Dataset Information

Pharmacologic Interventions for Breathlessness in Patients With Advanced Cancer: A Systematic Review and Meta-analysis.

ABSTRACT:

Importance

Improved survival in patients with advanced cancer has increased the need for better understanding of how to manage common symptoms that they may experience, such as breathlessness.

Objective

To assess the benefits and harms associated with pharmacologic interventions for breathlessness in adults with advanced cancer.

Data sources

PubMed, Embase, CINAHL, Web of Science, and the Cochrane Central Register of Controlled Trials were searched for studies published from database inception through May 31, 2020, using predefined eligibility criteria within a PICOTS (population, intervention, comparator, outcome, timing, setting) format.

Study selection

Randomized clinical trials (RCTs), non-RCTs, and observational studies with a comparison group that evaluated benefits and/or harms and cohort studies that reported harms were selected.

Data extraction and synthesis

Two reviewers independently screened studies for eligibility, serially abstracted data, independently assessed risk of bias, and graded strength of evidence (SOE).

Main outcomes and measures

Benefits and harms of pharmacologic interventions were compared, focusing on breathlessness, anxiety, exercise capacity, and health-related quality of life. When possible, meta-analyses were conducted and standardized mean differences (SMDs) calculated.

Results

In this systematic review and meta-analysis, a total of 7729 unique citations were identified, of which 19 studies (17 RCTs and 2 retrospective studies) that included a total of 1424 patients assessed the benefits of medications for management of breathlessness in advanced cancer or reported harms. The most commonly reported type of cancer was lung cancer. Opioids were not associated with more effectiveness than placebo for improving breathlessness (SMD, -0.14; 95% CI, -0.47 to 0.18) or exercise capacity ( SMD, 0.06; 95% CI, -0.43 to 0.55) (SOE, moderate); most studies examined exertional breathlessness. Specific dose and/or route of administration of opioids did not differ in effectiveness for breathlessness (SMD, 0.15; 95% CI, -0.22 to 0.52) (SOE, low). Anxiolytics were not associated with more effectiveness than placebo for breathlessness or anxiety (reported mean between-group difference, -0.52; 95% CI, -1.045 to 0.005) (SOE, low). Evidence for other pharmacologic interventions was limited. Pharmacologic interventions demonstrated some harms compared with usual care, but dropout attributable to adverse events was minimal in these short-term studies (range 3.2%-16%).

Conclusions and relevance

Evidence did not support the association of opioids or other pharmacologic interventions with improved breathlessness. Given that studies had many limitations, pharmacologic interventions should be considered in selected patients but need to be considered in the context of potential harms and evidence of an association of nonpharmacologic interventions with improved breathlessness.

SUBMITTER: Feliciano JL

PROVIDER: S-EPMC7907959 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Pharmacologic Interventions for Breathlessness in Patients With Advanced Cancer: A Systematic Review and Meta-analysis.

Feliciano Josephine L JL Waldfogel Julie M JM Sharma Ritu R Zhang Allen A Gupta Arjun A Sedhom Ramy R Day Jeff J Bass Eric B EB Dy Sydney M SM

JAMA network open 20210201 2

<h4>Importance</h4>Improved survival in patients with advanced cancer has increased the need for better understanding of how to manage common symptoms that they may experience, such as breathlessness.<h4>Objective</h4>To assess the benefits and harms associated with pharmacologic interventions for breathlessness in adults with advanced cancer.<h4>Data sources</h4>PubMed, Embase, CINAHL, Web of Science, and the Cochrane Central Register of Controlled Trials were searched for studies published fro ...[more]

PMID: 33630086

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Project description:BackgroundPrescribing trends suggest that pharmacologic alternatives to antipsychotics are gaining in popularity, but randomized trial (RCT) data of their comparative safety is scarce. Our objective was to describe the comparative safety of pharmacologic interventions for treating neuropsychiatric symptoms in dementia.MethodsWe searched MEDLINE, EMBASE, CENTRAL, CINAHL, and PsycINFO, from inception to May 28, 2019, for studies of pharmacologic interventions used to treat neuropsychiatric symptoms in dementia. Dementia care partners selected fracture risk as our primary outcome. Pairs of reviewers, working independently, conducted all study screening, data abstraction, and risk of bias appraisal. We conducted Bayesian random-effects network meta-analyses (NMAs) using data from RCTs to derive odds ratios (ORs). In secondary analyses, we conducted frequentist random-effects NMAs using data from RCTs and Bayesian three-level hierarchical random-effects NMAs incorporating data from RCTs and non-randomized studies.ResultsOur systematic review included 209 randomized and non-randomized studies (889,378 persons with dementia). In NMAs of data from randomized trials, there were no increased odds of fracture associated with any intervention in primary analyses; however, data were sparse. We found increased odds of cerebrovascular events associated with antipsychotics (odds ratio [OR] 2.12, 95% credible interval [CrI] 1.29 to 3.62; number needed to harm [NNH] = 99) and increased odds of falls associated with dextromethorphan-quinidine (OR 4.16, 95% CrI 1.47 to 14.22; NNH = 55) compared to placebo in persons with dementia. In a subgroup of persons with Alzheimer disease, antipsychotics were associated with increased odds of fracture compared to anticonvulsants (OR 54.1, 95% CrI 1.15 to 38,300; NNH = 18). In older persons (mean age ≥ 80 years) with dementia, anticonvulsants were associated with increased odds of death compared to placebo (OR 8.36, 95% CrI 1.17 to 203.4; NNH = 35) and antipsychotics were associated with increased odds of death compared to antidepressants (OR 5.28, 95% CrI 1.06 to 3.51; NNH = 47).ConclusionAlthough antipsychotics were associated with greater harm than antidepressants and anticonvulsants in subgroups of persons with dementia, medications used in lieu of antipsychotics for treating neuropsychiatric symptoms in dementia, such as anticonvulsants and dextromethorphan-quinidine, were also associated with harm. Decision-making concerning treatments prescribed in lieu of antipsychotics should include potential harms.Prospero registrationCRD42017050130.

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Dataset Information

Pharmacologic Interventions for Breathlessness in Patients With Advanced Cancer: A Systematic Review and Meta-analysis.

Importance

Objective

Data sources

Study selection

Data extraction and synthesis

Main outcomes and measures

Results

Conclusions and relevance

Publications

Pharmacologic Interventions for Breathlessness in Patients With Advanced Cancer: A Systematic Review and Meta-analysis.

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