Abstract

Botulinum toxins (BTX), predominately BotulinumtoxinA, have been used for medical and aesthetic purposes since 1997. With nearly eight billion treatments performed worldwide for aesthetic purposes alone, there is extensive post-market experience with this drug. The known mechanism of action (MOA) of the local neurotransmitter blockade of acetylcholine lasts approximately 90 days. However, patients frequently report symptom and wrinkle relief beyond the 90-day period. There is extensive evidence that peripherally injected BTX, even at low aesthetic doses, induces structural and functional changes in the human brain. The MOA in the central nervous system (CNS) is presently unclear, with several proposed hypotheses to include the Social Feedback Hypothesis (SFH), Facial Feedback Hypothesis (FFH) and Emotional Proprioception (EP), Monoamine Theory and Brain-Derived Neurotrophic Peptide (BDFP), and Neuronal Transport Hypothesis. With the ability to modify the CNS, BTX for aesthetic use may become a novel treatment for CNS disorders, such as major depressive disorder (MDD). Over 30% of persons diagnosed with MDD had inadequate response to first-line treatments. Over 30% of persons diagnosed with treatment resistant depression (TRD) attempt suicide. BotulinumtoxinA may offer an effective adjunctive treatment of MDD/TRD.

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