[Pharmwaste] Requested: Paxil CR(R) (paroxetine HCl) Controlled-Release Tablets a Unique, Effective SSRI

[Stevan Gressitt]

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 Las Vegas
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.

 

  _____  

 


Dear Doctor, 

Here is the information you requested (sponsored by GlaxoSmithKline). 

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.1 It is important to minimize adverse events
that may lead to early treatment dropout. 

  <http://image.epocrates.com/xns/images/Paxil_401.jpg> 

* 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.
† 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%).
‡ Causes of early dropout due to clinical reasons included no longer
depressed (12.8%), no improvement (11.9%), and physician stopped (0.4%). 

Controlled-Release of Medication
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 Tmax and low variability. 

Low Incidence of Dropouts due to Adverse Events 

  <http://image.epocrates.com/xns/images/Paxil_402.jpg> 

*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. 
† 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. 
‡ 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. 
§ 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. 
|| 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. 

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.3-10 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.8 

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.”7

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. 

Broad-Spectrum Efficacy
Besides having a generally well-tolerated profile, PAXIL CR demonstrates
broad-spectrum efficacy across 4 indications: MDD, PMDD, Panic Disorder, and
Social Anxiety Disorder. 

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. 

Important Safety Information
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. 

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. 

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. 

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. 

Please refer to Prescribing Information for PAXIL CR, including BOXED
WARNING, by clicking this URL link:
http://us.gsk.com/products/assets/us_paxilcr.pdf
<http://imageb.epocrates.com/mailbot/links?EdID=20348227&LinkID=1759> .

REFERENCES
1. Bull SA, Hunkeler EM, Lee JY, et al. Discontinuing or switching selective
serotonin-reuptake inhibitors. Ann Pharmacother. 2002;36:578-584. 
2. Stahl SM. At long last, long-lasting psychiatric medications: an overview
of controlled-release technologies. J Clin Psychiatry. 2003;64:355-356. 
3. Prescribing Information for PAXIL CR. 
4. Lepola U, Bergtholdt B, St. Lambert J, et al. Controlled-release
paroxetine in the treatment of patients with social anxiety disorder. J Clin
Psychiatry. 2004;65:222-229. 
5. Data on file (PXCDOF017), GlaxoSmithKline. 
6. Data on file (PXCDOF011), GlaxoSmithKline. 
7. Golden RN, Nemeroff CB, McSorley P, et al. Efficacy and tolerability of
controlled-release and immediate-release paroxetine in the treatment of
depression. J Clin Psychiatry. 2002;63:577-584. 
8. Rapaport MH, Schneider LS, Dunner DL, et al. Efficacy of
controlled-release paroxetine in the treatment of late-life depression. J
Clin Psychiatry. 2003;64:1065-1074. 
9. Data on file (PXCDOF010), GlaxoSmithKline. 
10. Data on file (PXCDOF007), GlaxoSmithKline. 

The above message was sponsored by GlaxoSmithKline, which is solely
responsible for its content. 
GlaxoSmithKline 
5 Moore Drive 
PO Box 13398 
Research Triangle Park, NC 27709 
http://www.gsk.com
<http://imageb.epocrates.com/mailbot/links?EdID=20348227&LinkID=1619>  

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