Company

Ticker Symbol

Product(s)

Alza Corporation, DE, USA

OROS methylphenidate

Eli Lilly’s

LLY

Strattera

Tenex

Guanfacine

Shire Pharmaceuticals

SHPGY

Lisdexamfetamine, SPD465

Wyeth

WYE

Desvenlafaxine

Inclusion Criteria

• <Board-certified or eligible electrophysiologist>
• <In practice between 2 and 30 years>
• <Spends at least 75% of professional time in clinical practice>
• <Performs at least 10 ICD implants per month>

Physician

Location

State

Steve Faraone, PhD

SUNY Upstate

NY

Peter Jensen, MD

Columbia University College of Physicians and Surgeons

NY

Philip Parker, MD

Wayne State University

MI

Fred Reimherr, MD

University of Utah

UT

Victor Reus, MD

University of California San Francisco

CA

Steven Safren, PhD

Massachusetts General Hospital

MA

John Vanin, MD

WVU Health Service

WV

James Waxmonsky, MD

University at Buffalo

NY

Question

Pages

Q1: Experience with adult ADHD

Please describe your experience with ADHD in adults. What has been the trend of the number and types of patients who you have diagnosed with this disorder? Do you think that the number of adult patients identified with this disorder will change in the next five years, and if so, how? What has been the response of patients when they have been given this diagnosis?

5

Click here to review abstract about OROS Methylphenidate

Q2: OROS Methylphenidate

Please see the abstract about OROS methylphenidate in adults. What is your opinion of this study? How does this data affect your clinical practice? How might it affect your choice of medication?

6

Click here to review abstract about atomoxetine

Q3: Atomoxetine

Please review the abstract about atomoxetine. Do you perceive the same benefits in executive function among your patients taking this medication? How do you use this medication relative to other drugs to treat ADHD in adults? Does this data impact how you might use this medication in adult ADHD?

8

Click here to review abstract about guanfacine

Q4: Guanfacine

Please review the attached abstract about the use of an extended release formulation of guanfacine in children. What is your opinion of this type of medication to treat ADHD – please review its strengths and weaknesses. Do you think this medication has a place in the treatment of adults with ADHD? How do you think the use of this medication would affect your current treatment practices if it were approved for adult use?

10

Click here to review abstract about lisdexamfetamine

Q5: Lisdexamfetamine

Please review the abstract about the use of lisdexamfetamine in children. What is your opinion of this type of medication to treat ADHD – please review its strengths and weaknesses? Do you think this medication has a place in the treatment of adults with ADHD? How do you think the use of this medication would affect your current treatment practices if it were approved for adult use?

11

Click here to review abstract about SPD465

Q6: SPD465

Please see the phase III trial results for SPD 465 in the attached abstract. What is your opinion of these results? If this drug were to become available, how would it affect your choice of medications to treat adult ADHD? What concerns might you have about this drug?

12

Click here to review abstract about BP in ADHD patients

Q7: Psychiatric co-morbidities in adult ADHD patients

A few of the conference abstracts discuss ADHD and potentially confounding psychiatric co-morbidities including bipolar disorder, depression and anxiety, eating disorders, personality disorders, and substance abuse. Please review the attached abstract about bipolar disorder and depression in young adults with ADHD. How do these findings compare to your own experience of treating adults with ADHD? Do you believe that older adults with ADHD have a similar prevalence of these co-morbidities?

14

Click here to review abstract about OROS methylphenidate & mood

Q8: OROS methylphenidate and mood disorders

Please review the attached abstract about the use of OROS methylphenidate in adults with ADHD and co-morbid depression or anxiety. Has it been your experience that response to stimulants appears to be independent of a history of anxiety and depression? Have you found that treatment for depression or anxiety does not interfere with the response to stimulant therapy? Do you think of treatment of mood disorders as being part of a holistic response to patients with ADHD? What medications do you use most regularly to treat mood disorders in patients with ADHD?

16

Click here to review abstracts about desvenlafaxine

Q9: Desvenlafaxine

Please review the attached abstracts about desvenlafaxine. What is your overall impression of this medication? What do you think are its strengths and weaknesses? How might you perceive utilizing this medication if it is approved? Given its similar mechanism to atomoxetine, could it possibly be used in the treatment of ADHD?

17

Q10: Most compelling information at APA

What do you expect to be the most compelling information coming out of APA this year? Why do you say this?

18

Introduction

Hello and welcome to MedPanel. We thank you for joining this special discussion among opinion-leading psychiatrists. Our goal in this discussion is to explore some of the data being presented at the APA conference, particularly related to adult ADHD. Along the way, you may be asked to consider certain questions and issues from a variety of perspectives, including those of clinician, researcher, and drug developer. As we begin, please keep in mind that these discussions are enhanced when you, as a panelist, not only respond to the posted questions, but also reply to comments made by our moderator and by your fellow panelists. In addition, because this is a sophisticated gathering, you may wish to take advantage of the opportunity to interact with and pose questions of your peers in this unique online setting. Again, we thank you for your participation and look forward to a lively and spirited discussion. In your participation on this panel, MedPanel expects and requires that you comply with the terms of the Consultant Confidentiality Agreement to which you previously agreed. If you have any questions about the terms of that agreement, please review them through the link provided on your MedPanel home page after you've logged in.

Q1: Experience with adult ADHD

Please describe your experience with ADHD in adults. What has been the trend of the number and types of patients who you have diagnosed with this disorder? Do you think that the number of adult patients identified with this disorder will change in the next five years, and if so, how? What has been the response of patients when they have been given this diagnosis?

Panelist 1: I am a psychologist who conducts CBT both clinically and through research with adults with ADHD. I have seen large numbers of adults with ADHD, though they are usually already diagnosed and on medications before coming to me. Adult ADHD has previously been a controversial diagnosis. Now that it is well-established as a valid, prevalent, interfering, and distressing condition, as education to psychiatrists and the public continues, I expect that more individuals with the disorder will be identified and treated. When adult patients discuss the process of being diagnosed, most are relieved but feel that they wish that this was diagnosed sooner.

Panelist 3: Yes, and I greater variety of patients will be seen as ADHD.

Panelist 3: I think it is very positive and they see it as key to their problems.

Panelist 6: I think there will continue to be an increase in the diagnosis over the next five years as the majority of cases remain undiagnosed. This is still largely a group of patients that comes seeking help so they are generally quite accepting of the diagnosis and treatment. Patients presently for voluntary outpatient ADHD evals tend to be fairly noncomorbid in my experience except for some depression but I mostly deal with professionals and students.

Panelist 7: I am a clinician (psychiatrist)at a very busy student health service. My colleagues and I evaluate and treat dozens of young adults with ADHD weekly. The number of students with mental disorders including adult ADHD has been increasing at our health service. Some of these patients come to the health service with an existing diagnosis of ADHD and treatment and many are recognized, diagnosed and treated for the first time after they are in college. It appears that with better recognition (including screening measures) the number of adults identified with ADHD will increase in the future. Most of our patient are grateful to learn about their disorder and what a difference treatment makes in their academic, work and personal/social life.

Panelist 8: There is no question but that the number of adult ADHD cases has grown over the last several years, and I think it is likely to grow for the next 5 years as well. This is probably due to better screening, and increased recognition on the part of clinicians, but I worry that some individuals are drawn to the diagnosis and diagnosed incorrectly because of their already embracing the category. It is clearly viewed as less stigmatizing than other competing diagnoses.

Panelist 2: I do not see patients clinically but have been researching adult adhd for over a decade. There is clearly an upward trend in identification and that should increase in coming years given that most research shows that the disorder is adults in currently underidentified.

Panelist 5: I am an adult psychiatrist in private practice and a Clinical Assistance Professor of Psychiatry who specializes in treating adults with AD/HD. I am seeing more college aged young adults with AD/HD as well as more middle aged adults (most of whom have been diagnosed and treated as a child). I expect that the number of adults diagnosed with AD/HD will continue to increase at a significant rate in the next five years. Many more adults are returning to treatment after a long absence in order to improve their functioning which has become impaired as an adult. As the diagnosis has become more acceptable in adulthood, more patients are seeing psychiatrists and other mental health professionals. These patients are relieved when they hear their diagnosis and are often eager to accept treatment in order to improve their functioning at work, home, and school.

Panelist 4: I see both children and adults with ADHD, principally in research settings. Because I principally focus on research, I have seen only about 100 adult patients with ADHD. I do think that we are likely to see more patients in the near and distant future with ADHD. Based on statistical extrapolations about what we think of the prevalence of ADHD, I think adults with ADHD are likely underdiagnosed by a factor of 10 or 20 to 1.

Click here to review abstract about OROS Methylphenidate

Q2: OROS Methylphenidate

Please see the abstract about OROS methylphenidate in adults. What is your opinion of this study? How does this data affect your clinical practice? How might it affect your choice of medication?

Panelist 3: I see this as a very positive study and I like the use of the Connors scale.

Panelist 6: It is a fairly standard adult ADHD trial. The effect sizes are low in comparison to the child studies with only the 72mg dose achieving a typical degree of response. Effect sizes tend to be lower in adult studies b/o comorbidity and reliance on self report. It could also be a dose issue- would like to see data on higher doses- at least up to 109mg per day.

Panelist 4: I agree. Higher doses should be studied.

Panelist 7: The study findings appear to correlate with clinical practice. It is nice to see helpful research results on adults with ADHD treated with OROS methylphenidate. Since OROS methylphenidate use in adults is "off label", this type of research helps support it's use in adult patients.

Panelist 8: The effect sizes are small, and it looks like you would have to use 72 mg or higher. Unfortunately the side effects are not analyzed by dose so you don't really know what the tolerability would be with the dose you would most likely use.

Panelist 2: This large well designed trial confirms what other studies have shown, ie., that adult ADHD responds well to methylphenidate. The effect sizes are rather low, even for the highest dose (72mg). Prior studies suggest that higher doses should be used, eg., Spencer et al. find titrating up to about 1mg/kg of methylphenidate produces optimal results. Also notable, the wide age range (18 to 65) shows that adhd can be identified in elderly individuals.

Off-label use of OROS methylphenidate

Are you using OROS methylphenidate “off-label” in your adult patients? Please explain why or why not. If you are, what doses do you generally use in your adult population?

Panelist 8: I am not, for legal reasons. There are other options that carry less risk, if an untoward event were to occur.

Panelist 7: We use OROS Methylphenidate "off label" in our adult patients. It is an excellent option either as a primary or as an alternate stimulant. The doses vary widely but generally 36-72mg/day appears to be most effective. We use the guidelines of medication effect, side effects and weight (1-2mg/kg/day for methylphenidate)as we adjust dosage and this usually works well.

Panelist 6: yes- I will use in adults and will exceed 72mg/kg- tend to push towards 1mg/kg at least for optimal response which can be 108mg

Panelist 5: I have used OROS from the beginning off label with adults. I have used 36 to 90mg or more; I have also prescribed IR methypheniate as an addition either early in AM or in PM to extend the duration of action.

Panelist 2: Note that because Spencer et al.'s work showed that doses of about 1mg/kg of MPH are often needed to treat ADHD effectively, high doses are sometimes needed

Panelist 4: Yes, it is my treatment of choice for adults, all things being equal.

Age range of adult ADHD patients

Panelist 2 noted the age range of patients in the study, which is from age 18 to 65. Please list the percentage breakdown of your adult ADHD patients into the following age categories: 18-29; 30-39; 40-49; 50-59; 60+. How does the presentation and treatment of adult ADHD differ in patients who are 50 years old or older? How do you expect the number of patients with adult ADHD in this age group to change over the next five years?

Panelist 8: All my adult patients have been under 50. I think patients older than that have usually made some accommodation to their deficit and are less likely to seek treatment.

Panelist 6: 70% 18-29 20% 30-39 8%-40's 2% 50's I have a few patients 50+ - mostly attention and organization issues. I am very careful with watching cardiovascular parameters. I think you will see a small gradual rise in the number of adults being treated in this age range for ADHD.

Panelist 5: 18-29 50% 30-39 25% 40-49 20% 50-59 3-5% 60+ 1-3%

Panelist 2: I know of no research that has yet described the presentation of adult ADHD in patients 50 years of age or older. The mean age in our clinic is about 40.

Panelist 4: My adult patients are roughly equally distributed across all age categories, with smaller N's above age 55. I expect we will see more in the older ranges over time, however.

Panelist 7: In our student health service, most of our patients are 18-late 20's. Our adult patients often present with reading difficulty, procrastination, disorganization, restlessness.

Panelist 1: The study looks informative. I do not prescribe, however see patients for therapy who have ADHD and believe in the utility of the OROS system to promote adherence.

Panelist 5: This study is evidence of what we all knew; I have use OROS off label in adults with AD/HD from the beginning. It's about time that the company is finally in the process of getting FDA approval. However, nothing new for me..

Panelist 1: I am not sure of the exact percentages, but I think most are between 25 and 40. We have had a few patients over 50 seeking CBT post medication treatment. I bet that this will grow in future years because recognition of the disorder is increasing.

Panelist 4: This study is quite sensible, and supports the notion that higher doses are often more effective, if side effects don't interfere.

Panelist 4: A sensible, not surprising result, and supports the idea that higher doses are usually more effective, if side effects don't get in the way.

Panelist 3: I also use it for older patients with depression.

Click here to review abstract about atomoxetine

Q3: Atomoxetine

Please review the abstract about atomoxetine. Do you perceive the same benefits in executive function among your patients taking this medication? How do you use this medication relative to other drugs to treat ADHD in adults? Does this data impact how you might use this medication in adult ADHD?

Panelist 6: I think there is value in using a scale to asses impact of treatment on neuropsychological performance. Ideally, would like to know how this scale correlates with real performance at work. I am not aware of stimulant studies in adults with ADHD using this scale so it is hard to compare results to other drugs. At first glance, an 8pt difference on a 50 item scale does not seem overly robust to me but I am not well versed in this scale.

Panelist 2: It is important to note that the Brown scale is not a neuropsychological test. It is a list of behavioral symptoms that Brown believes is associated with executive impairment but the link between his test and exec impairment as measured by testing has not been well validated.

Panelist 4: Excellent points, I agree with the panelist. pj

Panelist 7: We use stimulant medications primarily for our adult ADHD patients. Atomoxetine may help executive function symptoms. The atomoxetine abstract results are encouraging. Stimulants work faster and tend to have a broader effect on the core symptoms of inattention, impulsivity and hyperactivity. A "head-to-head" study regarding executive function using atomoxetine and stimulants might be interesting.

Panelist 8: I use atomoxetine interchangeably with stimulants in adult ADHD. These are interesting data, but I wonder if you might not see similar effects in a normal population. I wonder if this is a unique illness related effect....

Panelist 2: Treating executive dysfunction has been a "holy grail" for treatment studies of ADHD for some time. Current treatments tend to have little or know effect on ED as measure by standard neuropsych tests. The Brown scale is a measure of behavior that he believes reflects ED but this is not well validated. In any case, the drug-placebo differences appear small, which leads to questions about the clinical utility of the findings.

Panelist 1: I do not prescribe medications. However, I would say that this study is significant in that it assessed and documented executive function benefits from atomoxetine.

Panelist 5: In my experience atomoxetine helps to improve executive functioning in adults with AD/HD in a similar fashion. I now generally discuss the use of atomoxetine when talking about first line meds with the patient. However, we generally decide to use it after first considering the stimulants. It tends to be used mainly only after and when the stimulants are either not tolerated, not effective, or just not wanted at all. It certainly is useful for AD/HD with comorbid anxiety. The data will probably not change this usage pattern.

Panelist 3: I do not find the dependent variable in this study to be specific enough in actually demonstrating changes in ability too deal with complex real world situations and problems. Such an effect would be very impressive, but I am not convinced by this study.

Panelist 4: I agree. Does the medication change how someone functions in daily life, is the gold standard.

Atomoxetine and stimulants

In the discussion, it seems that patients are prescribed either stimulants or atomoxetine. Are there any circumstances under which you will prescribe atomoxetine in combination with stimulants?

Panelist 6: yes, either for cases where monotherapy is not effective or will add strattera to reduce the stimulant dose for improved tolerability, especially in the evening. With younger kids, may add strattera and reduce stim dose for better weight gain if strattera alone is not effective enough.

Panelist 8: no

Panelist 4: Yes, if someone has gotten only partial benefit with one or the other, and no single medication "does the trick."

Panelist 2: There are no data to support combined therapy with atomoxetine and stimulants. I recall an unpublished talk at AACAP suggesting that MPH augmentation of ATOX was not effective. All monotherapy options should be pursued before such an approach is considered, if at all.

Panelist 5: Yes. If a given stimulant works well but has anxiety as a side effect, we have sometimes added atomoxetine to successfully alleviate the anxiety while adding to the anti-AD/HD effect.

Panelist 7: Yes, but not often. May be helpful in some cases with anxiety.

Panelist 4: Yes, I do see these benefits, but I tend to use ATX after I have tried the stimulants, or in the event of side effects, BP, or other cardiovascular risk factors.

Click here to review abstract about guanfacine

Panelist 3: I would be particularly concerned with documentation of cognitive effects both by scales and actual testing.

Panelist 7: There is a need for effective, well-tolerated medicines in various classes. This study shows a well-tolerated medicine for children with a good effect size. Sedation maybe a concern. Also, persons with greater weight (adolescents) showed less significant results. Further studies in adults would be warranted to determine efficacy and side effects.

Q4: Guanfacine

Please review the attached abstract about the use of an extended release formulation of guanfacine in children. What is your opinion of this type of medication to treat ADHD – please review its strengths and weaknesses. Do you think this medication has a place in the treatment of adults with ADHD? How do you think the use of this medication would affect your current treatment practices if it were approved for adult use?

Panelist 6: I think there is still a need and a market for nonstimulant meds in ADHD, for children and adults. The alpha agonists are intriguing because of the animal data showing neuropsych benefits. The effect sizes seem large for a between group study, especially in light of the fact that adolescents failed to respond as a group. Results for children are encouraging. I would be concerned about the sedation as that is a problem with clonidine and would like more data on the severity of the sedation per dose level.

Panelist 8: I concur with panelist 6's thoughts re this. I'm not sure it would be as good in adults.

Panelist 2: I agree with Panelist 6 and also note that the low effect for adolescents may be because weight based dosing is needed. If so, the doses for adolescents were too low in this study.

Panelist 2: This large, well designed trial finds strong evidence for the efficacy of guanfacine in children. One would expect these results to generalize to adults although an adult trial is needed to be certain. The effect sizes at the highest mg/kg doses were very high, as good or better than stimulants. If this finding generalizes to adults, guanfacine will be an important addition to the clinical treatment of adults. Its effect size would be much higher than atomoxetine and it would not have the potential for abuse that plagues the stimulants.

Off-label use of guanfacine

Are there any circumstances under which you might be inclined to use guanfacine now in an “off-label” manner in adults? What factors would go into your decision about this?

Panelist 8: Not until I see more data re efficacy in this population. One needs to have a better data base for evidence based practice.

Panelist 7: Not at this time. Would like more data.

Panelist 5: See my response the original guanfacine question.

Panelist 6: I really don't use this drug much at all in adults. Will use bupropion, atomoextine or even TCA's if I need a late day treatment effect.

Panelist 2: We really need more data on this. Guanfacine as currently formulated has not been an impressive drug. Shire's new formulation has performed impressively in children but we need adult data before it would be sensible to use it as a first or second line choice.

Panelist 4: After failed trials of stims and ATX, and possibly tricyclics, would I turn to guanfacine, until more data are available.