A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Repeated OnabotulinumtoxinA Treatments in Subjects With Crow's Feet Lines and Glabellar Lines.

BACKGROUND: This is the third study in a Phase 3 program evaluating onabotulinumtoxinA treatment of crow's feet lines (CFL). OBJECTIVE: To assess the efficacy and safety of repeated onabotulinumtoxinA treatments of CFL alone or with glabellar lines (GL) in subjects with moderate-to-severe CFL and GL (maximum smile). MATERIALS AND METHODS: This 5-month extension of a 7-month study randomized subjects who originally received onabotulinumtoxinA 24 U (CFL only; n = 227) or 44 U (24 U for CFL + 20 U for GL; n = 260) to retreatment with the same dose. Placebo-treated subjects were rerandomized to onabotulinumtoxinA 44 U (n = 101) or placebo (n = 96). Primary efficacy end point (Day 30) was the proportion of subjects who achieved a CFL severity rating of none or mild (maximum smile) on the investigator-assessed Facial Wrinkle Scale (FWS). Additional efficacy end points and adverse events were evaluated. RESULTS: Responder rates (primary end point) were significantly greater in onabotulinumtoxinA-treated groups (24 U: 56.5%; 44 U: 63.6%; placebo: 1.1%; p < .001). Improvements on most patient-reported outcomes (PROs) favored the 44-U group over the 24-U group. Adverse events did not differ among groups; most were mild or moderate. CONCLUSION: Repeated onabotulinumtoxinA treatments significantly reduce CFL severity based on FWS and PROs. Adverse event profiles remain consistent with approved GL labeling.

Efficacy and safety of onabotulinumtoxinA for treating crow's feet lines alone or in combination with glabellar lines: a multicenter, randomized, controlled trial.

BACKGROUND: This was the second study in a Phase 3 program treating crow's feet lines (CFL) with onabotulinumtoxinA. OBJECTIVE: To evaluate the efficacy and safety of onabotulinumtoxinA treatment of CFL alone or with glabellar lines (GL). METHODS: This multicenter, double-blind, placebo-controlled, repeat treatment, 7-month study randomized subjects with moderate-to-severe CFL and GL (maximum contraction) to onabotulinumtoxinA 44 U (CFL: 24 U, GL: 20 U; n = 305), onabotulinumtoxinA 24 U (CFL: 24 U, GL: placebo; n = 306), or placebo (n = 306). Coprimary end points were investigator-assessed and subject-assessed proportion of subjects achieving a CFL Facial Wrinkle Scale Grade of 0 or 1 (maximum smile; Day 30, Cycle 1). Additional efficacy end points and safety/adverse events (AEs) were evaluated. RESULTS: All primary and secondary end points were achieved; statistically significant differences favored onabotulinumtoxinA (p < .001, all comparisons vs placebo). Investigator and subject responder rates were: CFL, 54.9% and 45.8%; CFL + GL, 59.0% and 48.5%; and placebo, 3.3% (both), respectively. Responder rates on other end points also significantly favored onabotulinumtoxinA treatments. Most AEs were mild or moderate. Two subjects discontinued: 1 serious AE unrelated to treatment (myocardial infarction) and 1 treatment-related AE (injection site pain). CONCLUSION: OnabotulinumtoxinA was effective and well tolerated for treating moderate-to-severe CFL alone or in combination with GL.

A retrospective review and observational study of outcomes and safety of bimatoprost ophthalmic solution 0.03% for treating eyelash hypotrichosis.

BACKGROUND: The efficacy and safety of bimatoprost ophthalmic solution 0.03% for treating hypotrichosis were shown in a randomized controlled trial and in an open-label study. To date, no data on real-world experience have been published. OBJECTIVE: To evaluate long-term patient satisfaction, usage patterns, and safety of bimatoprost 0.03% in clinical practice. MATERIALS AND METHODS: In this retrospective chart review with a cross-sectional design, adult patients exposed to bimatoprost 0.03% for at least 12 months were randomly sampled from 16 investigational sites. Charts were reviewed for medication usage characteristics and adverse events (AEs). At a study visit, questionnaires eliciting patient-reported outcomes were administered and spontaneously reported AEs were tabulated. RESULTS: Analysis included 585 subjects with a mean (SD) treatment duration of 19.3 (4.3) months. Patient satisfaction with bimatoprost 0.03% was 92.5%; on average, approximately 3 applications per week maintained benefits. Overall, 27.4% of patients spontaneously recalled experiencing AEs while on treatment; however, patient charts showed that only 4 AEs were documented. No instances of iris hyperpigmentation occurred. No serious or severe AEs were noted. CONCLUSION: Treatment with bimatoprost 0.03% for at least 12 months is safe, and long-term use is associated with a high degree of satisfaction.

An interrater and intrarater reliability study of 3 photographic scales for the classification of perioral aesthetic features.

BACKGROUND: Validated aesthetic rating scales for the perioral area provide objective evaluations for clinical trials and practice. OBJECTIVE: To confirm the reliability of 3 scales for evaluating dermal filler and neurotoxin treatments of the perioral area. MATERIALS AND METHODS: Three lip-specific photographic scales were developed from standardized 2-dimensional images to evaluate Perioral Lines at Rest (POL), Oral Commissures (OCS), and Perioral Lines at Maximum Contraction (POLM) severity scales. Each 4-grade scale (none to severe) had 3 representative images per grade. Physician validators rated volunteers on each scale (2 rounds of live review). Volunteers provided 2 series of self-assessments. Physician and subject intrarater reliability were based on the comparison of round 1 and round 2 scores (mean weighted kappa coefficient). Other measures were physician interrater agreement (intraclass correlation) and subject/physician interrater agreement (Pearson correlation). RESULTS: Physician intrarater agreement was almost perfect or substantial (POL, 0.725; OCS, 0.789; POLM, 0.826). Overall, physician interrater agreement was almost perfect for all 3 scales and ranged from moderate to substantial by grade. Subject intrarater agreement and subject/physician interrater agreement were substantial. CONCLUSION: All scales demonstrated a high degree of intrarater and interrater reliability during the validation process. Physician concordance was good; subject ratings were reliable and comparable to physician assessments.

Efficacy and safety of onabotulinumtoxinA for the treatment of crows feet lines: a multicenter, randomized, controlled trial.

BACKGROUND: This study was part of a Phase 3 program treating crow's feet lines (CFL) with onabotulinumtoxinA. OBJECTIVE: To evaluate the efficacy and safety of onabotulinumtoxinA treatment of CFL. METHODS: This multicenter, double-blind, placebo-controlled, 5-month study randomized subjects with moderate-to-severe CFL (maximum smile) to onabotulinumtoxinA (24 U; n = 222) or placebo (n = 223). Investigators and subjects assessed CFL severity (maximum smile and rest) using the 4-grade Facial Wrinkle Scale (FWS). Co-primary end points were investigator- and subject-assessed proportion of subjects achieving a CFL FWS grade of 0 (none) or 1 (mild) at maximum smile (Day 30). Additional efficacy end points, patient-reported outcomes, and safety/adverse events (AEs) were evaluated. RESULTS: All primary and secondary end points were achieved; statistically significant differences favored onabotulinumtoxinA (p < .001, all comparisons vs placebo). Co-primary responder rates were 66.7% compared with 6.7% for investigator-assessed and 58.1% compared with 5.4% for subject-assessed response (onabotulinumtoxinA group and placebo, respectively; p < .001). A significantly greater proportion of the onabotulinumtoxinA group than placebo group achieved a 1 grade or greater improvement on the FWS (maximum smile and rest assessed by both the investigator and subject; all time points; p < .001). Most AEs were mild or moderate and did not result in discontinuations. CONCLUSION: Treatment of moderate-to-severe CFL with onabotulinumtoxinA was effective and well tolerated.

Multicenter, randomized, parallel-group study of onabotulinumtoxinA and hyaluronic acid dermal fillers (24-mg/ml smooth, cohesive gel) alone and in combination for lower facial rejuvenation: satisfaction and patient-reported outcomes.

BACKGROUND: Patient-reported outcomes (PROs) are important assessment benchmarks after aesthetic procedures. Systematic studies of PROs have not been conducted in the lower face. OBJECTIVE: To study satisfaction and other PROs after treatment of the lower face with onabotulinumtoxinA and a 24-mg/mL smooth, cohesive hyaluronic acid (HA) gel filler, alone or in combination. METHODS: Ninety female participants aged 35 to 55 were randomized to one of three groups: 24-mg/mL cohesive gel alone (n=30), onabotulinumtoxinA alone (n=30), or the combination (n=30). Effectiveness outcomes were investigator- and participant-rated satisfaction and the participant Self-Perception of Age (SPA) and participant-rated Look and Feel of the Lips and Mouth (LAF) questionnaires. Participants maintained a 14-day diary to record severity of treatment site responses. RESULTS: All treatments resulted in significant improvements from baseline at all end points and on all PRO measures. For all measures and most time points, the 24-mg/mL cohesive gel treatment groups experienced greater improvements than onabotulinumtoxinA alone. Participant-rated severity of treatment-related reactions was mainly mild and transient. CONCLUSION: OnabotulinumtoxinA and 24-mg/mL cohesive HA gel treatments, used alone or in combination for lower face rejuvenation, resulted in significant improvement in investigator- and participant-reported outcomes.

Multicenter, randomized, parallel-group study of the safety and effectiveness of onabotulinumtoxinA and hyaluronic acid dermal fillers (24-mg/ml smooth, cohesive gel) alone and in combination for lower facial rejuvenation.

BACKGROUND: Combination treatment with toxins and fillers is the standard regimen in facial rejuvenation. Systematic studies of botulinum toxin alone and in combination with hyaluronic acid (HA) have not, however, been conducted in the lower face. OBJECTIVE: To evaluate safety and effectiveness and compare combination treatment with onabotulinumtoxinA and a 24-mg/mL smooth, cohesive HA gel filler with either treatment alone for rejuvenation of the perioral area and lower face in female subjects. METHODS: Ninety female participants aged 35 to 55 were randomized to one of three groups: 24-mg/mL cohesive gel alone (n=30), onabotulinumtoxinA alone (n=30), or the combination (n=30). Effectiveness outcomes included perioral, lip fullness, and oral commissure assessments and scores on the Cosmetic Improvement and Global Aesthetic Improvement Scales. Adverse events were monitored throughout. RESULTS: For all end points and most time points, subjects treated with onabotulinumtoxinA plus the 24-mg/mL cohesive gel had greater improvement from baseline than subjects treated with onabotulinumtoxinA or the 24-mg/mL cohesive gel filler alone. CONCLUSION: Based on a range of end points, onabotulinumtoxinA and 24-mg/mL cohesive HA gel treatments are effective and safe when either alone or in combination to rejuvenate the lower face. Combination therapy is superior to either modality used alone.

Combination treatment with benzodiazepines and SSRIs for comorbid anxiety and depression: a review.

OBJECTIVE: To review the literature on the co-occurrence of anxiety with depressive disorders and the rationale for and use of combination treatment with benzodiazepines and selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors (SSRIs/SNRIs) for treating comorbid anxiety and depression. DATA SOURCES: PubMed and PsycINFO were searched using terms identified as relevant based on existing practice guidelines. The primary search terms were anxiety, anxiety disorders, depression, depressive disorders, comorbidity, epidemiology, benzodiazepines, antidepressants, pharmacology, clinical trials, and pharmacotherapy. Reference lists of identified articles were also reviewed to ensure capture of relevant literature. STUDY SELECTION: Publications were selected for inclusion in the review if they applied to adult populations and specifically addressed the comorbidity of anxiety and depression, their epidemiology, or their management. Case reports and case series were not considered for inclusion. DATA EXTRACTION: Each author assessed the publications independently for content related to the review topics. Findings considered relevant to the clinical understanding and management of comorbid anxiety and depression were incorporated into the review. DATA SYNTHESIS: Comorbidity is very common among patients with anxiety and depressive disorders, and, even when full criteria for 2 separate disorders are not met, subsyndromal symptoms are often present. Little controlled research has explored how benzodiazepines and SSRIs/SNRIs may be usefully combined, yet their combination is frequently employed in clinical practice. Patients with comorbidities are likely to have poorer treatment outcomes and have greater utilization of health care resources. Currently SSRIs/SNRIs are considered first-line therapy and are effective in both anxiety and depressive states. Nevertheless, many patients have only a partial response or have difficulty tolerating efficacious doses of antidepressant monotherapy. Benzodiazepines appear to improve treatment outcomes when an anxiety disorder co-occurs with depression or for depression characterized by anxious features. Specifically, they may provide benefits both in terms of speed of response and overall response. CONCLUSIONS: Long-term management plans for anxiety disorder with or without comorbid depression should include strategies for acute or short-term care, long-term maintenance, and episodic or breakthrough symptoms. Combination therapy with benzodiazepines and antide-pressants in appropriate clinical settings may improve outcomes over monotherapy in some patients.