What was that anti-depressant??

hector · Dec 7, 2008

no dont remember either. why? you feeling a little down bro? need a hug? just jokeing i get tht way as well.

saturn1 · Dec 7, 2008

Ive tried the euro product and it doesnt live up to the hype.

The most similar ive found in the U.S. is cymbalta which was much stronger with immediate results.

Cymbalta® (duloxetine hydrochloride) is a selective serotonin and
norepinephrine reuptake inhibitor (SSNRI) for oral administration. Its chemical
designation is (+)-(S)-N-methyl-γ-(1-naphthyloxy)-2-thiophenepropylamine
hydrochloride. The empirical formula is C18H19NOS•HCl, which corresponds to a
molecular weight of 333.88. The structural formula is:

<img src="images/cymbalta1%5B1%5D.gif" width="226" border="0" height="144">
Duloxetine hydrochloride is a white to slightly brownish white solid,
which is slightly soluble in water.
Each capsule contains enteric-coated pellets of 22.4, 33.7, or 67.3 mg of
duloxetine hydrochloride equivalent to 20, 30, or 60 mg of duloxetine,
respectively. These enteric-coated pellets are designed to prevent
degradation of the drug in the acidic environment of the stomach. Inactive
ingredients include FD&C Blue No. 2, gelatin, hypromellose, hydroxypropyl
methylcellulose acetate succinate, sodium lauryl sulfate, sucrose, sugar
spheres, talc, titanium dioxide, and triethyl citrate. The 20 and 60 mg
capsules also contain iron oxide yellow.

Clinical <a name="pharmacology">Pharmacology</a>
Pharmacodynamics 
Although the exact mechanisms of the antidepressant and central pain inhibitory
action of duloxetine in humans are unknown, the antidepressant and pain
inhibitory actions are believed to be related to its potentiation of
serotonergic and noradrenergic activity in the CNS. Preclinical studies have
shown that duloxetine is a potent inhibitor of neuronal serotonin and
norepinephrine reuptake and a less potent inhibitor of dopamine reuptake.
Duloxetine has no significant affinity for dopaminergic, adrenergic,
cholinergic, histaminergic, opioid, glutamate, and GABA receptors in vitro.
Duloxetine does not inhibit monoamine oxidase (MAO). Duloxetine undergoes
extensive metabolism, but the major circulating metabolites have not been shown
to contribute significantly to the pharmacologic activity of duloxetine.
Pharmacokinetics 
Duloxetine has an elimination half-life of about 12 hours (range 8 to 17
hours) and its pharmacokinetics are dose proportional over the therapeutic
range. Steady-state plasma concentrations are typically achieved after 3
days of dosing. Elimination of duloxetine is mainly through hepatic
metabolism involving two P450 isozymes, CYP2D6 and CYP1A2.
Absorption and Distribution — Orally administered duloxetine
hydrochloride is well absorbed. There is a median 2-hour lag until
absorption begins (Tlag), with maximal plasma concentrations (Cmax) of
duloxetine occurring 6 hours post dose. Food does not affect the Cmax of
duloxetine, but delays the time to reach peak concentration from 6 to 10
hours and it marginally decreases the extent of absorption (AUC) by about
10%. There is a 3-hour delay in absorption and a one-third increase in
apparent clearance of duloxetine after an evening dose as compared to a
morning dose.

The apparent volume of distribution averages about 1640 L. Duloxetine is
highly bound (>90%) to proteins in human plasma, binding primarily to
albumin and α1-acid glycoprotein. The interaction between duloxetine and
other highly protein bound drugs has not been fully evaluated. Plasma
protein binding of duloxetine is not affected by renal or hepatic
impairment.
Metabolism and Elimination — Biotransformation and disposition of
duloxetine in humans have been determined following oral administration of
14C-labeled duloxetine. Duloxetine comprises about 3% of the total
radiolabeled material in the plasma, indicating that it undergoes extensive
metabolism to numerous metabolites. The major biotransformation pathways for
duloxetine involve oxidation of the naphthyl ring followed by conjugation
and further oxidation. Both CYP2D6 and CYP1A2 catalyze the oxidation of the
naphthyl ring in vitro. Metabolites found in plasma include 4-hydroxy
duloxetine glucuronide and 5-hydroxy, 6-methoxy duloxetine sulfate. Many
additional metabolites have been identified in urine, some representing only
minor pathways of elimination. Only trace (<1% of the dose) amounts of
unchanged duloxetine are present in the urine. Most (about 70%) of the
duloxetine dose appears in the urine as metabolites of duloxetine; about 20%
is excreted in the feces.
Special Populations
Gender — Duloxetine’s half-life is similar in men and women. Dosage
adjustment based on gender is not necessary.
Age — The pharmacokinetics of duloxetine after a single dose of 40 mg
were compared in healthy elderly females (65 to 77 years) and healthy
middle-age females (32 to 50 years). There was no difference in the Cmax,
but the AUC of duloxetine was somewhat (about 25%) higher and the half-life
about 4 hours longer in the elderly females. Population pharmacokinetic
analyses suggest that the typical values for clearance decrease by
approximately 1% for each year of age between 25 to 75 years of age; but age
as a predictive factor only accounts for a small percentage of
between-patient variability. Dosage adjustment based on the age of the
patient is not necessary (see <a href="#dosage">DOSAGE AND ADMINISTRATION</a>).

Smoking Status — Duloxetine bioavailability (AUC) appears to be reduced
by about one-third in smokers. Dosage modifications are not recommended for
smokers.
Race — No specific pharmacokinetic study was conducted to investigate the
effects of race.
Renal Insufficiency — Limited data are available on the effects of
duloxetine in patients with end-stage renal disease (ESRD). After a single
60-mg dose of duloxetine, Cmax and AUC values were approximately 100%
greater in patients with end-stage renal disease receiving chronic
intermittent hemodialysis than in subjects with normal renal function. The
elimination half-life, however, was similar in both groups. The AUCs of the
major circulating metabolites, 4-hydroxy duloxetine glucuronide and
5-hydroxy, 6-methoxy duloxetine sulfate, largely excreted in urine, were
approximately 7- to 9-fold higher and would be expected to increase further
with multiple dosing. For this reason, Cymbalta is not recommended for
patients with end-stage renal disease (requiring dialysis) or severe renal
impairment (estimated creatinine clearance [CrCl] <30 mL/min) (see
<a href="#dosage">DOSAGE AND ADMINISTRATION</a>). Population PK analyses
suggest that mild to moderate degrees of renal dysfunction (estimated CrCl
30-80 mL/min) have no significant effect on duloxetine apparent clearance.
Hepatic Insufficiency — Patients with clinically evident hepatic
insufficiency have decreased duloxetine metabolism and elimination. After a
single 20-mg dose of Cymbalta, 6 cirrhotic patients with moderate liver
impairment (Child-Pugh Class B) had a mean plasma duloxetine clearance about
15% that of age- and gender-matched healthy subjects, with a 5-fold increase
in mean exposure (AUC). Although Cmax was similar to normals in the
cirrhotic patients, the half-life was about 3 times longer (see
<a href="#precautions">PRECAUTIONS</a>). It is recommended that duloxetine
not be administered to patients with any hepatic insufficiency (see
<a href="#dosage">DOSAGE AND ADMINISTRATION</a>).

Drug-Drug Interactions (also see <a href="#precautions">PRECAUTIONS</a>,
<a href="#drug">Drug Interactions</a>)
Potential for Other Drugs to Affect Duloxetine 
Both CYP1A2 and CYP2D6 are responsible for duloxetine metabolism.
Inhibitors of CYP1A2 — When duloxetine was co-administered with
fluvoxamine, a potent CYP1A2 inhibitor, to male subjects (n=14) the AUC was
increased approximately 6-fold, the Cmax was increased about 2.5-fold, and
duloxetine t1/2 was increased approximately 3-fold. Other drugs that inhibit
CYP1A2 metabolism include cimetidine and quinolone antimicrobials such as
ciprofloxacin and enoxacin.
Inhibitors of CYP2D6 — Because CYP2D6 is involved in duloxetine
metabolism, concomitant use of duloxetine with potent inhibitors of CYP2D6
would be expected to, and does, result in higher concentrations of
duloxetine (see <a href="#precautions">PRECAUTIONS</a>, Drug Interactions).

Studies with Benzodiazepines 
Lorazepam — Under steady-state conditions for duloxetine (60 mg Q 12
hours) and lorazepam (2 mg Q 12 hours), the pharmacokinetics of duloxetine
were not affected by co-administration.
Temazepam — Under steady-state conditions for duloxetine (20 mg
qhs) and temazepam (30 mg qhs), the pharmacokinetics of duloxetine were not
affected by co-administration.
Potential for Duloxetine to Affect Other Drugs
Drugs Metabolized by CYP1A2 — In vitro drug interaction studies
demonstrate that duloxetine does not induce CYP1A2 activity. Therefore, an
increase in the metabolism of CYP1A2 substrates (e.g., theophylline,
caffeine) resulting from induction is not anticipated, although clinical
studies of induction have not been performed. Although duloxetine is an
inhibitor of the CYP1A2 isoform in in vitro studies, the pharmacokinetics of
theophylline, a CYP1A2 substrate, were not significantly affected by
co-administration with duloxetine (60 mg BID). Duloxetine is thus unlikely
to have a clinically significant effect on the metabolism of CYP1A2
substrates.

Drugs Metabolized by CYP2D6 — Duloxetine is a moderate inhibitor of
CYP2D6 and increases the AUC and Cmax of drugs metabolized by CYP2D6 (see
PRECAUTIONS). Therefore, co-administration of Cymbalta with other drugs that
are extensively metabolized by this isozyme and that have a narrow
therapeutic index should be approached with caution (see PRECAUTIONS, Drug
Interactions).
Drugs Metabolized by CYP2C9 — Duloxetine does not inhibit the in vitro
enzyme activity of CYP2C9. Inhibition of the metabolism of CYP2C9 substrates
is therefore not anticipated, although clinical studies have not been
performed.
Drugs Metabolized by CYP3A — Results of in vitro studies demonstrate that
duloxetine does not inhibit or induce CYP3A activity. Therefore, an increase
or decrease in the metabolism of CYP3A substrates (e.g., oral contraceptives
and other steroidal agents) resulting from induction or inhibition is not
anticipated, although clinical studies have not been performed.
Drugs Metabolized by CYP2C19 — Results of in vitro studies demonstrate
that duloxetine does not inhibit CYP2C19 activity at therapeutic
concentrations. Inhibition of the metabolism of CYP2C19 substrates is
therefore not anticipated, although clinical studies have not been
performed.
Studies with Benzodiazepines 
Lorazepam — Under steady-state conditions for duloxetine (60 mg Q 12
hours) and lorazepam (2 mg Q 12 hours), the pharmacokinetics of lorazepam
were not affected by co-administration.

Temazepam — Under steady-state conditions for duloxetine (20 mg
qhs) and temazepam (30 mg qhs), the pharmacokinetics of temazepam were not
affected by co-administration.
Drugs Highly Bound to Plasma Protein — Because duloxetine is highly bound
to plasma protein, administration of Cymbalta to a patient taking another
drug that is highly protein bound may cause increased free concentrations of
the other drug, potentially resulting in adverse events.
<a name="Clinical_Studies">Clinical
Studies</a>
Major Depressive Disorder
The efficacy of Cymbalta as a treatment for depression was established in
4 randomized, double-blind, placebo-controlled, fixed-dose studies in adult
outpatients (18 to 83 years) meeting DSM-IV criteria for major depression.
In 2 studies, patients were randomized to Cymbalta 60 mg once daily (N=123
and N=128, respectively) or placebo (N=122 and N=139, respectively) for 9
weeks; in the third study, patients were randomized to Cymbalta 20 or 40 mg
twice daily (N=86 and N=91, respectively) or placebo (N=89) for 8 weeks; in
the fourth study, patients were randomized to Cymbalta 40 or 60 mg twice
daily (N=95 and N=93, respectively) or placebo (N=93) for 8 weeks. There is
no evidence that doses greater than 60 mg/day confer any additional benefit.

In all 4 studies, Cymbalta demonstrated superiority over placebo as
measured by improvement in the 17-item Hamilton Depression Rating Scale
(HAMD-17) total score.
Analyses of the relationship between treatment outcome and age, gender,
and race did not suggest any differential responsiveness on the basis of
these patient characteristics.
Diabetic Peripheral Neuropathic Pain 
The efficacy of Cymbalta for the management of neuropathic pain
associated with diabetic peripheral neuropathy (DPN) was established in 2
randomized, 12-week, double-blind, placebo-controlled, fixed-dose studies in
adult patients having diabetic peripheral neuropathy for at least 6 months.
Study 1 and 2 enrolled a total of 791 patients of whom 592 (75%) completed
the studies. Patients enrolled had Type I or II diabetes mellitus with a
diagnosis of painful distal symmetrical sensorimotor polyneuropathy for at
least 6 months. The patients had a baseline pain score of ≥4 on an 11-point
scale ranging from 0 (no pain) to 10 (worst possible pain). Patients were
permitted up to 4 g of acetaminophen per day as needed for pain, in addition
to Cymbalta. Patients recorded their pain daily in a diary.
Both studies compared Cymbalta 60 mg once daily or 60 mg twice daily with
placebo. Study 1 additionally compared Cymbalta 20 mg with placebo. A total
of 457 patients (342 Cymbalta, 115 placebo) were enrolled in Study 1 and a
total of 334 patients (226 Cymbalta, 108 placebo) were enrolled in Study 2.
Treatment with Cymbalta 60 mg one or two times a day statistically
significantly improved the endpoint mean pain scores from baseline and
increased the proportion of patients with at least a 50% reduction in pain
score from baseline. For various degrees of improvement in pain from
baseline to study endpoint, Figures 1 and 2 show the fraction of patients
achieving that degree of improvement. The figures are cumulative, so that
patients whose change from baseline is, for example, 50%, are also included
at every level of improvement below 50%. Patients who did not complete the
study were assigned 0% improvement. Some patients experienced a decrease in
pain as early as Week 1, which persisted throughout the study.
<img src="images/cymbalta2%5B1%5D.gif" width="424" border="0" height="205">

Percent Improvement in Pain from Baseline 
Figure 1: Percentage of Patients Achieving Various Levels of Pain Relief
as Measured by 24-Hour Average Pain Severity - Study 1
<img src="images/cymbalta3%5B1%5D.gif" width="419" border="0" height="198">
Percent Improvement in Pain from Baseline 
Figure 2: Percentage of Patients Achieving Various Levels of Pain Relief
as Measured by 24-Hour Average Pain Severity - Study 2
<a href="#top">top</a>

<a name="indications">Indications</a>
and Usage
Major Depressive Disorder 
Cymbalta is indicated for the treatment of major depressive disorder
(MDD).
The efficacy of Cymbalta has been established in 8- and 9-week
placebo-controlled trials of outpatients who met DSM-IV diagnostic criteria
for major depressive disorder (see CLINICAL STUDIES).
A major depressive episode (DSM-IV) implies a prominent and relatively
persistent (nearly every day for at least 2 weeks) depressed or dysphoric
mood that usually interferes with daily functioning, and includes at least 5
of the following 9 symptoms: depressed mood, loss of interest in usual
activities, significant change in weight and/or appetite, insomnia or
hypersomnia, psychomotor agitation or retardation, increased fatigue,
feelings of guilt or worthlessness, slowed thinking or impaired
concentration, or a suicide attempt or suicidal ideation.

The effectiveness of Cymbalta in hospitalized patients with major
depressive disorder has not been studied.
The effectiveness of Cymbalta in long-term use for major depressive
disorder, that is, for more than 9 weeks, has not been systematically
evaluated in controlled trials. The physician who elects to use Cymbalta for
extended periods should periodically evaluate the long-term usefulness of
the drug for the individual patient.
Diabetic Peripheral Neuropathic Pain
Cymbalta is indicated for the management of neuropathic pain associated
with diabetic peripheral neuropathy (see <a href="#Clinical_Studies">
CLINICAL STUDIES</a>).
<a href="#top">top</a>

<a name="contraindications">Contraindications</a>
Hypersensitivity 
Cymbalta is contraindicated in patients with a known hypersensitivity to
duloxetine or any of the inactive ingredients.
Monoamine Oxidase Inhibitors 
Concomitant use in patients taking monoamine oxidase inhibitors (MAOIs)
is contraindicated (see WARNINGS).
Uncontrolled Narrow-Angle Glaucoma 

In clinical trials, Cymbalta use was associated with an increased risk of
mydriasis; therefore, its use should be avoided in patients with
uncontrolled narrow-angle glaucoma.
<a href="#top">top</a>
<a name="warnings">Warnings</a>
 
Clinical Worsening and
Suicide Risk — Patients with major depressive disorder (MDD), both adult and
pediatric, may experience worsening of their depression and/or the emergence of
suicidal ideation and behavior (suicidality) or unusual changes in behavior,
whether or not they are taking antidepressant medications, and this risk may
persist until significant remission occurs. There has been a long-standing
concern that antidepressants may have a role in inducing worsening of depression
and the emergence of suicidality in certain patients. 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.
Pooled analyses of short-term placebo-controlled trials of 9
antidepressant drugs (SSRIs and others) in children and adolescents with
MDD, OCD, or other psychiatric disorders (a total of 24 trials involving
over 4400 patients) have revealed a greater risk of adverse events
representing suicidal behavior or thinking (suicidality) during the first
few months of treatment in those receiving antidepressants. The average risk
of such events in patients receiving antidepressants was 4%, twice the
placebo risk of 2%. There was considerable variation in risk among drugs,
but a tendency toward an increase for almost all drugs studied. The risk of
suicidality was most consistently observed in the MDD trials, but there were
signals of risk arising from some trials in other psychiatric indications
(obsessive compulsive disorder and social anxiety disorder) as well. No
suicides occurred in any of these trials. It is unknown whether the
suicidality risk in pediatric patients extends to longer-term use, i.e.,
beyond several months. It is also unknown whether the suicidality risk
extends to adults.

All pediatric patients being treated with antidepressants for any
indication should be observed closely for clinical worsening, suicidality,
and unusual changes in behavior, especially during the initial few months of
a course of drug therapy, or at times of dose changes, either increases or
decreases. Such observation would generally include at least weekly
face-to-face contact with patients or their family members or caregivers
during the first 4 weeks of treatment, then every other week visits for the
next 4 weeks, then at 12 weeks, and as clinically indicated beyond 12 weeks.
Additional contact by telephone may be appropriate between face-to-face
visits.
Adults with MDD or co-morbid depression in the setting of other
psychiatric illness being treated with antidepressants should be observed
similarly for clinical worsening and suicidality, especially during the
initial few months of a course of drug therapy, or at times of dose changes,
either increases or decreases.
The following symptoms, anxiety, agitation, panic attacks, insomnia,
irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor
restlessness), hypomania, and mania, have been reported in adult and
pediatric patients being treated with antidepressants for major depressive
disorder as well as for other indications, both psychiatric and
nonpsychiatric.
Although a causal link between the emergence of such symptoms and either
the worsening of depression and/or the emergence of suicidal impulses has
not been established, there is concern that such symptoms may represent
precursors to emerging suicidality.
Consideration should be given to changing the therapeutic regimen,
including possibly discontinuing the medication, in patients whose
depression is persistently worse, or who are experiencing emergent
suicidality or symptoms that might be precursors to worsening depression or
suicidality, especially if these symptoms are severe, abrupt in onset, or
were not part of the patient’s presenting symptoms.
If the decision has been made to discontinue treatment, medication should
be tapered, as rapidly as is feasible, but with recognition that abrupt
discontinuation can be associated with certain symptoms (see
<a href="#precautions">PRECAUTIONS</a> and <a href="#overdose">DOSAGE AND
ADMINISTRATION</a>, Discontinuing Cymbalta, for a description of the risks
of discontinuation of Cymbalta).

Families and caregivers of pediatric patients being treated with
antidepressants for major depressive disorder or other indications, both
psychiatric and nonpsychiatric, should be alerted about the need to monitor
patients for the emergence of agitation, irritability, unusual changes in
behavior, and the other symptoms described above, as well as the emergence
of suicidality, and to report such symptoms immediately to health care
providers. Such monitoring should include daily observation by families and
caregivers.
Prescriptions for Cymbalta should be written for the smallest quantity of
capsules consistent with good patient management, in order to reduce the
risk of overdose. Families and caregivers of adults being treated for
depression should be similarly advised.
Screening Patients for Bipolar Disorder — A major depressive
episode may be the initial presentation of bipolar disorder. It is generally
believed (though not established in controlled trials) that treating such an
episode with an antidepressant alone may increase the likelihood of
precipitation of a mixed/manic episode in patients at risk for bipolar
disorder. Whether any of the symptoms described above represent such a
conversion is unknown. However, prior to initiating treatment with an
antidepressant, patients with depressive symptoms should be adequately
screened to determine if they are at risk for bipolar disorder; such
screening should include a detailed psychiatric history, including a family
history of suicide, bipolar disorder, and depression. It should be noted
that Cymbalta is not approved for use in treating bipolar depression.
Monoamine Oxidase Inhibitors (MAOI) — In patients receiving a
serotonin reuptake inhibitor in combination with a monoamine oxidase
inhibitor, there have been reports of serious, sometimes fatal, reactions
including hyperthermia, rigidity, myoclonus, autonomic instability with
possible rapid fluctuations of vital signs, and mental status changes that
include extreme agitation progressing to delirium and coma. These reactions
have also been reported in patients who have recently discontinued serotonin
reuptake inhibitors and are then started on an MAOI. Some cases presented
with features resembling neuroleptic malignant syndrome. The effects of
combined use of Cymbalta and MAOIs have not been evaluated in humans or
animals. Therefore, because Cymbalta is an inhibitor of both serotonin and
norepinephrine reuptake, it is recommended that Cymbalta not be used in
combination with an MAOI, or within at least 14 days of discontinuing
treatment with an MAOI. Based on the half-life of Cymbalta, at least 5 days
should be allowed after stopping Cymbalta before starting an MAOI.
<a href="#top">top</a>

<a name="precautions">Precautions</a>
General 
Hepatotoxicity — Cymbalta increases the risk of elevation of serum
transaminase levels. Liver transaminase elevations resulted in the
discontinuation of 0.4% (31/8454) of Cymbalta-treated patients. In these
patients, the median time to detection of the transaminase elevation was
about two months. In controlled trials in MDD, elevations of alanine
transaminase (ALT) to >3 times the upper limit of normal occurred in 0.9%
(8/930) of Cymbalta-treated patients and in 0.3% (2/652) of placebo-treated
patients. In controlled trials in DPN, elevations of ALT to >3 times the
upper limit of normal occurred in 1.68% (8/477) of Cymbalta-treated patients
and in 0% (0/187) of placebo-treated patients. In the full cohort of
placebo-controlled trials in any indication, 1% (39/3732) of
Cymbalta-treated patients had a >3 times the upper limit of normal elevation
of ALT compared to 0.2% (6/2568) of placebo-treated patients. In
placebo-controlled studies using a fixed-dose design, there was evidence of
a dose-response relationship for ALT and AST elevation of >3 times the upper
limit of normal and >5 times the upper limit of normal, respectively.
Postmarketing reports have described cases of hepatitis with abdominal pain,
hepatomegaly and elevation of transaminase levels to more than twenty times
the upper limit of normal with or without jaundice, reflecting a mixed or
hepatocellular pattern of liver injury. Cases of cholestatic jaundice with
minimal elevation of transaminase levels have also been reported.
 


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The combination of transaminase elevations and elevated bilirubin,
without evidence of obstruction, is generally recognized as an important
predictor of severe liver injury. In clinical trials, three Cymbalta
patients had elevations of transaminases and bilirubin, but also had
elevation of alkaline phosphatase, suggesting an obstructive process; in
these patients, there was evidence of heavy alcohol use and this may have
contributed to the abnormalities seen. Two placebo-treated patients also had
transaminase elevations with elevated bilirubin. Postmarketing reports
indicate that elevated transaminases, bilirubin and alkaline phosphatase
have occurred in patients with chronic liver disease or cirrhosis. Because
it is possible that duloxetine and alcohol may interact to cause liver
injury or that duloxetine may aggravate pre-existing liver disease, Cymbalta
should ordinarily not be prescribed to patients with substantial alcohol use
or evidence of chronic liver disease.
Effect on Blood Pressure — In MDD clinical trials, Cymbalta
treatment was associated with mean increases in blood pressure, averaging 2
mm Hg systolic and 0.5 mm Hg diastolic and an increase in the incidence of
at least one measurement of systolic blood pressure over 140 mm Hg compared
to placebo.
Blood pressure should be measured prior to initiating treatment and
periodically measured throughout treatment (see <a href="#adverse">ADVERSE
REACTIONS</a>, Vital Sign Changes).
Activation of Mania/Hypomania — In placebo-controlled trials in
patients with major depressive disorder, activation of mania or hypomania
was reported in 0.1% (1/1139) of Cymbalta-treated patients and 0.1% (1/777)
of placebo-treated patients. Activation of mania/hypomania has been reported
in a small proportion of patients with mood disorders who were treated with
other marketed drugs effective in the treatment of major depressive
disorder. As with these other agents, Cymbalta should be used cautiously in
patients with a history of mania.

Seizures — Cymbalta has not been systematically evaluated in
patients with a seizure disorder, and such patients were excluded from
clinical studies. In placebo-controlled clinical trials in patients with
major depressive disorder, seizures occurred in 0.1% (1/1139) of patients
treated with Cymbalta and 0% (0/777) of patients treated with placebo. In
placebo-controlled clinical trials in patients with diabetic peripheral
neuropathy, seizures did not occur in any patients treated with either
Cymbalta or placebo. Cymbalta should be prescribed with care in patients
with a history of a seizure disorder.
Controlled Narrow-Angle Glaucoma — In clinical trials, Cymbalta
was associated with an increased risk of mydriasis; therefore, it should be
used cautiously in patients with controlled narrow-angle glaucoma (see
<a href="#contraindications">CONTRAINDICATIONS</a>, Uncontrolled
Narrow-Angle Glaucoma).
Discontinuation of Treatment with Cymbalta — Discontinuation
symptoms have been systematically evaluated in patients taking Cymbalta.
Following abrupt discontinuation in MDD placebo-controlled clinical trials
of up to 9-weeks duration, the following symptoms occurred at a rate greater
than or equal to 2% and at a significantly higher rate in Cymbalta-treated
patients compared to those discontinuing from placebo: dizziness; nausea;
headache; paresthesia; vomiting; irritability; and nightmare.

During marketing of other SSRIs and SNRIs (serotonin and norepinephrine
reuptake inhibitors), there have been spontaneous reports of adverse events
occurring upon discontinuation of these drugs, particularly when abrupt,
including the following: dysphoric mood, irritability, agitation, dizziness,
sensory disturbances (e.g., paresthesias such as electric shock sensations),
anxiety, confusion, headache, lethargy, emotional lability, insomnia,
hypomania, tinnitus, and seizures. Although these events are generally
self-limiting, some have been reported to be severe.
Patients should be monitored for these symptoms when discontinuing
treatment with Cymbalta. A gradual reduction in the dose rather than abrupt
cessation is recommended whenever possible. If intolerable symptoms occur
following a decrease in the dose or upon discontinuation of treatment, then
resuming the previously prescribed dose may be considered. Subsequently, the
physician may continue decreasing the dose but at a more gradual rate (see
<a href="#dosage">DOSAGE AND ADMINISTRATION</a>).
Use in Patients with Concomitant Illness — Clinical experience
with Cymbalta in patients with concomitant systemic illnesses is limited.
There is no information on the effect that alterations in gastric motility
may have on the stability of Cymbalta’s enteric coating. As duloxetine is
rapidly hydrolyzed in acidic media to naphthol, caution is advised in using
Cymbalta in patients with conditions that may slow gastric emptying (e.g.,
some diabetics).
Cymbalta has not been systematically evaluated in patients with a recent
history of myocardial infarction or unstable coronary artery disease.
Patients with these diagnoses were generally excluded from clinical studies
during the product’s premarketing testing. However, the electrocardiograms
of 321 patients who received Cymbalta in MDD placebo-controlled clinical
trials and had qualitatively normal ECGs at baseline were evaluated;
Cymbalta was not associated with the development of clinically significant
ECG abnormalities (see <a href="#adverse">ADVERSE REACTIONS</a>,
Electrocardiogram Changes).

In DPN placebo-controlled clinical trials, Cymbalta-treated patients did
not develop abnormal ECGs at a rate different from that in placebo-treated
patients (see <a href="#adverse">ADVERSE REACTIONS</a>, Electrocardiogram
Changes).
In clinical trials of Cymbalta for the management of neuropathic pain
associated with diabetic peripheral neuropathy, the mean duration of
diabetes was approximately 11 years, the mean baseline fasting blood glucose
was 163 mg/dL, and the mean baseline hemoglobin A1c (HbA1c) was 7.8%. In
these studies, small increases in fasting blood glucose were observed in
Cymbalta-treated patients compared to placebo at 12 weeks and routine care
at 52 weeks. The increase was similar at both time points. Overall diabetic
control did not worsen as evidenced by stable HbA1c values and by no
differences in incidence of serious and non-serious diabetes-related adverse
events relative to placebo or routine care.
Increased plasma concentrations of duloxetine, and especially of its
metabolites, occur in patients with end-stage renal disease (requiring
dialysis). For this reason, Cymbalta is not recommended for patients with
end-stage renal disease or severe renal impairment (creatinine clearance <30
mL/min) (see <a href="#pharmacology">CLINICAL PHARMACOLOGY</a> and
<a href="#dosage">DOSAGE AND ADMINISTRATION</a>).

Markedly increased exposure to duloxetine occurs in patients with hepatic
insufficiency and Cymbalta should not be administered to these patients (see
<a href="#pharmacology">CLINICAL PHARMACOLOGY</a> and <a href="#dosage">
DOSAGE AND ADMINISTRATION</a>).
<h4>Information for Patients</h4>
Prescribers or other health professionals should inform patients, their
families, and their caregivers about the benefits and risks associated with
treatment with Cymbalta and should counsel them in its appropriate use. A
patient Medication Guide About Using Antidepressants in Children and
Teenagers is available for Cymbalta. The prescriber or health professional
should instruct patients, their families, and their caregivers to read the
Medication Guide and should assist them in understanding its contents.
Patients should be given the opportunity to discuss the contents of the
Medication Guide and to obtain answers to any questions they may have. The
complete text of the Medication Guide is reprinted at the end of this
document.
Patients should be advised of the following issues and asked to alert
their prescriber if these occur while taking Cymbalta.

Clinical Worsening and Suicide Risk — Patients, their families,
and their caregivers should be encouraged to be alert to the emergence of
anxiety, agitation, panic attacks, insomnia, irritability, hostility,
aggressiveness, impulsivity, akathisia (psychomotor restlessness),
hypomania, mania, other unusual changes in behavior, worsening of
depression, and suicidal ideation, especially early during antidepressant
treatment and when the dose is adjusted up or down. Families and caregivers
of patients should be advised to observe for the emergence of such symptoms
on a day-to-day basis, since changes may be abrupt. Such symptoms should be
reported to the patient’s prescriber or health professional, especially if
they are severe, abrupt in onset, or were not part of the patient’s
presenting symptoms. Symptoms such as these may be associated with an
increased risk for suicidal thinking and behavior and indicate a need for
very close monitoring and possibly changes in the medication.
Cymbalta should be swallowed whole and should not be chewed or crushed,
nor should the contents be sprinkled on food or mixed with liquids. All of
these might affect the enteric coating.
Any psychoactive drug may impair judgment, thinking, or motor skills.
Although in controlled studies Cymbalta has not been shown to impair
psychomotor performance, cognitive function, or memory, it may be associated
with sedation and dizziness. Therefore, patients should be cautioned about
operating hazardous machinery including automobiles, until they are
reasonably certain that Cymbalta therapy does not affect their ability to
engage in such activities.
Patients should be advised to inform their physicians if they are taking,
or plan to take, any prescription or over-the-counter medications, since
there is a potential for interactions.
Although Cymbalta does not increase the impairment of mental and motor
skills caused by alcohol, use of Cymbalta concomitantly with heavy alcohol
intake may be associated with severe liver injury. For this reason, Cymbalta
should ordinarily not be prescribed for patients with substantial alcohol
use.

saturn1 · Dec 7, 2008

Patients should be advised to notify their physician if they become
pregnant or intend to become pregnant during therapy.
While patients with MDD may notice improvement with Cymbalta therapy in 1
to 4 weeks, they should be advised to continue therapy as directed.
<h4>Laboratory Tests</h4>
No specific laboratory tests are recommended.
<a href="#top">top</a>
<a name="drug">Drug</a>
Interactions 

(also see <a href="#pharmacology">CLINICAL PHARMACOLOGY</a>, Drug-Drug
Interactions)
Potential for Other Drugs to Affect Cymbalta 
Both CYP1A2 and CYP2D6 are responsible for duloxetine metabolism.
Inhibitors of CYP1A2 — Concomitant use of duloxetine with
fluvoxamine, an inhibitor of CYP1A2, results in approximately a 6-fold
increase in AUC and about a 2.5-fold increase in Cmax of duloxetine. Some
quinolone antibiotics would be expected to have similar effects and these
combinations should be avoided.
Inhibitors of CYP2D6 — Because CYP2D6 is involved in duloxetine
metabolism, concomitant use of duloxetine with potent inhibitors of CYP2D6
may result in higher concentrations of duloxetine. Paroxetine (20 mg QD)
increased the concentration of duloxetine (40 mg QD) by about 60%, and
greater degrees of inhibition are expected with higher doses of paroxetine.
Similar effects would be expected with other potent CYP2D6 inhibitors (e.g.,
fluoxetine, quinidine).

Potential for Duloxetine to Affect Other Drugs 
Drugs Metabolized by CYP1A2 — In vitro drug interaction studies
demonstrate that duloxetine does not induce CYP1A2 activity, and it is
unlikely to have a clinically significant effect on the metabolism of CYP1A2
substrates (see <a href="#pharmacology">CLINICAL PHARMACOLOGY</a>,
<a href="#drug">Drug Interactions</a>).
Drugs Metabolized by CYP2D6 — Duloxetine is a moderate inhibitor
of CYP2D6. When duloxetine was administered (at a dose of 60 mg BID) in
conjunction with a single 50-mg dose of desipramine, a CYP2D6 substrate, the
AUC of desipramine increased 3-fold. Therefore, co-administration of
Cymbalta with other drugs that are extensively metabolized by this isozyme
and which have a narrow therapeutic index, including certain antidepressants
(tricyclic antidepressants [TCAs], such as nortriptyline, amitriptyline, and
imipramine), phenothiazines and Type 1C antiarrhythmics (e.g., propafenone,
flecainide), should be approached with caution. Plasma TCA concentrations
may need to be monitored and the dose of the TCA may need to be reduced if a
TCA is co-administered with Cymbalta. Because of the risk of serious
ventricular arrhythmias and sudden death potentially associated with
elevated plasma levels of thioridazine, Cymbalta and thioridazine should not
be co-administered.

Drugs Metabolized by CYP3A — Results of in vitro studies
demonstrate that duloxetine does not inhibit or induce CYP3A activity (see
<a href="#pharmacology">CLINICAL PHARMACOLOGY</a>, Drug Interactions).
Cymbalta May Have a Clinically Important Interaction with the
Following Other Drugs:
Alcohol — When Cymbalta and ethanol were administered several
hours apart so that peak concentrations of each would coincide, Cymbalta did
not increase the impairment of mental and motor skills caused by alcohol.
In the Cymbalta clinical trials database, three Cymbalta-treated patients
had liver injury as manifested by ALT and total bilirubin elevations, with
evidence of obstruction. Substantial intercurrent ethanol use was present in
each of these cases, and this may have contributed to the abnormalities seen
(see <a href="#precautions">PRECAUTIONS</a>, Hepatotoxicity).

CNS Acting Drugs — Given the primary CNS effects of Cymbalta, it
should be used with caution when it is taken in combination with or
substituted for other centrally acting drugs, including those with a similar
mechanism of action.
Potential for Interaction with Drugs that Affect Gastric Acidity —
Cymbalta has an enteric coating that resists dissolution until reaching a
segment of the gastrointestinal tract where the pH exceeds 5.5. In extremely
acidic conditions, Cymbalta, unprotected by the enteric coating, may undergo
hydrolysis to form naphthol. Caution is advised in using Cymbalta in
patients with conditions that may slow gastric emptying (e.g., some
diabetics). Drugs that raise the gastrointestinal pH may lead to an earlier
release of duloxetine. However, co-administration of Cymbalta with aluminum-
and magnesium-containing antacids (51 mEq) or Cymbalta with famotidine, had
no significant effect on the rate or extent of duloxetine absorption after
administration of a 40-mg oral dose. It is unknown whether the concomitant
administration of proton pump inhibitors affects duloxetine absorption.
Monoamine Oxidase Inhibitors — See <a href="#contraindications">
CONTRAINDICATIONS</a> and <a href="#warnings">WARNINGS</a>.

Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis — Duloxetine was administered in the diet to mice
and rats for 2 years. 
In female mice receiving duloxetine at 140 mg/kg/day (11 times the maximum
recommended human dose [MRHD, 60 mg/day] and 6 times the human dose of 120
mg/day on a mg/m2 basis), there was an increased incidence of hepatocellular
adenomas and carcinomas. The no-effect dose was 50 mg/kg/day (4 times the
MRHD and 2 times the human dose of 120 mg/day on a mg/m2 basis). Tumor
incidence was not increased in male mice receiving duloxetine at doses up to
100 mg/kg/day (8 times the MRHD and 4 times the human dose of 120 mg/day on
a mg/m2 basis).
In rats, dietary doses of duloxetine up to 27 mg/kg/day in females (4
times the MRHD and 2 times the human dose of 120 mg/day on a mg/m2 basis)
and up to 36 mg/kg/day in males (6 times the MRHD and 3 times the human dose
of 120 mg/day on a mg/m2 basis) did not increase the incidence of tumors.
Mutagenesis — Duloxetine was not mutagenic in the in vitro
bacterial reverse mutation assay (Ames test) and was not clastogenic in an
in vivo chromosomal aberration test in mouse bone marrow cells.
Additionally, duloxetine was not genotoxic in an in vitro mammalian forward
gene mutation assay in mouse lymphoma cells or in an in vitro unscheduled
DNA synthesis (UDS) assay in primary rat hepatocytes, and did not induce
sister chromatid exchange in Chinese hamster bone marrow in vivo.

Impairment of Fertility — Duloxetine administered orally to either
male or female rats prior to and throughout mating at doses up to 45
mg/kg/day (7 times the maximum recommended human dose of 60 mg/day and 4
times the human dose of 120 mg/day on a mg/m2 basis) did not alter mating or
fertility.
Pregnancy
Pregnancy Category C — In animal reproduction studies, duloxetine
has been shown to have adverse effects on embryo/fetal and postnatal
development.
When duloxetine was administered orally to pregnant rats and rabbits
during the period of organogenesis, there was no evidence of teratogenicity
at doses up to 45 mg/kg/day (7 times the maximum recommended human dose
[MRHD, 60 mg/day] and 4 times the human dose of 120 mg/day on a mg/m2 basis,
in rat; 15 times the MRHD and 7 times the human dose of 120 mg/day on a
mg/m2 basis in rabbit). However, fetal weights were decreased at this dose,
with a no-effect dose of 10 mg/kg/day (2 times the MRHD and ≈1 times the
human dose of 120 mg/day on a mg/m2 basis in rat; 3 times the MRHD and 2
times the human dose of 120 mg/day on a mg/m2 basis in rabbits).
When duloxetine was administered orally to pregnant rats throughout
gestation and lactation, the survival of pups to 1 day postpartum and pup
body weights at birth and during the lactation period were decreased at a
dose of 30 mg/kg/day (5 times the MRHD and 2 times the human dose of 120
mg/day on a mg/m2 basis); the no-effect dose was 10 mg/kg/day. Furthermore,
behaviors consistent with increased reactivity, such as increased startle
response to noise and decreased habituation of locomotor activity, were
observed in pups following maternal exposure to 30 mg/kg/day. Post-weaning
growth and reproductive performance of the progeny were not affected
adversely by maternal duloxetine treatment.

There are no adequate and well-controlled studies in pregnant women;
therefore, duloxetine should be used during pregnancy only if the potential
benefit justifies the potential risk to the fetus.
Nonteratogenic Effects — Neonates exposed to SSRIs or serotonin
and norepinephrine reuptake inhibitors (SNRIs), late in the third trimester
have developed complications requiring prolonged hospitalization,
respiratory support, and tube feeding. Such complications can arise
immediately upon delivery. Reported clinical findings have included
respiratory distress, cyanosis, apnea, seizures, temperature instability,
feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia,
hyperreflexia, tremor, jitteriness, irritability, and constant crying. These
features are consistent with either a direct toxic effect of SSRIs and SNRIs
or, possibly, a drug discontinuation syndrome. It should be noted that, in
some cases, the clinical picture is consistent with serotonin syndrome (see
<a href="#warnings">WARNINGS</a>, Monoamine Oxidase Inhibitors). When
treating a pregnant woman with Cymbalta during the third trimester, the
physician should carefully consider the potential risks and benefits of
treatment (see <a href="#dosage">DOSAGE AND ADMINISTRATION</a>).
Labor and Delivery 
The effect of duloxetine on labor and delivery in humans is unknown.
Duloxetine should be used during labor and delivery only if the potential
benefit justifies the potential risk to the fetus.

Nursing Mothers 
Duloxetine and/or its metabolites are excreted into the milk of lactating
rats. It is unknown whether or not duloxetine and/or its metabolites are
excreted into human milk, but nursing while on Cymbalta is not recommended.
Pediatric Use 
Safety and effectiveness in the pediatric population have not been
established (see <a href="#Boxedwarning">BOX WARNING</a> and
<a href="#warnings">WARNINGS</a>, Clinical Worsening and Suicide
Risk). Anyone considering the use of Cymbalta in a child or adolescent must
balance the potential risks with the clinical need.

Geriatric Use 
Of the 2418 patients in clinical studies of Cymbalta for MDD, 5.9% (143)
were 65 years of age or over. Of the 1074 patients in the DPN studies, 33%
(357) were 65 years of age or over. No overall differences in safety or
effectiveness were observed between these subjects and younger subjects, and
other reported clinical experience has not identified differences in
responses between the elderly and younger patients, but greater sensitivity
of some older individuals cannot be ruled out.
<a href="#top">top</a>
<a name="adverse">Adverse</a>
Reactions
Cymbalta has been evaluated for safety in 2418 patients diagnosed with major
depressive disorder who participated in multiple-dose premarketing trials,
representing 1099 patient-years of exposure. Among these 2418 Cymbalta-treated
patients, 1139 patients participated in eight 8- or 9-week, placebo-controlled
trials at doses ranging from 40 to 120 mg/day, while the remaining 1279 patients
were followed for up to 1 year in an open-label safety study using flexible
doses from 80 to 120 mg/day. Two placebo-controlled studies with doses of 80 and
120 mg/day had 6-month maintenance extensions. Of these 2418 patients, 993
Cymbalta-treated patients were exposed for at least 180 days and 445
Cymbalta-treated patients were exposed for at least 1 year.
Cymbalta has also been evaluated for safety in 1074 patients with
diabetic peripheral neuropathy representing 472 patient-years of exposure.
Among these 1074 Cymbalta-treated patients, 568 patients participated in two
12- to 13-week, placebo-controlled trials at doses ranging from 20 to 120
mg/day. An additional 449 patients were enrolled in an open-label safety
study using 120 mg/day for a duration of 6 months. Another 57 patients,
originally treated with placebo, were exposed to Cymbalta for up to 12
months at 60 mg twice daily in an extension phase. Among these 1074
patients, 484 had 6 months of exposure to Cymbalta, and 220 had 12 months of
exposure.

For both MDD and DPN clinical trials, adverse reactions were assessed by
collecting adverse events, results of physical examinations, vital signs,
weights, laboratory analyses, and ECGs.
Clinical investigators recorded adverse events using descriptive
terminology of their own choosing. To provide a meaningful estimate of the
proportion of individuals experiencing adverse events, grouping similar
types of events into a smaller number of standardized event categories is
necessary. In the tables and tabulations that follow, MedDRA terminology has
been used to classify reported adverse events.
The stated frequencies of adverse events represent the proportion of
individuals who experienced, at least once, a treatment-emergent adverse
event of the type listed. An event was considered treatment-emergent if it
occurred for the first time or worsened while receiving therapy following
baseline evaluation. Events reported during the studies were not necessarily
caused by the therapy, and the frequencies do not reflect investigator
impression (assessment) of causality.
The cited figures provide the prescriber with some basis for estimating
the relative contribution of drug and non-drug factors to the adverse event
incidence rate in the population studied. The prescriber should be aware
that the figures in the tables and tabulations cannot be used to predict the
incidence of adverse events in the course of usual medical practice where
patient characteristics and other factors differ from those that prevailed
in the clinical trials. Similarly, the cited frequencies cannot be compared
with figures obtained from other clinical investigations involving different
treatments, uses, and investigators.
<h4>Adverse Events Reported as Reasons for Discontinuation of Treatment in
Placebo-Controlled Trials</h4>
Major Depressive Disorder 

Approximately 10% of the 1139 patients who received Cymbalta in the MDD
placebo-controlled trials discontinued treatment due to an adverse event,
compared with 4% of the 777 patients receiving placebo. Nausea (Cymbalta
1.4%, placebo 0.1%) was the only common adverse event reported as reason for
discontinuation and considered to be drug-related (i.e., discontinuation
occurring in at least 1% of the Cymbalta-treated patients and at a rate of
at least twice that of placebo).
Diabetic Peripheral Neuropathic Pain 
Approximately 14% of the 568 patients who received Cymbalta in the DPN
placebo-controlled trials discontinued treatment due to an adverse event,
compared with 7% of the 223 patients receiving placebo. Nausea (Cymbalta
3.5%, placebo 0.4%), dizziness (Cymbalta 1.6%, placebo 0.4%), somnolence
(Cymbalta 1.6%, placebo 0%) and fatigue (Cymbalta 1.1%, placebo 0%) were the
common adverse events reported as reasons for discontinuation and considered
to be drug-related (i.e., discontinuation occurring in at least 1% of the
Cymbalta-treated patients and at a rate of at least twice that of placebo).
<h4>Adverse Events Occurring at an Incidence of 2% or More Among
Cymbalta-Treated Patients in Placebo-Controlled Trials</h4>
Major Depressive Disorder 
Table 1 gives the incidence of treatment-emergent adverse events that
occurred in 2% or more of patients treated with Cymbalta in the premarketing
acute phase of MDD placebo-controlled trials and with an incidence greater
than placebo. The most commonly observed adverse events in Cymbalta-treated
MDD patients (incidence of 5% or greater and at least twice the incidence in
placebo patients) were: nausea; dry mouth; constipation; decreased appetite;
fatigue; somnolence; and increased sweating (see Table 1).

<div align="center">
<table width="100%" bgcolor="#ffffdd" border="1" bordercolor="#5a7b9e" cellpadding="3" cellspacing="0">
<tbody><tr>
<td colspan="3" valign="top" height="36">
Table 1: Treatment-Emergent Adverse Events
Incidence in MDD Placebo-Controlled Trials1 </td>
</tr>
<tr>

<td rowspan="2" valign="top" width="50%">
System Organ Class / Adverse Event </td>
<td colspan="2" valign="top" width="50%">
Percentage of Patients Reporting Event 
</td>
</tr>
<tr>
<td valign="top" width="26%" height="19">

Cymbalta (N=1139) </td>
<td valign="top" width="24%" height="19">
Placebo (N=777) </td>
</tr>
<tr>
<td colspan="3" valign="top">
Gastrointestinal Disorders </td>

</tr>
<tr>
<td valign="top" width="50%">
Nausea </td>
<td valign="top" width="26%">
20 </td>
<td valign="top" width="24%">
7 </td>

</tr>
<tr>
<td valign="top" width="50%">
Dry mouth </td>
<td valign="top" width="26%">
15 </td>
<td valign="top" width="24%">
6 </td>

</tr>
<tr>
<td valign="top" width="50%">
Constipation </td>
<td valign="top" width="26%">
11 </td>
<td valign="top" width="24%">
4 </td>

</tr>
<tr>
<td valign="top" width="50%">
Diarrhea </td>
<td valign="top" width="26%">
8 </td>
<td valign="top" width="24%">
6 </td>

</tr>
<tr>
<td valign="top" width="50%">
Vomiting </td>
<td valign="top" width="26%">
5 </td>
<td valign="top" width="24%">
3 </td>

</tr>
<tr>
<td colspan="3" valign="top">
Metabolism and Nutrition Disorders </td>
</tr>
<tr>
<td valign="top" width="50%">
Appetite decreased2 </td>

<td valign="top" width="26%">
8 </td>
<td valign="top" width="24%">
2 </td>
</tr>
<tr>
<td colspan="3" valign="top">
Investigations </td>

</tr>
<tr>
<td valign="top" width="50%">
Weight decreased </td>
<td valign="top" width="26%">
2 </td>
<td valign="top" width="24%">
1 </td>

</tr>
<tr>
<td colspan="3" valign="top">
General Disorders and Administration Site
Conditions </td>
</tr>
<tr>
<td valign="top" width="50%">
Fatigue </td>

<td valign="top" width="26%">
8 </td>
<td valign="top" width="24%">
4 </td>
</tr>
<tr>
<td colspan="3" valign="top">
Nervous System Disorders </td>

</tr>
<tr>
<td valign="top" width="50%">
Dizziness </td>
<td valign="top" width="26%">
9 </td>
<td valign="top" width="24%">
5 </td>

</tr>
<tr>
<td valign="top" width="50%">
Somnolence </td>
<td valign="top" width="26%">
7 </td>
<td valign="top" width="24%">
3 </td>

</tr>
<tr>
<td valign="top" width="50%">
Tremor </td>
<td valign="top" width="26%">
3 </td>
<td valign="top" width="24%">
1 </td>

</tr>
<tr>
<td colspan="3" valign="top">
Skin and Subcutaneous Tissue Disorders 
</td>
</tr>
<tr>
<td valign="top" width="50%">

Sweating increased </td>
<td valign="top" width="26%">
6 </td>
<td valign="top" width="24%">
2 </td>
</tr>
<tr>

<td colspan="3" valign="top">
Vascular Disorders </td>
</tr>
<tr>
<td valign="top" width="50%">
Hot flushes </td>
<td valign="top" width="26%">
2 </td>

<td valign="top" width="24%">
1 </td>
</tr>
<tr>
<td colspan="3" valign="top">
Eye Disorders </td>
</tr>
<tr>

<td valign="top" width="50%">
Vision blurred </td>
<td valign="top" width="26%">
4 </td>
<td valign="top" width="24%">
1 </td>
</tr>

<tr>
<td colspan="3" valign="top">
Psychiatric Disorders </td>
</tr>
<tr>
<td valign="top" width="50%">
Insomnia3 </td>

<td valign="top" width="26%">
11 </td>
<td valign="top" width="24%">
6 </td>
</tr>
<tr>
<td valign="top" width="50%">
Anxiety </td>

<td valign="top" width="26%">
3 </td>
<td valign="top" width="24%">
2 </td>
</tr>
<tr>
<td valign="top" width="50%">
Libido decreased </td>

<td valign="top" width="26%">
3 </td>
<td valign="top" width="24%">
1 </td>
</tr>
<tr>
<td valign="top" width="50%">
Orgasm abnormal4 </td>

<td valign="top" width="26%">
3 </td>
<td valign="top" width="24%">
1 </td>
</tr>
<tr>
<td colspan="3" valign="top">
Reproductive System and Breast Disorders 

</td>
</tr>
<tr>
<td valign="top" width="50%">
Erectile dysfunction5 </td>
<td valign="top" width="26%">
4 </td>

<td valign="top" width="24%">
1 </td>
</tr>
<tr>
<td valign="top" width="50%">
Ejaculation delayed5 </td>
<td valign="top" width="26%">

3 </td>
<td valign="top" width="24%">
1 </td>
</tr>
<tr>
<td valign="top" width="50%">
Ejaculatory dysfunction5, 6 </td>

<td valign="top" width="26%">
3 </td>
<td valign="top" width="24%">
1 </td>
</tr>
<tr>
<td colspan="3" valign="top" height="72">
1 Events reported by at least 2%
of patients treated with Cymbalta and more often with placebo.
The following events were reported by at least 2% of patients
treated with Cymbalta for MDD and had an incidence equal to or
less than placebo: upper abdominal pain, palpitations,
dyspepsia, back pain, arthralgia, headache, pharyngitis, cough,
nasopharyngitis, and upper respiratory tract infection. </td>

</tr>
<tr>
<td colspan="3" valign="top">
2 Term includes anorexia. </td>
</tr>
<tr>
<td colspan="3" valign="top">

3 Term includes middle insomnia.
</td>
</tr>
<tr>
<td colspan="3" valign="top">
4 Term includes anorgasmia. </td>
</tr>

saturn1 · Dec 7, 2008

<tr>
<td colspan="3" valign="top">
5 Male patients only. </td>
</tr>
<tr>
<td colspan="3" valign="top">
6 Term includes ejaculation
disorder and ejaculation failure. </td>

</tr>
</tbody></table>
</div>
Diabetic Peripheral Neuropathic Pain 
Table 2 gives the incidence of treatment-emergent adverse events that
occurred in 2% or more of patients treated with Cymbalta in the premarketing
acute phase of DPN placebo-controlled trials (doses of 20 to 120 mg/day) and
with an incidence greater than placebo. The most commonly observed adverse
events in Cymbalta-treated DPN patients (incidence of 5% or greater and at
least twice the incidence in placebo patients) were: nausea; somnolence;
dizziness; constipation; dry mouth; hyperhidrosis; decreased appetite; and
asthenia (see Table 2).
<div align="center">
<table width="100%" bgcolor="#ffffdd" border="1" bordercolor="#5a7b9e" cellpadding="2" cellspacing="0">
<tbody><tr>

<td colspan="5" valign="top" height="36">
Table 2: Treatment-Emergent Adverse Events
Incidence
 in DPN Placebo-Controlled Trials1
</td>
</tr>
<tr>
<td rowspan="2" valign="top" width="39%">

System Organ Class /
 Adverse Event </td>
<td colspan="4" valign="top" width="61%">
Percentage of Patients Reporting Event 
</td>
</tr>
<tr>

<td valign="top" width="16%" height="55">
Cymbalta 60
<a href="javascript:defwindow('mg')">mg</a> BID (N=225) 
</td>
<td valign="top" width="17%" height="55">
Cymbalta 60
<a href="javascript:defwindow('mg')">mg</a> QD (N=228) </td>

<td valign="top" width="16%" height="55">
Cymbalta 20
<a href="javascript:defwindow('mg')">mg</a> QD (N=115) </td>
<td valign="top" width="12%" height="55">
Placebo (N=223) </td>
</tr>
<tr>

<td colspan="5" valign="top">
Gastrointestinal Disorders </td>
</tr>
<tr>
<td valign="top" width="39%">
Nausea </td>
<td valign="top" width="16%">
30 </td>

<td valign="top" width="17%">
22 </td>
<td valign="top" width="16%">
14 </td>
<td valign="top" width="12%">
9 </td>
</tr>

<tr>
<td valign="top" width="39%">
Constipation </td>
<td valign="top" width="16%">
15 </td>
<td valign="top" width="17%">
11 </td>

<td valign="top" width="16%">
5 </td>
<td valign="top" width="12%">
3 </td>
</tr>
<tr>
<td valign="top" width="39%">
Diarrhea </td>

<td valign="top" width="16%">
7 </td>
<td valign="top" width="17%">
11 </td>
<td valign="top" width="16%">
13 </td>
<td valign="top" width="12%">

6 </td>
</tr>
<tr>
<td valign="top" width="39%">
Dry mouth </td>
<td valign="top" width="16%">
12 </td>

<td valign="top" width="17%">
7 </td>
<td valign="top" width="16%">
5 </td>
<td valign="top" width="12%">
4 </td>
</tr>

<tr>
<td valign="top" width="39%">
Vomiting </td>
<td valign="top" width="16%">
5 </td>
<td valign="top" width="17%">
5 </td>

<td valign="top" width="16%">
6 </td>
<td valign="top" width="12%">
4 </td>
</tr>
<tr>
<td valign="top" width="39%">
Dyspepsia </td>

<td valign="top" width="16%">
4 </td>
<td valign="top" width="17%">
4 </td>
<td valign="top" width="16%">
4 </td>
<td valign="top" width="12%">

3 </td>
</tr>
<tr>
<td valign="top" width="39%">
Loose stools </td>
<td valign="top" width="16%">
2 </td>

<td valign="top" width="17%">
3 </td>
<td valign="top" width="16%">
2 </td>
<td valign="top" width="12%">
1 </td>
</tr>

<tr>
<td colspan="5" valign="top">
General Disorders and Administration Site
Conditions </td>
</tr>
<tr>
<td valign="top" width="39%">
Fatigue </td>
<td valign="top" width="16%">

12 </td>
<td valign="top" width="17%">
10 </td>
<td valign="top" width="16%">
2 </td>
<td valign="top" width="12%">
5 </td>

</tr>
<tr>
<td valign="top" width="39%">
Asthenia </td>
<td valign="top" width="16%">
8 </td>
<td valign="top" width="17%">
4 </td>

<td valign="top" width="16%">
2 </td>
<td valign="top" width="12%">
1 </td>
</tr>
<tr>
<td valign="top" width="39%">
Pyrexia </td>

<td valign="top" width="16%">
3 </td>
<td valign="top" width="17%">
1 </td>
<td valign="top" width="16%">
2 </td>
<td valign="top" width="12%">

1 </td>
</tr>
<tr>
<td colspan="5" valign="top">
Infections and Infestations </td>
</tr>
<tr>
<td valign="top" width="39%">

Nasopharyngitis </td>
<td valign="top" width="16%">
9 </td>
<td valign="top" width="17%">
7 </td>
<td valign="top" width="16%">
9 </td>

<td valign="top" width="12%">
5 </td>
</tr>
<tr>
<td colspan="5" valign="top">
Metabolism and Nutrition Disorders </td>
</tr>
<tr>

<td valign="top" width="39%">
Decreased appetite </td>
<td valign="top" width="16%">
11 </td>
<td valign="top" width="17%">
4 </td>
<td valign="top" width="16%">

3 </td>
<td valign="top" width="12%">
<1 </td>
</tr>
<tr>
<td valign="top" width="39%">
Anorexia </td>

<td valign="top" width="16%">
5 </td>
<td valign="top" width="17%">
3 </td>
<td valign="top" width="16%">
3 </td>
<td valign="top" width="12%">

<1 </td>
</tr>
<tr>
<td colspan="5" valign="top">
Musculoskeletal and Connective Tissue
Disorders </td>
</tr>
<tr>
<td valign="top" width="39%">

Muscle cramp </td>
<td valign="top" width="16%">
4 </td>
<td valign="top" width="17%">
4 </td>
<td valign="top" width="16%">
5 </td>

<td valign="top" width="12%">
3 </td>
</tr>
<tr>
<td valign="top" width="39%">
Myalgia </td>
<td valign="top" width="16%">
4 </td>

<td valign="top" width="17%">
1 </td>
<td valign="top" width="16%">
3 </td>
<td valign="top" width="12%">
<1 </td>
</tr>

<tr>
<td colspan="5" valign="top">
Nervous System Disorders </td>
</tr>
<tr>
<td valign="top" width="39%">
Somnolence </td>
<td valign="top" width="16%">

21 </td>
<td valign="top" width="17%">
15 </td>
<td valign="top" width="16%">
7 </td>
<td valign="top" width="12%">
5 </td>

</tr>
<tr>
<td valign="top" width="39%">
Headache </td>
<td valign="top" width="16%">
15 </td>
<td valign="top" width="17%">
13 </td>

<td valign="top" width="16%">
13 </td>
<td valign="top" width="12%">
10 </td>
</tr>
<tr>
<td valign="top" width="39%">
Dizziness </td>

saturn1 · Dec 7, 2008

<td valign="top" width="16%">
17 </td>
<td valign="top" width="17%">
14 </td>
<td valign="top" width="16%">
6 </td>
<td valign="top" width="12%">

6 </td>
</tr>
<tr>
<td valign="top" width="39%">
Tremor </td>
<td valign="top" width="16%">
5 </td>

<td valign="top" width="17%">
1 </td>
<td valign="top" width="16%">
0 </td>
<td valign="top" width="12%">
0 </td>
</tr>

<tr>
<td colspan="5" valign="top">
Psychiatric Disorders </td>
</tr>
<tr>
<td valign="top" width="39%">
Insomnia </td>
<td valign="top" width="16%">

13 </td>
<td valign="top" width="17%">
8 </td>
<td valign="top" width="16%">
9 </td>
<td valign="top" width="12%">
7 </td>

</tr>
<tr>
<td colspan="5" valign="top">
Renal and Urinary Disorders </td>
</tr>
<tr>
<td valign="top" width="39%">
Pollakiuria </td>

<td valign="top" width="16%">
5 </td>
<td valign="top" width="17%">
1 </td>
<td valign="top" width="16%">
3 </td>
<td valign="top" width="12%">

2 </td>
</tr>
<tr>
<td colspan="5" valign="top" height="2">
Reproductive System and Breast Disorders 
</td>
</tr>
<tr>

<td valign="top" width="39%">
Erectile dysfunction2 </td>
<td valign="top" width="16%">
4 </td>
<td valign="top" width="17%">
1 </td>

<td valign="top" width="16%">
0 </td>
<td valign="top" width="12%">
0 </td>
</tr>
<tr>
<td colspan="5" valign="top">
Respiratory, Thoracic and Mediastinal
Disorders </td>

</tr>
<tr>
<td valign="top" width="39%">
Cough </td>
<td valign="top" width="16%">
5 </td>
<td valign="top" width="17%">
3 </td>

<td valign="top" width="16%">
6 </td>
<td valign="top" width="12%">
4 </td>
</tr>
<tr>
<td valign="top" width="39%">
Pharyngolaryngeal pain </td>

<td valign="top" width="16%">
6 </td>
<td valign="top" width="17%">
1 </td>
<td valign="top" width="16%">
3 </td>
<td valign="top" width="12%">

1 </td>
</tr>
<tr>
<td colspan="5" valign="top">
Skin and Subcutaneous Tissue 
Disorders </td>

</tr>
<tr>
<td valign="top" width="39%">
Hyperhidrosis </td>
<td valign="top" width="16%">
8 </td>
<td valign="top" width="17%">
6 </td>

<td valign="top" width="16%">
6 </td>
<td valign="top" width="12%">
2 </td>
</tr>
<tr>
<td colspan="5" valign="top" height="28">
1 Events reported by at least 2%
of patients treated with Cymbalta and more often than placebo.
The following events were reported by at least 2% of patients
treated with Cymbalta for DPN and had an
<a href="javascript:defwindow('incidence')">incidence</a> equal
to or less than placebo: <a href="javascript:defwindow('edema')">

edema</a> peripheral, influenza, upper
<a href="javascript:defwindow('respiratory')">respiratory</a>
<a href="javascript:defwindow('tract')">tract</a> infection,
<a href="javascript:defwindow('back')">back</a> pain,
arthralgia, pain in extremity, and pruritus. </td>
</tr>
<tr>

<td colspan="5" valign="top">
2 Male patients only. </td>
</tr>
</tbody></table>
</div>
Adverse events seen in men and women were generally similar except for
effects on sexual function (described below). Clinical studies of Cymbalta
did not suggest a difference in adverse event rates in people over or under
65 years of age. There were too few non-Caucasian patients studied to
determine if these patients responded differently from Caucasian patients.
Effects on Male and Female Sexual Function 

Although changes in sexual desire, sexual performance and sexual
satisfaction often occur as manifestations of a psychiatric disorder, they
may also be a consequence of pharmacologic treatment. Reliable estimates of
the incidence and severity of untoward experiences involving sexual desire,
performance and satisfaction are difficult to obtain, however, in part
because patients and physicians may be reluctant to discuss them.
Accordingly, estimates of the incidence of untoward sexual experience and
performance cited in product labeling are likely to underestimate their
actual incidence. Table 3 displays the incidence of sexual side effects
spontaneously reported by at least 2% of either male or female patients
taking Cymbalta in MDD placebo-controlled trials.
<div align="center">
<table width="100%" bgcolor="#ffffdd" border="1" bordercolor="#5a7b9e" cellpadding="3" cellspacing="0">
<tbody><tr>
<td colspan="5" valign="top" height="36">
Table 3: Treatment-Emergent Sexual
Dysfunction-Related Adverse Events Incidence in MDD
Placebo-Controlled Trials1 </td>
</tr>

<tr>
<td rowspan="3" valign="top" width="38%">
Adverse Event </td>
<td colspan="4" valign="top" width="62%">
Percentage of Patients Reporting Event 
</td>
</tr>
<tr>

<td colspan="2" valign="top" width="33%">
% Male Patients </td>
<td colspan="2" valign="top" width="29%">
% Female Patients </td>
</tr>
<tr>
<td valign="top" width="17%">
Cymbalta (N=378) </td>

<td valign="top" width="15%">
Placebo (N=247) </td>
<td valign="top" width="17%">
Cymbalta (N=761) </td>
<td valign="top" width="12%">
Placebo (N=530) </td>
</tr>

<tr>
<td valign="top" width="38%">
Orgasm abnormal2 </td>
<td valign="top" width="17%">
4 </td>
<td valign="top" width="15%">
1 </td>

<td valign="top" width="17%">
2 </td>
<td valign="top" width="12%">
0 </td>
</tr>
<tr>
<td valign="top" width="38%">
Ejaculatory dysfunction3 </td>

<td valign="top" width="17%">
3 </td>
<td valign="top" width="15%">
1 </td>
<td valign="top" width="17%">
NA </td>
<td valign="top" width="12%">

NA </td>
</tr>
<tr>
<td valign="top" width="38%">
Libido decreased </td>
<td valign="top" width="17%">
6 </td>

<td valign="top" width="15%">
2 </td>
<td valign="top" width="17%">
1 </td>
<td valign="top" width="12%">
0 </td>
</tr>

<tr>
<td valign="top" width="38%">
Erectile dysfunction </td>
<td valign="top" width="17%">
4 </td>
<td valign="top" width="15%">
1 </td>

<td valign="top" width="17%">
NA </td>
<td valign="top" width="12%">
NA </td>
</tr>
<tr>
<td valign="top" width="38%">
Ejaculation delayed </td>

<td valign="top" width="17%">
3 </td>
<td valign="top" width="15%">
1 </td>
<td valign="top" width="17%">
NA </td>
<td valign="top" width="12%">

NA </td>
</tr>
<tr>
<td colspan="5" valign="top">
1 Events reported by at least 2%
of patients treated with Cymbalta and more often than with
placebo. </td>
</tr>
<tr>

<td colspan="5" valign="top">
2 Term includes anorgasmia. </td>
</tr>
<tr>
<td colspan="5" valign="top">
3 Term includes
<a href="javascript:defwindow('ejaculation')">ejaculation</a>

<a href="javascript:defwindow('disorder')">disorder</a> and
ejaculation failure. </td>
</tr>
<tr>
<td colspan="5" valign="top" height="5">
NA=Not applicable. </td>
</tr>
</tbody></table>

</div>
Because adverse sexual events are presumed to be voluntarily
underreported, the Arizona Sexual Experience Scale (ASEX), a validated
measure designed to identify sexual side effects, was used prospectively in
4 MDD placebo-controlled trials. In these trials, as shown in Table 4 below,
patients treated with Cymbalta experienced significantly more sexual
dysfunction, as measured by the total score on the ASEX, than did patients
treated with placebo. Gender analysis showed that this difference occurred
only in males. Males treated with Cymbalta experienced more difficulty with
ability to reach orgasm (ASEX Item 4) than males treated with placebo.
Females did not experience more sexual dysfunction on Cymbalta than on
placebo as measured by ASEX total score. These studies did not, however,
include an active control drug with known effects on female sexual
dysfunction, so that there is no evidence that its effects differ from other
antidepressants. Negative numbers signify an improvement from a baseline
level of dysfunction, which is commonly seen in depressed patients.
Physicians should routinely inquire about possible sexual side effects.
<div align="center">
<table width="100%" bgcolor="#ffffdd" border="1" bordercolor="#5a7b9e" cellpadding="3" cellspacing="0">
<tbody><tr>
<td colspan="5" valign="top" height="5">
Table 4: Mean Change in ASEX Scores by Gender
in MDD Placebo-Controlled Trials </td>
</tr>

<tr>
<td rowspan="2" valign="top" width="43%"> </td>
<td colspan="2" valign="top" width="27%">
Male Patients </td>
<td colspan="2" valign="top" width="30%">
Female Patients </td>
</tr>
<tr>

<td valign="top" width="14%" height="37">
Cymbalta (n=175)</td>
<td valign="top" width="14%" height="37">
Placebo (n=83)</td>
<td valign="top" width="14%" height="37">
Cymbalta (n=241)</td>
<td valign="top" width="16%" height="37">

Placebo (n=126)</td>
</tr>
<tr>
<td valign="top" width="43%">
ASEX Total (Items 1-5) </td>
<td valign="top" width="14%">
0.56* </td>

<td valign="top" width="14%">
-1.07 </td>
<td valign="top" width="14%">
-1.15 </td>
<td valign="top" width="16%">
-1.07 </td>
</tr>

<tr>
<td valign="top" width="43%">
Item 1 — Sex drive </td>
<td valign="top" width="14%">
-0.07 </td>
<td valign="top" width="14%">
-0.12 </td>

<td valign="top" width="14%">
-0.32 </td>
<td valign="top" width="16%">
-0.24 </td>
</tr>
<tr>
<td valign="top" width="43%">
Item 2 — Arousal </td>

<td valign="top" width="14%">
0.01 </td>
<td valign="top" width="14%">
-0.26 </td>
<td valign="top" width="14%">
-0.21 </td>
<td valign="top" width="16%">

-0.18 </td>
</tr>
<tr>
<td valign="top" width="43%">
Item 3 — Ability to achieve
<a href="javascript:defwindow('erection')">erection</a> (men);
Lubrication(women) </td>
<td valign="top" width="14%">

0.03 </td>
<td valign="top" width="14%">
-0.25 </td>
<td valign="top" width="14%">
-0.17 </td>
<td valign="top" width="16%">
-0.18 </td>

</tr>
<tr>
<td valign="top" width="43%">
Item 4 — Ease of reaching orgasm </td>
<td valign="top" width="14%">
0.40** </td>
<td valign="top" width="14%">
-0.24 </td>

<td valign="top" width="14%">
-0.09 </td>
<td valign="top" width="16%">
-0.13 </td>
</tr>
<tr>
<td valign="top" width="43%">
Item 5 — Orgasm satisfaction </td>

<td valign="top" width="14%">
0.09 </td>
<td valign="top" width="14%">
-0.13 </td>
<td valign="top" width="14%">
-0.11 </td>
<td valign="top" width="16%">

-0.17 </td>
</tr>
<tr>
<td colspan="5" valign="top">
n=Number of patients with non-missing change
<a href="javascript:defwindow('score')">score</a> for ASEX
total. </td>
</tr>

<tr>
<td colspan="5" valign="top">
*p=0.013 versus placebo. </td>
</tr>
<tr>
<td colspan="5" valign="top">
**p<0.001 versus placebo. </td>

</tr>
</tbody></table>
</div>
Urinary Hesitation 
Cymbalta is in a class of drugs known to affect urethral resistance. If
symptoms of urinary hesitation develop during treatment with Cymbalta,
consideration should be given to the possibility that they might be
drug-related.
Laboratory Changes 
Cymbalta treatment, for up to 9-weeks in MDD or 13-weeks in DPN
placebo-controlled clinical trials, was associated with small mean increases
from baseline to endpoint in ALT, AST, CPK, and alkaline phosphatase;
infrequent, modest, transient, abnormal values were observed for these
analytes in Cymbalta-treated patients when compared with placebo-treated
patients (see <a href="#precautions">PRECAUTIONS</a>).

Vital Sign Changes 
Cymbalta treatment, for up to 9-weeks in MDD placebo-controlled clinical
trials of 40 to 120 mg daily doses caused increases in blood pressure,
averaging 2 mm Hg systolic and 0.5 mm Hg diastolic compared to placebo and
an increase in the incidence of at least one measurement of systolic blood
pressure over 140 mm Hg (see <a href="#precautions">PRECAUTIONS</a>). 
Cymbalta treatment, for up to 9-weeks in MDD placebo-controlled clinical
trials and for up to 13-weeks in DPN placebo-controlled trials caused a
small increase in heart rate compared to placebo of about 2 beats per
minute.
Weight Changes 
In MDD placebo-controlled clinical trials, patients treated with Cymbalta
for up to 9-weeks experienced a mean weight loss of approximately 0.5 kg,
compared with a mean weight gain of approximately 0.2 kg in placebo-treated
patients. 

In DPN placebo-controlled clinical trials, patients treated with Cymbalta
for up to 13-weeks experienced a mean weight loss of approximately 1.1 kg,
compared with a mean weight gain of approximately 0.2 kg in placebo-treated
patients.
Electrocardiogram Changes 
Electrocardiograms were obtained from 321 Cymbalta-treated patients with
major depressive disorder and 169 placebo-treated patients in clinical
trials lasting up to 8-weeks. The rate-corrected QT (QTc) interval in
Cymbalta-treated patients did not differ from that seen in placebo-treated
patients. No clinically significant differences were observed for QT, PR,
and QRS intervals between Cymbalta-treated and placebo-treated patients. 
Electrocardiograms were obtained from 528 Cymbalta-treated patients with DPN
and 205 placebo-treated patients in clinical trials lasting up to 13-weeks.
The rate-corrected QT (QTc) interval in Cymbalta-treated patients did not
differ from that seen in placebo-treated patients. No clinically significant
differences were observed for QT, P
Other Adverse Events Observed During the Premarketing and
Postmarketing Clinical Trial Evaluation of Cymbalta for MDD and the Pain of
DPN
Following is a list of modified MedDRA terms that reflect
treatment-emergent adverse events as defined in the introduction to the
ADVERSE REACTIONS section reported by patients treated with Cymbalta at
multiple doses throughout the dose range studied during any phase of a trial
within the premarketing and postmarketing database. The events included are
those not already listed in both Table 1 and Table 2 and not considered in
the WARNINGS and PRECAUTIONS sections. The events were reported with an
incidence of greater than or equal to 0.05% and by more than one patient,
are not common as background events and were considered possibly drug
related (e.g., because of the drug’s pharmacology) or potentially important.

It is important to emphasize that, although the events reported occurred
during treatment with Cymbalta, they were not necessarily caused by it.
Events are further categorized by body system and listed in order of
decreasing frequency according to the following definitions: frequent
adverse events are those occurring in at least 1/100 patients; infrequent
adverse events are those occurring in 1/100 to 1/1000 patients; rare events
are those occurring in fewer than 1/1000 patients.
Blood and Lymphatic System Disorders — Infrequent: anemia,
leukopenia, increased white blood cell count, lymphadenopathy, and
thrombocytopenia.
Cardiac Disorders — Frequent: palpitations; Infrequent: atrial
fibrillation, bundle branch block right, cardiac failure, cardiac failure
congestive, coronary artery disease, myocardial infarction, and tachycardia.
Ear and Labyrinth Disorders — Frequent: vertigo.

Eye Disorders — Frequent: vision blurred; Infrequent: diplopia,
glaucoma, keroconjunctivitis sicca, macular degeneration, maculopathy,
photopsia, retinal detachment, and visual disturbance.
Gastrointestinal Disorders — Frequent: dyspepsia and gastritis;
Infrequent: apthous stomatitis, blood in stool, colitis, diverticulitis,
dysphagia, eructation, esophageal stenosis acquired, gastric irritation,
gastric ulcer, gastroenteritis, gingivitis, impaired gastric emptying,
irritable bowel syndrome, lower abdominal pain, melena, and stomatitis.
General Disorders and Administration Site Conditions — Frequent:
asthenia; Infrequent: edema, feeling abnormal, feeling hot and/or cold,
feeling jittery, influenza-like illness, malaise, rigors, and thirst.
Hepato-biliary Disorders — Infrequent: hepatic steatosis.

Investigations — Frequent: weight decreased; Infrequent: blood
cholesterol increased, blood creatinine increased, and urine output
decreased, and weight increased.
Metabolism and Nutrition Disorders — Frequent: hypoglycemia and
increased appetite; Infrequent: dehydration, dyslipidemia,
hypercholesterolemia, hyperlipidemia, and hypertriglyceridemia.
Musculoskeletal and Connective Tissue Disorders — Frequent: muscle
tightness and muscle twitching; Infrequent: muscular weakness.
Nervous System Disorders — Frequent: dysgeusia and hypoesthesia;
Infrequent: ataxia and dysarthria.

Psychiatric Disorders — Frequent: anorgasmia, anxiety,
hypersomnia, initial insomnia, irritability, lethargy, libido decreased,
middle insomnia, nervousness, nightmare, restlessness, and sleep disorder;
Infrequent: agitation, bruxism, completed suicide, disorientation, loss of
libido, mania, mood swings, orgasm abnormal, pressure of speech,
sluggishness, suicide attempt, and tension.
Renal and Urinary Disorders — Frequent: dysuria and urinary
hesitation; Infrequent: micturition urgency, nephropathy, nocturia, urinary
incontinence, urinary retention, and urine flow decreased.
Reproductive System and Breast Disorders — Frequent: ejaculation
delayed and ejaculation disorder.
Respiratory, Thoracic and Mediastinal Disorders — Frequent:
yawning; Infrequent: oropharyngeal swelling.

Skin and Subcutaneous Tissue Disorders — Frequent: night sweats,
pruritus, rash, and skin ulcer; Infrequent: acne, alopecia, cold sweat,
ecchymosis, eczema, erythema, erythematous rash, exfoliative dermatitis,
face edema, hyperkeratosis, increased tendency to bruise, photosensitivity
reaction, and pruritic rash.
Vascular Disorders — Frequent: hot flush; Infrequent: flushing,
hypertensive crisis, peripheral coldness, peripheral edema, and phlebitis.
Postmarketing Spontaneous Reports
Adverse events reported since market introduction that were temporally
related to Cymbalta therapy include rash reported rarely and the following
adverse events reported very rarely: alanine aminotransferase increased,
alkaline phosphatase increased, anaphylactic reaction, angioneurotic edema,
aspartate aminotransferase increased, bilirubin increased, glaucoma,
hepatitis, hyponatremia, jaundice, orthostatic hypotension (especially at
the initiation of treatment), Stevens-Johnson Syndrome, syncope (especially
at initiation of treatment), and urticaria.
<div align="center">

<table id="table1" border="0" cellpadding="0" cellspacing="5">
<tbody><tr>
<td align="center">



<table align="right">
<tbody><tr>
<td>
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</td>
</tr>
</tbody></table>
</div>

<a name="Drug_Abuse">Drug Abuse</a>
and Dependence
Controlled Substance Class 
Duloxetine is not a controlled substance.
Physical and Psychological Dependence
In animal studies, duloxetine did not demonstrate barbiturate-like
(depressant) abuse potential. In drug dependence studies, duloxetine did not
demonstrate dependence-producing potential in rats.

While Cymbalta has not been systematically studied in humans for its
potential for abuse, there was no indication of drug-seeking behavior in the
clinical trials. However, it is not possible to predict on the basis of
premarketing experience the extent to which a CNS active drug will be
misused, diverted, and/or abused once marketed. Consequently, physicians
should carefully evaluate patients for a history of drug abuse and follow
such patients closely, observing them for signs of misuse or abuse of
Cymbalta (e.g., development of tolerance, incrementation of dose,
drug-seeking behavior).
<a href="#top">top</a>
<a name="overdose">Overdose</a>

There is limited clinical experience with Cymbalta overdose in humans.
In premarketing clinical trials, as of October 2003, no cases of fatal
acute overdose of Cymbalta have been reported. Four non-fatal acute
ingestions of Cymbalta (300 to 1400 mg), alone or in combination with
other drugs, have been reported.
Management of Overdose 
There is no specific antidote to Cymbalta. In case of acute overdose,
treatment should consist of those general measures employed in the
management of overdose with any drug.

An adequate airway, oxygenation, and ventilation should be assured, and
cardiac rhythm and vital signs should be monitored. Induction of emesis is
not recommended. Gastric lavage with a large-bore orogastric tube with
appropriate airway protection, if needed, may be indicated if performed soon
after ingestion or in symptomatic patients.
Activated charcoal may be useful in limiting absorption of duloxetine
from the gastrointestinal tract. Administration of activated charcoal has
been shown to decrease AUC and Cmax by an average of one-third, although
some subjects had a limited effect of activated charcoal. Due to the large
volume of distribution of this drug, forced diuresis, dialysis,
hemoperfusion, and exchange transfusion are unlikely to be beneficial.
In managing overdose, the possibility of multiple drug involvement should
be considered. A specific caution involves patients who are taking or have
recently taken Cymbalta and might ingest excessive quantities of a TCA. In
such a case, decreased clearance of the parent tricyclic and/or its active
metabolite may increase the possibility of clinically significant sequelae
and extend the time needed for close medical observation (see PRECAUTIONS,
Drug Interactions). The physician should consider contacting a poison
control center for additional information on the treatment of any overdose.
Telephone numbers for certified poison control centers are listed in the
Physicians’ Desk Reference (PDR).
<a href="#top">top</a>
<a name="dosage">Dosage</a>
and Administration
Initial Treatment

Major Depressive Disorder 
Cymbalta should be administered at a total dose of 40 mg/day (given as
20 mg BID) to 60 mg/day (given either once a day or as 30 mg BID) without
regard to meals. 
There is no evidence that doses greater than 60 mg/day confer any additional
benefits.
Diabetic Peripheral Neuropathic Pain 
Cymbalta should be administered at a total dose of 60 mg/day given once a
day, without regard to meals.
While a 120 mg/day dose was shown to be safe and effective, there is no
evidence that doses higher than 60 mg confer additional significant benefit,
and the higher dose is clearly less well tolerated. For patients for whom
tolerability is a concern, a lower starting dose may be considered. Since
diabetes is frequently complicated by renal disease, a lower starting dose
and gradual increase in dose should be considered for patients with renal
impairment (see <a href="#pharmacology">CLINICAL PHARMACOLOGY</a>, Special
Populations and below).

Maintenance/Continuation/Extended Treatment
Major Depressive Disorder 
It is generally agreed that acute episodes of major depression require
several months or longer of sustained pharmacologic therapy. There is
insufficient evidence available to answer the question of how long a patient
should continue to be treated with Cymbalta. Patients should be periodically
reassessed to determine the need for maintenance treatment and the
appropriate dose for such treatment.
Diabetic Peripheral Neuropathic Pain 
As the progression of diabetic peripheral neuropathy is highly variable and
management of pain is empirical, the effectiveness of Cymbalta must be
assessed individually. Efficacy beyond 12 weeks has not been systematically
studied in placebo-controlled trials, but a one-year open-label safety study
was conducted.
Special Populations 

Dosage for Renally Impaired Patients — Cymbalta is not recommended
for patients with end-stage renal disease (requiring dialysis) or in severe
renal impairment (estimated creatinine clearance <30 mL/min) (see
<a href="#pharmacology">CLINICAL PHARMACOLOGY</a>).
Dosage for Hepatically Impaired Patients — It is recommended that
Cymbalta not be administered to patients with any hepatic insufficiency (see
<a href="#pharmacology">CLINICAL PHARMACOLOGY</a> and <a href="#precautions">
PRECAUTIONS</a>).

Dosage for Elderly Patients — No dose adjustment is recommended
for elderly patients on the basis of age. As with any drug, caution should
be exercised in treating the elderly. When individualizing the dosage in
elderly patients, extra care should be taken when increasing the dose.
Treatment of Pregnant Women During the Third Trimester — Neonates
exposed to SSRIs or SNRIs, late in the third trimester have developed
complications requiring prolonged hospitalization, respiratory support, and
tube feeding (see <a href="#precautions">PRECAUTIONS</a>). When treating
pregnant women with Cymbalta during the third trimester, the physician
should carefully consider the potential risks and benefits of treatment. The
physician may consider tapering Cymbalta in the third trimester.
Discontinuing Cymbalta
Symptoms associated with discontinuation of Cymbalta and other SSRIs and
SNRIs have been reported (see <a href="#precautions">PRECAUTIONS</a>).
Patients should be monitored for these symptoms when discontinuing
treatment. A gradual reduction in the dose rather than abrupt cessation is
recommended whenever possible. If intolerable symptoms occur following a
decrease in the dose or upon discontinuation of treatment, then resuming the
previously prescribed dose may be considered. Subsequently, the physician
may continue decreasing the dose but at a more gradual rate.

Switching Patients to or from a Monoamine Oxidase Inhibitor 
At least 14 days should elapse between discontinuation of an MAOI and
initiation of therapy with Cymbalta. In addition, at least 5 days should be
allowed after stopping Cymbalta before starting an MAOI (see
<a href="#contraindications">CONTRAINDICATIONS</a> and <a href="#warnings">
WARNINGS</a>).
<a href="#top">top</a>
How <a name="supplied">Supplied</a><a name="supplied"></a>

Cymbalta® (duloxetine hydrochloride) Delayed-release Capsules are
available in 20, 30, and 60 mg strengths.
The 20 mg* capsule has an opaque green body and cap, and is imprinted
with “20 mg” on the body and “LILLY 3235” on the cap:
NDC 0002-3235-60 (PU3235) — Bottles of 60 
NDC 0002-3235-33 (PU3235) — (ID†100) Blisters
The 30 mg* capsule has an opaque white body and opaque blue cap, and is
imprinted with “30 mg” on the body and “LILLY 3240” on the cap:
NDC 0002-3240-30 (PU3240) — Bottles of 30 

NDC 0002-3240-90 (PU3240) — Bottles of 90 
NDC 0002-3240-04 (PU3240) — Bottles of 1000 
NDC 0002-3240-33 (PU3240) — (ID†100) Blisters
The 60 mg* capsule has an opaque green body and opaque blue cap, and is
imprinted with “60 mg” on the body and “LILLY 3237” on the cap:
NDC 0002-3237-30 (PU3237) — Bottles of 30 
NDC 0002-3237-90 (PU3237) — Bottles of 90 

NDC 0002-3237-04 (PU3237) — Bottles of 1000 
NDC 0002-3237-33 (PU3237) — (ID†100) Blisters
*equivalent to duloxetine base. 
†Identi-Dose® (unit dose medication, Lilly).
Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP
Controlled Room Temperature].
<a href="cymbalta_guide.asp">Cymbalta Medication Guide</a>

saturn1 · Dec 7, 2008

<td><img src="../i/a2z/deprenyl.jpg" width="125" align="right" border="0" height="125"> <h1>Maintain healthy brain cells with Deprenyl</h1>Deprenyl reduces the age-related decline of dopamine, increasing its availability to preserve youthful brain activity Deprenyl was originally developed as a ‘psychic energizer’, designed to integrate some amphetamine-like brain effects with anti-depressant effects. It has since been shown to protect nerve cells against a wide, and growing, number of neurotoxins, and has been shown to be a neuroprotection / neurorescue agent when nerve cells are exposed to damaging or stressful conditions. Extending life-expectancy <a href="http://www.antiaging-systems.com/profiles.htm">Professor Joseph Knoll</a> proved that Deprenyl improves the availability of dopamine, slows its age-related decline and helps maintain healthy brain cells by acting as a selective MAO-B inhibitor. Professor Knoll emphasized that the nigrostriatal tract, the tiny DA-using nerve cluster in the basal ganglia (‘old brain’), typically dies off at an average rate of 13% per decade starting around age 45 in humans. This fact sets the human lifespan at about 115 years, since by that age the nigral neuron population would have dropped below 10% of its original number, at which time death ensues even if in all other respects the organism were healthy. Therefore, human longevity is in-part governed by the rate of dopamine decline. Its support and enhancement means not only longer life, but lucid mental capabilities too. In fact, four different rat studies and one dog study have shown Deprenyl to be an effective life-extension agent. Based on the sum total of research, Knoll has suggested that if Deprenyl were used from the 40s on, and only modestly lowered the nigrostriatal neuron death rate – say, from 13% to 10% per decade – then the average human lifespan might increase by 15 years. Other uses Deprenyl has become a standard treatment for Parkinson’s disease, and thanks to its aphrodisiac effects, helps to improve sexual function and desire (much more so for men than woman). Although Parkinson's disease remains the only FDA approved indication for Deprenyl in the USA, with a number of ongoing clinical studies evaluating its efficacy in Alzheimer's disease, anecdotal reports from both physicians and patients of dramatic improvement in an impressive number of diseases have been accumulating. Conditions for which Deprenyl appears to be therapeutic or ameliorative include: cerebral infarction (stroke), hormone inadequacy, amyotrophic lateralizing sclerosis (lou gherig's disease), fatigue, chronic pain, gastric ulcers, senile dementia, sexual dysfunction, multiple sclerosis, learning difficulties, blepharospasm, hypertension depression and cancer. Dr. Clyde Reynolds, a clinician who specializes in the metabolic therapy of cancer in Washington State, discovered that cancer patients invariably have imbalances of the neurotransmitters, epinephrine, norepinephrine and serotonin. Dr. Reynolds has found that Deprenyl is highly effective in restoring the normal levels and normal balance of these neurotransmitters. He believes that normalization of the balance of these neurotransmitters is an absolute necessity for the effective treatment of all cancers. Dosage: Parkinson and Alzheimer's disease patients are often treated with very high doses of 20mg daily (usually along with other drugs). Anti-aging doses (dependant on age and condition) are more likely to be 2.5mg to 5mg once, twice or three times a week, or, 1mg to 3mg per day, with regular breaks. Deprenyl tablets are selegiline hydrochloride, which is deprenyl bonded to an in-organic molecule. However, liquid deprenyl citrate (LDC) is selegiline bonded to an organic molecule, one reason why the liquid deprenyl citrate is considered to be superior. This form is generally recognized as the most pure and potent form of deprenyl available. It also allows precise titration for anti-aging purposes, as each ml drop in the bottle is equivalent to 1mg deprenyl citrate. The manufacturer recommends 1mg two times a week for 30 to 35 years olds up to 10mg daily for 80 year olds plus (an age/ dosage list in English is enclosed with order). Ward Dean, M.D., recommends reducing deprenyl doses after several months to lower levels and taking occasional sabbaticals. Side effects: Possible gastrointestinal symptoms, such as nausea, heartburn, upset stomach, etc. Some studies have found side effects such as irritability, hyper-excitability, psychomotor agitation and insomnia. These effects are probably due to Deprenyl catecholamine-enhancing effect, over-activating DA/NA neural systems at the expense of calming/sleep-inducing serotonergic systems, so taking magnesium and tryptophan or 5-HTP may suffice to counter these ‘psychic’ effects. <img src="../i/rule460.gif" alt="" width="435" border="0" height="1">What our customers say...<table width="100%" border="0" cellpadding="5" cellspacing="0"><tbody><tr><td class="tbltxt"><img src="../i/startquote.jpg" alt="" width="13" align="absmiddle" border="0" height="11">L-deprenyl is what good pharmaceuticals are all about. First it is exceptionally safe, second it protects and enhances mental function, mood and even libido, thirdly, it may even extend life. Imagine a safe agent that enhances both the quality and length of life.<img src="../i/endquote.jpg" alt="" width="13" align="absmiddle" border="0" height="11"> <a href="../profiles.htm">Julian Whitaker M.D.</a> Health and Healing Newsletter, Whitaker Wellness Institute, Newport Beach, California. <img src="../i/startquote.jpg" alt="" width="13" align="absmiddle" border="0" height="11">Many of us here in the States appreciate you making it possible for us to continue to get access to liquid deprenyl.<img src="../i/endquote.jpg" alt="" width="13" align="absmiddle" border="0" height="11"> R.S., New Mexico.</td></tr></tbody></table><img src="../i/rule460.gif" alt="" width="435" border="0" height="1"><table width="100%" border="0" cellpadding="5" cellspacing="0"><tbody><tr><td class="thinpink4tbltxt" bgcolor="#f0f8ff">To see the full ingredients in Deprenyl Oral Tablets and its "approved" uses please <a href="../apruses/deprenyljumex.htm">click here.</a> To see the full ingredients in Deprenyl Liquid and its "approved" uses please <a href="../apruses/deprenylselepryl.htm">click here.</a>To read articles about Deprenyl please <a href="../extract/bychemical/deprenyl.htm">click here</a>.<a href="../enews/jumex.htm">To read our back catalogue of E-News on Jumex please click here</a><a href="../enews/selepryl.htm">To read our back catalogue of E-News on Selepryl please click here</a>To read our back catalogue of e-News on Memory please <a href="../enews/memory.htm">click here</a></td></tr></tbody></table> <table width="100%" border="0" cellpadding="5" cellspacing="0"><tbody><tr><td class="tbltxt">Caution: Japan has classified Deprenyl as a <a href="../faqs.htm#controlled">controlled</a> substance.</td></tr></tbody></table> <table width="100%" border="0" cellpadding="5" cellspacing="0"><tbody><tr><td class="tbltxt">Caution: In rare circumstances, deprenyl can cause a false-positive dope test, if you need to know more about this, please <a href="#" onclick="FP_openNewWindow('300', '400', false, false, false, false, false, false, '', /*href*/'../popup/text/deprenyl.html')">click here</a>.</td></tr></tbody></table><div align="right"><a href="#top">TOP</a></div></td>

http://www.antiaging-systems.com/a2z/deprenyl.htm

saturn1 · Dec 7, 2008

Heres the euro stuff people claim to be very effective. Not for me.

Milnacipran relieves chronic pain and depression

Milnacipran is the first in a new class of antidepressants known as Norepinephrine Serotonin Reuptake Inhibitors (or NSRI's). It has equal potency for inhibiting the reuptake of both serotonin and noradrenaline. Extensive studies provide clear-cut evidence of its efficacy in both severe and moderate depression in hospitalized and community settings.

What makes Milnacipran different from the Selective Serotonin Reuptake Inhibitors (SSRIs) – drugs like Prozac® – and Selective Norepinephrine Reuptake Inhibitors (SNRIs) – drugs like Effexor – is that Milnacipran affects two neurotransmitters, norepinephrine and serotonin, almost equally (a 3:1 norepinephrine to serotonin balance). In contrast a SNRI, tends to act much more on serotonin than norepinephrine, (Effexor has a 1:30 norepinephrine to serotonin ratio).

Since the 1990s, treatment for depression has relied upon the single acting SSRIs, but in many ways, the SSRIs fall short. Most SSRIs have unwelcome side effects, the most common being an increase in erectile dysfunction and a decrease in libido (sex drive). Also, the vast body of evidence shows that drugs that increase serotonin alone, or norepinephrine alone, are equally effective in treating depression. However, norepinephrine is clearly more important in treating pain. Until recently, the most effective way to increase both norepinephrine and serotonin was through administering a tricyclic anti-depressants (TCAs).

TCAs affect 6 different targets, and as a consequence, they have numerous side effects including dry mouth, weight gain, drowsiness, fatigue, confusion, disorientation, cardiac abnormalities... Which is why Milnacipran is a potential lifeline for so many people. It can affect multiple pain mechanisms in a manner similar to that seen with some tricyclic anti-depressants, but without the negative side effects.

Trials involving 1032 patients show that Milnacipran provides antidepressant efficacy similar to that of imipramine and significantly superior to that of the SSRIs. Analysis of over 3300 patients shows that both the general and cardiovascular tolerability of Milnacipran are superior to those of the TCAs with fewer cholinergic side effects. The tolerability of Milnacipran was comparable to that of the SSRIs, with a higher incidence of dysuria with Milnacipran, and a higher frequency of nausea and anxiety with the SSRIs.

As a result of this, and other, research, Milnacipran is now the new therapeutic option for depression, offering clinical efficacy in the range of the TCAs combined with a tolerability equivalent to that of the SSRIs. In addition, Milnacipran is a promising treatment for chronic pain conditions like Fibromyalgia and Lupus.

Fibromyalgia and Lupus

Fibromyalgia Syndrome (FMS) is a chronic pain syndrome that is estimated to affect 2-4% of the general population. The symptoms of FMS can be debilitating, and are characterized by chronic and widespread pain throughout the body, often accompanied by severe fatigue and poor sleep. Treatment options are limited as there are no drugs specifically approved by the U.S. Food and Drug Administration for the treatment of FMS. In tests, Milnacipran-treated patients showed significant improvements in pain, fatigue and mood compared to those who received a placebo.

Systemic Lupus Erythematosus (Lupus) is an autoimmune disease where the body has turned on itself. In a Lupus sufferer, antibodies can attack over 116 different types of their own proteins as if they were foreign, dangerous viruses or bacteria. Trials using Milnacipran seem to demonstrate a large degree of pain relief in sufferers plus a general feeling of well-being.

Dosage:
Dosages for depression are usually in the order of 25mg to 50mg daily (maximum 100mg).

Caution:
Like most anti-depressants there are contraindications with other anti-depressants and MAO inhibiting drugs, including Gerovital-H3, Deprenyl and Manerix, therefore combined use is not advised unless under the guidance of a physician. Furthermore, we do not advise combination with other Serotonin or Noradrenaline enhancing agents such as Adrafinil, Modafinil, Paxil, Prozac®, Yohimbine and Zoloft unless you are under the guidance of a physician.

saturn1 · Dec 7, 2008

Sorry about the fudged up HTML

saudades · Dec 8, 2008

Wow, that html really freaked out the post. Don't like the sexual sides listed for cymbalta. My wife tried that--not that she's depressed, but she has more of an anxiety disorder. Made her feel awful. She still has the pills in the medicine drawer though. She's now on Paxil. Much better.

ballsoutpunk · Dec 9, 2008

I was on Cymbalta for several years. I think it worked better than any other antidepressant I've ever taken, which is probably close to 15, but it gave me a real "fuck it" attitude about everything; moreso than any other antidepressant I've ever taken. In the past few years I've been spending a lot more time exercising and I think that keeps me from feeling like I need any ADs, so I haven't taken anything in that regard for a while now. I can't say how awesome it is not to need that crap anymore, but I know depression sucks and I feel for you. Another note: coming off Cymbalta is not fun. Take that into account before you start. All of the usual withdrawl symptoms are there, but worse. It probably took me three weeks to get past the "brain zaps" and feeling weird. On the plus side, I didn't have any of the sexual side effects that I always got on SSRIs. I would say that, for me, it's slightly better than everything else available, but just slightly.

Presser · Dec 10, 2008

Thank god i dont need this type of stuff!

What was that anti-depressant??

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