key: cord-0968623-amcxlyam
authors: Cristel, Robert T; Gandhi, Nimit D; Issa, Tariq Z; Kola, Eljona; Demesh, Daniel; Dayan, Steven H
title: A Randomized, Single-Blind, Crossover Study Evaluating the Impact of OnabotulinumtoxinA Treatment on Mood and Appearance During the COVID-19 Pandemic
date: 2021-04-19
journal: Aesthet Surg J
DOI: 10.1093/asj/sjab196
sha: a712e390fccc30fb466e0244eb52760bc5a2134f
doc_id: 968623
cord_uid: amcxlyam

BACKGROUND: The emergence of Coronavirus disease of 2019 (COVID-19), quickly became one of the most severe disease outbreaks in modern history. This caused many aesthetic practices around the country to close temporarily and led to a unique time period to evaluate the impact neurotoxin has in the setting of an ongoing pandemic. OBJECTIVES: To examine whether the administration of onabotulinumtoxinA (BOTOX Cosmetic, Allergan plc, Coolock, Ireland), in regular users, synergistically amplifies the elevation in mood/happiness, self-satisfaction with appearance and overall satisfaction, in the context of the ongoing pandemic. METHODS: A randomized single-blind cross-over study was designed to evaluate the impact of neurotoxin treatment in the upper third of the face on mood, self-satisfaction with appearance, and overall satisfaction. The placebo group crossed over to treatment after 1 month. Surveys evaluating patient happiness, self-satisfaction with appearance and overall efficacy were completed among both groups, and again to the placebo group again following crossover to treatment. RESULTS: Forty-five subjects were enrolled with 30 in the treatment and 15 in the control/cross-over group. The placebo group demonstrated no change in happiness or self-satisfaction in appearance until cross-over to the treatment group. Both groups, once receiving, onabotulinumtoxinA reported increased happiness, self-satisfaction with appearance and overall treatment satisfaction. CONCLUSIONS: OnabotulinumtoxinA treatment to the upper face in the midst of the COVID-19 pandemic was found to increase patient happiness, self-satisfaction with appearance, and overall treatment satisfaction.

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The emergence of Coronavirus disease of 2019 (COVID- 19) , quickly became one of the most severe disease outbreaks in modern history 1 . As the contagion spread out of control, hospitals in major disease hotspots began to experience shortages in staffing, personal protective equipment, and other hospital resources. On March 13, 2020 , the American College of Surgeons (ACS) became the first group to officially recommend to reduce and cancel elective procedures to mitigate the strain on the healthcare system 2 . Aesthetic procedure providers including plastic surgeons, facial plastic surgeons, and dermatologists all put their practices on hold in efforts to help conserve limited personal protective equipment (PPE) and limit unnecessary staff and patient exposures to the new contagion. In one survey of American Council of Academic Plastic Surgeons (ACAPS) providers, less than 10% of those offering aesthetic procedures prior to the pandemic were still offering those procedures in April 3 .

At the same time, the pandemic forced non-essential workers to transition to a virtual life, with many employers shifting to video calls centering primarily one's face onto a screen for all their colleagues. Similarly, mask-wearing showcases the upper region of one's face while hiding the bottom two-thirds. Facial rhytides in the upper facial region are often associated both with signs of aging as well as signs of stress, anxiety and anger 4 . Potentially due to these effects, Google trends analysis showed growing interest in aesthetic procedures, especially facial plastic surgery procedures, as stay-at-home orders were initially being lifted 5, 6 . Key trends in searches for neurotoxin treatments especially noted a decrease in decline over the first few months of the pandemic before rising to pre-pandemic levels immediately after stay-at-home orders were lifted.

The effects of the pandemic on non-naïve patient mood/happiness, self-satisfaction of appearance, and overall treatment satisfaction after neurotoxin treatment in the upper facial region has yet to be examined. Amidst the constraints of a global pandemic, many patients have exceeded their normal treatment interval and their glabellar wrinkles returned to baseline. This is a once in a lifetime period of time in which regular users of neurotoxin are not able to receive their regular injections. It would not be surprising that these patients are experiencing a decrease in their mood secondary to weeks of social isolating and distancing.

This unique time period allows the opportunity to evaluate the impact neurotoxin has on mood/happiness, self-satisfaction of appearance, and overall treatment satisfaction on non-naïve patients in the setting of the COVID-19 pandemic. We primarily aim to examine whether the administration of onabotulinumtoxinA (BOTOX Cosmetic, Allergan plc, Coolock, Ireland), in regular users, synergistically amplifies the elevation in mood/happiness beyond what would be achieved A c c e p t e d M a n u s c r i p t had they not had treatment, in the context of the ongoing pandemic. We postulate that regular neurotoxin users have a secondary gain beyond wrinkle reduction, but also as a mood elevator.

We secondarily aim to examine the change in patient satisfaction and patient-reported efficacy in subjects returning for onabotulinumtoxinA treatment. Moreover, we aim to examine these effects against a placebo treatment to ensure that the changes in patient satisfaction are due to the neurotoxin treatment itself rather than other variables associated with their visit, such as easing of local and national restrictions due to COVID-19. We hypothesize high patient satisfaction and efficacy.

A total of 45 subjects were included with 30 in the treatment arm and 15 in the control arm. The study date range was from 7/20/2020 to 09/03/2020. Eligible subjects were enrolled in a cohort that included men and women between the ages of 18-75 who were non-naïve neurotoxin users that were at least 20 weeks from their most recent neurotoxin treatment. Subjects were excluded if they had received neuromodulator injections in the glabellar region within 20 weeks prior to enrollment and did not have a 2-3 glabellar wrinkle severity score on the Allergan Facial Wrinkle Scale (FWS).

Exclusion criteria included diagnoses of severe depression or bipolar disorder, recent changes in anti-depressant or anti-anxiety medications, known allergy or sensitivity to study ingredients.

Females who were pregnant, attempting to get pregnant, or breastfeeding were also excluded from this study. To complete enrollment, all subjects were expected to understand the aspects of this study, provide their consent, and complete the required treatment and follow up visits. All study protocols were approved Advarra Institutional Review Board (Columbia, MD, USA).

Participation in the study occurred over the course of 3-4 visits and all procedures were performed by the senior author (S. H. D.). At the first visit, subjects were evaluated to meet inclusionary criteria and then randomized to either a treatment or control group. All subjects underwent standardized 2D photography and video at baseline. Subjects were photographed at rest and with maximal contraction (ie, while frowning) ( Figure 1 ). Video was taken of the subjects while frowning, smiling, puckering, and reading of a short rhyme.

All subjects in both groups completed two questionnaires at baseline: FACE-Q Appraisal of Lines Between Eyebrows 7 and Subject Happiness Scale (SHS) 8 . These were printed out and completed before any treatment or any contact with the study senior author (SHD) to prevent any potential bias. The study coordinator distributed the survey. The subjects were randomized with 30 in the treatment group and 15 in the control group. An online randomizer A c c e p t e d M a n u s c r i p t at https://www.random.org/lists/ was used for randomization. All 45 subjects were included in the randomization and the first 30 listed were then placed into the treatment group.

Subjects in the treatment group received 20-64 units of onabotulinumtoxinA (BOTOX Cosmetic, Allergan plc, Coolock, Ireland), in the upper third of the face including glabella lines (GL), forehead lines (FL), and lateral canthal lines (LCL). Subjects returned after 2 weeks and were assessed by the investigator to determine whether or not optimal cosmetic result (OCR) was achieved and that subjects experienced a reduction of at least one point on the FWS. If OCR was achieved, subjects completed the same FACE-Q scale and happiness questionnaire they performed at baseline. They also completed the FACE-Q Satisfaction with Outcome 7 and a questionnaire comparing their perceived results of the onabotulinumtoxinA treatment compared to their prior neurotoxin treatments.

If additional correction was determined to be needed, then touch up treatment of up to 20 units was administered to patients at the second visit. These subjects then returned 2 weeks later to complete the FACE-Q survey, subject happiness scale, and questionnaire comparing this neurotoxin treatment to previous treatments.

Subjects in the control group underwent a similar assessment. However, the control group was administered saline rather than onabotulinumtoxinA at their initial treatment. Table 2 .

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In the onabotulinumtoxinA treatment group, all eight FACE-Q subscales showed significant improvement after treatment (P<0.0001). The total score in the treatment group improved from 23.66 pre-treatment to 10.56 post-treatment (P<0.0001). Specific mean scores for each item are reported in Table 2 . There were no significant differences between the FACE-Q scores from the control group after crossing over to the treatment arm compared to the initial onabotulinumtoxinA treatment group.

Subjects completed a FACE-Q satisfaction questionnaire at their final visit. No significant differences between satisfaction scores were reported between treatment and control group following crossover to the treatment arm. The survey was not given to the control group following Overall, both groups reported significant changes in overall happiness/mood scores as judged on the SHS following onabotulinumtoxinA treatment. The control SHS pre-treatment score remained unchanged following saline treatment alone. Once the control group crossed over to the treatment arm with onabotulinumtoxinA, SHS scores improved significantly ( Table 3 ). The treatment arm also reported significant improvements for all questions on the SHS (Table 3) . A higher score in question 1-3 indicated greater happiness, while a lower score on question 4 indicated greater happiness. The control group SHS scores following onabotulinumtoxinA treatment compared to the treatment group scores showed no significant differences (Table 3) .

To the authors' knowledge, this is the first trial to examine the direct effects of onabotulinumtoxinA treatment in non-naïve users on mood/happiness, self-satisfaction of appearance, and overall treatment satisfaction on non-naïve patients in relation to a pandemic. This study was performed Previous studies have demonstrated the powerful effects neurotoxins have on improving quality of life, self-esteem, and even as a treatment for depression. 15, 16 Many studies trial neurotoxin treatments on naïve subjects. This current study demonstrated that regular, non-naïve, uses of neurotoxin will continue to have an increase in mood/happiness, self-satisfaction of appearance, and overall treatment satisfaction, despite an ongoing pandemic. It would not be surprising that many patients will have decreased moods during the pandemic due to the long-term social isolation and distancing. This study was able to distinguish from an elevation in mood/happiness between the neurotoxin treatment or by the simple fact that the aesthetic office had been reopened through the use of the placebo saline injection. The saline did not increase mood/happiness, self-satisfaction of appearance, or overall treatment satisfaction. Once given onabotulinumtoxinA, all of these increased significantly. This demonstrates that easing of COVID-19 restrictions alone did not improve patient happiness and self-satisfaction of appearance, or overall treatment satisfaction. Thus, these increases, came from the onabotulinumtoxinA treatment.

Our study results demonstrated the improvement in patient-reported FACE-Q eyebrow appraisal compared to placebo. The control group in this study reported no changes from baseline in their eyebrow appraisal scores following administration of the saline placebo. After cross-over and administration of the onabotulinumtoxinA treatment, the control group reported improvements similar to the primary treatment group across all criteria of eyebrow appraisal. Subjective evaluations such as in this study, have several limitations that deserve mentioning. The study was performed at a single site. The small sample with predominantly Caucasian female subjects is noted and further study is warranted, though the unique time period of clinic shutdowns has passed in most areas of the country.

OnabotulinumtoxinA treatment to the upper face in the midst of the COVID-19 pandemic was found to increase patient happiness, self-satisfaction with appearance, and overall treatment satisfaction.

As the COVID-19 pandemic continues, aesthetic providers can offer the benefit of neurotoxin treatment to elevate mood/happiness and provide a sense of normalcy to our patients during these stressful times.

M a n u s c r i p t M a n u s c r i p t A c c e p t e d M a n u s c r i p t M a n u s c r i p t M a n u s c r i p t Figure 1A A c c e p t e d M a n u s c r i p t Figure 1B 

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