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BMJ Supportive & Palliative Care Sep 2023Cancer-related fatigue (CRF) is a very common symptom in patients with cancer, and one of the five areas of highest priority in cancer research. There is currently no... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Cancer-related fatigue (CRF) is a very common symptom in patients with cancer, and one of the five areas of highest priority in cancer research. There is currently no consensus on pharmacologic interventions for treating CRF. The aim of this systematic review is to provide more clarity on which pharmacologic interventions may be most promising, for future clinical trials. The network meta-analysis provides the ability to compare multiple agents when no direct head-to-head trials of all agents have been performed.
METHODS
Medline (PubMed), EMBASE and Cochrane Central Register of Controlled Trials were searched up until 5 March 2021. Studies were included if they reported on a pharmacologic intervention for CRF. Standardised mean differences and corresponding 95% CIs were computed using a random-effects maximum-likelihood model.
RESULTS
This review reports on 18 studies and 2604 patients, the most comprehensive review of pharmacologic interventions for CRF at the time of this publication. Methylphenidate, modafinil and paroxetine were superior to placebo. Methylphenidate and modafinil were equivalent to one another. Paroxetine was superior to modafinil.
CONCLUSION
Paroxetine should be further studied in future trials. As well, more safety data are needed on pharmacologic interventions.
Topics: Humans; Modafinil; Central Nervous System Stimulants; Paroxetine; Network Meta-Analysis; Methylphenidate; Fatigue; Neoplasms
PubMed: 34593386
DOI: 10.1136/bmjspcare-2021-003244 -
International Journal of Clinical... Nov 2021To evaluate the effect of "on-demand" use of tramadol vs "on-demand" use of paroxetine in the management of patients with premature ejaculation (PE). (Meta-Analysis)
Meta-Analysis
A systematic review and meta-analysis of randomized controlled trials of "on-demand" use of tramadol vs "on-demand" use of paroxetine in the management of patients with premature ejaculation.
AIM
To evaluate the effect of "on-demand" use of tramadol vs "on-demand" use of paroxetine in the management of patients with premature ejaculation (PE).
MATERIALS AND METHODS
A systematic search of PubMed, EMBASE, Cochrane Library databases and original references of the included articles was performed. PRISMA checklist was followed. The Cochrane Handbook was used to evaluate the quality of the included research.
RESULTS
A total of seven articles including 663 patients were studied. The results indicated that patients who received on-demand therapy of tramadol or paroxetine showed significant improvement compared with those treated with placebo, as assessed by intravaginal ejaculatory latency time (IELT) (P < .00001 and P = .02, respectively) and sexual satisfaction score (P < .00001 and P < .00001, respectively). Furthermore, Patients who were treated with on-demand tramadol had a better effect than those treated with on-demand paroxetine in respect of IELT (P = .01) and sexual satisfaction score (P = .03). With regard to safety, the most common adverse event for the tramadol group was sleep disturbance and the most common adverse event for the paroxetine group was a headache. No serious adverse event was observed in both groups.
CONCLUSIONS
Compared with placebo, on-demand therapy of tramadol or paroxetine showed a better improvements in IELT and sexual satisfaction scores. Besides, on-demand tramadol revealed a better effect than on-demand paroxetine for patients with PE, and patients in both groups showed good tolerance.
Topics: Ejaculation; Humans; Male; Paroxetine; Premature Ejaculation; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Tramadol; Treatment Outcome
PubMed: 34492139
DOI: 10.1111/ijcp.14825 -
Alpha Psychiatry Sep 2021The aim of the article is to review systematically current researches investigating the relationship between intrauterine exposure to antidepressants and neonatal... (Review)
Review
The aim of the article is to review systematically current researches investigating the relationship between intrauterine exposure to antidepressants and neonatal hypoglycemia. This paper included studies published in electronic databases from January 2005 to July 2020. The searched keywords were as follows: antidepressants, pregnancy, selective serotonin reuptake inhibitors (SSRIs), citalopram, fluoxetine, paroxetine, escitalopram, sertraline, fluvoxamine, selective serotonin-norepinephrine reuptake inhibitors (SNRIs), venlafaxine, tricyclic antidepressants (TCAs), neonatal outcomes, neonatal hypoglycemia, imipramine, clomipramine, amitriptyline, bupropion, trazodone, and mirtazapine. This review examined 10 relevant studies. The odds ratio/risk ratio reported in the studies were 1.33-1.73 for any antidepressant, 1.30-1.35 for SSRI, 1.42-2.11 for SNRI, and 2.07 for TCAs. The risk of neonatal hypoglycemia in infants exposed to maternal TCAs appears to be slightly higher compared to infants exposed to maternal SSRIs. Data from current studies consistently show that exposure to maternal antidepressants during pregnancy may be related to increased risk of neonatal hypoglycemia in infants.
PubMed: 36447450
DOI: 10.1530/alphapsychiatry.2021.21143 -
The Australian and New Zealand Journal... Mar 2022This paper describes the development of the third edition of the National Health and Medical Research Australian Guidelines for the Prevention and Treatment of Acute...
OBJECTIVE
This paper describes the development of the third edition of the National Health and Medical Research Australian Guidelines for the Prevention and Treatment of Acute Stress Disorder, posttraumatic stress disorder and Complex posttraumatic stress disorder, highlighting key changes in scope, methodology, format and treatment recommendations from the previous 2013 edition of the Guidelines.
METHOD
Systematic review of the international research was undertaken, with GRADE methodology used to assess the certainty of the evidence, and evidence to decision frameworks used to generate recommendations. The Guidelines are presented in an online format using MAGICApp.
RESULTS
Key changes since the publication of the 2013 Guidelines include a new conditional recommendation for Child and Family Traumatic Stress Intervention for children and adolescents with symptoms within the first 3 months of trauma, and a strong recommendation for trauma-focused cognitive behaviour therapy for the child alone or with a caregiver, for those with diagnosed posttraumatic stress disorder. For adults with posttraumatic stress disorder, strong recommendations are made for specific types of trauma-focused cognitive behaviour therapy and conditional recommendations are made for five additional psychological interventions. Where medication is indicated for adults with posttraumatic stress disorder, venlafaxine is now conditionally recommended alongside sertraline, paroxetine or fluoxetine.
CONCLUSION
These Guidelines, based on systematic review of the international literature, are intended to guide decision making for practitioners, service planners, funders and those seeking treatment for trauma related mental health concerns. For an Australian Guideline, a critical limitation is the absence of research on the treatment of Australian Aboriginal and Torres Strait Islander peoples. The new online format of the Australian posttraumatic stress disorder Guidelines means that they can be updated as sufficient new evidence becomes available.
Topics: Adolescent; Adult; Australia; Child; Cognitive Behavioral Therapy; Humans; Mental Health; Practice Guidelines as Topic; Stress Disorders, Post-Traumatic
PubMed: 34448406
DOI: 10.1177/00048674211041917 -
The Cochrane Database of Systematic... May 2021Major depressive disorders have a significant impact on children and adolescents, including on educational and vocational outcomes, interpersonal relationships, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Major depressive disorders have a significant impact on children and adolescents, including on educational and vocational outcomes, interpersonal relationships, and physical and mental health and well-being. There is an association between major depressive disorder and suicidal ideation, suicide attempts, and suicide. Antidepressant medication is used in moderate to severe depression; there is now a range of newer generations of these medications.
OBJECTIVES
To investigate, via network meta-analysis (NMA), the comparative effectiveness and safety of different newer generation antidepressants in children and adolescents with a diagnosed major depressive disorder (MDD) in terms of depression, functioning, suicide-related outcomes and other adverse outcomes. The impact of age, treatment duration, baseline severity, and pharmaceutical industry funding was investigated on clinician-rated depression (CDRS-R) and suicide-related outcomes.
SEARCH METHODS
We searched the Cochrane Common Mental Disorders Specialised Register, the Cochrane Library (Central Register of Controlled Trials (CENTRAL) and Cochrane Database of Systematic Reviews (CDSR)), together with Ovid Embase, MEDLINE and PsycINFO till March 2020.
SELECTION CRITERIA
Randomised trials of six to 18 year olds of either sex and any ethnicity with clinically diagnosed major depressive disorder were included. Trials that compared the effectiveness of newer generation antidepressants with each other or with a placebo were included. Newer generation antidepressants included: selective serotonin reuptake inhibitors; selective norepinephrine reuptake inhibitors (SNRIs); norepinephrine reuptake inhibitors; norepinephrine dopamine reuptake inhibitors; norepinephrine dopamine disinhibitors (NDDIs); and tetracyclic antidepressants (TeCAs).
DATA COLLECTION AND ANALYSIS
Two reviewers independently screened titles/abstracts and full texts, extracted data, and assessed risk of bias. We analysed dichotomous data as Odds Ratios (ORs), and continuous data as Mean Difference (MD) for the following outcomes: depression symptom severity (clinician rated), response or remission of depression symptoms, depression symptom severity (self-rated), functioning, suicide related outcomes and overall adverse outcomes. Random-effects network meta-analyses were conducted in a frequentist framework using multivariate meta-analysis. Certainty of evidence was assessed using Confidence in Network Meta-analysis (CINeMA). We used "informative statements" to standardise the interpretation and description of the results.
MAIN RESULTS
Twenty-six studies were included. There were no data for the two primary outcomes (depressive disorder established via clinical diagnostic interview and suicide), therefore, the results comprise only secondary outcomes. Most antidepressants may be associated with a "small and unimportant" reduction in depression symptoms on the CDRS-R scale (range 17 to 113) compared with placebo (high certainty evidence: paroxetine: MD -1.43, 95% CI -3.90, 1.04; vilazodone: MD -0.84, 95% CI -3.03, 1.35; desvenlafaxine MD -0.07, 95% CI -3.51, 3.36; moderate certainty evidence: sertraline: MD -3.51, 95% CI -6.99, -0.04; fluoxetine: MD -2.84, 95% CI -4.12, -1.56; escitalopram: MD -2.62, 95% CI -5.29, 0.04; low certainty evidence: duloxetine: MD -2.70, 95% CI -5.03, -0.37; vortioxetine: MD 0.60, 95% CI -2.52, 3.72; very low certainty evidence for comparisons between other antidepressants and placebo). There were "small and unimportant" differences between most antidepressants in reduction of depression symptoms (high- or moderate-certainty evidence). Results were similar across other outcomes of benefit. In most studies risk of self-harm or suicide was an exclusion criterion for the study. Proportions of suicide-related outcomes were low for most included studies and 95% confidence intervals were wide for all comparisons. The evidence is very uncertain about the effects of mirtazapine (OR 0.50, 95% CI 0.03, 8.04), duloxetine (OR 1.15, 95% CI 0.72, 1.82), vilazodone (OR 1.01, 95% CI 0.68, 1.48), desvenlafaxine (OR 0.94, 95% CI 0.59, 1.52), citalopram (OR 1.72, 95% CI 0.76, 3.87) or vortioxetine (OR 1.58, 95% CI 0.29, 8.60) on suicide-related outcomes compared with placebo. There is low certainty evidence that escitalopram may "at least slightly" reduce odds of suicide-related outcomes compared with placebo (OR 0.89, 95% CI 0.43, 1.84). There is low certainty evidence that fluoxetine (OR 1.27, 95% CI 0.87, 1.86), paroxetine (OR 1.81, 95% CI 0.85, 3.86), sertraline (OR 3.03, 95% CI 0.60, 15.22), and venlafaxine (OR 13.84, 95% CI 1.79, 106.90) may "at least slightly" increase odds of suicide-related outcomes compared with placebo. There is moderate certainty evidence that venlafaxine probably results in an "at least slightly" increased odds of suicide-related outcomes compared with desvenlafaxine (OR 0.07, 95% CI 0.01, 0.56) and escitalopram (OR 0.06, 95% CI 0.01, 0.56). There was very low certainty evidence regarding other comparisons between antidepressants.
AUTHORS' CONCLUSIONS
Overall, methodological shortcomings of the randomised trials make it difficult to interpret the findings with regard to the efficacy and safety of newer antidepressant medications. Findings suggest that most newer antidepressants may reduce depression symptoms in a small and unimportant way compared with placebo. Furthermore, there are likely to be small and unimportant differences in the reduction of depression symptoms between the majority of antidepressants. However, our findings reflect the average effects of the antidepressants, and given depression is a heterogeneous condition, some individuals may experience a greater response. Guideline developers and others making recommendations might therefore consider whether a recommendation for the use of newer generation antidepressants is warranted for some individuals in some circumstances. Our findings suggest sertraline, escitalopram, duloxetine, as well as fluoxetine (which is currently the only treatment recommended for first-line prescribing) could be considered as a first option. Children and adolescents considered at risk of suicide were frequently excluded from trials, so that we cannot be confident about the effects of these medications for these individuals. If an antidepressant is being considered for an individual, this should be done in consultation with the child/adolescent and their family/caregivers and it remains critical to ensure close monitoring of treatment effects and suicide-related outcomes (combined suicidal ideation and suicide attempt) in those treated with newer generation antidepressants, given findings that some of these medications may be associated with greater odds of these events. Consideration of psychotherapy, particularly cognitive behavioural therapy, as per guideline recommendations, remains important.
Topics: Adolescent; Antidepressive Agents; Bias; Child; Citalopram; Depressive Disorder, Major; Desvenlafaxine Succinate; Duloxetine Hydrochloride; Female; Fluoxetine; Humans; Male; Mirtazapine; Network Meta-Analysis; Paroxetine; Selective Serotonin Reuptake Inhibitors; Sertraline; Suicidal Ideation; Venlafaxine Hydrochloride; Vilazodone Hydrochloride; Vortioxetine
PubMed: 34029378
DOI: 10.1002/14651858.CD013674.pub2 -
Asian Journal of Psychiatry Jun 2021This systematic review aims to assess the efficacy and acceptability of the different types of antidepressants and benzodiazepines for the treatment of panic disorder... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This systematic review aims to assess the efficacy and acceptability of the different types of antidepressants and benzodiazepines for the treatment of panic disorder (PD) in adult patients.
METHODS
PubMed, Web of Science, EMBASE, MEDLINE, the Cochrane Library, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) published between 1995 and 2020 on the use of antidepressants and benzodiazepines for the treatment of PD. A systematic review and network meta-analysis were performed.
RESULTS
42 RCTs were included in the network meta-analysis, with a comparison of 11 interventions.Escitalopram (odds ratios OR 1.52, 95 % credible interval CI 1.09-2.10), venlafaxine (OR 1.33, 95 % CI 1.16-1.51) and benzodiazepines (OR 1.50, 95 % CI 1.29-1.75) had greater efficacy and acceptability than the placebo. Imipramine(OR 1.43, 95 % CI 1.15-1.79) was also demonstrated to be efficacious and tolerated but the results were restricted to small sample size. Moreover, paroxetine, sertraline, fluoxetine, citalopram and clomipramine (OR 1.37, 1.36, 1.45, 1.33 and 1.36, respectively) were more efficacious, although the acceptability of paroxetine and sertraline were significantly less tolerated than benzodiazepines. Notably, the efficacy of reboxetine and fluvoxamine were merely as equal as that of the placebo.
OUTCOMES
This is the first systematic review of antidepressants and benzodiazepines for the treatment of PD to use a network analysis. Escitalopram and venlafaxine as well as benzodiazepines may be effective choices as treatments for PD with relatively good acceptability, which still needs to be confirmed byhigh-quality RCTs.
Topics: Adult; Antidepressive Agents; Benzodiazepines; Humans; Network Meta-Analysis; Panic Disorder; Paroxetine
PubMed: 33965693
DOI: 10.1016/j.ajp.2021.102664 -
The World Journal of Biological... Nov 2021To address the extreme suicide risk period following a suicidal crisis, we aimed to assess the current evidence for specific healthcare system-based interventions on...
OBJECTIVES
To address the extreme suicide risk period following a suicidal crisis, we aimed to assess the current evidence for specific healthcare system-based interventions on suicide-related outcomes within one-week or one-month in individuals with current suicidal ideation (SI) or a recent suicide attempt (SA).
METHODS
We performed a database (Medline, Academic Search Complete, PsycARTICLES, the Cochrane library, PubMed) and manual reference search for randomised controlled trials, published between March 2000 and March 2020. Antisuicidal efficacy was defined as SI, SA, or a closely related concept. Quality was assessed with the Cochrane Risk of Bias 2 tool for randomised trials.
RESULTS
Out of 34 trials, five reported ketamine or esketamine superiority over placebo in reducing SI in depressed subjects within one week, while five studies had negative findings. Single trials reported positive results for one-month antisuicidal efficacy of buprenorphine, paroxetine, a crisis response plan, and assertive case management. Most trials were underpowered and had moderate-to-high risk of bias.
CONCLUSIONS
Preliminary mixed evidence suggests the possible utility of several pharmacological (ketamine, esketamine paroxetine, and buprenorphine) and non-pharmacological (a crisis response plan, and assertive case management) interventions. Only the immediate efficacy of ketamine was supported by multiple studies, and replication is needed.
Topics: Humans; Suicidal Ideation; Suicide, Attempted
PubMed: 33783294
DOI: 10.1080/15622975.2021.1907712 -
Advances in Experimental Medicine and... 2021Depression is a mental disorder and a major public health concern affecting millions of people worldwide. It is a common disorder that has been associated with several...
Depression is a mental disorder and a major public health concern affecting millions of people worldwide. It is a common disorder that has been associated with several medical comorbidities often linked with aging, such as dementia, type II diabetes, cardiovascular and cerebrovascular diseases, as well as metabolic syndrome. There are a variety of medications available for depression treatment. Selective serotonin reuptake inhibitors (SSRIs) are one of the antidepressant drug classes that are most widely used to treat depressive disorders and depressive symptoms in other diseases. Due to many contradictory findings on the adverse effects and toxicities of SSRIs (especially genotoxicities), we reviewed the genotoxic effects of these drugs. Based on the guidelines proposed in the PRISMA statement, we performed a systematic review by searching international electronic databases including PubMed, Scopus, Embase, and Web of Science to find the published documents on SSRIs and their genotoxic effects from January 1990 to November 2019. After the removal of 203 duplicate articles, 385 articles were screened and 167 articles met the inclusion criteria and qualified for evaluation of their full texts. After this, 26 articles were appropriate for final review. This revealed that the proportion of genotoxicities was highest for citalopram and fluoxetine, with a smaller proportion for sertraline. Limited documentations showed genotoxic and partial genotoxic effects for paroxetine and escitalopram, respectively. Although a number of studies have found genotoxic effects of SSRIs, there are also some factors including doses, duration of exposure, model of experiments, and the type of technique assay that may affect the results.
Topics: Citalopram; DNA Damage; Diabetes Mellitus, Type 2; Humans; Paroxetine; Selective Serotonin Reuptake Inhibitors
PubMed: 33725349
DOI: 10.1007/978-3-030-55035-6_8 -
CNS Spectrums Feb 2021More than 50% patients with major depressive disorder (MDD) have severe functional impairment. The restoration of patient functioning is a critical therapeutic goal...
Comparative efficacy of pharmacological treatments on measures of self-rated functional outcomes using the Sheehan Disability Scale in patients with major depressive disorder: a systematic review and network meta-analysis.
OBJECTIVE
More than 50% patients with major depressive disorder (MDD) have severe functional impairment. The restoration of patient functioning is a critical therapeutic goal among patients with MDD. We conducted a systematic review and network meta-analysis to evaluate the efficacy of pharmacological treatments on self-rated functional outcomes using the Sheehan Disability Scale in adults with MDD in randomized clinical trials.
METHODS
PubMed, EMBASE, PsycINFO, Cochrane Library, and ClinicalTrials.gov were searched from inception to December 10, 2019. Summary statistics are reported as weighted mean differences with 95% confidence intervals. Interventions were ranked using the surface under the cumulative ranking probabilities.
RESULTS
We included 42 randomized controlled trials (RCTs) (n = 18 998) evaluating the efficacy of 13 different pharmacological treatments on functional outcomes, as measured by the Sheehan Disability Scale (SDS). Duloxetine was the most effective pharmacological agent on functional outcomes, followed by (ranked by efficacy): paroxetine, levomilnacipran, venlafaxine, quetiapine, desvenlafaxine, agomelatine, escitalopram, amitriptyline, bupropion, sertraline, vortioxetine, and fluoxetine. Serotonin and norepinephrine reuptake inhibitors were more effective than other drug classes. Additionally, the comparison-adjusted funnel plot suggested the publication bias between small and large studies was relatively low.
CONCLUSIONS
Our results indicate that there may be differences across antidepressant agents and classes with respect to self-reported functional outcomes. Validation and replication of these findings in large-scale RCTs are warranted. Our research results will be clinically useful for guiding psychiatrists in treating patients with MDD and functional impairment. PROSPERO registration number CRD42018116663.
PubMed: 33583460
DOI: 10.1017/S1092852921000171 -
Progress in Neuro-psychopharmacology &... Jul 2021Gastrointestinal side effects (SEs) are frequently observed in patients with major depressive disorder (MDD) while taking antidepressants and may lead to treatment... (Meta-Analysis)
Meta-Analysis
Gastrointestinal side effects (SEs) are frequently observed in patients with major depressive disorder (MDD) while taking antidepressants and may lead to treatment discontinuation. The aim of this meta-analysis is to provide quantitative measures on short-term rates of gastrointestinal SEs in MDD patients treated with second-generation antidepressants. An electronic search of the literature was conducted by using MEDLINE, ISI Web of Science - Web of Science Core Collection, and Cochrane Library databases. Eligible studies had to focus on the use of at least one of 15 antidepressants commonly used in MDD (i.e., agomelatine, bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, levomilnacipran, mirtazapine, paroxetine, reboxetine, sertraline, venlafaxine, and vortioxetine) and report data on treatment-emergent gastrointestinal SEs (i.e. nausea/vomiting, diarrhoea, constipation, abdominal pain, dyspepsia, anorexia, increased appetite and dry mouth) within 12 weeks of treatment. Overall, 304 studies were included in the meta-analyses. All the considered antidepressants showed higher rates of gastrointestinal SEs than placebo. Escitalopram and sertraline were shown to be the least tolerated antidepressants on the gastrointestinal tract, being associated with all the considered SEs with the exception of constipation and increased appetite, while mirtazapine was shown to be the antidepressant with fewer side effects on the gut, being only associated with increased appetite. In conclusion, commonly used antidepressants showed different profiles of gastrointestinal SEs, possibly related to their mechanisms of action. The specific tolerability profile of each compound should be considered by clinicians when prescribing antidepressants in order to improve adherence to treatment and increase positive outcomes in patients with MDD.
Topics: Antidepressive Agents; Constipation; Depressive Disorder, Major; Diarrhea; Humans; Nausea; Vomiting
PubMed: 33549697
DOI: 10.1016/j.pnpbp.2021.110266