Improvement of Sustained Attention and Visual and Movement Skills, but Not Clinical Symptoms, After Dehydroepiandrosterone Augmentation in Schizophrenia

Tel Aviv University, Tell Afif, Tel Aviv, Israel
Journal of Clinical Psychopharmacology (Impact Factor: 3.24). 11/2006; 26(5):495-9. DOI: 10.1097/
Source: PubMed


Dehydroepiandrosterone (DHEA) augmentation has been reported, in a preliminary fashion, to be useful in the management of schizophrenia symptoms and side effects. In this study, the intention was to investigate the efficacy and safety of DHEA administration to ongoing antipsychotic medication in a multicenter, 12-week, double-blind, randomized, placebo-controlled, crossover trial.
Fifty-five of 62 inpatients and outpatients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of schizophrenia completed the trial. Patients were randomly allocated to 2 treatment groups receiving either DHEA (200 mg/d) or placebo for 6 weeks with the crossover between DHEA and placebo occurring after 6 weeks. Patients continued to receive their regular antipsychotic medication for the duration of the study.
Compared with placebo, DHEA administration did not produce significant improvement in clinical symptoms, side effects, and quality-of-life scores. However, 6 weeks of DHEA administration (but not placebo) was associated with a significant improvement in Positive and Negative Symptom Scale ratings compared with baseline. Furthermore, 6 weeks of DHEA treatment was associated with significant improvement in cognitive functions of visual sustained attention and visual and movement skills compared with placebo conditions. The DHEA augmentation was associated with elevations of serum concentrations of both DHEA and its sulfate ester. The DHEA treatment was well tolerated without any serious adverse effects.
This short-term study does not support DHEA's value as an effective adjunct in the treatment of symptoms, side effects, and quality-of-life impairment in schizophrenia, while suggesting that DHEA improves sustained attention and visual and movement skills. A long-term, large-scale study with a broader dose range is warranted to further investigate DHEA's role in the management of schizophrenia.

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Available from: Michael S. Ritsner
    • "They did not show a consistent and unequivocal significant favorable effect of DHEA administration on negative symptoms compared to placebo. In order to resolve some of the concerns that have risen in the cross sectional trials, a randomized, double-blind, placebo-controled crossover study was conducted in two mental health centers (Ritsner et al., 2006b). During this trial 55 patients received either DHEA (200 mg/d) or placebo in identical capsules for 6 weeks following which they were switched to either placebo or DHEA for a further 6 weeks. "

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    • "By contrast, higher DHEA(S) concentrations and DHEAS – cortisol ratios are associated with panic disorders (Fava et al. 1989; Eser et al. 2006). Inconsistently, DHEA(S) values have been linked to schizophrenia (Ritsner et al. 2006), dementia (Bernardi et al. 2000) as well as functional abilities in the elderly. Interestingly , consistent positive relationships have been observed between DHEA(S) (or DHEAS –cortisol) level and PTSD (Pico-Alfonso et al. 2004; Butterfield et al. 2005). "
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    ABSTRACT: Dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) are anabolic prehormones involved in the synthesis of testosterone. Both have been shown to exert neuroprotective effects during stress. In this randomized, controlled, double-blind field study, we examined the effects of a 12-day DHEA regimen on stress indices in military men undergoing survival training. Forty-eight men were randomized to either a DHEA treatment group or placebo control group. The treatment group received 50 mg of oral DHEA supplementation daily for 5 days during classroom training followed by 7 days of 75 mg during stressful field operations. Control subjects received identical placebo pills. Salivary assays (DHEA[S], testosterone, and cortisol) were conducted at four time points: distal pre-stress (T1), proximal pre-stress (T2), mock-captivity stress (T3), and 24 h recovery (T4). Subjective distress was also assessed at T1, T3, and T4. As expected, DHEA treatment resulted in higher salivary concentrations of DHEA and DHEAS during daily living, mock-captivity stress, and recovery. Similar patterns were observed for salivary markers of anabolic balance: DHEA/cortisol, DHEAS/cortisol, and testosterone/cortisol concentration ratios. Despite notable time effects, no group differences emerged for subjective distress. A brief, low dose DHEA regimen yielded large increases in salivary DHEA(S) concentrations and enhanced anabolic balance throughout sustained military stress. These physiological changes did not extrapolate to subjective distress.
    Full-text · Article · Jul 2011 · Stress (Amsterdam, Netherlands)
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    • "In order to resolve some of the concerns that have risen in the cross sectional trials, a randomized, double-blind, placebo-controled crossover study was conducted in two mental health centers (Ritsner et al., 2006b). "
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    ABSTRACT: Neurosteroids such as dehydroepiandrosterone (DHEA), pregnenolone (PREG), and their sulfates (DHEAS and PREGS) display multiple effects on the central nervous system. Specifically, neurosteroids have various functions associated with neuroprotection, response to stress, mood regulation, and cognitive performance. In addition, neurosteroid levels are altered in stress-related neuropsychiatric disorders. This review focuses on the alterations of these neurosteroids in schizophrenia and on their association with clinical and neurocognitive manifestations. As described henceforth, findings from clinical studies have revealed that PREG, DHEA, and their sulfates might be involved in the pathophysiology of schizophrenia, and in some of its manifestations. Clinical trials for the evaluation of these neurosteroids face challenges in terms of experimental design, dosing strategy, data analysis, and interpretation. The review concludes with a list of suggested topics for future research. This article is part of a Special Issue entitled: Neuroactive Steroids: Focus on Human Brain.
    Full-text · Article · Apr 2011 · Neuroscience
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