- Email: [email protected]
Subjective responses to LY139603 (atomoxetine) and methylphenidate
S318
p4. Degenerative and neurological disorders
Twenty-five patients had stopped taking donepezil. Forty were lost to follow-up and 17 had died. A logistical regression analysis using baseline predictors as covariates indicated that only the initial Mini-Mental State Exam scores were a significant predictor (‘p < 0.03). Higher baseline scores predicted continued donepezil treatment. Patient age, age at symptom onset, gender, and years of education were not useful predictors. Conclusion: About l/4* of our California AD patients stopped taking donepezil before our one year follow-up. In another routine clinical practice follow-up study in Leeds, England, 38 out of 113 AD patients (34%) prescribed donepezil at initial assessment stopped donepezil treatment before or at their 3 month visit (1). In the California sample, patients who had lower initial Mini-mental State Exam scores were more likely to stop medication.
the ARCI, were all greater for methylphenidate 40 mg than those measured after placebo. Scores for atomoxetine were not different from placebo for any of these measures (stimulant subscales). Scores for non-pleasurable subscales of the VAS and ARC1 were significantly higher with atomoxetine 90 mg than with placebo. Conclusions: The profile associated with atomoxetine differed from that typically observed with stimulants, and significant scores on non-pleasurable sub-scales suggest atomoxetine is unlikely to have significant abuse liability. References
VI American Psychiatric Association. (1994) Diagnostic and Statistical Manual of Mental Disorders: DSM It: Fourth Edition. 4th ed. Washington, DC: American Psychiatric Association.
PI Biederman J, Spencer TJ. (1999) Attention-deficitiweractivitv &&4DHD)
References [l] Cameron, I., Curran, S., Newton, F!, Petty, D., Wattis, .I., 2000. Use of Donepezil for the treatment of mild-moderate Alzheimer’s disease:
An audit of the assessment and treatment of patients in routine clinical practice, Int J Geriatr Psych, 15, 887-891.
asa noradrenekgic disorder. Biol Psych&y
disor46 (91 1234-
t31 Murphy K, Barkby RA. (1996) Prevalence of DSM-IV symptoms of ADHD in adult licensed drivers: Implications Attention Disord 1 (3), 147-161.
for clinical diagnosis. J
IP.4.006( Atomoxetine and methylphenidate treatment Jp.4.005)
Subjective responses to LY139603 (atomoxetine) and methylphenidate
H.F. Laws’, S.H. Heil*, W.K. Bickel*, ST. Higgins*, D.E. Faries’, G. Badge?. ‘Eli Lilly and Company, Indianapolis, IN; ‘University of Vermont, Burlington, m, USA
Statement of Purpose: The onset of Attention-DeficitHyperactivity Disorder (ADHD) occurs early in childhood that affects 3% to 5% of school age children (1). Its pathophysiology appears to involve alterations in dopaminergic and noradrenergic pathways associated with control of attention and impulsivity (2) resulting in impairment of academic and social functioning. The extent of the burden associated with this disorder is compounded, as ADHD is also associated with familial and social dysfunction (3). Symptoms of this disorder have been shown to respond favorably to several pharmacological interventions, most notably stimulants such as methylphenidate and d-amphetamine. However, some patients fail to respond to stimulants or are unable to tolerate them. Additionally, many parents, caregivers, and physicians are concerned by the fact that these medications are considered controlled substances. For all of these reasons, there has been considerable interest in developing new treatments for ADHD. LY 139603 (atomoxetine, formerly known as tomoxetine) is an investigational non-stimulant compound being studied in children with ADHD. Atomoxetine enhances noradrenergic function through highly selective blockade of the pre-synaptic norepinephrine transporter. Atomoxetine has low afIinities for other neuronal transporters and for norepinephrine, dopamine and serotonin receptor sites. This mechanism of action is expected to have a different profile from that of the stimulants with respect to patient perception of drug effects. Methods: Subjects were healthy volunteers who had used recreational drugs previously. Each condition atomoxetine 20 mg, 45 mg, and 90 mg; methylphenidate 20 mg, and 40 mg; and placebo) was assessed on a separate day using a 7-item visual analog scale (VAS), the Addiction Research Center Inventory (ARCI) short form, and Adjective Rating Scale (ARS) questionnaires in an order-randomized, double-blind crossover study design. Results: Mean scores on the stimulant sub-scales of the VAS and ARCI, as well as the amphetamine and euphoria sub-scales of
in children with ADHD: A prospective, randomized, open-label trial R.W. Dittmann' , D.S. Fouche’, C. Kratochvi13, J.H. Heiligenstein4, T. SpenceI.5, J. Biedern&. ‘Eli Lilly and Company, Germany; ‘Eli Lilly and Company-Erl Wood, Surrey, UK; ‘University of Nebmsk-a Medical Center; Omaha, NE; 4Eli Lilly and Company, Indianapolis, IN; ‘Massachusetts General Hospital, Boston, MA, USA
Statement of Purpose: Attention-Deficit/Hyperactivity Disorder (ADHD) is a common disorder of childhood that affects 3% to 5% of school age children in the United States (1). The pathophysiology is not well understood, however it appears to involve alterations in dopaminergic and noradrenergic pathways associated with attention and control of impulsivity (2) resulting in impairment of academic and social functioning. Supportive of the above hypothesis is that ADHD symptoms have shown a favorable response to pharmacological interventions, in particular stimulants such as methylphenidate and d-amphetamine. However, some patients fail to respond to stimulants or are unable to tolerate them. Additionally, many parents, caregivers, and physicians are concerned with using stimulants due to their status as controlled substances. The underlying reason for DEA control is the fear for potential abuse. Additionally, there is also a concern of the potential impact of long-term use of stimulants on development. For these reasons, there has been considerable interest in developing new treatments for ADHD. The purpose of this study was to assess the comparability of atomoxetine, an investigational, nonstimulant therapy for ADHD and methylphenidate. Methods: Children with ADHD were randomized under openlabel conditions to either atomoxetine or methylphenidate therapy for an approximately lo-week period. Gutcomes were assessed using the Attention-Deficit/Hyperactivity Disorder Rating Scale-IVParent Version:Investigator Administered and Scored (ADHDRSIV-Parem:Inv). Results: A total of 228 patients were randomized to treatment (atomoxetine N = 184, methylphenidate N = 44). Both drugs were associated with marked improvement in inattentive and hyperactive/impulsive symptom clusters, and thus there were no statistically significant differences between treatment groups on
p4. Degenerative and neurological disorders
Twenty-five patients had stopped taking donepezil. Forty were lost to follow-up and 17 had died. A logistical regression analysis using baseline predictors as covariates indicated that only the initial Mini-Mental State Exam scores were a significant predictor (‘p < 0.03). Higher baseline scores predicted continued donepezil treatment. Patient age, age at symptom onset, gender, and years of education were not useful predictors. Conclusion: About l/4* of our California AD patients stopped taking donepezil before our one year follow-up. In another routine clinical practice follow-up study in Leeds, England, 38 out of 113 AD patients (34%) prescribed donepezil at initial assessment stopped donepezil treatment before or at their 3 month visit (1). In the California sample, patients who had lower initial Mini-mental State Exam scores were more likely to stop medication.
the ARCI, were all greater for methylphenidate 40 mg than those measured after placebo. Scores for atomoxetine were not different from placebo for any of these measures (stimulant subscales). Scores for non-pleasurable subscales of the VAS and ARC1 were significantly higher with atomoxetine 90 mg than with placebo. Conclusions: The profile associated with atomoxetine differed from that typically observed with stimulants, and significant scores on non-pleasurable sub-scales suggest atomoxetine is unlikely to have significant abuse liability. References
VI American Psychiatric Association. (1994) Diagnostic and Statistical Manual of Mental Disorders: DSM It: Fourth Edition. 4th ed. Washington, DC: American Psychiatric Association.
PI Biederman J, Spencer TJ. (1999) Attention-deficitiweractivitv &&4DHD)
References [l] Cameron, I., Curran, S., Newton, F!, Petty, D., Wattis, .I., 2000. Use of Donepezil for the treatment of mild-moderate Alzheimer’s disease:
An audit of the assessment and treatment of patients in routine clinical practice, Int J Geriatr Psych, 15, 887-891.
asa noradrenekgic disorder. Biol Psych&y
disor46 (91 1234-
t31 Murphy K, Barkby RA. (1996) Prevalence of DSM-IV symptoms of ADHD in adult licensed drivers: Implications Attention Disord 1 (3), 147-161.
for clinical diagnosis. J
IP.4.006( Atomoxetine and methylphenidate treatment Jp.4.005)
Subjective responses to LY139603 (atomoxetine) and methylphenidate
H.F. Laws’, S.H. Heil*, W.K. Bickel*, ST. Higgins*, D.E. Faries’, G. Badge?. ‘Eli Lilly and Company, Indianapolis, IN; ‘University of Vermont, Burlington, m, USA
Statement of Purpose: The onset of Attention-DeficitHyperactivity Disorder (ADHD) occurs early in childhood that affects 3% to 5% of school age children (1). Its pathophysiology appears to involve alterations in dopaminergic and noradrenergic pathways associated with control of attention and impulsivity (2) resulting in impairment of academic and social functioning. The extent of the burden associated with this disorder is compounded, as ADHD is also associated with familial and social dysfunction (3). Symptoms of this disorder have been shown to respond favorably to several pharmacological interventions, most notably stimulants such as methylphenidate and d-amphetamine. However, some patients fail to respond to stimulants or are unable to tolerate them. Additionally, many parents, caregivers, and physicians are concerned by the fact that these medications are considered controlled substances. For all of these reasons, there has been considerable interest in developing new treatments for ADHD. LY 139603 (atomoxetine, formerly known as tomoxetine) is an investigational non-stimulant compound being studied in children with ADHD. Atomoxetine enhances noradrenergic function through highly selective blockade of the pre-synaptic norepinephrine transporter. Atomoxetine has low afIinities for other neuronal transporters and for norepinephrine, dopamine and serotonin receptor sites. This mechanism of action is expected to have a different profile from that of the stimulants with respect to patient perception of drug effects. Methods: Subjects were healthy volunteers who had used recreational drugs previously. Each condition atomoxetine 20 mg, 45 mg, and 90 mg; methylphenidate 20 mg, and 40 mg; and placebo) was assessed on a separate day using a 7-item visual analog scale (VAS), the Addiction Research Center Inventory (ARCI) short form, and Adjective Rating Scale (ARS) questionnaires in an order-randomized, double-blind crossover study design. Results: Mean scores on the stimulant sub-scales of the VAS and ARCI, as well as the amphetamine and euphoria sub-scales of
in children with ADHD: A prospective, randomized, open-label trial R.W. Dittmann' , D.S. Fouche’, C. Kratochvi13, J.H. Heiligenstein4, T. SpenceI.5, J. Biedern&. ‘Eli Lilly and Company, Germany; ‘Eli Lilly and Company-Erl Wood, Surrey, UK; ‘University of Nebmsk-a Medical Center; Omaha, NE; 4Eli Lilly and Company, Indianapolis, IN; ‘Massachusetts General Hospital, Boston, MA, USA
Statement of Purpose: Attention-Deficit/Hyperactivity Disorder (ADHD) is a common disorder of childhood that affects 3% to 5% of school age children in the United States (1). The pathophysiology is not well understood, however it appears to involve alterations in dopaminergic and noradrenergic pathways associated with attention and control of impulsivity (2) resulting in impairment of academic and social functioning. Supportive of the above hypothesis is that ADHD symptoms have shown a favorable response to pharmacological interventions, in particular stimulants such as methylphenidate and d-amphetamine. However, some patients fail to respond to stimulants or are unable to tolerate them. Additionally, many parents, caregivers, and physicians are concerned with using stimulants due to their status as controlled substances. The underlying reason for DEA control is the fear for potential abuse. Additionally, there is also a concern of the potential impact of long-term use of stimulants on development. For these reasons, there has been considerable interest in developing new treatments for ADHD. The purpose of this study was to assess the comparability of atomoxetine, an investigational, nonstimulant therapy for ADHD and methylphenidate. Methods: Children with ADHD were randomized under openlabel conditions to either atomoxetine or methylphenidate therapy for an approximately lo-week period. Gutcomes were assessed using the Attention-Deficit/Hyperactivity Disorder Rating Scale-IVParent Version:Investigator Administered and Scored (ADHDRSIV-Parem:Inv). Results: A total of 228 patients were randomized to treatment (atomoxetine N = 184, methylphenidate N = 44). Both drugs were associated with marked improvement in inattentive and hyperactive/impulsive symptom clusters, and thus there were no statistically significant differences between treatment groups on