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The Cochrane Database of Systematic... Jun 2016This review is one of a series on drugs used to treat fibromyalgia. Fibromyalgia is a clinically well-defined chronic condition of unknown aetiology characterised by... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This review is one of a series on drugs used to treat fibromyalgia. Fibromyalgia is a clinically well-defined chronic condition of unknown aetiology characterised by chronic widespread pain that often co-exists with sleep problems and fatigue. It affects approximately 2% of the general population. Up to 70% of patients with fibromyalgia meet the criteria for a depressive or anxiety disorder. People often report high disability levels and poor health-related quality of life. Drug therapy focuses on reducing key symptoms and disability, and improving health-related quality of life. Antipsychotics might reduce fibromyalgia and associated mental health symptoms.
OBJECTIVES
To assess the efficacy, tolerability and safety of antipsychotics in fibromyalgia in adults.
SEARCH METHODS
We searched CENTRAL (2016, Issue 4), MEDLINE and EMBASE to 20 May 2016, together with reference lists of retrieved papers and reviews and two clinical trial registries. We also contacted trial authors.
SELECTION CRITERIA
We selected controlled trials of at least four weeks duration of any formulation of antipsychotics used for the treatment of fibromyalgia in adults.
DATA COLLECTION AND ANALYSIS
We extracted the data from all included studies and two review authors independently assessed study risks of bias. We resolved discrepancies by discussion. We performed analysis using three tiers of evidence. We derived first tier evidence from data meeting current best standards and subject to minimal risk of bias (outcome equivalent to substantial pain intensity reduction, intention-to-treat analysis without imputation for drop-outs, at least 200 participants in the comparison, eight to 12 weeks duration, parallel design), second tier evidence from data that failed to meet one or more of these criteria and that we considered at some risk of bias but with adequate numbers in the comparison, and third tier evidence from data involving small numbers of participants that we considered very likely to be biased or used outcomes of limited clinical utility, or both. We rated the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.
MAIN RESULTS
We included a total of four studies with 296 participants.Three studies with 206 participants compared quetiapine, an atypical (second-generation) antipsychotic, with placebo. One study used a cross-over design and two studies a parallel-group design. Study duration was eight or 12 weeks. Quetiapine was used in all studies with a bedtime dosage between 50 and 300 mg/day. All studies had one or more sources of potential major bias and we judged them to be at moderate risk of bias overall. The primary outcomes in this review were participant-reported pain relief of 50% or greater, Patient Global Impression of Change (PGIC) much or very much improved, withdrawal due to adverse events (tolerability) and serious adverse events (safety).Second tier evidence indicated that quetiapine was not statistically superior to placebo in the number of participants with a 50% or more pain reduction (very low quality evidence). No study reported data on PGIC. A greater proportion of participants on quetiapine reported a 30% or more pain reduction (risk difference (RD) 0.12, 95% confidence interval (CI) 0.00 to 0.23; number needed to treat for an additional benefit (NNTB) 8, 95% CI 5 to 100) (very low quality evidence). A greater proportion of participants on quetiapine reported a clinically relevant improvement of health-related quality of life compared to placebo ( RD 0.18, 95% CI 0.05 to 0.31; NNTB 5, 95% CI 3 to 20) (very low quality evidence). Quetiapine was statistically superior to placebo in reducing sleep problems (standardised mean difference (SMD) -0.67, 95% CI -1.10 to -0.23), depression (SMD -0.39, 95% CI -0.74 to -0.04) and anxiety (SMD -0.40, 95% CI -0.69 to -0.11) (very low quality evidence). Quetiapine was statistically superior to placebo in reducing the risk of withdrawing from the study due to a lack of efficacy (RD -0.14, 95% CI -0.23 to -0.05) (very low quality evidence). There was no statistically significant difference between quetiapine and placebo in the proportion of participants withdrawing due to adverse events (tolerability) (very low quality evidence), in the frequency of serious adverse events (safety) (very low quality evidence) and in the proportion of participants reporting dizziness and somnolence as an adverse event (very low quality evidence). In more participants in the quetiapine group a substantial weight gain was noted (RD 0.08, 95% CI 0.02 to 0.15; number needed to treat for an additional harm (NNTH) 12, 95% CI 6 to 50) (very low quality evidence). We downgraded the quality of evidence by three levels to a very low quality rating because of limitations of study design, indirectness (patients with major medical diseases and mental disorders were excluded) and imprecision (fewer than 400 patients were analysed).One parallel design study with 90 participants compared quetiapine (50 to 300 mg/day flexible at bedtime) to amitriptyline (10 to 75 mg/day flexible at bedtime). The study had three major risks of bias and we judged it to be at moderate risk of bias overall. We downgraded the quality of evidence by two levels to a low quality rating because of indirectness (patients with major medical diseases and mental disorders were excluded) and imprecision (fewer than 400 patients were analysed). Third tier evidence indicated no statistically significant differences between the two drugs. Both drugs did not statistically significantly differ in the reduction of average scores for pain, fatigue, sleep problems, depression, anxiety and for limitations of health-related quality of life and in the proportion of participants reporting dizziness, somnolence and weight gain as a side effect (low quality evidence). Compared to amitriptyline, more participants left the study due to adverse events (low quality evidence). No serious adverse events were reported (low quality evidence).We found no relevant study with other antipsychotics than quetiapine in fibromyalgia.
AUTHORS' CONCLUSIONS
Very low quality evidence suggests that quetiapine may be considered for a time-limited trial (4 to 12 weeks) to reduce pain, sleep problems, depression and anxiety in fibromyalgia patients with major depression. Potential side effects such as weight gain should be balanced against the potential benefits in shared decision making with the patient.
Topics: Adult; Amitriptyline; Analgesics, Non-Narcotic; Antipsychotic Agents; Fibromyalgia; Humans; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Sleep Wake Disorders
PubMed: 27251337
DOI: 10.1002/14651858.CD011804.pub2 -
International Urogynecology Journal May 2021The objective was to compare the clinical efficacy and safety of pharmacological interventions for interstitial cystitis and bladder pain syndrome (IC/BPS) with direct... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION AND HYPOTHESIS
The objective was to compare the clinical efficacy and safety of pharmacological interventions for interstitial cystitis and bladder pain syndrome (IC/BPS) with direct and indirect evidence from randomized trials.
METHODS
We searched PubMed, the Cochrane library, and EMBASE for randomized controlled trials (RCTs) that assessed the pharmacological therapies for IC/BPS. Primary efficacy outcomes included ICSI (O'Leary Sant Interstitial Cystitis Symptom Index), ICPI (O'Leary Sant Interstitial Cystitis Problem Index), 24-h micturition frequency, visual analog scale (VAS), and Likert score for pain. Safety outcomes are total adverse events (AEs, intravesical instillation, and others), gastrointestinal symptoms, headache, pain, and urinary symptoms. A systematic review and Bayesian network meta-analysis were performed.
RESULTS
A total of 23 RCTs with 1,871 participants were identified. The ICSI was significantly reduced in the amitriptyline group (MD = -4.9, 95% CI: -9.0 to -0.76), the cyclosporine A group (MD = -7.9, 95% CI: -13.0 to -3.0) and the certolizumab pegol group (MD = -3.6, 95% CI:-6.5 to -0.63) compared with placebo group. Moreover, for ICPI, cyclosporine A showed superior benefit compared to placebo (MD = -7.6, 95% CI: -13 to -2.3). VAS score improved significantly in cyclosporine A group than pentosan polysulfate sodium (MD = 3.09, 95% CI: 0.13 to 6.07). None of the agents revealed a significant alleviation of 24-h micturition frequency. In terms of safety outcomes, the incidence rate on urinary symptoms for botulinum toxin A was the only variate higher than chondroitin sulfate (MD = -2.02, 95% CI: -4.99 to 0.66) and placebo (MD = -1.60, 95% CI:-3.83 to 0.17). No significant difference was found among the other treatments.
CONCLUSIONS
Cyclosporine A might be superior to other pharmacological treatments in efficacy. Amitriptyline and certolizumab pegol were capable of lowering the ICSI as well.
Topics: Administration, Intravesical; Botulinum Toxins, Type A; Cystitis, Interstitial; Humans; Network Meta-Analysis; Pain Measurement; Treatment Outcome
PubMed: 33638677
DOI: 10.1007/s00192-020-04659-w -
The Cochrane Database of Systematic... Feb 2021Functional Abdominal Pain Disorders (FAPDs) present a considerable burden to paediatric patients, impacting quality of life, school attendance and causing higher rates... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Functional Abdominal Pain Disorders (FAPDs) present a considerable burden to paediatric patients, impacting quality of life, school attendance and causing higher rates of anxiety and depression disorders. There are no international guidelines for the management of this condition. A previous Cochrane Review in 2011 found no evidence to support the use of antidepressants in this context.
OBJECTIVES
To evaluate the current evidence for the efficacy and safety of antidepressants for FAPDs in children and adolescents.
SEARCH METHODS
In this updated review, we searched the Cochrane Library, PubMed, MEDLINE, Embase, PsycINFO and two clinical trial registers from inception until 03 February 2020. We also updated our search of databases of ongoing research, reference lists and 'grey literature' from inception to 03 February 2020.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing antidepressants to placebo, to no treatment or to any other intervention, in children aged 4 to 18 years with a FAPD diagnosis as per the Rome or any other defined criteria (as defined by the authors). The primary outcomes of interest included treatment success (as defined by the authors), pain severity, pain frequency and withdrawal due to adverse events.
DATA COLLECTION AND ANALYSIS
Two review authors checked all citations independently, resolving disagreement with a third-party arbiter. We reviewed all potential studies in full text, and once again made independent decisions, with disagreements resolved by consensus. We conducted data extraction and 'Risk of bias' assessments independently, following Cochrane methods. Where homogeneous data were available, we performed meta-analysis using a random-effects model. We conducted GRADE analysis.
MAIN RESULTS
We found one new study in this updated search, making a total of three trials (223 participants) eligible for inclusion: two using amitriptyline (AMI) and one using citalopram. For the primary outcome of treatment success, two studies used reports of success on a symptom-based Likert scale, with either a two-point reduction or the two lowest levels defined as success. The third study defined success as a 15% improvement in quality of life (QOL) ratings scales. Therefore, meta-analysis did not include this final study due to the heterogeneity of the outcome measure. There is low-certainty evidence that there may be no difference when antidepressants are compared with placebo (risk ratio (RR) 1.17, 95% confidence interval (CI) 0.87 to 1.56; 2 studies, 205 participants; I = 0%). We downgraded the evidence for significant imprecision due to extremely sparse data (see Summary of findings table 1). The third study reported that participants receiving antidepressants were significantly more likely than those receiving placebo to experience at least a 15% improvement in overall QOL score at 10 and 13 weeks (P = 0.007 and P = 0.002, respectively (absolute figures were not given)). The analysis found no difference in withdrawals due to adverse events between antidepressants and placebo: RR 3.17 (95% CI 0.65 to 15.33), with very low certainty due to high risk of bias in studies and imprecision due to low event and participant numbers. Sensitivity analysis using a fixed-effect model and analysing just for AMI found no change in this result. Due to heterogeneous and limited reporting, no further meta-analysis was possible.
AUTHORS' CONCLUSIONS
There may be no difference between antidepressants and placebo for treatment success of FAPDs in childhood. There may be no difference in withdrawals due to adverse events, but this is also of low certainty. There is currently no evidence to support clinical decision making regarding the use of these medications. Further studies must consider sample size, homogenous and relevant outcome measures and longer follow up.
Topics: Abdominal Pain; Adolescent; Amitriptyline; Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Child; Citalopram; Gastrointestinal Diseases; Humans; Irritable Bowel Syndrome; Placebos; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 33560523
DOI: 10.1002/14651858.CD008013.pub3 -
The Cochrane Database of Systematic... Jun 2015Fibromyalgia is a clinically well-defined chronic condition with a biopsychosocial aetiology. Fibromyalgia is characterized by chronic widespread musculoskeletal pain,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fibromyalgia is a clinically well-defined chronic condition with a biopsychosocial aetiology. Fibromyalgia is characterized by chronic widespread musculoskeletal pain, sleep problems, cognitive dysfunction, and fatigue. Patients often report high disability levels and poor quality of life. Since there is no specific treatment that alters the pathogenesis of fibromyalgia, drug therapy focuses on pain reduction and improvement of other aversive symptoms.
OBJECTIVES
The objective was to assess the benefits and harms of selective serotonin reuptake inhibitors (SSRIs) in the treatment of fibromyalgia.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 5), MEDLINE (1966 to June 2014), EMBASE (1946 to June 2014), and the reference lists of reviewed articles.
SELECTION CRITERIA
We selected all randomized, double-blind trials of SSRIs used for the treatment of fibromyalgia symptoms in adult participants. We considered the following SSRIs in this review: citalopram, fluoxetine, escitalopram, fluvoxamine, paroxetine, and sertraline.
DATA COLLECTION AND ANALYSIS
Three authors extracted the data of all included studies and assessed the risks of bias of the studies. We resolved discrepancies by discussion.
MAIN RESULTS
The quality of evidence was very low for each outcome. We downgraded the quality of evidence to very low due to concerns about risk of bias and studies with few participants. We included seven placebo-controlled studies, two with citalopram, three with fluoxetine and two with paroxetine, with a median study duration of eight weeks (4 to 16 weeks) and 383 participants, who were pooled together.All studies had one or more sources of potential major bias. There was a small (10%) difference in patients who reported a 30% pain reduction between SSRIs (56/172 (32.6%)) and placebo (39/171 (22.8%)) risk difference (RD) 0.10, 95% confidence interval (CI) 0.01 to 0.20; number needed to treat for an additional beneficial outcome (NNTB) 10, 95% CI 5 to 100; and in global improvement (proportion of patients who reported to be much or very much improved: 50/168 (29.8%) of patients with SSRIs and 26/162 (16.0%) of patients with placebo) RD 0.14, 95% CI 0.06 to 0.23; NNTB 7, 95% CI 4 to 17.SSRIs did not statistically, or clinically, significantly reduce fatigue: standard mean difference (SMD) -0.26, 95% CI -0.55 to 0.03; 7.0% absolute improvement on a 0 to 10 scale, 95% CI 14.6% relative improvement to 0.8% relative deterioration; nor sleep problems: SMD 0.03, 95 % CI -0.26 to 0.31; 0.8 % absolute deterioration on a 0 to 100 scale, 95% CI 8.3% relative deterioration to 6.9% relative improvement.SSRIs were superior to placebo in the reduction of depression: SMD -0.39, 95% CI -0.65 to -0.14; 7.6% absolute improvement on a 0 to 10 scale, 95% CI 2.7% to 13.8% relative improvement; NNTB 13, 95% CI 7 to 37. The dropout rate due to adverse events was not higher with SSRI use than with placebo use (23/146 (15.8%) of patients with SSRIs and 14/138 (10.1%) of patients with placebo) RD 0.04, 95% CI -0.06 to 0.14. There was no statistically or clinically significant difference in serious adverse events with SSRI use and placebo use (3/84 (3.6%) in patients with SSRIs and 4/84 (4.8%) and patients with placebo) RD -0.01, 95% CI -0.07 to 0.05.
AUTHORS' CONCLUSIONS
There is no unbiased evidence that SSRIs are superior to placebo in treating the key symptoms of fibromyalgia, namely pain, fatigue and sleep problems. SSRIs might be considered for treating depression in people with fibromyalgia. The black box warning for increased suicidal tendency in young adults aged 18 to 24, with major depressive disorder, who have taken SSRIs, should be considered when appropriate.
Topics: Amitriptyline; Citalopram; Fibromyalgia; Fluoxetine; Humans; Melatonin; Musculoskeletal Pain; Paroxetine; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Syndrome
PubMed: 26046493
DOI: 10.1002/14651858.CD011735 -
Clinical Toxicology (Philadelphia, Pa.) Dec 2016Although intravenous lipid emulsion (ILE) was first used to treat life-threatening local anesthetic (LA) toxicity, its use has expanded to include both non-local... (Review)
Review
BACKGROUND
Although intravenous lipid emulsion (ILE) was first used to treat life-threatening local anesthetic (LA) toxicity, its use has expanded to include both non-local anesthetic (non-LA) poisoning and less severe manifestations of toxicity. A collaborative workgroup appraised the literature and provides evidence-based recommendations for the use of ILE in poisoning.
METHODS
Following a systematic review of the literature, data were summarized in four publications: LA and non-LA poisoning efficacy, adverse effects, and analytical interferences. Twenty-two toxins or toxin categories and three clinical situations were selected for voting. Voting statements were proposed using a predetermined format. A two-round modified Delphi method was used to reach consensus on the voting statements. Disagreement was quantified using RAND/UCLA Appropriateness Method.
RESULTS
For the management of cardiac arrest, we recommend using ILE with bupivacaine toxicity, while our recommendations are neutral regarding its use for all other toxins. For the management of life-threatening toxicity, (1) as first line therapy, we suggest not to use ILE with toxicity from amitriptyline, non-lipid soluble beta receptor antagonists, bupropion, calcium channel blockers, cocaine, diphenhydramine, lamotrigine, malathion but are neutral for other toxins, (2) as part of treatment modalities, we suggest using ILE in bupivacaine toxicity if other therapies fail, but are neutral for other toxins, (3) if other therapies fail, we recommend ILE for bupivacaine toxicity and we suggest using ILE for toxicity due to other LAs, amitriptyline, and bupropion, but our recommendations are neutral for all other toxins. In the treatment of non-life-threatening toxicity, recommendations are variable according to the balance of expected risks and benefits for each toxin. For LA-toxicity we suggest the use of Intralipid 20% as it is the formulation the most often reported. There is no evidence to support a recommendation for the best formulation of ILE for non-LAs. The voting panel is neutral regarding ILE dosing and infusion duration due to insufficient data for non-LAs. All recommendations were based on very low quality of evidence.
CONCLUSION
Clinical recommendations regarding the use of ILE in poisoning were only possible in a small number of scenarios and were based mainly on very low quality of evidence, balance of expected risks and benefits, adverse effects, laboratory interferences as well as related costs and resources. The workgroup emphasizes that dose-finding and controlled studies reflecting human poisoning scenarios are required to advance knowledge of limitations, indications, adverse effects, effectiveness, and best regimen for ILE treatment.
Topics: Administration, Intravenous; Anesthetics; Animals; Calcium Channel Blockers; Cocaine; Diphenhydramine; Disease Models, Animal; Evidence-Based Medicine; Fat Emulsions, Intravenous; Humans; Lamotrigine; Poisoning; Randomized Controlled Trials as Topic; Triazines
PubMed: 27608281
DOI: 10.1080/15563650.2016.1214275 -
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 -
Pharmacological Research Dec 2022Widespread musculoskeletal pain characterizes fibromyalgia (FM), accompanied by sleep, fatigue, and mood problems. Chronic stress and depression play a crucial role in... (Review)
Review
Widespread musculoskeletal pain characterizes fibromyalgia (FM), accompanied by sleep, fatigue, and mood problems. Chronic stress and depression play a crucial role in the etiology and pathophysiology of FM. They may contribute to a dysregulation of the central pain mechanisms together with the neuroendocrine and immune systems. Pharmacological treatments are the first-line therapy to reduce the symptoms of FM. The US Food and Drug Administration (FDA) indicated gabapentinoid, pregabalin, duloxetine, and milnacipran for adult patients. An alternative approach is widely used, based on therapies including interventions in patient education, behavioral therapy, exercise, pain management, and a healthy diet. A systematic search was performed on PubMed, MEDLINE, EMBASE, and Web of Science databases. The authors established the selection, inclusion, and exclusion criteria. We found a total of 908 articles. This systematic review will include ten articles selected after excluding duplicates and reading the abstracts and full texts. All studies related the effect of drugs to various symptoms caused by fibromyalgia patients with depression, such as insomnia/sleepiness, depression, suicide, difficulty walking/working, pain, fatigue, and nervousness. Although, we concluded that antidepressant drugs are effective in treating depression and pain in fibromyalgia, further studies are needed to understand the etiology of this disease and to find a combination of therapies to increase tolerability and adherence of the patient to the drug, decreasing the adverse effects.
Topics: Adult; Humans; Fibromyalgia; Antidepressive Agents; Fatigue; Musculoskeletal Pain; Employment
PubMed: 36336218
DOI: 10.1016/j.phrs.2022.106547 -
CNS Spectrums Jan 2022Clozapine is the most effective medication for treatment-refractory schizophrenia but is associated with significant adverse drug reactions, including nocturnal enuresis... (Review)
Review
BACKGROUND
Clozapine is the most effective medication for treatment-refractory schizophrenia but is associated with significant adverse drug reactions, including nocturnal enuresis and urinary incontinence. This side effect can be burdensome and lead to medication nonadherence and psychotic relapse. Evidence to guide treatment of clozapine-induced nocturnal enuresis and urinary incontinence is sparse. We therefore aimed to synthesize the evidence base to guide management for clinicians, patients, and their carers.
METHODS
We systematically searched PubMed, Embase, PsycInfo, CINAHL, and the Cochrane Trial Registry databases from inception to May 2021 for publications on management of clozapine-induced nocturnal enuresis and urinary incontinence using a PROSPERO preregistered search strategy.
RESULTS
We identified 22 case reports and case series describing 74 patients. Interventions included clozapine dose reduction, nonpharmacological treatment, and pharmacological treatments. Among pharmacological treatments, desmopressin, oxybutynin, trihexyphenidyl, tolterodine, imipramine, amitriptyline, ephedrine, pseudoephedrine, aripiprazole, and verapamil were associated with complete resolution of nocturnal enuresis and urinary incontinence. Balancing evidence for effectiveness against risk of adverse effects, we developed a management framework for clozapine-induced nocturnal enuresis and urinary incontinence.
CONCLUSIONS
Following assessment of urological, psychiatric, pharmacological, and common comorbid medical issues, first-line treatments should be nonpharmacological, including bathroom alarms, voiding before bedtime, and nocturnal fluid restriction. If these interventions do not provide adequate relief, aripiprazole should be trialed. Desmopressin may be considered for severe refractory cases, but monitoring for hyponatremia is essential.
PubMed: 35086595
DOI: 10.1017/S1092852922000050 -
European Urology Open Science Oct 2023Radiotherapy of the pelvis is a widely used method for the treatment of malignancies, and local complications including pain following pelvic radiation therapy are... (Review)
Review
The Benefits and Harms of Pharmacological Treatment for Postradiation Pelvic Pain: A Systematic Review by the European Association of Urology Chronic Pelvic Pain Panel with Recommendations for Clinical Practice.
CONTEXT
Radiotherapy of the pelvis is a widely used method for the treatment of malignancies, and local complications including pain following pelvic radiation therapy are acknowledged complications.
OBJECTIVE
The primary objective is to assess the clinical effectiveness and safety of pharmacological therapies on postradiation pelvic pain.
EVIDENCE ACQUISITION
A systematic review of the use of different pharmacological treatments in the management of post-radiation pelvic pain was conducted (PROSPERO-ID: CRD42021249026). Comprehensive searches of EMBASE, Medline, and Cochrane library were performed for publications between January 1980 and April 2021. The primary outcomes were improvement in pain and adverse events following treatment. The secondary outcomes included quality of life, bowel function, and urinary function.
EVIDENCE SYNTHESIS
After screening 1514 abstracts, four randomised controlled trials were identified, enrolling 355 patients with bladder and anorectal subtypes of postradiotherapy chronic pelvic pain (CPP). A narrative synthesis was performed as heterogeneity of included studies precluded a meta-analysis. A single study reported a significant reduction in pain after 6 mo in patients with bladder pain syndrome treated with hyaluronic acid or hyperbaric oxygen. Anorectal pain was reported to be reduced by the application of 4% formalin, but the use of hyperbaric oxygen in postradiotherapy anorectal pain remains controversial. Adverse event reporting was generally poor. Studies looking at medications used routinely in guidelines for neuropathic pain, such as gabapentin, pregabalin, amitriptyline, and duloxetine, were absent or of poor quality when it came to postradiation pelvic pain.
CONCLUSIONS
Beneficial effects of hyperbaric oxygen or formalin on pain, quality of life, and functional symptoms were seen in patients with certain CPP subtypes, but the current evidence level is too weak to allow recommendations about the use of any pharmacological treatment for postradiation pelvic pain.
PATIENT SUMMARY
Different pharmacological treatments are used to treat pain after radiotherapy, but current studies are of insufficient quality to determine whether these should be recommended and many chronic pelvic pain subtypes are not covered. Further research is needed.
PubMed: 37711669
DOI: 10.1016/j.euros.2023.08.009 -
The Cochrane Database of Systematic... May 2023Harmful alcohol use is defined as unhealthy alcohol use that results in adverse physical, psychological, social, or societal consequences and is among the leading risk... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Harmful alcohol use is defined as unhealthy alcohol use that results in adverse physical, psychological, social, or societal consequences and is among the leading risk factors for disease, disability and premature mortality globally. The burden of harmful alcohol use is increasing in low- and middle-income countries (LMICs) and there remains a large unmet need for indicated prevention and treatment interventions to reduce harmful alcohol use in these settings. Evidence regarding which interventions are effective and feasible for addressing harmful and other patterns of unhealthy alcohol use in LMICs is limited, which contributes to this gap in services.
OBJECTIVES
To assess the efficacy and safety of psychosocial and pharmacologic treatment and indicated prevention interventions compared with control conditions (wait list, placebo, no treatment, standard care, or active control condition) aimed at reducing harmful alcohol use in LMICs.
SEARCH METHODS
We searched for randomized controlled trials (RCTs) indexed in the Cochrane Drugs and Alcohol Group (CDAG) Specialized Register, the Cochrane Clinical Register of Controlled Trials (CENTRAL) in the Cochrane Library, PubMed, Embase, PsycINFO, CINAHL, and the Latin American and Caribbean Health Sciences Literature (LILACS) through 12 December 2021. We searched clinicaltrials.gov, the World Health Organization International Clinical Trials Registry Platform, Web of Science, and Opengrey database to identify unpublished or ongoing studies. We searched the reference lists of included studies and relevant review articles for eligible studies.
SELECTION CRITERIA
All RCTs comparing an indicated prevention or treatment intervention (pharmacologic or psychosocial) versus a control condition for people with harmful alcohol use in LMICs were included.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included 66 RCTs with 17,626 participants. Sixty-two of these trials contributed to the meta-analysis. Sixty-three studies were conducted in middle-income countries (MICs), and the remaining three studies were conducted in low-income countries (LICs). Twenty-five trials exclusively enrolled participants with alcohol use disorder. The remaining 51 trials enrolled participants with harmful alcohol use, some of which included both cases of alcohol use disorder and people reporting hazardous alcohol use patterns that did not meet criteria for disorder. Fifty-two RCTs assessed the efficacy of psychosocial interventions; 27 were brief interventions primarily based on motivational interviewing and were compared to brief advice, information, or assessment only. We are uncertain whether a reduction in harmful alcohol use is attributable to brief interventions given the high levels of heterogeneity among included studies (Studies reporting continuous outcomes: Tau² = 0.15, Q =139.64, df =16, P<.001, I² = 89%, 3913 participants, 17 trials, very low certainty; Studies reporting dichotomous outcomes: Tau²=0.18, Q=58.26, df=3, P<.001, I² =95%, 1349 participants, 4 trials, very low certainty). The other types of psychosocial interventions included a range of therapeutic approaches such as behavioral risk reduction, cognitive-behavioral therapy, contingency management, rational emotive therapy, and relapse prevention. These interventions were most commonly compared to usual care involving varying combinations of psychoeducation, counseling, and pharmacotherapy. We are uncertain whether a reduction in harmful alcohol use is attributable to psychosocial treatments due to high levels of heterogeneity among included studies (Heterogeneity: Tau² = 1.15; Q = 444.32, df = 11, P<.001; I²=98%, 2106 participants, 12 trials, very low certainty). Eight trials compared combined pharmacologic and psychosocial interventions with placebo, psychosocial intervention alone, or another pharmacologic treatment. The active pharmacologic study conditions included disulfiram, naltrexone, ondansetron, or topiramate. The psychosocial components of these interventions included counseling, encouragement to attend Alcoholics Anonymous, motivational interviewing, brief cognitive-behavioral therapy, or other psychotherapy (not specified). Analysis of studies comparing a combined pharmacologic and psychosocial intervention to psychosocial intervention alone found that the combined approach may be associated with a greater reduction in harmful alcohol use (standardized mean difference (standardized mean difference (SMD))=-0.43, 95% confidence interval (CI): -0.61 to -0.24; 475 participants; 4 trials; low certainty). Four trials compared pharmacologic intervention alone with placebo and three with another pharmacotherapy. Drugs assessed were: acamprosate, amitriptyline, baclofen disulfiram, gabapentin, mirtazapine, and naltrexone. None of these trials evaluated the primary clinical outcome of interest, harmful alcohol use. Thirty-one trials reported rates of retention in the intervention. Meta-analyses revealed that rates of retention between study conditions did not differ in any of the comparisons (pharmacologic risk ratio (RR) = 1.13, 95% CI: 0.89 to 1.44, 247 participants, 3 trials, low certainty; pharmacologic in addition to psychosocial intervention: RR = 1.15, 95% CI: 0.95 to 1.40, 363 participants, 3 trials, moderate certainty). Due to high levels of heterogeneity, we did not calculate pooled estimates comparing retention in brief (Heterogeneity: Tau² = 0.00; Q = 172.59, df = 11, P<.001; I = 94%; 5380 participants; 12 trials, very low certainty) or other psychosocial interventions (Heterogeneity: Tau² = 0.01; Q = 34.07, df = 8, P<.001; I = 77%; 1664 participants; 9 trials, very low certainty). Two pharmacologic trials and three combined pharmacologic and psychosocial trials reported on side effects. These studies found more side effects attributable to amitriptyline relative to mirtazapine, naltrexone and topiramate relative to placebo, yet no differences in side effects between placebo and either acamprosate or ondansetron. Across all intervention types there was substantial risk of bias. Primary threats to validity included lack of blinding and differential/high rates of attrition.
AUTHORS' CONCLUSIONS
In LMICs there is low-certainty evidence supporting the efficacy of combined psychosocial and pharmacologic interventions on reducing harmful alcohol use relative to psychosocial interventions alone. There is insufficient evidence to determine the efficacy of pharmacologic or psychosocial interventions on reducing harmful alcohol use largely due to the substantial heterogeneity in outcomes, comparisons, and interventions that precluded pooling of these data in meta-analyses. The majority of studies are brief interventions, primarily among men, and using measures that have not been validated in the target population. Confidence in these results is reduced by the risk of bias and significant heterogeneity among studies as well as the heterogeneity of results on different outcome measures within studies. More evidence on the efficacy of pharmacologic interventions, specific types of psychosocial interventions are needed to increase the certainty of these results.
Topics: Humans; Male; Acamprosate; Alcoholism; Amitriptyline; Developing Countries; Disulfiram; Mirtazapine; Naltrexone; Ondansetron; Topiramate
PubMed: 37158538
DOI: 10.1002/14651858.CD013350.pub2