Elective mutism is a now outdated term which was defined as a refusal to speak in almost all social situations (despite normal ability to do so), while selective mutism was considered to be a failure to speak in specific situations and is strongly associated with social anxiety disorder. In contrast to selective mutism, it was thought someone who was electively mute may not speak in any situation, as is usually shown in books and films. Elective mutism was often attributed to defiance or the effect of trauma. Those who are able to speak freely in some situations but not in others are now better described by selective mutism. History
In 1877, a German physician named the disorder aphasia voluntaria to describe children who were able to speak normally but often "refused" to.In 1980, a study by Torey Hayden identified four "subtypes" of Elective Mutism:
Symbiotic mutism: the most common of the forms, caused by a vocal and dominating mother and absent father (very rarely the other way around) and characterized by the use of mutism as controlling behavior around other adults. Speech phobic mutism: the least common, in which the child showed distinct fear at hearing a recording of their voice. This also involved ritualistic behaviors, which may reflect OCD, and was thought to be caused by the child having been told to keep a family secret. Reactive mutism: a reaction to trauma and/or abuse, with all children showing symptoms of depression and being notably withdrawn, usually showing no facial expressions.
Pharmacology
Setmelanotide binds to and activates MC4 receptors in the paraventricular nucleus (PVN) of the hypothalamus and in the lateral hypothalamic area (LHA), areas involved in the regulation of appetite, and this action is thought to underlie its appetite suppressant effects. In addition to reducing appetite, setmelanotide increases resting energy expenditure in both obese animals and humans. Importantly, unlike certain other MC4 receptor agonists, such as LY-2112688, setmelanotide has not been found to produce increases in heart rate or blood pressure.Setmelanotide has been reported to possess the following activity profile (cAMP, EC50): MC4 (0.27 nM) > MC3 (5.3 nM) ≈ MC1 (5.8 nM) > MC5 (1600 nM) ≟ MC2 (>1000 nM). (19.6-fold selectivity for MC4 over MC3, the second target of highest activity.) History
Setmelanotide was invented at Ipsen by Jesse Z. Dong. It was initially known as BIM-22493 and then as RM-493 and IRC-022493. It was evaluated in two one-year clinical studies. The first study enrolled 10 participants with obesity and confirmed or suspected POMC or PCSK1 deficiency while the second study enrolled 11 participants with obesity and confirmed or suspected LEPR deficiency; all participants were six years or older. Most participants had lost more than 10% of their initial body weight after a year of treatment. Some participants also reported feeling less hungry.The U.S. Food and Drug Administration (FDA) granted the application for setmelanotide orphan disease designation, breakthrough therapy designation, and priority review.