Improvement of extrapyramidal symptoms following dehydroepiandrosterone (DHEA) administration in antipsychotic treated schizophrenia patients: A randomized, double-blind placebo controlled trial
ABSTRACT Recent investigation in schizophrenia indicated dehydroepiandrosterone (DHEA) levels to be inversely correlated with extrapyramidal symptomatology (EPS). This study thus investigates the effect of DHEA administration on medication-induced EPS. Inpatients with schizophrenia or schizoaffective disorder were randomized in double-blind fashion to receive either 100 mg DHEA or placebo in addition to a constant dosage of antipsychotic medication. Parkinsonism showed a favorable effect of DHEA with a significant time effect (p < 0.0001), as well as a significant group by time interaction (p < 0.05) and with no change noted on akathisia. Change of DHEA blood levels was negatively associated with change of Parkinsonism (p < 0.05) as well as with change of total EPS ratings (p < 0.05). DHEA appears to demonstrate a significant effect on EPS, with improvement observed particularly in Parkinsonian symptoms.
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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.Neuroscience 04/2011; 191:91-100. DOI:10.1016/j.neuroscience.2011.04.017 · 3.33 Impact Factor
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ABSTRACT: Neurosteroids, such as pregnenolone (PREG), dehydroepiandrosterone (DHEA), and their sulfates (PREGS and DHEAS) are reported to have a modulatory effect on neuronal excitability and synaptic plasticity. They also have many other functions associated with neuroprotection, response to stress, mood regulation, and cognitive performance. Furthermore, these neurosteroids have been linked to, and their levels are altered in, neuropsychiatric disorders. This review highlights what is currently known about the metabolism and mode of action of PREG and DHEA, as well as about alterations of these neurosteroids in schizophrenia. This review also provides substantial information about clinical trials with DHEA and PREG augmentation with of antipsychotic agents in schizophrenia.CNS Neuroscience & Therapeutics 02/2010; 16(1):32-44. DOI:10.1111/j.1755-5949.2009.00118.x · 3.78 Impact Factor
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ABSTRACT: Hypercortisolaemia is a feature of many severe psychiatric illnesses and has been suggested to be both a causal and exacerbating factor of clinical symptoms and neurocognitive impairment. The adrenal steroid dehydroepiandrosterone (DHEA) has antiglucocorticoid properties that may have regulatory effects on glucocorticoid action in the brain. However, there is a paucity of data on these steroids and their ratio in schizophrenia and bipolar disorder. We therefore sought to assess cortisol and DHEA levels and the cortisol-DHEA ratio in patients with schizophrenia (n=20) and bipolar disorder (n=20), on stable medication for a minimum of 6 weeks, and healthy age- and sex-matched control subjects (n=20). Steroid levels were measured from plasma samples collected at 30 min intervals from 1:00 p.m. to 4:00 p.m. Cortisol levels were found to be significantly elevated in both patient groups compared with controls. DHEA levels were elevated in schizophrenic patients compared with bipolar patients and controls, but there was no evidence of a difference in the cortisol-DHEA ratio of the groups. These data suggest that afternoon hypercortisolaemia is evident in symptomatic bipolar and schizophrenic patients compared to controls. However, an elevation in DHEA levels may represent a specific endocrine marker in schizophrenia.Schizophrenia Research 03/2007; 90(1-3):258-65. DOI:10.1016/j.schres.2006.11.020 · 4.43 Impact Factor