ADHD Drug Makers To Notify Patients About Health Risks

Makers of drugs approved to treat Attention Deficit Hyperactivity Disorder (ADHD) have been instructed by the US Food and Drug Administration (FDA) to notify patients of certain health risks.


The manufacturers affected include Eli Lilly and Co, Novartis AG, Johnson & Johnson, and Shire plc.


The ADHD drug manufacturers have been instructed to produce Patient Medication Guides that tell patients about possible risks of adverse cardiovascular and psychiatric symptoms and the precautions they should take.


Director of the Center for Drug Evaluation and Research (CDER), Dr Steven Galson, said that "Medicines approved for the treatment of ADHD have real benefits for many patients but they may have serious risks as well."


"In our ongoing commitment to strengthen drug safety, FDA is working closely with manufacturers of all ADHD medicines to include important information in the product labeling and in developing new Patient Medication Guides to better inform doctors and patients about these concerns," he added.


According to the FDA, ADHD affects around 3 to 7 per cent of schoolchildren and 4 per cent of adults. The main symptoms are hyperactive behaviour, difficulty paying attention, and low impulse control.


Children and adults with ADHD tend to have low self-esteem, problems at school and work, and difficult relationships with family and peers.


Patient Medication Guides are leaflets that accompany the drug when it is given to the patient. They are aimed at patients, their families and caregivers. The information is FDA approved and is intended to prevent potentially serious side-effects.



The FDA advises doctors to look carefully at patients' health history (including family history) and current status to assess cardiovascular or psychiatric symptoms and risk before recommending a treatment plan that includes ADHD drugs.


The Patient Medication Guide should be read fully before the medication is taken, and any questions or concerns should be discussed with the doctor.


The FDA has reviewed reports of a small number of patients with underlying serious heart conditions on normal doses of ADHD drugs who have suffered strokes and heart attacks, which in a few cases have been fatal.


The FDA has also conducted a separate review that showed a small increased risk of 1 in 1,000 of adverse psychiatric events linked to ADHD drugs. The adverse psychiatric events include hearing voices, becoming manic, or becoming suspicious for no reason. These events have even happened to people with no history of psychiatric conditions.


In 2006 the FDA directed manufacturers to revise their labelling to take into account these concerns about cardiovascular and psychiatric risks. This new notification is to help patients understand these risks via the Patient Medication Guide.















The new instruction affects 15 products, including various forms of Adderall, Concerta, Daytrana, Dexedrine, Focalin, Metadate, Methylin, Ritalin, and Strattera.


The FDA has been criticized for failing to notify the public sooner. On the other hand, there also fears that this action will stop people who need the drugs from taking them.


Click here to view exact products affected and their relevant draft Patient Medication Guides.


Click here for CDC's "Learn the Signs, Act Early" Campaign on ADHD.


Written by: Catharine Paddock





View drug information on Adderall XR; Concerta; Focalin.

ADHD Seems To Be Linked To Low Dopamine Brain Activity

Adults with *ADHD do not respond as well as children do to Ritalin (methylphenidate). Ritalin boosts brain dopamine levels. According to an article in Archives of General Psychiatry (JAMA/Archives), it is suggested that dopamine dysfunction may be linked to ADHD symptoms, and may be a factor in substance abuse that often takes place simultaneously.


* (ADHD = attention-deficit/hyperactivity disorder)


ADHD is the most common psychiatric disorder among kids, say the authors. "Despite decades of research, the specific neurobiological mechanisms underlying this disorder still remain unclear," the authors write. "Genetic, clinical and imaging studies point to a disruption of the brain dopamine system, which is corroborated by the clinical effectiveness of stimulant drugs (methylphenidate hydrochloride and amphetamine), which increase extracellular dopamine in the brain."


Nora D. Volkow, M.D., National Institute on Drug Abuse, Bethesda, Md., and team studied 19 adults, average age 32 - they all suffered from ADHD. None of them had received medication. They were compared to 24 healthy controls, with an average age of 30.


All the participants had their brains scanned using PET (positron emission tomography) and raclopride labeled with carbon 11 - this binds with dopamine receptors. They were all scanned twice, after a placebo injection and after receiving methylphenidate injection. It was a blind trial - the participants did not know when they were receiving the placebo or the methylphenidate. The volunteers were asked to describe the severity of their ADHD symptoms, and also whether they could sense the drug. They were also asked whether the drug was pleasant, unpleasant, whether it made them anxious, restless, alert, tired, and if it made them feel high.


The methylphenidate caused less of a decrease in the amount of Carbon 11 that was bound to dopamine receptors in areas of the brain linked to attention among those with ADHD than those without ADHD. Given that methylphenidate blood levels were identical in both groups, it seems that the people with ADHD released less dopamine in response to the drug compared to the controls. This poorer response was associated with symptoms of inattention. Exploratory analyses discovered evidence the Carbon 11 levels were binding in reduced numbers in the hippocampus and amygdala among those with ADHD. The hippocampus and amygdala are part of the limbic system which deals with emotional responses and consolidating and retrieving memories.


The authors wrote "The findings of reduced dopamine release in subjects with ADHD are consistent with the notion that the ability of stimulant medications to enhance extracellular dopamine underlies their therapeutic effects in ADHD."


Those with ADHD said they liked methylphenidate more than those without ADHD, the researchers said. They added "The reinforcing responses to methylphenidate were negatively correlated with the dopamine increases, suggesting that decreased dopaminergic activity may also be involved in modulating the magnitude of the reinforcing effects of methylphenidate. This suggests that dopamine dysfunction is involved with symptoms of inattention but may also contribute to substance abuse comorbidity in ADHD."


Arch Gen Psychiatry. 2007;64(8):932-940.

http://archpsyc.ama-assn


Written by: Christian Nordqvist


View drug information on Ritalin LA.

Study Suggests Strattera® Was Effective In Treating ADHD In Children And Adolescents With ADHD And Reading Disorders

New data suggest that Strattera® (atomoxetine HCl) improved ADHD symptoms in children and adolescents who had both ADHD and a reading disorder, like dyslexia. Results were announced today at a meeting of child and adolescent psychiatrists.


The primary objective of the study was to measure Strattera's efficacy in treating the symptoms of ADHD in children and adolescents with ADHD and a comorbid reading disorder (ADHD+RD). Patients with ADHD alone were compared to patients with ADHD+RD. After taking Strattera for 16 weeks, both groups of patients aged 10 to 16 reported an improvement of nearly 50 percent in ADHD symptoms like inattentiveness, hyperactivity and impulsivity. Additionally, patients with ADHD+RD displayed an average reading composite improvement of approximately two years compared to 17 months for participants with ADHD alone. Reading composite is defined as the combined score for reading decoding and reading comprehension. Strattera is not approved to treat reading disorders.


"We are encouraged by the results of this study which highlight the importance of considering appropriate treatment options when treating ADHD in patients with ADHD and comorbid conditions," said Richard Rubin, M.D., clinical associate professor of psychiatry, University of Vermont College of Medicine. "Since ADHD is often combined with reading disabilities, considering treatment options that are effective in treating ADHD without having an adverse effect on reading performance may provide the best outcome."


The two most common developmental disabilities of school-age children are ADHD and learning disabilities, including a reading disorder, like dyslexia.(1,2) It is estimated that 15 - 30 percent of children with ADHD will also have a reading disorder.(2,3,4,5) While research suggests that students with both ADHD and a reading disorder are no more anxious, hyperactive or aggressive than students with ADHD only, the reading disorder does impact school performance, which may subsequently impact family and peer relationships.(6)



Study Highlights



At the study endpoint, mean change from baseline to endpoint analysesrevealed statistically significant improvement for both the patients with ADHD and the patients with ADHD and a comorbid reading disorder (ADHD+RD) on the ADHD RS Total Score (improved 52 percent and 49.2 percent, respectively)


Age equivalence improvements (in months) were statistically significant
for both groups on the following items:


-- Total reading composite: improved 17.2 months for the ADHD group
and 23.5 months for the ADHD+RD group


-- Reading decoding (+17.8 months and +16.9 months, respectively)















-- Reading comprehension (+17.0 months and +26.0 months,
respectively)


-- Spelling (+9.7 months and +8.7 months, respectively)


In this study, Strattera was well tolerated with no differences between
groups and commonly reported adverse events similar to those reported
in previous studies. The most common adverse events (occurring in
greater than 5 percent of patients taking Strattera) were somnolence,
nausea, decreased appetite, headache, abdominal pain, vomiting,
nasopharyngitis and cough.



Methods


In this open-label, parallel-design pilot study conducted in the United States, patients received 1.0 to 1.4 mg/kg of Strattera once daily for approximately 16 weeks. Patients with ADHD (n = 20) were compared to patients with ADHD+RD (n = 36).


All patients were required to have an ADHD symptom severity score at least 1.5 standard deviations above age and gender norms for at least one of the diagnostic subtypes: inattentive, hyperactive/impulsive, or the total score for the combined subtype as assessed by the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD RS). Patients diagnosed as ADHD+RD were also required to have at least a 22-point discrepancy between ability and achievement, based on intelligence quotient (K-BIT) and reading composite (K- TEA) scores. An IQ Composite score of >80 was required on the Kaufman Brief Intelligence Test (K-BIT) for the patient to participate in the study.


The ADHD RS was the primary efficacy measure. The second analysis measured patients' reading performance using the Kaufman Test of Educational Achievement (K-TEA) Reading Decoding, Comprehension and Spelling Subtests and Reading Composite Scale. The Working Memory Test Battery for Children (WMTB- C) and Life Participation Scale Investigator and Parent-Rated versions (LPS-C) were additional secondary measures. The patients were allowed to continue to receive educational services/assistance throughout the study.


About ADHD


ADHD is a complex disorder that often occurs in tandem with other conditions like reading disorders(7). Therefore, proper diagnosis of all a patient's symptoms is vital for choosing appropriate treatment and monitoring for both safety and efficacy.(8)


Untreated ADHD can have lifelong consequences, including poor peer relations, poor academic and work performance and increased risk-taking behaviors, such as substance abuse.(9)


About Strattera


Strattera is indicated for the treatment of Attention- Deficit/Hyperactivity Disorder (ADHD) in children, adolescents and adults.


Strattera, a selective norepinephrine reuptake inhibitor, is the first FDA-approved non-stimulant to treat ADHD. It is not known precisely how Strattera reduces ADHD symptoms, but scientists believe it works by blocking or slowing reabsorption of norepinephrine, a chemical in the brain considered important in regulating attention, impulsivity and activity levels. This keeps more norepinephrine at work in the spaces between neurons in the brain. Improved efficiency in the norepinephrine system is associated with improvement in symptoms of ADHD.(10) Since its first approval in the United States in 2002, more than 4.2 million patients have taken Strattera worldwide. It has been studied in more than 6,000 patients in clinical trials, some for as long as three years.


Important Safety Information


In some children and teens, Strattera increases the risk of suicidal thoughts. A combined analysis of 12 studies of Strattera showed that, in children and teens, this risk was 0.4 percent for those taking Strattera compared to none for those taking a sugar pill. A similar analysis in adults treated with Strattera did not reveal an increased risk of suicidal thoughts. Parents should call their doctor right away if their child has thoughts of suicide or sudden changes in mood or behavior, especially at the beginning of treatment or after a change in dose. Strattera should not be taken at the same time as, or within two weeks of taking, a monoamine oxidase inhibitor (MAOI) or by patients with narrow angle glaucoma.


Tell your doctor if you or a family member has a history of high or low blood pressure, increased heart rate, heart or blood vessel disease or structural heart defects. If you experience any cardiac symptoms, such as chest pain or fainting while taking Strattera, you should report them to your doctor right away.


In rare cases, Strattera can cause liver problems. Call your doctor right away if you have itching, dark urine, yellow skin/eyes, upper right-side abdominal tenderness, or unexplained "flu-like" symptoms. If your child develops new psychological symptoms, such as abnormal thoughts/behaviors and/or extreme elevated or irritable moods while taking Strattera, you should report them to your child's doctor right away.


For male patients, if you are taking Strattera and experience priapism, a painful or prolonged erection lasting more than four hours, call your doctor right away. As with all ADHD medications, growth should be monitored during treatment, although height and weight data measured for up to three years indicates minimal, if any, long-term effects.


Most people in clinical studies who experienced side effects were not bothered enough to stop using Strattera. The most common side effects in children and adolescents in medical studies were upset stomach, decreased appetite, nausea and vomiting, dizziness, tiredness and mood swings. In adults, the most common side effects were constipation, dry mouth, nausea, decreased appetite, dizziness, problems sleeping, sexual side effects, problems urinating and menstrual cramps.


For Medication Guide, visit Strattera.


For full Prescribing Information, including Boxed Warning information, visit Strattera/.


About Eli Lilly and Company


Lilly, a leading innovation-driven corporation, is developing a growing portfolio of first-in-class and best-in-class pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Ind., Lilly provides answers -- through medicines and information -- for some of the world's most urgent medical needs. Additional information about Lilly is available at lilly.


P-LLY


This press release contains forward-looking statements about Strattera for the treatment of ADHD and reflects Lilly's current beliefs. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of development and commercialization, including the risk of side effects and other safety concerns. There is no guarantee that the product will continue to be commercially successful. For further discussion of these and other risks and uncertainties, see Lilly's filings with the United States Securities and Exchange Commission. Lilly undertakes no duty to update forward-looking statements.


(1) Goldman LS, Genel M, Bezman RJ, Slanetz PJ. 1998. Diagnosis and treatment of attention-deficit/hyperactivity disorder in children and adolescents. Journal of the American Medical Association; 279(14): 1100-1107.

(2) Shaywitz BA and Shaywitz SE. 1994. Learning disabilities and attention disorders. In: KF Swaiman (Ed.), Pediatric Neurology: Principles and practice, Vol II: 1119-1151; St. Louis, MO: CV Mosby.

(3) Barkley RA. 2002. Major Life Activity and Health Outcomes Associated with Attention-Deficit/Hyperactivity Disorder. J Clin Psychiatry; 63 (suppl 12): 10-15.

(4) Brown TE. 2000. Attention-Deficit Disorders and Comorbidities in Children, Adolescents, and Adults. Washington DC American Psychiatric Press.

(5) Semrud-Clikeman M, Biederman J, Sprich-Buckminster S, Lehman BK, Faraone SV, Norman D. 1992. Comorbidity between ADHD and learning disability: A review and report in a clinically referred sample. J Am Acad Child Adolesc Psychiatry 31(3):439-48.

(6) ADHD and Coexisting Disorders,help4adhd/treatment/coexisting/WWK5

(7) Greenhill LL. Diagnosing attention-deficit/hyperactivity disorder in children. J Clin Psychiatry 1998; 59 (Suppl 7): 31-41.

(8) Barkley. ADHD: A Handbook for Diagnosis and Treatment. New York: Guilford Press; 1998.

(9) Faraone S, Beiderman J, et al. ADHD in adults: an overview. Biol Psychiatry 2000; 48:9-20.

(10) Pliszka SR, et al. Journal of the American Academy of Child and Adolescent Psychiatry. 1996, 35(264-272).


Eli Lilly and Company

lilly/


View drug information on Strattera.

Major Follow-Up Study Following ADHD Treatment Showed Sustained Improvement In Most Children

Most children treated in a variety of ways for attention deficit hyperactivity disorder (ADHD) showed sustained improvement after three years in a major follow-up study funded by the National Institutes of Health's (NIH) National Institute of Mental Health (NIMH). Yet increased risk for behavioral problems, including delinquency and substance use, remained higher than normal.



The study followed-up children who had participated in the Multimodal Treatment Study of Children with Attention Deficit Hyperactivity Disorder (MTA).



Initial advantages of medication management alone or in combination with behavioral treatment over purely behavioral or routine community care waned in the years after 14 months of controlled treatment ended. However, Peter Jensen, M.D., Columbia University, and colleagues emphasized that "it would be incorrect to conclude from these results that treatment makes no difference or is not worth pursuing."



Their report is among four on the outcome of the MTA study published in the August, 2007 Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP).



"We were struck by the remarkable improvement in symptoms and functioning across all treatment groups," explained Jensen.



After three years, 45-71 percent of the youth in the original treatment groups were taking medication. However, continuing medication treatment was no longer associated with better outcomes by the third year.



"Our results suggest that medication can make a long-term difference for some children if it's continued with optimal intensity, and not started or added too late in a child's clinical course," added Jensen.



For the followup study, a multi-site research team evaluated, at ages 10-13, 485 children from the original MTA study, the first major randomized trial comparing different treatments for ADHD, published in l999. That study found that intensive medication management alone or in combination with behavioral therapy produced better outcomes than just behavioral therapy or usual community care.



Ratings from families and teachers favored the combination treatment, which allowed for somewhat lower medication doses. Also, the careful management of medication by MTA physicians produced better outcomes than medication provided through usual community care sources.



After the 14 months of assigned treatments ended, families were free to choose from treatments available in their communities.



To understand why the initial advantage of medication wore off, the researchers examined medication use patterns that emerged after formal treatment in the study ended. They found that children who had been assigned to intensive behavioral treatment were more likely to begin taking medication, while those who had been taking medication were more likely to stop. For example, among children originally in the behavioral treatment group, the incidence of high medication use increased from 14 to 45 percent.
















In a secondary analysis of the data that searched for possible explanations for the findings, in the same issue of the JAACAP, researchers led by James Swanson, Ph.D., University of California at Irvine, reported finding substantial individual variability in responses to medication. They identified three groups of children with different patterns of response. One group, about a third of the children, showed a gradual, moderate improvement; a second group, about half of the children, showed larger initial improvement, which was sustained through the third year; a third group, about 14 percent of the children, responded well initially, but then deteriorated as symptoms returned during the second and third years. Swanson and colleagues suggested "trial withdrawals" for some children to determine if they still need to take medications.



Another report by Swanson and colleagues in the same issue of the JAACAP confirmed an earlier finding from the MTA study that taking medication slowed growth. A group of 65 children with ADHD who had never taken medication grew somewhat larger -- about three-fourths of an inch and 6 pounds more, on average -- than a group of 88 peers who stayed on medication over the three years. Growth rates normalized for the children on medication by the third year, but they had not made up for the earlier slowing in growth.



In a fourth article, Brooke Molina, Ph.D., University of Pittsburgh, and colleagues reported that, despite treatment, the children with ADHD showed significantly higher-than-normal rates of delinquency (27.1 percent vs. 7.4 percent) and substance use (17.4 percent vs. 7.8 percent) after three years. Earlier evidence of lower substance use rates among children who had received intensive behavioral therapy had lessened by the third year. "These findings underscore the point that ADHD treatment for one year does not prevent serious problems from emerging later," noted Molina.



The follow-up of the MTA sample will continue as the participating children go through adolescence and enter adulthood.






The following researchers participated in the studies:



Three-year Follow-up of the NIMH MTA Study. Peter S. Jensen, L. Eugene Arnold, James M. Swanson, Benedetto Vitiello, Howard B. Abikoff, Laurence L. Greenhill, Lily Hechtman, Stephen P. Hinshaw, William E. Pelham, Karen C. Wells, C. Keith Conners, Glen R. Elliott, Jeffery N. Epstein, Betsy Hoza, John S. March, Brooke S.G. Molina, Jeffrey H. Newcorn, Joanne B. Severe, Timothy Wigal, Robert D. Gibbons, Kwan Hur



Secondary Evaluations of MTA 36-Month Outcomes: Propensity Score and Growth Mixture Model Analyses. James M. Swanson, Stephen P. Hinshaw, L. Eugene Arnold, Robert D. Gibbons, Sue Marcus, Kwan Hur, Peter S. Jensen, Benedetto Vitiello, Howard B. Abikoff, Laurence L. Greenhill, Lily Hechtman, William E. Pelham, Karen C. Wells, C. Keith Conners, John S. March, Glen R. Elliott, Jeffery N. Epstein, Kimberly Hoagwood, Betsy Hoza, Brooke S.G. Molina, Jeffrey H. Newcorn, Joanne B. Severe, Timothy Wigal, and the MTA Cooperative Group



Effects of Stimulant Medication on Growth Rates Across 3 Years in the MTA Follow-up. James M. Swanson, Glen R. Elliott, Laurence L. Greenhill, Timothy Wigal, L. Eugene Arnold, Benedetto Vitiello, Lily Hechtman, Jeffery Epstein, William E. Pelham, Howard B. Abikoff, Jeffrey H. Newcorn, Brooke S.G. Molina, Stephen P. Hinshaw, Karen C.Wells, Betsy Hoza, Peter S. Jensen, Robert D. Gibbons, Kwan Hur, Annamarie Stehli, Mark Davies, John S. March, C. Keith Conners, Mark Caron, Nora D. Volkow, for the MTA Collaborative Group



Delinquent Behavior and Emerging Substance Use in the MTA at 36-Months: Prevalence, Course, and Treatment Effects. Brooke S. G. Molina, Kate Flory, Stephen P. Hinshaw, Andrew R. Greiner, L. Eugene Arnold, James M. Swanson, Lily Hechtman, Peter S. Jensen, Benedetto Vitiello, Betsy Hoza, William E. Pelham, Glen R. Elliott, Karen C. Wells, Howard B. Abikoff, Robert D. Gibbons, Sue Marcus, C. Keith Conners, Jeffery N. Epstein, Laurence L. Greenhill, John S. March, Jeffrey H. Newcorn, Joanne B. Severe, Timothy Wigal, and the MTA Cooperative Group. The Office of Special Education Programs of the U.S. Department of Education, the Office of Juvenile Justice and Delinquency Prevention of the Justice Department, and the National Institute on Drug Abuse (NIDA) also participated in funding this study.



The National Institute of Mental Health (NIMH) mission is to reduce the burden of mental and behavioral disorders through research on mind, brain, and behavior. More information is available at the NIMH website, nimh.nih.gov/. The National Institutes of Health (NIH) - The Nation's Medical Research Agency - includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit nih.gov/.



Source: Jules Asher


NIH/National Institute of Mental Health

Concerta Showed Significant Improvement Of ADHD Symptom Management In Adults, New Study Finds

Interim results from open-label follow-up include longer-term safety findings



Adults with Attention Deficit Hyperactivity Disorder (ADHD) treated with CONCERTA® OROS® methylphenidate HCl Extended-release Tablets showed significant improvements in ADHD symptom management compared to adults taking placebo, according to study results presented at a major psychiatric medical meeting.



"Pharmacological treatment of children and adolescents with ADHD is clearly established but relatively less is known about the treatment of adults with ADHD," notes the study's medical director, Sally Berry, M.D., PhD., of Johnson & Johnson Pharmaceutical Research and Development, LLC. "We're encouraged that the CONCERTA® findings presented ... -- in which CONCERTA® significantly improved ADHD symptom management in adults -- can benefit the growing body of knowledge in this important therapeutic area."



The data presented are part of a Supplemental New Drug Application (sNDA) submitted in August 2007 to the Food and Drug Administration for use of CONCERTA® to treat adults with ADHD. CONCERTA® is already approved for the treatment of ADHD in children and adolescents ages six to 17.



About the Study



In the study, efficacy was measured as a change in the Adult ADHD Investigator Symptom Rating Scale (AISRS) total score. The results showed that CONCERTA® achieved a significantly superior reduction in AISRS total score compared to placebo (p=0.012) (mean change was -10.6 ?±1.09 for the CONCERTA® group vs. -6.8 ?±1.06 for the placebo group.



In addition, CONCERTA® was significantly superior compared to placebo for the key secondary efficacy variables: change in Clinical Global Impression-Improvement (CGI-I) rating (p=0.008); change in Conners' Adult ADHD Rating Scale-Self Report (CAARS-S:S) total score (p=0.029) and change in percent of subjects meeting pre-defined Responder criteria (p=0.009).



In the study, 229 patients with ADHD aged 18-65 years were randomized to receive CONCERTA® 36-108 mg/day or placebo, for seven weeks. The final analysis set contained data from 226 patients . Patients in the CONCERTA® group received a starting dose of 36 mg/day and the dose was increased in 18 mg increments every seven days (?±2 days) for up to five weeks until response (AISRS scores decreased by 30% and CGI-I rating of 1 "very much" or 2 "much" improved) was achieved or titration to the maximum dose of 108 mg. The dose could be reduced one time during the study for tolerability reasons. The mean final dose was 67.7 mg/day.



Adverse events were reported by 93 (84.5%) of patients in the CONCERTA® group compared with 74 (63.8%) in the placebo group. The most commonly reported adverse events with CONCERTA® included decreased appetite (25.5%), headache (25.5%), dry mouth (20%), anxiety (16.4%), nausea (12.7%), increased blood pressure (10%), insomnia (9.1%), initial insomnia (7.3%), increased heart rate (7.3%), bruxism (6.4%), irritability (6.4%) and muscle tightness (6.4%). There were no serious treatment emergent adverse events reported and 16 (14.5%) and 6 (5.2%) subjects in the CONCERTA® and placebo groups, respectively, discontinued due to adverse events.
















This data presentation included interim results from a long-term, open-label safety study. A similar dose titration protocol was used as in the double-blind study during the first weeks of the study after which the dose was flexible within the range of 36 to 108 mg. Interim results show that CONCERTA® was well tolerated in an adult population with ADHD in a dose range from 36mg to 108 mg per day for up to six months.







About ADHD



Attention Deficit Hyperactivity Disorder (ADHD) is a common and treatable neuropsychiatric condition, which includes inattention, hyperactivity and impulsivity. According to the National Institutes of Health (NIH), ADHD is one of the most common mental disorders in childhood. It affects an estimated four million children and adolescents in the United States. Although once considered to be a disorder only seen in children, ADHD is now known to be a common neuropsychiatric disorder associated with a wide range of functional impairments throughout the lifespan, according to the Journal American Occupational Environmental Medicine (Kessler, RC et al 2005.)



About CONCERTA®



CONCERTA® is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in children and adolescents ages six-17. For more information about CONCERTA®, including full U.S. prescribing information, please visit concerta/ or contact your health care provider.



Important Safety Information



CONCERTA® should not be taken by patients with: significant anxiety, tension or agitation; allergies to methylphenidate or other ingredients in CONCERTA®; glaucoma; Tourette's syndrome, tics or family history of Tourette's syndrome. Abuse of methylphenidate may lead to dependence. Tell your health care professional if your child has had problems with alcohol or drugs, has had depression, abnormal thoughts or visions, bipolar disorder, seizures, high blood pressure or has had any heart problems or defects. If your child develops abnormal thinking or hallucinations, abnormal, extreme moods and/or excessive activity, or if aggressive behavior or hostility develops or worsens while taking CONCERTA®, consult your health care professional. The most common adverse events reported in children receiving up to 54 mg were headache, upper respiratory tract infection and abdominal pain. The most common adverse events reported by adolescents receiving up to 72 mg were headache, accidental injury and insomnia.



About McNeil Pediatrics



McNeil Pediatrics Division of McNeil-PPC, Inc. is committed to meeting the needs of pediatric medicine through the development of therapies specifically formulated for children. McNeil Pediatrics markets CONCERTA® OROS® methylphenidate HCL for treatment of children and adolescents with ADHD in the US. McNeil Pediatrics is continuing to explore other new therapies to meet the special needs of children and the pediatric community. Visit mcneilpediatrics/ for more information.



CONCERTA® and OROS® are registered trademarks of ALZA Corporation.



Source: Tricia Geoghegan


Golin/Harris International



View drug information on Concerta.

ADHD: Excuse Or Misunderstood? 57% Of British Public Believe Disorder Used To Excuse Children's Bad Behaviour

New research conducted this year shows that over half of the British public believe Attention Deficit Hyperactivity Disorder (ADHD) is merely a term for excusing unacceptable or uncontrollable behaviour.1 This latest set of data suggest that the public's perception of ADHD as a legitimate clinical condition has not improved since 2006, when this view was held by 54% of respondents.2


ADHD is a well-established and serious condition that causes people to lose concentration quickly, act impulsively or be generally overactive.* Despite this, it is still often seen as an excuse for poor parenting or a "lack of control" by a large proportion of the public.


Dr. Graeme Lamb, Consultant Child and Adolescent Psychiatrist working in the field of ADHD, has voiced his concerns surrounding this misconception. "ADHD is a serious and under-diagnosed medical condition." Dr. Lamb also commented, "Living with this condition is distressing for the patient, but it also places an enormous strain on parents who have to deal with the stress of coping with their child as well as the stigma associated with the disorder. Often parents are accused of poor parenting when this is simply not the case."


The latest survey results suggest this misconception continues to have an impact on the management of the symptoms. Four percent of parents surveyed reported that if they suspected their child suffered from ADHD they would do nothing as they thought their child would grow out of the condition.1 However, in reality the symptoms of ADHD can continue into adulthood for three in five children.3


And, more worrying, 16% of parents revealed they would try and deal with ADHD in the home, without seeking any advice or professional help.1 This approach can be detrimental as ADHD not only affects a child's behaviour, it can also cause developmental difficulties which can present in various ways. For example, children with ADHD may suffer from learning difficulties and may take longer to develop language skills. This may result in reduced motivation, problems expressing ideas and emotions, and difficulties when interacting with others. Professional help and advice can often be helpful in overcoming some of these developmental difficulties.3


For parents who have children with ADHD it is not just the school day that is of concern. Unsurprisingly, 31% of respondents reported that weekends and holidays are a concern, with the early evening, (breakfast time and) before school and late evening also proving to be a problem (24%, 23% and 15% respectively).1



Without the proper attention, children and adolescents with ADHD may continue to experience problems with school performance as well as social and family relationships. If a child is diagnosed with ADHD, it is important that their condition is managed appropriately to ensure that they achieve their full potential.


References


1. 2007 Tickbox Survey: Data on file ConcertaXL_DoF_19oct07_MI_JCJ_001; Janssen-Cilag 2007.

2. 2006 Tickbox Survey: Data on file ConcertaXL_DoF_19oct07_MI_JCJ_002; Janssen-Cilag 2006.

3. Baren M. ADHD in adolescents: will you know it when you see it? Contemp Pediatr. 2002;19:124-141.


What is ADHD?


Attention-deficit hyperactivity disorder (ADHD) is a medical condition that is defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM IV).


ADHD is characterised by three core symptoms: inattention, hyperactivity and impulsivity. Inattention can include an inability to focus and pay attention, a pattern of careless mistakes, difficulty listening or finishing tasks and easy distractibility. Hyperactivity may be manifested through fidgeting, talking excessively, and a tendency to run around at inappropriate times and interrupt others. Impulsivity may be exhibited as an inability to curb immediate reactions, often causing children to blurt out inappropriate comments or to run into the street without looking.


Research


Research commissioned by independent online research agency Tickbox in 2006 and 2007, on behalf of Janssen-Cilag, with a random sample of 1,963 and 1,343 people in the UK, respectively.

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Shire Bioequivalence Study Results Of SPD465, Investigational Drug For Adults With ADHD

Shire plc (LSE: SHP, NASDAQ: SHPGY, TSX: SHQ) announced that a single once-daily morning dose of the investigational amphetamine compound SPD465, extended release triple-bead mixed amphetamine salts, designed to reduce symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD) in adults for up to 16 hours, was bioequivalent to a dose of ADDERALL XR (mixed salts of a single-entity amphetamine product) followed by a dose of mixed amphetamine salts immediate release ("MAS IR") eight hours later. The results of this phase I clinical trial in healthy adults were presented at the 2006 U.S. Psychiatric & Mental Health Congress (USPMHC) annual meeting in New Orleans.



"Adults with ADHD are particularly challenged by a normal day's activities that often extend into the evening, and SPD465 offers the possibility of full-day symptom control," said Lenard A. Adler, M.D., director of the Adult ADHD Program in the Departments of Psychiatry and Neurology at New York University (NYU) School of Medicine and author of Scattered Minds: Hope and Help for Adults with ADHD (Putnam).



On July 21, 2006, Shire submitted a New Drug Application for SPD465, which is now under FDA review. If approved, SPD465 would be the first and only ADHD stimulant product designed to control inattention, hyperactivity and impulsivity in adults for up to 16 hours with one daily dose, thus potentially eliminating the need for augmenting a long-acting stimulant medication with a short-acting stimulant during the latter part of the day. More than nine million American adults currently exhibit symptoms of ADHD.



About the Study


In the study, investigators randomized 20 healthy adults (average age of 30 years), to either of two treatments, once-daily SPD465 37.5 mg or 25 mg ADDERALL XR followed by 12.5 mg of MAS IR administered eight hours later. The researchers dispensed the assigned medication regimen to the participants after an overnight fast and collected blood plasma samples before dosing; hourly thereafter through the first 10 hours after dosing; and then periodically for the next two and a half days. After a washout period of seven days, each participant was crossed over to receive the alternate treatment.



Bioequivalency of the two medication regimens is supported by the pharmacokinetic data collected for both d-amphetamine and l-amphetamine. Maximum plasma concentrations for both d-amphetamine and l-amphetamine were similar between the SPD465 group and the ADDERALL XR plus MAS IR group (50.3 ng/ML and 49.3 ng/mL, respectively). Both d-amphetamine and l-amphetamine were quantifiable in plasma at one hour after dosing in both treatment groups. Mean plasma concentration profiles of d-amphetamine and l-amphetamine were similar throughout the day and into the evening hours for both SPD465 and ADDERALL XR augmented with MAS IR.
















No clinically meaningful differences occurred between the two study groups regarding adverse events. The reported adverse events were generally considered mild and resolved before study end, except one reported case of acne. The most frequently reported adverse events in the SPD465 group of healthy adults were hypervigilance, decreased appetite, headache, eye irritation, back pain, increased energy and anorexia.



About ADHD


ADHD is one of the most common psychiatric disorders in children and adolescents. Although many people tend to think of ADHD as a childhood problem, up to 80 percent of children with ADHD may exhibit symptoms into adolescence and up to 65 percent of children with ADHD may still exhibit symptoms into adulthood. In fact, ADHD affects approximately 9 million adults. ADHD is a neurobiological psychiatric disorder that manifests as a persistent pattern of inattention and/or hyperactivity-impulsivity that is more frequent and severe than is typically observed in individuals at a comparable level of development. A diagnosis of Attention-Deficit Hyperactivity Disorder in adults (ADHD; DSM-IV) implies the presence of hyperactive-impulsive and/or inattentive symptoms that cause impairment and were present before the age of 7 years. The symptoms must cause clinically significant impairment, e.g., in social, academic, or occupational functioning, and be present in two or more settings, e.g., work (or school) and at home. The symptoms must not be better accounted for by another mental disorder.



Although there is no "cure" for ADHD, there are accepted treatments that specifically target its symptoms. The most common standard treatments include educational approaches, psychological or behavioral modification, and medication.






Shire Development Inc. supported the study.
Shire plc



For further information on ADHD please visit add/ or nmha/.



About SPD465



SPD465, a single entity, mixed amphetamine salt formulation designed to provide extended release of medication with symptom control for up to 16 hours, is being studied for the treatment of ADHD in adults. The most common adverse events reported in the phase I study were hypervigilance, decreased appetite, headache, eye irritation, back pain, increased energy and anorexia.



About ADDERALL XR



Tell your doctor about any heart conditions, including structural abnormalities, that you, your child, or a family member, may have. Inform your doctor immediately if you or your child develop symptoms that suggest heart problems, such as chest pain or fainting.



ADDERALL XR should not be taken by patients who have advanced disease of the blood vessels (arteriosclerosis); symptomatic heart disease; moderate to severe high blood pressure; overactive thyroid gland (hyperthyroidism); known allergy or unusual reactions to drugs called sympathomimetic amines (for example, pseudoephedrine); seizures; glaucoma; a history of problems with alcohol or drugs; agitated states; taken a monoamine oxidase inhibitor (MAOI) within the last 14 days.



Tell your doctor before using ADDERALL XR if you or your child are being treated for or have symptoms of depression (sadness, worthlessness, or hopelessness) or bipolar disorder; have abnormal thought or visions, hear abnormal sounds, or have been diagnosed with psychosis; have had seizures or abnormal EEGs; have or have had high blood pressure; exhibit aggressive behavior or hostility. Tell your doctor immediately if any of these conditions or symptoms develop while using ADDERALL XR.



Abuse of amphetamines may lead to dependence. Misuse of amphetamine may cause sudden death and serious cardiovascular adverse events. These events have also been reported rarely with amphetamine use.



ADDERALL XR was generally well tolerated in clinical studies. The most common side effects in studies included: children - decreased appetite, difficulty falling asleep, stomachache, and emotional lability; adolescents - loss of appetite, difficulty falling asleep, stomachache, and weight loss; adults - dry mouth, loss of appetite, difficulty falling asleep, headache, and weight loss. Aggression, new abnormal thoughts/behaviors, mania, growth suppression, worsening of motion or verbal tics and Tourette's syndrome have been associated with use of drugs of this type. Tell your doctor if you or your child have blurred vision while taking ADDERALL XR.



Shire plc


Shire's strategic goal is to become the leading specialty pharmaceutical company that focuses on meeting the needs of the specialist physician. Shire focuses its business on central nervous system, gastrointestinal, general products and human genetic therapies. The structure is sufficiently flexible to allow Shire to target new therapeutic areas to the extent opportunities arise through acquisitions. Shire believes that a carefully selected portfolio of products with a strategically aligned and relatively small-scale sales force will deliver strong results.



Shire's focused strategy is to develop and market products for specialty physicians. Shire's in-licensing, merger and acquisition efforts are focused on products in niche markets with strong intellectual property protection either in the US or Europe.



For further information on Shire, please visit the Company's website: shire/.



"SAFE HARBOR" STATEMENT UNDER THE PRIVATE SECURITIES LITIGATION REFORM ACT OF 1995
Statements included herein that are not historical facts are forwarding-looking statements. Such forward-looking statements involve a number of risks and uncertainties and are subject to change at any time. In the event such risks or uncertainties materialize, Shire's results could be materially affected. The risks and uncertainties include, but are not limited to: risks associated with the inherent uncertainty of pharmaceutical research, product development, manufacturing and commercialization; the impact of competitive products, including, but not limited to, the impact of those on Shire's Attention Deficit and Hyperactivity Disorder (ADHD) franchise; patents, including but not limited to, legal challenges relating to Shire plc's ADHD franchise; government regulation and approval, including but not limited to the expected product approval dates of SPD503 (guanfacine extended release) (ADHD), SPD465, extended release triple-bead mixed amphetamine salts (ADHD), MESAVANCE (mesalamine) with MMX technology (SPD 476) (ulcerative colitis), ELAPRASE (idursulfase) (Hunter Syndrome) and NRP104 (lisdexamfetamine dimesylate) (ADHD), including its scheduling classification by the Drug Enforcement Administration in the United States; Shire's ability to secure new products for commercialization and/or development; and other risks and uncertainties detailed from time to time in Shire's and its predecessor registrant Shire Pharmaceuticals Group plc's filings with the Securities and Exchange Commission, particularly Shire plc's Annual Report on Form 10-K for the year ended December 31, 2005.



Contact: Sherry Goldberg


Porter Novelli




View drug information on Adderall XR; Elaprase.