Issue Vol. 22, No. 1 Winter/Spring 2011
The PRI Bulletin Antidepressant Medications: How Good Are They? « Depression and
Memory Loss Page 2
« When Depression
Doesn’t Get Better « What’s New at PRI
« You Are So Good
and We Are So Grateful!! Page 4
« Risk Factors for
Cognitive Aging Page 5
« Spotlight on a PRI
Team Member Page 6
About two-thirds of people who take antidepressant medications receive significant benefit. Half of this group is “cured” - completely, well, maybe not for life, but at least from the current episode of depression. Some of those “cured” may be truly “cured for life,” but often this requires lifetime “maintenance” antidepressant medication. So, the glass is at least onethird full. It is also at least onethird empty ~ one-third of p e o p l e w h o t a k e antidepressant medications receive no benefit at all. These statistics hold true for all antidepressant medications. There is more variation between people than between medications. Some people respond to all medications. Most respond to some and not others. A few people respond to none of the twenty-some marketed antidepressants.
by: Jon F. Heiser, M.D. Same thing with side effects, The challenge is clear. Develop some people get no side effects better treatments, medications to any antidepressants. Most or otherwise. PRI has been people get a few side effects to doing this for over thirty-five some of the antidepressants. years, including participating in And a few cannot tolerate any the development of Prozac, antidepressant medication Zoloft, Paxil, Celexa and many because of the side effects. o t h e r a n t i d e p r e s s a n t There is no relationship medications and continues to between responding (or not) do so. A second strategy is to and getting side effects (or not). predict response ~ benefit or side effects. Much research is Worst of all perhaps, we can underway identifying genetic predict none of the above. predictors, blood test indicators Medication treatment for and close scrutiny of the first d e p r e s s i o n i s a l m o s t week or two responses to completely trial and error. A treatment, to better predict a history of a good or bad favorable or unfavorable antidepressant medication ultimate response and at least experience, or that of a close abort apparently unhelpful blood relative, may be a helpful treatments. step toward a rational choice of medication. Testimonials of Plus, if medications are not celebrities or TV drug ads are helpful, there are endless not helpful. Trials of second, alternative treatments; at last third, or fourth antidepressant count over 400 schools of medications may be extremely behavioral therapy, including helpful.
Depression and Memory Loss by: Don F. De Francisco, M.D., Ph.D.
People with depression often complain of memory problems and wonder if they are prematurely developing old age-related memory problems even in their 20’s or 30’s. We can look at this experience in a couple of ways. One vantage point is the psychological: our own internal subjective mental experience and those described to us by people who are profoundly depressed. We all have the occasional experience of walking into a room and forgetting why we’ve come. This is more likely to happen when we are distracted, e.g. normally worried about all the things we have to do in a limited time. Our distraction just makes our tasks harder because now we’re standing in a room waiting to remember why we’re here. People who suffer from major depression are very highly distracted. They often complain that there is a constant negative chatter going on inside that intrudes into every spare moment and often feels like a relentless treadmill. Depressed people often say they can’t shut their minds off. In depression,
where people suffer from continuous and painful negative thinking, forgetting why you’re in that room is the rule rather than the exception. We can also now look at depression from the vantage point of the brain, especially with the vast refinements in brain imaging technology. There is an area of the brain centrally involved in memory function called the hippocampus. This area is severely damaged in Alzheimer’s disease. We now have scans that are sharp enough to demonstrate that part of the hippocampus actually shrinks in volume during depression. The good news is that this damage and shrinkage is reversible with treatment, either m e d i c a t i o n o r psychotherapy. We think this shrinkage in the hippocampus occurs because it is highly sensitive to circulating stress hormones and these hormones are usually quite elevated in depression.
Research also indicates that memory is consolidated when the mind and brain seem to be doing nothing much. Consolidation refers to the process of making shortterm memories into longerterm memories so that we remember what happened yesterday or six months ago, etc. The mind can be at relative rest when peacefully gardening or actually practicing meditation, but also just walking from one room to another or sitting waiting for the bus or for a kid to get out of class. This resting activity seems to be when the psychological and brain physical processes of consolidation do their best work. The problem for most people with major depression is that their minds are never at rest.
Let’s finish off by returning to the vantage point of the mind once again.
diet, exercise, meditation, counseling and many others. Electroconvulsive therapy, despite much unwarranted phobic avoidance by the general public, remains the “gold standard” for treatment of serious depression. Additionally, now we have, for very serious and treatment-resistant
Continued from page 1 Antidepressant Medications: How Good Are They? depression, vagal nerve stimulation and deep direct brain stimulation - two different brain “pacemakers” to eliminate depression. In summary, available antidepressant medications are more alike than different; yet people are more different
than they are alike. Many alternatives to treatment failures exist. And even more help is on the way, including medications currently under study here at PRI, that are more different than they are alike!
When Depression Doesn’t Get Better: What Can Be Done About Treatment-Resistant Depression by: Daniel E. Grosz, M.D. Is your treatment for depression working? You still don’t feel as well as you used to? If you’ve been treated for depression but your symptoms haven’t fully improved, you may have treatment-resistant depression. Medications and psychotherapy work for most people. But with treatment-resistant depression, standard treatments don’t help much or don’t help at all. Months or even years can go by without any or with limited relief. But if your depression treatment isn’t working, don’t give up. Many people can get their treatment-resistant depression under control. You and your doctor just need to find the right approach. Here are some things to consider: Confirm the diagnosis: Some people who apparently have treatment-resistant depression might be mis-diagnosed. The most common mis-diagnosis is bipolar disorder (also known as manic depression), especially when the manic phases are mild. This condition requires a different treatment and might even get worse when using antidepressants alone. Often depression coexists with other conditions such as panic disorder, post traumatic stress disorder or attention deficit hyperactivity disorder. The presence of additional diagnoses makes depression more difficult to treat. In these cases a consultation with a psychiatrist might be necessary. Are you taking your medications correctly? Up to half of all people who get prescribed antidepressants don’t take them as recommended, either missing doses or not taking them due to side effects. Some give up too soon - it can take up to 12 weeks for a medicine to take effect. Rule out other health problems: Other medical conditions ranging from thyroid problems to anemia to substance abuse can sometimes mimic or worsen depression. Strategies for treating TreatmentResistant Depression: Even if the initial trials of antidepressants didn’t work, there are other options for you and your doctor to consider:
Switching medications: In nearly one in three people, the first antidepressant tried doesn’t work at all. You may need to try several antidepressants before you find one that works.
Eye on It What’s New at PRI
Tr y i n g a m e d i c a t i o n l o n g e r : Antidepressants typically take four to eight weeks to become fully effective and for side effects to ease up. For some people it might take even longer, so it helps to be patient. Increasing your dose: Often people respond to medications differently. You might benefit from a higher dose than is usually prescribed. Discuss with your doctor if this is an option for you. Don’t increase your dose on your own. Combination: In this approach, different classes of antidepressants are prescribed at the same time. The goal is to target several kinds of brain chemicals at once. Augmentation: Augmentation means taking an antidepressant along with a medication generally used for another mental health condition. Talk therapy: For some people with depression, psychotherapy works as well as medications. The combination of medication and psychotherapy is generally the most effective approach. Additional treatment options: If standard treatment with medications and psychotherapy haven’t been effective for your treatment-resistant depression, you may wish to consult with a psychiatrist who specializes in one or some of these additional treatment options: Transcranial Magnetic Stimulation (TMS), Electroconvulsive Therapy (ECT) or vagus nerve stimulation. So if your depression treatment isn’t working, don’t give up. You can get your treatment-resistant depression under control. Work with your doctor until you find the right approach. Reference: WebMD.com, mayoclinics.com
Thank You! Merci! Grazie! Mahalo! Merci! Danke! Gracias! Grazie! Danke! Merci! Mahalo! Gracias! Thank You! Merci! You Are So Good and We Are So Grateful!! by: Charles S. Wilcox, Ph.D.
Yes! You, our many readers of The PRI Bulletin, really overwhelmed us with the comments, compliments, stories-ofsuccess and suggestions for future newsletters that you submitted to us near the end of 2010 ~ Thank you!
Whether you are a current or former study participant, a referring physician/health care provider, or the caregiver of a current or former study participant, we were truly amazed by the literally hundreds (and hundreds!) of you who took the time to write and share with us how PRI has improved your quality of life! We also appreciated hearing your requests and recommendations for the content of future newsletters, including this first PRI Bulletin of 2011! While it may not be possible for us to incorporate all of your ideas into future newsletters, beginning with this edition, we are including articles based on the number of specific requests we received from you ~ our readers!
In this newest PRI Bulletin, the articles by Jon F. Heiser, M.D., Don F. De Francisco, M.D., Ph.D., Daniel E. Grosz, M.D., and Nader Oskooilar, M.D., Ph.D. are in direct response to your most frequent requests.
All of us here at PRI also want to convey our most sincere “Thank you” to each and every one of you for the PRI Research Study Success Stories that you have most recently shared with us. We heard from people who participated
in research programs from well over 25 years ago, here at PRI! It was especially rewarding and inspirational for us to read the various vignettes, where so many of you even remembered the specific PRI research nurse(s) and physician(s) with whom you interacted...and in numerous instances even the name of the research medication that was the focus of the study.
It seems that whether you are a former study participant, the relative of a former study participant, or the primary care doctor who may have referred one or more of your patients to PRI, you have seen how beneficial these research programs have proven to be for people suffering from Anxiety, Alzheimer’s Disease, Attention Deficit/Hyperactivity Disorder, Depression, Migraine Headaches, Mild Cognitive Impairment, Nicotine Addiction, Obesity, TreatmentResistant Depression and numerous other medical conditions, over our 36 years of conducting leading edge research!
We were truly touched by your PRI study-related stories... Moreover, as we read about so many different “successes,” both during one’s study participation and/or vis-a-vis PRI’s After Care Programs, we were reminded that because of people like you, literally millions of people all over the world have also had their quality of life improved as well! Yes, you are good and we are grateful!!
Eye on It What’s New at PRI Mild Cognitive Impairment (MCI) What is normal forgetfulness versus “MCI”? MCI is a condition or stage of 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 serious enough to 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 enrolling 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!
Mild-to-Moderate Alzheimer’s Disease (AD) PRI’s internationally 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 types of medications. Sometimes categorized as the next Global Epidemic – with estimates as high as 100 million sufferers worldwide by 2050 – enrolling in an antiAlzheimer ’s research program may help you, your loved ones and millions of other people as well.
Risk Factors for Cognitive Aging by: Nader Oskooilar, M.D., Ph.D.
Many factors can lead to or accelerate cognitive aging and memory loss in humans. Familiar causes are brain injury (e.g. accidents) and brain disease (e.g. stroke, dementia). Some of the other crucial contributing sources of cognitive aging are briefly reviewed in this article. Under acute physical or emotional stress, our body activates a large number of biological mechanisms that seek to diminish the impact of the stressors and restore balance; among them, are compounds such as adrenaline and cortisol from the adrenal gland and cytokines from the cells of the immune system. In chronic stress, the body is not able to shut off these mediators of stress when they are no longer needed; they may then tax a person’s physiological and psychological resources and harm the brain and its functions. Poor lifestyle habits may also overstress the body and contribute to cognitive deterioration. Examples are overeating, unhealthy food choices, excessive alcohol use, smoking tobacco, sedentary life, poor sleep and deficient anger management skills. The third factor is chronic low-grade inflammation. The human body’s shortterm response to acute injury - due to any cause - is to have local or circulating cells secrete chemicals called inflammatory mediators (cytokines), and the liver to produce acute-phase reactants (e.g. Creactive protein); the goal of both sets of chemicals is to restore physiological balance. The plasma concentrations of these chemicals (collectively called inflammatory markers), however, might increase with aging and stay high, which results in chronic low-grade inflammation. In turn, this might lead to chronic agingrelated disorders, such as cardiovascular disease, arthritis, and cognitive deterioration. Weight loss and regular physical activity may often lower the levels of the inflammatory markers. Additionally, there is a link between type 2 diabetes and cognitive decline and dementia. Clinical factors which predispose individuals to diabetes may, even in the absence of diabetes, also
increase the risk of late-life cognitive dysfunction. These factors include obesity, insulin resistance, and the metabolic syndrome. Overweight and obese individuals may heighten their risk of dementia, including Alzheimer’s disease. Obesity is moreover associated with cerebral vascular damage that may then contribute to cognitive decline and vascular dementia. Excessive weight also increases the odds for chronic low-grade inflammation, diabetes, insulin resistance, and metabolic syndrome that can all increase the chances of cognitive impairment. Insulin resistance (the body cannot use insulin efficiently) appears to be a risk for cognitive decline and dementia. This condition is seen more in obese individuals. It also frequently accompanies chronic elevations of inflammatory markers, compromising cognitive functions. Metabolic syndrome is a combination of excessive fat in and around the abdomen (especially in men), blood cholesterol disorders, high blood pressure, insulin resistance, and pro-inflammatory states. Conditions associated with this syndrome include sedentary life, obesity, aging, hormonal imbalance and genetic predisposition. People with the metabolic syndrome are at increased risk of coronary heart disease, stroke, type 2 diabetes, cognitive impairment and dementia. Finally, depression and anxiety seem to have contributory roles in the etiology of cognitive deterioration and dementia. Depression also worsens outcomes for cardiac disease, obesity, diabetes mellitus, and attendant metabolic problems. Anxiety puts the body in a state of alarm (fight or flight) which, when chronic, may often be harmful to the body and to the brain. In summary, many factors pose significant threats to cognitive aging. Regular physical activity, periodic physical checkups, healthy diet, stress management, weight reduction/control, and prevention or treatment of psychiatric disorders can prevent or decrease the risks of cognitive decline. page 5
THE PRI BULLETIN
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Pharmacology Research Institute PO Box 1645 Los Alamitos, CA 90720
The PRI Bulletin
Issue Vol. 22 No. 1 Winter/Spring 2011
This Issue’s Featured Team Member Michelle Panlilio, R.N., M.S.N., N.P. by: Christine Ziegwied
PRI is pleased to introduce our newsletter readers to a key member of our research team, Michelle Panlilio, R.N., M.S.N., N.P., who works in our Encino office. Michelle has been a resident of Los Angeles since age 11. She has spent most of her life in the San Fernando Valley, graduating from Kennedy High School.
Before joining the PRI Team, Michelle worked at UCLA as Nurse Practitioner in Internal Medicine. She also has extensive experience with medical aesthetics and cardiology. Michelle loves her work at PRI as a Research Nurse Practitioner and she is clearly passionate about helping people! Her outlook on life is consistently positive and you can always count on a big smile from Michelle! Outside of the workplace, Michelle enjoys spending time with her husband Paolo and daughter Isabella. She is an avid runner and enjoys “researching” different ethnic foods.
She did not go too far to attend college at Mount St. Mary’s, Los Angeles, where she earned a Bachelor’s Degree in the Science of Nursing. She then decided to further pursue her education and attended UCLA, where she earned her 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. page 6
The PRI Bulletin is an official publication of Pharmacology Research Institute and is intended for patients and friends of the Institute. PRI does not rent, sell or trade its mailing list with any other organization or company. Your personal information is kept completely confidential. Inquiries and changes of address may be directed to any of the sites below. Medical Directors Jon F. Heiser, M.D. Daniel E. Grosz, M.D. Nader Oskooilar, M.D., Ph.D. Associate Medical Directors Don F. De Francisco, M.D., Ph.D. Clifford Feldman, M.D., J.D. Executive Director Charles S. Wilcox, Ph.D. PRI Bulletin Editors Rachel Gotiong Janet L. Minter Site Coordinators/Office Locations Mellissa Henry, R.N., M.S.N., N.P. 4281 Katella Ave., Suite 115 Los Alamitos, CA 90720 714/827-3668/ Fax: 714/827-3669 Email: email@example.com Barbara B. Katz, R.N., C.C.R.C. 1601 Dove Street, Suite 290 Newport Beach, CA 92660 949/752-7936/ Fax: 949/752-1412 Email: firstname.lastname@example.org Judy Morrissey, R.N., M.S.N., C.C.R.C. 6345 Balboa Blvd. Bldg III, Suite 363 Encino, CA 91316 818/705-7450/ Fax: 818/705-7454 Email: email@example.com Check out our newly updated website at: www.priresearch.com