How Ritalin Works In Brain To Boost Cognition, Focus Attention
medications such as Ritalin have been prescribed for decades to treat attention deficit hyperactivity disorder (ADHD), and their popularity as "cognition enhancers" has recently surged among the healthy, as well.
What's now starting to catch up is knowledge of what these drugs actually do in the brain. In a paper publishing
online this week in Biological Psychiatry, University of Wisconsin-Madison psychology researchers David Devilbiss and
Craig Berridge report that Ritalin fine-tunes the functioning of neurons in the prefrontal cortex (PFC) - a brain region involved
in attention, decision-making and impulse control - while having few effects outside it.
of the potential for addiction and abuse, controversy has swirled for years around the use of stimulants to treat ADHD, especially
in children. By helping pinpoint Ritalin's action in the brain, the study should give drug developers a better road map to
follow as they search for safer alternatives.
At the same time, the results support
the idea that today's ADHD drugs may be safer than people think, says Berridge. Mounting behavioral and neurochemical evidence
suggests that clinically relevant doses of Ritalin primarily target the PFC, without affecting brain centers linked to over-arousal
and addiction. In other words, Ritalin at low doses doesn't appear to act like a stimulant at all.
"It's the higher doses of these drugs that are normally associated with their effects as stimulants, those that
increase locomotor activity, impair cognition and target neurotransmitters all over the brain," says Berridge. "These lower
doses are diametrically opposed to that. Instead, they help the PFC better do what it's supposed to do."
A behavioral disorder marked by hyperactivity, impulsivity and the inability to concentrate, ADHD has been treated
for more than a half-century with Ritalin, Adderall and other stimulant drugs. New reports also indicate these meds
have lately been embraced by healthy Americans of all ages as a means to boost mental performance.
Yet, despite their prevalence, we know remarkably little about how these drugs work, especially at lower doses
that have been proven clinically to calm behavior and focus attention in ADHD patients, says Berridge. In 2006, his team reported
that therapeutic doses of Ritalin boosted neurotransmitter levels primarily in the PFC, suggesting a selective targeting of
this region of the brain. Since then, he and Devilbiss have focused on how Ritalin acts on PFC neurons to enhance cognition.
To answer this, the pair studied PFC neurons in rats under a variety of Ritalin
doses, including one that improved the animals' performance in a working memory task of the type that ADHD patients have trouble
completing. Using a sophisticated new system for monitoring many neurons at once through a set of microelectrodes, the scientists
observed both the random, spontaneous firings of PFC neurons and their response to stimulation of an important pathway into
the PFC, the hippocampus.
Much like tiny microphones, the electrodes record a pop
every time a neuron fires, Devilbiss explains. Analyzing the complex patterns of "voices" that emerge is challenging but also
powerful, because it allows study of neurons on many levels.
"Similar to listening
to a choir, you can understand the music by listening to individual voices," says Devilbiss, "or you can listen to the interplay
between the voices of the ensemble and how the different voices combine."
listened to individual PFC neurons, the scientists found that while cognition-enhancing doses of Ritalin had little effect
on spontaneous activity, the neurons' sensitivity to signals coming from the hippocampus increased dramatically. Under higher,
stimulatory doses, on the other hand, PFC neurons stopped responding to incoming information.
"This suggests that the therapeutic effects of Ritalin likely stem from this fine-tuning of PFC sensitivity,"
says Berridge. "You're improving the ability of these neurons to respond to behaviorally relevant signals, and that translates
into better cognition, attention and working memory." Higher doses associated with drug abuse and cognitive impairment, in
contrast, impair functioning of the PFC.
More intriguing still were the results
that came from tuning into the entire chorus of neurons at once. When groups of neurons were already "singing" together strongly,
Ritalin reinforced this coordinated activity. At the same time, the drug weakened activity that wasn't well coordinated to
begin with. All of this suggests that Ritalin strengthens dominant and important signals within the PFC, while lessening weaker
signals that may act as distractors, says Berridge.
"These results show a new level
of action for cognition-enhancing doses of Ritalin that couldn't have been predicted from single neuron analyses," he says.
"So, if you're searching for drugs that might replace Ritalin, this is one effect you could potentially look for."
He and Devilbiss also hope the research will help unravel an even deeper mystery: exactly how
neurons encode complex behavior and cognition.
"Most studies look at how something
that impairs cognition affects PFC neurons. But to really understand how neurons encode cognitive function, you want to see
what neurons do when cognition is improved," says Berridge. "So this work sets the stage for examining the interplay among
PFC neurons, higher cognition, and the action of therapeutic drugs."
by Medical News Today from original press release.
The work was funded by the
National Institute on Drug Abuse, the National Institute of Mental Health and the UW-Madison Discovery Seed Grant Program.
Source: David Devilbiss
University of Wisconsin-Madison
ADHD is the most common emotional, cognitive and behavioral
disorder treated in children1, and according to the National Institute of Mental Health (NIMH), between 30 percent and 70
percent of children with ADHD continue to exhibit symptoms in the adult years 2. ADHD is thought to affect about eight million,
or one in 20, adults in the United States3, and research on the life span of the condition notes the disorder impairs academic,
social and occupational functioning1, and is associated with academic underachievement, conduct problems, underemployment,
motor vehicle safety and difficulties with personal relationships1.
Today, there's a new treatment option for the
millions of adults in the United States with ADHD: Johnson & Johnson Pharmaceutical Research & Development L.L.C.
(J&JPRD) announced the U.S. Food and Drug Administration (FDA) approved J&JPRD's Supplemental New Drug Application
(sNDA) for CONCERTA® treatment of ADHD in adults ages 18-65. The doses approved for
adults range from 18 to 72 mg daily.
Today's approval expands the CONCERTA® indication from children and adolescents
into adults with ADHD, and offers these patients a patented once-daily formulation. Using its unique OROS® delivery system,
the CONCERTA® formulation delivers an initial dose of medication when the tablet is ingested. Medication is then delivered
into the bloodstream at a controlled rate throughout the day.
The CONCERTA® brand, which was the first 12-hour extended-release
methylphenidate (MPH) treatment for ADHD, is the market leader for MPH treatment of children and adolescents with ADHD. CONCERTA®
is marketed in the United States by McNeil Pediatrics™, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc.
we've seen in the growing body of knowledge on adult ADHD suggests a challenging burden of impairment in everyday functioning,"
said Janet Vergis, President of McNeil Pediatrics™. "Recognizing this need - and as the market leader in extended-release
MPH for children and adolescents - we see today's approval as a treatment option milestone for adults with ADHD and their
healthcare professionals. We are proud to offer patients ages 6 to 65 with ADHD our CONCERTA® product knowledge based on more
than seven years of clinical experience."
Researchers examining ADHD across the lifespan have noted the condition
is often chronic, with prominent symptoms and impairment spanning into adulthood, and is often associated with co-occurring
anxiety, mood and disruptive disorders as well as substance abuse3. According to the NIMH, ADHD is thought to be a biological
condition, usually inherited, and tends to run in some families more than others. Often when a child is diagnosed with the
disorder, a parent will recognize that he or she had many of the same symptoms, and for the first time, will begin to understand
some of the traits that have troubled them for years4. All aspects of an individual's life must be considered in the diagnosis
and treatment of ADHD3.
Today's FDA approval was based on clinical trial data in adults ages 18 to 65. In these studies,
use of CONCERTA® was shown to significantly improve ADHD symptoms such as attention, impulsivity and hyperactivity compared
to placebo, and the medication was shown to be generally well tolerated.
approved for the treatment of attention deficit hyperactivity disorder (ADHD) as part of a total treatment program that may
include counseling or other therapies.
IMPORTANT SAFETY INFORMATION
Talk to your healthcare professional for
a proper diagnosis and treatment of ADHD. Only a healthcare professional can decide whether medication is right for you or
CONCERTA® should not be taken by patients who have: allergies to methylphenidate or other ingredients
in CONCERTA®; significant anxiety, tension, or agitation; glaucoma; tics, Tourette's syndrome, or family history of Tourette's
syndrome; current or past use of monoamine oxidase inhibitor (MAOI); esophagus, stomach, or intestinal narrowing. Children
under six years of age should not take CONCERTA®.
Abuse of methylphenidate may lead to dependence. Tell your healthcare
professional if you or your child has had problems with alcohol or drugs; has had any heart problems, heart defects, high
blood pressure, or a family history of these problems; has had depression, abnormal thoughts or visions, bipolar disorder,
or seizure. Contact your healthcare professional immediately if you or your child: develops abnormal thinking or hallucinations,
abnormal or extreme moods and/or excessive activity; or if aggressive behavior or hostility develops or worsens while taking
Stimulants may impair the ability of the patient to operate potentially hazardous machinery or vehicles.
Caution should be used accordingly until you are reasonably certain that CONCERTA® does not adversely affect your ability
to engage in such activities.
The most common adverse reaction (> 5%) reported in children and adolescents was
upper abdominal pain. The most common adverse reactions (>10%) reported in adults were dry mouth, nausea, decreased appetite,
headache, and insomnia. Visit www.concerta.net/concerta/pages/full.jsp for full prescribing information.
About McNeil Pediatrics
Pediatrics™, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc., is committed to meeting the needs of pediatric
medicine through the development of therapies specifically formulated for children. McNeil Pediatrics markets CONCERTA® for
the treatment of children, adolescents and adults with ADHD in the United States. McNeil Pediatrics continues to explore other
new therapies to meet the needs of children and the pediatric community. Visit www.mcneilpediatrics.net for more information.
& Johnson Pharmaceutical Research & Development L.L.C. (J&JPRD) is part of Johnson & Johnson, the world's
most broadly based producer of healthcare products. J&JPRD is headquartered in Raritan, N.J., and has facilities throughout
Asia, Europe and the United States. J&JPRD is leveraging drug discovery and drug development in a variety of therapeutic
areas to address unmet medical needs worldwide. www.jnjpharmarnd.com
1. Wilens, T.E., Dodson, W. A
Clinical Perspective of Attention-Deficit Hyperactivity Disorder into Adulthood. Journal of Clinical Psychology 65:10. October
2. National Institute of Mental Health. "ADHD in Adults." Available at http://www.nimh.nih.gov/health/topics/attention-deficit-hyperactivity-disorder-adhd/index.shtml.
Accessed June 19, 2008.
3. Wilens, T.E., Biederman J., Spencer T.J. Attention Deficit/Hyperactivity Disorder Across the
Lifespan. Annual Review of Medicine, Vol. 53. 2002.
4. National Institute of Mental Health. "Genetics." Available at http://www.nimh.nih.gov/health/publications/adhd/attention-deficit-hyperactivity-disorder-in-adults.shtml.
Accessed June 19, 2008.
Benefits Of Antidepressants Out-Weigh Risks In Treating Pediatric Depression, Anxiety Disorders
According to a new study, conducted by the Center for Innovation
in Pediatric Practice (CIPP) at Columbus Children's Hospital and published in the April 18 issue of The Journal of the
American Medical Association (JAMA), there is more information for parents about the risks and benefits of antidepressant
treatment for children with depression and anxiety disorders.
The Children's Hospital study found the overall benefits
of antidepressants in treating pediatric major depressive disorder (MDD), obsessive-compulsive disorder (OCD) and non-OCD
anxiety disorders (ANX) in children 19-years-old and younger appear to out-weigh the risks of suicidal thoughts and attempts
associated with these medications.
"Although our findings regarding suicidal thoughts and attempts are in the same
direction as the Food and Drug Administration (FDA) meta-analysis, we found a much lower overall risk and we added analyses
of the potential benefit of these medications," said lead author Jeff Bridge, PhD, CIPP principal investigator and assistant
professor of pediatrics at The Ohio State University College of Medicine. "This is good news for parents because it gives
them more information for discussions with their family's physician about their child's treatment options."
found that for every 100 children and adolescents younger than 19 years who were treated with antidepressants for MDD, OCD
and ANX, about one child would have thoughts of suicide or attempt suicide beyond the risk associated with the condition itself.
The FDA study, which included seven fewer trials, found that for every 100 patients, approximately two would be expected to
have suicidal thoughts or attempt suicide beyond the anticipated risks due to short-term treatment with antidepressants.
findings mean that antidepressants should be considered as a first-line treatment option for pediatric depression and anxiety
disorders, with the recognition that these medications are more effective for anxiety disorders, including OCD and modestly
effective for MDD," said Bridge.
Bridge said the study also looked at whether the effectiveness of antidepressants
was influenced by age. The only antidepressant effective in treating depression in children younger than 12 years was fluoxetine
(PROZAC). In children 12 years or older, several antidepressants were
effective in treating depression.
Data for the study were collected from a meta-analysis of published and unpublished
randomized, controlled and clinical trial reports looking at both the benefits and risks of antidepressants in treating children
and adolescents younger than 19 years for MDD, OCD and ANX.
"We recognize that there are other therapies, aside from
antidepressants, to treat pediatric depression and anxiety disorders including psychotherapies," said Bridge. "While there
is a small overall increased risk of suicidal thoughts and attempts with antidepressants, the risk-benefit ratio appears favorable."
study collaborators are currently with the University of Pittsburgh, Columbia University, the RAND Corporation and the University
Hospital of Geneva, Switzerland.
Columbus Children's Hospital
No Data Supporting Antipsychotic Drug For Low-IQ Kids With ADHD
Article Date: 29 Apr 2009 - 2:00 PDT
A new Cochrane review finds no evidence to support the use of
risperidone to treat attention- deficit/hyperactivity disorder (ADHD) in people with intellectual disabilities, even though
the review authors say this is a common prescribing pattern.........
Risperidone, or Risperdal, is a second-generation antipsychotic
drug. Long-term use of these drugs is associated with serious side effects, including weight gain and increased risk for type
"People who have intellectual disability are more likely to
receive treatment with second- generation antipsychotics for ADHD," said lead review author Dr. Alex Thomson. "Doctors should
be aware that there is no research to demonstrate the effectiveness of risperidone for ADHD in people with intellectual disability,
and should carefully monitor each case and consider alternative treatments before trying risperidone."....
AS with most conventional medicine more sales and belief
than science. The question arises are MD's the real quacks?
source site: click here