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Journal of the Neurological Sciences Apr 2022Tremor is one of the most common movement disorders, though it can arise in the context of several unrelated neurological disorders whose pharmacology and anatomical... (Review)
Review
Tremor is one of the most common movement disorders, though it can arise in the context of several unrelated neurological disorders whose pharmacology and anatomical origins differ greatly. Treatment of tremors can take advantage of several medications and neurosurgical treatments. Medications useful for treating tremor are discussed in this review, including those for action tremor as seen in essential tremor, the resting tremor of Parkinson's disease, orthostatic tremor, cerebellar tremor, Holmes tremor, dystonic tremor, and drug-induced tremors. A medication that is useful for most types of tremors is the beta-blocker propranolol, though even in essential tremor it can fail to be effective at tremor control. This article is part of the Special Issue "Tremor" edited by Daniel D. Truong, Mark Hallett, and Aasef Shaikh.
Topics: Ataxia; Essential Tremor; Humans; Parkinson Disease; Propranolol; Tremor
PubMed: 35279634
DOI: 10.1016/j.jns.2022.120194 -
Journal of Psychopharmacology (Oxford,... Feb 2016The effects of propranolol in the treatment of anxiety disorders have not been systematically evaluated previously. The aim was to conduct a systematic review and... (Comparative Study)
Comparative Study Meta-Analysis Review
The effects of propranolol in the treatment of anxiety disorders have not been systematically evaluated previously. The aim was to conduct a systematic review and meta-analysis of randomised controlled trials, addressing the efficacy of oral propranolol versus placebo or other medication as a treatment for alleviating either state or trait anxiety in patients suffering from anxiety disorders. Eight studies met the inclusion criteria. These studies concerned panic disorder with or without agoraphobia (four studies, total n = 130), specific phobia (two studies, total n = 37), social phobia (one study, n = 16), and posttraumatic stress disorder (PTSD) (one study, n = 19). Three out of four panic disorder trials qualified for pooled analyses. These meta-analyses found no statistically significant differences between the efficacy of propranolol and benzodiazepines regarding the short-term treatment of panic disorder with or without agoraphobia. Also, no evidence was found for effects of propranolol on PTSD symptom severity through inhibition of memory reconsolidation. In conclusion, the quality of evidence for the efficacy of propranolol at present is insufficient to support the routine use of propranolol in the treatment of any of the anxiety disorders.
Topics: Administration, Oral; Adrenergic beta-Antagonists; Anti-Anxiety Agents; Anxiety Disorders; Humans; Propranolol; Randomized Controlled Trials as Topic; Severity of Illness Index
PubMed: 26487439
DOI: 10.1177/0269881115612236 -
JAMA Pediatrics Jan 2022Propranolol for infantile hemangiomas (IH) has been shown to be effective and relatively safe. However, other less lipophilic β-blockers, such as nadolol, may be... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Propranolol for infantile hemangiomas (IH) has been shown to be effective and relatively safe. However, other less lipophilic β-blockers, such as nadolol, may be preferable in individuals who experience propranolol unresponsiveness or adverse events.
OBJECTIVE
To document the noninferiority and safety of oral nadolol compared with oral propranolol in infants with IH.
DESIGN, SETTING, AND PARTICIPANTS
This double-blind noninferiority prospective study with a noninferiority margin of 10% compared propranolol with nadolol in infants aged 1 to 6 months with problematic IH. The study was conducted in 2 academic pediatric dermatology centers in Canada between 2016 and 2020. Infants aged 1 to 6 months with a hemangioma greater than 1.5 cm on the face or 3 cm or greater on another body part causing or with potential to cause functional impairment or cosmetic disfigurement.
INTERVENTIONS
Oral propranolol and nadolol in escalating doses up to 2 mg/kg/d.
MAIN OUTCOMES AND MEASURE
Between-group differences comparing changes in the bulk (size and extent) and color of the IH at week 24 with baseline using a 100-mm visual analog scale.
RESULTS
The study included 71 patients. Of these, 36 were treated with propranolol. The mean (SD) age in this group was 3.1 (1.4) months, and 31 individuals (86%) were female. Thirty-five infants were treated with nadolol. The mean (SD) age in this group was 3.2 (1.6) months, and 26 individuals (74%) were female. The difference in IH between groups by t test was 8.8 (95% CI, 2.7-14.9) for size and 17.1 (95% CI, 7.2-30.0) for color in favor of the nadolol group, demonstrating that nadolol was noninferior to propranolol. Similar differences were noted at 52 weeks: 6.0 (95% CI, 1.9-10.1) and 10.1 (95% CI, 2.9-17.4) for size and color improvement, respectively. For each doubling of time unit (week), the coefficient of involution was 2.4 (95% CI, 0.5-4.4) higher with nadolol compared with propranolol. Safety data were similar between the 2 interventions.
CONCLUSIONS AND RELEVANCE
Oral nadolol was noninferior to oral propranolol, indicating it may be an efficacious and safe alternative in cases of propranolol unresponsiveness or adverse events, or when faster involution is required.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02505971.
Topics: Administration, Oral; Adrenergic beta-Antagonists; Double-Blind Method; Equivalence Trials as Topic; Female; Hemangioma, Capillary; Humans; Infant; Male; Nadolol; Neoplastic Syndromes, Hereditary; Ontario; Propranolol; Prospective Studies; Treatment Outcome
PubMed: 34747977
DOI: 10.1001/jamapediatrics.2021.4565 -
JAMA Otolaryngology-- Head & Neck... Jul 2021Propranolol has become the first-line therapy for problematic infantile hemangiomas (IHs) that require systemic therapy. However, different adverse events have been... (Comparative Study)
Comparative Study Randomized Controlled Trial
IMPORTANCE
Propranolol has become the first-line therapy for problematic infantile hemangiomas (IHs) that require systemic therapy. However, different adverse events have been reported during propranolol treatment. The positive efficacy and safety of atenolol raise the question of whether it could be used as a promising therapy for IH.
OBJECTIVE
To compare the efficacy and safety of propranolol vs atenolol in infants (between age 5 and 20 weeks) with problematic IHs who required systemic therapy.
DESIGN, SETTING, AND PARTICIPANTS
This was a prospective, multicenter, randomized, controlled, open-label clinical trial conducted in collaboration among 6 separate investigation sites in China from February 1, 2015, to December 31, 2018. A total of 377 patients met the criteria for inclusion and were randomized to the propranolol (190 [50.4%]) and atenolol (187 [49.6%]) groups. Data were analyzed in June 2020.
INTERVENTIONS
Participants were randomized to receive either propranolol or atenolol for at least 6 months. They completed efficacy assessments at 2 years after the initial treatment.
MAIN OUTCOMES AND MEASURES
The primary outcome was any response or nonresponse at 6 months. The key secondary outcome was changes in the hemangioma activity score.
RESULTS
Of 377 participants, 287 (76.1%) were female, and the mean (SD) age was 10.2 (4.0) weeks in the propranolol group and 9.8 (4.1) weeks in the atenolol group. After 6 months of treatment, in the propranolol and atenolol groups, the overall response rates were 93.7% and 92.5%, respectively (difference, 1.2%; 95% CI, -4.1% to 6.6%). At 1 and 4 weeks after treatment, and thereafter, the hemangioma activity score in the atenolol group aligned with the propranolol group (odds ratio, 1.034; 95% CI, 0.886-1.206). No differences between the propranolol group and atenolol group were observed in successful initial responses, quality of life scores, complete ulceration healing times, or the rebound rate. Both groups presented a similar percentage of complete/nearly complete responses at 2 years (82.1% vs 79.7%; difference, 2.4%; 95% CI, -5.9% to 10.7%). Adverse events were more common in the propranolol group (70.0% vs 44.4%; difference, 25.6%; 95% CI, 15.7%-34.8%), but the frequency of severe adverse events did not differ meaningfully between the groups.
CONCLUSIONS AND RELEVANCE
In this randomized clinical trial, when compared with propranolol, atenolol had similar efficacy and fewer adverse events in the treatment of infants with problematic IHs. The results suggest that oral atenolol can be used as an alternative treatment option for patients with IH who require systemic therapy.
TRIAL REGISTRATION
ClinicalTrial.gov Identifier: NCT02342275.
Topics: Adrenergic beta-1 Receptor Antagonists; Adrenergic beta-Antagonists; Atenolol; China; Female; Hemangioma, Capillary; Humans; Infant; Male; Propranolol; Prospective Studies
PubMed: 33856430
DOI: 10.1001/jamaoto.2021.0454 -
Critical Care (London, England) Jun 2023To evaluate the safety, feasibility, and efficacy of combined adrenergic blockade with propranolol and clonidine in patients with severe traumatic brain injury (TBI). (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To evaluate the safety, feasibility, and efficacy of combined adrenergic blockade with propranolol and clonidine in patients with severe traumatic brain injury (TBI).
BACKGROUND
Administration of adrenergic blockade after severe TBI is common. To date, no prospective trial has rigorously evaluated this common therapy for benefit.
METHODS
This phase II, single-center, double-blinded, pilot randomized placebo-controlled trial included patients aged 16-64 years with severe TBI (intracranial hemorrhage and Glasgow Coma Scale score ≤ 8) within 24 h of ICU admission. Patients received propranolol and clonidine or double placebo for 7 days. The primary outcome was ventilator-free days (VFDs) at 28 days. Secondary outcomes included catecholamine levels, hospital length of stay, mortality, and long-term functional status. A planned futility assessment was performed mid-study.
RESULTS
Dose compliance was 99%, blinding was intact, and no open-label agents were used. No treatment patient experienced dysrhythmia, myocardial infarction, or cardiac arrest. The study was stopped for futility after enrolling 47 patients (26 placebo, 21 treatment), per a priori stopping rules. There was no significant difference in VFDs between treatment and control groups [0.3 days, 95% CI (- 5.4, 5.8), p = 1.0]. Other than improvement of features related to sympathetic hyperactivity (mean difference in Clinical Features Scale (CFS) 1.7 points, CI (0.4, 2.9), p = 0.012), there were no between-group differences in the secondary outcomes.
CONCLUSION
Despite the safety and feasibility of adrenergic blockade with propranolol and clonidine after severe TBI, the intervention did not alter the VFD outcome. Given the widespread use of these agents in TBI care, a multi-center investigation is warranted to determine whether adrenergic blockade is of therapeutic benefit in patients with severe TBI. Trial Registration Number NCT01322048.
Topics: Humans; Propranolol; Clonidine; Pilot Projects; Treatment Outcome; Brain Injuries, Traumatic; Adrenergic Agents
PubMed: 37296432
DOI: 10.1186/s13054-023-04479-6 -
Journal of the American College of... May 2018Electrical storm (ES), characterized by unrelenting recurrences of ventricular arrhythmias, is observed in approximately 30% of patients with implantable... (Comparative Study)
Comparative Study
BACKGROUND
Electrical storm (ES), characterized by unrelenting recurrences of ventricular arrhythmias, is observed in approximately 30% of patients with implantable cardioverter-defibrillators (ICDs) and is associated with high mortality rates.
OBJECTIVES
Sympathetic blockade with β-blockers, usually in combination with intravenous (IV) amiodarone, have proved highly effective in the suppression of ES. In this study, we compared the efficacy of a nonselective β-blocker (propranolol) versus a β-selective blocker (metoprolol) in the management of ES.
METHODS
Between 2011 and 2016, 60 ICD patients (45 men, mean age 65.0 ± 8.5 years) with ES developed within 24 h from admission were randomly assigned to therapy with either propranolol (160 mg/24 h, Group A) or metoprolol (200 mg/24 h, Group B), combined with IV amiodarone for 48 h.
RESULTS
Patients under propranolol therapy in comparison with metoprolol-treated individuals presented a 2.67 times decreased incidence rate (incidence rate ratio: 0.375; 95% confidence interval: 0.207 to 0.678; p = 0.001) of ventricular arrhythmic events (tachycardia or fibrillation) and a 2.34 times decreased rate of ICD discharges (incidence rate ratio: 0.428; 95% CI: 0.227 to 0.892; p = 0.004) during the intensive care unit (ICU) stay, after adjusting for age, sex, ejection fraction, New York Heart Association functional class, heart failure type, arrhythmia type, and arrhythmic events before ICU admission. At the end of the first 24-h treatment period, 27 of 30 (90.0%) patients in group A, while only 16 of 30 (53.3%) patients in group B were free of arrhythmic events (p = 0.03). The termination of arrhythmic events was 77.5% less likely in Group B compared with Group A (hazard ratio: 0.225; 95% CI: 0.112 to 0.453; p < 0.001). Time to arrhythmia termination and length of hospital stay were significantly shorter in the propranolol group (p < 0.05 for both).
CONCLUSIONS
The combination of IV amiodarone and oral propranolol is safe, effective, and superior to the combination of IV amiodarone and oral metoprolol in the management of ES in ICD patients.
Topics: Adrenergic beta-Antagonists; Aged; Defibrillators, Implantable; Female; Humans; Length of Stay; Male; Metoprolol; Middle Aged; Propranolol; Prospective Studies; Tachycardia; Ventricular Fibrillation
PubMed: 29699616
DOI: 10.1016/j.jacc.2018.02.056 -
International Journal of Molecular... Sep 2022Propranolol, a non-cardioselective β blocker, is most commonly recognised for its application in the therapy of various cardiovascular conditions, such as hypertension,... (Review)
Review
Propranolol versus Other Selected Drugs in the Treatment of Various Types of Anxiety or Stress, with Particular Reference to Stage Fright and Post-Traumatic Stress Disorder.
Propranolol, a non-cardioselective β blocker, is most commonly recognised for its application in the therapy of various cardiovascular conditions, such as hypertension, coronary artery disease, and tachyarrhythmias. However, due to its ability to cross the blood-brain barrier and affinity towards multiple macromolecules, not only adrenoreceptors, it has also found application in other fields. For example, it is one of the very few medications successfully applied in the treatment of stage fright. This review focuses on the application of propranolol in the treatment of various types of anxiety and stress, with particular reference to stage fright and post-traumatic stress disorder (PTSD). Both mechanisms of action as well as comparison with other therapies are presented. As those indications for propranolol are, in most countries, considered off-label, this review aims to gather information that can be useful while making a decision about the choice of propranolol as a drug in the treatment of those mental conditions.
Topics: Anxiety; Anxiety Disorders; Humans; Propranolol; Stress Disorders, Post-Traumatic
PubMed: 36077489
DOI: 10.3390/ijms231710099 -
The New England Journal of Medicine Feb 2015Oral propranolol has been used to treat complicated infantile hemangiomas, although data from randomized, controlled trials to inform its use are limited. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Oral propranolol has been used to treat complicated infantile hemangiomas, although data from randomized, controlled trials to inform its use are limited.
METHODS
We performed a multicenter, randomized, double-blind, adaptive, phase 2-3 trial assessing the efficacy and safety of a pediatric-specific oral propranolol solution in infants 1 to 5 months of age with proliferating infantile hemangioma requiring systemic therapy. Infants were randomly assigned to receive placebo or one of four propranolol regimens (1 or 3 mg of propranolol base per kilogram of body weight per day for 3 or 6 months). A preplanned interim analysis was conducted to identify the regimen to study for the final efficacy analysis. The primary end point was success (complete or nearly complete resolution of the target hemangioma) or failure of trial treatment at week 24, as assessed by independent, centralized, blinded evaluations of standardized photographs.
RESULTS
Of 460 infants who underwent randomization, 456 received treatment. On the basis of an interim analysis of the first 188 patients who completed 24 weeks of trial treatment, the regimen of 3 mg of propranolol per kilogram per day for 6 months was selected for the final efficacy analysis. The frequency of successful treatment was higher with this regimen than with placebo (60% vs. 4%, P<0.001). A total of 88% of patients who received the selected propranolol regimen showed improvement by week 5, versus 5% of patients who received placebo. A total of 10% of patients in whom treatment with propranolol was successful required systemic retreatment during follow-up. Known adverse events associated with propranolol (hypoglycemia, hypotension, bradycardia, and bronchospasm) occurred infrequently, with no significant difference in frequency between the placebo group and the groups receiving propranolol.
CONCLUSIONS
This trial showed that propranolol was effective at a dose of 3 mg per kilogram per day for 6 months in the treatment of infantile hemangioma. (Funded by Pierre Fabre Dermatologie; ClinicalTrials.gov number, NCT01056341.).
Topics: Administration, Oral; Adrenergic beta-Antagonists; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Hemangioma; Humans; Hypotension; Infant; Male; Propranolol; Treatment Outcome
PubMed: 25693013
DOI: 10.1056/NEJMoa1404710 -
Ugeskrift For Laeger Mar 2019
Topics: Adrenergic beta-Antagonists; Anxiety Disorders; Humans; Propranolol
PubMed: 30931879
DOI: No ID Found -
Clinical Gastroenterology and... Aug 2023Carvedilol induces stronger decreases in hepatic venous pressure gradient (HVPG) than conventional nonselective β-blockers (ie, propranolol). Limited data exist on the...
BACKGROUND & AIMS
Carvedilol induces stronger decreases in hepatic venous pressure gradient (HVPG) than conventional nonselective β-blockers (ie, propranolol). Limited data exist on the efficacy of carvedilol in secondary prophylaxis of variceal bleeding.
METHODS
Patients undergoing paired HVPG measurements for guiding secondary prophylaxis with either carvedilol or propranolol were included in this retrospective analysis. All patients also underwent band ligation. Changes in HVPG and systemic hemodynamics were compared between the 2 groups. Long-term follow-up data on rebleeding, acute kidney injury, nonbleeding decompensation, and liver-related death were analyzed applying competing risk regression.
RESULTS
Eighty-seven patients (carvedilol/propranolol, n = 45/42) were included in our study. The median baseline HVPG was 21 mm Hg (interquartile range, 18-24 mm Hg), and 39.1%/48.3%/12.6% had Child-Turcotte-Pugh A/B/C cirrhosis, respectively. Upon nonselective β-blocker initiation, HVPG decreased more strongly in carvedilol users (median relative decrease, -20% [interquartile range: -29% to -10%] vs -11% [-22% to -5%] for propranolol; P = .027), who also achieved chronic HVPG response more often (53.3% vs 28.6%; P = .034). Cumulative incidences for rebleeding (Gray test, P = .027) and liver-related death (P = .036) were significantly lower in patients taking carvedilol compared with propranolol. Notably, ascites development/worsening also was observed less commonly in carvedilol patients (P = .012). Meanwhile, acute kidney injury rates did not differ between the 2 groups (P = .255). Stratifying patients by HVPG response status yielded similar results. The prognostic value of carvedilol intake was confirmed in competing risk regression models.
CONCLUSIONS
Carvedilol induces more marked reductions in HVPG than propranolol in secondary prophylaxis of variceal bleeding, and thus is associated with lower rates of rebleeding, liver-related death, and further nonbleeding decompensation.
Topics: Humans; Propranolol; Carvedilol; Esophageal and Gastric Varices; Retrospective Studies; Gastrointestinal Hemorrhage; Adrenergic beta-Antagonists; Hemodynamics; Liver Cirrhosis; Varicose Veins
PubMed: 35842118
DOI: 10.1016/j.cgh.2022.06.007