Mifepristone versus Placebo in the Treatment of Psychosis in Patients with Psychotic Major Depression

DeBattista, Charles; Belanoff, Joseph K.; Glass, Steven; Khan, Arif; Horne, Robert Lynn; Blasey, Christine; Carpenter, Linda L.; Alva, Gustavo

doi:10.1016/j.biopsych.2006.05.034

Cited by 148 publications

(86 citation statements)

References 47 publications

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“…[115][116][117] Consistent with the results of behavioral studies, chronic corticosterone administration and isolation rearing enhanced dopaminergic neurotransmission in the prefrontal cortex, and this enhanced neurotransmission was reversed by RU-43044 110) (Fig. 5).…”

Section: Corticosterone Modelsupporting

confidence: 85%

Neuropharmacologic Studies on the Brain Serotonin<sub>1A</sub> Receptor Using the Selective Agonist Osemozotan

Matsuda

2013

Biological & Pharmaceutical Bulletin

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Alterations in serotonin (5-HT) neurochemistry have been implicated in the etiology of major neuropsychiatric disorders such as anxiety-spectrum disorders, depression, and schizophrenia. The neuromodulatory effects of 5-HT are mediated through 14 receptor subtypes, and those receptors, including the 5-HT 1A receptor, are considered to be potential targets for the treatment of psychiatric disorders. We developed the novel 5-HT 1A receptor agonist MKC-242 (called osemozotan) and characterized its neurochemical and pharmacological profiles. 5-HT 1A receptor agonists modulate the release of amine neurotransmitters through the activation of presynaptic or postsynaptic 5-HT 1A receptors in the brain. The agonist has antianxiety and antidepressant effects and improves abnormal behaviors such as aggressive behavior and deficits of prepulse inhibition in isolation-reared mice. We also demonstrated that spinal 5-HT 1A receptor activation is involved in isolation rearing-induced hypoalgesia. Concerning the mechanism for induction of isolation-induced abnormal behaviors, we have recently found that the raphe-prefrontal 5-HT system plays a key role in encounter stimulation-induced hyperactivity in isolation-reared mice. Furthermore, we showed that osemozotan attenuates psychostimulant-induced behavioral sensitization and that prefrontal dopamine release is enhanced by functional interaction between the 5-HT 1A receptor and other receptors. This review summarizes the neuropharmacology of the 5-HT 1A receptor, focusing on our studies using osemozotan, and suggests that the 5-HT 1A receptor may be a target molecule for the treatment of psychiatric disorders, pain, and drug dependence.

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Section: Corticosterone Modelsupporting

confidence: 85%

Neuropharmacologic Studies on the Brain Serotonin<sub>1A</sub> Receptor Using the Selective Agonist Osemozotan

Matsuda

2013

Biological & Pharmaceutical Bulletin

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“…The expected cell sizes in this study were not less than 5 given the high placebo response rates observed in a recent PMD in-patient, add-on trial (DeBattista et al, 2003). Moreover, in a previous criticism of the Belanoff case series (Rubin and Carroll, 2004), they themselves applied an uncorrected w 2 to even smaller cell sizes.…”

Section: Sirmentioning

confidence: 68%

Reply: Clinical and Biological Effects of Mifepristone Treatment for Psychotic Treatment

Keller

Schatzberg

2006

Neuropsychopharmacol

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“…130,131 Initial open 130 and small, double-blind, placebo-controlled 131 trials in patients with psychotic depression suggested efficacy. Subsequent, larger, randomized controlled trials by the same group showed a benefit for psychotic but not mood symptoms in one trial 132 and no benefit on primary outcome measures in a second. 133 A further trial has shown the importance of plasma levels of mifepristone, with a benefit seen in patients whose levels were above a cut-off point.…”

Section: Glucocorticoid Receptor Antagonistsmentioning

confidence: 98%

Role of corticosteroids in the antidepressant response

Pierscionek¹,

Adekunte²,

Watson³

et al. 2014

CPT

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Anything that engenders a homeostatic response in the tightly regulated hypothalamic-pituitary-adrenal (HPA) axis may be thought of as a stressor and may exert an allostatic load, engendering a sustained change in the regulation of this system. Genetic, epigenetic, endocrine, post mortem, and animal studies suggest that dysregulation of the HPA axis plays a part in the pathophysiology of mood disorders and negatively impacts the antidepressant response and prognosis. Neuropsychological impairment, which is a common and disabling concomitant of depression, has been linked to disturbance of the HPA axis. A number of HPA axis-mediated treatment strategies have shown benefit in open or smallscale preliminary trials, and there are ongoing studies seeking both to replicate these initial findings and to develop new targets. HPA axis-based treatments are a fertile area of research, and much current thought pertains to the optimum targets, optimum population (including the potential for stratified medicine), and optimum outcome measures. We have, for instance, argued here that neuropsychological performance may be more sensitive and robust than scores on traditional depression rating scales.

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Mifepristone versus Placebo in the Treatment of Psychosis in Patients with Psychotic Major Depression

Cited by 148 publications

References 47 publications

Neuropharmacologic Studies on the Brain Serotonin<sub>1A</sub> Receptor Using the Selective Agonist Osemozotan

Neuropharmacologic Studies on the Brain Serotonin<sub>1A</sub> Receptor Using the Selective Agonist Osemozotan

Reply: Clinical and Biological Effects of Mifepristone Treatment for Psychotic Treatment

Role of corticosteroids in the antidepressant response

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