In 1994 Richwood Pharmaceuticals acquired Rexar and began promoting Obetrol as a treatment for ADHD (and later narcolepsy as well), now marketed under the new brand name of Adderall, a contraction of the phrase "A.D.D. for All" intended to convey that "it was meant to be kind of an inclusive thing" for marketing purposes. The FDA cited the company for numerous significant CGMP violations related to Obetrol discovered during routine inspections following the acquisition (including issuing a formal warning letter for the violations), then later issued a second formal warning letter to Richwood Pharmaceuticals specifically due to violations of "the new drug and misbranding provisions of the FD&C Act". Following extended discussions with Richwood Pharmaceuticals regarding the resolution of a large number of issues related to the companys numerous violations of FDA regulations, the FDA formally approved the first Obetrol labeling/sNDA revisions in 1996, including a name change to Adderall and a restoration of its status as an approved drug product. In 1997 Richwood Pharmaceuticals was acquired by Shire Pharmaceuticals in a $186 million transaction.Richwood Pharmaceuticals, which later merged with Shire plc, introduced the current Adderall brand in 1996 as an instant-release tablet. In 2006, Shire agreed to sell rights to the Adderall name for the instant-release form of the medication to Duramed Pharmaceuticals. DuraMed Pharmaceuticals was acquired by Teva Pharmaceuticals in 2008 during their acquisition of Barr Pharmaceuticals, including Barrs Duramed division.The first generic version of Adderall IR was introduced to market in 2002.
Prognosis
A significant proportion of those with CPVT will experience a life-threatening abnormal heart rhythm, with estimates of this risk ranging from 13 to 20% over the course of 7–8 years. Life-threatening arrhythmias are more likely to occur if CPVT has been diagnosed in childhood, if a person with CPVT does not take beta blockers, and if arrhythmias occur on exercise testing despite taking beta blockers.During treatment with nadolol, the preferred beta blocker for the treatment of CPVT, event rates have been estimated to be 0.8% per year. In patients treated with beta blockers, life-threatening arrhythmias are more likely if a person had already survived a cardiac arrest, had a syncope, or are carriers of disease-causing mutations affecting the highly conserved terminal portion of RYR2 gene, called the C-terminal domain (amino acids 4889–4969). Epidemiology
CPVT is estimated to affect 1 in 10,000 people. Symptoms from CPVT are typically first seen in the first or second decade of life, and more than 60% of affected individuals experience their first episode of syncope or cardiac arrest by age 20. Syncope during exercise or strong emotion should be considered a red flag, as it is a characteristic of the disease. Lastly, a small number of patients may present later in life, and genetic testing in these patients frequently fails to identify a causative gene. History
In 1960, Norwegian cardiologist Knut Berg published a report on three sisters who had blackouts during exercise or emotional stress in what is now recognised as the first description of CPVT.