ThePRI Bulletin

Issue Vol. 22, No. 1Winter/Spring 2011

«You Are So Good and We Are So Grateful!! Page 4

«Depression and Memory Loss

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«

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When Depression Doesn’t Get BetterWhat’s New at PRI

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«Risk Factors for Cognitive AgingPage 5

«Spotlight on a PRI Team MemberPage 6

About two-thirds of people who Same thing with side effects, The challenge is clear. Develop t a k e a n t i d e p r e s s a n t some people get no side effects better treatments, medications medications receive significant to any antidepressants. Most or otherwise. PRI has been benefit. Half of this group is people get a few side effects to doing this for over thirty-five “cured” - completely, well, some of the antidepressants. years, including participating in maybe not for life, but at least And a few cannot tolerate any the development of Prozac, from the current episode of antidepressant medication Zoloft, Paxil, Celexa and many depression. Some of those because of the side effects. o t h e r a n t i d e p r e s s a n t “cured” may be truly “cured for There is no relationship medications and continues to life,” but often this requires between responding (or not) do so. A second strategy is to l i f e t i m e “ m a i n t e n a n c e ” and getting side effects (or not). predict response ~ benefit or antidepressant medication. side effects. Much research is So, the glass is at least one- Worst of all perhaps, we can underway identifying genetic third full. It is also at least one- predict none of the above. predictors, blood test indicators third empty ~ one-third of Medication treatment for and close scrutiny of the first p e o p l e w h o t a k e d e p r e s s i o n i s a l m o s t week or two antidepressant medications completely trial and error. A receive no benefit at all. history of a good or bad

antidepressant medication These statistics hold true for all experience, or that of a close antidepressant medications. blood relative, may be a helpful There is more var iat ion step toward a rational choice of between people than between medication. Testimonials of medications. Some people celebrities or TV drug ads are respond to all medications. not helpful. Trials of second, Most respond to some and not third, or fourth antidepressant others. A few people respond to medications may be extremely none of the twenty-some helpful.marketed antidepressants.

responses to treatment, to better predict a favorable or unfavorable ultimate response and at least abort apparently unhelpful treatments.

Plus, if medications are not helpful, there are endless alternative treatments; at last count over 400 schools of behavioral therapy, including

Antidepressant Medications: How Good Are They?

by: Jon F. Heiser, M.D.

diet, exercise, meditation, counseling depression, vagal nerve stimulation than they are alike. Many alternatives and many others. Electroconvulsive and deep direct brain stimulation - two to treatment failures exist. And even therapy, despite much unwarranted different brain “pacemakers” to more help is on the way, including phobic avoidance by the general eliminate depression. medications currently under study public, remains the “gold standard” for here at PRI, that are more different treatment of serious depression. In summary, available antidepressant than they are alike!Additionally, now we have, for very medications are more alike than serious and treatment-resistant different; yet people are more different

People with depression where people suffer from Research also indicates often complain of memory continuous and painful t h a t m e m o r y i s problems and wonder if n e g a t i v e t h i n k i n g , consolidated when the they are prematurely forgetting why you’re in that mind and brain seem to be developing old age-related room is the rule rather than doing noth ing much. memory problems even in the exception. Consolidation refers to the their 20’s or 30’s. We can process of making short-look at this experience in a We can also now look at term memories into longer-couple of ways. One depress ion f rom the term memories so that we vantage point is the vantage point of the brain, remember what happened psychological: our own especially with the vast yesterday or six months internal subjective mental re f inements in bra in ago, etc. The mind can be experience and those imaging technology. There at relative rest when described to us by people is an area of the brain peacefully gardening or w h o a r e p r o f o u n d l y cent ra l ly invo lved in a c t u a l l y p r a c t i c i n g depressed. We all have memory function called the meditation, but also just the occasional experience hippocampus. This area is walking from one room to of walking into a room and severely damaged in another or sitting waiting forgetting why we’ve come. Alzheimer’s disease. We for the bus or for a kid to get This is more likely to now have scans that are out of class. This resting happen when we are s h a r p e n o u g h t o activity seems to be when distracted, e.g. normally demonstrate that part of the psychological and brain worried about all the things the hippocampus actually physical processes of we have to do in a limited shrinks in volume during consolidation do their best time. Our distraction just depression. The good work. The problem for makes our tasks harder news is that this damage most people with major b e c a u s e n o w w e ’ r e and shrinkage is reversible depression is that their standing in a room waiting with treatment, either minds are never at rest.to remember why we’re m e d i c a t i o n o r here. People who suffer psychotherapy. We think from major depression are this shrinkage in the very highly distracted. They h ippocampus occu rs often complain that there is because i t is h ighly a constant negative chatter sensitive to circulating going on inside that stress hormones and these intrudes into every spare hormones are usually quite moment and often feels like elevated in depression. a relentless treadmill. Depressed people often Let’s finish off by returning say they can’t shut their to the vantage point of the minds off. In depression, m i n d o n c e a g a i n .

Depression and Memory Loss

by: Don F. De Francisco, M.D., Ph.D.

Continued from page 1Antidepressant Medications:

How Good Are They?

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When Depression Doesn’t Get Better: What Can BeDone About Treatment-Resistant Depression

by: Daniel E. Grosz, M.D.

Is your treatment for depression working? Switching medications: In nearly one in You still don’t feel as well as you used to? If three people, the first antidepressant tried you’ve been treated for depression but your doesn’t work at all. You may need to try symptoms haven’t fully improved, you may several antidepressants before you find have treatment-resistant depression. one that works.Medications and psychotherapy work for most people. But with treatment-resistant Tr y i n g a m e d i c a t i o n l o n g e r : depression, standard treatments don’t help Antidepressants typically take four to eight much or don’t help at all. Months or even weeks to become fully effective and for side years can go by without any or with limited effects to ease up. For some people it relief. might take even longer, so it helps to be

patient.But if your depression treatment isn’t working, don’t give up. Many people can Increas ing your dose: Of ten get their treatment-resistant depression people respond to medications differently. under control. You and your doctor just You might benefit from a higher dose than need to find the right approach. Here are is usually prescribed. Discuss with your some things to consider: doctor if this is an option for you. Don’t

increase your dose on your own.Confirm the diagnosis: Some people who apparently have treatment-resistant Combinat ion: In th is approach, depression might be mis-diagnosed. The different classes of antidepressants are most common mis-diagnosis is bipolar prescribed at the same time. The goal is to d iso rder (a lso known as man ic target several kinds of brain chemicals at depression), especially when the manic once.phases are mild. This condition requires a different treatment and might even get Augmentation: Augmentation means worse when using antidepressants alone. taking an antidepressant along with a Often depression coexists with other medication generally used for another conditions such as panic disorder, post mental health condition.traumatic stress disorder or attention deficit hyperactivity disorder. The presence of Talk therapy: For some people with additional diagnoses makes depression depression, psychotherapy works as well more difficult to treat. In these cases a as medications. The combination of consultation with a psychiatrist might be medication and psychotherapy is generally necessary. the most effective approach.

Are you taking your medications Additional treatment options: If correctly? Up to half of all people who get standard treatment with medications and prescribed antidepressants don’t take them psychotherapy haven’t been effective for as recommended, either missing doses or your treatment-resistant depression, you not taking them due to side effects. Some may wish to consult with a psychiatrist who give up too soon - it can take up to 12 weeks specializes in one or some of these for a medicine to take effect. additional treatment options: Transcranial

M a g n e t i c S t i m u l a t i o n ( T M S ) , Rule out other health problems: Other Electroconvulsive Therapy (ECT) or vagus medical conditions ranging from thyroid nerve stimulation.problems to anemia to substance abuse can sometimes mimic or worsen So if your depression treatment isn’t depression. working, don’t give up. You can get your

treatment-resistant depression under Strategies for treating Treatment- control. Work with your doctor until you find Resistant Depression: Even if the initial the right approach.trials of antidepressants didn’t work, there

Reference: WebMD.com, mayoclinics.comare other options for you and your doctor to consider:

Eye on ItWhat’s New at

PRI

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Thank You!

Thank You!

Merci!

Merci!

Merci!

Merci!

Danke!

Danke!Gracias!

Gracias!

Grazie!

Grazie!

Mahalo!

Mahalo!

You Are So Good and We Are So Grateful!!

by: Charles S. Wilcox, Ph.D.

Yes! You, our many readers of The PRI in research programs from well over 25 Bulletin, really overwhelmed us with the years ago, here at PRI! It was comments, compliments, stories-of- especially rewarding and inspirational success and suggestions for future for us to read the various vignettes, newsletters that you submitted to us where so many o f you even near the end of 2010 ~ Thank you! remembered the specific PRI research

nurse(s) and physician(s) with whom Whether you are a current or former you interacted...and in numerous s tudy par t i c ipan t , a re fe r r ing instances even the name of the physician/health care provider, or the research medication that was the focus caregiver of a current or former study of the study.participant, we were truly amazed by the literally hundreds (and hundreds!) of It seems that whether you are a former you who took the time to write and share study participant, the relative of a former with us how PRI has improved your study participant, or the primary care quality of life! We also appreciated doctor who may have referred one or h e a r i n g y o u r r e q u e s t s a n d more of your patients to PRI, you have recommendations for the content of seen how beneficial these research future newsletters, including this first programs have proven to be for people PRI Bulletin of 2011! While it may not be suffering from Anxiety, Alzheimer’s possible for us to incorporate all of your Disease, Attention Deficit/Hyperactivity ideas into future newsletters, beginning Disorder, Depression, Migraine with this edition, we are including Headaches, Mild Cognitive Impairment, articles based on the number of specific Nicotine Addiction, Obesity, Treatment- requests we received from you ~ our Resistant Depression and numerous readers! other medical conditions, over our 36

years of conducting leading edge In this newest PRI Bulletin, the articles research!by Jon F. Heiser, M.D., Don F. De Francisco, M.D., Ph.D., Daniel E. We were truly touched by your PRI Grosz, M.D., and Nader Oskooilar, study-related stories... Moreover, as we M.D., Ph.D. are in direct response to read about so many di fferent your most frequent requests. “successes,” both during one’s study

participation and/or vis-a-vis PRI’s After All of us here at PRI also want to convey Care Programs, we were reminded that our most sincere “Thank you” to each because of people like you, literally and every one of you for the PRI millions of people all over the world Research Study Success Stories that have also had their quality of life you have most recently shared with us. improved as well! Yes, you are good We heard from people who participated and we are grateful!!

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Risk Factors for Cognitive Aging

by: Nader Oskooilar, M.D., Ph.D.

Eye on ItWhat’s New at

PRI

M i l d C o g n i t i v e Impairment (MCI)

What is normal forgetfulness versus “MCI”? MCI is a cond i t i on o r s t age o f forgetfulness where a person has mild problems with memory, language (perhaps “word finding”), or another mental function that is just beginning to be noticeable and detectable when carefully evaluated/tested, yet not s e r i o u s e n o u g h t o significantly interfere with one’s quality of daily life. The potential short- and long-term benefits of detecting MCI early cannot be over-stated! Although enroll ing very quickly, as of this printing we have an ongoing MCI study at all three locations. For your confidential no-cost MCI assessment, please call the PRI office nearest to you, today!

M i l d - t o - M o d e r a t e Alzheimer’s Disease (AD)

P R I ’ s i n t e r n a t i o n a l l y recognized expertise in the evaluation of anti-Alzheimer’s medications positions us to work with some of the newest and most novel treatments available, including vaccines as well as more traditional t y p e s o f m e d i c a t i o n s . Sometimes categorized as the next Global Epidemic – with estimates as high as 100 million sufferers worldwide by 2050 – enrolling in an anti-A l z h e i m e r ’ s r e s e a r c h program may help you, your loved ones and millions of other people as well.

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Many factors can lead to or accelerate increase the risk of late-life cognitive cognitive aging and memory loss in dysfunction. These factors include obesity, humans. Familiar causes are brain injury insulin resistance, and the metabolic (e.g. accidents) and brain disease (e.g. syndrome.stroke, dementia). Some of the other

Overweight and obese individuals may crucial contributing sources of cognitive

heighten their risk of dementia, including aging are briefly reviewed in this article.

Alzheimer’s disease. Obesity is moreover Under acute physical or emotional stress, associated with cerebral vascular damage our body activates a large number of that may then contribute to cognitive biological mechanisms that seek to decline and vascular dementia. Excessive diminish the impact of the stressors and weight also increases the odds for chronic restore balance; among them, are low-grade inflammation, diabetes, insulin compounds such as adrenaline and cortisol resistance, and metabolic syndrome that from the adrenal gland and cytokines from can all increase the chances of cognitive the cells of the immune system. In chronic impairment.stress, the body is not able to shut off these

Insulin resistance (the body cannot use mediators of stress when they are no longer

insulin efficiently) appears to be a risk for needed; they may then tax a person’s

cognitive decline and dementia. This physiological and psychological resources

condition is seen more in obese individuals. and harm the brain and its functions.

It also frequently accompanies chronic Poor lifestyle habits may also overstress the elevations of inflammatory markers, body and contr ibute to cognit ive compromising cognitive functions.deterioration. Examples are overeating,

Metabolic syndrome is a combination of unhealthy food choices, excessive alcohol

excessive fat in and around the abdomen use, smoking tobacco, sedentary life, poor

(especially in men), blood cholesterol sleep and deficient anger management

disorders, high blood pressure, insulin skills.

resistance, and pro-inflammatory states. The third factor is chronic low-grade Conditions associated with this syndrome inflammation. The human body’s short- include sedentary life, obesity, aging, term response to acute injury - due to any hormonal imbalance and genet ic cause - is to have local or circulating cells predisposition. People with the metabolic secrete chemicals called inflammatory syndrome are at increased risk of coronary mediators (cytokines), and the liver to heart disease, stroke, type 2 diabetes, produce acute-phase reactants (e.g. C- cognitive impairment and dementia.reactive protein); the goal of both sets of

Finally, depression and anxiety seem to chemicals is to restore physiological

have contributory roles in the etiology of balance. The plasma concentrations of

cognitive deterioration and dementia. these chemicals (collectively called

Depression also worsens outcomes for inflammatory markers), however, might

cardiac disease, obesity, diabetes mellitus, increase with aging and stay high, which

and attendant metabolic problems. Anxiety results in chronic low-grade inflammation.

puts the body in a state of alarm (fight or In turn, this might lead to chronic aging-

flight) which, when chronic, may often be related disorders, such as cardiovascular

harmful to the body and to the brain.d isease, a r th r i t i s , and cogn i t i ve deterioration. Weight loss and regular In summary, many factors pose significant physical activity may often lower the levels threats to cognitive aging. Regular physical of the inflammatory markers. activity, periodic physical checkups, healthy

diet , s t ress management, weight Additionally, there is a link between type 2

reduction/control, and prevention or diabetes and cognitive decline and

treatment of psychiatric disorders can dementia. Clinical factors which

prevent or decrease the risks of cognitive predispose individuals to diabetes may,

decline.even in the absence of diabetes, also

THE PRI BULLETIN

Pharmacology Research InstitutePO Box 1645Los Alamitos, CA 90720

The PRI Bulletin is an official publicationof Pharmacology Research Institute

and is intended for patients and friendsof the Institute. PRI does not rent, sell or trade its mailing list with any other

organization or company. Your personalinformation is kept completely confidential.

Inquiries and changes of address may bedirected to any of the sites below.

Medical DirectorsJon F. Heiser, M.D.

Daniel E. Grosz, M.D.Nader Oskooilar, M.D., Ph.D.

Associate Medical DirectorsDon F. De Francisco, M.D., Ph.D.

Clifford Feldman, M.D., J.D.

Executive DirectorCharles S. Wilcox, Ph.D.

PRI Bulletin EditorsRachel GotiongJanet L. Minter

Site Coordinators/Office LocationsMellissa Henry, R.N., M.S.N., N.P.

4281 Katella Ave., Suite 115Los Alamitos, CA 90720

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Check out our newly updated website at:www.priresearch.com

PRI is pleased to introduce our newsletter Before joining the PRI Team, Michelle readers to a key member of our research worked at UCLA as Nurse Practitioner in team, Michelle Panlilio, R.N., M.S.N., Internal Medicine. She also has N.P., who works in our Encino office. extensive experience with medical Michelle has been a resident of Los aesthetics and cardiology.Angeles since age 11. She has spent most of her life in the San Fernando Michelle loves her work at PRI as a Valley, graduating from Kennedy High Research Nurse Practitioner and she is School. clearly passionate about helping people!

Her outlook on life is consistently positive She did not go too far to attend college at and you can always count on a big smile Mount St. Mary’s, Los Angeles, where from Michelle! Outside of the workplace, she earned a Bachelor’s Degree in the Michelle enjoys spending time with her Science of Nursing. She then decided to husband Paolo and daughter Isabella. further pursue her education and She is an avid runner and enjoys attended UCLA, where she earned her “researching” different ethnic foods.Master’s Degree in the Science of Nursing, specializing in the area of We are very fortunate to have Michelle as Geriatrics. While attending UCLA, such an important member of the PRI Michelle completed her internship at Team!Kaiser Permanente Long Term Care Facility in Downey, the Veteran’s Association Internal Medicine in West Los Angeles, and Cedar Sinai Medical Center Cardiology Clinic in Los Angeles.

This Issue’s FeaturedTeam Member

Michelle Panlilio, R.N., M.S.N., N.P.

by: Christine Ziegwied

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PRSRT STDUS POSTAGE

PAIDLOS ALAMITOS,

CAPERMIT NO. 16

The PRI Bulletin Issue Vol. 22 No. 1 Winter/Spring 2011