-
Current Drug Targets 2015Post-traumatic stress disorder (PTSD) is a chronic psychiatric disorder that may develop after exposure to a life-threatening trauma. As veterans and armed forces may... (Meta-Analysis)
Meta-Analysis Review
Post-traumatic stress disorder (PTSD) is a chronic psychiatric disorder that may develop after exposure to a life-threatening trauma. As veterans and armed forces may deal with diverse health problems compared with civilians, they have a greater risk for psychiatric disorders, including PTSD, than civilians, even if the disorder may be also frequent in the general population. PTSD is associated with significant comorbidity, especially with mood disorders and substance abuse. Moreover, the suicide risk is higher in PTSD patients than in the general population. Selective Serotonin Reuptake Inhibitors (SSRIs), atypical antipsychotics and benzodiazepines are commonly employed in the management of PTSD, but often these treatments fail or are discontinued due to adverse effects. It has been demonstrated that high noradrenergic activity may be associated with hyperarousal, trauma nightmares and sleep disturbances in PTSD subjects, probably through the stimulation of α -1 adrenergic receptors in the brain prefrontal cortex. The α -1 adrenoreceptor antagonist prazosin decreases noradrenaline effects at brain α-1 adrenoreceptors and may be a promising agent in the treatment of PTSD, as some studies have found it effective and well tolerated. Therefore, the present review is aimed to examine the role of noradrenergic system in the pathophysiology of PTSD. Moreover, we conducted a systematic review to evaluate the effectiveness and tolerability of prazosin in PTSD patients. Meta-analysis was used to combine data from multiple studies and better estimate the effect of prazosin on specific outcomes. We found prazosin to be significantly more efficacious than placebo in reducing distressing dreams in PTSD patients, even though our results should be interpreted with caution due to the small number of studies included in our quantitative synthesis.
Topics: Adrenergic alpha-1 Receptor Antagonists; Humans; Neuroimaging; Norepinephrine; Prazosin; Randomized Controlled Trials as Topic; Sleep Wake Disorders; Stress Disorders, Post-Traumatic; Treatment Outcome
PubMed: 25944011
DOI: 10.2174/1389450116666150506114108 -
Rheumatology International Sep 2015To evaluate the efficacy of current treatments for the Raynaud phenomenon (RP) in patients with systemic sclerosis (SSc), a systematic literature search was performed... (Review)
Review
To evaluate the efficacy of current treatments for the Raynaud phenomenon (RP) in patients with systemic sclerosis (SSc), a systematic literature search was performed using Medline, EMBASE, and Cochrane Central Register of Controlled Trials (from 1961 to October 2011). We included meta-analyses, systematic reviews, clinical trials, and high-quality cohort studies published in English or Spanish. Patient populations had to include adults diagnosed with limited cutaneous or diffuse SSc who had associated RP and/or digital ulcers under pharmacological treatment. Efficacy of treatments was evaluated based on: number of RP episodes, RP severity, episode-free time, ulcer improvement/healing, and appearance of new ulcers. We used the Jadad scale of methodological quality to evaluate the quality of randomized clinical trials, and the 2009 Oxford Centre for Evidence-Based Medicine classification for other studies. Of a total of 1617 studies identified, only 27 fulfilled inclusion criteria. Drugs received the following grade recommendations: Grade A for nifedipine, nicardipine, quinapril, IV iloprost, bosentan, tadalafil, and MQx-503; Grade B for beraprost, cicaprost, DMSO, cyclofenil, and atorvastatin; and Grade C for misoprostol, prazosin, OPC-2826, enalapril, sildenafil, antioxidant, and stanazolol. Calcium channel blockers, prostanoids, tadalafil, and bosentan received the highest recommendation level for their effectiveness. However, most systematic reviews reviewed just a handful of studies with small sample sizes and short follow-ups. Our review shows that the existing evidence on the efficacy of RP treatment in SSc patients is inconclusive which calls for further research, especially in the form of prospective studies of high quality with long-term follow-ups.
Topics: Humans; Raynaud Disease; Scleroderma, Systemic; Skin Ulcer; Treatment Outcome; Vasodilator Agents
PubMed: 25824427
DOI: 10.1007/s00296-015-3241-1 -
The role of alpha blockers prior to removal of urethral catheter for acute urinary retention in men.The Cochrane Database of Systematic... Jun 2014Acute urinary retention is a urological emergency in men and requires urgent catheterisation. Any intervention which aims at improving urinary symptoms following an... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acute urinary retention is a urological emergency in men and requires urgent catheterisation. Any intervention which aims at improving urinary symptoms following an acute urinary retention episode could be potentially beneficial. Alpha blockers relax prostatic smooth muscle cells thereby decreasing the resistance to urinary flow and by doing so could improve urinary symptoms.
OBJECTIVES
To assess the effectiveness of alpha blockers on successful resumption of micturition following removal of a urethral urinary catheter after an episode of acute urinary retention in men. In the absence of internationally agreed outcome measures for the success of a trial without catheter, success was defined as the return to satisfactory voiding without need for re-catheterisation within 24 hours.
SEARCH METHODS
We searched the Cochrane Incontinence Group Specialised Trials Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE in process, and handsearching of journals and conference proceedings (searched 9 October 2013), CENTRAL (2013, Issue 5) (searched 5 June 2013), MEDLINE 1946 to May Week 4 2013, MEDLINE in Process (covering to 3 June 2013), EMBASE Classic and EMBASE 1947 to 2013 Week 22 (all searched 4 June 2013) and the reference lists of relevant articles. No language or other restrictions were imposed on the searches.
SELECTION CRITERIA
Only randomised and quasi-randomised clinical trials of alpha blockers for trial without a urethral catheter following an episode of acute urinary retention in men were included.
DATA COLLECTION AND ANALYSIS
Two review authors independently examined all the citations and abstracts derived from the search strategy. Any disagreement about trial selection and inclusion was resolved by discussion. A third independent judgement was sought where disagreement persisted. Two review authors extracted independently, cross-checked and processed the data as described in the Cochrane Handbook for Systematic Reviews of Intervention. Quality of evidence of the critical outcomes was assessed by adopting the GRADE approach.
MAIN RESULTS
Nine randomised clinical trials were included in this review. Eight trials compared alpha blockers versus placebo (five trials tested alfuzosin and two trials tested tamsulosin, one trial tested both alfuzosin and tamsulosin, one trial tested silodosin) and one trial compared an alpha blocker (doxazosin) versus no treatment. Trial without catheter was performed after treatment with the drug for one to three days in seven trials and for eight and 32 days in two other trials respectively. There was moderate quality evidence to suggest that the rate of successful trial without catheter favoured alpha blockers over placebo ( 366/608, 60.2%, of men using an alpha blocker were able to void spontaneously after catheter removal compared with 185/486, 38.1%, using placebo, risk ratio (RR) 1.55, 95% confidence interval (CI) 1.36 to 1.76). The incidence of recurrent acute urinary retention was lower in groups treated with an alpha blocker (RR 0.69, 95% CI 0.60 to 0.79). This evidence was of moderate quality and was statistically significant for alfuzosin, tamsulosin and silodosin, though not for doxazosin. Of the trials mentioning adverse effects (for example, postural hypotension, dizziness), there was not enough information to detect statistically significant differences between the groups (RR 1.19, 95% CI 0.75 to 1.89) and the evidence was of low quality. Overall, adverse effect rates were low for both placebo and alpha blockers and, for example, vasodilatation-related adverse effects did not often result in discontinuation.
AUTHORS' CONCLUSIONS
There was some evidence to suggest that alpha blockers increase the success rates of trial without catheter, and the incidence of adverse effects was low. There was some evidence of a decreased incidence of acute urinary retention. The need for further surgery, cost effectiveness and recommended duration of alpha blocker treatment after successful trial without catheter remain unknown as these were not reported by any trial. There is a lack of internationally agreed outcome measures for what constitutes successful trial without catheter. This makes meta-analysis difficult. Large, well-designed controlled trials, which use the recommendations set out in the CONSORT statement, and include clinically important outcome measures, are required.
Topics: Acute Disease; Adrenergic alpha-Antagonists; Adult; Device Removal; Doxazosin; Humans; Indoles; Male; Quinazolines; Randomized Controlled Trials as Topic; Recovery of Function; Sulfonamides; Tamsulosin; Urinary Catheterization; Urinary Retention; Urination
PubMed: 24913721
DOI: 10.1002/14651858.CD006744.pub3 -
The Journal of Sexual Medicine Jun 2014Several drugs, currently used to treat lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH), can be associated with bothersome sexual side... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Several drugs, currently used to treat lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH), can be associated with bothersome sexual side effects, including ejaculatory dysfunction (EjD).
AIM
To provide a systematic review and meta-analysis of the available randomized clinical trials (RCTs) reporting the impact of medical treatments for LUTS due to BPH on ejaculatory function.
MAIN OUTCOME MEASURE
EjD related to medical treatments for LUTS.
METHODS
A systematic literature search was performed using PubMed, Scopus and Cochrane databases. EjD was identified using both free text ("ejaculat*," "retrograde ejaculation," "anejaculation," "ejaculatory dysfunction") and Mesh ("Ejaculation") searches.
RESULTS
Of 101 retrieved articles, 23 were included in the present meta-analysis. EjD was significantly more common with alpha-blockers (ABs) than with placebo (OR:5.88; P < 0.0001), in particular, considering Tamsulosin (OR:8.58; P = 0.006) or Silodosin (OR:32.5; P < 0.0001), with Tamsulosin associated with significantly lower risk of EjD than Silodosin (OR:0.09; P < 0.00001). Conversely, Doxazosin and Terazosin were associated with a risk similar to placebo. Meta-regression showed that EjD was associated with IPSS and with Qmax both before and after treatment with ABs, while multivariate analysis demonstrated that EjD was independently associated with the improvement of IPSS (adj.r:0.2012; P < 0.0001) and Qmax (adj.r:0.522; P < 0.0001). EjD was significantly more common with 5ARIs as compared with placebo (OR:2.73; P < 0.0001). Both Finasteride (OR 2.70; P < 0.0001) and Dutasteride (OR 2.81; P = 0.0002) were associated with significantly higher risk of EjD than placebo. EjD was significantly more common with combination therapy as compared with ABs alone (OR:3.75; P < 0.0001),or with 5ARIs alone (OR:2.76; P = 0.02).
CONCLUSIONS
ABs and 5ARI were both associated with significantly higher risk of EjD than placebo. More the AB is effective over time, greater is the incidence of EjD. Finasteride has the same risk of Dutasteride to cause EjD. Combination therapy with ABs and 5ARIs resulted in a 3-fold increased risk of EjD as compared with ABs or 5ARIs alone. These data can be relevant both for drug selection and patients counseling.
Topics: Adrenergic alpha-1 Receptor Antagonists; Azasteroids; Doxazosin; Dutasteride; Ejaculation; Finasteride; Humans; Lower Urinary Tract Symptoms; Male; Prostatic Hyperplasia; Sexual Dysfunction, Physiological; Sulfonamides; Tamsulosin; Urological Agents
PubMed: 24708055
DOI: 10.1111/jsm.12525 -
International Psychogeriatrics Feb 2013Medications are frequently prescribed for neuropsychiatric symptoms (NPS) associated with dementia, although information on the efficacy and safety of medications for... (Review)
Review
BACKGROUND
Medications are frequently prescribed for neuropsychiatric symptoms (NPS) associated with dementia, although information on the efficacy and safety of medications for NPS specifically in long-term care (LTC) settings is limited. The objective of this study was to provide a current review of the efficacy and safety of pharmacological treatments for NPS in LTC.
METHODS
We searched MEDLINE, EMBASE, PsychINFO, and the Cochrane Library for randomized controlled trials comparing medications with either placebo or other interventions in LTC. Study quality was described using the Cochrane collaboration risk of bias tool. The efficacy of medications was evaluated using NPS symptom rating scales. Safety was evaluated through rates of trial withdrawals, trial withdrawals due to adverse events, and mortality.
RESULTS
A total of 29 studies met inclusion criteria. The most common medications evaluated in studies were atypical antipsychotics (N = 15), typical antipsychotics (N = 7), anticonvulsants (N = 4), and cholinesterase inhibitors (N = 3). Statistically significant improvements in NPS were noted in some studies evaluating risperidone, olanzapine, and single studies of aripiprazole, carbamazepine, estrogen, cyproterone, propranolol, and prazosin. Study quality was difficult to rate in many cases due to incomplete reporting of details. Some studies reported higher rates of trial withdrawals, adverse events, and mortality associated with medications.
CONCLUSIONS
We conclude that there is limited evidence to support the use of some atypical antipsychotics and other medications for NPS in LTC populations. However, the generally modest efficacy and risks of adverse events highlight the need for the development of safe and effective pharmacological and non-pharmacological interventions for this population.
Topics: Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Behavioral Symptoms; Cholinesterase Inhibitors; Dementia; Diagnostic Techniques, Neurological; Humans; Long-Term Care; Practice Patterns, Physicians'; Psychiatric Status Rating Scales; Psychomotor Disorders; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 23083438
DOI: 10.1017/S1041610212001627 -
Mayo Clinic Proceedings Sep 2012Nightmares, frequently associated with posttraumatic stress disorder and clinically relevant in today's world of violence, are difficult to treat, with few pharmacologic... (Review)
Review
Nightmares, frequently associated with posttraumatic stress disorder and clinically relevant in today's world of violence, are difficult to treat, with few pharmacologic options. We performed a systematic review to evaluate the evidence for the use of prazosin in the treatment of nightmares. A comprehensive search was performed using the databases EMBASE, Ovid MEDLINE, PubMed, Scopus, Web of Science, and Cochrane Database of Systematic Reviews, from their inception to March 9, 2012, using keywords prazosin and nightmares/PTSD or associated terms (see text). Two authors independently reviewed titles and abstracts and selected relevant studies. Descriptive data and outcomes of interest from eligible studies were extracted by 1 author, and checked by 2 others. The risk of bias of randomized controlled trials (RCTs) was assessed independently by 2 reviewers. Articles met criteria for inclusion if prazosin was used to treat nightmares, and outcome measures included nightmares or related symptoms of sleep disorders. Our search yielded 21 studies, consisting of 4 RCTs, 4 open-label studies, 4 retrospective chart reviews, and 9 single case reports. The prazosin dose ranged from 1 to 16 mg/d. Results were mixed for the 4 RCTs: 3 reported significant improvement in the number of nightmares, and 1 found no reduction in the number of nightmares. Reduced nightmare severity with use of prazosin was consistently reported in the open-label trials, retrospective chart reviews, and single case reports.
Topics: Adrenergic alpha-1 Receptor Antagonists; Dreams; Humans; Prazosin; Sleep Wake Disorders; Stress Disorders, Post-Traumatic
PubMed: 22883741
DOI: 10.1016/j.mayocp.2012.05.015 -
Spinal Cord Dec 2012Systematic review. (Meta-Analysis)
Meta-Analysis Review
STUDY DESIGN
Systematic review.
OBJECTIVES
Review the literature on the acute or prophylactic treatment of autonomic dysreflexia in the context of sexual activities.
SETTING
International.
METHODS
Medline search using AD and spinal cord injury and all years of publication.
RESULTS
Thirty-seven papers on the specific treatment of AD showed that nifedipine, prazosin, captopril and clonidine are candidates in the context of sexual activities. Prazosin, however, has an initial hypotensive effect requiring to begin treatment 12 h before intercourse, which makes it less ideal for spontaneous sexual activities. Captopril has an initial hypotensive effect and was only studied in acute AD. Its usefulness in prophylaxis remains to be demonstrated. Clonidine has successfully been used clinically for decades, but never studied in randomized control trials. Nifedipine remains the most widely studied and significant treatment of AD whether in acute or prophylactic conditions. Recent concerns suggest increased cardiovascular risks with sublingual nifedipine in non-SCI populations, but negative long-term effects have not been reported in the SCI population.
CONCLUSION
Sexual function is a priority for men with SCI. As sexual activities, in particular ejaculation, can be a source of AD, adequate treatments and prophylaxis must be considered in the context of sexual activities. Experts must meet and conclude on the thresholds, parameters and treatments that should be considered in the long-term management of AD in the context of sexual function in men with SCI.
Topics: Adult; Autonomic Dysreflexia; Ejaculation; Humans; Male; Randomized Controlled Trials as Topic; Sexual Dysfunction, Physiological; Spinal Cord Injuries
PubMed: 22869221
DOI: 10.1038/sc.2012.83 -
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 -
BMJ Clinical Evidence Mar 2011Raynaud's phenomenon is an episodic vasospasm of the peripheral arteries, causing pallor, followed by cyanosis and redness with pain, and sometimes paraesthesia. On rare... (Review)
Review
INTRODUCTION
Raynaud's phenomenon is an episodic vasospasm of the peripheral arteries, causing pallor, followed by cyanosis and redness with pain, and sometimes paraesthesia. On rare occasions it can lead to ulceration of the fingers and toes (and in some cases of the ears or nose). This review focuses on primary (idiopathic) Raynaud's phenomenon, occurring in the absence of an underlying disease. The prevalence of primary Raynaud's phenomenon varies by sex, country, and exposure to workplace vibration.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for primary Raynaud's phenomenon? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 16 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: amlodipine, diltiazem, exercise, inositol nicotinate, keeping warm, moxisylyte (thymoxamine), naftidrofuryl oxalate, nicardipine, nifedipine, prazosin, and smoking cessation.
Topics: Administration, Oral; Humans; Nifedipine; Prevalence; Raynaud Disease; Ulcer; Vibration
PubMed: 21401971
DOI: No ID Found -
Ophthalmology Apr 2011To evaluate risk factors (hypertension, diabetes mellitus, and current tamsulosin, alfuzosin, terazosin, or doxazosin use) for intraoperative floppy iris syndrome (IFIS)... (Meta-Analysis)
Meta-Analysis
PURPOSE
To evaluate risk factors (hypertension, diabetes mellitus, and current tamsulosin, alfuzosin, terazosin, or doxazosin use) for intraoperative floppy iris syndrome (IFIS) in patients undergoing phacoemulsification cataract surgery.
DESIGN
Systematic review and meta-analysis of the literature.
PARTICIPANTS
Seventeen eligible studies (17 588 eyes) examining the association between IFIS and risk factors.
METHODS
Pertinent publications were identified through a systematic search of PubMed. All references of relevant reviews and eligible articles were also screened. Language restrictions were not used, and data were extracted from each eligible study by 2 investigators working independently. For medications, 2 separate analyses were performed: an analysis using a dichotomous criterion (use/non-use of the examined agent) and an alternative analysis performing comparisons with patients not receiving any α(1)-blocker. The fixed-effects model (Mantel-Haenszel method) or the random-effects (DerSimonian Laird) model was appropriately used to calculate the pooled odds ratio (OR). Publication bias was appropriately assessed.
MAIN OUTCOME MEASURES
Pooled OR for the incidence of IFIS.
RESULTS
The pooled OR for IFIS after tamsulosin use was approximately 40-fold greater (or 16.5 at the alternative analysis) than that after alfuzosin use, that is, the second α(1)-blocker in order of effect size. Alfuzosin and terazosin were also associated with IFIS with comparable ORs; the effect of doxazosin reached formal statistical significance at the alternative analysis. Intraoperative floppy iris syndrome was positively associated with hypertension (pooled OR = 2.2, 95% confidence interval [CI], 1.2-4.2, fixed effects) but not with diabetes mellitus (pooled OR = 1.3, 95% CI, 0.7-2.2, fixed effects).
CONCLUSIONS
This meta-analysis has highlighted a hierarchy concerning the role of α(1)-blockers in IFIS, indicating an extremely sizeable effect size of tamsulosin; this may entail important physiologic implications. Alfuzosin, terazosin, and doxazosin presented with comparable effect sizes. Hypertension, but not diabetes mellitus, emerged as a risk factor for IFIS.
Topics: Adrenergic alpha-1 Receptor Antagonists; Diabetes Complications; Doxazosin; Humans; Hypertension; Incidence; Intraoperative Complications; Iris; Iris Diseases; Odds Ratio; Phacoemulsification; Prazosin; Quinazolines; Risk Factors; Sulfonamides; Syndrome; Tamsulosin
PubMed: 21168223
DOI: 10.1016/j.ophtha.2010.08.039