{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T04:56:20Z","timestamp":1777352180872,"version":"3.51.4"},"reference-count":68,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,7,30]],"date-time":"2020-07-30T00:00:00Z","timestamp":1596067200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,7,30]],"date-time":"2020-07-30T00:00:00Z","timestamp":1596067200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The World Health Organization estimates the number of people suffering from depression to be over 264 million. Current monoamine transmission modulating therapeutics, even with proper adherence and acceptable tolerability, are not effective for nearly one third of the patients, leading clinicians to explore other therapeutic options such as electroconvulsive therapy, transcranial magnetic stimulation, ketamine infusions, and, more recently, glabellar botulinum toxin, BoNT, injections. The scale and mechanism of antidepressant action of BoNT is unclear and maybe hypothetically attributed to the disruption of proprioceptive facial feedback reinforcing negative emotions. Here we verify the antidepressant effect of botulinum toxin by analysis of over 40 thousand BoNT treatment reports out of thirteen million postmarketing safety reports in the FDA Adverse Event Reporting System, FAERS. The results of the analysis indicate that patients who received BoNT injections to treat hyperhidrosis, facial wrinkles, migraine prophylaxis, spasticity, and spasms, had a significantly lower number of depression reports when compared to patients undergoing different treatments for the same conditions. These findings suggest that the antidepressant effect of BoNT is significant, and, surprisingly, is observed for a broad range of injection sites.<\/jats:p>","DOI":"10.1038\/s41598-020-69773-7","type":"journal-article","created":{"date-parts":[[2020,7,30]],"date-time":"2020-07-30T10:24:33Z","timestamp":1596104673000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Postmarketing safety surveillance data reveals antidepressant effects of botulinum toxin across various indications and injection sites"],"prefix":"10.1038","volume":"10","author":[{"given":"Tigran","family":"Makunts","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc Axel","family":"Wollmer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruben","family":"Abagyan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,7,30]]},"reference":[{"key":"69773_CR1","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1002\/mpr.138","volume":"12","author":"L Andrade","year":"2003","unstructured":"Andrade, L. et al. The epidemiology of major depressive episodes: results from the International Consortium of Psychiatric Epidemiology (ICPE) Surveys. Int. J. Methods Psychiatr. Res. 12, 3\u201321 (2003).","journal-title":"Int. J. Methods Psychiatr. Res."},{"key":"69773_CR2","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1186\/1741-7015-9-90","volume":"9","author":"E Bromet","year":"2011","unstructured":"Bromet, E. et al. Cross-national epidemiology of DSM-IV major depressive episode. BMC Med 9, 90. https:\/\/doi.org\/10.1186\/1741-7015-9-90 (2011).","journal-title":"BMC Med"},{"key":"69773_CR3","doi-asserted-by":"publisher","unstructured":"Collaborators, G. D. a. I. I. a. P. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990\u20132017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 392, 1789\u20131858. https:\/\/doi.org\/10.1016\/S0140-6736(18)32279-7 (2018).","DOI":"10.1016\/S0140-6736(18)32279-7"},{"key":"69773_CR4","doi-asserted-by":"publisher","first-page":"22","DOI":"10.4088\/PCC.v03n0105","volume":"3","author":"JM Ferguson","year":"2001","unstructured":"Ferguson, J. M. SSRI antidepressant medications: adverse effects and tolerability. Prim. Care Companion J. Clin. Psychiatry 3, 22\u201327 (2001).","journal-title":"Prim. Care Companion J. Clin. Psychiatry"},{"key":"69773_CR5","first-page":"41","volume":"9","author":"RA Sansone","year":"2012","unstructured":"Sansone, R. A. & Sansone, L. A. Antidepressant adherence: are patients taking their medications?. Innov. Clin. Neurosci. 9, 41\u201346 (2012).","journal-title":"Innov. Clin. Neurosci."},{"key":"69773_CR6","doi-asserted-by":"publisher","first-page":"148","DOI":"10.4088\/jcp.v66n0201","volume":"66","author":"MA Posternak","year":"2005","unstructured":"Posternak, M. A. & Zimmerman, M. Is there a delay in the antidepressant effect? A meta-analysis. J. Clin. Psychiatry 66, 148\u2013158. https:\/\/doi.org\/10.4088\/jcp.v66n0201 (2005).","journal-title":"J. Clin. Psychiatry"},{"key":"69773_CR7","doi-asserted-by":"publisher","first-page":"1905","DOI":"10.1176\/ajp.2006.163.11.1905","volume":"163","author":"AJ Rush","year":"2006","unstructured":"Rush, A. J. et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am. J. Psychiatry 163, 1905\u20131917. https:\/\/doi.org\/10.1176\/ajp.2006.163.11.1905 (2006).","journal-title":"Am. J. Psychiatry"},{"key":"69773_CR8","doi-asserted-by":"publisher","first-page":"1374","DOI":"10.4088\/JCP.14r09528","volume":"76","author":"AU Haq","year":"2015","unstructured":"Haq, A. U., Sitzmann, A. F., Goldman, M. L., Maixner, D. F. & Mickey, B. J. Response of depression to electroconvulsive therapy: a meta-analysis of clinical predictors. J Clin Psychiatry 76, 1374\u20131384. https:\/\/doi.org\/10.4088\/JCP.14r09528 (2015).","journal-title":"J Clin Psychiatry"},{"key":"69773_CR9","doi-asserted-by":"publisher","first-page":"1549","DOI":"10.2147\/NDT.S67477","volume":"11","author":"PG Janicak","year":"2015","unstructured":"Janicak, P. G. & Dokucu, M. E. Transcranial magnetic stimulation for the treatment of major depression. Neuropsychiatr Dis Treat 11, 1549\u20131560. https:\/\/doi.org\/10.2147\/NDT.S67477 (2015).","journal-title":"Neuropsychiatr Dis Treat"},{"key":"69773_CR10","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1001\/jamapsychiatry.2017.3739","volume":"75","author":"EJ Daly","year":"2018","unstructured":"Daly, E. J. et al. Efficacy and safety of intranasal esketamine adjunctive to oral antidepressant therapy in treatment-resistant depression: a randomized clinical trial. JAMA Psychiatry 75, 139\u2013148. https:\/\/doi.org\/10.1001\/jamapsychiatry.2017.3739 (2018).","journal-title":"JAMA Psychiatry"},{"key":"69773_CR11","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1016\/j.jpsychires.2012.01.027","volume":"46","author":"MA Wollmer","year":"2012","unstructured":"Wollmer, M. A. et al. Facing depression with botulinum toxin: a randomized controlled trial. J. Psychiatr. Res 46, 574\u2013581. https:\/\/doi.org\/10.1016\/j.jpsychires.2012.01.027 (2012).","journal-title":"J. Psychiatr. Res"},{"key":"69773_CR12","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1097\/YIC.0000000000000290","volume":"35","author":"MF Brin","year":"2020","unstructured":"Brin, M. F. et al. OnabotulinumtoxinA for the treatment of major depressive disorder: a phase 2 randomized, double-blind, placebo-controlled trial in adult females. Int. Clin. Psychopharmacol. 35, 19\u201328. https:\/\/doi.org\/10.1097\/YIC.0000000000000290 (2020).","journal-title":"Int. Clin. Psychopharmacol."},{"issue":"2","key":"69773_CR13","doi-asserted-by":"publisher","first-page":"224","DOI":"10.3163\/1536-5050.95.2.224","volume":"95","author":"V Craigle","year":"2007","unstructured":"Craigle, V. MedWatch: the FDA safety information and adverse event reporting program. J. Med. Libr. Assoc. 95(2), 224\u2013225. https:\/\/doi.org\/10.3163\/1536-5050.95.2.224 (2007).","journal-title":"J. Med. Libr. Assoc."},{"key":"69773_CR14","doi-asserted-by":"publisher","first-page":"e0195521","DOI":"10.1371\/journal.pone.0195521","volume":"13","author":"T Makunts","year":"2018","unstructured":"Makunts, T., Cohen, I. V., Lee, K. C. & Abagyan, R. Population scale retrospective analysis reveals distinctive antidepressant and anxiolytic effects of diclofenac, ketoprofen and naproxen in patients with pain. PLoS ONE 13, e0195521. https:\/\/doi.org\/10.1371\/journal.pone.0195521 (2018).","journal-title":"PLoS ONE"},{"key":"69773_CR15","doi-asserted-by":"publisher","first-page":"1450","DOI":"10.1038\/s41598-017-01590-x","volume":"7","author":"IV Cohen","year":"2017","unstructured":"Cohen, I. V., Makunts, T., Atayee, R. & Abagyan, R. Population scale data reveals the antidepressant effects of ketamine and other therapeutics approved for non-psychiatric indications. Sci. Rep. 7, 1450. https:\/\/doi.org\/10.1038\/s41598-017-01590-x (2017).","journal-title":"Sci. Rep."},{"key":"69773_CR16","unstructured":"Allergan Pharmaceutical Company. OnabotulinumtoxinA [package insert].\u00a0U.S. Food\u00a0and Drug Administration. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2011\/103000s5232lbl.pdf. Revised (2019). Accessed (2020)."},{"key":"69773_CR17","doi-asserted-by":"publisher","first-page":"CD006499","DOI":"10.1002\/14651858.CD006499.pub2","volume":"1","author":"FJ Rowe","year":"2009","unstructured":"Rowe, F. J. & Noonan, C. P. Botulinum toxin for the treatment of strabismus. Cochrane Database Syst. Rev. 1, CD006499. https:\/\/doi.org\/10.1002\/14651858.CD006499.pub2 (2009).","journal-title":"Cochrane Database Syst. Rev."},{"key":"69773_CR18","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1007\/s00702-005-0323-3","volume":"113","author":"P Roggenk\u00e4mper","year":"2006","unstructured":"Roggenk\u00e4mper, P. et al. Efficacy and safety of a new Botulinum Toxin Type A free of complexing proteins in the treatment of blepharospasm. J. Neural Transm. (Vienna) 113, 303\u2013312. https:\/\/doi.org\/10.1007\/s00702-005-0323-3 (2006).","journal-title":"J. Neural Transm. (Vienna)"},{"key":"69773_CR19","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1067\/mjd.2002.121356","volume":"46","author":"JA Carruthers","year":"2002","unstructured":"Carruthers, J. A. et al. A multicenter, double-blind, randomized, placebo-controlled study of the efficacy and safety of botulinum toxin type A in the treatment of glabellar lines. J Am Acad Dermatol 46, 840\u2013849. https:\/\/doi.org\/10.1067\/mjd.2002.121356 (2002).","journal-title":"J Am Acad Dermatol"},{"key":"69773_CR20","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1056\/NEJM200102153440704","volume":"344","author":"Heckmann, M., Ceballos-Baumann, A. O., Plewig, G. & Group, H. S","year":"2001","unstructured":"Heckmann, M., Ceballos-Baumann, A. O., Plewig, G. & Group, H. S. Botulinum toxin A for axillary hyperhidrosis (excessive sweating). N. Engl. J. Med. 344, 488\u2013493. https:\/\/doi.org\/10.1056\/NEJM200102153440704 (2001).","journal-title":"N. Engl. J. Med."},{"key":"69773_CR21","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1111\/j.1526-4610.2010.01678.x","volume":"50","author":"DW Dodick","year":"2010","unstructured":"Dodick, D. W. et al. OnabotulinumtoxinA for treatment of chronic migraine: pooled results from the double-blind, randomized, placebo-controlled phases of the PREEMPT clinical program. Headache 50, 921\u2013936. https:\/\/doi.org\/10.1111\/j.1526-4610.2010.01678.x (2010).","journal-title":"Headache"},{"key":"69773_CR22","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1097\/01.ju.0000162035.73977.1c","volume":"174","author":"B Schurch","year":"2005","unstructured":"Schurch, B. et al. Botulinum toxin type a is a safe and effective treatment for neurogenic urinary incontinence: results of a single treatment, randomized, placebo controlled 6-month study. J. Urol. 174, 196\u2013200. https:\/\/doi.org\/10.1097\/01.ju.0000162035.73977.1c (2005).","journal-title":"J. Urol."},{"key":"69773_CR23","doi-asserted-by":"publisher","first-page":"2186","DOI":"10.1016\/j.juro.2012.12.022","volume":"189","author":"VW Nitti","year":"2013","unstructured":"Nitti, V. W. et al. OnabotulinumtoxinA for the treatment of patients with overactive bladder and urinary incontinence: results of a phase 3, randomized, placebo controlled trial. J. Urol. 189, 2186\u20132193. https:\/\/doi.org\/10.1016\/j.juro.2012.12.022 (2013).","journal-title":"J. Urol."},{"key":"69773_CR24","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1097\/PHM.0000000000000208","volume":"94","author":"K Dashtipour","year":"2015","unstructured":"Dashtipour, K., Chen, J. J., Walker, H. W. & Lee, M. Y. Systematic literature review of abobotulinumtoxinA in clinical trials for adult upper limb spasticity. Am. J. Phys. Med. Rehabil. 94, 229\u2013238. https:\/\/doi.org\/10.1097\/PHM.0000000000000208 (2015).","journal-title":"Am. J. Phys. Med. Rehabil."},{"key":"69773_CR25","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1097\/01.sla.0000114217.52941.c5","volume":"239","author":"G Zaninotto","year":"2004","unstructured":"Zaninotto, G. et al. Randomized controlled trial of botulinum toxin versus laparoscopic heller myotomy for esophageal achalasia. Ann. Surg. 239, 364\u2013370. https:\/\/doi.org\/10.1097\/01.sla.0000114217.52941.c5 (2004).","journal-title":"Ann. Surg."},{"key":"69773_CR26","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1542\/peds.2003-1104-L","volume":"114","author":"PH Jongerius","year":"2004","unstructured":"Jongerius, P. H. et al. Effect of botulinum toxin in the treatment of drooling: a controlled clinical trial. Pediatrics 114, 620\u2013627. https:\/\/doi.org\/10.1542\/peds.2003-1104-L (2004).","journal-title":"Pediatrics"},{"key":"69773_CR27","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1159\/000083259","volume":"53","author":"D Dressler","year":"2005","unstructured":"Dressler, D. & Adib Saberi, F. Botulinum toxin: mechanisms of action. Eur. Neurol. 53, 3\u20139. https:\/\/doi.org\/10.1159\/000083259 (2005).","journal-title":"Eur. Neurol."},{"key":"69773_CR28","doi-asserted-by":"publisher","first-page":"837","DOI":"10.4088\/JCP.13m08845","volume":"75","author":"M Magid","year":"2014","unstructured":"Magid, M. et al. Treatment of major depressive disorder using botulinum toxin A: a 24-week randomized, double-blind, placebo-controlled study. J. Clin. Psychiatry 75, 837\u2013844. https:\/\/doi.org\/10.4088\/JCP.13m08845 (2014).","journal-title":"J. Clin. Psychiatry"},{"key":"69773_CR29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jpsychires.2013.11.006","volume":"52","author":"E Finzi","year":"2014","unstructured":"Finzi, E. & Rosenthal, N. E. Treatment of depression with onabotulinumtoxinA: a randomized, double-blind, placebo controlled trial. J. Psychiatr. Res. 52, 1\u20136. https:\/\/doi.org\/10.1016\/j.jpsychires.2013.11.006 (2014).","journal-title":"J. Psychiatr. Res."},{"key":"69773_CR30","first-page":"982","volume":"46","author":"A Zamanian","year":"2017","unstructured":"Zamanian, A., Ghanbari Jolfaei, A., Mehran, G. & Azizian, Z. Efficacy of botox versus placebo for treatment of patients with major depression. Iran J. Public Health 46, 982\u2013984 (2017).","journal-title":"Iran J. Public Health"},{"key":"69773_CR31","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1111\/j.1524-4725.2006.32136.x","volume":"32","author":"E Finzi","year":"2006","unstructured":"Finzi, E. & Wasserman, E. Treatment of depression with botulinum toxin A: a case series. Dermatol. Surg. 32, 645\u2013649. https:\/\/doi.org\/10.1111\/j.1524-4725.2006.32136.x (2006).","journal-title":"Dermatol. Surg."},{"key":"69773_CR32","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1067\/mhn.2000.110960","volume":"123","author":"WJ Binder","year":"2000","unstructured":"Binder, W. J., Brin, M. F., Blitzer, A., Schoenrock, L. D. & Pogoda, J. M. Botulinum toxin type A (BOTOX) for treatment of migraine headaches: an open-label study. Otolaryngol. Head Neck Surg. 123, 669\u2013676. https:\/\/doi.org\/10.1067\/mhn.2000.110960 (2000).","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"69773_CR33","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1016\/j.jaad.2007.10.649","volume":"58","author":"M Alam","year":"2008","unstructured":"Alam, M., Barrett, K. C., Hodapp, R. M. & Arndt, K. A. Botulinum toxin and the facial feedback hypothesis: can looking better make you feel happier?. J. Am. Acad. Dermatol 58, 1061\u20131072. https:\/\/doi.org\/10.1016\/j.jaad.2007.10.649 (2008).","journal-title":"J. Am. Acad. Dermatol"},{"key":"69773_CR34","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1016\/j.jrp.2009.06.005","volume":"43","author":"JI Davis","year":"2009","unstructured":"Davis, J. I., Senghas, A. & Ochsner, K. N. How does facial feedback modulate emotional experience?. J. Res. Pers. 43, 822\u2013829. https:\/\/doi.org\/10.1016\/j.jrp.2009.06.005 (2009).","journal-title":"J. Res. Pers."},{"key":"69773_CR35","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1093\/cercor\/bhn104","volume":"19","author":"A Hennenlotter","year":"2009","unstructured":"Hennenlotter, A. et al. The link between facial feedback and neural activity within central circuitries of emotion: new insights from botulinum toxin-induced denervation of frown muscles. Cereb. Cortex 19, 537\u2013542. https:\/\/doi.org\/10.1093\/cercor\/bhn104 (2009).","journal-title":"Cereb. Cortex"},{"key":"69773_CR36","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.jaad.2015.08.051","volume":"74","author":"JS Reichenberg","year":"2016","unstructured":"Reichenberg, J. S. et al. Botulinum toxin for depression: does patient appearance matter?. J. Am. Acad. Dermatol. 74, 171-173.e171. https:\/\/doi.org\/10.1016\/j.jaad.2015.08.051 (2016).","journal-title":"J. Am. Acad. Dermatol."},{"key":"69773_CR37","doi-asserted-by":"publisher","first-page":"109","DOI":"10.2165\/00002018-199920020-00002","volume":"20","author":"EG Brown","year":"1999","unstructured":"Brown, E. G., Wood, L. & Wood, S. The medical dictionary for regulatory activities (MedDRA). Drug Saf. 20, 109\u2013117. https:\/\/doi.org\/10.2165\/00002018-199920020-00002 (1999).","journal-title":"Drug Saf."},{"key":"69773_CR38","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1002\/phar.1196","volume":"33","author":"JJ Chen","year":"2013","unstructured":"Chen, J. J. & Dashtipour, K. Abo-, inco-, ona-, and rima-botulinum toxins in clinical therapy: a primer. Pharmacotherapy 33, 304\u2013318. https:\/\/doi.org\/10.1002\/phar.1196 (2013).","journal-title":"Pharmacotherapy"},{"key":"69773_CR39","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1111\/j.1365-2125.2011.04037.x","volume":"72","author":"JL Montastruc","year":"2011","unstructured":"Montastruc, J. L., Sommet, A., Bagheri, H. & Lapeyre-Mestre, M. Benefits and strengths of the disproportionality analysis for identification of adverse drug reactions in a pharmacovigilance database. Br. J. Clin. Pharmacol. 72, 905\u2013908. https:\/\/doi.org\/10.1111\/j.1365-2125.2011.04037.x (2011).","journal-title":"Br. J. Clin. Pharmacol."},{"key":"69773_CR40","doi-asserted-by":"publisher","first-page":"12490","DOI":"10.1038\/s41598-019-48955-y","volume":"9","author":"TUA Makunts","year":"2019","unstructured":"Makunts, T. U. A., Atayee, R. S. & Abagyan, R. Retrospective analysis reveals significant association of hypoglycemia with tramadol and methadone in contrast to other opioids. Sci. Rep. 9, 12490. https:\/\/doi.org\/10.1038\/s41598-019-48955-y (2019).","journal-title":"Sci. Rep."},{"key":"69773_CR41","doi-asserted-by":"publisher","first-page":"17280","DOI":"10.1038\/s41598-019-53622-3","volume":"9","author":"T Makunts","year":"2019","unstructured":"Makunts, T., Alpatty, S., Lee, K. C., Atayee, R. S. & Abagyan, R. Proton-pump inhibitor use is associated with a broad spectrum of neurological adverse events including impaired hearing, vision, and memory. Sci. Rep. 9, 17280. https:\/\/doi.org\/10.1038\/s41598-019-53622-3 (2019).","journal-title":"Sci. Rep."},{"key":"69773_CR42","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1111\/j.0006-341x.1999.00597.x","volume":"55","author":"A Agresti","year":"1999","unstructured":"Agresti, A. On logit confidence intervals for the odds ratio with small samples. Biometrics 55, 597\u2013602. https:\/\/doi.org\/10.1111\/j.0006-341x.1999.00597.x (1999).","journal-title":"Biometrics"},{"key":"69773_CR43","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.jpsychires.2016.06.009","volume":"80","author":"E Finzi","year":"2016","unstructured":"Finzi, E. & Rosenthal, N. E. Emotional proprioception: treatment of depression with afferent facial feedback. J. Psychiatr. Res. 80, 93\u201396. https:\/\/doi.org\/10.1016\/j.jpsychires.2016.06.009 (2016).","journal-title":"J. Psychiatr. Res."},{"key":"69773_CR44","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1016\/j.toxicon.2008.12.026","volume":"54","author":"M Caleo","year":"2009","unstructured":"Caleo, M. & Schiavo, G. Central effects of tetanus and botulinum neurotoxins. Toxicon 54, 593\u2013599. https:\/\/doi.org\/10.1016\/j.toxicon.2008.12.026 (2009).","journal-title":"Toxicon"},{"key":"69773_CR45","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1016\/j.neuint.2012.05.001","volume":"61","author":"I Matak","year":"2012","unstructured":"Matak, I., Riederer, P. & Lackovi\u0107, Z. Botulinum toxin\u2019s axonal transport from periphery to the spinal cord. Neurochem. Int. 61, 236\u2013239. https:\/\/doi.org\/10.1016\/j.neuint.2012.05.001 (2012).","journal-title":"Neurochem. Int."},{"key":"69773_CR46","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1113\/jphysiol.2012.239178","volume":"591","author":"V Marchand-Pauvert","year":"2013","unstructured":"Marchand-Pauvert, V. et al. Beyond muscular effects: depression of spinal recurrent inhibition after botulinum neurotoxin A. J. Physiol. 591, 1017\u20131029. https:\/\/doi.org\/10.1113\/jphysiol.2012.239178 (2013).","journal-title":"J. Physiol."},{"key":"69773_CR47","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/toxins11010021","volume":"11","author":"D Weise","year":"2019","unstructured":"Weise, D., Weise, C. M. & Naumann, M. Central effects of botulinum neurotoxin-evidence from human studies. Toxins 11, 1. https:\/\/doi.org\/10.3390\/toxins11010021 (2019).","journal-title":"Toxins"},{"key":"69773_CR48","doi-asserted-by":"publisher","first-page":"1919","DOI":"10.2169\/internalmedicine.55.5843","volume":"55","author":"A Kikuchi","year":"2016","unstructured":"Kikuchi, A. et al. Brain metabolic changes of cervical dystonia with spinocerebellar ataxia type 1 after botulinum toxin therapy. Intern. Med 55, 1919\u20131922. https:\/\/doi.org\/10.2169\/internalmedicine.55.5843 (2016).","journal-title":"Intern. Med"},{"key":"69773_CR49","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.toxicon.2015.07.013","volume":"107","author":"M Hallett","year":"2015","unstructured":"Hallett, M. Explanation of timing of botulinum neurotoxin effects, onset and duration, and clinical ways of influencing them. Toxicon 107, 64\u201367. https:\/\/doi.org\/10.1016\/j.toxicon.2015.07.013 (2015).","journal-title":"Toxicon"},{"key":"69773_CR50","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1080\/08039480600790358","volume":"60","author":"L Nyboe Jacobsen","year":"2006","unstructured":"Nyboe Jacobsen, L., Smith Lassen, I., Friis, P., Videbech, P. & Wentzer Licht, R. Bodily symptoms in moderate and severe depression. Nord J. Psychiatry 60, 294\u2013298. https:\/\/doi.org\/10.1080\/08039480600790358 (2006).","journal-title":"Nord J. Psychiatry"},{"key":"69773_CR51","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1080\/15622970902812072","volume":"10","author":"RK Gupta","year":"2009","unstructured":"Gupta, R. K. Major depression: an illness with objective physical signs. World J. Biol Psychiatry 10, 196\u2013201. https:\/\/doi.org\/10.1080\/15622970902812072 (2009).","journal-title":"World J. Biol Psychiatry"},{"key":"69773_CR52","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1001\/archopht.124.1.116","volume":"124","author":"TA Hall","year":"2006","unstructured":"Hall, T. A. et al. Health-related quality of life and psychosocial characteristics of patients with benign essential blepharospasm. Arch. Ophthalmol. 124, 116\u2013119. https:\/\/doi.org\/10.1001\/archopht.124.1.116 (2006).","journal-title":"Arch. Ophthalmol."},{"key":"69773_CR53","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1097\/01.NMD.0000081667.02656.21","volume":"191","author":"H G\u00fcndel","year":"2003","unstructured":"G\u00fcndel, H. et al. High psychiatric comorbidity in spasmodic torticollis: a controlled study. J. Nerv. Ment. Dis. 191, 465\u2013473. https:\/\/doi.org\/10.1097\/01.NMD.0000081667.02656.21 (2003).","journal-title":"J. Nerv. Ment. Dis."},{"key":"69773_CR54","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1007\/s10072-019-3719-9","volume":"40","author":"D Ceylan","year":"2019","unstructured":"Ceylan, D., Erer, S., Zarifo\u011flu, M., T\u00fcrke\u015f, N. & \u00d6zkaya, G. Evaluation of anxiety and depression scales and quality of LIFE in cervical dystonia patients on botulinum toxin therapy and their relatives. Neurol. Sci. 40, 725\u2013731. https:\/\/doi.org\/10.1007\/s10072-019-3719-9 (2019).","journal-title":"Neurol. Sci."},{"key":"69773_CR55","doi-asserted-by":"publisher","first-page":"adv00044","DOI":"10.2340\/00015555-3393","volume":"100","author":"JK Kristensen","year":"2020","unstructured":"Kristensen, J. K., Vestergaard, D. G., Swartling, C. & Bygum, A. Association of primary hyperhidrosis with depression and anxiety: a systematic review. Acta Derm. Venereol. 100, adv00044. https:\/\/doi.org\/10.2340\/00015555-3393 (2020).","journal-title":"Acta Derm. Venereol."},{"key":"69773_CR56","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1007\/s11940-017-0475-0","volume":"19","author":"KE Green","year":"2017","unstructured":"Green, K. E., Rastall, D. & Eggenberger, E. Treatment of blepharospasm\/hemifacial spasm. Curr. Treat. Options Neurol 19, 41. https:\/\/doi.org\/10.1007\/s11940-017-0475-0 (2017).","journal-title":"Curr. Treat. Options Neurol"},{"key":"69773_CR57","doi-asserted-by":"publisher","first-page":"14720","DOI":"10.1038\/s41598-018-33119-1","volume":"8","author":"MB Lewis","year":"2018","unstructured":"Lewis, M. B. The interactions between botulinum-toxin-based facial treatments and embodied emotions. Sci. Rep. 8, 14720. https:\/\/doi.org\/10.1038\/s41598-018-33119-1 (2018).","journal-title":"Sci. Rep."},{"key":"69773_CR58","doi-asserted-by":"publisher","first-page":"1861","DOI":"10.2147\/NDT.S141066","volume":"13","author":"JR Bedarf","year":"2017","unstructured":"Bedarf, J. R., Kebir, S., Michelis, J. P., Wabbels, B. & Paus, S. Depression in blepharospasm: a question of facial feedback?. Neuropsychiatr. Dis. Treat. 13, 1861\u20131865. https:\/\/doi.org\/10.2147\/NDT.S141066 (2017).","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"69773_CR59","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/j.parkreldis.2007.03.006","volume":"13","author":"S Ochudlo","year":"2007","unstructured":"Ochudlo, S., Bryniarski, P. & Opala, G. Botulinum toxin improves the quality of life and reduces the intensification of depressive symptoms in patients with blepharospasm. Parkinson. Relat. Disord. 13, 505\u2013508. https:\/\/doi.org\/10.1016\/j.parkreldis.2007.03.006 (2007).","journal-title":"Parkinson. Relat. Disord."},{"key":"69773_CR60","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1136\/jnnp.55.3.229","volume":"55","author":"M Jahanshahi","year":"1992","unstructured":"Jahanshahi, M. & Marsden, C. D. Psychological functioning before and after treatment of torticollis with botulinum toxin. J. Neurol. Neurosurg. Psychiatry 55, 229\u2013231. https:\/\/doi.org\/10.1136\/jnnp.55.3.229 (1992).","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"69773_CR61","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1111\/j.1365-2133.2004.06334.x","volume":"152","author":"A Weber","year":"2005","unstructured":"Weber, A. et al. Psychosocial aspects of patients with focal hyperhidrosis: marked reduction of social phobia, anxiety and depression and increased quality of life after treatment with botulinum toxin A. Br. J. Dermatol. 152, 342\u2013345. https:\/\/doi.org\/10.1111\/j.1365-2133.2004.06334.x (2005).","journal-title":"Br. J. Dermatol."},{"key":"69773_CR62","doi-asserted-by":"publisher","first-page":"33","DOI":"10.2147\/NDT.S181820","volume":"15","author":"H Dong","year":"2019","unstructured":"Dong, H., Fan, S., Luo, Y. & Peng, B. Botulinum toxin relieves anxiety and depression in patients with hemifacial spasm and blepharospasm. Neuropsychiatr. Dis. Treat. 15, 33\u201336. https:\/\/doi.org\/10.2147\/NDT.S181820 (2019).","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"69773_CR63","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1136\/jnnp-2018-319290","volume":"90","author":"AM Blumenfeld","year":"2019","unstructured":"Blumenfeld, A. M. et al. Effects of onabotulinumtoxinA treatment for chronic migraine on common comorbidities including depression and anxiety. J. Neurol. Neurosurg Psychiatry 90, 353\u2013360. https:\/\/doi.org\/10.1136\/jnnp-2018-319290 (2019).","journal-title":"J. Neurol. Neurosurg Psychiatry"},{"key":"69773_CR64","doi-asserted-by":"publisher","first-page":"1218","DOI":"10.1111\/head.12657","volume":"55","author":"K Maasumi","year":"2015","unstructured":"Maasumi, K., Thompson, N. R., Kriegler, J. S. & Tepper, S. J. Effect of OnabotulinumtoxinA injection on depression in chronic migraine. Headache 55, 1218\u20131224. https:\/\/doi.org\/10.1111\/head.12657 (2015).","journal-title":"Headache"},{"key":"69773_CR65","doi-asserted-by":"publisher","first-page":"99","DOI":"10.3389\/fnbeh.2014.00099","volume":"8","author":"T Nekovarova","year":"2014","unstructured":"Nekovarova, T. et al. Common mechanisms of pain and depression: are antidepressants also analgesics?. Front Behav. Neurosci. 8, 99. https:\/\/doi.org\/10.3389\/fnbeh.2014.00099 (2014).","journal-title":"Front Behav. Neurosci."},{"key":"69773_CR66","doi-asserted-by":"publisher","first-page":"139","DOI":"10.2165\/00023210-200822020-00005","volume":"22","author":"G McCleane","year":"2008","unstructured":"McCleane, G. Antidepressants as analgesics. CNS Drugs 22, 139\u2013156. https:\/\/doi.org\/10.2165\/00023210-200822020-00005 (2008).","journal-title":"CNS Drugs"},{"key":"69773_CR67","doi-asserted-by":"publisher","first-page":"1","DOI":"10.7554\/eLife.25818","volume":"6","author":"M Maciejewski","year":"2017","unstructured":"Maciejewski, M. et al. Reverse translation of adverse event reports paves the way for de-risking preclinical off-targets. Elife 6, 1. https:\/\/doi.org\/10.7554\/eLife.25818 (2017).","journal-title":"Elife"},{"key":"69773_CR68","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1080\/14740338.2017.1323867","volume":"16","author":"YM Alatawi","year":"2017","unstructured":"Alatawi, Y. M. & Hansen, R. A. Empirical estimation of under-reporting in the US Food and Drug administration adverse event reporting system (FAERS). Expert Opin. Drug Saf. 16, 761\u2013767. https:\/\/doi.org\/10.1080\/14740338.2017.1323867 (2017).","journal-title":"Expert Opin. Drug Saf."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-69773-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-69773-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-69773-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T14:54:19Z","timestamp":1670338459000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-69773-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,30]]},"references-count":68,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["69773"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-69773-7","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,30]]},"assertion":[{"value":"16 April 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 July 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 July 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Dr. M. Axel Wollmer has consulted for Allergan pharmaceuticals. Other authors declare no conflict of financial or non-financial interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"12851"}}