Title: Effect of postinjection facial exercise on time of onset of botulinum toxin for glabella and forehead wrinkles: A randomized, controlled, crossover clinical trial
Abstract: To the Editor: Many clinicians recommend exercising treated muscles for 4 hours after botulinum toxin injection in order to enhance cellular uptake; however, no data exist in the literature to substantiate the physiology or the clinical efficacy of this method.1Hsu T.-S. Dover J.S. Kaminer M.S. Arndt K.A. Tan M.-H. Why make patients exercise facial muscles for 4 hours after botulinum toxin treatment.Arch Dermatol. 2003; 139: 948Google Scholar The purpose of this study was to determine whether facial muscle exercises after injection of botulinum toxin into forehead and glabella rhytids results in more rapid improvement in wrinkle appearance than injections without exercise. Eligible participants were women who were 18 to 65 years of age and were in good health with dynamic rhytids of the forehead and glabella who were recruited from an urban hospital-based dermatology practice. Participants were randomized to either perform a prescribed facial exercise regimen (3 sets, separated by 10 minutes, of 40 forehead raises followed by 40 scowls, or knitting of the brows) or to refrain from facial contractions for 4 hours after toxin injections. Two blinded dermatologist photoraters assessed forehead and glabella dynamic creases at baseline and on days 1, 2, 3, 4, 7, and 14 using the 5-point Carruthers’ forehead lines dynamic grading scale and 4-point Gladys rating scale for glabellar frown lines. Each participant also live-assessed their own dynamic creases using a 7-point subject self-evaluation improvement Scale (−3 to +3). At 7 months, participants were crossed over to the other arm. Of the 25 women who consented and enrolled, 22 participants with a mean age of 46.7 years (range 27-66 years) completed the study per protocol. Both dermatologists and participants rated dynamic glabellar and static forehead wrinkles to be significantly better by day 3 when injections were followed by facial contractions (dermatologists' ratings P = .002 and P = .02, respectively; participants' ratings P = .01 and P = .02, respectively; Tables I and II). Participants also reported noticeable glabellar improvement by days 2 and 3 when injections were followed by facial exercise compared with days 3 and 4 without exercise (P = .02). A significant advantage in the exercise group was detectable as early as day 3, at which point patients’ self-evaluation wrinkle scores increased by approximately twice as much in exercisers compared with nonexercisers. However, the overall degree of effect was the same in both exercise and nonexercise arms at 14 days, and the duration of action also did not appear to differ between the 2 arms.Table IBlinded dermatologists’ photoratings of glabella and forehead wrinkles at rest and action contraction over timeTime after botulinum toxin, daysTreatment armGlabellaForeheadStaticDynamicStaticDynamicMeanSDMeanSDMeanSDMeanSD0No muscle contraction0.7270.632.0910.681.3180.842.5001.01Active muscle contraction0.5910.592.0450.720.9550.582.3640.90P value.381.00.03.581No muscle contraction0.5710.511.7620.890.9050.701.9520.86Active muscle contraction0.5000.511.6360.790.8640.562.0450.90P value.50.631.00.622No muscle contraction0.4550.511.5000.670.9050.531.3640.66Active muscle contraction0.4550.511.1820.850.7270.631.5910.67P value1.00.12.22.263No muscle contraction0.5910.591.5450.670.9050.541.4760.60Active muscle contraction0.5240.600.8570.650.5710.511.3330.48P value.63.002.02.504No muscle contraction0.1670.381.0000.690.5000.511.2220.65Active muscle contraction0.3180.480.7270.700.5450.511.2730.70P value1.00.111.001.007No muscle contraction0.3330.580.8570.650.5240.511.1430.65Active muscle contraction0.4000.600.5500.690.3500.490.9500.51P value.63.11.73.4514No muscle contraction0.2270.430.4090.590.4090.590.9550.65Active muscle contraction0.2270.430.4550.510.2270.430.8640.64P value1.001.00.22.75SD, Standard deviation. Open table in a new tab Table IIPatient self-evaluation of glabella and forehead wrinkle improvement over timeTime after botulinum toxin, daysTreatment armGlabellaForeheadMeanSDMeanSD1No muscle contraction0.7730.870.5910.59Active muscle contraction0.6820.650.6360.58P value.83.982No muscle contraction0.8640.890.8640.71Active muscle contraction1.4090.731.1820.66P value.02.213No muscle contraction1.2730.881.4550.80Active muscle contraction1.8100.681.8570.57P value.01.024No muscle contraction1.5001.141.7730.81Active muscle contraction2.0000.622.1360.47P value.13.087No muscle contraction2.0910.972.1361.08Active muscle contraction2.2860.722.3810.50P value.67.5314No muscle contraction2.0451.132.4550.74Active muscle contraction2.4550.672.5910.50P value.16.5390No muscle contraction1.7270.911.8180.98Active muscle contraction1.4551.031.3181.14P value.61.87SD, Standard deviation. Open table in a new tab SD, Standard deviation. SD, Standard deviation. In general, the facial exercise regimen was well-tolerated by participants; 59% of participants reported that muscle contractions were very easy to perform. Sixty-eight percent believed that contractions sped the onset of action and increased toxin efficiency but did not impact duration of effectiveness. The results of this study suggest that a postinjection facial exercise regimen is a safe and effective method for achieving an earlier onset of clinical effect of botulinum toxin injections. Expediting the time to noticeable benefit, even by 1 day, may be clinically significant for some patients.2Yu K.C. Nettar K.D. Bapna S. Boscardin W.J. Maas C.S. Split-face double-blind study comparing the onset of action of onabotulinumtoxinA and abobotulinumtoxinA.Arch Facial Plast Surg. 2012; 14: 198-204Google Scholar, 3Rappl T. Parvizi D. Friedl H. et al.Onset and duration of effect of incobotulinumtoxinA, onabotulinumtoxinA, and abobotulinumtoxinA in the treatment of glabellar frown lines: a randomized, double-blind study.Clin Cosmet Investig Dermatol. 2013; 6: 211-219Crossref PubMed Scopus (41) Google Scholar To avoid needless inconvenience, exercise could be recommended only for those who desire more rapid results. To precisely delineate the time of exercise-mediated onset, a future study might measure contractions every 12 hours, especially considering that toxin binding to cholinergic receptor sites is complete by 64 minutes postinjection.1Hsu T.-S. Dover J.S. Kaminer M.S. Arndt K.A. Tan M.-H. Why make patients exercise facial muscles for 4 hours after botulinum toxin treatment.Arch Dermatol. 2003; 139: 948Google Scholar, 4Huang W. Foster J.A. Rogachefsky A.S. Pharmacology of botulinum toxin.J Am Acad Dermatol. 2000; 43: 249-259Abstract Full Text Full Text PDF PubMed Scopus (227) Google Scholar, 5Benedetto A.V. The cosmetic uses of botulinum toxin type A.Int J Dermatol. 1999; 38: 641-655Crossref PubMed Scopus (77) Google Scholar Future studies may include men, other neuromodulators, different injection sites, and different exercise regimens to determine minimal needs.