<META HTTP-EQUIV="Content-Type" CONTENT="text/html; charset=windows-1251">
<html xmlns:v="urn:schemas-microsoft-com:vml" xmlns:o="urn:schemas-microsoft-com:office:office" xmlns:w="urn:schemas-microsoft-com:office:word" xmlns:st1="urn:schemas-microsoft-com:office:smarttags" xmlns="http://www.w3.org/TR/REC-html40">
<head>
<meta name=Generator content="Microsoft Word 11 (filtered medium)">
<!--[if !mso]>
<style>
v\:* {behavior:url(#default#VML);}
o\:* {behavior:url(#default#VML);}
w\:* {behavior:url(#default#VML);}
.shape {behavior:url(#default#VML);}
</style>
<![endif]-->
<title>Requested DocAlert</title>
<o:SmartTagType namespaceuri="urn:schemas-microsoft-com:office:smarttags"
name="City"/>
<o:SmartTagType namespaceuri="urn:schemas-microsoft-com:office:smarttags"
name="place"/>
<!--[if !mso]>
<style>
st1\:*{behavior:url(#default#ieooui) }
</style>
<![endif]-->
<style>
<!--
/* Style Definitions */
p.MsoNormal, li.MsoNormal, div.MsoNormal
{margin:0in;
margin-bottom:.0001pt;
font-size:12.0pt;
font-family:"Times New Roman";}
a:link, span.MsoHyperlink
{color:blue;
text-decoration:underline;}
a:visited, span.MsoHyperlinkFollowed
{color:blue;
text-decoration:underline;}
p
{mso-margin-top-alt:auto;
margin-right:0in;
mso-margin-bottom-alt:auto;
margin-left:0in;
font-size:12.0pt;
font-family:"Times New Roman";}
span.EmailStyle20
{mso-style-type:personal-reply;
font-family:Arial;
color:navy;}
@page Section1
{size:8.5in 11.0in;
margin:1.0in 1.25in 1.0in 1.25in;}
div.Section1
{page:Section1;}
-->
</style>
</head>
<body lang=EN-US link=blue vlink=blue>
<div class=Section1>
<p class=MsoNormal><font size=2 color=navy face=Arial><span style='font-size:
10.0pt;font-family:Arial;color:navy'>The question of rate of adherence or
non-compliance has come up on this list several times. I am forwarding this for
“general background.” It of course only refers to one drug.
Generally drop out rates increase with time rather than decrease. How in this
cohort anyone could see their way to stating a 3% wastage rate ( a number
quoted as I recall at one point at the <st1:City w:st="on"><st1:place w:st="on">Las
Vegas</st1:place></st1:City> meeting) would be beyond me. By 3-6 months it
would be common practice for many patients to have received a 90 day supply
through their mail-order pharmacy to save on co-pays. Stevan Gressitt, M.D.<o:p></o:p></span></font></p>
<p class=MsoNormal><font size=2 color=navy face=Arial><span style='font-size:
10.0pt;font-family:Arial;color:navy'><o:p> </o:p></span></font></p>
<div>
<div class=MsoNormal align=center style='text-align:center'><font size=3
face="Times New Roman"><span style='font-size:12.0pt'>
<hr size=2 width="100%" align=center tabindex=-1>
</span></font></div>
</div>
<p class=MsoNormal><font size=3 face="Times New Roman"><span style='font-size:
12.0pt'><o:p> </o:p></span></font></p>
<div align=center>
<table class=MsoNormalTable border=0 cellpadding=0 width=640 style='width:480.0pt'>
<tr>
<td style='padding:.75pt .75pt .75pt .75pt'>
<p><font size=3 face="Times New Roman"><span style='font-size:12.0pt'>Dear
Doctor, <o:p></o:p></span></font></p>
<p><font size=3 face="Times New Roman"><span style='font-size:12.0pt'>Here is
the information you requested (sponsored by GlaxoSmithKline). <o:p></o:p></span></font></p>
<p><font size=3 face="Times New Roman"><span style='font-size:12.0pt'>Early
patient dropout is a limiting factor for many medications, including
immediate-release SSRIs. In a study conducted with 672 patients who were
started on an immediate-release SSRI for new or recurrent depression, 43% and
27% of patients stopped taking their medications at 3 and 6 months due to an
adverse event, respectively. Common patient-reported adverse events leading
to dropout with immediate-release SSRIs included drowsiness/fatigue,
headache, anxiety, and nausea.</span></font><sup><font size=1><span
style='font-size:9.0pt'>1</span></font></sup> It is important to minimize
adverse events that may lead to early treatment dropout. <o:p></o:p></p>
<p class=MsoNormal align=center style='text-align:center'><font size=3
face="Times New Roman"><span style='font-size:12.0pt'><img width=600
height=332 id="_x0000_i1025"
src="http://image.epocrates.com/xns/images/Paxil_401.jpg"><o:p></o:p></span></font></p>
<blockquote style='margin-top:5.0pt;margin-right:0in;margin-bottom:5.0pt'>
<p><font size=2 face="Times New Roman"><span style='font-size:10.0pt'>*
Results based on telephone surveys conducted at 3 and 6 months after patients
(n=672) were started on an immediate-release SSRI (fluoxetine or paroxetine)
for new or recurrent depression. 43% and 27% of patients stopped taking their
medication at 3 months and 6 months due to an adverse event, respectively.<br>
† Causes of early dropout due to adverse events include
drowsiness/fatigue (10.2%), anxiety (6.2%), headache (5.8%), nausea (5.3%),
sexual dysfunction (3.1%), emotionally flat (3.1%), insomnia (2.7%),
dizziness (2.7%), dry mouth (1.3%), weight gain (1.3%), diarrhea (0.9%), and
rash/itching (0.9%).<br>
‡ Causes of early dropout due to clinical reasons included no longer
depressed (12.8%), no improvement (11.9%), and physician stopped (0.4%). </span></font><o:p></o:p></p>
</blockquote>
<p><strong><b><font size=3 face="Times New Roman"><span style='font-size:
12.0pt'>Controlled-Release of Medication</span></font></b></strong><br>
PAXIL CR is the first and only controlled-release SSRI with both a
Geomatrix™ core and enteric coating. The unique Geomatrix core allows a
slow release of medication further down the digestive tract. The result is a
pharmacokinetic profile with a delayed T<sub><font size=1><span
style='font-size:9.0pt'>max</span></font></sub> and low variability. <br>
<br>
<strong><b><font face="Times New Roman">Low Incidence of Dropouts due to
Adverse Events</font></b></strong> <o:p></o:p></p>
<p class=MsoNormal align=center style='text-align:center'><font size=3
face="Times New Roman"><span style='font-size:12.0pt'><img width=600
height=472 id="_x0000_i1026"
src="http://image.epocrates.com/xns/images/Paxil_402.jpg"><o:p></o:p></span></font></p>
<blockquote style='margin-right:0in;margin-bottom:5.0pt'>
<p class=MsoNormal><font size=2 face="Times New Roman"><span
style='font-size:10.0pt'>*These data are from a randomized, double-blind,
flexible-dose, placebo-controlled study in patients with social anxiety
disorder. Dose ranged from 12.5 mg to 37.5 mg. <br>
† These data are pooled from 3 randomized, double-blind, flexible-dose,
placebo-controlled panic disorder studies identical in design. Dose ranged
from 12.5 mg to 75 mg. <br>
‡ These data are pooled from 3 randomized, double-blind,
placebo-controlled, continuous-dosing Premenstrual Dysphoric Disorder (PMDD)
studies identical in design. Dose was 12.5 mg or 25 mg. <br>
§ These data are pooled from 2 randomized, double-blind, flexible-dose,
placebo-controlled MDD adult studies identical in design. Dose ranged from 25
mg to 62.5 mg. <br>
|| These data are from a randomized, double-blind, flexible-dose,
placebo-controlled MDD study in elderly patients. Dose ranged from 12.5 mg to
50 mg. </span></font><o:p></o:p></p>
</blockquote>
<p><font size=3 face="Times New Roman"><span style='font-size:12.0pt'>PAXIL
CR is associated with a low rate of dropouts due to adverse events across
indications—Major Depressive Disorder (MDD), Premenstrual Dysphoric
Disorder (PMDD), Panic Disorder, and Social Anxiety Disorder.</span></font><sup><font
size=1><span style='font-size:9.0pt'>3-10</span></font></sup> For example, a
study of PAXIL CR vs placebo in an elderly population with depression found
consistently lower weekly rates of dropout due to adverse events in PAXIL CR
versus patients on placebo.<sup><font size=1><span style='font-size:9.0pt'>8</span></font></sup>
<br>
<br>
A study comparing PAXIL CR to placebo for treatment of MDD in 640 patients,
reported, “of particular note was the observation that no significant
difference emerged in rates of premature study withdrawal due to adverse
events in the paroxetine CR and placebo groups, a rare finding in SSRI
treatment studies.”<sup><font size=1><span style='font-size:9.0pt'>7</span></font></sup><br>
<br>
This low rate of adverse events may help a patient stay on PAXIL CR.
Increasing average patient length of therapy may increase the likelihood of
symptom resolution and of reaching clinical treatment goals. <br>
<br>
<strong><b><font face="Times New Roman">Broad-Spectrum Efficacy</font></b></strong><br>
Besides having a generally well-tolerated profile, PAXIL CR demonstrates
broad-spectrum efficacy across 4 indications: MDD, PMDD, Panic Disorder, and
Social Anxiety Disorder. <o:p></o:p></p>
<p><font size=3 face="Times New Roman"><span style='font-size:12.0pt'>PAXIL
CR is a first-line treatment for patients with symptoms of MDD, PMDD, Panic
Disorder, or Social Anxiety Disorder. Patients can stay with PAXIL CR to
achieve clinical goals. <br>
<br>
<strong><b><u><font face="Times New Roman">Important Safety Information</font></u></b></strong><br>
Most common adverse events (incidence of 5% or greater and incidence for
PAXIL CR at least twice that for placebo) include infection, trauma, nausea,
diarrhea, dry mouth, constipation, decreased appetite, somnolence, dizziness,
decreased libido, tremor, yawning, sweating, abnormal vision, asthenia,
insomnia, abnormal ejaculation, female genital disorders and impotence.
Patients should not be abruptly discontinued from antidepressant medication,
including PAXIL CR. Concomitant use of PAXIL CR in patients taking monoamine
oxidase inhibitors (MAOIs), thioridazine, or pimozide is contraindicated. <br>
<br>
Antidepressants increased the risk of suicidal thinking and behavior
(suicidality) in short-term studies in children and adolescents with major
depressive disorder (MDD) and other psychiatric disorders. The average risk
of these events in a pooled analysis of nine antidepressants in 24 trials
involving over 4400 patients was twice that of placebo (4% vs. 2%). No
suicides occurred in these trials. This risk must be balanced with clinical
need when considering any use of antidepressants in children or adolescents.
It is not known whether this risk extends to adults. PAXIL CR is not approved
for use in the pediatric population. <br>
<br>
Adult and pediatric patients may experience worsening of depression,
emergence of suicidality, and unusual changes in behavior, whether or not
they are being treated with antidepressants. Patients at particular risk for
suicidality include young adults and those who have experienced or are experiencing
suicidal thoughts or behaviors. Physicians, families and caregivers should
closely monitor all patients on antidepressants, especially at the beginning
of therapy or with changes in dose, for suicidality as well as anxiety,
agitation, panic attacks, insomnia, irritability, hostility, aggressiveness,
impulsivity, akathisia (psychomotor restlessness), hypomania, mania, and
other unusual changes in behavior. All such symptoms should be reported
immediately to the patient's healthcare provider. See the prescribing
information for PAXIL CR for additional monitoring recommendations. There is
concern that such symptoms may be precursors to suicidality, although a
causal link has not been proven. If such symptoms occur, prescribers should
consider changing or discontinuing treatment. Patients should be screened for
bipolar disorder prior to initiating treatment with an antidepressant. <br>
<br>
PAXIL CR should be used during pregnancy only if the potential benefit to the
mother outweighs the potential risks to the fetus. Recent studies have
suggested an increase in the risk of congenital malformations, including
cardiovascular malformations, with the use of paroxetine during the first
trimester compared to other antidepressants. However, a separate pregnancy
registry reported no increase in the overall risk of malformations due to
paroxetine exposure in early pregnancy. Additionally, there have been reports
of neonatal complications, including premature births, in pregnant women
exposed to SSRIs during the third trimester. <br>
<br>
Please refer to Prescribing Information for PAXIL CR, including BOXED
WARNING, by clicking this URL link: <a
href="http://imageb.epocrates.com/mailbot/links?EdID=20348227&LinkID=1759">http://us.gsk.com/products/assets/us_paxilcr.pdf</a>.<br>
<br>
<strong><b><font face="Times New Roman">REFERENCES</font></b></strong><br>
1. Bull SA, Hunkeler EM, Lee JY, et al. Discontinuing or switching selective
serotonin-reuptake inhibitors. <em><i><font face="Times New Roman">Ann
Pharmacother</font></i></em>. 2002;36:578-584. <br>
2. Stahl SM. At long last, long-lasting psychiatric medications: an overview
of controlled-release technologies. <em><i><font face="Times New Roman">J
Clin Psychiatry</font></i></em>. 2003;64:355-356. <br>
3. Prescribing Information for PAXIL CR. <br>
4. Lepola U, Bergtholdt B, St. Lambert J, et al. Controlled-release
paroxetine in the treatment of patients with social anxiety disorder. <em><i><font
face="Times New Roman">J Clin Psychiatry</font></i></em>. 2004;65:222-229. <br>
5. Data on file (PXCDOF017), GlaxoSmithKline. <br>
6. Data on file (PXCDOF011), GlaxoSmithKline. <br>
7. Golden RN, Nemeroff CB, McSorley P, et al. Efficacy and tolerability of
controlled-release and immediate-release paroxetine in the treatment of
depression. <em><i><font face="Times New Roman">J Clin Psychiatry</font></i></em>.
2002;63:577-584. <br>
8. Rapaport MH, Schneider LS, Dunner DL, et al. Efficacy of
controlled-release paroxetine in the treatment of late-life depression. <em><i><font
face="Times New Roman">J Clin Psychiatry</font></i></em>. 2003;64:1065-1074. <br>
9. Data on file (PXCDOF010), GlaxoSmithKline. <br>
10. Data on file (PXCDOF007), GlaxoSmithKline. <br>
<br>
The above message was sponsored by GlaxoSmithKline, which is solely
responsible for its content. <br>
GlaxoSmithKline <br>
5 Moore Drive <br>
PO Box 13398 <br>
Research Triangle Park, NC 27709 <br>
<a href="http://imageb.epocrates.com/mailbot/links?EdID=20348227&LinkID=1619">http://www.gsk.com</a>
<o:p></o:p></span></font></p>
<p><font size=3 face="Times New Roman"><span style='font-size:12.0pt'><img
border=0 width=1 height=1 id="_x0000_i1027"
src="http://imageb.epocrates.com/imagelib/20348227/rx_logo.jpg"
alt=Epocrates><o:p></o:p></span></font></p>
</td>
</tr>
</table>
</div>
<p class=MsoNormal><font size=3 face="Times New Roman"><span style='font-size:
12.0pt'><o:p> </o:p></span></font></p>
</div>
</body>
</html>