-
Neurosurgical Focus Feb 2015OBJECT Cushing's disease (CD) can lead to significant morbidity secondary to hormonal sequelae or mass effect from the pituitary tumor. A transsphenoidal approach to... (Review)
Review
OBJECT Cushing's disease (CD) can lead to significant morbidity secondary to hormonal sequelae or mass effect from the pituitary tumor. A transsphenoidal approach to resection of the adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma is the first-line treatment. However, in the setting in which patients are unable to undergo surgery, have acute hypercortisolism, or have recurrent disease, medical therapy can play an important role. The authors performed a systematic review to highlight the efficacy of medical treatment of CD and discuss novel molecular insights that could guide the development of future medical treatments of CD. METHODS A search on current medical therapies for CD was performed. After individual medical therapeutic agents for CD were identified, each agent underwent a formal systematic search. The phrase "(name of agent) and Cushing's" was used as a search term in PubMed for all years up to 2014. The abstract of each article was reviewed for studies that evaluated the efficacy of medical treatment of CD. Only studies that enrolled at least 20 patients were included in the review. RESULTS A total of 11 articles on 6 individual agents were included in this review. Specific medical therapies were categorized based on the level of action: pituitary directed (cabergoline and pasireotide), adrenal/steroidogenesis directed (ketoconazole, metyrapone, and mitotane), and end-tissue directed/cortisol receptors (mifepristone). The studies identified consisted of a mix of retrospective reviews and small clinical trials. Only pasireotide and mifepristone have undergone Phase III clinical trials, from which they garnered FDA approval for the treatment of patients with CD. Overall, agents targeting ACTH secretion and steroidogenesis were found to be quite effective in reducing urine free cortisol (UFC) to levels near normal. A significant reduction in UFC was observed in 45%-100% of patients and a majority of patients gained clinical improvement. Similarly, inhibition at the end-tissue level led to clinical improvement in 87% of patients. However, side-effect rates associated with these drugs are high (up to 88%). Ketoconazole has been shown to enhance tumor appearance on MRI to facilitate pituitary resection. Promising molecular targets have been identified, including epidermal growth factor receptor, retinoic acid receptors, and cyclin dependent kinases. These pathways have been linked to the regulation of pro-opiomelanocortin expression, ACTH secretion, and tumor growth. CONCLUSIONS Despite encouraging Phase III clinical trials leading to FDA approval of 2 agents for treatment of patients with CD, no agent has yet produced results comparable to resection. As a result, the molecular insights gained into CD pathogenesis will need to continue to be expanded until they can lead to the development of medical therapies for CD with a favorable side-effect profile and efficacy comparable to resection. Ideally these agents should also reduce tumor size, which could potentially permit their eventual discontinuation.
Topics: Clinical Trials as Topic; Drug Delivery Systems; Female; Forecasting; Humans; Male; Mitotane; Pituitary ACTH Hypersecretion; Receptors, Retinoic Acid; Retrospective Studies; Somatostatin
PubMed: 25639313
DOI: 10.3171/2014.10.FOCUS14700 -
The Cochrane Database of Systematic... Jan 2011With the improvement of ultrasound technology, the likelihood of detection of major fetal structural anomalies in mid-pregnancy has increased considerably. Upon the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
With the improvement of ultrasound technology, the likelihood of detection of major fetal structural anomalies in mid-pregnancy has increased considerably. Upon the detection of serious anomalies, women typically are offered the option of pregnancy termination. Additionally, there are still many reasons other than fetal anomalies why women seek abortion in the mid-trimester.
OBJECTIVES
To compare different methods of second trimester medical termination of pregnancy for their efficacy and side-effects.
SEARCH STRATEGY
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, Popline and reference lists of retrieved papers and other sources.
SELECTION CRITERIA
All randomised controlled trials (RCTs) examining medical regimens for termination of pregnancy of a singleton living fetus between 12-28 weeks' gestation were analysed. The outcome measures were the induction to abortion interval, abortion rate within 24 hours, need for surgical evacuation, blood loss, uterine rupture, pain, and side-effects.Trials including >20% fetal death, multiple pregnancies, previous uterine scars and regimens which involved cervical preparation were excluded.
DATA COLLECTION AND ANALYSIS
Two authors selected the trials and three authors extracted data.
MAIN RESULTS
Fourty RCTs were included, addressing various agents for pregnancy termination and methods of administration. When used alone, misoprostol was an effective inductive agent, though it appeared to be more effective in combination with mifepristone. However, the evidence from RCTs is limited.Misoprostol was preferably administered vaginally, although among multiparous women sublingual administration appeared equally effective. A range of doses of vaginally administered misoprostol has been used. No randomised trials comparing doses of misoprostol were identified; however low doses of misoprostol appear to be associated with fewer side-effects while moderate doses appear to be more efficient in completing abortion. Four RCTs showed that the induction to abortion interval with 3-hourly vaginal administration of prostaglandins is shorter than 6-hourly administration without an increase in side-effects.Many studies reported the need for surgical evacuation. Indications for surgical evacuation include retained products of the placenta and heavy vaginal bleeding. Fewer women required surgical evacuation when misoprostol was administrated vaginally compared with women receiving intra-amniotical PGF(2a) . Mild, self-limiting diarrhoea was more common among women who received misoprostol compared to other agents.
AUTHORS' CONCLUSIONS
Medical abortion in the second trimester using the combination of mifepristone and misoprostol appeared to have the highest efficacy and shortest abortion time interval. Where mifepristone is not available, misoprostol alone is a reasonable alternative. The optimal route for administering misoprostol is vaginally, preferably using tablets at 3-hourly intervals. Apart from pain, the side-effects of vaginal misoprostol are usually mild and self limiting. Conclusions from this review are limited by the gestational age ranges and variable medical regimens, including dosing, administrative routes and intervals of medication, of the included trials.
Topics: Abortifacient Agents; Abortion, Induced; Administration, Intravaginal; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Mifepristone; Misoprostol; Pregnancy; Pregnancy Trimester, Second; Prostaglandins A; Randomized Controlled Trials as Topic
PubMed: 21249669
DOI: 10.1002/14651858.CD005216.pub2 -
The Cochrane Database of Systematic... Jan 2016Hypothalamic-pituitary-adrenal (HPA) axis dysregulation has been implicated in the development and relapse of psychotic disorders. Elevated cortisol secretion has been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hypothalamic-pituitary-adrenal (HPA) axis dysregulation has been implicated in the development and relapse of psychotic disorders. Elevated cortisol secretion has been positively linked with symptom severity in people with psychosis. Antiglucocorticoid and related drugs that target the HPA axis may be useful for the treatment of individuals with psychosis.
OBJECTIVES
1. To determine the effects of antiglucocorticoid and related drugs for the treatment of psychosis, when used alone or in combination with antipsychotic medication.2. To determine whether the effects of these medications differs between those in a prodromal phase or first episode of psychosis, and those with more established illness.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group's Trials Register (August 2009 and April 2014).
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing antiglucocorticoid and related drugs compared to placebo (either as a sole treatment or as an adjunct to atypical antipsychotics, typical antipsychotics, antidepressants or other combination treatment) for people with a primary diagnosis of a psychotic disorder, or for individuals at high risk of developing a psychotic disorder.
DATA COLLECTION AND ANALYSIS
Review authors independently selected trials, assessed methodological quality and extracted data. We used a fixed-effect meta-analysis. We calculated risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous outcomes, and mean differences (MDs) and standardised mean differences (SMDs) with 95% CIs for continuous measures. We assessed risk of bias for included studies and used GRADE (Grading of Recommendations Assessment, Development and Evaluation) to create a 'Summary of findings' table.
MAIN RESULTS
We included 11 studies that randomly assigned 509 people with schizophrenia, schizoaffective disorder or psychotic depression. No trials were conducted in patients at their first episode of psychotic illness and none included populations at high risk for developing psychosis. Our pre-stated outcomes of interest were mental state, global state, general functioning, adverse effects and quality of life.Two trials compared antiglucocorticoid drugs (mifepristone) versus placebo as sole treatment. Limited data from one trial showed no difference in the proportion responding to mifepristone when mental state was assessed immediately post intervention using the Brief Psychiatric Rating Scale (BPRS) (n = 5, 1 RCT, MD -5.20, 95% CI -17.91 to 7.51; very low-quality evidence); depressive symptoms (Hamilton Rating Scale for Depression (HAMD) total) were also similar between groups (n = 5, 1 RCT, MD 1.67, 95% CI -16.44 to 19.78; very low-quality evidence). However, a significant difference favoured treatment at short-term follow-up for global state (30% reduction in total BPRS, n = 221, 1 RCT, RR 0.58, 95% CI 0.38 to 0.89; low-grade quality evidence). This effect was also seen for short-term positive psychotic symptoms (50% reduction in BPRS positive symptom subscale, n = 221, 1 RCT, RR 0.60, 95% CI 0.43 to 0.84; low-grade quality evidence). Participants receiving mifepristone experienced a similar overall number of adverse effects as those receiving placebo (n = 226, 2 RCTs, RR 0.92, 95% CI 0.77 to 1.09; moderate-quality evidence). No data on general functioning or quality of life were available.One trial compared an antiglucocorticoid, dehydroepiandrosterone (DHEA), as an adjunct to atypical antipsychotic treatment to adjunctive placebo. Data for main outcomes of interest were of low quality, and analysis of useable data showed no significant effects of treatment on mental state or adverse effects. Data on global state, general functioning and quality of life were not available.Data from six trials comparing antiglucocorticoid drugs as an adjunct to combination treatment versus adjunctive placebo showed no significant differences between groups in mean endpoint scores for overall psychotic symptoms (n = 171, 6 RCTs, SMD 0.01, 95% CI - 0.29 to 0.32) or positive psychotic symptoms (n = 151, 5 RCTs, SMD -0.07, 95% CI - 0.40 to 0.25). Data from three trials showed no differences between groups in mean endpoint scores for negative symptoms (n = 94, 3 RCTs, MD 2.21, 95% CI -0.14 to 4.55). One study found improvements in global state that were similar between groups (n = 30, 1 RCT, RR 0.58, 95% CI 0.32 to 1.06; very low-quality evidence). In this comparison, pooled results showed that antiglucorticoids caused a greater overall number of adverse events (n = 199, 7 RCTs, RR 2.66, 95% CI 1.33 to 5.32; moderate quality evidence), but no quality of life data were available.
AUTHORS' CONCLUSIONS
Good evidence is insufficient to conclude whether antiglucocorticoid drugs provide effective treatment for psychosis. Some global state findings suggest a favourable effect for mifepristone, and a few overall adverse effect findings favour placebo. Additional large randomised controlled trials are needed to justify findings.
Topics: Dehydroepiandrosterone; Dexamethasone; Glucocorticoids; Humans; Hypothalamo-Hypophyseal System; Ketoconazole; Mifepristone; Pituitary-Adrenal System; Psychotic Disorders; Randomized Controlled Trials as Topic
PubMed: 26725721
DOI: 10.1002/14651858.CD006995.pub2 -
Contraception Dec 2022Abortion is common worldwide and increasingly abortions are performed at less than 14 weeks' gestation using medical methods, specifically using a combination of... (Review)
Review
INTRODUCTION
Abortion is common worldwide and increasingly abortions are performed at less than 14 weeks' gestation using medical methods, specifically using a combination of mifepristone and misoprostol. Medical abortion is known to be a painful process, but the optimal method of pain management is unclear. We sought to identify and compare pain management regimens for medical abortion before 14 weeks' gestation.
STUDY DESIGN
We conducted our search in August 2019 and included randomized controlled trials (RCT) and observational studies of any pain relief intervention (pharmacological and non-pharmacological) for mifepristone-misoprostol combination medical abortion of pregnancies less than 14 weeks' gestation.
RESULTS
We included four RCTs and one observational study. Due to the heterogeneity of study designs, interventions and outcome reporting, meta-analysis was not possible. Only one study found evidence of an effect between interventions on pain score: a prophylactic dose of ibuprofen 1600mg likely reduces the pain score when compared to a dose of paracetamol 2000mg (MD 2.26/10 [CI 3-1.52 lower]). For other interventions (pregabalin 300mg vs placebo; ibuprofen 800mg vs placebo; therapeutic vs prophylactic administration of ibuprofen 800mg; ambulation vs non-ambulation during treatment) there appeared to be little to no difference with comparator.
CONCLUSIONS
The findings of this review provide some support for the use of ibuprofen as a single dose given with misoprostol prophylactically, or in response to pain as needed. The optimal dosing of ibuprofen is unclear, but a single dose of ibuprofen 1600mg was shown to be effective and it was less certain whether 800mg was effective.
Topics: Humans; Female; Pregnancy; Pain Management; Misoprostol; Mifepristone; Ibuprofen; Pain; Observational Studies as Topic
PubMed: 36055363
DOI: 10.1016/j.contraception.2022.08.005 -
The Cochrane Database of Systematic... Jul 2009The steroid hormone, progesterone, inhibits contractions of the pregnant uterus at all gestations. Antiprogestins (including mifepristone) have been developed to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The steroid hormone, progesterone, inhibits contractions of the pregnant uterus at all gestations. Antiprogestins (including mifepristone) have been developed to antagonise the action of progesterone, and have a recognised role in medical termination of early or mid-trimester pregnancy. Animal studies have suggested that mifepristone may also have a role in inducing labour in late pregnancy.
OBJECTIVES
To determine the effects of mifepristone for third trimester cervical ripening or induction of labour.
SEARCH STRATEGY
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register and reference lists of relevant papers (May 2009).
SELECTION CRITERIA
Clinical trials comparing mifepristone used for third trimester cervical ripening or labour induction with placebo/no treatment or other labour induction methods.
DATA COLLECTION AND ANALYSIS
A strategy was developed to deal with the large volume and complexity of trial data relating to labour induction. This involved a two-stage method of data extraction. For this update, two review authors independently assessed trial quality and extracted data.
MAIN RESULTS
Ten trials (1108 women) are included. Compared to placebo, mifepristone treated women were more likely to be in labour or to have a favourable cervix at 48 hours (risk ratio (RR) 2.41, 95% confidence intervals (CI) 1.70 to 3.42) and this effect persisted at 96 hours (RR 3.40, 95% CI 1.96 to 5.92). They were less likely to need augmentation with oxytocin (RR 0.80, 95% CI 0.66 to 0.97). Mifepristone treated women were less likely to undergo caesarean section (RR 0.74, 95% CI 0.60 to 0.92) but more likely to have an instrumental delivery (RR 1.43, 95% CI 1.04 to 1.96). Women receiving mifepristone were less likely to undergo a caesarean section as a result of failure to induce labour (RR 0.40, 95% CI 0.20 to 0.80). There is insufficient evidence to support a particular dose but a single dose of 200 mg mifepristone appears to be the lowest effective dose for cervical ripening (increased likelihood of cervical ripening at 72 hours (RR 2.13, 95% CI 1.15 to 3.97). Abnormal fetal heart rate patterns were more common after mifepristone treatment (RR 1.85, 95% CI 1.17 to 2.93), but there was no evidence of differences in other neonatal outcomes. There is insufficient information on the occurrence of uterine rupture/dehiscence in the reviewed studies.
AUTHORS' CONCLUSIONS
There is insufficient information available from clinical trials to support the use of mifepristone to induce labour. However, the studies suggest that mifepristone is better than placebo in reducing the likelihood of caesarean sections being performed for failed induction of labour; therefore, this may justify future trials comparing mifepristone with the routine cervical ripening agents currently in use. There is little information on effects on the baby.
Topics: Female; Humans; Labor Stage, First; Labor, Induced; Mifepristone; Oxytocics; Pregnancy; Progesterone; Randomized Controlled Trials as Topic
PubMed: 19588336
DOI: 10.1002/14651858.CD002865.pub2 -
The Cochrane Database of Systematic... Aug 2010Induction of labour is carried out for a variety of indications and using a range of pharmacological, mechanical and other methods. For women at low risk, some methods... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Induction of labour is carried out for a variety of indications and using a range of pharmacological, mechanical and other methods. For women at low risk, some methods of induction of labour may be suitable for use in outpatient settings.
OBJECTIVES
To examine pharmacological and mechanical interventions to induce labour in outpatient settings in terms of feasibility, effectiveness, maternal satisfaction, healthcare costs and, where information is available, safety. The review complements existing reviews on labour induction examining effectiveness and safety.
SEARCH STRATEGY
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (December 2009) and reference lists of retrieved studies.
SELECTION CRITERIA
We included randomised controlled trials examining outpatient cervical ripening or induction of labour with pharmacological agents or mechanical methods.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data and assessed eligible papers for risk of bias. We checked all data after entry into review manager software.
MAIN RESULTS
We included 28 studies with 2616 women examining different methods of induction of labour where women received treatment at home or were sent home after initial treatment and monitoring in hospital.Studies examined vaginal and intracervical PGE(2), vaginal and oral misoprostol, isosorbide mononitrate, mifepristone, oestrogens, and acupuncture. Overall, the results demonstrate that outpatient induction of labour is feasible and that important adverse events are rare. There was no strong evidence that agents used to induce labour in outpatient settings had an impact (positive or negative) on maternal or neonatal health. There was some evidence that, compared to placebo or no treatment, induction agents reduced the need for further interventions to induce labour, and shortened the interval from intervention to birth. We were unable to pool results on outcomes relating to progress in labour as studies tended to measure a very broad range of outcomes.There was no evidence that induction agents increased interventions in labour such as operative deliveries. Only two studies provided information on women's views about the induction process, and overall there was very little information on the costs to health service providers of different methods of labour induction in outpatient settings.
AUTHORS' CONCLUSIONS
Induction of labour in outpatient settings appears feasible. We do not have sufficient evidence to know which induction methods are preferred by women, or the interventions that are most effective and safe to use in outpatient settings.
Topics: Acupuncture Therapy; Ambulatory Care; Feasibility Studies; Female; Humans; Labor, Induced; Oxytocics; Pregnancy; Randomized Controlled Trials as Topic
PubMed: 20687092
DOI: 10.1002/14651858.CD007701.pub2 -
The Cochrane Database of Systematic... Jan 2010The introduction of a new progestin-only oral contraceptive in Europe has renewed interest in this class of oral contraceptives. Unlike the more widely used combined... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The introduction of a new progestin-only oral contraceptive in Europe has renewed interest in this class of oral contraceptives. Unlike the more widely used combined oral contraceptives containing an estrogen plus progestin, these pills contain only a progestin (progestogen) and are taken without interruption. How these pills compare to others in their class or to combined oral contraceptives is not clear.
OBJECTIVES
This review examined randomized controlled trials of progestin-only pills for differences in efficacy, acceptability, and continuation rates.
SEARCH STRATEGY
We searched the computerized databases MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), POPLINE, LILACS, and EMBASE for studies of progestin-only pills. We also searched for current trials via ClinicalTrials.gov and ICTRP.
SELECTION CRITERIA
We included all randomized controlled trials in any language that included progestin-only pills for contraception. We incorporated any comparison with a progestin-only pill; this could include different doses, other progestin-only pills, combined oral contraceptives, or other contraceptives.
DATA COLLECTION AND ANALYSIS
The first author abstracted the data and entered the information into RevMan 5. Another author performed a second, independent data abstraction to verify the initial data entry. Because of disparate exposures, we were not able to combine studies in meta-analysis.
MAIN RESULTS
Six trials met the inclusion criteria. In the trial comparing the desogestrel versus levonorgestrel progestin-only pill, desogestrel was not associated with a significantly lower risk of accidental pregnancy; the rate ratio was 0.27 (95% CI 0.06 to 1.19). However, the desogestrel progestin-only pill caused more bleeding problems, although this difference was not statistically significant. The trial comparing low-dose mifepristone versus a levonorgestrel progestin-only pill found similar pregnancy rates. In the trial comparing ethynodiol diacetate versus a combined oral contraceptive, irregular cycles occurred in all women assigned to the progestin-only pill (odds ratio 135.96; 95% CI 7.61 to 2421.02). In a trial comparing two progestin-only and two combined oral contraceptives, the progestin-only pill containing levonorgestrel 30 mug had higher efficacy than did the pill containing norethisterone 350 mug. An early trial found megestrol acetate inferior to other progestin-only pills in terms of efficacy. A study of the timing of pill initiation after birth found no important differences, but high losses to follow up undermined the trial.
AUTHORS' CONCLUSIONS
Evidence is insufficient to compare progestin-only pills to each other or to combined oral contraceptives.
Topics: Contraceptives, Oral, Combined; Contraceptives, Oral, Hormonal; Desogestrel; Ethynodiol Diacetate; Female; Humans; Levonorgestrel; Progestins; Randomized Controlled Trials as Topic; Uterine Hemorrhage
PubMed: 20091638
DOI: 10.1002/14651858.CD007541.pub2 -
The Cochrane Database of Systematic... Mar 2013Induction of labour is a common obstetric intervention, with between 20% and 30% of births reported to occur following induction of labour. Women with a prior caesarean... (Review)
Review
BACKGROUND
Induction of labour is a common obstetric intervention, with between 20% and 30% of births reported to occur following induction of labour. Women with a prior caesarean delivery have an increased risk of uterine rupture, particularly when labour is induced. For women who have had a previous caesarean birth and who require induction of labour in a subsequent pregnancy, it is unclear which method of cervical ripening and labour induction is preferable.
OBJECTIVES
To assess the benefits and harms associated with different methods used to induce labour in women who have had a previous caesarean birth and require induction of labour in a subsequent pregnancy.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 July 2012) and reference lists of retrieved studies.
SELECTION CRITERIA
All randomised controlled trials comparing any method of third trimester cervical ripening or labour induction, with placebo/no treatment or other methods in women with prior caesarean section requiring labour induction in a subsequent pregnancy were included.Methods of cervical ripening or labour induction could include: prostaglandin medication (including oral or vaginal prostaglandin E2 (PGE2) and misoprostol); mifepristone; mechanical methods (including Foley catheters and double balloon catheters); oxytocin, or placebo.
DATA COLLECTION AND ANALYSIS
The two review authors independently assessed studies for inclusion and trial quality. Any disagreement was resolved by discussion. Both review authors independently extracted data and data were checked for accuracy.
MAIN RESULTS
Two studies (involving a total of 80 women) were included. However, the two included studies used different methods and thus, meta-analysis was not appropriate. The two included studies compared 2.5 mg vaginal PGE2 inserts versus oxytocin (Taylor and colleagues) and misoprostol versus oxytocin (Wing and colleagues). Risk of bias in the included studies was judged 'low' and 'unclear' respectively.Vaginal PGE2 inserts versus oxytocin - Taylor and colleagues included 42 women, equally distributed over both groups. Baseline characteristics, and reasons for labour induction were comparable between the groups. There were no significant differences in any of the outcome measures reported (caesarean section, instrumental vaginal deliveries, epidural analgesia, Apgar score, perinatal death). One uterine rupture occurred in the prostaglandin group, after the use of prostaglandins and oxytocin, while no ruptures occurred in the oxytocin group (one study, 42 women; risk ratio (RR) 3.00, 95% confidence interval (CI) 0.13 to 69.70).Misoprostol versus oxytocin - the study conducted by Wing and colleagues was stopped prematurely due to safety concerns after the inclusion of 38 women. Seventeen women had been included in the misoprostol group, and 21 women in the oxytocin group. There were no significant difference in the only outcome measure reported by the authors, uterine rupture, which occurred twice in the misoprostol group, and did not occur in the oxytocin group (one study; 38 women; RR 6.11, 95% CI 0.31 to 119.33).
AUTHORS' CONCLUSIONS
There is insufficient information available from randomised controlled trials on which to base clinical decisions regarding the optimal method of induction of labour in women with a prior caesarean birth.
Topics: Dinoprostone; Early Termination of Clinical Trials; Female; Humans; Labor, Induced; Misoprostol; Oxytocics; Oxytocin; Pregnancy; Randomized Controlled Trials as Topic; Uterine Rupture; Vaginal Birth after Cesarean
PubMed: 23543582
DOI: 10.1002/14651858.CD009792.pub2 -
The Cochrane Database of Systematic... Jan 2008Antiglucocorticoids may have antidepressant effects and have been reported to be efficacious in the treatment of severe psychiatric disorders. The efficacy and safety of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antiglucocorticoids may have antidepressant effects and have been reported to be efficacious in the treatment of severe psychiatric disorders. The efficacy and safety of antiglucocorticoid treatments for mood disorders is the subject of this systematic review.
OBJECTIVES
To compare the efficacy and safety of antiglucocorticoid agents in the treatment of mood episodes (manic, mixed affective or depressive) with placebo or alternative drug treatment in mood disorders.
SEARCH STRATEGY
CCDANCTR-Studies and CCDANCTR-References were searched on 11-9-2007. Additional searches of electronic databases were conducted in December 2006. Conference proceedings were searched. Experts and pharmaceutical companies were contacted.
SELECTION CRITERIA
Randomised controlled trials comparing antiglucocorticoid drugs in the treatment of mood episodes with placebo or alternative drug treatment in mood disorders were selected.
DATA COLLECTION AND ANALYSIS
Data were extracted and the methodological quality of each study was assessed independently by two review authors. Meta-analyses were performed using Review Manager software. Relative risk (RR) with 95% confidence intervals (CI) were calculated for dichotomous outcomes. For continuous data, weighted mean differences (WMD) were calculated.
MAIN RESULTS
Nine studies met criteria for inclusion. A number of drugs were examined, including mifepristone [RU-486], ketoconazole, metyrapone and DHEA. Three trials were in patients with psychotic major depression (pMDD), five trials in non-psychotic major depression and one trial in bipolar disorder. When examining all trials together across all affective episodes, there was no significant difference in the overall proportion of patients responding to antiglucocorticoid treatment over placebo, although the mean change in HAM-D scores indicated a significant difference in favour of treatment (WMD -4.54, 95%CI -6.78 to -2.29). Of the five trials in non-psychotic depression (unipolar or bipolar), there was a significant difference favouring treatment (HAM-D 50% reduction: RR 0.72, 95%CI 0.56 to 0.91). In pMDD, there was no evidence of an overall antidepressant effect (HAM-D 50% reduction: RR 0.98, 95%CI 0.79 to 1.22) or an effect on overall psychopathology (BPRS 30% reduction: RR 0.96, 95%CI 0.76 to 1.22). In these subtypes, the mean change in HAM-D indicated a significant difference in favour of treatment.
AUTHORS' CONCLUSIONS
The use of antiglucocorticoids in the treatment of mood disorders is at the proof-of-concept stage. Considerable methodological differences exist between studies with respect to the compounds used and the patient cohorts studied. Results in some diagnostic subtypes are promising and warrant further investigation to establish the clinical utility of these drugs in the treatment of mood disorders.
Topics: Bipolar Disorder; Depressive Disorder; Glucocorticoids; Humans; Hydrocortisone; Mood Disorders; Randomized Controlled Trials as Topic
PubMed: 18254070
DOI: 10.1002/14651858.CD005168.pub2 -
European Journal of Obstetrics,... Mar 2006to compare the benefits and harms of misoprostol to induce labour in the second and third trimester of pregnancy with cervagem. (Review)
Review
AIMS
to compare the benefits and harms of misoprostol to induce labour in the second and third trimester of pregnancy with cervagem.
METHODS
MEDLINE was searched using the terms abortion, induced; abortifacient agents; pregnancy, second trimester; pregnancy, third trimester; misoprostol; cervagem; and gemeprost to identify randomised controlled trials in which misoprostol was compared with cervagem, for induction of labour to terminate pregnancy in the second or third trimester. Outcomes included vaginal birth not achieved within 24h; induction to delivery interval; analgesia requirements; blood loss; blood transfusion; surgical evacuation of the uterus; maternal death or serious maternal morbidity; side effects.
RESULTS
Six randomised trials were included. Five compared vaginal misoprostol with cervagem [el Refaey H, Hinshaw K, Templeton A. The abortifacient effect of misoprostol in the second trimester: a randomized comparison with gemeprost in patients pre-treated with mifepristone (RU486). Hum Reprod 1993;8(10):1744-6; Ho PC, Chan YF, Lau W. Misoprostol is as effective as gemeprost in termination of second trimester pregnancy when combined with mifepristone: a randomised comparative trial. Contraception 1996;53(5):281-3; Nuutila M, Toivonen J, Ylikorkala O, Halmesmaki E. A comparison between two doses of intravaginal misoprostol and gemeprost for induction of second trimester abortion. Obstetr Gynecol 1997;90(6):896-900; Wong KS, Ngai CS, Wong AY, Tang LC, Ho PC. Vaginal misoprostol compared with vaginal gemeprost in termination of pregnancy: a randomized controlled trial. Contraception 1998;58(4):207-10; Dickinson JE, Godfrey M, Evans SF. Efficacy of intravaginal misoprostol in second trimester termination of pregnancy: a randomized controlled trial. J Mater Fetal Med 1999;7(3):115-9], and one oral misoprostol with gemeprost [Bartley J, Baird DT. A randomised study of misoprostol and gemeprost in combination with mifepristone for induction of abortion in the second trimester of pregnancy. Br J Obstetr Gynaecol 2002;109(11):1290-4]. Vaginal misoprostol compared with cervagem was associated with reduced narcotic analgesia (3 studies, 169 women, RR 0.64 95% CI 0.49-0.84), and surgical evacuation of the uterus (5 studies, 319 women, RR 0.71 95% CI 0.53-0.95). No other statistically significant differences were observed for other outcomes with reported data. In the single trial comparing oral misoprostol with gemeprost, reported outcomes were similar.
CONCLUSIONS
Vaginal misoprostol for the termination of second and third trimester of pregnancy appears as effective as cervagem, but information about maternal safety is limited.
Topics: Abortifacient Agents, Nonsteroidal; Abortion, Induced; Administration, Intravaginal; Administration, Oral; Alprostadil; Female; Humans; Labor, Induced; Misoprostol; Pregnancy; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 16466671
DOI: 10.1016/j.ejogrb.2005.10.021