To Give Or Not To Give Antidepressants To Young People

More and more children are being diagnosed with depression. However, whether or not children should be treated with antidepressants is hotly disputed. You can read a Head to Head - where one person writes in favor, while another writes against, in this week's issue of The British Medical Journal (BMJ).


Yes - Children should be given antidepressants


We should not deny depressed children one of the few evidence-based available treatments, says Andrew Cotgrove, Clinical Director and Consultant in Adolescent Psychiatry at Pine Lodge Young People's Centre, Chester England.


The most controversial prescribing has been that of SSRIs (selective serotonin reuptake inhibitors) for children. Nevertheless, objective analysis of studies demonstrates a substantial benefit, when compared to a placebo, for some SSRIs. Guidelines recommend their use for young people with depression and OCD (obsessive-compulsive disorder).


Previous research has indicated that the use of SSRIs raises the risk of suicide related events. However, the risk is tiny and can be lessened even further with careful monitoring, Cotgrove writes.


Although cognitive behavioral therapy, interpersonal therapy and family therapy have some effect for young depressed patients, their effects are very small.


Cotgrove explains that disturbing procedural mistakes, exclusion of evidence in the conducting and reporting of some SSRI clinical trials, have justifiably alarmed doctors and members of the public. However, when one reviews the evidence carefully and objectively, the indications are that antidepressants have a role to play in treating young people with depression and OCD.


Young patients and their parents need to be told of the benefits and risks, given advice and support when choosing an evidence-based treatment. If we removed antidepressants as one of the options we would be taking away one of the few potentially effective interventions for these disabling conditions, Cotgrove concludes.


No - Children should not be given antidepressants


Prescribing SSRIs for young people is dangerous, not ethically sound, and poor value for money, writes Sami Timimi, Consultant Child and Adolescent Psychiatrist, Lincolnshire, England.


Timimi explains that as far as childhood depression is concerned, none of the SSRI studies has shown significant benefits over a placebo. Even so, national guidelines indicate the fuoxetine has more benefits than risks for young patients.


However, fluoxetine's profile is not that different from that of other SSRIs - efficacy is small and there is a potential danger. Timimi does acknowledge that a high placebo response makes it difficult for doctors to accept that SSRIs may be ineffective when faced with a distressed young person.


Timimi adds that a combination of fuzzy reporting and marketing spin have taken precedence over scientific accuracy, which have not helped the situation.


A reason for carrying out the studies in the first place was to validate well established prescribing patterns. It led to a trend which has been hard to undo, in spite of all the evidence. This does not mean we do not reverse it - for that we must, Timimi argues. SSRIs are neither value for money, nor clinically useful, moreover a small but tragic number of deaths may have happened because of their use.


In the majority of childhood cases distress is self limiting and does not need extensive intervention. However, when intervention is needed psychotherapy has shown itself to be effective, Timimi concludes.


"Should young people be given antidepressants? Yes"

Andrew Cotgrove

BMJ 2007;335:750 (13 October), doi:10.1136/bmj.39316.399931.94

Click here to read first 150 words online


"Should young people be given antidepressants? No"

Sami Timimi

BMJ 2007;335:751 (13 October), doi:10.1136/bmj.39316.406470.94

Click here to read first 150 words online

Targacept Initiates Phase I Clinical Trial Of TC-2216

Targacept, Inc.
(Nasdaq: TRGT), a clinical-stage biopharmaceutical company developing a new
class of drugs known as NNR Therapeutics(TM), today announced that it has
initiated a Phase I clinical trial of TC-2216, its product candidate for
the treatment of depression and anxiety disorders.


The trial is designed to evaluate the safety and tolerability of
TC-2216 and to assess its pharmacokinetic profile. The trial is a
double-blind, placebo-controlled crossover study, with sequential ascending
single oral doses administered to healthy male volunteers.



TC-2216 is a novel compound discovered using Targacept's proprietary
drug design platform known as Pentad(TM). The compound targets specific
neuronal nicotinic receptors (NNRs), a class of receptors found in the
central nervous system that play a critical role in regulating nervous
system activity. TC- 2216 selectively inhibits the alpha4beta2 NNR to
modulate the release of neurotransmitters that are involved in mood
regulation. In preclinical studies, TC-2216 showed greater potency than and
anti-depressant effects comparable to selective serotonin reuptake
inhibitors and tricyclics, which are commonly used treatments for
depression, as well as anxiety-relieving effects.



Targacept currently plans to develop TC-2216 as an oral monotherapy. In
November, the company announced positive top line results from a Phase II
clinical trial of TRIDMAC(TM), a treatment combination comprised of
mecamylamine hydrochloride as an augmentation therapy to citalopram
hydrobromide, in patients who did not respond adequately to citalopram
alone. Mecamylamine hydrochloride binds non-selectively to various NNR
subtypes, but there is a body of scientific evidence that suggests that its
anti-depressant activity is derived through its antagonism at the
alpha4beta2 NNR.



"Depression is a highly debilitating illness, and millions of people
who suffer with it are not gaining adequate relief from existing
therapies," said J. Donald deBethizy, Ph.D., Targacept's President and
Chief Executive Officer. "The results of our TRIDMAC trial not only
substantiate the promise of the NNR mechanism in the treatment of
depression and other mood disorders, but also further bolster our
enthusiasm for the potential of TC-2216."



About Targacept



Targacept is a clinical-stage biopharmaceutical company that discovers
and develops NNR Therapeutics(TM), a new class of drugs for the treatment
of central nervous system diseases and disorders. Targacept's product
candidates selectively modulate neuronal nicotinic receptors that serve as
key regulators of the nervous system activity to promote therapeutic
effects and limit adverse side effects. Targacept has product candidates in
development for Alzheimer's disease and cognitive deficits in
schizophrenia, pain and depression, and multiple preclinical programs.
Targacept is located in Winston-Salem, North Carolina. For more information
about Targacept, please visit targacept.

















Forward-Looking Statements



Any statements in this press release about expectations, plans and
prospects for Targacept, Inc., including, without limitation, statements
regarding the progress, timing and scope of research and development of TC-
2216 and related regulatory filings and clinical trials, and all other
statements that are not purely historical in nature, constitute "forward-
looking statements" within the meaning of the Private Securities Litigation
Reform Act of 1995. Without limiting the foregoing, the words "may,"
"will," "could," "would," "should," "expect," "intend," "plan,"
"anticipate," "believe," "estimate," "predict," "project," "potential,"
"promise," "continue," "ongoing" and similar expressions are intended to
identify forward-looking statements. Actual results may differ materially
from those expressed or implied by forward-looking statements as a result
of various important factors, including our critical accounting policies
and risks and uncertainties relating to: the results of non-clinical
studies and assessments and clinical trials with respect to TC-2216 or our
other current and future product candidates in development; the conduct of
clinical trials, including the performance of third parties that we engage
to execute the trials and difficulties or delays in the completion of
patient enrollment or data analysis; and the timing and success of
submission, acceptance and approval of regulatory filings. These and other
risks and uncertainties are described in greater detail under the heading
"Risk Factors" in our most recent Quarterly Report on Form 10-Q and in
other filings that we make with the Securities and Exchange Commission. As
a result of the risks and uncertainties, the results or events indicated by
the forward-looking statements may not occur. We caution you not to place
undue reliance on any forward-looking statement.



In addition, any forward-looking statements in this release represent
our views only as of the date of this release and should not be relied upon
as representing our views as of any subsequent date. We anticipate that
subsequent events and developments may cause our views to change. Although
we may elect to update these forward-looking statements publicly at some
point in the future, whether as a result of new information, future events
or otherwise, we specifically disclaim any obligation to do so, except as
required by applicable law. Our forward-looking statements do not reflect
the potential impact of any future acquisitions, mergers, dispositions,
joint ventures or investments we may make.


Targacept, Inc.

targacept

Scientists Identify Elusive Neuronal Targets Of Deep Brain Stimulation

Shooting steady pulses of electricity through slender electrodes into a brain area that controls complex behaviors has proven to be effective against several therapeutically stubborn neurological and neuropsychiatric disorders. Now, a new study has found that this technique, called deep brain stimulation (DBS), targets the same class of neuronal cells that are known to respond to physical exercise and drugs such as Prozac.



The study, led by Associate Professor Grigori Enikolopov, Ph.D., of Cold Spring Harbor Laboratory (CSHL), is the cover story in the January 1st issue of The Journal of Comparative Neurology, which is currently available online.



The targeted neuronal cells, which increase in number in response to DBS, are a type of precursor cell that ultimately matures into adult neurons in the brain's hippocampus, the control center for spatial and long-term memory, emotion, behavior and other functions that go awry in diseases such as Alzheimer's, Parkinson's, epilepsy and depression. DBS has been successful in treating some cases of Parkinson's. And recently, it has also proven to work against other brain disorders such as epilepsy and severe depression.



"But the clinical application of DBS to treat neuropsychiatric disorders is still problematic because there isn't a clear rationale or a guide for which brain regions need to be stimulated to achieve maximum therapeutic benefit," says Enikolopov. "Our study now points to the brain region whose stimulation results in new cell growth in the hippocampus, an area that is implicated in many behavioral and cognitive disorders."



Enikolopov has long been interested in understanding how neuronal and neuroendocrine circuits are involved in mood regulation. "To that end, the question we've been asking is whether different types of stimuli, such as exercise or drugs or DBS, target different types of brain cells and circuits or converge on the same targets," he explains.



"There is a well-established correlation between the use of antidepressants and new neuronal growth in the hippocampus," says Enikolopov. "But what we didn't know was which steps in the cascade of events that eventually leads to the birth of new neurons are actually affected." Brain stem cells eventually differentiate into mature neurons following a cascade of steps, each of which produces a different intermediary cell type or precursor.



To identify the specific cell type affected by DBS, the CSHL team developed mouse models in which different classes of neural cells such as stem and progenitor cells produce different fluorescent colors. This enabled the scientists to visually track these cell populations and quantitatively assess how they change in response to neuronal triggers such as DBS.



To examine the effect of DBS on the hippocampus, Enikolopov teamed up with Andres Lozano, M.D., a leading Canadian neurosurgeon who pioneered its use against depression. The scientists found that stimulating the anterior thalamic nucleus - an area in the mouse brain that is equivalent to a human brain area where DBS is often therapeutically applied - resulted in an increase in cell division among the neural stem and progenitor cells, which in turn manifested as an increase in the number of new adult neurons in the hippocampus.



"By tracking new cell growth in the hippocampus and using it as a sensitive readout, we could potentially pinpoint other brain sites at which therapeutic DBS or other stimuli such as drugs might work best for various neurological and psychiatric conditions," explains Enikolopov.


Notes:


"Neurogenic hippocampal targets of deep brain stimulation" appears in the January 1 issue of the Journal of Comparative Neurology. The full citation is: Juan M. Encinas, Clement Hamani, Andres M. Lozano, and Grigori Enikolopov.

FDA Approves EMSAM(R) (selegiline Transdermal System), The First Transdermal Patch For The Treatment Of Major Depressive Disorder

Bristol-Myers Squibb Company (NYSE: BMY) and Somerset Pharmaceuticals, Inc., a joint venture between Mylan Laboratories Inc. (NYSE: MYL) and Watson Pharmaceuticals, Inc., (NYSE:WPI), announced today that the U.S. Food and Drug Administration (FDA) approved EMSAM(R) (selegiline transdermal system), the first transdermal patch for the treatment of major depressive disorder (MDD) in adults. EMSAM, a transdermal delivery system manufactured by Mylan Technologies, Inc. for Somerset, is a monoamine oxidase inhibitor (MAOI) that has been shown to relieve depressive symptoms in patients with MDD.


"We are pleased to be able to provide this important treatment to people with major depressive disorder," said Peter R. Dolan, chief executive officer, Bristol-Myers Squibb Company. "We believe EMSAM will help physicians treat their patients living with this illness through a new and unique delivery system."


"Together with Bristol-Myers Squibb, we are excited to be able to utilize transdermal technology to administer EMSAM, belonging to the MAOI class of agents that have proven antidepressant efficacy," said Mel Sharoky, M.D., president and chief executive officer, Somerset Pharmaceuticals.


About Monoamine Oxidase Inhibitors (MAOIs)


Although their mechanisms of action are not fully understood, MAOIs, including EMSAM, are presumed to work through potentiation of monoamine neurotransmitter activity in the brain by inhibiting the MAO enzyme. In an in vivo animal model, EMSAM exhibited antidepressant properties only at doses that inhibited both MAO-A and MAO-B in the brain. In the brain, MAO-A and MAO-B play important roles in the breakdown of neurotransmitter amines such as norepinephrine, dopamine and serotonin.


Oral MAOI antidepressants pass through the digestive tract, thus inhibiting intestinal
MAO-A, which is needed to break down tyramine,1 a substance found in certain foods and beverages such as aged cheese and tap beer.2 If a large amount of tyramine is absorbed systemically it can lead to a sudden and large increase in blood pressure called a hypertensive crisis, which is potentially life-threatening and requires immediate medical treatment. While most foods contain negligible amounts or no tyramine, a few food products may contain large amounts of tyramine that represent a potential risk for patients with significant inhibition of intestinal MAO-A resulting from administration of MAO inhibitors. As a result, patients taking oral MAOIs for MDD are required to avoid foods high in tyramine.3


About Transdermal Delivery of EMSAM


Through transdermal delivery, EMSAM is directly and continuously absorbed into the bloodstream over a 24-hour period. As a result, initial exposure of the drug to the digestive tract is minimized. As indicated in animal studies, the EMSAM 6 mg/24 hr patch allows for levels of medicine to inhibit MAO in the brain thought to be necessary for antidepressant effect while sufficiently preserving MAO-A in the digestive tract to break down tyramine. In its entirety, the data for EMSAM 6 mg/24 hr support the recommendation that tyramine dietary modifications are not needed. To reduce the risk of hypertensive crisis, dietary modifications are required with the EMSAM 9 mg/24 hr patch and the 12 mg/24 hr patch.















Clinical Studies


The efficacy of EMSAM in relieving depressive symptoms was established in two double-blind, placebo-controlled studies of six- (N=176) and eight- (N=265) week durations that included adult outpatients ages 18- to 70-years-old with single and recurrent episodes of MDD. The antidepressant action of EMSAM in hospitalized depressed patients has not been studied.


The six-week trial showed that a 6 mg/24 hr dose of EMSAM was significantly more effective than placebo in improving depressive symptoms as determined using the 17-item Hamilton Depression Rating Scale (HAM-D).


In the eight-week dose titration trial, patients with major depressive disorder who received EMSAM or placebo at a starting dose of 6 mg/24 hr, with possible increases to 9 mg/24 hr or 12 mg/24 hr based on clinical response, showed significant improvement compared with placebo on the primary outcome measure, the 28-item HAM-D total score.


The benefit of maintaining patients with MDD on therapy with EMSAM after achieving a responder status for an average of 25 days was demonstrated in controlled clinical trial. Three hundred twenty-two patients with major depressive disorder who had responded to EMSAM
6 mg/24 hr during an initial 10-week open-label treatment phase were randomized either to continuation of EMSAM 6 mg/24 hr (n=159), or to placebo (n=163) under double-blind conditions for observation of relapse. Approximately 52 percent of the EMSAM-treated patients as well as about 52 percent of the placebo-treated patients had discontinued treatment by week 12 of the double-blind phase. Patients continually receiving EMSAM experienced a significantly longer time to relapse.


"Using an innovative antidepressant delivery system, EMSAM provides significant relief of depressive symptoms with demonstrated safety and tolerability," said Alexander Bodkin, M.D., chief of the Clinical Psychopharmacology Research Program at Harvard University-affiliated McLean Hospital. "Major depressive disorder is a serious illness and not all treatments work equally well in all patients. The FDA approval of EMSAM is important because it adds another valuable treatment option to our armamentarium."


In clinical trials with EMSAM, application site reaction was the most commonly reported adverse event (EMSAM, 24 percent; placebo, 12 percent). Most were mild to moderate in severity with only two percent resulting in discontinuation. Overall, the rate of discontinuation due to adverse events was low (EMSAM 7.1 percent; placebo 3.6 percent). Additionally, EMSAM patients reported sexual dysfunction at a rate similar to placebo and experienced minimal weight change (mean weight change from baseline: EMSAM -1.2 lbs.; placebo +0.3 lbs.).


Dosing and Dietary ModificationsThe recommended starting and target dose of EMSAM is one 6 mg/24 hr patch administered once daily without tyramine dietary modifications. EMSAM will also be available in 9 mg/24 hr and 12 mg/24 hr once-daily doses (one patch per day). The trials were not designed to assess if higher doses are more effective than the starting and target dose of 6 mg/24 hr. To reduce the risk of hypertensive crisis, which is potentially life-threatening, foods and beverages high in tyramine must be avoided while on EMSAM 9 mg/24 hr or 12 mg/24 hr, and for two weeks following discontinuation of EMSAM at these doses or reducing the dose to EMSAM 6 mg/24 hr. Patients should be instructed to inform all of their health care professionals that they are using EMSAM, and not to stop or change treatment with EMSAM without consulting their health care professional.


Important Safety Information


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. All pediatric patients being treated with antidepressants for any indication should be observed closely for clinical worsening, suicidality, or unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at time of dose changes, either increases or decreases. Families and caregivers should be advised for the need for close observation and communication with the prescriber. EMSAM is not approved for use in pediatric patients (see Boxed WARNING).


Pooled analyses of short-term (4 to 16 weeks) placebo-controlled trials of nine antidepressant drugs (SSRIs and others) in children and adolescents with major depressive disorder (MDD), obsessive compulsive disorder (OCD), or other psychiatric disorders (a total of 24 trials involving over 4,400 patients) have revealed a greater risk of adverse events representing suicidal thinking and behavior (suicidality) during the first few months of treatment in those receiving antidepressants. The average risk of such events in patients
receiving antidepressants was 4 percent, twice the placebo risk of 2 percent. No suicides occurred in these trials.


To reduce the risk of hypertensive crisis, which is potentially life-threatening, foods and beverages high in tyramine must be avoided while on EMSAM 9 mg/24 hr or 12 mg/24 hr, and for two weeks following discontinuation of EMSAM at these doses or reducing the dose to EMSAM 6 mg/24 hr.


Due to the potential for serotonin syndrome, which is potentially life-threatening, EMSAM should not be used with the following antidepressants: selective serotonin reuptake inhibitors (SSRIs), dual serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), mirtazapine, and bupropion; meperidine and analgesics such as tramadol, methadone, propoxyphene, and pentazocine; the antitussive dextromethorphan; cyclobenzaprine; oral selegiline; and St. John's wort.


After stopping treatment with SSRIs, SNRIs, TCAs, MAOIs, mirtazapine, bupropion; meperidine and analgesics such as: tramadol, methadone, and propoxyphene; dextromethophan; St. John's wort; and buspirone, approximately 1 week (5 weeks for fluoxetine) should elapse before starting therapy with EMSAM. At least 2 weeks should elapse after stopping EMSAM before starting therapy with buspirone or a drug that is contraindicated with EMSAM.


Carbamazepine and oxcarbazepine are contraindicated in patients taking MAO inhibitors, including EMSAM.


The use of EMSAM is contraindicated for use with sympathomimetic amines, including amphetamines as well as cold products and weight-reducing preparations that contain vasoconstrictors (e.g., pseudoephedrine, phenylephrine, phenylpropanolamine, and ephedrine).


Patients taking EMSAM should not undergo elective surgery requiring general anesthesia or be given local anesthesia containing sympathomimetic vasoconstrictors.


EMSAM should not be used in the presence of pheochromocytoma since such tumors secrete pressor substances.


Adults with MDD or co-morbid depression in the setting of other psychiatric illness being treated with antidepressants should be observed 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.


Risk of bipolar disorder should be ruled out prior to initiating antidepressant therapy. EMSAM is not approved for the treatment of bipolar depression.


Due to the potential for elevated blood pressure, the use of EMSAM with buspirone is not recommended.


As with other MAOIs, postural hypotension can occur with EMSAM therapy. Dose increases in the elderly should be made with caution and patients should be observed closely for postural changes in blood pressure throughout treatment.


EMSAM should be used with caution in patients with certain concomitant systemic illnesses that can produce altered metabolism or hemodynamic responses.


As with other psychoactive drugs, EMSAM may have the potential to impair judgment, thinking, or motor skills. Patients should not drive or operate hazardous machinery until they are certain EMSAM does not impair their ability to engage in such activities.


The use of alcohol is not recommended while taking EMSAM.


EMSAM should not be used in combination with tyramine-containing nutritional supplements.


EMSAM should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. Caution should be exercised when administering EMSAM to a nursing mother. EMSAM is contraindicated in patients with known hypersensitivity to selegiline or to any component of the transdermal system.


Treatment-emergent adverse events in short-term clinical trials that occurred at a greater than or equal to 2 percent incidence with EMSAM and for which the incidence was greater than placebo include: application site reaction (24 percent vs 12 percent), headache (18 percent vs 17 percent), insomnia (12 percent vs 7 percent), diarrhea (9 percent vs 7 percent), dry mouth (8 percent vs 6 percent), dyspepsia (4 percent vs 3 percent), rash (4 percent vs 2 percent), pharyngitis (3 percent vs 2 percent), and sinusitis (3 percent vs 1 percent).


Full EMSAM (Selegiline Transdermal System) Prescribing Information, including Boxed WARNING


About Major Depression


According to the DSM-IV diagnosis, major depressive disorder is characterized by one or more major depressive episodes, (i.e., at least two weeks of depressed mood or loss of interest accompanied by at least four additional symptoms of depression)4 and impairs social and occupational or other important areas of functioning.4 Major depression affects approximately 14 million American adults in a given year5 and is the most common mental health disorder after anxiety.6 It is a leading cause of disability and disease burden worldwide.7


The illness is one and a half to three times more common among people with a family history than among the general population,4 and studies indicate that depressive episodes occur twice as frequently in women as in men.4


Today many patients with MDD do not achieve adequate symptom relief.8 If depression is not treated successfully, the chances that it will become recurrent increase.8 More than 80 percent of patients who have one episode of MDD will have at least one subsequent episode.9


Bristol-Myers Squibb and Somerset Pharmaceuticals, Inc.


EMSAM was developed by Somerset Pharmaceuticals, Inc. In December 2004, Bristol-Myers Squibb and Somerset entered into an agreement that provides Bristol-Myers Squibb with exclusive distribution rights to commercialize EMSAM after approval in the U.S. and Canada.


About Bristol-Myers Squibb


Bristol-Myers Squibb is a global pharmaceutical and related health care products company whose mission is to extend and enhance human life.


About Somerset Pharmaceuticals, Inc.


Somerset Pharmaceuticals, Inc. is a joint venture between Mylan Laboratories Inc. (NYSE: MYL) and Watson Pharmaceuticals, Inc. (NYSE: WPI). For more information about Somerset, visit somersetpharm.


References


1 - Youdim, MBH. Therapeutic Applications of Selective and Non-Selective Inhibitors of Monoamine Oxidase A and B that do not Cause Significant Tyramine Potentiation, Neuro Toxicology, 2003: 25. P. 243-250.

2 - Shulman KI, Walker SE. Psychiatric Annals. A Reevaluation of Dietary Restrictions for Irreversible Monoamine Oxidase Inhibitors. Psychiatric Annals, June 2001, 31:6;378-384.

3 - Kennedy SH, McKenna KF, Baker GB. Monamine Oxidase Inhibitors. In: Sadock BJ, Sadock BA. Kaplan & Sadock's Comprehensive Textbook of Psychiatry, 7th Edition. New York, NY: Lippincott, Williams & Wilkins; 2000: 2398-2406.

4 - Diagnostic and Statistical Manual of Mental Disorders. Fourth ed. Washington, DC. American Psychiatric Association; 1994.

5 - Kessler RC, Berglund P, Demler O, et al. The Epidemiology of Major Depressive Disorder: Results from the National Comorbidity Survey Replication (NCS-R). Journal of the American Medical Association (JAMA), 2003; 289(23);3095-3105. P. 3099.

6 - Merck Manual of Medical Information - Second Home Edition. Whitehouse Station, NJ: Merck Research Laboratories; Copyright 1995-2005 Merck & Co.

7 - Ustun TB, et al. Global Burden of Depressive Disorders. British J Psychiatry. 2004; 184. 386-392.

8 Greden, JF. Unmet Need: What Justifies the Search for a New Antidepressant? J Clin Psychiatry, 2002;63 (suppl. 2), 3-6.

9 - Hirschfeld RMA. Clinical Importance of Long-Term Antidepressant Treatment. British J Psychiatry. 2001; 179 (suppl. 42): s4-s8.9.


bms


View drug information on Selegiline tablets.

Study Suggests Salt Might Be 'Nature's Antidepressant'

UI psychologist Kim Johnson and colleagues found in their research that when rats are deficient in sodium chloride, common table salt, they shy away from activities they normally enjoy, like drinking a sugary substance or pressing a bar that stimulates a pleasant sensation in their brains.


"Things that normally would be pleasurable for rats didn't elicit the same degree of relish, which leads us to believe that a salt deficit and the craving associated with it can induce one of the key symptoms associated with depression," Johnson said.


The UI researchers can't say it is full-blown depression because several criteria factor into such a diagnosis, but a loss of pleasure in normally pleasing activities is one of the most important features of psychological depression. And, the idea that salt is a natural mood-elevating substance could help explain why we're so tempted to over-ingest it, even though it's known to contribute to high blood pressure, heart disease and other health problems.


Past research has shown that the worldwide average for salt intake per individual is about 10 grams per day, which is greater than the U.S. Food and Drug Administration recommended intake by about 4 grams, and may exceed what the body actually needs by more than 8 grams.


Johnson, who holds appointments in psychology and integrative physiology in the College of Liberal Arts and Sciences and in pharmacology in the Carver College of Medicine, published a review of these findings in the July issue of the journal Physiology & Behavior with Michael J. Morris and Elisa S. Na, UI graduate students. In addition to reporting their own findings, the authors reviewed others' research on the reasons behind salt appetite.


High levels of salt are contained in everything from pancakes to pasta these days, but once upon a time, it was hard to come by. Salt consumption and its price skyrocketed around 2000 B.C. when it was discovered as a food preservative. Roman soldiers were paid in salt; the word salary is derived from the Latin for salt. Even when mechanical refrigeration lessened the need for salt in the 19th century, consumption continued in excess because people liked the taste and it had become fairly inexpensive. Today, 77 percent of our salt intake comes from processed and restaurant foods, like frozen dinners and fast food.


Evolution might have played an important part in the human hankering for salt. Humans evolved from creatures that lived in salty ocean water. Once on land, the body continued to need sodium and chloride because minerals play key roles in allowing fluids to pass in and out of cells, and in helping nerve cells transfer information throughout the brain and body. But as man evolved in the hot climate of Africa, perspiration robbed the body of sodium. Salt was scarce because our early ancestors ate a veggie-rich diet and lived far from the ocean.


"Most of our biological systems require sodium to function properly, but as a species that didn't have ready access to it, our kidneys evolved to become salt misers," Johnson said.


Behavior also came to play a key role in making sure we have enough salt on board. Animals like us come equipped with a taste system designed to detect salt and a brain that remembers the location of salt sources -- like salt licks in a pasture. A pleasure mechanism in the brain is activated when salt is consumed.


So the body needs salt and knows how to find it and how to conserve it. But today scientists are finding evidence that it's an abused, addictive substance -- almost like a drug.


One sign of addiction is using a substance even when it's known to be harmful. Many people are told to reduce sodium due to health concerns, but they have trouble doing so because they like the taste and find low-sodium foods bland.


Another strong aspect of addiction is the development of intense cravings when drugs are withheld. Experiments by Johnson and colleagues indicate similar changes in brain activity whether rats are exposed to drugs or salt deficiency.


"This suggests that salt need and cravings may be linked to the same brain pathways as those related to drug addiction and abuse," Johnson said.


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No Matter What Stage Of Cancer, Including Remission, Physical Symptoms Prevalent

Twenty-two physical symptoms associated with cancer - symptoms often unrecognized and undertreated - are prevalent in all types of cancers regardless of whether the patient is newly diagnosed, undergoing treatment or is a cancer survivor, according to researchers from the Regenstrief Institute and the Indiana University schools of medicine and nursing.



Common symptoms include fatigue, pain, weakness, appetite loss, dry mouth, constipation, insomnia and nausea. These physical symptoms are associated with substantial functional impairment, disability and diminished quality of life.



The study of 405 patients was reported in the Oct. 11, 2010, issue of the Archives of Internal Medicine. Numerous physical symptoms, rather than just a few, were prevalent in patients with cancer and this prevalence did not diminish after completion of therapy.



"We found that regardless of where they are in the course of their diseases, many individuals with cancer have a high symptom burden," said Kurt Kroenke, M.D., the study's principal investigator and first author. Dr. Kroenke is a Regenstrief Institute investigator and a Chancellor's Professor of Medicine in the IU School of Medicine.



"These symptoms impact them at home and at work throughout their lives," he said.



Study participants, all of whom had pain, depression or both, experienced substantial disability, reporting on average 17 of the past 28 days as either bed days or days in which they had to cut down on activities by at least 50%. Almost all patients reported feeling tired (97.5%) and most (78.8%) were bothered "a lot" by this symptom. Of the 22 symptoms studied, 15 were reported by more than half of the study participants.



In spite of high symptom prevalence, the researchers did not uncover greater use of the health care system. There may be several explanations for this including patients' inclinations to focus on cancer treatment while with their physicians or to accept the symptoms as an inevitable result of the disease or its treatment. Alternatively, the explanation may lie with the fact that those in the study, as cancer patients or former patients, were already frequently interacting with many parts of the health care system.



"Patients and their families should be encouraged to bring up symptoms like pain or insomnia with physicians. But because oncologists are necessarily focused on treatment of the cancer itself, they often have insufficient time to optimally evaluate and manage symptoms and other factors impacting quality of life. We have shown in an earlier study that one effective solution might be a partnership between a telephone-based symptom management team and community-based oncology practices,," said Dr. Kroenke, who is a research scientist with the Center for Implementing Evidence-Based Practice at the Richard Roudebush VA Medical Center and an Indiana University Melvin and Bren Simon Cancer Center member.



The previous study, published earlier in 2010 in the Journal of the American Medical Association, reported that an economical, centralized approach is feasible to conduct and significantly improved symptoms of pain and depression in patients in any phase of cancer. That approach gave patients, many of whom lived in underserved rural areas, one-stop assistance they probably wouldn't have had access to unless they went to a major cancer center, Kroenke said.



Recognizing and managing physical symptoms such as fatigue, pain, nausea, and insomnia may make a significant difference regardless of type or phase of cancer. The researchers plan to investigate medical and behavioral strategies and combinations of both approaches to control these symptoms.



Notes:

In addition to Dr. Kroenke, co-authors of "Somatic Symptoms in Patients with Cancer Experiencing Pain or Depression" are "Xin Zhong, R.N. and Janet Carpenter, Ph.D., R.N., of the IU School of Nursing; Dale Theobald, M.D., Ph.D. of Community Home Health Hospice and Symptom Management Group; Jingwei Wu, M.S., of the IU School of Medicine; and Wanzhu Tu, Ph.D., of the Regenstrief Institute and the IU School of Medicine. The study was supported by a grant from the National Cancer Institute.

Workplace Burden Of Depression Magnified By Co-morbid Fatigue And Anxiety, New Study Shows

Depression, well known to reduce workplace productivity, causes significantly greater productivity declines when accompanied by common co-occurring conditions such as fatigue, sleep problems or anxiety, according to a large new study presented today at the American Psychiatric Association's 160th Annual Meeting in San Diego.[i] The study also showed that co-occurring fatigue or sleep problems significantly increased depression-related healthcare costs.1



In the study, which used an integrated database of healthcare claims and surveys of almost 14,000 employees at two large U.S. firms, researchers analyzed data on healthcare spending and presenteeism (i.e., employees' estimates of their own productivity while at work) to assess the impact of depression and other chronic conditions. 1


Overall, among the ten most prevalent physical and mental conditions measured, depression had the single largest negative effect on work productivity. That effect was magnified when fatigue, sleep problems and anxiety - conditions that often co-occur with depression - were also present. Further, while depression had significant adverse effects on productivity in the absence of other co-morbid conditions, effects of these other conditions in the absence of depression were not as pronounced. 1



"While depression itself has a significant economic impact, the negative effect on both workplace productivity and healthcare costs can be considerably increased when employees who are depressed also suffer from other conditions," said Ronald C. Kessler, Ph.D., Professor of Health Care Policy, Harvard Medical School, Boston, Mass. "These findings suggest we should aim to identify and minimize multiple factors associated with depression early to reduce this burden."



About the Study1



Methodology



Two large U.S. firms surveyed their employees about their productivity. The first sample, from a firm in the high-tech industry, consisted of 7,320 employees; the second, from a manufacturing company, included 6,490 employees. The companies then hired an independent data aggregation company to combine the survey data with medical and pharmacy claims data into a single database. The aggregation firm, in compliance with U.S. privacy laws, stripped out all information that could identify individual patients. This de-identified database was then used to compare and contrast the effects of depression and other conditions that often co-occur with depression, such as anxiety, chronic fatigue, and chronic sleep problems on absenteeism, work productivity and direct healthcare costs. Productivity was measured partly by reviewing absenteeism and partly by asking employees to rate their own "presenteeism"??????" their productivity on days when they were present but not performing at their usual standards ??????" using the WHO Health and Work Performance Questionnaire (HPQ). Each worker's rating was compared with the average productivity score for all employees at the company. Statistical regression analysis was used to assess the effect of the target health problems on absenteeism and productivity while controlling for socio-demographics and claims-based measures of utilization in the six-month pre-survey period. Results were weighted to adjust for differential survey non-response.
















Employee samples were geographically diverse, however study findings are not nationally representative of the U.S. employed population. Employee sample characteristics include:




-- Average age

Employer #1 - 40.3

Employer #2 - 37.0



-- Proportion female

Employer #1 - 23%

Employer #2 - 34%



-- Proportion paid hourly (vs. salaried employees)

Employer #1 - 2%

Employer #2 - 26%



-- Proportion with covered spouse


Employer #1 - 77%

Employer #2 - 63%



-- Number of children (average)

Employer #1 - 1.3

Employer #2 - 1.1%




Additional Results

Among the most prevalent physical and mental conditions, depression had the largest negative effect on overall work performance, followed by fatigue, anxiety, chronic sleeping problems, obesity. Painful conditions also had large effects. However, when the effect of each condition was examined while controlling for comorbid depression, the independent effect of the condition was diminished. This suggests that the other conditions examined in this study have their biggest impact on work performance when they occur with depression.



At one of the companies, depression in the absence of anxiety or fatigue/sleep disturbance was associated with a 3.5 percent reduction in the presenteeism score, equivalent to seven to eight full-time workdays per year. Depression with anxiety or fatigue/sleep disturbance was associated with larger negative effects (6-8 percent reduction in average presenteeism score), and having depression with both anxiety and fatigue/sleep problems was associated with a 13.2 percent reduction.



Employees experiencing depression had average annual costs in excess of both employer sample averages ($4,132 and $3,504 compared to $3,286 and 2,653, respectively). Employees who reported experiencing fatigue or sleep problems with depression had significantly higher average annual costs than those with depression alone ($6,665 and $5,306). (All results noted above statistically significant, p