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CNS Drugs Dec 2022Research comparing levodopa/carbidopa intestinal gel (LCIG), deep brain stimulation (DBS), and continuous subcutaneous apomorphine infusion (CSAI) for advanced... (Meta-Analysis)
Meta-Analysis
Comparative Effectiveness of Device-Aided Therapies on Quality of Life and Off-Time in Advanced Parkinson's Disease: A Systematic Review and Bayesian Network Meta-analysis.
INTRODUCTION
Research comparing levodopa/carbidopa intestinal gel (LCIG), deep brain stimulation (DBS), and continuous subcutaneous apomorphine infusion (CSAI) for advanced Parkinson's disease (PD) is lacking. This network meta-analysis (NMA) assessed the comparative effectiveness of LCIG, DBS, CSAI and best medical therapy (BMT) in reducing off-time and improving quality of life (QoL) in patients with advanced PD.
METHODS
A systematic literature review was conducted for randomized controlled trials (RCTs), observational and interventional studies from January 2003 to September 2019. Data extracted at baseline and 6 months were off-time, as reported by diary or Unified Parkinson's Disease Rating Scale Part IV item 39, and QoL, as reported by Parkinson's Disease Questionnaire (PDQ-39/PDQ-8). Bayesian NMA was performed to estimate pooled treatment effect sizes and to rank treatments in order of effectiveness.
RESULTS
A total of 22 studies fulfilled the inclusion criteria (n = 2063 patients): four RCTs, and 16 single-armed, one 2-armed and one 3-armed prospective studies. Baseline mean age was between 55.5-70.9 years, duration of PD was 9.1-15.3 years, off-time ranged from 5.4 to 8.7 h/day in 9 studies, and PDQ scores ranged from 28.8 to 67.0 in 19 studies. Levodopa/carbidopa intestinal gel and DBS demonstrated significantly greater improvement in off-time and QoL at 6 months compared with CSAI and BMT (p < 0.05). There was no significant difference in the effects of LCIG and DBS, but DBS was ranked first for reduction in off-time, and LCIG was ranked first for improvement in QoL.
CONCLUSIONS
This NMA found that LCIG and DBS were associated with superior improvement in off-time and PD-related QoL compared with CSAI and BMT at 6 months after treatment initiation. This comparative effectiveness research may assist providers, patients, and caregivers in the selection of the optimal device-aided therapy.
Topics: Humans; Middle Aged; Aged; Carbidopa; Levodopa; Quality of Life; Network Meta-Analysis; Parkinson Disease; Apomorphine
PubMed: 36414908
DOI: 10.1007/s40263-022-00963-9 -
Current Problems in Cardiology Feb 2023Heart failure (HF) is one of the leading causes of maternal mortality and morbidity in the United States. Peripartum cardiomyopathy (PPCM) constitutes up to 70% of all... (Meta-Analysis)
Meta-Analysis Review
Heart failure (HF) is one of the leading causes of maternal mortality and morbidity in the United States. Peripartum cardiomyopathy (PPCM) constitutes up to 70% of all HF in pregnancy. Cardiac angiogenic imbalance caused by cleaved 16kDa prolactin has been hypothesized to contribute to the development of PPCM, fueling investigation of prolactin inhibitors for the management of PPCM. We conducted a systematic review and meta-analysis to assess the impact of prolactin inhibition on left ventricular (LV) function and mortality in patients with PPCM. We included English language articles from PubMed and EMBASE published upto March 2022. We pooled the mean difference (MD) for left ventricular ejection fraction (LVEF) at follow-up, odds ratio (OR) for LV recovery and risk ratio (RR) for all-cause mortality using random-effects meta-analysis. Among 548 studies screened, 10 studies (3 randomized control trials (RCTs), 2 retrospective and 5 prospective cohorts) were included in the systematic review. Patients in the Bromocriptine + standard guideline directed medical therapy (GDMT) group had higher LVEF% (pMD 12.56 (95% CI 5.84-19.28, I2=0%) from two cohorts and pMD 14.25 (95% CI 0.61-27.89, I2=88%) from two RCTs) at follow-up compared to standard GDMT alone group. Bromocriptine group also had higher odds of LV recovery (pOR 3.55 (95% CI 1.39-9.1, I2=62)). We did not find any difference in all-cause mortality between the groups. Our analysis demonstrates that the addition of Bromocriptine to standard GDMT was associated with a significant improvement in LVEF% and greater odds of LV recovery, without significant reduction in all-cause mortality.
Topics: Pregnancy; Female; Humans; Bromocriptine; Prolactin; Peripartum Period; Cardiomyopathies; Ventricular Function, Left; Heart Failure; Stroke Volume; Pregnancy Complications, Cardiovascular
PubMed: 36261102
DOI: 10.1016/j.cpcardiol.2022.101461 -
Gynecological Endocrinology : the... Nov 2022The aim of this systematic review is to recap the data obtained from randomized controlled trials looking at new pharmacologic treatments for endometriosis published...
The aim of this systematic review is to recap the data obtained from randomized controlled trials looking at new pharmacologic treatments for endometriosis published over the last decade with a focus on non-hormonal therapeutic options alleviating endometriosis-associated pelvic pain. We identified relevant original studies in the English language through a search of the MEDLINE, Scopus, and EMBASE (2012 to present) databases using the appropriate MeSH terms and applying the article type filter 'randomized controlled trials'. A total of 179 records were found during the electronic search. After a detailed evaluation and review of the manuscripts, seven primary articles met the inclusion criteria. A systematic review of the data was conducted. This review included several, non-hormonal emerging drug therapies for endometriosis-associated pelvic pain. Based on our results, we divided well-founded studies into three subgroups: antiangiogenic agents, immunomodulators, and natural components. Randomized control trials showed promising results with dopamine agonists (cabergoline, quinagolide, and bromocriptine), and the immunomodulatory JNK inhibitor bentamapimod. Agents that have not been represented in randomized control trials or have failed to demonstrate efficacy include statins and TNF-α inhibitors. Although there are substantial improvements in non-hormonal therapy options, majority of the currently available treatment options are supressive rather than curative and do not present a final solution for patients. Future research priorities should be to identify novel target therapies and to evalute the effects of available drugs through different routes of administration.
Topics: Female; Humans; Cabergoline; Dopamine Agonists; Endometriosis; Pelvic Pain
PubMed: 36237165
DOI: 10.1080/09513590.2022.2133105 -
Psychopharmacology Nov 2022While one of the basic axioms of pharmacology postulates that there is a relationship between the concentration and effects of a drug, the value of measuring blood... (Meta-Analysis)
Meta-Analysis Review
RATIONALE
While one of the basic axioms of pharmacology postulates that there is a relationship between the concentration and effects of a drug, the value of measuring blood levels is questioned by many clinicians. This is due to the often-missing validation of therapeutic reference ranges.
OBJECTIVES
Here, we present a prototypical meta-analysis of the relationships between blood levels of aripiprazole, its target engagement in the human brain, and clinical effects and side effects in patients with schizophrenia and related disorders.
METHODS
The relevant literature was systematically searched and reviewed for aripiprazole oral and injectable formulations. Population-based concentration ranges were computed (N = 3,373) and pharmacokinetic influences investigated.
RESULTS
Fifty-three study cohorts met the eligibility criteria. Twenty-nine studies report blood level after oral, 15 after injectable formulations, and nine were positron emission tomography studies. Conflicting evidence for a relationship between concentration, efficacy, and side effects exists (assigned level of evidence low, C; and absent, D). Population-based reference ranges are well in-line with findings from neuroimaging data and individual efficacy studies. We suggest a therapeutic reference range of 120-270 ng/ml and 180-380 ng/ml, respectively, for aripiprazole and its active moiety for the treatment of schizophrenia and related disorders.
CONCLUSIONS
High interindividual variability and the influence of CYP2D6 genotypes gives a special indication for Therapeutic Drug Monitoring of oral and long-acting aripiprazole. A starting dose of 10 mg will in most patients result in effective concentrations in blood and brain. 5 mg will be sufficient for known poor metabolizers.
Topics: Humans; Aripiprazole; Schizophrenia; Reference Values; Antipsychotic Agents; Cytochrome P-450 CYP2D6
PubMed: 36195732
DOI: 10.1007/s00213-022-06233-2 -
Molecular Psychiatry Jan 2023People with mood disorders have increased risk of comorbid medical diseases versus the general population. It is paramount to identify interventions to improve physical...
The impact of pharmacological and non-pharmacological interventions on physical health outcomes in people with mood disorders across the lifespan: An umbrella review of the evidence from randomised controlled trials.
OBJECTIVE
People with mood disorders have increased risk of comorbid medical diseases versus the general population. It is paramount to identify interventions to improve physical health in this population.
METHODS
Umbrella review of meta-analyses of randomised controlled trials (RCTs) on pharmacological/non-pharmacological interventions for physical health outcomes/intolerability-related discontinuation in mood disorders (any age).
RESULTS
Ninety-seven meta-analyses were included. Among youths, against placebo, in depression, antidepressants/antipsychotics had higher discontinuation rates; in bipolar depression, olanzapine+fluoxetine worsened total cholesterol (TC)/triglycerides/weight gain (WG) (large ES). In adults with bipolar disorder, olanzapine worsened HbA1c/TC/WG (moderate/large ES); asenapine increased fasting glucose (small ES); quetiapine/cariprazine/risperidone induced WG (small/moderate ES). In bipolar depression, lurasidone was metabolically neutral. In depression, psychological interventions improved physical health-related quality of life (PHQoL) (small ES), fasting glucose/HbA1c (medium/large ES); SSRIs improved fasting glucose/HbA1c, readmission for coronary disease, pain (small ES); quetiapine/aripiprazole/olanzapine induced WG (small to large ES). Exercise improved cardiorespiratory fitness (moderate ES). In the elderly, fluoxetine yielded more detrimental cardiovascular effects than sertraline/escitalopram (large ES); antidepressants were neutral on exercise tolerance and PHQoL. In mixed age groups, in bipolar disorder aripiprazole was metabolically neutral; in depression, SSRIs lowered blood pressure versus placebo and serotonin-noradrenaline reuptake inhibitors (small ES); brexpiprazole augmentation caused WG and was less tolerated (small ES); exercise improved PHQoL (moderate ES).
CONCLUSIONS
Some interventions (psychological therapies, exercise and SSRIs) improve certain physical health outcomes in mood disorders, few are neutral, but various pharmacological interventions are associated with negative effects. Evidence from this umbrella review has limitations, should consider evidence from other disorders and should be integrated with recent evidence from individual RCTs, and observational evidence. Effective treatments with either beneficial or physically neutral profiles should be prioritized.
Topics: Adult; Humans; Aged; Adolescent; Fluoxetine; Olanzapine; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors; Aripiprazole; Longevity; Glycated Hemoglobin; Antipsychotic Agents; Antidepressive Agents; Bipolar Disorder; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic
PubMed: 36138129
DOI: 10.1038/s41380-022-01770-w -
Journal of Child and Adolescent... Sep 2022Antipsychotic-related prolactin changes may expose children and adolescents to severe adverse reactions (ARs) related to pubertal development and growth. We therefore... (Meta-Analysis)
Meta-Analysis Review
Antipsychotic-related prolactin changes may expose children and adolescents to severe adverse reactions (ARs) related to pubertal development and growth. We therefore aimed to assess the effects of antipsychotics on prolactin levels and associated somatic ARs in children and adolescents. We systematically searched PubMed and CENTRAL for placebo-controlled randomized trials of antipsychotics in children and adolescents aged ≤18 years, reporting prolactin levels and related ARs. We conducted a random-effect meta-analysis and assessed risk of bias version 2 (ROB2). Thirty-two randomized controlled trials with an average trial duration of 6 weeks, covering 4643 participants with an average age of 13 years and a male majority of 65.3%. Risk of bias across domains was low or unclear. The following antipsychotic compounds: aripiprazole ( = 810), asenapine ( = 506), lurasidone ( = 314), olanzapine ( = 179), paliperidone ( = 149), quetiapine ( = 381), risperidone ( = 609), and ziprasidone ( = 16) were compared with placebo ( = 1658). Compared with placebo, statistically significant higher prolactin increase occurred with risperidone (mean difference [MD] = 28.24 ng/mL), paliperidone (20.98 ng/mL), and olanzapine (11.34 ng/mL). Aripiprazole significantly decreased prolactin (MD = -4.91 ng/mL), whereas quetiapine, lurasidone, and asenapine were not associated with significantly different prolactin levels than placebo. Our results on ziprasidone are based on a single study, making it insufficient to draw strong conclusions. On average, 20.8% of patients treated with antipsychotic developed levels of prolactin that were too high (hyperprolactinemia), whereas only 1.03% of patients reported prolactin-related ARs. Data were highly limited for long-term effects. In children and adolescents, risperidone, paliperidone, and olanzapine are associated with significant prolactin increase, whereas aripiprazole is associated with significant decrease. Despite the significant changes in prolactin level, few ARs were reported. Study protocol on PROSPERO: CRD42018116451.
Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Child; Dibenzocycloheptenes; Humans; Hyperprolactinemia; Lurasidone Hydrochloride; Male; Olanzapine; Paliperidone Palmitate; Piperazines; Prolactin; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Thiazoles
PubMed: 36074098
DOI: 10.1089/cap.2021.0140 -
Psychopharmacology Oct 2022Mania (or manic episodes) is a common symptom of bipolar disorder and is frequently accompanied by hyperactivity and delusions; given the cost and resources available,... (Meta-Analysis)
Meta-Analysis
RATIONALE
Mania (or manic episodes) is a common symptom of bipolar disorder and is frequently accompanied by hyperactivity and delusions; given the cost and resources available, there is a paucity of evidence for direct comparison of different drugs.
OBJECTIVES
We aimed to provide evidence-based recommendations on the efficacy of overall currently used pharmacological treatments for patients with acute bipolar mania.
METHOD
We conducted a systematic review and network meta-analysis (NMA) using a Bayesian network frame. We searched the primary literature databases without language restrictions until Dec 18, 2021, for reports of randomized controlled trials (RCTs) of suspected antimanic drugs used as monotherapy for patients with acute bipolar mania, with the primary outcomes being efficacy (mean difference (MD), standardized mean difference (SMD) in the change of mania score).
RESULTS
Eighty-seven studies were included in which 18,724 manic participants (mean age = 34.6 years, with 50.36% males) were allocated at random to one of 25 active medication drug therapies or placebo, resulting in 87 direct comparisons on 192 data points. Tamoxifen (- 22·00 [- 26·00 to - 18·00]) had the best efficacy over the placebo. Meanwhile, risperidone (- 6·60 [- 8·40 to - 4·90]) was substantially more effective than placebo in treating acute mania. Carbamazepine, haloperidol, ziprasidone, cariprazine, olanzapine, quetiapine, aripiprazole, lithium, paliperidone, asenapine, and divalproex were noticeably more effective than placebo.
CONCLUSIONS
Overall, tamoxifen appears to be the most effective of the currently known pharmaceutical therapy available to treat acute mania or manic episodes; however, this conclusion is restricted by the scale of RCTs conducted, and risperidone was found to be the most effective medication among antipsychotics. Carbamazepine, haloperidol, ziprasidone, cariprazine, olanzapine, quetiapine, aripiprazole, lithium, paliperidone, asenapine, and divalproex were noticeably effective in treating acute mania or manic episodes.
Topics: Adult; Antimanic Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Carbamazepine; Dibenzocycloheptenes; Haloperidol; Humans; Lithium; Mania; Network Meta-Analysis; Olanzapine; Paliperidone Palmitate; Pharmaceutical Preparations; Piperazines; Quetiapine Fumarate; Risperidone; Tamoxifen; Thiazoles; Valproic Acid
PubMed: 36063207
DOI: 10.1007/s00213-022-06230-5 -
International Journal of Environmental... Aug 2022There is evidence of an association between cancer and certain types of altered eating behaviors, including orthorexia, food cravings, and food addiction. Given the... (Meta-Analysis)
Meta-Analysis Review
There is evidence of an association between cancer and certain types of altered eating behaviors, including orthorexia, food cravings, and food addiction. Given the growing interest in the topic throughout the scientific community we conducted a systematic review to summarize current evidence on the development of altered food behavior, including food addiction and cancer. The Cochrane Collaboration and the Meta-analysis Of Observational Studies in Epidemiology guidelines were followed to perform this systematic review. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was used to report the process and results. The structured literature search was conducted on 19 April 2022, on PubMed/Medline and Scopus, combining free-text terms and medical subject headings. A total of seven articles were included once the selection process was completed. Food craving has been associated with different types of cancer in adults and young patients, as well as with orthorexia; conversely, compulsive eating has only been explored in patients with prolactinoma treated with dopamine agonists. This systematic review explored a new area of research that warrants further investigation. More research is required to better understand the relationship between cancer and food behavior.
Topics: Adult; Feeding Behavior; Humans; Neoplasms; Observational Studies as Topic; PubMed
PubMed: 36011935
DOI: 10.3390/ijerph191610299 -
BMC Neurology Aug 2022Quality of life (QoL) in patients with Parkinson's disease (PD) is increasingly used as an efficacy outcome in clinical studies of PD to evaluate the impact of treatment... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Quality of life (QoL) in patients with Parkinson's disease (PD) is increasingly used as an efficacy outcome in clinical studies of PD to evaluate the impact of treatment from the patient's perspective. Studies demonstrating the treatment effect of pramipexole on QoL remain inconclusive. This study aims to evaluate the effect of pramipexole on QoL in patients with PD by conducting a systematic review and meta-analysis of existing clinical trials.
METHODS
A systematic literature search of PubMed, Embase and the Cochrane Library was performed from inception to 30 April 2022 to identify randomised, placebo-controlled trials of patients with idiopathic PD receiving pramipexole, who reported a change from baseline in their QoL as measured by the 39-item Parkinson's Disease Questionnaire (PDQ-39). Risk of bias was independently assessed by two reviewers using the Cochrane Collaboration's tool for bias assessment.
RESULTS
Of 80 eligible articles screened, six trials consisting of at least 2000 patients with early or advanced PD were included. From the synthesis of all six selected trials, a significant mean change from baseline in the PDQ-39 total score of -2.49 (95% CI, -3.43 to -1.54; p < 0.0001) was observed with pramipexole compared with placebo. A trend toward improvement in QoL was consistently observed among patients who received optimal doses of pramipexole (≥ 80% of the study population on 1.5 mg dosage), regardless of disease severity (advanced versus early) or baseline QoL levels.
CONCLUSION
This meta-analysis provides evidence for the potential treatment benefit of pramipexole in improving QoL in patients with PD.
Topics: Antiparkinson Agents; Humans; Parkinson Disease; Pramipexole; Quality of Life; Severity of Illness Index
PubMed: 36008796
DOI: 10.1186/s12883-022-02830-y -
The Journal of Family Practice Jul 2022YES. Augmentation with second generation antipsychotics, especially aripiprazole and quetiapine, appears to be effective in patients with moderate-to-severe depression...
YES. Augmentation with second generation antipsychotics, especially aripiprazole and quetiapine, appears to be effective in patients with moderate-to-severe depression who have had a suboptimal response to a selective serotonin reuptake inhibitor or a serotonin-norepinephrine reuptake inhibitor (strength of recommendation [SOR]: A, based on a systematic review of randomized controlled trials [RCTs] and an individual RCT). Augmenting antidepressant therapy with cariprazine, ziprasidone, or olanzapine also appears to improve depressive symptoms over the short term. All antipsychotics studied carried an increased likelihood of adverse effects that could lead to discontinuation (SOR: A, based on a systematic review of RCTs).
Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Depression; Humans; Olanzapine; Quetiapine Fumarate
PubMed: 35994758
DOI: 10.12788/jfp.0445