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Wed 22 Jul 2009

EXCITING PARASOMNIA DEVELOPMENTS TO SHARE WITH VISITORS TO MY WEBSITE:

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I am very happy to share some news with those people who are interested in the latest developments with the Parasomnias. First, I will start off with an email I received yesterday from the President of the prestigious, longstanding, "granddaddy" scientific organization that uses the acronym CINP that stands for (in Latin, that venerable and old, and perhaps not completely alive language that I studied for 3 years at my Jesuit high school, Loyola, in my home town of New York City) Collegium Internationale Neuro-Psychopharmacologicum. In other words, the CINP is an international scientific organization (with Nobel Prize winners) devoted to the latest findings in the pharmacology of neurological and psychiatric disorders--and the "new kid on the block", which is sleep disorders. I am fortunate to have been invited two years ago to lecture at the previous CINP congress (that meets biannually) in Munich, Germany, on the topic of REM sleep behavior disorder (RBD--our sleep center's first discovery in 1982, with the first patient being my second patient in my fledgling career as a sleep doctor--as described first-hand in my book Paradox Lost featured in this website) and its association with Parkinson's disease and related disorders, and also the association of RBD with most antidepressant medications that can trigger or exacerbate RBD. The notable exception is Wellbutrin (bupropion is the generic name) which is a dopamine-enhancing antidepressant medication that has not been reported to cause or aggravate RBD--which is scientifically fascinating since RBD has a strong link with Parkinsonism that is a dopamine-deficient disorder! On a practical clinical level, Wellbutrin should be considered to be the treatment of choice for a RBD patient who has depression, since it should not aggravate RBD, in contrast to the SSRIs and most other antidepressants. [Important interjection: I have absolutely no conflict of interest in regards to never being a spokesman for the maker of Wellbutrin, nor any other pharmaceutical company. Therefore, all my comments about medications are based on an unbiased clinical and scientific foundation, without any financial interest on my part.]. At any rate, here is the email regarding the acceptance of a symposium proposal that I submitted as Co-Chairman (with Prof. YK Wing, M.D. of the Chinese University in Hong Kong) and as a speaker in that symposium:

July 21, 2009

Dear Professor Schenck,

It is my pleasure to inform you that the symposium:

"Sedative-hypnotic medication induced complex sleep behaviors: clinical and epidemiologic data, risk predictors, and underlying mechanisms"

including your lecture has been chosen by the International Scientific Program Committee as a central symposia at CINP Hong Kong 2010. Over 160 abstracts were submitted and only 35 were chosen, an indication of the high regard that the scientific program committee had for your work. Each of the four lecturers will speak for 30 minutes and we hope you will give an introduction to your specific research topic as well as a report of your breaking research. This will maximize the usefulness of the symposia for larger number of psychopharmacology researchers.

We hope you will remain in Hong Kong for the full four days of the CINP congress to maximize interaction between scientists in the spirit of the CINP. Moreover, those of you who would like to volunteer to give an additional general lecture in the educational track of CINP Hong Kong or to participate in our unique "Have dinner with a leading world scientist" program are invited to write directly to me (belmaker@bgu.ac.il).

With best wishes.

RH Belmaker, MD

Chairman, International Scientific Program Committee

President, CINP

The lectures titles for that symposium are:

1. Current Understanding of Complex Sleep Behaviors (CSBs) – clinical scenarios and significance (with video demonstration) (Carlos H. Schenck, M.D. USA)

2. Epidemiology of CSBs in the psychiatric clinic – prevalence, risk factors and outcomes (YK Wing, M.D., Hong Kong)

3. Risk Factors For CSBs in the psychiatric clinic – Taiwan perspective (Tzung-Jeng Hwang, M.D., Taiwan)

4. From Zzzz to CSBs – the molecular mechanism for specificity (David Nutt, M.D., United Kingdom)

Symposium Submission Abstract (written by Carlos H. Schenck, MD):

Sedative-Hypnotic Medication Induced Sleep-Related Eating and Other Complex Sleep Behaviors: Clinical and Epidemiologic Data, Risk Predictors, and Underlying Mechanisms

On March 14, 2007 the United States Food and Drug Administration (FDA) issued a press release requesting that all manufacturers of sedative-hypnotic drugs change their product labeling to include stronger language on potential risks, including complex sleep-related behaviors (CSBs) such as sleepwalking (SW), sleep-related eating disorder (SRED), and sleep-driving. This FDA ruling reflected a growing medical literature, and public safety awareness concerning the hazards of CSBs associated with the pharmacotherapy of insomnia. Zolpidem in particular has been implicated for being the most likely agent for inducing CSBs. Thus, it is both timely and of considerable clinical, epidemiologic, and basic science importance to organize a symposium at the CINP 2010 congress to address these issues. The 4 speakers are all actively engaged in this area of research, 3 in the clinical domain and 1 in the basic research domain.

CSBs are officially classified as “Parasomnias” in the International Classification of Sleep Disorders (ICSD), 2nd Edition (2005, American Academy of Sleep Medicine), defined as “undesirable physical or experiential events that accompany sleep, occurring during entry into sleep, within sleep, or during arousals from sleep. Parasomnias encompass abnormal sleep-related movements, behaviors, emotions, perceptions, dreaming, and autonomic nervous system functioning…‘basic drive states’ can emerge in pathological forms with the parasomnias, as seen with sleep aggression, sleep-related eating disorder, and abnormal sleep-related sexual behaviors.” SRED was formally identified and named in 1991 by Schenck et al. (Sleep 1991;14:419-31), and is listed in the ICSD-2 as a parasomnia. SRED can result from SW, restless legs syndrome, sleep apnea, and pharmacotherapy—in particular zolpidem. SRED is often a chronic, nightly condition that features excessive, peculiar, and often bizarre and dangerous eating while the individual is partially/completely asleep, with subsequent partial or complete amnesia. The emerging literature on zolpidem-SRED includes: Harazin J & Berigan TR, 1999 (Military Med 164;669-70); Morgenthaler TI & Silber MH, 2002 (Sleep Med;3:323-7); Schenck CH, et al. 2005 (Sleep;28:A259); Najjar M, 2007 (J Clin Sleep Med;3:637-8); Lam SP, et al. 2008 (J Clin Psychiatry69;1374-82); Chiang A & Krystal A, 2008 (J Clin Sleep Med;4:155-6); Sansone RA & Sansone LA, 2008 (Gen Hosp Psychiatry;30:90-1). Other forms of CSBs associated with zolpidem have been published, and SRED/other CSBs have been reported across a spectrum of sedative-hypnotics, as reflected in the FDA ruling.

The symposium is proposed as follows:

Chairs: Dr. Carlos H. Schenck (USA), Dr. YK Wing (Hong Kong)

In this symposium, Schenck will summarize current understanding of CSBs (in particular SRED), show sleep laboratory video examples of sleep-eating, and present current data on zolpidem-induced SRED in >40 patients presenting to both sleep and psychiatry clinics affiliated with the University of Minnesota. The current series both expands on and confirms findings from the previously reported series of 19 cases (Schenck et al. 2005, cited above) in which female gender, 10-20 mg dose range, and complex pharmacotherapies were the most prominent risk factors. Most of the patients served as their own “controls” in that various other sedative-hypnotics had rarely induced CSBs. Thus, for this group, zolpidem conferred a selective vulnerability for CSBs.

Wing, the second speaker, will discuss findings from his group’s clinical and epidemiologic study of parasomnias among psychiatric outpatients at the Shatin Hospital, The Chinese University of Hong Kong, which were published in 2008 (Lam SP, et al., cited above). The estimated prevalence of lifetime diagnoses of sleepwalking, SRED, sleep-related injury and sleep violence were 8.5%, 4.0%, 21.0%, and 3.6% respectively. The 1-year prevalence of these conditions were 2.9%, 2.4%, 8.8%, and 2.5% respectively. Furthermore, the combination of zolpidem (but not zopiclone) and antidepressant use conferred preferential vulnerability for SRED. In addition, the speaker will also report the outcome of a subset of patients who had undergone certain interventions, including cessation of zolpidem therapy.

Hwang, the third speaker, will present findings from a recently completed psychiatric outpatient clinic study (currently under journal peer-review) entitled, “Risk Predictors for Hypnosedative-Related Complex Sleep Behaviors: A Pilot Study.” Patients were enrolled during a 3 month period and CSBs were defined as somnambulism with object manipulation, sleep-related eating and other amnestic sleep-related behaviors. Demographic and clinical variables were compared in those with CSBs and those without. Stepwise backward and forward logistic regression analyses were performed in order to identify significant risk predictors for CSBs. Results: of the 125 subjects, 19 (15.2%) reported CSBs, all of whom took zolpidem. Among a total of 67 subjects taking zolpidem, those with CSBs were significantly more likely to be younger (p=0.023), female (p=0.011), to take a higher dose of zolpidem (>10 mg/day) (p<0.001), and to not go to sleep immediately after taking zolpidem (p=0.047). Stepwise backward and forward logistic regression analyses showed that a higher dose of zolpidem (>10 mg/day) was the most significant predictor of CSBs (OR=12–15, 95% C.I. 2.7–59.5)

Nutt, the fourth speaker, will discuss the clinical and preclinical differences among the “z drugs” (zolpidem, zopiclone, eszopiclone, zaleplon), including the presentation of new data demonstrating how zolpidem differs from other benzodiazepine receptor agonists and benzodiazepines (e.g. alprazolam), and discuss proposed mechanisms underlying the preferential vulnerability for zolpidem inducing CSBs.

A general discussion will follow, pointing to future clinical and basic science research directions.

Please keep in mind that the CSBs to be discussed in this symposium often relate to Sleep Related Eating Disorder (SRED) induced by hypnotic medication. In other words, the treatment of one sleep disorder--Insomnia--can induce the new-onset of another sleep disorder--a Parasomnia such as SRED. Our sleep center identified and named SRED back in 1991 and we have published extensively on this parasomnia, and its link with hypnotic medication, particularly Zolpidem (Ambien)--and again, no Conflict of Interest on my part (I don't work for the competitors of Ambien, and I often prescribe Ambien for my insomniac patients, with careful discussion about side effects and with careful follow-up of my patients).

My book Paradox Lost has ample stories provided by my SRED patients, including some with Ambien-induced SRED (two of my patients were featured in a People magazine story on this topic). These SRED stories and all the Parasomnia stories are timeless--even though Paradox Lost was published in December 2005, the stories and the clinical and scientific content are still fresh and current, and will remain so "for time immemorial" since they reflect the "human condition" at night during sleep as the human condition has always been experienced during the nighttime hours. Therefore, don't be mislead by the time gap between the publication of my book and the current date, since the stories are still fresh and real, and the clinical approach on my part remains unchanged. I am forever grateful and honored that my patients have agreed to share their intimate Parasomnia stories with the general public in my book as a public service. They are my heroes, and I hope that you the readers will find that the text and photos reflect this special sentiment, along with all the fascinating and important information imparted.

Of course, in a year I will report back in my website Newsletter about the CINP Hong Kong symposium, and offer insights and perspectives to my readers. I will be participating in a number of other high-profile educational events related to the Parasomnias and other sleep disorders, which I shall share with you as well, along with my most recent peer-reviewed medical publications. (Sneak preview: we are up to 85% conversion rate to parkinsonism in our original series of male RBD patients aged >50 years, with the average lag between onset of RBD to onset of parkinsonism being 14 years. I am working on that manuscript currently, so stay tuned...).

Finally, here is a listing of my most recent national and international media appearances in regards to the Parasomnias. It is important to keep spreading the word, since as I have mentioned many times, the Parasomnias are far more common than most people--including doctors--realize, and yet they can be readily diagnosed and effectively treated:

ABC-TV News NIGHTLINE: “Science of Sleep: Parasomnias,” November 27, 2007.

Cosmopolitan magazine: “5 Fascinating Facts About Sleep and Sex,” page 110, January 2008.

“Temple of Health” Radio Show, Atlanta, Georgia (1620 AM): “Sleep,” January 26, 2008.

“China Times” newspaper, Taiwan (Republic of China): “REM Sleep Behavior Disorder,” February 20, 2008.

“Oprah & Friends Radio” Show, hosted by Dr. Mehmet Oz (XM Radio): “All About Sleep,” February 28, 2008, and March 21, 2008.

“Oprah Winfrey Show”: “Parasomnias: Sleep-Eating and Night Terrors,” April 1, 2008 and December 23, 2008.

“To Cut Risks of Sleeping Pills, Hide Car Keys, Unplug Phone,” Wall Street Journal, May 6, 2008, page D1.

“Lesser-Known Sleep Disorders: Parasomnias, Sleepwalking, Teeth Grinding, and More.” www.health.com ,

May 2008.

“Sleep: What’s Your Problem? Frequently Asked Questions: Advise From Carlos H. Schenck, MD, On Sleep

Problems, Strange Behaviors, and When To See a Doctor.” www.health.com , July 2008.

“Sleep Disorders,” "Vibrant Living" on Webtalkradio.net, July 29, 2008.

“Fear of Sleep,” National Public Radio (NPR) program “This American Life,” hosted by Ira Glass, August 9, 2008

“Sleep-Eating,” ABC-TV “Primetime” (Medical Mysteries), August 19, 2008.

“Bizarre Sleep Disorders,” Popular Science magazine (on-line publication, September 2008).

Review of the book “Sleep: The Mysteries, The Problems, and The Solutions”. Heal-India, December 2008,

volume 2, number 12, page 68.

“Is The Terrorist A Pathological Psycho?” (“Mumbai Terror: The Psychological Impact of Terrorism Coverage:

Creating a Prozac Nation?”). Heal-India, January 2009, volume 3, number 1, page 40.

“Deadly Dreams,” NBC-TV “Dateline”, March 13, 2009.

“Dangerous Sleep,” Wprost 24 magazine, Poland, March 26, 2009.

“Sexsomnia,” Cosmopolitan Magazine (“The Cosmo Post”), page 142, March 2009.

“Sleep Related Eating Disorder,” (“Health Essentials”), New York Times on-line, April 2009.

“Night Terrors and Other Parasomnias,” KABC-TV Eyewitness News, Los Angeles, California, April 20, 2009.

“REM Sleep Behavior Disorder,” KCBS/KCAL-TV, Los Angeles, California, April 30, 2009.

“How Sleep Sex (and Other Parasomnias) Can Get You in Trouble with the Law,” by Lindsay Lyon, US News &

World Report (http:health.usnews.com/articles/health/sleep/2009/05/08), May 12, 2009.

“When Sleep Problems Become Legal Problems, Neuroscience Can Help: Sleepwalking, Sleep Driving, and

Other ‘Parasomnias’ Can Get You Entangled With The Law”, by Lindsay Lyon, US News &

World Report (http:health.usnews.com/articles/health/sleep/2009/05/08)), May 12, 2009.

“Sleep”radio interview on Co-op Radio, CFRO 102.7 FM, “Dynamic Health” program, Vancouver, British

Columbia, Canada, May 20, 2009.

“REM Sleep Behavior Disorder,” Sleep Medicine (popular magazine), Italian Association of Sleep Medicine,

Italy, Spring 2009.

“Sleep Talking,” Men’s Health magazine, June 2009.

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