|
Psychopharmacology Alert readers: You have permission to
forward Psychopharmacology Alert, in its entirety only, to your colleagues,
provided this copyright notice remains as part of your message. They are also
welcome to visit http://www.manisses.com.
They should then click on Online Services, and from there click on the
"sign up for our mailing list" icon to subscribe directly. All other
rights reserved. For further information, contact Karienne Stovell at mailto:kstovell@manisses.com
, or call (800) 333-7771.
--------------- PSYCHOPHARMACOLOGY ALERT
---------------
The latest news and research from the editors of Manisses'
psychopharmacology publications.
December 5, 2002
In this issue: Editor's Note, Question of the Week, Clinical Updates: Special
focus on atomoxetine, Industry News and Featured Resource
-----------------------------------------------
EDITOR'S NOTE
-----------------------------------------------
We had some rather lengthy, but interesting responses to the last question of
the week - Do you advocate for the use of ECT in the geriatric population? Have
you utilized it in your patients? If so, what were the benefits and drawbacks? -
so I thought I'd dedicate my editor's note this week to airing your opinions on
a fairly contentious topic. I'd love to hear from more of you on this issue and
on this week's question regarding a proposal for restructuring the FDA.
Karienne Stovell
Senior Managing Editor
mailto:kstovell@manisses.com
One reader wrote:
"Although this was in the early '90s, I assisted with a number of patients
who were elderly and were treated with ECT for depression. The most common
rationale was a prior successful treatment with ECT for depression and/or a
known lack of responsiveness/sensitivity to the usual medications. Clinically,
the depressive symptoms tended to include lack of focus, mild memory problems,
rather chronic/intermittent history of prior depressive episodes, lessened
social interest and/or irritability with family. Sleep and appetite were not
markedly changed. Patients treated tended to be clear of any psychotic features
or significant bipolar patterns.
It was interesting (given their age and earlier pattern of depressive history)
that although TCA trials were not helpful; neither were trials with various
SSRIs. Not uncommonly there was a sensitivity to the anticholinergic side
effects of TCA - which limited an adequate dose/trial. But as I remember, when
the SSRIs were tried at adequate dosage, they did not seem effective.
Other significant past medical history or concurrent medical problems tended to
be minimal. The general level of function, despite the depressive history, was
usually pretty good. There did not seem to be significant history of any mild
dementia processes; and while perhaps not able to track/plan as well when
depressed, this seemed to be from moderate dysphoria...
The response to ECT seemed to be moderate to quite good. The most notable area
of improvement (in my eyes) tended to be in the overall return of interest in
the usual social and inter-personal tasks. Their ability to plan and carry out
tasks improved quite a lot; the level of spontaneous affect seemed good. The
patients' awareness of the treatment success was usually not as marked as the
relief of significant others/family. Perhaps a sign of the positive effects of
the ECT, the patients immediately began to do the usual behaviors of someone
eager to get out of the unit and back to the outside world!
More often than not, either low dose TCAs or some form of SSRI was begun and
adjusted prior to discharge. The general belief of the Attendings was that the
medications might be useful in preventing relapse down the road." [Jim]
Another reader whose mother has received ECT treatment wrote:
"I'm writing [regarding] your interest in ECT for the older patient. My mom
is now almost 93, and has ECT on an outpatient basis every 3 weeks. I can truly
say it has been most therapeutic for her - the anesthesia is managed very
carefully and her only complaint is having a headache later in the day. She can
readily 'sleep off' the headache with a nap and mild over-the-counter
medication.
Prior to ECT, the range and variety of tried medications was extensive, as my
mother is hypersensitive to meds and would become so anxious that achieving any
kind of good therapeutic dose was a challenge, and often impossible. For a
number of years, lithium was the medication of choice. However, with
intermittent bouts of refusal to eat/drink, lithium became less and less
helpful; since nutrition supports the absorption of the 'salts' comprising
lithium, we were sometimes facing many side effects. With ECT, we no longer deal
with lithium toxicity in the event of interruptions in the blood levels.
She has now had ECT for the past several years, and can continue indefinitely.
Her physicians are at a local hospital that is affiliated with a university
medical school in Boston." [Carol Cook]
-----------------------------------------------
QUESTION OF THE WEEK
-----------------------------------------------
Henry I. Miller recently wrote an opinion piece in Nature, calling for wholesale
reform of the FDA. Miller recommends decentralizing the approval process by
allowing newly formed Drug Certifying Bodies (DCBs) to oversee much of the
regulatory process, leaving the FDA to act more as a certifier of the DCBs,
retaining certain overarching powers to audit and monitor the whole process.
Read Miller's very thought-provoking article and let me know what you think - http://www.nature.com/reviews/drugdisc
(search for "A proposal for FDA reform" in the August 2002 issue; the
abstract is free or pay to read the full article). It's worth the time, as
Miller brings up some very salient points regarding the length and cost of the
approval process and its direct effect on patient care.
Send responses to mailto:kstovell@manisses.com
-----------------------------------------------
CLINICAL UPDATES: Special focus on atomoxetine
-----------------------------------------------
Forest Laboratories recently announced FDA approval of its selective
norepinephrine reuptake inhibitor atomoxetine (Strattera) for the treatment of
ADHD in children, adolescents and adults. The safety and efficacy of atomoxetine,
a nonpsychostimulant, is presumed to work by blocking a neurotransmitter that
plays an important role in modulating the brain systems that control attention
and activity. We've summarized some of the research from the past year on this
newly approved medication.
RESULTS FROM SOME EARLIER STUDIES
Two 2001 studies demonstrated promising results for atomoxetine.
Originally called tomoxetine, the drug's name was changed to atomoxetine in
order to avoid any potential confusion with tamoxifen that might lead to
dispensing errors. The safety of atomoxetine has been demonstrated in short- and
longer-term exposures in more than 1,000 adult patients.
The need for alternative and effective nonstimulant pharmacological treatment
options is evident, as an estimated 30 percent of children, adolescents and
adults with the disorder do not respond, or cannot tolerate, treatment with a
stimulant medication. Growing concern over issues related to prescribing
controlled substances long term, including their potential for diversion, has
also generated considerable support for the development
of alternative nonstimulant treatments.
RESEARCH
According to David Michelson, M.D., of Lilly Research Laboratories and the
Indiana University School of Medicine, "atomoxetine appears to offer a new
alternative to stimulants with excellent symptom control but without abuse
liability."
Michelson and colleagues conducted a large 13-site study of children and
adolescents with ADHD to assess the efficacy and safety of atomoxetine in
reducing the core symptoms of the disorder. The eight-week, double-blind,
randomized, placebo-controlled, dose-response study examined 297 children and
adolescents (212 males, 85 females) between the ages of eight and 18, all of
whom met the DSM-IV criteria for ADHD.
Patients had to meet severity criteria of a symptom score of at least 1.5
standard deviations (SD) above norms on the ADHD Rating Scale-IV – Parent
Version: Investigator Administered and Scored (ADHD RS) on the total of either
inattentive or hyperactive/impulsive subscales. After an initial 12- to 18-day
evaluation and medication wash-out period, patients were randomly assigned to
receive either placebo (N=84) or atomoxetine dosed on a weight-adjusted basis at
0.5 mg/kg/day (N=44), 1.2 mg/kg/day (N=84) or 1.8 mg/kg/day (N=85) for eight
weeks. All patients in the active arms of the study began treatment at
0.5/mg/kg/day and received the drug as equally divided doses (morning and
afternoon).
In the upper-dose treatment arms, atomoxetine was titrated in increments of 0.8
mg/kg/day and 1.2 mg/kg/day at one-week intervals. To get a complete
dose-response curve for the study, the investigators took the mean final dose
(1.5 mg/kg/day) from two previous placebo-controlled studies that used a dose
titration, selected that as the middle dose and bracketed it with a higher and
lower dose.
To measure efficacy, the investigators used the 18-item ADHD Rating Scale
(ADHD-RS), which is based on a semi-structured interview with the patient's
parent or guardian. Each item corresponds to one of the 18 DSM-IV diagnostic
criteria. Other measures included, the Hyperactivity/Impulsivity and Inattention
subscales of the ADHD-RS, the Connors' Parent Rating Scale Revised: Short Form (CPRS-R),
the Clinical Global Impressions of Severity (CGI-S) and the revised Children's
Depression Rating Scale (CDRS-R).
RESULTS AND ADVERSE EVENTS
Two hundred forty-eight patients completed the study, with 85.7% in the placebo
group, 77.3% in the 0.5 mg/kg/day group, 82.1% in the 1.2 mg/kg/day group and
85.9% in the 1.8 mg/kg/day group. Adverse event-related discontinuations were
low and comparable for all treatment groups.
"No single adverse event was statistically significantly more frequent in
either of the 2 higher atomoxetine dose groups as compared with placebo,"
say the authors. However, decreased appetite and somnolence increased with dose,
and the investigators observed a potentially important dose-related loss of
weight; a finding that is being further investigated in other, long-term trials.
The study found that patients receiving atomoxetine in the two upper-dose groups
consistently experienced superior outcomes in ADHD symptoms compared with
patients receiving placebo. While both the 1.2 mg/kg/day and 1.8 mg/kg/day were
superior to placebo and treatment with the 0.5 mg/kg/day, the investigators
report that the two upper-dose groups were not different from each another in
response. Additionally, although the response to 0.5 mg/kg/day did not differ
significantly from placebo, the scores were midway between placebo and 1.2
mg/kg/day, suggesting that there is a graded dose
response.
"Looking at the dose response curve, the average improvement at the highest
(1.8 mg/kg/d) dose is similar to that of 1.2 mg/kg/d. Thus on average, we would
expect that dose increases above 1.2 mg/kg/d will not lead to greater responses,
though for an individual patient a dose increase might be of benefit," says
Michelson.
The study also investigated how reducing ADHD symptoms improved the quality of
life for affected children and their families. Investigators found that
treatment with atomoxetine was correlated with improvements in social and family
functioning, as measured by the Child Health Questionnaire (CHQ), a parent-rated
scale that measures physical and psychosocial well being.
EXTENSIVE VS. POOR METABOLIZERS
In addition to observing a graded dose response, the investigators found that
poor metabolizers (as determined by CYP-2D6 genotype) demonstrated extremely
robust symptom reduction at the two higher atomoxetine doses. [Editor's note: 17
of those randomized were poor metabolizers; six in the placebo group and 11 in
the atomoxetine groups.]
Michelson explains, "Compared with extensive metabolizers, poor
metabolizers had better responses at comparable doses, and compared with
extensive metabolizers, poor metabolizers also had a longer plasma half-life and
higher drug exposures. Either of these factors could account for the better
response in poor metabolizers."
While higher drug exposures can lead to differences in safety or tolerability in
some patients, this study revealed no differences between atomoxetine and
placebo in the percentages of poor metabolizers reporting new or exacerbated
side effects. Heart rate did increase more among the poor metabolizers compared
with extensive metabolizers, but the increase was not symptomatic.
Michelson noted that this study is absent of an active comparator, thus
rendering it impossible to determine atomoxetine's therapeutic value relative to
stimulants. It is also important to note that dose-related decreases in weight
were observed but no adverse effect reached clinical significance.
A one-year study extension period is currently ongoing. According to Michelson,
the extension will enable patients who benefited from the drug during the acute
phase of the study to continue receiving treatment.
SECOND STUDY
A second study conducted by Thomas Spencer, M.D., of Massachusetts General
Hospital, and colleagues sought to evaluate the efficacy and safety of different
doses of atomoxetine for ADHD using an open-label, prospective, dose-ranging
study design. Spencer assigned 30 children ages 7 to 14 to twice daily treatment
with atomoxetine 0.25 mg/kg/day (range = 0.1 to 0.4 mg/kg/day), increasing the
dose weekly by 0.25 mg/kg/day. For the first nine weeks of treatment, the mean
dose increased steadily up to 1.9 mg/kg/day, remaining constant until the end of
the 11-week treatment period.
Seventy-three percent (N=22) completed the study, with eight withdrawing
prematurely due to problems with swallowing the capsule (N=1), noncompliance
and/or headaches (N=3), needle phobia (N=2), unexpected family relocation (N=1)
and family conflict (N=1).
The investigators report that core ADHD symptoms decreased steadily over the
11-week study period, with a statistically significant reduction in ADHD-RS-IV
scores observed one week (p<0.05) and three weeks post-treatment (p<0.01).
The mean reduction in symptoms measured by the ADHD-RS-IV from baseline was 38.6
percent. Significant reductions were also noted for both Inattention and
Hyperactivity/Impulsivity subscales (p<0.001 and p<0.001 respectively).
Clinically and statistically significant improvement was associated with
atomoxetine treatment in all but one of the individual items in the ADHD-RS-IV.
The investigators report robust reductions in all nine items of the Inattention
subscale (all p<0.01) and in eight of nine items on the
Hyperactivity/Impulsivity subscale (p<0.05). The severity of ADHD symptoms
had a significant mean decrease of 29 percent, as measured by the
CGI-ADHD-S.
The investigators say that response to atomoxetine was dose-related and
continued steadily with each incremental dose increase. Treatment with
atomoxetine (average final dose = 1.9 mg/kg/day) was very well tolerated at all
doses, and was efficacious in alleviating the symptoms of ADHD.
Adverse events did occur in some patients, including rhinitis (33.3%), headache
(20%), anorexia (16.7%), and dizziness (16.7%). No serious side effects were
observed and no patients stopped medication or discontinued the study due to
adverse events. Also encouraging, say the authors, "are the benign
cardiovascular findings associated with atomoxetine treatment."
COMORBIDITY
In contrast to the Michelson study sample, the presence of at least one comorbid
psychiatric disorder in the patient sample was high (89%). Although their sample
was small, Spencer states that their findings suggest that atomoxetine may
provide an added treatment benefit to some patients with comorbid anxiety or
depression.
In a few patients meeting the criteria for anxiety or depression at baseline,
treatment with atomoxetine was associated with reduced severity and mild to
moderate improvement in symptoms. The investigators also found that psychiatric
disorders did not affect the robust response to atomoxetine treatment.
"Consistent with our adult study, response to atomoxetine was not affected
by the presence of psychiatric comorbidity," say the authors (Spencer et
al., 1998). "These results suggest that the observed positive results were
not due to the punitive antidepressants or antianxiety effects of this
compound."
They continue, "Considering that stimulants can be anxiogenic and
depressogenic in some patients with ADHD, if confirmed in future controlled
studies, atomoxetine treatment could offer an advantage for patients with
comorbid anxiety or depression."
The dosing target and gradual-dose titration study design (e.g., target dose not
reached until 3-4 weeks) renders it difficult to separate dose and time effects.
In addition, the omission of teacher assessments prohibits any direct
conclusions regarding atomoxetine's effects on classroom behavior. Nonetheless,
the significant clinical response and the well-tolerated side-effect profile are
compelling.
CLINICAL IMPLICATIONS
Treatment with atomoxetine appears to significantly improve ADHD symptoms and is
generally well tolerated at all doses. The relatively benign side effect profile
of atomoxetine is especially promising. No serious side effects or changes in
cardiac conduction have been associated with atomoxetine.
Several nonstimulants that have been shown in studies to be efficacious for ADHD
include some of the tricyclic antidepressants (desipramine, protriptyline,
nortriptyline) and buproprion, but dose-response and safety in the pediatric
population merit further study. The tricyclics have an anticholinergic side
effect profile and require EKG monitoring for cardiac conduction delays.
Atomoxetine appears to offer a safe alternative to stimulants and tricyclic
antidepressants with excellent symptom control.
[The Michelson et al. study was supported by Eli Lilly and Company. The Spencer
et al. study was supported in part by the Lilly Research Laboratories and
National Institute of Mental Health grant R29MH57511.]
Michelson D, Faries D, Wernicke J, et al.: Atomoxetine in the treatment of
children and adolescents with attention-deficit/hyperactivity disorder: A
randomized, placebo-controlled, dose-response study. Pediatrics 2001; 108(5): http://www.pediatrics.org/cgi/content/full/108/5/e83
.
Correspondence to: Dr. Michelson, Lilly Corporate Center, DC 6026, Indianapolis,
IN 46285; e-mail: mailto:dmichelson@lilly.com
Spencer T, Biederman J, Heiligenstein J, et al.: An open-label, dose-ranging
study of atomoxetine in children with attention deficit hyperactivity disorder.
Journal of Child and Adolescent Psychopharmacology 2001; 11:521-265.
Correspondence to: Dr. Spencer, Pediatric Psychopharmacology Unit (ACC-725),
Massachusetts General Hospital, 15 Parkman St., Boston, MA 02114.
Spencer T, Biederman J, Wilens T, et al.: Effectiveness and tolerability of
tomoxetine in adults with attention deficit hyperactivity disorder. Am J
Psychiatry 1998; 155:693-695.
POSTERS PRESENTED AT THE AACAP 2002 ANNUAL MEETING
In a randomized, double-blind, placebo-controlled, multicenter trial, a
once-a-day formulation of atomoxetine was found to be superior to placebo in
treating children and adolescents with DSM-IV ADHD.
After a one- to two-week washout period, 171 children and adolescents, aged 6 to
16 years, were randomized for six weeks to atomoxetine, up to 1.5 mg/kg/day
daily (N=85), or placebo (N=86). Efficacy was measured using the
Attention-Deficit/Hyperactivity Disorder-IV-Parent Version: Investigator
Administered and Scored (ADHD-RS), Conners' Parent Rating Scale-Revised (CPRS-R),
Conners' Teacher Rating Scale-Revised (CTRS-R), Clinical Global Impressions of
Severity (CGI-ADHD-S) and parent-rated daily diaries.
One patient in the placebo group discontinued from the study prior to receiving
treatment. The study showed that atomoxetine was superior to placebo, as
assessed by investigator, parent and teacher ratings. The treatment effect size
(0.7) was similar to those found in previous atomoxetine studies using
twice-a-day dosing. The investigators report that daily parent diary ratings
suggested that some drug specific effects were sustained late in the day.
Discontinuations due to adverse effects were low (<3%) for both the
atomoxetine and placebo groups. No serious safety concerns were observed.
[Michelson D, Allen AJ, Kelsey D, et al.: Once-daily atomoxetine treatment for
children and adolescents with ADHD.]
COMORBIDITY
Additional data from two identical randomized, double-blind, placebo-controlled,
multicenter trials found that atomoxetine was superior to placebo in the
management of pediatric ADHD with or without comorbid Oppositional-Defiant
Disorder (ODD). No medications are currently approved for the treatment of ODD.
Two hundred fifty-three children, aged 7 to 12 years, who met the DSM-IV
criteria for ADHD, with (N=98) and without (N=151) comorbid ODD, were randomized
for nine weeks to atomoxetine or placebo. Efficacy assessments included the ADHD
Rating Scale-IV-Parent Version: Investigator Scored (ADHD RS), Conners' Parent
Rating Scale-Revised: Short Form (CPRS-R) and the Clinical Global Impressions of
Severity (CGI-ADHD-S). Safety was assessed by adverse events monitoring.
The results showed that ADHD RS, CGI and CPRS ADHD Index scores from baseline to
endpoint were markedly improved in patients taking atomoxetine compared to the
placebo group, with no significant difference attributable to the presence or
absence of comorbid ODD. In the atomoxetine group, clinical response was 65.4
percent for those with ODD and 58.9 percent for those without the comorbid
disorder versus 36.4 percent and 29.3 percent in the placebo group (all p values
less than or equal to 0.007). The most
commonly reported treatment-emergent adverse events were headache, rhinitis and
abdominal pain. Diarrhea was the only statistically significant side effect that
occurred more often in children with comorbid ODD when compared with those
without ODD.
The authors note, "The presence of comorbid [Oppositional-Defiant Disorder]
in children does not appear to complicate the pharmacologic treatment of ADHD
with atomoxetine as evidenced by a robust response similar to children without
[Oppositional-Defiant Disorder]."
[Heiligenstein J, Kaplan S, Harder D, et al.: Atomoxetine: Clinical outcomes in
pediatric ADHD with comorbid ODD.]
CARDIOVASCULAR EFFECTS
In another study, findings from combined data suggest that the cardiovascular
effects of atomoxetine are minimal. In particular, the findings indicate that
the drug is not associated with QTc prolongation.
Data were collected on 550 children and adolescents treated with atomoxetine or
placebo in three double-blind trials and on 144 children treated with
atomoxetine in extension studies. Safety assessments included blood pressure and
pulse monitoring, and ECGs.
The data showed that compared to placebo, atomoxetine use was associated with a
statistically significant increases in mean pulse (+7.8 bpm) and diastolic blood
pressure (+2.1 mm Hg) that were sustained during long-term treatment, but
returned to baseline levels after drug discontinuation. According to the
authors, there were no reports of adverse events associated with increased heart
rate or blood pressure. They note that mean QTcD decreased in both groups.
"Increases in heart rate and blood pressure were small and of no apparent
clinical significance," write the authors. They note that atomoxetine was
not associated with QT interval prolongation, and that cardiovascular effects
were minimal and well tolerated. [Wernicke JF, Faries D, Kovacs R, et al.:
Cardiovascular effects of atomoxetine in children and adolescents.]
ATOMOXETINE FOR ADULTS WITH ADHD
The safety and efficacy of atomoxetine for adults with ADHD were also
established in two identical 10-week, randomized, double-blind,
placebo-controlled multicenter studies to be published in a forthcoming issue of
Biological Psychiatry.
The data showed that atomoxetine was statistically superior to placebo in
reducing both inattentive and hyperactive/impulsive symptoms in adults with
DSM-IV-defined ADHD, as assessed by primary and secondary measures, including
Conners' Adult ADHD Rating Scale. In the studies, which involved more than 500
adults, discontinuations due to adverse events among atomoxetine patients were
under 10 percent.
MOST RECENT STUDIES:
1. Biederman J, Heiligenstein JH, Faries DE, Galil N, Dittmann R, Emslie GJ,
Kratochvil CJ, Laws HF, Schuh KJ: Efficacy of atomoxetine versus placebo in
school-age girls with attention-deficit/hyperactivity disorder. Pediatrics 2002;
110(6):e75.
2. Michelson D, Allen AJ, Busner J, Casat C, Dunn D, Kratochvil C, Newcorn J,
Sallee FR, Sangal RB, Saylor K, West S, Kelsey D, Wernicke J, Trapp NJ, Harder
D: Once-daily atomoxetine treatment for children and adolescents with attention
deficit hyperactivity disorder: a randomized, placebo-controlled study. Am J
Psychiatry 2002; 159(11):1896-901.
3. Kratochvil CJ, Heiligenstein JH, Dittmann R, Spencer TJ, Biederman J,
Wernicke J, Newcorn JH, Casat C, Milton D, Michelson D: Atomoxetine and
methylphenidate treatment in children with ADHD: a prospective, randomized,
open-label trial. J Am Acad Child Adolesc Psychiatry 2002; 41(7):776-84.
-----------------------------------------------
INDUSTRY NEWS
-----------------------------------------------
ATOMOXETINE APPROVED BY FDA
On Nov. 26, Eli Lilly announced FDA approval of atomoxetine, a selective
norepinephrine reuptake inhibitor, for the treatment of ADHD in children,
adolescents and adults. The new drug will be marketed under the trade name
Strattera and is not classified as a stimulant under the Controlled Substances
Act. The safety and efficacy of atomoxetine for ADHD has been demonstrated with
data from six placebo-controlled clinical studies. To date, more than 4,000
patients have taken atomoxetine in all completed and ongoing clinical trials,
some for as long as two and a half years. Atomoxetine is the first ADHD
medication proven clinically effective in adults. Atomoxetine comes in a capsule
and can be taken once or twice a day. Lilly expects the drug to be available in
pharmacies in January. [Lilly; http://www.lilly.com
]
NICOTINE LOZENGE APPROVED BY FDA
The FDA has approved GlaxoSmithKline's nicotine lozenge for over-the-counter
sales, the Associated Press reported recently. The Commit Lozenge comes in
varying strengths and will offer smokers an alternative to nicotine patches or
gum for smoking cessation. Smokers can suck a lozenge when they have a craving,
gradually reducing the number and strength over a 12-week weaning period,
according to GlaxoSmithKline. Commit lozenges are the first nicotine-containing
lozenges to gain the FDA's approval, the Associated Press reported. They are
expected to be available this month in 72 lozenge packs for $39.95. [GlaxoSmithKline;
http://www.gsk.com ]
ORAL SOLUTION OF ESCITALOPRAM APPROVED BY FDA
On Dec. 2, Forest Laboratories Inc. announced FDA approval of an oral solution
of escitalopram oxalate (Lexapro). The selective serotonin reuptake inhibitor,
previously approved for the initial and maintenance treatment of major
depressive disorder, is the single isomer of citalopram (Celexa). Forest expects
to have the oral solution of escitalopram available commercially by the first
quarter 2003. [Forest; http://www.forestlaboratories.com
]
FOREST SUBMITS NDA FOR ESCITALOPRAM FOR GAD
Forest Laboratories Inc. has submitted to the FDA a supplemental New Drug
Application (sNDA) to expand the labeling of escitalopram oxalate (Lexapro) to
include the treatment of generalized anxiety disorder (GAD). The sNDA is based
on data from three placebo-controlled studies in patients with GAD. [Forest; http://www.forestlaboratories.com
]
PRE-CLINICAL STUDIES COMPARE ABSORPTION OF GABAPENTIN PRODRUG VS. GABAPENTIN
Scientific data presented recently at the fifth International Conference on the
Mechanisms of Treatment of Neuropathic Pain in Bermuda suggest that XenoPort
Inc.'s novel gabapentin prodrug (Gabapentin-XP) is better absorbed in the
gastrointestinal tract than gabapentin itself. Once absorbed, studies show that
gabapentin prodrug is rapidly converted to the active drug gabapentin, a
molecule that is currently marked under the brand name Neurontin. XenoPort, a
privately held biopharmaceutical company, is currently conducting late-stage
pre-clinical studies with a goal of submitting an Investigational New Drug (IND)
application and conducting Phase I studies with the drug in 2003. XenoPort's
Engineered Drug Transport technology improves the oral absorption, distribution
and pharmacokinetics of drugs by harnessing the body's intrinsic cellular
transport systems, which exist to ferry nutrients and other substances into the
body. Gabapentin-XP is designed to exploit high-capacity absorption mechanisms
found throughout the length of the gastrointestinal tract and, once absorbed, to
be rapidly converted within the bloodstream to active gabapentin. [XenoPort; http://www.xenoport.com
]
-----------------------------------------------
Featured Resource
-----------------------------------------------
Where do you start when you're trying to provide culturally competent services?
You'll find the all answers in Cultural Competency in Managed Behavioral
Healthcare, with an entire chapter dedicated to psychopharmacology.
Here's how to figure out where your clients are coming from...And get better
results by adapting your treatment to ensure cultural competency!
Order now for $89 (plus shipping and handling) at (800) 333-7771 (9-5 EST) or
visit http://www.bhrpress.com/bookstore/write-ups/990630_cult_comp.htm
to order online.
Order now! Your satisfaction is 100% guaranteed - you may return the book(s)
within 30 days for a full refund.
Here's how you can take advantage of this special offer
1) Call the publisher (Manisses Communications Group) at (800) 333-7771 (9-5
EST) and make sure to mention the special charter offer
2) E-mail: mailto:ManissesCS@manisses.com
and mention the special charter offer
3) Print the form below and fax it to Manisses at (401)
861-6370
**********************************************************
ORDER FORM - reply/send or print and fax to (401) 861-6370
[ ] Yes! I want to order Cultural Competency for $89 and start to provide
culturally competent services?
+ RI residents add 7.00% sales tax
$ _____________ TOTAL ORDER
I would like to PAY BY (check one):
[ ] CHECK (Enclosed with mailed order)
[ ] PURCHASE ORDER # ____________________________
[ ] VISA [ ] AMEX [ ] MASTERCARD [ ] DISCOVER
Account #________________________________ Exp. Date ______
Signature ________________________________ (n/a if sending by e-mail)
Phone # ________________________________
SHIP MY ORDER TO:
Name _____________________________________________
Title _____________________________________________
Organization ________________________________________
Address (no PO boxes, please)
__________________________________________________
___________________________________________________
City/State/Zip _______________________________________
_____________________________________________________________
To Order:
CALL: (800) 333-7771
FAX YOUR ORDER TO: 401-861-6370
MAIL YOUR ORDER TO:
Manisses Communications Group Inc.
208 Governor Street
Providence RI 02906
-----------------------------------------------
Visit Manisses' Professional Opportunities page, a listing of job openings in
mental health and addiction fields. Go to http://www.manisses.com/classifieds/classifieds.htm
.
|
