Bettina; Heuser, Isabella

doi:10.1159/000079980

Cited by 13 publications

(6 citation statements)

References 23 publications

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“…Plasma P, Preg, DHEA, 5α-DHP, and 5α-DHDOC were not altered after successful treatment with either SSRIs or TCAs (Romeo et al, 1998;Strohle et al, 1999). It has also been shown that treatment for 35 days with either amitriptyline or paroxetine resulted in a significant decline in plasma DHEAS concentrations, an effect that was more prominent in patients taking amitriptyline than paroxetine (Deuschle et al, 2004). Given that ALLO and 3α,5β-THP appear to be elevated in patients with depression, whereas THDOC and perhaps DHEA and DHEAS are decreased, it is possible that drug-induced regulation of these steroid concentrations contribute to the clinical effectiveness of these drugs.…”

Section: Antidepressant Potential Of Neuroactive Steroidsmentioning

confidence: 95%

The Relevance of Neuroactive Steroids in Schizophrenia, Depression, and Anxiety Disorders

et al. 2007

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1. Neuroactive steroids are steroid hormones that exert rapid, nongenomic effects at ligand-gated ion channels. There is increasing awareness of the possible role of these steroids in the pathology and manifestation of symptoms of psychiatric disorders. The aim of this paper is to review the current knowledge of neuroactive steroid functioning in the central nervous system, and to assess the role of neuroactive steroids in the pathophysiology and treatment of symptoms of schizophrenia, depression, and anxiety disorders. Particular emphasis will be placed on GABAA receptor modulation, given the extensive knowledge of the interactions between this receptor complex, neuroactive steroids, and psychiatric illness. 2. A brief description of neuroactive steroid metabolism is followed by a discussion of the interactions of neuroactive steroids with acute and chronic stress and the HPA axis. Preclinical and clinical studies related to psychiatric disorders that have been conducted on neuroactive steroids are also described. 3. Plasma concentrations of some neuroactive steroids are altered in individuals suffering from schizophrenia, depression, or anxiety disorders compared to values in healthy controls. Some drugs used to treat these disorders have been reported to alter plasma and brain concentrations in clinical and preclinical studies, respectively. 4. Further research is warranted into the role of neuroactive steroids in the pathophysiology of psychiatric illnesses and the possible role of these steroids in the successful treatment of these disorders.

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Section: Antidepressant Potential Of Neuroactive Steroidsmentioning

confidence: 95%

The Relevance of Neuroactive Steroids in Schizophrenia, Depression, and Anxiety Disorders

et al. 2007

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“…Furthermore, some antidepressants have been shown to lower total cortisol concentrations in saliva [16], though little is known about how antidepressants interfere with glucocorticoid metabolism. Thus, the aim of this study was to investigate the activity pattern of local modulators of glucocorticoid action during major depression and observe changes during antidepressive treatment.…”

Section: Introductionmentioning

confidence: 99%

Cortisol Metabolism in Depressed Patients and Healthy Controls

et al. 2009

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Background: Chronic stress as well as major depressive disorders are associated with hypercortisolemia and impaired hypothalamic-pituitary-adrenocortical axis functioning. The aim of this study was to determine whether in major depression changes in the activity patterns of local modulators of glucocorticoid action might contribute to an increase in cortisol bioavailability and if they change during antidepressant treatment and clinical response. Methods: Concentrations of urinary total cortisol (UFF), urinary total cortisone (UFE), tetrahydrocortisone (THE), tetrahydrocortisol (THF) and allo-THF (5α-THF) were measured in 10-hour nocturnal urine samples of 19 depressed patients and 15 healthy controls. The activity of 11β-hydroxysteroid dehydrogenases (11β-HSD) as well as 5α- and 5β-reductases was assessed by calculating the ratios of glucocorticoid metabolites. Patients were treated for 28 days with either mirtazapine or venlafaxine. Enzyme activity was observed during the course of treatment and compared to healthy controls. Responders to treatment were selected for this analysis. Results: Depressed patients showed reduced 5α-reductase activity manifested as a significantly lower amount of 5α-THF (102.8 ± 167.2 vs. 194.6 ± 165.8 μg, p = 0.019). The increase in the UFF/UFE ratio (0.73 ± 0.32 vs. 0.29 ± 0.13, p < 0.0001) indicates reduced activity of renal 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). During pharmacological treatment, 5α-reductase activity in patients returned to the level of the control group, while the decrease in 11β-HSD2 activity persisted until day 28. Conclusions: Our results show changes in activity of intracellular modulators of steroid action in major depressive disorders, particularly a reduced activity of the intracellular cortisol-deactivating enzymes 5α-reductase and 11β-HSD2. These changes suggest an increase in cortisol bioavailability within tissues.

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“…We did not find any significant changes in pre-to-post-treatment DHEA(S) levels in the whole MDD sample or in the Remitters or Non-remitters separately, nor did we find a significant correlation between change in DHEA(S) and change in depression severity. Several studies have examined the association between change in DHEA(S) levels and clinical improvement after antidepressant treatment (Deuschle et al, 2004; Fabian et al, 2001; Hsiao, 2006; Markopoulou et al, 2009; Morita et al, 2014; Paslakis et al, 2010; Romeo et al, 1998; Schüle et al, 2009; Takebayashi et al, 1998), several of which have reported decreases in pre-to-post treatment DHEA(S) levels in depressed patients (Schüle et al, 2009; Takebayashi et al, 1998; Zhu et al, 2015), at least in those who responded to treatment (Deuschle et al, 2004; Fabian et al, 2001; Hsiao, 2006; Morita et al, 2014; Paslakis et al, 2010; Schüle et al, 2009); however, findings are mixed (Markopoulou et al, 2009; Morgan et al, 2010; Romeo et al, 1998). The reasons for these inconsistencies are uncertain, however, few of these studies had similar designs to ours, including differences in age groups, medication status, measurements of improvement, etc., making direct comparisons difficult.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have examined changes in peripheral endogenous DHEA(S) levels over the course of antidepressant treatment (Berardelli et al, 2010; Deuschle et al, 2004; Fabian et al, 2001; Hsiao, 2006; Markopoulou et al, 2009; Morgan et al, 2010; Morita et al, 2014; Paslakis et al, 2010; Romeo et al, 1998; Schüle et al, 2009; Takebayashi et al, 1998; Zhu et al, 2015) and in relation to treatment response (Deuschle et al, 2004; Fabian et al, 2001; Hsiao, 2006; Markopoulou et al, 2009; Morita et al, 2014; Paslakis et al, 2010; Schüle et al, 2009; Takebayashi et al, 1998). However, to the best of our knowledge, only three previous studies have examined peripheral endogenous DHEA or DHEA-S levels in MDD in relation to clinical response/remission after pharmacological treatment (Fabian et al, 2001; Hsiao, 2006; Markopoulou et al, 2009), and none has examined response to selective serotonin reuptake inhibitors (SSRIs) specifically.…”

Section: Introductionmentioning

confidence: 99%

“…As previous research is limited, and as other studies have suggested that the mechanisms related to DHEA and antidepressant-response may differ between serotonin/SSRIs, compared to other classes of neurotransmitters and antidepressants (Deuschle et al, 2004; Pérez-Neri et al, 2008; Romeo et al, 1998), the current study sought to assess whether baseline serum DHEA(S) levels predict improvement of depression after SSRI treatment and whether post-treatment DHEA(S) levels are associated with improvement of depression. To accomplish this, we determined morning fasting serum DHEA(S) levels in 36 unmedicated adults (ages 19 – 65) with a current DSM-IV diagnosis of MDD, who were then treated in an open-label manner with an SSRI for eight weeks prior to having serum DHEA(S) levels reevaluated.…”

Section: Introductionmentioning

confidence: 99%

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Higher serum DHEA concentrations before and after SSRI treatment are associated with remission of major depression

Hough

Lindqvist

Epel

et al. 2017

Psychoneuroendocrinology

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Background Dehydroepiandrosterone (DHEA) and its sulfated ester DHEA-sulfate (DHEA-S), (together DHEA[S]), are the most abundant adrenal steroids in humans and are found in blood and the brain, where they function as neurosteroids with direct receptor affinities. Preclinical studies suggest that DHEA(S) has antidepressant/neuroprotective properties, and exogenously administered DHEA has shown antidepressant efficacy in humans. Nonetheless, the role of endogenous DHEA(S) levels in major depressive disorder (MDD) and antidepressant outcomes remains unclear. Methods Morning fasting serum DHEA(S) concentrations were determined in 36 healthy, unmedicated MDD adults with Hamilton Depression (HDRS) ratings ≥17, and 75 healthy controls. MDD participants then completed eight weeks of open-label SSRI treatment before DHEA(S) levels were re-sampled; those with post-treatment HDRS ratings ≤7 were classified as “Remitters.” Pre- and post-treatment DHEA(S) levels of Remitters and Non-remitters were compared, controlling for age, sex, and BMI. Results Pre-treatment HDRS ratings did not differ between Remitters and Non-remitters (p=0.179). Baseline DHEA levels of Remitters were significantly higher than both Non-remitters (p=0.008) and controls (p=0.004); baseline DHEA-S levels of Remitters were also higher than Non-remitters (p=0.040) but did not significantly differ from controls (p=0.096). Non-remitters did not significantly differ from controls. Post-treatment DHEA(S) levels remained higher in Remitters compared to Non-remitters (DHEA: p=0.013; DHEA-S: p=0.040). Conclusions These data suggest that higher circulating DHEA(S) levels (while unmedicated and after eight weeks of SSRI treatment) predict SSRI-associated remission in MDD. This raises the possibility that endogenous DHEA(S) abundance is a physiological adjunct to SSRI efficacy, as suggested by prior preclinical and clinical studies.

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Antidepressant Treatment and Dehydroepiandrosterone Sulfate: Different Effects of Amitriptyline and Paroxetine

Cited by 13 publications

References 23 publications

The Relevance of Neuroactive Steroids in Schizophrenia, Depression, and Anxiety Disorders

The Relevance of Neuroactive Steroids in Schizophrenia, Depression, and Anxiety Disorders

Cortisol Metabolism in Depressed Patients and Healthy Controls

Higher serum DHEA concentrations before and after SSRI treatment are associated with remission of major depression

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