Dose-Ranging Study of Botulinum Toxin Type A in the Treatment of Glabellar Rhytids in Females

OBJECTIVE: To compare the efficacy, safety, and duration of effect of four doses of botulinum toxin type A in the treatment of glabellar rhytids in females. DESIGN: Double-blind, randomized, parallel-group, dose-ranging trial followed by an open-label extension. SETTING: Private dermatologic clinic. SUBJECTS: Eighty female subjects with moderate to severe wrinkles at maximum frown entered the study. The first 40 subjects completing the double-blind phase entered the open-label extension. INTERVENTION: Random administration of 10, 20, 30, or 40 U botulinum toxin type A in divided doses. Open-label trial: 30 U botulinum toxin type A at the same sites in divided doses. MAIN OUTCOME MEASUREMENTS: Trained observer and subject assessments of wrinkle severity at maximum frown and repose using the Facial Wrinkle Scale (0 = none to 3 = severe), subject satisfaction, and adverse events. Follow-up monthly for up to 1 year postinjection. RESULTS: Relapse rates and responder rates revealed benefits lasting 3 to 6 months or longer. Objectively, 10 U of botulinum toxin type A was significantly less effective than 20, 30, or 40 U. The relapse rate at 4 months was significantly higher in the 10 U group (83%) versus 40, 30, or 20 U (28%, 30%, and 33%, respectively). Subject satisfaction was high in all groups. Duration of effect and response rates were sustained during the open-label extension. Adverse effects were mild and infrequent. CONCLUSION: Twenty to 40 U botulinum toxin type A doses were significantly more effective at reducing glabellar lines than 10 U. Most subjects experienced benefits for 3 to 4 months; some subjects demonstrated effect for up to 12 months.     

A Prospective, Double-Blind, Randomized, Parallel- Group, Dose-Ranging Study of Botulinum Toxin Type A in Female Subjects With Horizontal Forehead Rhytides

BACKGROUND: Botulinum toxin type A is used cosmetically to improve facial lines, but it has not been thoroughly investigated for the treatment of horizontal forehead rhytides. OBJECTIVE: To compare the efficacy and safety of three doses of botulinum toxin type A in females with horizontal forehead rhytides and to establish whether the response rate and the duration of response are dose dependent. METHODS: Fifty-nine female patients with horizontal forehead rhytides scoring 2 (moderate) or 3 (severe) on the facial wrinkle scale (FWS) were randomly assigned to receive 16, 32, or 48 U of botulinum toxin type A (BOTOX, BOTOX Cosmetic; Allergan, Irvine, CA), which was administered to eight injection sites. Half of the dose was administered to the brow depressors and the other half to the elevators. Wrinkle severity was assessed by the investigator and patient using the FWS at baseline, at Weeks 2 and 4, and then every 4 weeks for 48 weeks. RESULTS: Improvements in horizontal rhytides were observed in all dosage groups. Significant dose-response trends were observed for rate of improvement at maximum brow elevation (53% in the 48-U group vs. 15% in the 16-U group at 16 weeks) and rate of relapse to baseline (35% in the 48-U group vs. 75% in the 16-U group at 16 weeks) by a trained observer. CONCLUSION: Higher botulinum toxin type A doses resulted in greater efficacy and longer duration of effect in the reduction of horizontal rhytides.     

Dose-Finding, Safety, and Tolerability Study of Botulinum Toxin Type B for the Treatment of Hyperfunctional Glabellar Lines

BACKGROUND Previous open-label studies have demonstrated that botulinum toxin type B (BTX-B, Myobloc, Solstice Neurosciences) in doses of up to 3,000 U is safe and effective in the treatment of glabellar wrinkles.
OBJECTIVE This double-blind, randomized, placebo-controlled, sequential-dose-escalation study evaluated the safety and tolerability of seven BTX-B doses ranging from 250 to 3,000 U in the treatment of subjects with hyperfunctional glabellar lines.
METHODS Participants received a single intramuscular treatment of either BTX-B or placebo at five facial sites with a 12-week follow-up period. Primary efficacy outcome measure was the Investigator Global Scale score of subject's glabellar lines at rest and at full frown. Safety was evaluated primarily on the occurrence of adverse events (AEs).
RESULTS The investigator scores demonstrated a statistically significant increasing dose–response trend in the percentage of subjects with no lines or mild lines at rest from Weeks 1 to 12 ( p= .0420) and at full frown from Weeks 1 to 8 ( p< .0001). Fifty-one subjects (36.7%) experienced AEs; the most common AE was headache not otherwise specified, experienced by 19 subjects (13.7%).
CONCLUSIONS BTX-B at doses up to 3,000 U was safe and well tolerated in the treatment of hyperfunctional glabellar lines. Treatment with BTX-B reduced hyperfunctional glabellar lines in subjects, and the duration of action appeared to be related to the dose administered. Further studies using higher doses of BTX-B for treatment of glabellar wrinkles are planned.     

Prospective Open-Label Study of Botulinum Toxin Type B (Myobloc) at Doses of 2,400 and 3,000 U for the Treatment of Glabellar Wrinkles

BACKGROUND: A previous open-label study evaluated botulinum toxin type B (BTX-B; Myobloc) for the treatment of glabellar wrinkles and showed that it is safe and effective at a dose of 1,800 U. The duration of effect at this dose was approximately 8 weeks, and it was felt that higher doses would result in a longer duration of effect. OBJECTIVE: This is a prospective open-label study to assess the safety, efficacy, and duration of response following BTX-B injection at doses of 2,400 and 3,000 U for the treatment of glabellar frown lines. METHODS: A total of 39 patients were enrolled: 16 patients received 2,400 U. Eighteen patients received 3,000 U, and 5 patients received saline injections (control group). Doses were divided equally among six sites. RESULTS: All subjects had rapid improvement of interglabellar rhytides, with full response seen within 2 to 3 days. The duration of effect was 9.6 and 10.4 weeks with 2,400 and 3,000 U, respectively. Five subjects (two in the 2,400-U group and three in 3,000-U group) reported adverse events related to the BTX-B injection. Three subjects complained of mild pain at the injection site, and two subjects complained about lid droop/ptosis (one with the occurrence of headache). CONCLUSIONS: BTX-B injection is safe and effective for the treatment of glabellar wrinkles. It has a very rapid onset of action, and increasing the dose appears to prolong the duration of response. At 3,000 U, the duration of response was 10.4 weeks and was associated with minimal adverse effects. Adverse events were mild and were similar to those seen in previous studies with BTX-A. Additional studies evaluating BTX-B at higher doses are recommended to prolong the duration of response in the treatment of glabellar wrinkles.     

Patient-Reported Outcomes with Botulinum Toxin Type A Treatment of Glabellar Rhytids: A Double-Blind, Randomized, Placebo-Controlled Study

BACKGROUND Global patient-reported outcomes do not evaluate specific aspects of treatment that are important to patients.
OBJECTIVE The objective was to evaluate self-perception of age and specific outcomes that are important to patients receiving botulinum toxin type A or placebo for moderate to severe glabellar lines (using the Facial Line Outcomes Questionnaire to assess how much facial lines bother them, make them look older, detract from their facial appearance, prevent a smooth facial appearance, and make them look tired, stressed, or angry).
METHODS AND MATERIALS In the double-blind phase of this 12-week study, 70 patients were randomly assigned to treatment with 20 U botulinum toxin type A (BOTOX Cosmetic) or placebo. At Week 4, those still with moderate or severe glabellar lines were offered open-label 20 U botulinum toxin type A.
RESULTS Median glabellar line severity was significantly lower after botulinum toxin treatment than after placebo. Compared with placebo, botulinum toxin also resulted in significantly superior patient assessments and a greater proportion of patients considering they looked younger than their current age.
CONCLUSIONS Botulinum toxin type A can achieve specific goals of treatment that are important to patients and help them feel that they look younger than their current age.     

Botulinum Toxin Type B for Glabellar Wrinkles: A Prospective Open-Label Response Study

BACKGROUND: Botulinum toxin type B (BTX-B) is U.S. Food and Drug Administration (FDA)-approved for the treatment of cervical dystonia. There are no published studies investigating its efficacy for treatment of glabellar (frown) wrinkles; however, anecdotal reports of its efficacy are promising. OBJECTIVE: The current pilot study is an initial screening study to assess the safety and efficacy of a single, set dose of BTX-B in the treatment of glabellar (frown) lines and to document current clinical experience with BTX-B. METHODS: Thirty subjects (28 women, 2 men) were injected in six sites with 300 U per site for a total dose of 1800 U. RESULTS: At 2 and 4 weeks, patient and physician assessment scores showed an average score of 2 ("complete disappearance of wrinkles"). Three patients reported mild adverse events. CONCLUSION: Injections of BTX-B proved to be very efficacious, with rapid onset, with all patients responding within 3 days (mean 1.5 days). Adverse events were mild. The mean duration of effect with this low dose of BTX-B was 8 weeks. Since the duration may be dose related and minimal adverse events were observed at 1800 U, further studies are in progress to look at the duration of response resulting from higher doses of BTX-B in the treatment of glabellar wrinkles.     

透明质酸与肉毒毒素联合注射治疗重度眉间纹

目的探讨透明质酸与肉毒毒素联合注射治疗眉间纹的适应证、注射方法和临床效果。方法选择67例严重眉间纹患者,联合应用透明质酸（0．3～0．8m1）和肉毒毒素（9～14U）注射治疗,观察注射后的临床效果、疗效时间和不良反应等。结果透明质酸与肉毒毒素联合注射后,静态眉间纹即刻得到明显改善;注射后2、3d,动态皱眉纹开始逐渐减轻;约1个月时,效果明显改善。随访3～12个月,术后皱纹改善满意,最长可达18个月。结论对重度眉间纹（同时具有静态和动态皱眉纹）的患者,应用透明质酸行皱纹内填充,并结合肉毒毒素对眉间复合体肌肉进行注射,可达到更好的治疗效果。     

A 型肉毒素在注射整形美容中的临床应用效果

目的 探究A型肉毒素对注射整形美容的效果。方法 选取2022年3月-2023年1月我院收治的120例 注射整形美容的患者作为研究对象，以患者面部情况分为额纹组、鱼尾纹组、眉间纹组，每组40例。所 有研究对象均予以A型肉毒素注射治疗，比较三组临床疗效、不良反应发生情况、治疗满意度、心理情 绪。结果 额纹组治疗总有效率高于鱼尾纹组和眉间纹组，差异有统计学意义（ P ＜0.05）；额纹组不良 反应发生率低于鱼尾纹组和眉间纹组，但差异无统计学意义（ P ＞0.05）；额纹组治疗满意度高于鱼尾纹 组和眉间纹组，差异有统计学意义（ P ＜0.05）；额纹组心理情绪优于鱼尾纹组及眉间纹组，差异有统计学 意义（ P ＜0.05）。结论 A型肉毒素应用于各种面部问题中均能够取得较为满意的治疗结果，且在额纹改善 中的应用效果更高，能清除患者面部皱纹，提高整形满意度，值得临床使用。     

Dilution Volume of Botulinum Toxin Type A for the Treatment of Glabellar Rhytides: Does It Matter?

BACKGROUND Because well-controlled studies examining the efficacy and safety of various dilutions of botulinum toxin type A (BTX-A) have not been performed, dilutions used in clinical practice are chosen at the discretion of the clinician.
OBJECTIVES The objectives were to determine the most effective BTX-A dilution for the glabellar region, the relationship between dilution and duration of effect, and the side effect profile of each dilution in women with glabellar rhytides.
METHODS Eighty women with moderate-to-severe wrinkles at maximum frown were randomized to one of four dilution groups in a 48-week, single-center, double-blind, parallel-group study. Subjects received 30 U BTX-A (BOTOX, Allergan, Inc.) injected into the glabellar region at dilutions of 100, 33.3, 20, or 10 U/mL. Outcome measures included trained-observer and subject assessment of wrinkle severity at repose and at maximum muscle contraction using the Facial Wrinkle Scale (FWS) and adverse events.
RESULTS All dilutions of BTX-A effectively improved glabellar rhytides as assessed by both trained observers and subjects using the FWS. No significant differences on FWS scores were seen among the dilution groups by trained observers at any time point. Although a difference among groups was seen in subject-assessed responder rates, there was no obvious relationship between dilution and response. BTX-A treatment was well tolerated, and there were no significant differences between the four dilution groups in the number of subjects reporting adverse effects.
CONCLUSION In this study, the dilution of BTX-A was not critical to the success of treatment.     

A Phase III Study of IncobotulinumtoxinA in the Treatment of Glabellar Frown Lines

Objective: To investigate the efficacy and safety of incobotulinumtoxinA (also known as botulinum toxin type A [150 kDa], free from complexing proteins, or previously as NT 201), for the treatment of glabellar frown lines, in a prospective, open-label, multicenter, Phase III trial. Design: The study was a prospective, open-label, multicenter, international, Phase III clinical study. Subjects with moderate-to-severe glabellar frown lines at maximum frown, as assessed by the investigator according to the facial wrinkle scale, were given one intramuscular treatment of 20U incobotulinumtoxinA, administered as 0. 1mL to each of five injection sites, and assessed over 84 days. Missing values were imputed using the baseline value or next observation carried backwards. Adverse events were documented for the duration of the study. Settings: Two centers in Russia and one center in Germany. Participants: A total of 105 subjects (18-65 years) with moderate-to-severe glabellar frown lines at maximum frown were enrolled. Measurement: The primary endpoint was the percentage of responders at maximum frown (improvement of ≥1 on the facial wrinkle scale when compared with Day 0) on Day 28, as assessed by the investigator. Results: Response to treatment with incobotulinumtoxinA with respect to the facial wrinkle scale at maximum frown on Day 28 and Day 84 was 98.1 and 80.0 percent, respectively (missing values imputed). At rest, 94.3 percent (imputed values) of subjects were responders on Day 28 while 81.9 percent were responders on Day 84 (imputed values). Consistent with assessment by the investigators, subjects also rated treatment success highly. Incidence of treatment-related adverse events was low and no patients developed neutralizing antibodies. Conclusion: IncobotulinumtoxinA is effective in the treatment of glabellar frown lines and is well tolerated.     

A Double-Blind,Randomized, Placebo-Controlled,Two-Dose Comparative Study of Botulinum Toxin Type A for Treating Glabellar Lines in Japanese Subjects

BACKGROUND: Systematic, well-controlled clinical trials of botulinum toxin type A (BoNTA) in diverse patient populations are needed. The aim of this study was to characterize the safety and efficacy of 10-U and 20-U BoNTA doses versus placebo for treating glabellar lines in Japanese subjects. METHODS: A 16-week, multicenter, double-blind, randomized, placebo-controlled trial comparing 10 or 20 U of BoNTA versus placebo in 142 Japanese subjects with glabellar lines of at least moderate severity at maximal contraction. The primary efficacy endpoint was physician-rated line severity at maximal contraction 4 weeks after treatment. Secondary efficacy endpoints included physician/subject ratings and estimates of the effect's duration. RESULTS: Response rates by physician-rated line severity at maximal contraction (week 4) were 86.4% (10 U), 88.6% (20 U), and 0% (placebo, p < 0.001). Line severity at maximal contraction in each BoNTA group (p < 0.001) improved significantly from baseline at each visit. BoNTA and placebo differed significantly on all other efficacy measures. Mean duration of effect was 9.4 weeks in the 20-U group and 7.9 weeks in the 10-U BoNTA group. No serious adverse events occurred. CONCLUSION: Doses of BoNTA of 10 and 20 U are effective and safe for treating glabellar lines in Japanese subjects, and the 20-U dose provides greater efficacy and longer duration of effect.     

A Randomized, Double-Blind, Placebo-Controlled Study of Botulinum Toxin Type A for the Treatment of Glabellar Lines: Determination of Optimal Dose

BACKGROUND Botulinum toxin is used to treat glabellar lines, but the optimal dose of Reloxin (Dysport, Ipsen Biopharm Ltd.) for this indication remains to be established.
OBJECTIVE The objective was to evaluate three doses of Reloxin to determine its efficacy and safety in treating glabellar lines.
METHODS AND MATERIALS Participants were given 20, 50, or 75 U of Reloxin, or placebo, injected across the glabella. Follow-up was on Days 7, 30, 60, 90, and 120. Adverse events were also elicited by telephone on Day 3.
RESULTS From investigators' and participants' assessments at Day 30, there were significantly more responders in each Reloxin-treated group than placebo ( p≤ 0.001). The 50-U dose was as effective as the 75-U dose, with a similar duration. The most common adverse events were mild headache and nasopharyngitis, occurring similarly in all groups.
CONCLUSIONS Reloxin (Dysport/botulinum toxin type A) treatment resulted in a significant improvement in glabellar lines, and the 50-U dose was identified as optimal. All doses were well tolerated.     

Treatment of Depression with Botulinum Toxin A: A Case Series

BACKGROUND: Major depression is a common and serious disease that may be resistant to routine pharmacologic and psychotherapeutic treatment approaches. OBJECTIVE: To evaluate the efficacy of botulinum toxin A treatment of glabellar frown lines in treating patients with major depression, using a small open pilot trial. METHODS: Patients who met DSM-IV criteria for ongoing major depression in spite of pharmacologic or psychotherapeutic treatment were evaluated with the Beck Depression Inventory II (BDI-II) before receiving botulinum toxin A to their glabellar frown lines. Two months later, all patients were re-evaluated clinically and with the BDI-II. RESULTS: Ten depressed patients were treated with botulinum toxin A, and 9 of 10 patients were no longer depressed 2 months after treatment. The tenth patient had an improvement in mood. CONCLUSION: To our knowledge, these are the first reported cases of depression treated with botulinum toxin A.     

A Comparison of Two Botulinum Type A Toxin Preparations for the Treatment of Glabellar Lines: Double-Blind, Randomized, Pilot Study

BACKGROUND: Botulinum toxins have been proven effective for reducing facial lines. There are two commercial types of botulinum toxin type A available in many countries but no published comparison studies. OBJECTIVE: To compare the efficacy and tolerability of Botox Cosmetic and Dysport 50 U in the treatment of glabellar lines (using 20 U of Botox Cosmetic, which is the dose approved by the US Food and Drug Administration for the treatment of glabellar lines, and 50 U of Dysport, which has been reported to be the optimal dose for this formulation). STUDY DESIGN: Parallel-group double-blind pilot study. Evaluation by observing physician, photographic, and patient evaluations. CONCLUSION: Botox 20 U provided better and more prolonged efficacy than Dysport 50 U in the treatment of glabellar lines.     

A型肉毒毒素注射联合透明质酸填充术治疗眉间纹的临床效果

探讨对眉间纹患者应用A型肉毒毒素注射联合透明质酸填充术治疗的效果。方法 选取 2022年10月-2023年6月青县人民医院收治的120例眉间纹患者为研究对象,根据随机数字表法分为对照 组和观察组,每组60例。对照组采用A型肉毒毒素注射治疗,观察组采用A型肉毒毒素注射联合透明质 酸填充术治疗,比较两组临床疗效、皱纹情况及复发情况。结果 观察组治疗总有效率为96.67%,高 于对照组的73.33%,差异有统计学意义（P ＜0.05）;两组术后皱纹评分均低于术前,且观察组低于对 照组,差异有统计学意义（P ＜0.05）;观察组复发率为3.33%,低于对照组的16.67%,差异有统计学 意义（P ＜0.05）。结论 对眉间纹患者予以A型肉毒毒素注射联合透明质酸填充术治疗的效果良好,可 有效淡化皱纹,且治疗后复发率较低,值得临床应用。     

Botulinum Toxin A Treatment of Perioral Rhytides

BACKGROUND: Botulinum toxin A is well documented as a useful therapy for smoothing dynamic facial rhytides of the upper face. Most controlled studies have focused on the treatment of glabellar frown lines, horizontal forehead lines, and crow's feet. Reports of botulinum toxin A use in the lower face are few and anecdotal. OBJECTIVE: We present our experience using botulinum toxin A in the lip as a treatment of vertical perioral rhytides, which resulted in the added cosmetic benefits of lip eversion and enhanced lip fullness. METHODS: Eighteen patients were injected with botulinum toxin A into the vertical lip rhytides. The effect of treatment was evaluated at 2 to 3 weeks after procedure. RESULTS: Smoothening of hyperfunctional lines and upper lip fullness/eversion is observed in patients treated with perioral botulinum toxin A injections; 72% of patients continued treatment. CONCLUSIONS: In select patients, perioral botulinum toxin A results in amelioration of perioral rhytides and enhancement of lip fullness and lip eversion.     

局部注射少量A型肉毒毒素治疗上半面部皱纹的临床研究

目的：观察局部注射少量A型肉毒毒素（BTXA）去除上半面部皱纹的临床疗效。方法：应用A型肉毒毒素的198例患者,其中眉间纹65例,鱼尾纹80例,额纹20例,鼻背部皱纹33例。所有患者行局部多点注射A型肉毒毒素,浓度为4U/0.1ml,并根据不同的患者调整剂量和浓度。记录患者疗效、维持时间与不良反应。结果：A型肉毒毒素治疗面部上三分之一皱纹有效率为100%,显效率94.4%。肌肉麻痹的效果通常持续3～6个月不等,不良反应主要为4例上睑下垂,3例局部水肿和4例青紫,各占2.0%、1.5%和2.0%。上述症状于3～10内自行完全消失。结论：A型肉毒毒素局部注射治疗面部上三分之一皱纹起效迅速、无创伤、简便易行。     

Treatment of Nasal Wrinkles with Botulinum Toxin

BACKGROUND: Nasal wrinkles on the dorsum of the nose can frequently be treated with botulinum toxin type A by injecting a few units into the nasalis muscle. Between 2 and 5 U of botulinum toxin have commonly been used. However, clinicians have observed that some nasal wrinkles persist following nasalis treatment. OBJECTIVE: To detail remaining nasal and perinasal rhytids and further injection sites, which can lead to improvement. METHODS: Two hundred fifty patients with nasal rhytids were treated between 1997 and 2004. Three units of botulinum toxin type A were injected bilaterally into the nasalis muscle. Patients were seen at 1 month for follow-up, and the remaining rhytids were documented. RESULTS: Forty percent of patients had satisfactory treatment of nasal wrinkles with the initial bilateral 3 U injections. Sixty percent of subjects had remaining nasal rhytids following the nasalis muscle injections. Thirty percent o f subjects hadpersistent wrinkles at the root of the nose (nasal orbicular wrinkles), and 30% had wrinkles at the nasal root and between the eyes (nasociliary wrinkles). The injection of botulinum toxin into additional locations according to the anatomic differences of each person showed excellent resolution of the rhytids without complications. CONCLUSION: Understanding nasal wrinkle patterns allows for complete wrinkle treatment of the nose beyond simple bilateral treatment of the nasalis. New points of botulinum toxin application improve not only wrinkles at the root of the nose but also wrinkles in the nasoalar area.     

Botulinum toxin type A (BOTOX) for treatment of migraine headaches: An open-label study

OBJECTIVE: The object of this clinical experience was to evaluate the correlation between pericranial botulinum toxin type A (BOTOX, Allergan Corp, Irvine, CA) administration and alleviation of migraine headache symptoms. Study Design and Setting: A nonrandomized, open-label study was performed at 4 different test sites. The subjects consisted of 106 patients, predominantly female, who either (1) initially sought BOTOX treatment for hyperfunctional facial lines or other dystonias with concomitant headache disorders, or (2) were candidates for BOTOX treatment specifically for headaches. Headaches were classified as true migraine, possible migraine, or nonmigraine, based on baseline headache characteristics and International Headache Society criteria. BOTOX was injected into the glabellar, temporal, frontal, and/or suboccipital regions of the head and neck. Main outcome measures were determined by severity and duration of response. The degrees of response were classified as: (1) complete (symptom elimination), (2) partial > or =50% reduction in headache frequency or severity), and (3) no response [neither (1) nor (2)]. Duration of response was measured in months for the prophylactic group. RESULTS: Among 77 true migraine subjects treated prophylactically, 51% (95% confidence interval, 39% to 62%) reported complete response with a mean (SD) response duration of 4.1 (2.6) months; 38% reported partial response with a mean (SD) response duration of 2.7 (1.2) months. Overall improvement was independent of baseline headache characteristics. Seventy percent (95% confidence interval, 35% to 93%) of 10 true migraine patients treated acutely reported complete response with improvement 1 to 2 hours after treatment. No adverse effects were reported. CONCLUSIONS: BOTOX was found to be a safe and effective therapy for both acute and prophylactic treatment of migraine headaches. Further research is needed to explore and develop the complete potential for the neuroinhibitory effects of botulinum toxin.