MAY 2007: News on SSRIs, other Psych Drugs and Related Issues

MAY 2007: News on SSRIs, other Psych Drugs and Related Issues

Joined: January 1st, 1970, 12:00 am

June 4th, 2007, 11:30 pm #1

MAY 2007: News on SSRIs, other Psych Drugs and Related Issues
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Joined: January 1st, 1970, 12:00 am

June 18th, 2007, 12:50 pm #2


Depakote:  Sodium Valproate and Valproic Acid

<P class=post-title>http://ahrp.blogspot.com/2007/05/24-of-children-of-mothers-prescribed.html

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<DIV><FONT color=#000066><IMG height=138 hspace=10 src="http://www.thejabberwock.org/blog/kids1.jpg" width=287 align=left vspace=10 border=0></FONT>24 percent of the children of mothers who took valproate (Depakote) during pregnancy showed an IQ in the mental retardation range. That alarming finding was presented at the American Academy of Neurology's 59th Annual Meeting in Boston, April 28 - May 5, 2007.

The class of drugs known as anticonvulsants or, anti-epileptics, are prescribed mostly for unapproved, off-label uses including: bipolar disorder and migraine headaches, according to an analysis by the Epilepsy Foundation. Such reckless prescribing of drugs for unapproved uses are disrupting normal brain function with devastating results.

Doctors' indiscriminate prescribing practices are condemning millions of children to drug-produced mental disabilities. Do we really want to continue to give doctors the unrestricted license to prescribe toxic substances that cause permanent brain damage without any constraints?

"Depakote looks worse than the other drugs in all of these recent studies," said Dr. Kimford J. Meador, a professor of neurology at the University of Florida and the lead author of the new study. "In all, it is compelling evidence that this drug should not be used as a first-line choice for treatment in pregnant women." How long will the FDA drag its feet before issuing label warnings to indicate the use of Valproic acid drugs are contraindicated for pregnant women?

Furthermore, how do we know that prescribing these same drugs for children--as is currently the practice among mental health professionals--that the drugs won't cause the children mental retardation--or worse? Rebecca Riley was a four year old Boston drug casualty: she was prescribed a psychotropic drug cocktail by a psychiatrist. Among the drugs prescribed for her since the tender age of 28 months, was Depakote.

We have documented evidence showing that Rebeca Riley's is not the only child to be heavily medicated: New Jersy's Medicaid roster docments more than 39,000 children who are prescribed psychotropic drugs. Of these, 647 prescriptions were for children age 4 or less. Psychotropic drug prescriptions for children age 2, included 13 antipsychotics, 10 benzodiazepines, and 2 antidepressants

Michigan's Medicaid roster shows that 933 patients under age 5 were prescribed anticonvulsants /Mood Stabilizers; 972 patients under age 5 were prescribed Antidyskinetics--for what condition? One child under Michigan's Medicaid program is currently prescribed 17 psychotropic drugs.

Psychiatrists who defend the practice of medicating children with psychotropic drugs, such as: Dr. Janet Wozniak, director fo the Pediatric Bipolar program at Harvard affiliate, Mass General, and Dr. Nancy Rappaport of the Cambridge Health Alliance, claim without evidence that their prescriptions benefit children: "the overall number of prescriptions is probably small relative to the number of children who need help."

When will sanity and the "First, do no harm" principle in medicine be restored? When will we have a public health policy that bans interaction between pharmaceutical industry and children's care givers? Children's health care and educational providers should not come under drug industry influence.



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Joined: January 1st, 1970, 12:00 am

June 18th, 2007, 12:54 pm #3

MAY 2007: News on SSRIs, other Psych Drugs and Related Issues
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Hepatotoxicity
Hepatic failure resulting in fatalities has occurred in patients receiving valproic acid. These incidents usually have occurred during the first six months of treatment. Serious or fatal hepatotoxicity may be preceded by non-specific symptoms such as malaise, weakness, lethargy, facial edema, anorexia, and vomiting. In patients with epilepsy, a loss of seizure control may also occur. Patients should be monitored closely for appearance of these symptoms. Liver function tests should be performed prior to therapy and at frequent intervals thereafter, especially during the first six months. However, physicians should not rely totally on serum biochemistry since these tests may not be abnormal in all instances, but should also consider the results of careful interim medical history and physical examination.

Caution should be observed when administering DEPAKOTE products to patients with a prior history of hepatic disease. Patients on multiple anticonvulsants, children, those with congenital metabolic disorders, those with severe seizure disorders accompanied by mental retardation, and those with organic brain disease may be at particular risk. Experience has indicated that children under the age of two years are at a considerably increased risk of developing fatal hepatotoxicity, especially those with the aforementioned conditions. When DEPAKOTE is used in this patient group, it should be used with extreme caution and as a sole agent. The benefits of therapy should be weighed against the risks. Above this age group, experience in epilepsy has indicated that the incidence of fatal hepatotoxicity decreases considerably in progressively older patient groups.

The drug should be discontinued immediately in the presence of significant hepatic dysfunction, suspected or apparent. In some cases, hepatic dysfunction has progressed in spite of discontinuation of drug.

Pancreatitis
Cases of life-threatening pancreatitis have been reported in both children and adults receiving valproate. Some of the cases have been described as hemorrhagic with rapid progression from initial symptoms to death. Some cases have occurred shortly after initial use as well as after several years of use. The rate based upon the reported cases exceeds that expected in the general population and there have been cases in which pancreatitis recurred after rechallenge with valproate. In clinical trials, there were 2 cases of pancreatitis without alternative etiology in 2416 patients, representing 1044 patient-years experience. Patients and guardians should be warned that abdominal pain, nausea, vomiting, and/or anorexia can be symptoms of pancreatitis that require prompt medical evaluation. If pancreatitis is diagnosed, valproate should ordinarily be discontinued. Alternative treatment for the underlying medical condition should be initiated as clinically indicated (See BOXED WARNING).

Urea Cycle Disorders (UCD)
Divalproex sodium is contraindicated in patients with known urea cycle disorders.

Hyperammonemic encephalopathy, sometimes fatal, has been reported following initiation of valproate therapy in patients with urea cycle disorders, a group of uncommon genetic abnormalities, particularly ornithine transcarbamylase deficiency. Prior to the initiation of valproate therapy, evaluation for UCD should be considered in the following patients: 1) those with a history of unexplained encephalopathy or coma, encephalopathy associated with a protein load, pregnancy-related or postpartum encephalopathy, unexplained mental retardation, or history of elevated plasma ammonia or glutamine; 2) those with cyclical vomiting and lethargy, episodic extreme irritability, ataxia, low BUN, or protein avoidance; 3) those with a family history of UCD or a family history of unexplained infant deaths (particularly males); 4) those with other signs or symptoms of UCD. Patients who develop symptoms of unexplained hyperammonemic encephalopathy while receiving valproate therapy should receive prompt treatment (including discontinuation of valproate therapy) and be evaluated for underlying urea cycle disorders (See CONTRAINDICATIONS and PRECAUTIONS).

Somnolence in the Elderly
In a double-blind, multicenter trial of valproate in elderly patients with dementia (mean age = 83 years), doses were increased by 125 mg/day to a target dose of 20 mg/kg/day. A significantly higher proportion of valproate patients had somnolence compared to placebo, and although not statistically significant, there was a higher proportion of patients with dehydration. Discontinuations for somnolence were also significantly higher than with placebo. In some patients with somnolence (approximately one-half), there was associated reduced nutritional intake and weight loss. There was a trend for the patients who experienced these events to have a lower baseline albumin concentration, lower valproate clearance, and a higher BUN. In elderly patients, dosage should be increased more slowly and with regular monitoring for fluid and nutritional intake, dehydration, somnolence, and other adverse events. Dose reductions or discontinuation of valproate should be considered in patients with decreased food or fluid intake and in patients with excessive somnolence (See DOSAGE AND ADMINISTRATION).

Thrombocytopenia
The frequency of adverse effects (particularly elevated liver enzymes and thrombocytopenia [see PRECAUTIONS]) may be dose-related. In a clinical trial of DEPAKOTE as monotherapy in patients with epilepsy, 34/126 patients (27%) receiving approximately 50 mg/kg/day on average, had at least one value of platelets &#8804; 75 x 109/L. Approximately half of these patients had treatment discontinued, with return of platelet counts to normal. In the remaining patients, platelet counts normalized with continued treatment. In this study, the probability of thrombocytopenia appeared to increase significantly at total valproate concentrations of &#8805; 110 µg/mL (females) or &#8805; 135 µg/mL (males). The therapeutic benefit which may accompany the higher doses should therefore be weighed against the possibility of a greater incidence of adverse effects.

Usage In Pregnancy
VALPROATE CAN PRODUCE TERATOGENIC EFFECTS. DATA SUGGEST THAT THERE IS AN INCREASED INCIDENCE OF CONGENITAL MALFORMATIONS ASSOCIATED WITH THE USE OF VALPROATE BY WOMEN WITH SEIZURE DISORDERS DURING PREGNANCY WHEN COMPARED TO THE INCIDENCE IN WOMEN WITH SEIZURE DISORDERS WHO DO NOT USE ANTIEPILEPTIC DRUGS DURING PREGNANCY, THE INCIDENCE IN WOMEN WITH SEIZURE DISORDERS WHO USE OTHER ANTIEPILEPTIC DRUGS, AND THE BACKGROUND INCIDENCE FOR THE GENERAL POPULATION. THEREFORE, VALPROATE SHOULD BE CONSIDERED FOR WOMEN OF CHILDBEARING POTENTIAL ONLY AFTER THE RISKS HAVE BEEN THOROUGHLY DISCUSSED WITH THE PATIENT AND WEIGHED AGAINST THE POTENTIAL BENEFITS OF TREATMENT.

THERE ARE MULTIPLE REPORTS IN THE CLINICAL LITERATURE THAT INDICATE THE USE OF ANTIEPILEPTIC DRUGS DURING PREGNANCY RESULTS IN AN INCREASED INCIDENCE OF CONGENITAL MALFORMATIONS IN OFFSPRING. ANTIEPILEPTIC DRUGS, INCLUDING VALPROATE, SHOULD BE ADMINISTERED TO WOMEN OF CHILDBEARING POTENTIAL ONLY IF THEY ARE CLEARLY SHOWN TO BE ESSENTIAL IN THE MANAGEMENT OF THEIR MEDICAL CONDITION.

Antiepileptic drugs should not be discontinued abruptly in patients in whom the drug is administered to prevent major seizures because of the strong possibility of precipitating status epilepticus with attendant hypoxia and threat to life. In individual cases where the severity and frequency of the seizure disorder are such that the removal of medication does not pose a serious threat to the patient, discontinuation of the drug may be considered prior to and during pregnancy, although it cannot be said with any confidence that even minor seizures do not pose some hazard to the developing embryo or fetus.

Human Data
Congenital Malformations
The North American Antiepileptic Drug Pregnancy Registry reported 16 cases of congenital malformations among the offspring of 149 women with epilepsy who were exposed to valproic acid monotherapy during the first trimester of pregnancy at doses of approximately 1,000 mg per day, for a prevalence rate of 10.7% (95% CI 6.3%-16.9%). Three of the 149 offspring (2%) had neural tube defects and 6 of the 149 (4%) had less severe malformations. Among epileptic women who were exposed to other antiepileptic drug monotherapies during pregnancy (1,048 patients) the malformation rate was 2.9% (95% CI 2.0% to 4.1%). There was a 4-fold increase in congenital malformations among infants with valproic acid-exposed mothers compared with those treated with other antiepileptic monotherapies as a group (Odds Ratio 4.0; 95% CI 2.1 to 7.4). This increased risk does not reflect a comparison versus any specific antiepileptic drug, but the risk versus the heterogeneous group of all other antiepileptic drug monotherapies combined. The increased teratogenic risk from valproic acid in women with epilepsy is expected to be reflected in an increased risk in other indications (e.g., migraine or bipolar disorder).

THE STRONGEST ASSOCIATION OF MATERNAL VALPROATE USAGE WITH CONGENITAL MALFORMATIONS IS WITH NEURAL TUBE DEFECTS (AS DISCUSSED UNDER THE NEXT SUBHEADING). HOWEVER, OTHER CONGENITAL ANOMALIES (E.G. CRANIOFACIAL DEFECTS, CARDIOVASCULAR MALFORMATIONS AND ANOMALIES INVOLVING VARIOUS BODY SYSTEMS), COMPATIBLE AND INCOMPATIBLE WITH LIFE, HAVE BEEN REPORTED. SUFFICIENT DATA TO DETERMINE THE INCIDENCE OF THESE CONGENITAL ANOMALIES IS NOT AVAILABLE.

Neural Tube Defects
THE INCIDENCE OF NEURAL TUBE DEFECTS IN THE FETUS IS INCREASED IN MOTHERS RECEIVING VALPROATE DURING THE FIRST TRIMESTER OF PREGNANCY. THE CENTERS FOR DISEASE CONTROL (CDC) HAS ESTIMATED THE RISK OF VALPROIC ACID EXPOSED WOMEN HAVING CHILDREN WITH SPINA BIFIDA TO BE APPROXIMATELY 1 TO 2%. THE AMERICAN COLLEGE OF OBSTETRICIANS AND GYNECOLOGISTS (ACOG) ESTIMATES THE GENERAL POPULATION RISK FOR CONGENITAL NEURAL TUBE DEFECTS AS 0.14% TO 0.2%.

Tests to detect neural tube and other defects using current accepted procedures should be considered a part of routine prenatal care in pregnant women receiving valproate.

Evidence suggests that pregnant women who receive folic acid supplementation may be at decreased risk for congenital neural tube defects in their offspring compared to pregnant women not receiving folic acid. Whether the risk of neural tube defects in the offspring of women receiving valproate specifically is reduced by folic acid supplementation is unknown. DIETARY FOLIC ACID SUPPLEMENTATION BOTH PRIOR TO AND DURING PREGNANCY SHOULD BE ROUTINELY RECOMMENDED TO PATIENTS CONTEMPLATING PREGNANCY.

Other Adverse Pregnancy Effects
PATIENTS TAKING VALPROATE MAY DEVELOP CLOTTING ABNORMALITIES (See <B>PRECAUTIONS -GENERAL AND WARNINGS). A PATIENT WHO HAD LOW FIBRINOGEN WHEN TAKING MULTIPLE ANTICONVULSANTS INCLUDING VALPROATE GAVE BIRTH TO AN INFANT WITH AFIBRINOGENEMIA WHO SUBSEQUENTLY DIED OF HEMORRHAGE. IF VALPROATE IS USED IN PREGNANCY, THE CLOTTING PARAMETERS SHOULD BE MONITORED CAREFULLY.</B>

PATIENTS TAKING VALPROATE MAY DEVELOP HEPATIC FAILURE (See <B>WARNINGS - HEPATOTOXICITY AND BOX WARNING). FATAL HEPATIC FAILURES, IN A NEWBORN AND IN AN INFANT, HAVE BEEN REPORTED FOLLOWING THE MATERNAL USE OF VALPROATE DURING PREGNANCY.</B>

Animal Data
Animal studies have demonstrated valproate-induced teratogenicity. Increased frequencies of malformations, as well as intrauterine growth retardation and death, have been observed in mice, rats, rabbits, and monkeys following prenatal exposure to valproate. Malformations of the skeletal system are the most common structural abnormalities produced in experimental animals, but neural tube closure defects have been seen in mice exposed to maternal plasma valproate concentrations exceeding 230 µg/mL (2.3 times the upper limit of the human therapeutic range) during susceptible periods of embryonic development. Administration of an oral dose of 200 mg/kg/day or greater (50% of the maximum human daily dose or greater on a mg/m2 basis) to pregnant rats during organogenesis produced malformations (skeletal, cardiac, and urogenital) and growth retardation in the offspring. These doses resulted in peak maternal plasma valproate levels of approximately 340 µg/mL or greater (3.4 times the upper limit of the human therapeutic range or greater). Behavioral deficits have been reported in the offspring of rats given a dose of 200 mg/kg/day throughout most of pregnancy. An oral dose of 350 mg/kg/day (approximately 2 times the maximum human daily dose on a mg/m2 basis) produced skeletal and visceral malformations in rabbits exposed during organogenesis. Skeletal malformations, growth retardation, and death were observed in rhesus monkeys following administration of an oral dose of 200 mg/kg/day (equal to the maximum human daily dose on a mg/m2 basis) during organogenesis. This dose resulted in peak maternal plasma valproate levels of approximately 280 µg/mL (2.8 times the upper limit of the human therapeutic range).
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PRECAUTIONS
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Hepatic Dysfunction
See BOXED WARNING, CONTRAINDICATIONS and WARNINGS.

Pancreatitis
See BOXED WARNING and WARNINGS.

Hyperammonemia
Hyperammonemia has been reported in association with valproate therapy and may be present despite normal liver function tests. In patients who develop unexplained lethargy and vomiting or changes in mental status, hyperammonemic encephalopathy should be considered and an ammonia level should be measured. If ammonia is increased, valproate therapy should be discontinued. Appropriate interventions for treatment of hyperammonemia should be initiated, and such patients should undergo investigation for underlying urea cycle disorders (See CONTRAINDICATIONS and WARNINGS – Urea Cycle Disorders and PRECAUTIONS - Hyperammonemia and Encephalopathy Associated with Concomitant Topiramate Use).

Asymptomatic elevations of ammonia are more common and when present, require close monitoring of plasma ammonia levels. If the elevation persists, discontinuation of valproate therapy should be considered. In patients who develop unexplained lethargy, vomiting, or changes in mental status, hyperammonemic encephalopathy should be considered and an ammonia level should be measured. (See CONTRAINDICATIONS and WARNINGS - Urea Cycle Disorders and PRECAUTIONS - Hyperammonemia).

Hyperammonemia and Encephalopathy Associated with Concomitant Topiramate Use
Concomitant administration of topiramate and valproic acid has been associated with hyperammonemia with or without encephalopathy in patients who have tolerated either drug alone. Clinical symptoms of hyperammonemic encephalopathy often include acute alterations in level of consciousness and/or cognitive function with lethargy or vomiting. In most cases, symptoms and signs abated with discontinuation of either drug. This adverse event is not due to a pharmacokinetic interaction. It is not known if topiramate monotherapy is associated with hyperammonemia. Patients with inborn errors of metabolism or reduced hepatic mitochondrial activity may be at an increased risk for hyperammonemia with or without encephalopathy. Although not studied, an interaction of topiramate and valproic acid may exacerbate existing defects or unmask deficiencies in susceptible persons. In patients who develop unexplained lethargy, vomiting, or changes in mental status, hyperammonemic encephalopathy should be considered and an ammonia level should be measured. (See CONTRAINDICATIONS and WARNINGS - Urea Cycle Disorders and PRECAUTIONS - Hyperammonemia). General

Because of reports of thrombocytopenia (See WARNINGS), inhibition of the secondary phase of platelet aggregation, and abnormal coagulation parameters, (e.g., low fibrinogen), platelet counts and coagulation tests are recommended before initiating therapy and at periodic intervals. It is recommended that patients receiving DEPAKOTE be monitored for platelet count and coagulation parameters prior to planned surgery. In a clinical trial of DEPAKOTE as monotherapy in patients with epilepsy, 34/126 patients (27%) receiving approximately 50 mg/kg/day on average, had at least one value of platelets &#8804; 75 x 109/L. Approximately half of these patients had treatment discontinued, with return of platelet counts to normal. In the remaining patients, platelet counts normalized with continued treatment. In this study, the probability of thrombocytopenia appeared to increase significantly at total valproate concentrations of &#8805; 110 µg/mL (females) or &#8805; 135 µg/mL (males). Evidence of hemorrhage, bruising, or a disorder of hemostasis/coagulation is an indication for reduction of the dosage or withdrawal of therapy.

Since DEPAKOTE may interact with concurrently administered drugs which are capable of enzyme induction, periodic plasma concentration determinations of valproate and concomitant drugs are recommended during the early course of therapy. (See PRECAUTIONS-DRUG INTERACTIONS.)

Valproate is partially eliminated in the urine as a keto-metabolite which may lead to a false interpretation of the urine ketone test.

There have been reports of altered thyroid function tests associated with valproate. The clinical significance of these is unknown.

Suicidal ideation may be a manifestation of certain psychiatric disorders, and may persist until significant remission of symptoms occurs. Close supervision of high risk patients should accompany initial drug therapy.

There are in vitro studies that suggest valproate stimulates the replication of the HIV and CMV viruses under certain experimental conditions. The clinical consequence, if any, is not known. Additionally, the relevance of these in vitro findings is uncertain for patients receiving maximally suppressive antiretroviral therapy. Nevertheless, these data should be borne in mind when interpreting the results from regular monitoring of the viral load in HIV infected patients receiving valproate or when following CMV infected patients clinically.

Multi-organ Hypersensitivity Reaction
Multi-organ hypersensitivity reactions have been rarely reported in close temporal association to the initiation of valproate therapy in adult and pediatric patients (median time to detection 21 days: range 1 to 40 days). Although there have been a limited number of reports, many of these cases resulted in hospitalization and at least one death has been reported. Signs and symptoms of this disorder were diverse; however, patients typically, although not exclusively, presented with fever and rash associated with other organ system involvement. Other associated manifestations may include lymphadenopathy, hepatitis, liver function test abnormalities, hematological abnormalities (e.g., eosinophilia, thrombocytopenia, neutropenia), pruritis, nephritis, oliguria, hepato-renal syndrome, arthralgia, and asthenia. Because the disorder is variable in its expression, other organ system symptoms and signs, not noted here, may occur. If this reaction is suspected, valproate should be discontinued and an alternative treatment started. Although the existence of cross sensitivity with other drugs that produce this syndrome is unclear, the experience amongst drugs associated with multi-organ hypersensitivity would indicate this to be a possibility.

Information for Patients
Patients and guardians should be warned that abdominal pain, nausea, vomiting, and/or anorexia can be symptoms of pancreatitis and, therefore, require further medical evaluation promptly.

Patients should be informed of the signs and symptoms associated with hyperammonemic encephalopathy (See PRECAUTIONS – Hyperammonemia) and be told to inform the prescriber if any of these symptoms occur.

Since DEPAKOTE products may produce CNS depression, especially when combined with another CNS depressant (eg, alcohol), patients should be advised not to engage in hazardous activities, such as driving an automobile or operating dangerous machinery, until it is known that they do not become drowsy from the drug.

Since DEPAKOTE has been associated with certain types of birth defects, female patients of child-bearing age considering the use of DEPAKOTE should be advised of the risk and of alternative therapeutic options and to read the Patient Information Leaflet, which appears as the last section of the labeling. This is especially important when the treatment of a spontaneously reversible condition not ordinarily associated with permanent injury or risk of death (e.g., migraine) is considered.

Patients should be instructed that a fever associated with other organ system involvement (rash, lymphadenopathy, etc.) may be drug-related and should be reported to the physician immediately (See PRECAUTIONS - Multi-organ Hypersensitivity Reaction).

Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis
Valproic acid was administered orally to Sprague Dawley rats and ICR (HA/ICR) mice at doses of 80 and 170 mg/kg/day (approximately 10 to 50% of the maximum human daily dose on a mg/m2 basis) for two years. A variety of neoplasms were observed in both species. The chief findings were a statistically significant increase in the incidence of subcutaneous fibrosarcomas in high dose male rats receiving valproic acid and a statistically significant dose-related trend for benign pulmonary adenomas in male mice receiving valproic acid. The significance of these findings for humans is unknown.

Mutagenesis
Valproate was not mutagenic in an in vitro bacterial assay (Ames test), did not produce dominant lethal effects in mice, and did not increase chromosome aberration frequency in an in vivo cytogenetic study in rats. Increased frequencies of sister chromatid exchange (SCE) have been reported in a study of epileptic children taking valproate, but this association was not observed in another study conducted in adults. There is some evidence that increased SCE frequencies may be associated with epilepsy. The biological significance of an increase in SCE frequency is not known.

Fertility
Chronic toxicity studies in juvenile and adult rats and dogs demonstrated reduced spermatogenesis and testicular atrophy at oral doses of 400 mg/kg/day or greater in rats (approximately equivalent to or greater than the maximum human daily dose on a mg/m2 basis) and 150 mg/kg/day or greater in dogs (approximately 1.4 times the maximum human daily dose or greater on a mg/m2 basis). Segment I fertility studies in rats have shown doses up to 350 mg/kg/day (approximately equal to the maximum human daily dose on a mg/m2 basis) for 60 days to have no effect on fertility. THE EFFECT OF VALPROATE ON TESTICULAR DEVELOPMENT AND ON SPERM PRODUCTION AND FERTILITY IN HUMANS IS UNKNOWN.

Pregnancy
Pregnancy Category D:
See WARNINGS.

Nursing Mothers
Valproate is excreted in breast milk. Concentrations in breast milk have been reported to be 1-10% of serum concentrations. It is not known what effect this would have on a nursing infant. Consideration should be given to discontinuing nursing when divalproex sodium is administered to a nursing woman.

Pediatric Use
Experience has indicated that pediatric patients under the age of two years are at a considerably increased risk of developing <STRONG><FONT size=4>fatal hepatotoxicity</FONT></STRONG>, especially those with the aforementioned conditions (See BOXED WARNING). When DEPAKOTE is used in this patient group, it should be used with extreme caution and as a sole agent. The benefits of therapy should be weighed against the risks. Above the age of 2 years, experience in epilepsy has indicated that the incidence of fatal hepatotoxicity decreases considerably in progressively older patient groups.

Younger children, especially those receiving enzyme-inducing drugs, will require larger maintenance doses to attain targeted total and unbound valproic acid concentrations.

The variability in free fraction limits the clinical usefulness of monitoring total serum valproic acid concentrations. Interpretation of valproic acid concentrations in children should include consideration of factors that affect hepatic metabolism and protein binding.

The safety and effectiveness of DEPAKOTE for the treatment of acute mania has not been studied in individuals below the age of 18 years.

The safety and effectiveness of DEPAKOTE for the prophylaxis of migraines has not been studied in individuals below the age of 16 years.

The basic toxicology and pathologic manifestations of valproate sodium in neonatal (4-day old) and juvenile (14-day old) rats are similar to those seen in young adult rats. However, additional findings, including renal alterations in juvenile rats and renal alterations and retinal dysplasia in neonatal rats, have been reported. These findings occurred at 240 mg/kg/day, a dosage approximately equivalent to the human maximum recommended daily dose on a mg/m2 basis. They were not seen at 90 mg/kg, or 40% of the maximum human daily dose on a mg/m2 basis.

Geriatric Use
No patients above the age of 65 years were enrolled in double-blind prospective clinical trials of mania associated with bipolar illness. In a case review study of 583 patients, 72 patients (12%) were greater than 65 years of age. A higher percentage of patients above 65 years of age reported accidental injury, infection, pain, somnolence, and tremor. Discontinuation of valproate was occasionally associated with the latter two events. It is not clear whether these events indicate additional risk or whether they result from preexisting medical illness and concomitant medication use among these patients.

A study of elderly patients with dementia revealed drug related somnolence and discontinuation for somnolence (See WARNINGS-Somnolence in the Elderly). The starting dose should be reduced in these patients, and dosage reductions or discontinuation should be considered in patients with excessive somnolence (See DOSAGE AND ADMINISTRATION).

There is insufficient information available to discern the safety and effectiveness of DEPAKOTE for the prophylaxis of migraines in patients over 65.


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Joined: January 1st, 1970, 12:00 am

June 18th, 2007, 3:04 pm #4

MAY 2007: News on SSRIs, other Psych Drugs and Related Issues
no need to worry, as at 1 minute after midnight on your 24th birthday&nbsp; you no longer are prone to suffering drug induced suicidal ideation.&nbsp; &nbsp;Must be some sudden&nbsp;&nbsp;bodyclockological thing that kicks in at age 24 and neutralises the harmful parts of the chemical concoction you're taking. I'd just <STRONG>LOVE </STRONG>to see the&nbsp;'science' that supports this 'hypothesis' of a sudden defence against chemical/physio/neurological interactions at&nbsp;a particular age, but until we get evidenced&nbsp;based&nbsp;medicine and&nbsp;drug regulatory officials that make SCIENCE-based decisions - we have to be grateful for SOME extended warning - as the past option was none at all... then kids... now up to 24.

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<!-- #BeginEditable "H2 Title Head" -->FDA Proposes New Warnings About Suicidal Thinking, Behavior in Young Adults Who Take Antidepressant Medications <!-- #EndEditable --><!-- #BeginEditable "Body of Text" -->
The U.S. Food and Drug Administration (FDA) today proposed that makers of all antidepressant medications update the existing black box warning on their products' labeling to include warnings about increased risks of suicidal thinking and behavior, known as suicidality, in young adults ages 18 to 24 during initial treatment (generally the first one to two months).

The proposed labeling changes also include language stating that scientific data did not show this increased risk in adults older than 24, and that adults ages 65 and older taking antidepressants have a decreased risk of suicidality. The proposed warning statements emphasize that depression and certain other serious psychiatric disorders are themselves the most important causes of suicide.

"Today's actions represent FDA's commitment to a high level of post-marketing evaluation of drug products," said Steven Galson, M.D., MPH, director of FDA's Center for Drug Evaluation and Research. "Depression and other psychiatric disorders can have significant consequences if not appropriately treated. Antidepressant medications benefit many patients, but it is important that doctors and patients are aware of the risks."

People currently prescribed antidepressant medications should not stop taking them. Those who have concerns should notify their health care providers.

The proposed labeling changes apply to the entire category of antidepressants. Results of individual placebo-controlled scientific studies are reasonably consistent in showing a slight increase in suicidality for patients taking antidepressants in early treatment for most of the medications. Available data are not sufficient to exclude any single medication from the increased risk of suicidality.

The proposed labeling update follows similar labeling changes made in 2005 that warned of a suicidality risk in children and adolescents who use antidepressants. At that time, FDA asked manufacturers to add a black box warning to the labeling of all antidepressants to describe this risk and to emphasize the need for appropriate monitoring and close observation, particularly for younger patients taking these medications. In addition, FDA directed manufacturers to develop Medication Guides, FDA-approved user-friendly information for patients, families and caregivers, that could help improve monitoring. Medication Guides are intended to be distributed at the pharmacy with each prescription or refill of a medication.

Also in 2005, FDA began a comprehensive review of 295 individual antidepressant trials that included over 77,000 adult patients with major depressive disorder (MDD) and other psychiatric disorders, to examine the risk of suicidality in adults who are prescribed antidepressants.

In December 2006, FDA's Psychopharmacologic Drugs Advisory Committee agreed that labeling changes were needed to inform health care professionals about the increased risk of suicidality in younger adults using antidepressants. Additionally, the committee noted product labeling needed to reflect the apparent beneficial effect of antidepressants in older adults and to remind health care professionals that the disorders themselves are the most important cause of suicidality.

FDA has been developing language to revise product labeling and update the Patient Medication Guides for these products. Manufacturers of antidepressants will now have 30 days to submit their revised product labels and revised Medication Guides to FDA for review.

Products involved in today's action include:

Anafranil (clomipramine)
Asendin (amoxapine)
Aventyl (nortriptyline)
Celexa (citalopram hydrobromide)
Cymbalta (duloxetine)
Desyrel (trazodone HCl)
Elavil (amitriptyline)
Effexor (venlafaxine HCl)
Emsam (selegiline)
Etrafon (perphenazine/amitriptyline)
fluvoxamine maleate
Lexapro (escitalopram hydrobromide)
Limbitrol (chlordiazepoxide/amitriptyline)
Ludiomil (maprotiline)
Marplan (isocarboxazid)
Nardil (phenelzine sulfate)
nefazodone HCl
Norpramin (desipramine HCl)
Pamelor (nortriptyline)
Parnate (tranylcypromine sulfate)
Paxil (paroxetine HCl)
Pexeva (paroxetine mesylate)
Prozac (fluoxetine HCl)
Remeron (mirtazapine)
Sarafem (fluoxetine HCl)
Seroquel (quetiapine)
Sinequan (doxepin)
Surmontil (trimipramine)
Symbyax (olanzapine/fluoxetine)
Tofranil (imipramine)
Tofranil-PM (imipramine pamoate)
Triavil (perphenazine/amitriptyline)
Vivactil (protriptyline)
Wellbutrin (bupropion HCl)
Zoloft (sertraline HCl)
Zyban (bupropion HCl)

For more information:

Antidepressant use in children, adolescents, and adults, including the draft labeling and draft Medication Guides www.fda.gov/cder/drug/antidepressants/default.htm

FDA's Psychopharmacologic Drugs Advisory Committee, including transcripts from the December 2006 meeting www.fda.gov/ohrms/dockets/ac/cder06.html#Psychopharmacologic

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Joined: January 1st, 1970, 12:00 am

June 18th, 2007, 3:28 pm #5

MAY 2007: News on SSRIs, other Psych Drugs and Related Issues
<P class=""><FONT color=#0000ff>http://www.insidezyprexa.com/index.jsp#</FONT><A class=navLevel1Link href="http://www.insidezyprexa.com/about_zyprexa.jsp"></A>
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</DIV>
<STRONG>Answers to questions you may have regarding agreements that Eli Lilly and Company entered into to settle the vast majority of the remaining cases in the ZYPREXA® (olanzapine) product liability litigation
</STRONG>

Q:&nbsp;&nbsp; What are the implications for health care professionals? Have any healthcare professionals had judgments against them?
A:&nbsp;&nbsp; As a part of these agreements, plaintiffs' attorneys have agreed to dismiss all claims that had been made against healthcare professionals in any cases, relating to the prescribing of ZYPREXA, covered by these settlements. Health care professionals will not have to pay a penny toward the settlements and will not have a judgment or settlement to report. To date, no health care professional who was a party in these ZYPREXA product liability claims has had to pay anything or has had a judgment against him or her.

Q:&nbsp;&nbsp; If I was a party in a claim that was included in these settlements, what do I need to do?
A:&nbsp;&nbsp; You do not have to do anything. You or your counsel will receive notification that your case has been dismissed.

Q:&nbsp;&nbsp; Do you have resources to help me discuss the benefits and risks of ZYPREXA with my patients?
A:&nbsp;&nbsp; Yes, your Lilly sales representatives have simple-to-use materials you can use to discuss ZYPREXA's benefits and potential adverse events with those you treat. They also carry tools that are consistent with established care guidelines to help you monitor your patients as they continue their treatment.

Q:&nbsp;&nbsp; Why did Lilly settle?
A:&nbsp;&nbsp; We have been vigorously defending against these claims involving ZYPREXA because we believe they are without merit, and we will continue to do so with any remaining cases going forward. However, we decided that it was in the best interests of patients, healthcare professionals, shareholders, and employees to try to place this product liability litigation behind us.

We have heard from many of you that these lawsuits and lawyer ads stirred concern and interfered with your process of making decisions about which medication best suits an individual patient's needs.

In reaching these agreements with this collection of plaintiffs' attorneys, we have attempted to alleviate this concern. These agreements include the vast majority of current ZYPREXA product liability claims. As a part of these agreements, plaintiffs' attorneys have agreed that all claims against healthcare professionals named in any cases relating to the prescribing of ZYPREXA covered by these settlements will be dismissed. Healthcare professionals will not have to pay a penny toward these settlements and will not have a judgment or settlement to report.

Q:&nbsp;&nbsp; Will I continue to see legal ads from plaintiff attorneys related to ZYPREXA?
A:&nbsp;&nbsp; Despite concerns expressed by the Court about the validity of these claims, some lawyers continue to solicit cases. Indeed, similar product liability law suits have been filed against manufacturers of other atypical antipsychotics. <STRONG><FONT size=4>Plaintiffs' attorneys have been actively running legal ads mentioning a single agent or several agents within the class. Ads mentioning multiple agents may still include ZYPREXA. If you see such an ad, please call 1-800-LILLYRX to report it.</FONT></STRONG>

Q:&nbsp;&nbsp; What is the purported basis for the claims?
A:&nbsp;&nbsp; In September 2003, the FDA required label changes for all atypical antipsychotics to alert doctors to the potential risk of diabetes and hyperglycemia. Information that hyperglycemia and diabetes were infrequent adverse events has, in fact, been in the product label since ZYPREXA was introduced in 1996. In most lawsuits, plaintiffs' attorneys claimed that before the label change, the information conveying the risk as an infrequent adverse event was not adequately described.

Q:&nbsp;&nbsp; How can I get a question about the settlement answered?
A:&nbsp;&nbsp; Please call 1-800-LillyRX if you have any other questions.

For complete safety profile, see the full Prescribing Information provided below.

ZYPREXA is a registered trademark of Eli Lilly and Company.
Zyrtec is a registered trademark of UCB, SA.

&nbsp;

<DIV style="MARGIN-RIGHT: 70px">Important Safety Information for ZYPREXA®(Olanzapine)

<TABLE class=tableBlackBorder cellSpacing=0 cellPadding=3 border=1>
<TBODY>
<TR>
<TD class=maincopy>

Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared to placebo. Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks) in these patients revealed a risk of death in the drug-treated patients of between 1.6 to 1.7 times that seen in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. ZYPREXA (olanzapine) is not approved for the treatment of elderly patients with dementia-related psychosis.
</TD></TR></TBODY></TABLE>


Cerebrovascular adverse events (CVAE), including stroke, in elderly patients with dementia — Cerebrovascular adverse events (eg, stroke, transient ischemic attack), including fatalities, were reported in trials of olanzapine in elderly patients with dementia-related psychosis. In placebo-controlled trials, there was a significantly higher incidence of CVAE in patients treated with olanzapine compared to patients treated with placebo. Olanzapine is not approved for the treatment of patients with dementia-related psychosis.

Hyperglycemia and diabetes mellitus — Hyperglycemia, in some cases associated with ketoacidosis, coma, or death, has been reported in patients treated with atypical antipsychotics including olanzapine. All patients taking atypicals should be monitored for symptoms of hyperglycemia. Persons with diabetes who are started on atypicals should be monitored regularly for worsening of glucose control; those with risk factors for diabetes should undergo baseline and periodic fasting blood glucose testing. Patients who develop symptoms of hyperglycemia during treatment should undergo fasting blood glucose testing.

Neuroleptic malignant syndrome (NMS) — As with all antipsychotic medications, a rare and potentially fatal condition known as NMS has been reported with olanzapine. If signs and symptoms appear, immediate discontinuation is recommended. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmia). Additional signs may include elevated creatinine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure.

Tardive dyskinesia (TD) — As with all antipsychotic medications, prescribing should be consistent with the need to minimize the risk of TD. The risk of developing TD and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic increase. The syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn.

Medication dispensing and prescribing errors have occurred between ZYPREXA (olanzapine) and Zyrtec (cetirizine HCl). These errors could result in unnecessary adverse events or potential relapse in patients suffering from schizophrenia or bipolar disorder. To reduce the potential for dispensing errors, please write ZYPREXA clearly.

The most common treatment-emergent adverse event associated with intramuscular olanzapine vs placebo IM in 3 short-term (24-hour treatment) trials involving agitated patients with schizophrenia or bipolar mania was somnolence (6% vs 3%). Also observed (intramuscular olanzapine vs placebo IM) were dizziness (4% vs 2%), hypotension (2% vs 0%), asthenia (2% vs 1%), tremor (1% vs 0%), and postural hypotension (1% vs 0%).

The most common treatment-emergent adverse event associated with oral olanzapine (vs placebo) in 6-week acute-phase schizophrenia trials was somnolence (26% vs 15%). Other common events were dizziness (11% vs 4%), weight gain (6% vs 1%), personality disorder (COSTART term for nonaggressive objectionable behavior; 8% vs 4%), constipation (9% vs 3%), akathisia (5% vs 1%), and postural hypotension (5% vs 2%).

The most common treatment-emergent adverse event associated with oral olanzapine (vs placebo) in 3- and 4-week bipolar mania trials was somnolence (35% vs 13%). Other common events were dry mouth (22% vs 7%), dizziness (18% vs 6%), asthenia (15% vs 6%), constipation (11% vs 5%), dyspepsia (11% vs 5%), increased appetite (6% vs 3%), and tremor (6% vs 3%).

To view the entire Important Safety Information, click here.


ZYPREXA is a registered trademark of Eli Lilly and Company.
Zyrtec is a registered trademark of UCB, SA.&nbsp; "

&nbsp;

<STRONG><EM>Download Lilly's confidential Zyprexa documents here:&nbsp; </EM></STRONG><FONT size=5><STRONG>http://www.furiousseasons.com/zyprexadocs.html</STRONG></FONT>



<STRONG><EM>and phone Eli Lilly to discuss the following: </EM></STRONG><STRONG><FONT size=5>http://home.comcast.net/~11.5.dcqp/AdjustmentDisorder.html</FONT>
</STRONG>
<DIV><STRONG></STRONG>&nbsp;</DIV>
<DIV><STRONG><FONT size=6>"GET AN ATTORNEY LILLY</FONT></STRONG></DIV>
<DIV>&nbsp;</DIV>
<DIV><IMG alt=AdjustmentDisorder.jpg src="http://www.network54.com/Realm/peageepics/AdjustmentDisorder.jpg">&nbsp;</DIV>
<DIV>&nbsp;</DIV>
<DIV>&nbsp;</DIV>
<DIV><FONT size=4><STRONG>If you see such an ad, please call 1-800-LillyRX to report it!</STRONG></FONT></DIV>
<DIV>http://www.insidezyprexa.com/index.jsp</DIV>
<DIV>&nbsp;</DIV>
<DIV>
<DIV><STRONG>(olanzapine) Zyprexa® / Adjustment Disorder</STRONG></DIV>
<DIV><STRONG>Call 1-800-LillyRX if you have any other questions! "</STRONG></DIV></DIV></DIV>
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June 18th, 2007, 3:36 pm #6

MAY 2007: News on SSRIs, other Psych Drugs and Related Issues
http://www.dailymail.co.uk/pages/live/a ... ge_id=1799




Additives blamed for children's tantrums
Last updated at 09:50am on 8th May 2007


Join the debate » Parents have been advised by food safety experts to omit several additives from their children's diets, with new research set to confirm a link between the ingredients and behavioural problems.

The study, conducted by Southampton University for the Food Standards Agency, has analysed the effects of a number of preservatives and colourings found in sweets, drinks and processed foods commonly consumed by children. It is thought to have concluded a definite link between the additives and problems such as temper tantrums and hyperactivity.

Although the findings are not due to be released until much later this year, the results have been viewed and considered by the FSA's Committee on Toxicity of Chemicals in Food which officially noted "the public health importance of the findings" which are thought to have been consistent with a similar study in 2000 disputed by the committee.

The first trial, known as the Isle of Wight study, concluded that " significant changes in children's behaviour could be produced by the removal of colourings and additives from their diet and benefit would accrue for all children from such a change."

The committee, however, declared in 2002 that the study was inconclusive.

The FSA then set up the further study to provide conclusive evidence, with a working group of independent experts. The experts have advised consumers to consider removing these additives from children's diets immediately.

The colours, tested on both threeyearolds and eight- to nine-year olds, are tartrazine (E102), ponceau 4R (E124), sunset yellow (E110), carmoisine (E122), quinoline yellow (E104) and allura red AC (E129). The preservative tested was sodium benzoate (E211).

While these additives are widely used in Britain and approved by the EU, some are banned in Scandinavian countries and in the US.

Vyvyan Howard, professor of bioimaging at Ulster University and an expert on the FSA's additives and behaviour working group, said: "It is biologically plausible that there could be an effect from these additives. While you are waiting for the results to come out you can choose not to expose your children to these substances. These compounds have no nutritonal value and I personally do not feed these sorts of foods to my 15-month-old daughter."
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Joined: January 1st, 1970, 12:00 am

June 18th, 2007, 3:50 pm #7

MAY 2007: News on SSRIs, other Psych Drugs and Related Issues
<P align=left>http://us.gsk.com/products/assets/us_paxil.pdf

<P align=left>see page 35

<P align=left>"...Nervous System: Frequent: Emotional lability, vertigo; infrequent: Abnormal thinking, <STRONG><FONT size=5>alcohol abuse</STRONG>, ataxia, dystonia, dyskinesia, euphoria, hallucinations, hostility, hypertonia, hypesthesia, hypokinesia, incoordination, lack of emotion, libido increased, manic reaction, neurosis, paralysis, paranoid reaction; </FONT>rare: Abnormal gait, akinesia, antisocial reaction, aphasia, choreoathetosis, circumoral paresthesias, convulsion, delirium, delusions, diplopia, <STRONG><EM><FONT size=5>drug dependence</EM></STRONG>, dysarthria, extrapyramidal syndrome, fasciculations, grand mal convulsion, hyperalgesia, hysteria, manic-depressive reaction, meningitis, myelitis, neuralgia, neuropathy, nystagmus, peripheral neuritis, psychotic depression, psychosis, reflexes decreased, reflexes increased, stupor, torticollis, trismus, withdrawal syndrome..."</FONT>

<P align=left>&nbsp;

<P align=left>http://www.wyeth.com/content/ShowLabeling.asp?id=100

<P align=left>See page 38

<P align=left>
"...Nervous system - Frequent: amnesia, confusion, depersonalization, hypesthesia, thinking abnormal, trismus, vertigo; Infrequent: akathisia, apathy, ataxia, circumoral paresthesia, CNS stimulation, emotional lability, euphoria, hallucinations, hostility, hyperesthesia, hyperkinesia,hypotonia, incoordination, manic reaction, myoclonus, neuralgia, neuropathy, psychosis, seizure,abnormal speech, stupor, suicidal ideation; Rare: abnormal/changed behavior, adjustment disorder, akinesia, <STRONG><FONT size=5>alcohol abuse</FONT></STRONG>, aphasia, bradykinesia, buccoglossal syndrome, cerebrovascular accident, feeling drunk, loss of consciousness, delusions, dementia, dystonia, energy increased, facial paralysis, abnormal gait, Guillain-Barre Syndrome, <STRONG><EM><FONT size=5>homicidal ideation</FONT></EM></STRONG>, hyperchlorhydria,hypokinesia, hysteria, impulse control difficulties, libido increased, motion sickness, neuritis,nystagmus, paranoid reaction, paresis, psychotic depression, reflexes decreased, reflexes increased, torticollis..."

<P align=left>&nbsp;
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Joined: January 1st, 1970, 12:00 am

June 18th, 2007, 3:56 pm #8

MAY 2007: News on SSRIs, other Psych Drugs and Related Issues
http://www.latimes.com/features/health/medicine/la-na-nih9may09,1,3051769.story?coll=la-health-medicine

"Penalized researcher retires




WASHINGTON — A senior researcher at the National Institutes of Health, who became a symbol of the agency's improper entanglements with drug companies and whose lasting presence on the federal payroll enraged members of Congress, has retired from the government.

Dr. P. "Trey" Sunderland III accepted about $612,000 in consulting and speaking fees from Pfizer Inc. and about $200,000 from other companies from 1998 to 2004, all without getting required approvals in advance from the NIH. He pleaded guilty five months ago to a federal conflict-of-interest charge and agreed to pay $300,000 to the government and to perform community service.

Word of Sunderland's retirement surfaced in a probation report filed Thursday with a U.S. District Court in Baltimore. The probation officer, Rasheed J. Tahir, wrote that Sunderland "<STRONG><FONT size=4>is now privately practicing psychiatry</FONT></STRONG>."

Sunderland has paid the government about one-third of the $300,000 in restitution and performed three-fourths of his required community service, the report said. <STRONG><FONT size=4>Sunderland, 55, a psychiatrist who specialized in researching Alzheimer's disease</FONT></STRONG>, had remained on the federal payroll through March. His case was among scores that prompted a sweeping ban of drug-company consulting fees and other industry compensation to NIH employees.

The ban, which was ordered in 2005 by the director of the NIH, was <STRONG><FONT size=4>fought by many scientists at the agency who wanted the income from the drug companies</FONT></STRONG>.

The timing of the ban is of renewed relevance for Sunderland: He told colleagues at a national psychiatric research conference in December 2006 that he was a <STRONG>consultant to Pfizer and another drug-maker, AstraZeneca.</STRONG> Conference materials also show that Sunderland reported that he had received honoraria, typically fees for speaking or making appearances, from Pfizer, Bristol-Myers Squibb and Janssen Pharmaceuticals.

Reached by telephone at the NIH headquarters in Bethesda, Md., Deputy Director Raynard S. Kington declined to say whether the agency had granted Sunderland special permission to accept compensation from any of the four drug companies.

<STRONG>Sunderland's lawyer, Robert F. Muse, declined comment on his client's disclosures at the December conference. He also declined to discuss terms of Sunderland's discharge and retirement.
</STRONG>
Three of the four drug companies listed by Sunderland in December had no comment. A spokeswoman for <STRONG>Pfizer, Liz Powers, said: "Sunderland was, at one time, a consultant to Pfizer Inc. He is not currently a consultant."
</STRONG>
Sunderland's retirement ended an inquiry by the U.S. Commissioned Corps, the uniformed branch of the Public Health Service of which he had been a member since arriving at the NIH in 1982."

The official who oversees the Commissioned Corps, Adm. John O. Agwunobi, referred inquiries to an aide, who declined to say whether Sunderland had been granted an honorable discharge with full federal retirement benefits.

While accepting the earlier fees from Pfizer, Sunderland had collaborated with the company in his official role. From 1998 to 2003, he and his staff collected samples of spinal fluid from patients at the NIH's Clinical Center, in Bethesda.

Under terms of an agreement between the NIH and Pfizer, Sunderland then provided the samples to the drug company for its analysis and use in seeking clues that might develop a treatment for Alzheimer's disease.

Members of Congress had questioned months ago why the NIH had allowed Sunderland to remain on the federal payroll long after it was first established, in mid-2004, that he had flouted the agency's rules.

At congressional hearings last year, Sunderland's superiors at the NIH's mental-health institute said they were powerless to act against him because he belonged to the Commissioned Corps. Agwunobi told the House Energy and Commerce Committee's investigations subcommittee in September that his staff needed to gather more information.

The then-chairman of the full committee, Rep. Joe L. Barton (R-Texas), called the NIH "an ethical Potemkin village, where a hollow system appears to provide the illusion of integrity, but transgressors never leave."

Regarding Sunderland, Barton told Agwunobi: "You're sitting on your bottom, and you're not doing anything about it. It's a farce."

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Joined: January 1st, 1970, 12:00 am

June 18th, 2007, 4:00 pm #9

MAY 2007: News on SSRIs, other Psych Drugs and Related Issues
<STRONG><EM><FONT size=4>Email from&nbsp;N in Ireland:</FONT></EM></STRONG>


&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; <BIG><FONT size=4><BIG><FONT class=headlineblack>"OxyContin's Deception Costs Firm $634M </FONT></BIG>
</FONT></BIG>
<DIV class=body><FONT size=3><BIG>ROANOKE, Va., May 10, 2007</BIG>
</FONT><BIG><FONT size=3>(CBS/AP)&nbsp;Two days after agreeing to pay states nearly $20 million for falsely marketing OxyContin, the drug's maker, Perdue Pharma, and three current and former executives plead guilty to federal charges.

</FONT></BIG>
<BIG>
<FONT size=3>Purdue Pharma L.P., its president, top lawyer and former chief medical officer will pay $634.5 million in fines for claiming the drug was less addictive and less subject to abuse than other pain medications, U.S. Attorney John Brownlee said in a news release.

The plea agreement comes after the company agreed to pay $19.5 million to 26 states and the District of Columbia to settle complaints that it encouraged physicians to overprescribe OxyContin.

"With its OxyContin, Purdue unleashed a highly abusable, addictive, and potentially dangerous drug on an unsuspecting and unknowing public," Brownlee said. "For these misrepresentations and crimes, Purdue and its executives have been brought to justice."

Purdue learned from focus groups with physicians in 1995 that they were worried about the abuse potential of OxyContin. The company then gave false information to its sales representatives that the drug had less potential for addiction and abuse than other painkillers, the U.S. attorney said.

Even though the company was warned by health professionals, the media and members of its own sales force, "Perdue continued to push a fraudulent marketing campaign that promoted OxyContin as less addictive, less subject to abuse and less likely to cause withdrawal when they knew in fact that that was not true," Brownlee told CBS News correspondent Barry Bagnato.

"People who are suffering from chronic pain want a drug that can relieve them of that pain and yet the same time is safe not only for themselves but for society," Brownlee said. "And Perdue promised that."

"Doctors are often approached right in their offices by pharmaceutical company sales reps dispensing information about one medication or another," said CBS News medical correspondent Dr. Jon LaPook. "This case is a reminder to doctors not to believe everything they hear — and to drug companies that the FDA will hold them accountable for fraudulent practices."

Purdue Pharma said it accepted responsibility for its employees' actions.

"During the past six years, we have implemented changes to our internal training, compliance and monitoring systems that seek to assure that similar events do not occur again," the company said in a news release.

OxyContin, a trade name for oxycodone, is designed to have a time-released effect on a patient's pain, but people who abuse the medication will crush the pills and then swallow, snort or inject the drug so that its pain-killing properties — meant to be spread out over 12 hours — are absorbed all at once.

From 1996 to 2001, the number of oxycodone-related deaths nationwide increased 400 percent while the annual number of OxyContin prescriptions increased nearly 20-fold, according to a report by the U.S. Drug Enforcement Administration. In 2002, the DEA said the drug caused 146 deaths and contributed to another 318.

The drug became a major problem in Virginia — particularly southwest Virginia and other areas of the Appalachian region, where it got the nickname "hillbilly heroin."

In western Virginia, 228 people died from overdoses of oxycodone from 1996 to 2005, Brownlee said.

Brownlee said the guilty pleas were entered Thursday morning in U.S. District Court in Abingdon, about 135 miles south of Roanoke. In addition to Purdue's plea, company chief executive officer Michael Friedman, general counsel Howard Udell and chief medical officer Paul Goldenheim each pleaded guilty to misdemeanor counts of misbranding the drug. They individually will pay fines totaling $34.5 million.

The fines will be distributed to state and federal law enforcement agencies, the federal government, federal and state Medicaid programs, a Virginia prescription monitoring program and individuals who had sued the company. At least $5 million will go toward a six-year company program to monitor compliance with the agreement. </FONT></BIG></DIV><BIG>

<FONT face="Arial, Helvetica, Sans" size=1><BIG>© MMVII, CBS Interactive Inc. All Rights Reserved. This material may not be published, broadcast, rewritten, or redistributed. The Associated Press contributed to this report.

</BIG></FONT></BIG>



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June 18th, 2007, 4:03 pm #10

MAY 2007: News on SSRIs, other Psych Drugs and Related Issues
http://www.kaisernetwork.org/daily_reports/rep_index.cfm?DR_ID=44836


<DIV class=bodytext><FONT size=-1>[May 10, 2007]</FONT>
&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; The <CITE><FONT color=#000000>New York Times</FONT></CITE> on Thursday examined how "the intersection of money and medicine, and its effect on the well-being of patients, has become one of the most contentious issues in health care" -- and "[n]owhere is that more true than in psychiatry, where<STRONG> increasing payments to doctors have coincided with the growing use in children of a relatively new class of drugs known as atypical antipsychotics</STRONG>." Drugs in the best-selling class of antipsychotics -- which includes Risperdal, Seroquel, Zyprexa, Abilify and Geodon -- are being prescribed to more than 500,000 U.S. children "to help parents deal with behavior problems despite profound risks and almost no approved uses for minors," the <CITE>Times</CITE> reports.

The <CITE>Times</CITE> conducted an analysis of records in Minnesota, the only state that requires public reports of all drug company marketing payments to doctors. The analysis found that from 1997 to 2005, more than one-third of Minnesota's licensed psychiatrists took money from drug manufacturers, <STRONG><FONT size=4>including the last eight presidents of the </FONT></STRONG><FONT color=#394b6b size=4><STRONG>Minnesota Psychiatric Society</STRONG></FONT>. The analysis found that from 2000 to 2005, drug maker payments to Minnesota psychiatrists increased more than sixfold to $1.6 million.

During the same period, prescriptions of antipsychotics for children in Minnesota's Medicaid program rose more than ninefold, the <CITE>Times</CITE> analysis found. The analysis also found that doctors "who took the most money from makers of atypicals tended to prescribe the drugs to children the most often," the <CITE>Times</CITE> reports. <STRONG>Further, Minnesota psychiatrists who received at least $5,000 from manufacturers of atypicals from 2000 to 2005 appear to have written three times as many atypical prescriptions for children as psychiatrists who received less or no money. </STRONG>The analysis found that payments to individual psychiatrists ranged from $51 to more than $689,000, with a median of $1,750.

According to the <CITE>Times</CITE>, because the records are "incomplete, these figures probably underestimate doctors' actual incomes." The <CITE>Times</CITE> notes that "[n]o one has proved that psychiatrists prescribe atypicals to children because of drug company payments" (Harris et al., <CITE>New York Times</CITE>, 5/10). "
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