Combined Therapy for Migraine Prevention? Clinical Experience with A β-Blocker Plus Sodium Valproate in 52 Resistant Migraine Patients

The aim was to explore whether combining a β-blocker and sodium valproate could lead to an advantage in efficacy in patients with migraine previously resistant to the two medications in monotherapy. Fifty-two patients (43 women) with a history of episodic migraine with or without aura, and previously unresponsive to β-blockers and sodium valproate in monotherapy, were treated with a combination of propranolol or nadolol and sodium valproate in an open-label fashion. Eight patients (15%) discontinued due to adverse events. Fifteen (29%) did not respond. The remaining 29 cases (56%) showed response (>50% reduction in migraine days). The response was excellent in nine (17%). From this open trial, combination therapy with a β-blocker and sodium valproate appears to be a good migraine preventative in some previously resistant migraine cases. Controlled trials are now necessary to determine the true advantage in efficacy of this combination in difficult to treat migraineurs.

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Effect of Rosiglitazone and Insulin Combination Therapy on Inflammation Parameters and Adipocytokine Levels in Patients with Type 1 DM

Journal of Diabetes Research ◽

10.1155/2015/807891 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Metin Guclu ◽

Ozen Oz Gul ◽

Soner Cander ◽

Oguzkaan Unal ◽

Guven Ozkaya ◽

...

Keyword(s):

Insulin Sensitivity ◽

Combination Therapy ◽

Combined Therapy ◽

Diabetes Mellitus Type 1 ◽

Open Label ◽

Metabolic Complications ◽

Inflammatory Parameters ◽

Type 1 Dm ◽

Group 1

Aim.To investigate the efficacy of combined therapy of insulin and rosiglitazone on metabolic and inflammatory parameters, insulin sensitivity, and adipocytokine levels in patients with type 1 diabetes mellitus (type 1 DM).Material and Methods.A total of 61 adults with type 1 DM were randomly and prospectively assigned in open-label fashion to take insulin and rosiglitazone 4 mg/day (n=30) or insulin alone (n=31) for a period of 18 weeks while undergoing insulin therapy without acute metabolic complications.Results.Combination therapy did not significantly improve metabolic and inflammatory parameters, insulin sensitivity, and adiponectin levels. While leptin and resistin levels decreased in both groups (group 1: resistin 6.96 ± 3.06 to 4.99 ± 2.64,P=0.006; leptin 25.8 ± 17.6 to 20.1 ± 12.55,P=0.006; group 2: resistin 7.16 ± 2.30 to5.57±2.48,P=0.031; leptin 16.72 ± 16.1 to 14.0 ± 13.4,P=0.007) Hgb and fibrinogen levels decreased only in group 1 (Hgb 13.72 ± 1.98 to 13.16 ± 1.98,P=0.015, and fibrinogen 4.00 ± 1.08 to 3.46 ± 0.90,P=0.002). Patients in both groups showed weight gain and the incidence of hypoglycemia was not lower.Discussion.The diverse favorable effects of TZDs were not fully experienced in patients with type 1 DM. These results are suggesting that insulin sensitizing and anti-inflammatory characteristics of TZDs were likely to be more pronounced in patients who were not totally devoid of endogenous insulin secretion.

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Preventing microalbuminuria with benazepril, valsartan, and benazepril–valsartan combination therapy in diabetic patients with high-normal albuminuria: A prospective, randomized, open-label, blinded endpoint (PROBE) study

PLoS Medicine ◽

10.1371/journal.pmed.1003691 ◽

2021 ◽

Vol 18 (7) ◽

pp. e1003691

Author(s):

Piero Ruggenenti ◽

Monica Cortinovis ◽

Aneliya Parvanova ◽

Matias Trillini ◽

Ilian P. Iliev ◽

...

Keyword(s):

Combination Therapy ◽

Angiotensin Receptor Blockers ◽

Combined Therapy ◽

Accelerated Failure Time Model ◽

Diabetic Patients ◽

Open Label ◽

Type 2 Diabetic Patients ◽

Link Type ◽

Type 2 Diabetic

Background Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) prevent microalbuminuria in normoalbuminuric type 2 diabetic patients. We assessed whether combined therapy with the 2 medications may prevent microalbuminuria better than ACE inhibitor or ARB monotherapy. Methods and findings VARIETY was a prospective, randomized, open-label, blinded endpoint (PROBE) trial evaluating whether, at similar blood pressure (BP) control, combined therapy with benazepril (10 mg/day) and valsartan (160 mg/day) would prevent microalbuminuria more effectively than benazepril (20 mg/day) or valsartan (320 mg/day) monotherapy in 612 type 2 diabetic patients with high-normal albuminuria included between July 2007 and April 2013 by the Istituto di Ricerche Farmacologiche Mario Negri IRCCS and 8 diabetology or nephrology units in Italy. Time to progression to microalbuminuria was the primary outcome. Analyses were intention to treat. Baseline characteristics were similar among groups. During a median [interquartile range, IQR] follow-up of 66 [42 to 83] months, 53 patients (27.0%) on combination therapy, 57 (28.1%) on benazepril, and 64 (31.8%) on valsartan reached microalbuminuria. Using an accelerated failure time model, the estimated acceleration factors were 1.410 (95% CI: 0.806 to 2.467, P = 0.229) for benazepril compared to combination therapy, 0.799 (95% CI: 0.422 to 1.514, P = 0.492) for benazepril compared to valsartan, and 1.665 (95% CI: 1.007 to 2.746, P = 0.047) for valsartan compared to combination therapy. Between-group differences in estimated acceleration factors were nonsignificant after adjustment for predefined confounders. BP control was similar across groups. All treatments were safe and tolerated well, with a slight excess of hyperkalemia and hypotension in the combination therapy group. The main study limitation was the lower than expected albuminuria at inclusion. Conclusions Risk/benefit profile of study treatments was similar. Dual renin–angiotensin system (RAS) blockade is not recommended as compared to benazepril or valsartan monotherapy for prevention of microalbuminuria in normoalbuminuric type 2 diabetic patients. Trial registration EudraCT 2006-005954-62; ClinicalTrials.gov NCT00503152.

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Do β-Blockers Cause Depression?

Hypertension ◽

10.1161/hypertensionaha.120.16590 ◽

2021 ◽

Author(s):

Thomas G. Riemer ◽

Linda E. Villagomez Fuentes ◽

Engi A.E. Algharably ◽

Marie S. Schäfer ◽

Eva Mangelsen ◽

...

Keyword(s):

Randomized Controlled Trials ◽

Psychological Health ◽

Odds Ratio ◽

Controlled Trials ◽

Double Blind ◽

Blocker Therapy ◽

Randomized Controlled ◽

Cardiovascular Morbidity And Mortality ◽

Β Blocker ◽

Β Blockers

β-Blockers are important drugs in the treatment of cardiovascular diseases. They are suspected of inducing various psychiatric adverse events (PAEs), particularly depression, affecting cardiovascular morbidity and mortality. We performed a systematic search for double-blind, randomized controlled trials investigating β-blockers to analyze the risk of PAEs or withdrawal of therapy due to PAEs. We extracted the frequencies of PAEs and rates of withdrawals and reviewed them to the number of exposed patients. For β-blockers versus placebo or other active treatment, we calculated odds ratios for individual PAEs and withdrawal rates. We retrieved overall 285 eligible studies encompassing 53 533 patients. The risk of bias was judged to be high in 79% of the studies. Despite being the most frequently reported PAE with a total of 1600 cases, depression did not occur more commonly during β-blockers than during placebo (odds ratio, 1.02 [95% CI, 0.83–1.25]). β-Blocker use was also not associated with withdrawal for depression (odds ratio, 0.97 [95% CI, 0.51–1.84]). Similar results were obtained for comparisons against active agents. Among other PAEs, only unusual dreams, insomnia, and sleep disorder were possibly related to β-blocker therapy. In conclusion, this analysis of large-scale data from double-blind, randomized controlled trials does not support an association between β-blocker therapy and depression. Similarly, no effect for β-blockers was found for other PAEs, with the possible exceptions of sleep-related disorders. Consequently, concerns about β-blockers’ impact on psychological health should not affect their use in clinical practice.

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Antiepileptics in migraine prophylaxis: An updated Cochrane review

Cephalalgia ◽

10.1177/0333102414534325 ◽

2014 ◽

Vol 35 (1) ◽

pp. 51-62 ◽

Cited By ~ 43

Author(s):

Wim M Mulleners ◽

Douglas C McCrory ◽

Mattias Linde

Keyword(s):

Sodium Valproate ◽

Cochrane Review ◽

Preventive Treatment ◽

Episodic Migraine ◽

Dose Effect ◽

Adverse Event Rate ◽

Controlled Trials ◽

Cochrane Central Register ◽

Central Register ◽

Related Quality

Introduction The efficacy of several antiepileptics in the preventive treatment of episodic migraine in adults has been systematically reviewed. Because many trial reports have been published since then, an updated systematic review was warranted. Methods We searched the Cochrane Central Register of Controlled Trials, PubMed/MEDLINE (1966 to January 15, 2013), MEDLINE In-Process (current week, January 15, 2013), and EMBASE (1974 to January 15, 2013) and hand-searched Headache and Cephalalgia through January 2013. Prospective, controlled trials of antiepileptics taken regularly to prevent the occurrence of migraine attacks, to improve migraine-related quality of life, or both, were selected. Results Mean headache frequency on topiramate and sodium valproate is significantly lower than placebo. Likewise, topiramate and divalproex demonstrated favorable results for the proportion of subjects with ≥50% reduction of migraine attacks. For topiramate, 100 mg and 200 mg outperformed 50 mg, but this was paralleled by a higher adverse event rate. For valproate/divalproex, a dose-effect correlation could not be established. There was no unequivocal evidence of efficacy for any of the other antiepileptics. Conclusion Topiramate, sodium valproate and divalproex are effective prophylactic treatments for episodic migraine in adults. In contrast to previous reports, there is insufficient evidence to further support the use of gabapentin.

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The Efficacy and Safety of Topical β-Blockers in Treating Infantile Hemangiomas: A Meta-Analysis Including 11 Randomized Controlled Trials

Dermatology ◽

10.1159/000510029 ◽

2020 ◽

pp. 1-11

Author(s):

Xinhui Wang ◽

Wei Feng ◽

Xufeng Zhao ◽

Ziyu Liu ◽

Liang Dong

Keyword(s):

Adverse Effects ◽

Randomized Controlled Trials ◽

Meta Analysis ◽

Pulsed Dye Laser ◽

Controlled Trials ◽

Efficacy And Safety ◽

Randomized Controlled ◽

Β Blocker ◽

Β Blockers ◽

Oral Propranolol

Background: To evaluate the efficacy and safety of topical β-blockers in the treatment of superficial infantile hemangiomas (SIH) and mixed infantile hemangiomas (MIH), respectively, and compare the efficacy and safety of topical β-blockers with other interventions. Methods: The PRISMA guidelines were adhered to. We searched for randomized controlled trials in databases from 2010 to 2018 comparing topical β-blockers with other interventions for infantile hemangiomas. The outcomes evaluated were efficacy and adverse effects. Data analyses were performed using RevMan 5.3. Publication bias was assessed to account for bias in patient selection. Results: Eleven studies, involving 1,235 patients, were subjected to this meta-analysis. Six studies compared topical β-blockers with other interventions (propranolol, placebo, corticosteroids or pulsed dye laser) in treating SIH, and 5 studies evaluated the efficacy and safety of a topical β-blocker when it was combined with another intervention in treating MIH. A topical β-blocker was discovered to be as effective as oral propranolol in treating SIH (risk ratio, RR, 0.96, 95% confidence interval, CI, 0.91–1.02, p = 0.20, I2 = 0%), and topical β-blockers were more beneficial than placebo, corticosteroids or pulsed dye laser in treating SIH (RR 2.25, 95% CI 1.66–3.05, p < 0.00001, I2 = 0%). Topical β-blockers combined with another intervention gave rise to a better clinical response in the treatment of MIH than intervention alone (RR 1.99, 95% CI 1.10–3.60, p = 0.02, I2 = 55%) (standard mean difference 0.80, 95% CI 0.28–1.31, p = 0.002, I2 = 0%). Compared with oral propranolol, topical β-blockers were associated with fewer incidences of adverse effects (RR 0.05, 95% CI 0.01–0.39, p = 0.004, I2 = 0%). No significant difference in adverse effects was found when a topical β-blocker was combined with another intervention in treating MIH (RR 1.01, 95% CI 0.58–1.74, p = 0.98, I2 = 0%). Conclusions: This meta-analysis provided evidence that topical β-blockers may replace oral propranolol as first-line therapy for SIH and that they are of additive value in treating MIH.

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Timing of β-Blocker Reintroduction and the Occurrence of Postoperative Atrial Fibrillation after Cardiac Surgery

Anesthesiology ◽

10.1097/aln.0000000000003064 ◽

2020 ◽

Vol 132 (2) ◽

pp. 267-279 ◽

Cited By ~ 4

Author(s):

Camille Couffignal ◽

Julien Amour ◽

Nora Ait-Hamou ◽

Bernard Cholley ◽

Jean-Luc Fellahi ◽

...

Keyword(s):

Atrial Fibrillation ◽

Cardiac Surgery ◽

Odds Ratio ◽

Adjusted Odds Ratio ◽

Postoperative Atrial Fibrillation ◽

Secondary Outcome ◽

Outcome Relationship ◽

History Of ◽

Β Blocker ◽

Β Blockers

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background For cardiac surgery patients under chronic β-blocker therapy, guidelines recommend their early postoperative reintroduction to decrease the incidence of postoperative atrial fibrillation. The authors hypothesized that the timing of β-blocker reintroduction affects their effectiveness on the incidence of postoperative atrial fibrillation. Methods This multicenter prospective French cohort study included patients on β-blockers (more than 30 days before surgery) in sinus rhythm without a pacemaker. The primary outcome, time sequence of β-blocker reintroduction, was analyzed for 192 h after surgery. The secondary outcome, relationship between the occurrence of postoperative atrial fibrillation and timing of β-blocker reintroduction, was analyzed based on pre- and intraoperative predictors (full and selected sets) according to landmark times (patients in whom atrial fibrillation occurred before a given landmark time were not analyzed). Results Of 663 patients, β-blockers were reintroduced for 532 (80%) but for only 261 (39%) patients in the first 48 h after surgery. Median duration before reintroduction was 49.5 h (95% CI, 48 to 51.5 h). Postoperative atrial fibrillation or death (N = 4) occurred in 290 (44%) patients. After performing a landmark analysis to take into account the timing of β-blocker reintroduction, the adjusted odds ratios (95% CI) for predictor full and selected (increased age, history of paroxysmal atrial fibrillation, and duration of aortic cross clamping) sets for the occurrence of postoperative atrial fibrillation were: adjusted odds ratio (full) = 0.87 (0.58 to 1.32; P = 0.517) and adjusted odds ratio (selected) = 0.84 (0.58 to 1.21; P = 0.338) at 48 h; adjusted odds ratio (full) = 0.64 (0.39 to 1.05; P = 0.076) and adjusted odds ratio (selected) = 0.58 (0.38 to 0.89; P = 0.013) at 72 h; adjusted odds ratio (full) = 0.58 (0.31 to 1.07; P = 0.079) and adjusted odds ratio (selected) = 0.53 (0.31 to 0.91; P = 0.021) at 96 h. Conclusions β-Blockers were reintroduced early (after less than 48 h) in fewer than half of the cardiac surgery patients. Reintroduction decreased postoperative atrial fibrillation occurrence only at later time points and only in the predictor selected set model. These results are an incentive to optimize (timing, doses, or titration) β-blocker reintroduction after cardiac surgery.

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Open Label Trial of Coenzyme Q10 as A Migraine Preventive

Cephalalgia ◽

10.1046/j.1468-2982.2002.00335.x ◽

2002 ◽

Vol 22 (2) ◽

pp. 137-141 ◽

Cited By ~ 101

Author(s):

TD Rozen ◽

ML Oshinsky ◽

CA Gebeline ◽

KC Bradley ◽

WB Young ◽

...

Keyword(s):

Coenzyme Q10 ◽

Preventive Treatment ◽

Baseline Period ◽

Episodic Migraine ◽

Significant Response ◽

Open Label ◽

Migraine Headaches ◽

Migraine Frequency ◽

History Of ◽

Open Label Trial

The objective was to assess the efficacy of coenzyme Q10 as a preventive treatment for migraine headaches. Thirty-two patients (26 women, 6 men) with a history of episodic migraine with or without aura were treated with coenzyme Q10 at a dose of 150 mg per day. Thirty-one of 32 patients completed the study; 61.3% of patients had a greater than 50% reduction in number of days with migraine headache. The average number of days with migraine during the baseline period was 7.34 and this decreased to 2.95 after 3 months of therapy, which was a statistically significant response ( P < 0.0001). Mean reduction in migraine frequency after 1 month of treatment was 13.1% and this increased to 55.3% by the end of 3 months. Mean migraine attack frequency was 4.85 during the baseline period and this decreased to 2.81 attacks by the end of the study period, which was a statistically significant response ( P < 0.001). There were no side-effects noted with coenzyme Q10. From this open label investigation coenzyme Q10 appears to be a good migraine preventive. Placebo-controlled trials are now necessary to determine the true efficacy of coenzyme Q10 in migraine prevention.

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Clinical experience of combination therapy of infliximab and total glucosides of paeony for severe psoriasis with liver disorder history

Trends in Immunotherapy ◽

10.24294/ti.v1.i2.42 ◽

2017 ◽

Vol 1 (2) ◽

Author(s):

Yu Hu ◽

Lin Lin ◽

Pangen Cui ◽

Xu Yao ◽

Chao Luan ◽

...

Keyword(s):

Combination Therapy ◽

Combined Therapy ◽

Liver Disorder ◽

Severe Psoriasis ◽

Hepatic Toxicity ◽

Pasi Score ◽

History Of ◽

The Mean ◽

Mean Time

Severe psoriasis patients are reported to have a higher risk of liver abnormalities. Treatment option for severe psoriasis patients with liver disorder history remains a great challenge. Hepatic toxicity and long-term safety are the major concerns. Hence it is necessary to look for safer and more effective treatment for those patients. This retrospective review evaluated safety and efficacy of combination therapy of infliximab and TGP in treating 13 severe psoriasis patients with liver disorder history.Thirteen patients with severe psoriasis, including 8 men and 5 women, with a mean age of 37.3 ± 12.3 were observed. The patients experienced a mean course of psoriasis of 11.2 ± 7.1 years. The mean PASI score was 29.3 ± 12.9. All patients have the history of liver disorder. In our study, these patients were treated with infliximab at a dose of 5mg/kg and TGP at a dose of 1.8g/day. No liver test abnormalities were seen during combination therapy. After treatment, 61.5% patients showed PASI 50 response at week 2, and 81.8% patients have PASI 75 response at week 6. The mean time for achieving PASI 75 and PASI 90 improvement was 4.2 week and 9.6 week, respectively. Conclusion: Our observation demonstrates that combined therapy of infliximab and TGP is effective and safe in the treatment of severe psoriasis, especially for the patients with liver disorder history.

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Clinical experience of combination therapy of infliximab and total glucosides of paeony for severe psoriasis with liver disorder history

Trends in Immunotherapy ◽

10.24294/ti.v3.i2.42 ◽

2019 ◽

Vol 3 (2) ◽

pp. 62

Author(s):

Yu Hu ◽

Lin Lin ◽

Pangen Cui ◽

Xu Yao ◽

Chao Luan ◽

...

Keyword(s):

Combination Therapy ◽

Combined Therapy ◽

Severity Index ◽

Liver Disorder ◽

Severe Psoriasis ◽

Total Glucosides Of Paeony ◽

Pasi Score ◽

History Of ◽

The Mean

Severe psoriasis patients are reported to have a higher risk of liver abnormalities. Treatment option for severe psoriasis patients with liver disorder history remains a great challenge. Hepatic toxicity and long-term safety are the major concerns. Hence it is necessary to look for safer and more effective treatment for those patients. This retrospective review evaluated the safety and efficacy of combination therapy of infliximab and total glucosides of paeony (TGP) in treating 13 severe psoriasis patients with liver disorder history. Patients with severe psoriasis, comprising eight men and five women with a mean age of 37.3 ± 12.3, were observed. The patients experienced a mean course of psoriasis of 11.2 ± 7.1 years. The mean psoriasis area and severity index (PASI) score was 29.3 ± 12.9. All patients have the history of liver disorder. In our study, these patients were treated with infliximab at a dose of 5 mg/kg and TGP at a dose of 1.8 g/day. No liver test abnormalities were seen during combination therapy. After treatment, 61.5% patients showed PASI 50 response at week 2, and 81.8% patients have PASI 75 response at week 6. The mean time for achieving PASI 75 and PASI 90 improvement was 4.2 weeks and 9.6 weeks, respectively. Our observation demonstrates that combined therapy of infliximab and TGP is effective and safe in the treatment of severe psoriasis, especially for patients with liver disorder history.

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Efficacy of Ivabradine versus β-Blockers for Heart Rate Reduction during Computed Tomography Coronary Angiography: A Meta-Analysis of Randomized Controlled Trials

Cardiology ◽

10.1159/000447236 ◽

2016 ◽

Vol 135 (3) ◽

pp. 133-140 ◽

Cited By ~ 3

Author(s):

Shuang Qiu ◽

Shaobo Shi ◽

Haiqin Ping ◽

Sanfeng Zhou ◽

Hui Wang ◽

...

Keyword(s):

Computed Tomography ◽

Heart Rate ◽

Meta Analysis ◽

Controlled Trials ◽

Heart Rate Reduction ◽

Rate Reduction ◽

Randomized Controlled ◽

Β Blocker ◽

The Mean ◽

Β Blockers

Objective: To quantify the efficacy of pretreatment with ivabradine compared to β-blockers before computed tomography coronary angiography (CTCA) via a meta-analysis of clinical randomized controlled trial data. Methods: We conducted a search for randomized controlled trials of pretreatment with ivabradine compared to β-blockers before CTCA in Medline, PubMed, Embase, SCI/SSCI/A&HCI, SAS Publishers, Web of Science, and the Cochrane Central Register. The Jadad quality score of the included studies, and the mean difference (MD) in heart rate reduction, were indicators of efficacy. RevMan 5.2 and Stata 12.0 software were used for the meta-analysis. Results: Eight studies involving a total of 1,324 patients were included in the final analysis. The results showed that ivabradine was significantly more effective at improving the heart rate of patients achieving the target heart rate (<65 bpm) during CTCA (OR 5.02; 95% CI 3.16-7.98, p < 0.00001, I2 = 20%). A comparison of efficacy between ivabradine and β-blockers showed a statistically significant effect of ivabradine on heart rate reduction during CTCA (MD -4.39; 95% CI −4.80 to −3.99, p < 0.00001, I2 = 0%). Ivabradine also led to a significant reduction in heart rate prior to CTCA (MD −5.33; 95% CI −10.26 to −0.39, p = 0.03, I2 = 92%). In terms of the total reduction in heart rate during CTCA, significant differences were noted between the ivabradine group and the β-blocker group (MD 2.64; 95% CI 1.25-4.02, p = 0.0002, I2 = 0%). The mean percentage reduction in heart rate in the ivabradine group was significantly higher than that in the β-blocker group (MD 7.18; 95% CI 5.64-8.72, p < 0.00001, I2 = 43%). Ivabradine had no significant effect on either systolic blood pressure (BP) (MD 11.41; 95% CI 6.43-16.40, p < 0.00001, I2 = 85%) or diastolic BP (MD 1.79; 95% CI -0.00 to 3.58, p = 0.05, I2 = 56%). Conclusion: Compared to β-blockers for heart rate reduction, ivabradine is a potentially attractive alternative for patients undergoing CTCA.

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