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Health Technology Assessment... Mar 2015Premature ejaculation (PE) is commonly defined as ejaculation with minimal sexual stimulation before, on or shortly after penetration and before the person wishes it. PE... (Review)
Review
BACKGROUND
Premature ejaculation (PE) is commonly defined as ejaculation with minimal sexual stimulation before, on or shortly after penetration and before the person wishes it. PE can be either lifelong and present since first sexual experiences (primary), or acquired (secondary), beginning later (Godpodinoff ML. Premature ejaculation: clinical subgroups and etiology. J Sex Marital Ther 1989;15:130-4). Treatments include behavioural and pharmacological interventions.
OBJECTIVE
To systematically review evidence for clinical effectiveness of behavioural, topical and systemic treatments for PE.
DATA SOURCES
The following databases were searched from inception to 6 August 2013 for published and unpublished research evidence: MEDLINE; EMBASE; Cumulative Index to Nursing and Allied Health Literature; The Cochrane Library including the Cochrane Systematic Reviews Database, Cochrane Controlled Trials Register, Database of Abstracts of Reviews of Effects and the Health Technology Assessment database; ISI Web of Science, including Science Citation Index, and the Conference Proceedings Citation Index-Science. The US Food and Drug Administration website and the European Medicines Agency (EMA) website were also searched.
METHODS
Randomised controlled trials (RCTs) in adult men with PE were eligible (or non-RCTs in the absence of RCTs). RCT data were extrapolated from review articles when available. The primary outcome was intravaginal ejaculatory latency time (IELT). Data were meta-analysed when possible. Other outcomes included sexual satisfaction, control over ejaculation, relationship satisfaction, self-esteem, quality of life, treatment acceptability and adverse events (AEs).
RESULTS
A total of 103 studies (102 RCTs, 65 from reviews) were included. RCTs were available for all interventions except yoga. The following interventions demonstrated significant improvements (p < 0.05) in arithmetic mean difference in IELT compared with placebo: topical anaesthetics - eutectic mixture of local anaesthetics (EMLA(®), AstraZeneca), topical eutectic mixture for PE (Plethora Solutions Ltd) spray; selective serotonin reuptake inhibitors (SSRIs) - citalopram (Cipramil(®), Lundbeck), escitalopram (Cipralex(®), Lundbeck), fluoxetine, paroxetine, sertraline, dapoxetine (Priligy(®), Menarini), 30 mg or 60 mg; serotonin-noradrenaline reuptake inhibitors - duloxetine (Cymbalta(®), Eli Lilly & Co Ltd); tricyclic antidepressants - inhaled clomipramine 4 mg; phosphodiesterase-5 (PDE5) inhibitors - vardenafil (Levitra(®), Bayer), tadalafil (Cialis(®), Eli Lilly & Co Ltd); opioid analgesics - tramadol (Zydol SR(®), Grünenthal). Improvements in sexual satisfaction and other outcomes compared with placebo were evident for SSRIs, PDE5 inhibitors and tramadol. Outcomes for interventions not compared with placebo were as follows: behavioural therapies - improvements over wait list control in IELT and other outcomes, behavioural therapy plus pharmacotherapy better than either therapy alone; alpha blockers - terazosin (Hytrin(®), AMCO) not significantly different to antidepressants in ejaculation control; acupuncture - improvements over sham acupuncture in IELT, conflicting results for comparisons with SSRIs; Chinese medicine - improvements over treatment as usual; delay device - improvements in IELT when added to stop-start technique; yoga - improved IELT over baseline, fluoxetine better than yoga. Treatment-related AEs were evident with most pharmacological interventions.
LIMITATIONS
Although data extraction from reviews was optimised when more than one review reported data for the same RCT, the reliability of the data extraction within these reviews cannot be guaranteed by this assessment report.
CONCLUSIONS
Several interventions significantly improved IELT. Many interventions also improved sexual satisfaction and other outcomes. However, assessment of longer-term safety and effectiveness is required to evaluate whether or not initial treatment effects are maintained long term, whether or not dose escalation is required, how soon treatment effects end following treatment cessation and whether or not treatments can be stopped and resumed at a later time. In addition, assessment of the AEs associated with long-term treatment and whether or not different doses have differing AE profiles is required.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42013005289.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Adult; Anesthetics, Local; Behavior Therapy; Humans; Male; Phosphodiesterase 5 Inhibitors; Premature Ejaculation; Selective Serotonin Reuptake Inhibitors; Treatment Outcome
PubMed: 25768099
DOI: 10.3310/hta19210 -
The Cochrane Database of Systematic... Sep 2011Lower urinary tract symptoms associated with benign prostatic obstruction (BPO) occur in up to 70% of men over the age of 60 years. To relieve these bothersome symptoms,... (Review)
Review
BACKGROUND
Lower urinary tract symptoms associated with benign prostatic obstruction (BPO) occur in up to 70% of men over the age of 60 years. To relieve these bothersome symptoms, treatment options include alpha-antagonists, also know as alpha-blockers.
OBJECTIVES
We conducted a systematic review to evaluate the effectiveness and adverse effects of the alpha-blocker, terazosin, for treatment of urinary symptoms associated with BPO.
SEARCH STRATEGY
Trials were searched in computerized general and specialized databases (MEDLINE, Cochrane Library), by checking bibliographies, and by contacting manufacturers and researchers.
SELECTION CRITERIA
Studies were included if they (1) were randomized trials of at least 1 month duration, and (2) included men with symptomatic BPO and compared terazosin with placebo or active controls.
DATA COLLECTION AND ANALYSIS
Study, patient characteristics and outcomes data were extracted in duplicate onto standardized forms utilizing a prospectively developed protocol. The main outcome measure for comparing the effectiveness of terazosin with placebo or other BPO medications was change in urological symptoms as measured by validated symptom scores. Secondary outcomes included urodynamic measures. The main outcome measure for adverse effects was the number of men reporting side effects. We also evaluated the number of men withdrawing from treatment and the number withdrawing due to adverse effects.
MAIN RESULTS
Seventeen studies involving 5151 subjects met inclusion criteria (placebo-controlled (n = 10); alpha-blockers (n = 7); finasteride alone or in combination with terazosin as well as placebo (1); microwave therapy (TUMT) (1). Study duration ranged from 4 to 52 weeks. Mean age was 65 years and 82% of men were white. Baseline urologic symptom scale scores and flow rates demonstrated that men had moderate BPO. Efficacy outcomes were rarely reported in a fashion that allowed for data pooling but indicated that terazosin improved symptom scores and flow rates more than placebo or finasteride and similarly to other alpha antagonists. The pooled mean percentage improvements for the Boyarsky symptom score was 37% for terazosin versus 15% for placebo (n = 4 studies). The mean percentage improvement for the American Urological Association symptom score (AUA) was 38% compared to 17% and 20% for placebo and finasteride, respectively (n = 2 studies). The pooled mean improvement in the International Prostate Symptom Score (IPSS) (40%) was similar to tamsulosin (43%). Peak urine flow rates improved greater with terazosin (22%), than placebo (11%) and finasteride (15%) but did not differ significantly from the other alpha-blockers. The percentage of men discontinuing terazosin was comparable to men receiving placebo and finasteride but was greater then with other alpha-antagonists. Adverse effects were greater than placebo and included dizziness, asthenia, headache, and postural hypotension.
AUTHORS' CONCLUSIONS
The available evidence suggests that terazosin improves urinary symptoms and flow measures associated with BPO. Effectiveness is superior to placebo or finasteride, similar to other alpha-blockers but less than TUMT. Adverse effects were generally mild but more frequent than other alpha-blockers and associated with between a two-to-four fold increase in treatment discontinuation.
Topics: Adrenergic alpha-Antagonists; Aged; Antineoplastic Agents; Humans; Male; Middle Aged; Prazosin; Prostatic Hyperplasia
PubMed: 21901686
DOI: 10.1002/14651858.CD003851.pub2 -
Medicine Sep 2021Alpha-adrenergic blockers are commonly used as a medical expulsive therapy (MET) for patients with ureteral calculi. The aim of this meta-analysis was to evaluate the... (Meta-Analysis)
Meta-Analysis
PURPOSE
Alpha-adrenergic blockers are commonly used as a medical expulsive therapy (MET) for patients with ureteral calculi. The aim of this meta-analysis was to evaluate the efficacy and safety of alpha-adrenergic blockers compared with a placebo when used as a MET.
MATERIALS AND METHODS
We carried out a systematic search of the PubMed, EMBASE, and Web of Science databases, and the Cochrane Library, for relevant articles from inception to November 2020. Our aim was to identify placebo-controlled trails in which patients were randomized to receive either alpha-adrenergic blockers (tamsulosin, alfuzosin, doxazosin, terazosin, naftopidil, or silodosin) or a placebo for the treatment of ureteral calculi.
RESULTS
According to strict inclusion criteria, database searches identified 8 placebo-controlled studies that included 2284 patients. Generally, α-blockers had no significant effect on the clearance of stones in the urinary tract (risk ratio [RR] = 1.05; 95% confidence interval [CI] = 1.00-1.11). However, subgroup analysis showed that α-blockers were effective in treating distal urinary tract stones (RR = 1.08; 95% CI = 1.02-1.15). With regards to adverse events, our analysis showed that the combination of MET with α-blockers was likely to cause dizziness (RR = 1.37; 95% CI = 1.06-1.79) and retrograde ejaculation (RR = 3.10; 95% CI = 1.81-5.29).
CONCLUSION
Although α-blockers cannot improve the overall ureteral stone clearance rate, these drugs are still effective for the treatment of stones in the distal urinary tract. However, the application of α-blockers is likely to cause dizziness and/or retrograde ejaculation.
Topics: Adrenergic alpha-Antagonists; Humans; Odds Ratio; Placebos; Treatment Outcome; Ureteral Calculi
PubMed: 34664882
DOI: 10.1097/MD.0000000000027272 -
The Cochrane Database of Systematic... Oct 2010Benign prostatic hyperplasia (BPH), a non-malignant enlargement of the prostate in aging men, can cause bothersome urinary symptoms (intermittency, weak stream,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Benign prostatic hyperplasia (BPH), a non-malignant enlargement of the prostate in aging men, can cause bothersome urinary symptoms (intermittency, weak stream, straining, urgency, frequency, incomplete emptying). Finasteride, a five-alpha reductase inhibitor (5ARI), blocks the conversion of testosterone to dihydrotestosterone, reduces prostate size, and is commonly used to treat symptoms associated with BPH.
OBJECTIVES
To compare the clinical effectiveness and harms of finasteride versus placebo and active controls in the treatment of lower urinary tract symptoms (LUTS).
SEARCH STRATEGY
We searched The Cochrane Library (which includes CDSR (Cochrane Database of Systematic Reviews), DARE (Database of Abstracts of Reviews of Effects), HTA (Heath Technology Assessments), and CENTRAL (Cochrane Central Register of Controlled Trials, and which includes EMBASE and MEDLINE), LILACS (Latin American and Caribbean Center on Health Sciences Information) and Google Scholar for randomized, controlled trials (RCTs). We also handsearched systematic reviews, references, and clinical-practice guidelines.
SELECTION CRITERIA
Randomized trials in the English language with placebo and/or active arms with a duration of at least 6 months.
DATA COLLECTION AND ANALYSIS
JT extracted the data, which included patient characteristics, outcomes, and harms. Our primary outcome was change in a validated, urinary symptom-scale score, such as the AUA/IPSS. A clinically meaningful change was defined as 4 points. We also categorized outcomes by trial lengths of ≤ 1 year (short term) and > 1 year (long term).
MAIN RESULTS
Finasteride consistently improved urinary symptom scores more than placebo in trials of > 1 year duration, and significantly lowered the risk of BPH progression (acute urinary retention, risk of surgical intervention, ≥ 4 point increase in the AUASI/IPSS). In comparison to alpha-blocker monotherapy, finasteride was less effective than either doxazosin or terazosin, but equally effective compared to tamsulosin. Both doxazosin and terazosin were significantly more likely than finasteride to improve peak urine flow and nocturia, versus finasteride. Versus tamsulosin, peak urine flow and QoL improved equally well versus finasteride. However, finasteride was associated with a lower risk of surgical intervention compared to doxazosin, but not to terazosin, while finasteride and doxazosin were no different for risk of acute urinary retention. Two small trials reported no difference in urinary symptom scores between finasteride and tamsulosin. Finasteride + doxazosin and doxazosin monotherapy improved urinary symptoms equally well (≥ 4 point improvement).For finasteride, there was an increased risk of ejaculation disorder, impotence, and lowered libido, versus placebo. Versus doxazosin, finasteride had a lower risk of asthenia, dizziness, and postural hypotension, and versus terazosin, finasteride had a significant, lower risk of asthenia, dizziness, and postural hypotension.
AUTHORS' CONCLUSIONS
Finasteride improves long-term urinary symptoms versus placebo, but is less effective than doxazosin. Long-term combination therapy with alpha blockers (doxazosin, terazosin) improves symptoms significantly better than finasteride monotherapy. Finasteride + doxazosin improves symptoms equally - and clinically - to doxazosin alone. In comparison to doxazosin, finasteride + doxazosin appears to improve urinary symptoms only in men with medium (25 to < 40 mL) or large prostates (≥ 40 mL), but not in men with small prostates (25 mL).Comparing short to long-term therapy, finasteride does not improve symptoms significantly better than placebo at the short term, but in the long term it does, although the magnitude of differences was very small (from < 1.0 point to 2.2 points). Doxazosin improves symptoms better than finasteride both short and long term, with the magnitude of differences ∼2.0 points and 1.0 point, respectively. Finasteride + doxazosin improves scores versus finasteride alone at both short and long term, with mean differences ∼2.0 points for both time points. Finasteride + doxazosin versus doxazosin improves scores equally for short and long term.Drug-related adverse effects for finasteride are rare; nevertheless, men taking finasteride are at increased risk for impotence, erectile dysfunction, decreased libido, and ejaculation disorder, versus placebo. Versus doxazosin, which has higher rates of dizziness, postural hypotension, and asthenia, men taking finasteride are at increased risk for impotence, erectile dysfunction, decreased libido, and ejaculation disorder. Finasteride significantly reduces asthenia, postural hypotension, and dizziness versus terazosin. Finasteride significantly lowers the risk of asthenia, dizziness, ejaculation disorder, and postural hypotension, versus finasteride + terazosin.
Topics: 5-alpha Reductase Inhibitors; Adrenergic alpha-Antagonists; Disease Progression; Doxazosin; Drug Therapy, Combination; Enzyme Inhibitors; Finasteride; Humans; Male; Prostatic Hyperplasia; Prostatism; Randomized Controlled Trials as Topic
PubMed: 20927745
DOI: 10.1002/14651858.CD006015.pub3 -
The Cochrane Database of Systematic... Sep 2011Benign prostatic hyperplasia (BPH) is a nonmalignant enlargement of the prostate which can result in bothersome lower urinary tract symptoms. The treatment goal for men... (Review)
Review
BACKGROUND
Benign prostatic hyperplasia (BPH) is a nonmalignant enlargement of the prostate which can result in bothersome lower urinary tract symptoms. The treatment goal for men with BPH is to relieve these bothersome symptoms.
OBJECTIVES
This systematic review assessed the effects of tamsulosin in the treatment of lower urinary tract symptoms (LUTS) compatible with BPH.
SEARCH STRATEGY
Trials were searched in computerized general and specialized databases (MEDLINE, EMBASE, Cochrane Library), by checking bibliographies, and by contacting manufacturers and researchers.
SELECTION CRITERIA
Trials were eligible if they (1) randomized men with BPH to receive tamsulosin in comparison with placebo, other BPH medications or surgical interventions and (2) included clinical outcomes such as urologic symptom scales, symptoms, or urodynamic measurements, and (3) had a treatment duration of 30 days or longer. Eligibility was assessed by at least two independent observers.
DATA COLLECTION AND ANALYSIS
Information on patients, interventions, and outcomes were extracted by at least two independent reviewers using a standard form. The main outcome measure for comparing the effectiveness of tamsulosin with placebo, medical or surgical interventions was the change in urologic symptom scale scores. Secondary outcomes included changes in urinary flow measures (peak urine flow rate). The main outcome measure for adverse effects was the number of men reporting adverse effects.
MAIN RESULTS
Fourteen studies involving 4122 subjects met inclusion criteria. Study duration ranged from 4 to 26 weeks, and no placebo-controlled study lasted longer than 13 weeks. The mean age of subjects was 64 years. Baseline symptom scores and urine flow rates demonstrated that men had moderate LUTS. Tamsulosin improved symptoms and peak urine flow relative to placebo. The weighted mean differences (WMD) for mean change from baseline for the Boyarsky symptom score for 0.4 mg and 0.8 mg doses of tamsulosin relative to placebo were -1.1 points (95% CI = -1.49 to -0.72; 12% improvement) and -1.6 points (95% CI = -2.3 to -1.0; 16% improvement), respectively. The WMD for mean change from baseline in peak urine flow were 1.1 mL/sec (95% CI = 0.59 to 1.51) and 1.1 mL/sec (95% CI= 0.65 to 1.48) for 0.4 mg and 0.8 mg, respectively. Tamsulosin (0.2 mg to 0.4 mg) was as effective as other alpha antagonists and the phytotherapeutic agent Permixon® in improving symptoms and flow rates though the doses of all alpha-antagonists studied may not have been optimal. Discontinuations from treatment for any reason and discontinuations "due to adverse events" were similar in the low dose tamsulosin (0.2 mg) and placebo groups but increased to 16% in trials utilizing a 0.8 mg dose of tamsulosin. Low dose tamsulosin was generally well tolerated although not all the trials reported specific adverse events. The most frequently reported adverse events that were significantly greater than placebo included dizziness, rhinitis and abnormal ejaculation. Adverse effects increased markedly as tamsulosin dosing increased, and were reported in 75% of men receiving the 0.8 mg dose. Men receiving a 0.2 mg dose tamsulosin were less likely to discontinue treatment compared to men receiving terazosin.
AUTHORS' CONCLUSIONS
Tamsulosin provided a small to moderate improvement in urinary symptoms and flow compared to men receiving placebo in men with BPH. Effectiveness was similar to other alpha antagonists and increased only slightly with higher doses. Long term effectiveness and ability to reduce complications due to BPH progression could not be determined. Adverse effects were generally mild but their frequency, including withdrawals, increased substantially with the higher doses that are generally available for treatment.
Topics: Adrenergic alpha-Antagonists; Humans; Male; Middle Aged; Prostatic Hyperplasia; Randomized Controlled Trials as Topic; Sulfonamides; Urinary Bladder Neck Obstruction; Urinary Retention
PubMed: 21901681
DOI: 10.1002/14651858.CD002081.pub2 -
Age and Ageing Sep 2015we aimed to systematically review drugs to treat lower urinary tract symptoms (LUTS) regularly used in older persons to classify appropriate and inappropriate drugs... (Review)
Review
Appropriateness of oral drugs for long-term treatment of lower urinary tract symptoms in older persons: results of a systematic literature review and international consensus validation process (LUTS-FORTA 2014).
AIM
we aimed to systematically review drugs to treat lower urinary tract symptoms (LUTS) regularly used in older persons to classify appropriate and inappropriate drugs based on efficacy, safety and tolerability by using the Fit fOR The Aged (FORTA) classification.
METHODS
to evaluate the efficacy, safety and tolerability of drugs used for treatment of LUTS in older persons, a systematic review was performed. Papers on clinical trials and summaries of individual product characteristics were analysed regarding efficacy and safety in older persons (≥65 years). The most frequently used drugs were selected based on current prescription data. An interdisciplinary international expert panel assessed the drugs in a Delphi process.
RESULTS
for the 16 drugs included here, a total of 896 citations were identified; of those, only 25 reported clinical trials with explicit data on, or solely performed in older people, underlining the lack of evidence in older people for drug treatment of LUTS. No drug was rated at the FORTA-A-level (indispensable). Only three were assigned to FORTA B (beneficial): dutasteride, fesoterodine and finasteride. The majority was rated FORTA C (questionable): darifenacin, mirabegron, extended release oxybutynin, silodosin, solifenacin, tadalafil, tamsulosin, tolterodine and trospium. FORTA D (avoid) was assigned to alfuzosin, doxazosin, immediate release oxybutynin, propiverine and terazosin.
CONCLUSIONS
dutasteride, fesoterodine and finasteride were classified as beneficial in older persons or frail elderly people (FORTA B). For most drugs, in particular those from the group of α-blockers and antimuscarinics, use in this group seems questionable (FORTA C) or should be avoided (FORTA D).
Topics: 5-alpha Reductase Inhibitors; Administration, Oral; Adrenergic alpha-Antagonists; Age Factors; Aged; Aging; Consensus; Delphi Technique; Humans; Lower Urinary Tract Symptoms; Muscarinic Antagonists; Patient Selection; Risk Assessment; Risk Factors; Treatment Outcome; Urological Agents
PubMed: 26104505
DOI: 10.1093/ageing/afv077 -
Urologia Internationalis 2007This article reviews the rationale and data supporting alpha blocker therapy for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), the most common and... (Review)
Review
INTRODUCTION
This article reviews the rationale and data supporting alpha blocker therapy for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), the most common and difficult prostatitis syndrome.
METHODS
Systematic review identified ten clinical trials evaluating alpha blocker therapy for patients with CP/CPPS, including five open-label or small prospective studies and five double-blinded and placebo-controlled clinical trials.
RESULTS
Encouraging results in uncontrolled and small clinical trials led to the development of reasonably powered, double-blinded, placebo-controlled, randomized clinical trials evaluating terazosin, doxazosin, tamsulosin, and alfuzosin.
CONCLUSIONS
Current data suggest that treatment-naïve and/or newly diagnosed patients appear more likely to respond than long-term, chronic refractory patients. Longer courses of treatment (12 weeks to 6 months) appear superior to shorter courses, and less selective agents appear superior to more selective alpha1 blockers. These observations outline important questions that must be answered to define optimal treatment strategies for patients with CP/CPPS.
Topics: Adrenergic alpha-Antagonists; Humans; Male; Prostatitis; Randomized Controlled Trials as Topic
PubMed: 17293646
DOI: 10.1159/000098064 -
The Cochrane Database of Systematic... Nov 2020Shock wave lithotripsy (SWL) is a widely used method to treat renal and ureteral stone. It fragments stones into smaller pieces that are then able to pass spontaneously... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Shock wave lithotripsy (SWL) is a widely used method to treat renal and ureteral stone. It fragments stones into smaller pieces that are then able to pass spontaneously down the ureter and into the bladder. Alpha-blockers may assist in promoting the passage of stone fragments, but their effectiveness remains uncertain. OBJECTIVES: To assess the effects of alpha-blockers as adjuvant medical expulsive therapy plus usual care compared to placebo and usual care or usual care alone in adults undergoing shock wave lithotripsy for renal or ureteral stones.
SEARCH METHODS
We performed a comprehensive literature search of the Cochrane Library, the Cochrane Database of Systematic Reviews, MEDLINE, Embase, several clinical trial registries and grey literature for published and unpublished studies irrespective of language. The date of the most recent search was 27 February 2020.
SELECTION CRITERIA
We included randomized controlled trials of adults undergoing SWL. Participants in the intervention group had to have received an alpha-blocker as adjuvant medical expulsive therapy plus usual care. For the comparator group, we considered studies in which participants received placebo.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies for inclusion/exclusion, and performed data abstraction and risk of bias assessment. We conducted meta-analysis for the identified dichotomous and continuous outcomes using RevManWeb according to Cochrane methods using a random-effects model. We judged the certainty of evidence on a per outcome basis using GRADE.
MAIN RESULTS
We included 40 studies with 4793 participants randomized to usual care and an alpha-blocker versus usual care alone. Only four studies were placebo controlled. The mean age of participants was 28.6 to 56.8 years and the mean stone size prior to SWL was 7.1 mm to 13.2 mm. The most widely used alpha-blocker was tamsulosin; others were silodosin, doxazosin, terazosin and alfuzosin. Alpha-blockers may improve clearance of stone fragments after SWL (risk ratio (RR) 1.16, 95% confidence interval (CI) 1.09 to 1.23; I² = 78%; studies = 36; participants = 4084; low certainty evidence). Based on the stone clearance rate of 69.3% observed in the control arm, an alpha-blocker may increase stone clearance to 80.4%. This corresponds to 111 more (62 more to 159 more) participants per 1000 clearing their stone fragments. Alpha-blockers may reduce the need for auxiliary treatments after SWL (RR 0.67, 95% CI 0.45 to 1.00; I² = 16%; studies = 12; participants = 1251; low certainty evidence), but also includes the possibility of no effect. Based on a rate of auxiliary treatments in the usual care arm of 9.7%, alpha-blockers may reduce the rate to 6.5%. This corresponds 32 fewer (53 fewer to 0 fewer) participants per 1000 undergoing auxiliary treatments. Alpha-blockers may reduce major adverse events (RR 0.60, 95% CI 0.46 to 0.80; I² = 0%; studies = 7; participants = 747; low certainty evidence). Major adverse events occurred in 25.8% of participants in the usual care group; alpha-blockers would reduce this to 15.5%. This corresponds to 103 fewer (139 fewer to 52 fewer) major adverse events per 1000 with alpha-blocker treatment. None of the reported major adverse events appeared drug-related; most were emergency room visits or rehospitalizations. Alpha-blockers may reduce stone clearance time in days (mean difference (MD) -3.74, 95% CI -5.25 to -2.23; I² = 86%; studies = 14; participants = 1790; low certainty evidence). We found no evidence for the outcome of quality of life. For those outcomes for which we were able to perform subgroup analyses, we found no evidence of interaction with stone location, stone size or type of alpha-blocker. We were unable to conduct an analysis by lithotripter type. The results were also largely unchanged when the analyses were limited to placebo controlled studies and those in which participants explicitly only received a single SWL session.
AUTHORS' CONCLUSIONS
Based on low certainty evidence, adjuvant alpha-blocker therapy following SWL in addition to usual care may result in improved stone clearance, less need for auxiliary treatments, fewer major adverse events and a reduced stone clearance time compared to usual care alone. We did not find evidence for quality of life. The low certainty of evidence means that our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.
Topics: Adrenergic alpha-1 Receptor Antagonists; Adult; Chemotherapy, Adjuvant; Combined Modality Therapy; Doxazosin; Humans; Indoles; Kidney Calculi; Lithotripsy; Middle Aged; Prazosin; Quinazolines; Randomized Controlled Trials as Topic; Tamsulosin; Ureteral Calculi
PubMed: 33179245
DOI: 10.1002/14651858.CD013393.pub2 -
Therapeutic Advances in... Dec 2012Parotid gland swelling is a less frequently reported side effect of clozapine and has no licensed treatment. A 58-year-old man treated with clozapine for...
Parotid gland swelling is a less frequently reported side effect of clozapine and has no licensed treatment. A 58-year-old man treated with clozapine for treatment-resistant schizophrenia developed bilateral painful parotid swellings and hypersalivation. Initial trials of dose alteration and antihypersalivatory medication had limited success. A combination of benzatropine and terazosin was successful in treating the parotid hyperplasia. Clozapine was the probable cause of parotid swelling in our case, as established using the Naranjo adverse drug reaction probability scale and World Health Organization causality categories. Literature for treatments of clozapine-induced parotid gland swellings was reviewed. None of the published articles suggested a treatment regimen for clozapine-induced parotid hyperplasia. Most reports only highlighted the occurrence of salivary gland swelling with clozapine. Others mentioned management strategies, which included spontaneous resolution, or resolution on discontinuing clozapine. One report, a trial with benzatropine and ipratropium, had variable success. In this case the re-emergence of parotid swelling when terazosin and benzatropine doses were missed followed by a quick resolution upon recompliance, goes some way in proving that this combination is indeed effective. The combination of terazosin and benzatropine appears to have a role in treating parotid gland swellings induced by clozapine.
PubMed: 23983982
DOI: 10.1177/2045125312455187