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The physician’s psychoactive medication resource guide
25% of your patients taking an antidepressant will have
weight gain and the weight gain is directly caused by the antidepressant.
Cymbalta withdrawal. Cymbalta withdrawal side effects, Cymbalta withdrawal warnings,
Cymbalta withdrawal precautions, Cymbalta withdrawal adverse effects, overdose, withdrawal
symptoms and Cymbalta natural alternatives. Before you begin the spiral down with Cymbalta
try giving your body what it really wants.
Cymbalta side effects can be debilitating and most side effects are not understood by
patients due to the medical terminology used to define the side effects.
You may have prescribed Cymbalta to your patients for neuropathy, depression, urinary
disorders or other off-label usage. When adverse drug reactions begin, withdrawal symptoms
will not ease, use the information at The Road Back. Maybe you have attended a medical
conference and received CME's with their presenters, put the information to use and save your
patients. Click here and re-read How to get Off Psychiatric Drugs safely.
Cymbalta - Alert from the F.D.A.
FDA ALERT [07/2005]: Suicidal Thoughts or Actions in Children and Adults
Patients with depression or other mental illnesses often think about or attempt suicide. Closely
watch anyone taking antidepressants, especially early in treatment or when the dose is
changed. Patients who become irritable or anxious, or have new or increased thoughts of
suicide or other changes in mood or behavior (or their care givers) should contact their
healthcare professional right away.
Taking antidepressants may increase suicidal thoughts and actions in about 1 out of 50 people
18 years or younger. FDA has approved Zoloft for use in children only if they have obsessive-
Several recent scientific publications report the possibility of an increased risk for suicidal
behavior in adults who are being treated with antidepressant medications. Even before these
reports became available, FDA began a complete review of all available data to determine
whether there is an increased risk of suicidal thinking or behavior in adults being treated with
antidepressant medications. It is expected that this review will take a year or longer to complete.
In the meantime, FDA is highlighting that adults being treated with antidepressant medication,
particularly those being treated for depression, should be watched closely for worsening of
depression and for increased suicidal thinking or behavior.
This information reflects FDA’s preliminary analysis of data concerning this drug. FDA is
considering, but has not reached a final conclusion about, this information. FDA intends to
update this sheet when additional information or analyses become available.
What is Cymbalta?
Cymbalta is a new antidepressant manufactured by Eli Lilly and Company, the approval of
which Has finally been granted by the U.S. Food and Drug Administration. This happens on the
heals of one suicide of a 19 year-old, in perfect health, no mental disorder, hanging herself at
the Eli Lilly complex, after taking Cymbalta. This is approved when pressure is being put on all
of the pharmaceutical firs to fully disclose their clinical trials.
Did the FDA feel a little pressure from the current Administration? If you have an adverse event
or commit suicide while taking Cymbalta, odds are the current Administration will pay for and
support Eli Lilly to beat you in court. The current administration admits this.
August 11, 2004 - The FDA states Cymbalta had nothing to do with the hanging death at
the Eli Lilly facility. Let's look at the known data here:
1.You have a healthy 19 year old female as part of the Cymbalta clinical trials.
2.She is given a much higher dosage then recommended.
3.Part of her trial was to quit the Cymbalta quickly
4.She hangs herself
5.She has no mental illness
6.She was in perfect physical health per Eli Lilly
7.She was in the trial to earn money for college
8.The current administration will supply Eli Lilly with their attorneys to help fight consumer
lawsuits because "the FDA is never wrong"
9.The FDA uses their own lead attorney to help Eli Lilly and others fight consumer lawsuits
because the FDA is never wrong.
10.The current administration is full of Eli Lilly past executives.
11.You would think if the FDA clears Cymbalta as the cause of death, they would disclose why
or what the reason was.
12.Amazing, the FDA statement of Cymbalta having nothing to do with this suicide, would
come within 1 week of Cymbalta being approved by the FDA and within 3 weeks of the
massive launch of Cymbalta by Eli Lilly. Eli Lilly will have more drug reps hit the streets to visit
physicians then with any other drug of theirs in the past.
13.If Cymbalta fails, Eli Lilly will suffer on Wall Street.
Eli Lilly is being sued again after a SWAT captain commits suicide after only 3 days of Prozac use. Eli Lilly has already
settled 2 suits out of court for the same issue. Know what can happen before you take these medications. There is a way to
know. Click here for story. (Opens new browser)
August 4, 2004 - Now that Cymbalta is approved by the FDA will Eli Lilly disclose all of their clinical trials? With a high profile
suicide occurring during the clinical trial, will the pressure be enough on Eli Lilly? When a healthy volunteer, with no known mental
illness or physical problem commits suicide on Cymbalta, will Eli Lilly disclose all of the facts?
Eli Lilly, I know you are on this Web Site daily, especially when it comes up first on most search engines for your new
antidepressant Cymbalta, what are you going to do? Disclose all of the facts or not? If you work with Eli Lilly and feel it is time for
you to come clean and disclose all you know about Cymbalta hidden information, Click here and send an e-mail.
Click here for Cymbalta Adverse Reactions and more
Cymbalta is a brand-name for a drug called duloxetine. It is in a class of drugs known as dual uptake inhibitors. So what is a dual
uptake inhibitor -- or an uptake inhibitor, for that matter?
The way a neurotransmitter works is, it is passed along from one nerve to another. A bit of it is sent out at a time from one nerve
to the next. After a bit is sent out and received by the next nerve, any of the neurotransmitter remaining between the nerves is
taken back by the first nerve, a process called reuptake.
A reuptake inhibitor prevents this reuptake process from occurring, which means that, when Cymbalta is active, certain
neurotransmitters are transmitted in steady streams from one nerve ending to the next, instead of being sent in bits periodically,
which they normally are. The neurotransmitters affected by Cymbalta are known as serotonin and norepinephrine. And now we
can explain what "dual uptake inhibitor" means -- it simply means a drug that affects the reuptake of two neurotransmitters
instead of one.
Does Cymbalta cure depression?
Good question. If depression has never been proven to be caused by neurotransmitters (or the lack of them), that question
cannot obviously be answered conclusively.
Apparently, Eli Lilly and Company knows this. According to a recent news release from Eli Lilly regarding Cymbalta: "Many
experts believe treating the complete spectrum of depression symptoms is intrinsic to a lasting recovery. As well, combined action
through two key neurotransmitters - serotonin and norepinephrine - may provide a more rapid and sustained clinical effect."
Note the subtle uncertainties in these statements, for there is absolutely no scientific proof behind them. "Many experts believe
treating the complete spectrum of depression symptoms..." "...combined action through two key neurotransmitters - serotonin and
norepinephrine - may provide..."
Translation: They don't know how, why, or if their drug works. This is evident in the numerous -- and serious -- side effects
provided by other antidepressants. Lilly's press release did not even address side effects, but another of their releases regarding
Cymbalta's clinical trials revealed three of the exact same side effects as other antidepressants: Dizziness, anxiety, and nausea.
In that Cymbalta has the exact same action as Wyeth's drug Effexor, one could assume the same side effects. (See "Precautions"
section on Effexor page). (Opens new browser)
What is Depression?
Depression is defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM), published by the American Psychiatric
Association, this way:
The essential feature of a Major Depressive Episode is a period of at least 2 weeks during which there is either depressed mood
or the loss of interest or pleasure in nearly all activities. In children and adolescents, the mood may be irritable rather than sad.
The individual must also experience at least four additional symptoms drawn from a list that includes major changes in appetite or
weight, sleep, and psychomotor [of or relating to movement or muscular activity associated with mental processes] activity;
decreased energy; feelings of worthlessness or guilt; difficulty thinking, concentrating, or making decisions; or recurrent thoughts
of death or suicidal ideation, plans, or attempts."
While these elements can certainly be seen to exist and have been experienced by many, labeling "depression" as an illness has
been criticized by many as simply labeling part of life itself as a physical "disease" which must be "cured".
This could be debated endlessly, however, and whole long texts have been written on the subject. Depression as a state of mind
certainly does exist, and can be painful. The question to be addressed here, though, is, does depression truly have a physical
cause that can be addressed with medication?
For the answer, let's go back to the DSM. The only information given there as to physical causes of depression is:
Neurotransmitters implicated in the pathophysiology [study of the physical effects of a disease] of a Major Depressive Episode
include norepinephrine, serotonin, acetylcholine, dopamine, and gamma-aminobutryric acid.
All right, what does all that mean? Here's a simple explanation. A neurotransmitter is a chemical that helps transmit nerve
impulses through the nervous system. There are many different neurotransmitters used by the body. What the DSM definition is
saying is that, by some method, the neurotransmitter chemicals known as norepinephrine, serotonin, acetylcholine
, dopamine, and gamma-aminobutryric acid seemed to be lower in some depressed people, or higher in non-depressed people.
Note carefully the use of the word implicated in the DSM definition, however. And therein is the first clue, for it has never been
clinically proven that depression is based in neurotransmitters. We repeat: Never. And believe it or not, there is not a doctor on
Earth that will disagree with that statement.
Which leads to the conclusion that a physical cause for depression has never been isolated. Why, then, is Eli Lilly and Company,
Cymbalta's manufacturer, so insistent that Cymbalta is a great treatment for depression?
For the answer to this, let's turn to Eli Lilly and find out exactly what Cymbalta is, and how it works.
Should You Take Cymbalta?
The answer is, of course, up to you. Before you do, however, become fully informed of the dangers from the manufacturer. As yet
the full list of side effects have not been published.
You should also be aware of a dangerous metabolism issue that may affect you, and for which you should be tested before you
take such a drug.
CYMBALTA 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
CYMBALTA is mainly through hepatic metabolism involving two P450 isozymes, CYP2D6 and CYP1A2.
Absorption and Distribution – Orally administered CYMBALTA is well absorbed. There is a median 2-hour lag until absorption
begins (T lag), with maximal plasma concentrations C max) of CYMBALTA occurring 6 hours post dose. Food does not affect the
Cmax of CYMBALTA, 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
CYMBALTA after an evening dose as compared to a morning dose.
The apparent volume of distribution averages about 1640 L. CYMBALTA is highly bound (>90%) to proteins in human plasma,
binding primarily to albumin and ą1-acid glycoptrotein. Plasma protein binding of CYMBALTA is not affected by renal or hepatic
Metabolism and Elimination – Biotransformation and disposition of CYMBALTA in humans have been determined following oral
administration of 14C-labeled CYMBALTA. CYMBALTA comprises about 3% of the total radiolabeled material in the plasma,
indication that it undergoes extensive metabolism to numerous metabolites. The major biotransformation pathways for
CYMBALTA 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 CYMBALTA are present in the urine. Most (about
70%) of the CYMBALTA dose appears I the urine as metabolites of CYMBALTA; about 20% is excreted in the feces.
Smoking Status – CYMBALTA 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 CYMBALTA in patients with end stage renal disease (ESRD).
After a single 60-mg dose of CYMBALTA, Cmax and AUC values were approximately 100% greater inpatients with end stage
renal disease receiving chronic intermittent hemodialysis than in subjects with normal renal fuction. The elimination half-life,
however, was similar in both groups. The AUC’s of the major circulation 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 ESRD (see DOSAGE
AND ADMINISTATION). Studies have not been conducted in patients with a moderate degree of renal dysfunction, but population
PK analyses suggest that mild renal dysfunction has no significant effect on CYMBALTA apparent clearance.
Hepatic Insufficiency – Patients with clinically evident hepatic insufficiency have decreased CYMBALTA 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 CYMBALTA 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
PRECAUTIONS). It is recommended that CYMBALTA no be administered to patients with any hepatic insufficiency (see DOSAGE
Drug-Drug Interactions (also see PRECAUTIONS, Drug Interactions)
Potential for Other Drugs to Affect CYMBALTA.
Both CYP1A2 and CYP2D6 are responsible for CYMBALTA metabolism.
Indications and Usage
CYMBALTA is indicated for the treatment of major depressive disorder (MDD).
CYMBALTA is contraindicated in patients with a known hypersensitivity to the product.
Clinical Worsening and Suicide Risk – Patients with major depressive disorder, both adult and pediatric, may experience
worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality), whether or not they are taking
antidepressant medications, and this risk may persist until significant remission occurs. Although there was been a long-standing
concern that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain
patients, a causal role for antidepressants in inducing such behaviors has not been established. Nevertheless, patients being
treated with antidepressants should be observed closely for clinical worsening and suicidality, especially at the beginning of a
course of drug therapy, or at the time of dose changes, either increases of decreases. Consideration should be given to changing
the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse or
whose emergent suicidality is severe, abrupt in onset, or was not part of the patient’s presenting symptoms.
Because of the possibility of co-morbidity between major depressive disorder and other psychiatric and nonpsychiatric disorders,
the same precautions observed when treating patients with major depressive disorder should be observed when treating patients
with other psychiatric and nonpsychiatric disorders.
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, consideration should be given to changing the therapeutic
regimen, including possibly discontinuing the medications, in patients for whom such symptoms are severe, abrupt in
onset, or were not part of the patient’s presenting symptoms.
Families and caregivers of 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 suicidality,
and to report such symptoms immediately to health care providers. 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.
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 PRECAUTIONS and DOSAGE
AND ADMINISTRATION, Discontinuing CYMBALTA (duloxetine hydrochloride), for a description of the risks of
discontinuation of CYMBALTA).
Information of Patients
Physicians are advised to discuss the following issues with patients for whom they prescribe CYMBALTA.
Patients and their families should be encouraged to be alert to the emergence of anxiety, agitation, panic attacks, insomnia,
irritability, hostility, impulsivity, akathisia, hypomania, mania, worsening of depression, and suicidal ideation, especially early
during antidepressant treatment. Such symptoms should be reported to the patient’s physician, especially if they are severe,
abrupt in onset, or were not part of the patient’s presenting symptoms.
Any psychoactive drug may impair judgment, thinking, or motor skills.
Drug Interactions (also see CLINICAL PHARMACOLOGY, Drug – Drug
Inhibitors of CYP2D6 – Because CYP2D6 is involved in CYMBALTA metabolism, concomitant use of CYMBALTA with potent
inhibitors of CYP2D6 may result in higher concentrations of CYMBALTA. Paroxetine (20 mg QD) increased the concentration of
CYMBALTA (40 mg QD) by about 60%, and greater degrees of inhibition are expected with higher doses of Paroxetine. Similar
effect would be expected with other potent CYP2D6 inhibitors (e.g., fluoxetine, quinidine).
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 to 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. 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.
Adverse Events Reported as Reasons for Discontinuation of Treatment in Placebo-Controlled Trials
Approximately 10% of the 1139 patients who received CYMBALTA in the 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).
Adverse Events Occurring at an Incidence of 2% or More Among CYMBALTA-Treated Patients in Placebo-Controlled Trials Table
1 gives the incidence of treatment-emergent adverse events that occurred in 2% or more of patients treated with CYMBALTA in
the 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.
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.
Other Adverse Events Observed During the Premarketing Evaluation of CYMBALTA
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 database. The events included are those not already listed elsewhere
in ADVERSE REACTIONS and not considered in the WARNINGS and PRECAUTIONS sections, that were reported with an
incidence of greater than or equal to 0.05%, 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 (only those not already listed in
the tabulated results from placebo-controlled trials appear in this listing); 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 whit blood cell count, lymphadenopathy, and
Gastrointestinal Disorders – Frequent: gastritis: Infrequent: blood in stool, colitis, dysphagia, esophageal stenosis acquired,
gastric ulcer, gingivitis, irritable bowel syndrome, and lower abdominal pain.
Psychiatric Disorders – Frequent: initial insomnia, irritability, lethargy, nervousness, nightmare, restlessness, and sleep disorder;
Infrequent: completed suicide, mania, mood swings, pressure of speech, sluggishness, and suicide attempt.
Renal and Urinary Disorders – Frequent: dysuria; infrequent: micturition urgency, urinary hesitation, urinary incontinence, urinary
retention, and urine flow decreased.
Skin and Subcutaneous Tissue Disorders – Frequent: night swats, pruritus, and rash; Infrequent: acne, alopecia, cold sweat,
ecchymosis, eczema, erythema, face edema, increased tendency to bruise, and photosensitivity reaction.
Vascular Disorders – Infrequent: peripheral edema and phlebitis.
Discontinuing CYMBALTA (duloxetine hydrochloride)
Symptoms associated with discontinuation of CYMBALTA and other SSRIs and SNRIs have been reported (see PRECAUTIONS).
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.