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Antiglucocorticoid treatments for mood disorders

Many patients with mood disorders report problems with memory and concentration, alongside their mood symptoms. There is some evidence that a possible cause of these problems is an overactivity of the hypothalamic‐pituitary‐adrenal (HPA) axis, the body's natural stress system. This leads to an overproduction of the stress‐hormone, cortisol. Therefore, it is possible that drugs which target the HPA axis may be of benefit. The efficacy and safety of antiglucocorticoids in the treatment of mood disorders was the subject of this systematic review. Nine studies met criteria for inclusion. Of these, a number of drugs were examined, including: mifepristone [RU‐486] (n=4), ketoconazole (n=2), metyrapone (n=2), and DHEA (n=1). Three of the trials were in patients with psychotic major depression (pMDD), five trials in non‐psychotic major depression and one trial in patients with bipolar disorder (currently depressed; non‐psychotic). Overall, when examining all trials together over all affective episodes, there was no significant difference in the overall proportion of patients responding (HAM‐D 50% reduction) to treatment with antiglucocorticoids over placebo. However the mean change (WMD; baseline to end‐point) in HAM‐D scores indicated a significant difference in favour of treatment . There is clearer evidence of efficacy in specific diagnostic subtypes. Of the five trials in non‐psychotic depression (unipolar or bipolar), there was a significant difference in favour of treatment. In psychotic depression, there was no evidence of an overall antidepressant effect or an effect on overall psychopathology (BPRS 30% reduction). In these subtypes the mean change (WMD) in scores indicated a significant difference in favour of treatment . To date only one trial has examined the impact of antiglucocorticoids on neuropsychological functioning. There are limited reports on side effects; overall, the only event to reach significance was the incidence of a rash occurring more often after active treatment, and this was reported in two studies . In summary, the use of antiglucocorticoids in the treatment of mood disorders and psychosis is very much at the proof‐of‐concept stage. A great deal of difference exists between studies with respect to the compounds used, patient cohort under investigation and methodology. Results in some diagnostic subtypes are promising and warrant further examination to better examine the clinical utility of this class of drug.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2009

Pituitary Tumors Treatment (PDQ®): Health Professional Version

Expert-reviewed information summary about the treatment of pituitary tumors.

PDQ Cancer Information Summaries [Internet] - National Cancer Institute (US).

Version: May 14, 2015

Adrenocortical Carcinoma Treatment (PDQ®): Health Professional Version

Expert-reviewed information summary about the treatment of adrenocortical carcinoma.

PDQ Cancer Information Summaries [Internet] - National Cancer Institute (US).

Version: November 15, 2012

Primary Care Management of Abnormal Uterine Bleeding [Internet]

The Vanderbilt Evidence-based practice Center systematically reviewed evidence about interventions for symptomatic abnormal uterine bleeding (AUB), both irregular and cyclic. We focused on interventions that are suitable for use in primary care practice including medical, behavioral, and complementary and alternative medicine approaches.

Comparative Effectiveness Reviews - Agency for Healthcare Research and Quality (US).

Version: March 2013
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Depression in Adults with a Chronic Physical Health Problem: Treatment and Management

This clinical guideline was commissioned by NICE and developed by the National Collaborating Centre for Mental Health. It sets out clear, evidenceand consensus-based recommendations for healthcare staff on how to treat and manage depression in adults with a chronic physical health problem.

NICE Clinical Guidelines - National Collaborating Centre for Mental Health (UK).

Version: 2010
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Hypothalamic-pituitary-adrenal axis suppression in asthmatic children on inhaled corticosteroids (Part 2) - the risk as determined by gold standard adrenal function tests: a systematic review

The evidence for hypothalamic-pituitary-adrenal axis (HPA) suppression by inhaled corticosteroids (ICS) was found to be conflicting. Reviewers have not distinguished between gold standard and basal adrenal function tests. The utility of the latter is limited by physiological and pathological variability as well as by methodological concerns. The risk of HPA suppression in asthmatic children and adolescents treated with ICS, as determined by gold standard adrenal function tests, needs to be established. A systematic review of the literature from January 1973 to July 2005 was performed. The Medline and Cochrane databases were searched, the reference lists of retrieved articles were inspected and pharmaceutical companies were approached. Randomized-controlled trials, cohort and case-control studies designed to detect HPA suppression caused by ICS, diagnosed by the insulin tolerance test (ITT) or the metyrapone test, performed on asthmatics of all ages not on oral steroids, were included and assessed for methodological quality. Of the 22 identified studies only four met the criteria for inclusion. All of these were published before 1988 and only one was methodologically sound. The cohort study showed that the baseline risk for HPA suppression is 0% while the absolute risk is 100% in asthmatic children treated with a beclomethasone dipropionate metered dose inhaler at a dose of 250-600 mug/m(2)/day for 6-42 months. As suggested by other observations these results could be generalized to other ICS. They may be of clinical significance especially if children are subjected to stress. Further research is needed to establish the cumulative dose for all ICS at which HPA suppression will be precipitated. Guidelines for future trials are suggested.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2007

Systematic Reviews in PubMed

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