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 Research & Giving News Article  Ninth Annual Sarasota Mental Health Research Symposium, January 7 Third Annual Palm Beach Research Symposium, March 11 Featuring Experts on Depression, Bipolar Disorder and Nicotine Dependency The ninth annual Sarasota “Sunshine from Darkness” Mental Health Research Symposium was held on January 7th, 2006, at Sarasota’s Van Wezel Performing Arts Hall. It attracted more than 1,100 people and offered Continuing Education Units (CEUs) through Sarasota Memorial Hospital. The third annual Palm Beach “Sunshine from Darkness” Symposium took place on March 11, 2006. It was held at the Palm Beach County Convention Center and attended by over 700 people. Unrestricted education grants received from Bristol-Myers Squibb Company and Eli Lilly and Company helped support the Palm Beach symposium, and Continuing Education Units (CEUs) were provided courtesy of Columbia Hospital. The symposia were moderated by Wade Berrettini, M.D., Ph.D., who also spoke on the subject of nicotine addiction. He is the Karl E. Rickels Professor of Psychiatry and director of the Center for Neurobiology and Behavior at the University of Pennsylvania and a leader in studies of the genetics of mental illness. A member of NARSAD’s Scientific Council, Dr. Berrettini received the 1996 NARSAD Selo Prize for Outstanding Achievement in Affective Disorders Research, as well as NARSAD Distinguished Investigator Awards in 1992, 1999 and 2004. Dr. A. John Rush, Jr. - Depression Treatments The first report, on depression, was presented by A. John Rush, Jr., M.D., who holds the Betty Jo Hay Distinguished Chair in Mental Health and the Rosewood Corporation Chair in Biomedical Science at the University of Texas Southwestern Medical Center at Dallas, where he is vice chairman of research. For the past several years, Dr. Rush has been directing a National Institute of Mental Health-supported study, STAR*D (Sequenced Treatment Alternatives to Relieve Depression), and the Texas Medication Algorithm Project (TMAP). Twice honored by NARSAD, he received a Distinguished Investigator Award in 1991 and the 2000 Falcone Prize for Outstanding Achievement in Affective Disorders Research. Dr. Rush began by reviewing the range of current depression treatments. These include some 20 medications and a variety of targeted psychotherapies, as well as several device-based procedures, such as electroconvulsive therapy and the newer methods of vagus nerve stimulation and transcranial magnetic stimulation, described later in the program by another speaker. The challenge, Dr. Rush stated, lies in determining which treatment, or combination of treatments, will work for a particular patient, as well as appropriate dosages and duration of treatment, since premature discontinuation can increase the risk of relapse. The current relapse rate, he said, is 50 percent after one episode; after three episodes, the risk of a fourth soars to 90 percent or higher. Emphasizing the goal of treatment as remission, he pointed out that a significant percentage of people with treatment-resistant depression never achieve it. Even among non-treatment-resistant patients, he said, only about 40 percent remit with the first treatment. TMAP, which is supported by the Texas Department of Health Services, was established in 1996 to develop medication algorithms for the treatment of major psychiatric disorders. Dr. Rush explained medication algorithms to mean step-by-step, concise guidelines that can be modified and individualized for each patient. This process carefully measures and assesses symptoms and side effects of treatments and the results of various combinations, augmentations and changes of treatment. Dr. Rush reported that the patients managed with this measurement-based care, which has not been standard practice in psychiatry, appear to have better outcomes than patients receiving conventional treatment, but he cautioned that the evidence is not definitive at this stage of the study. STAR*D, the NIMH study, was begun in 2001 and concludes in September 2006. It involves 14 regional centers and 41 clinical sites across the country, with the coordinating center at UT Dallas, Dr. Rush’s home base. A major goal of the project has been to seek ways to help those with treatment-resistant depression. A distinctive aspect of STAR*D, Dr. Rush stated, is that patients who fail to remit on the first go-round are given the chance to assess their treatment and to choose further treatment options: whether to continue on the initial treatment for a longer period, to augment it by combining it with other treatments, or to switch to entirely new treatments. Dr. Rush cited as a significant finding coming out of the study that some patients take longer than others to show improvement on a particular treatment, and therefore it is important that treatments not be switched too quickly. As STAR*D approaches conclusion, he reported that one-third of 2,876 previously treatment-resistant patients in the program have achieved remission, and another 10 to 20 percent had a good response, if not full remission. Dr. Joseph Calabrese - Bipolar Disorder Treatments The medical management of bipolar disorder was the focus of the symposia’s second speaker, Joseph R. Calabrese, M.D., recipient of NARSAD’s 2004 Falcone Prize for Outstanding Affective Disorders Research and professor of psychiatry at Case Western Reserve University, where he directs the Mood Disorders Program and co-directs the Bipolar Research Center. Dr. Calabrese prefaced his remarks by stating that the first task in treating bipolar disorder, a condition characterized by episodes of mania and of depression, is to recognize it; that is, to be able to distinguish between a patient with unipolar depression and one in the depressive phase of bipolar disorder. He pointed out that in patients with type 2 bipolar depression, for example, the manic phase is mild and easy to miss. Also, bipolar disorder can present with other illnesses, such as drug or alcohol abuse or anxiety. As a result, he said, initial assessments are frequently wrong; family physicians misdiagnose it around 75 percent of the time and mental health professionals perhaps half the time. The way to correct this, he said, contrary to usual practice, is to have family members participate in the assessment process. Turning to his main topic, Dr. Calabrese listed five categories of medications currently used with bipolar disorder, starting with lithium, the treatment of choice for many years, which he described as good at managing mania, but not depression. The problem, he explained, is that in bipolar type 1 the ratio of time spent depressed as opposed to manic is three to one; in type 2, the ratio is from 30 to 50 to one. Bipolar patients are also now treated with anticonvulsant medications, originally developed as antiepileptics. Some, like Tegritol (carbamazepine) and Depakote and Depakeen (valproates), work to relieve mania; some, like Neurontin (gabapentin), counter anxiety; and some, like Lomictol (lomotrogine), treat depression. The most commonly prescribed medications for bipolar disorder are antidepressants, primarily the selective serotonin reuptake inhibitors (SSRIs) and, less frequently, the older tricyclics. The fifth category, sleeping pills, particularly Ativan (lorazepan), treat the insomnia and anxiety that can accompany bipolar disorders. Dr. Calabrese cautioned that none of these medications prevents recurrence, the ultimate goal of treatment, and all have side effects. With lithium, he said, the most clinically important side effects are tremors and hypothyroidism. Unlike most newer medications, lithium requires blood monitoring to assure a dosage high enough to be effective, but not so high as to induce undesirable side effects. The valproate anticonvulsants also need to be monitored to prevent liver damage, and they can induce weight gain, somnolence, fatigue and stomach upset. Carbamazepine can interact negatively with other drugs, a significant consideration since most bipolar patients need to be on more than one medication; and carbamazepine can occasionally cause a drop in white-cell count. The most frequent side effect of lomotrogine is headache; rare but more serious is rash, which in extreme cases can be life-threatening. Dr. Calabrese then described the atypical antipsychotics, a new generation of drugs developed to treat delusions and hallucinations in schizophrenia and other psychoses. While such symptoms do not generally occur in bipolar disorder, these medications appear to relieve bipolar mania, particularly Zyprexa (olanzapine), Risperdal (risperidone) and Seroquel (quetiapine). Dr. Calabrese and his colleagues have conducted studies of Seroquel, and recently applied for FDA approval for its use in bipolar disorder. Of the antidepressants currently prescribed for bipolar disorder, the SSRIs, like Prozac (fluoxetine), are generally better tolerated than the older tricyclics, but they have serious drawbacks, Dr. Calabrese stated. Side effects include disturbed sexual functioning and weight gain. The serotonin norepinephrine reuptake inhibitors cause less sexual dysfunction, but they can trigger an overreaction into mania. Dr. Calabrese concluded by stressing that antidepressants used alone can worsen moods and cause mood cycling to accelerate, and that the foundation for bipolar treatment at the present time requires careful layering of medications; balancing mood stabilizers such as lithium, anticonvulsants and the atypical antipsychotic agents to handle mania, and lomotrogine to manage the depressed phase. Dr. John O’Reardon - Devices To Treat Depression The next speaker, John O’Reardon, M.D., described new devices designed to treat depression by stimulating the brain. A 1999 NARSAD Young Investigator Award recipient, Dr. O’Reardon is an assistant professor of psychiatry at the University of Pennsylvania, where he directs the Treatment-Resistant Depression Clinic, the Electroconvulsive Therapy (ECT) Clinical Service and Training Program, and the Laboratory for Transcranial Magnetic Stimulation (TMS). Vagus nerve stimulation (VNS), which Dr. O’Reardon likened to a pacemaker for the brain, was recently approved by the FDA for treatment-resistant depression. The vagus is a long nerve with which the brain sends and receives messages. Dr. O’Reardon explained that VNS works by piggybacking on the vagus nerve to activate brain areas that are shut off in depression. Approved for patients ages 18 and over, it has been used safely with people in their 80s. Unlike some of the other treatments discussed earlier in the symposium, VNS has the advantage of working for both unipolar and bipolar depression. The pulses sent in VNS are intermittent – active for about 30 seconds every five minutes – and the pulse intensity is about one eight-hundredth that of the pulses sent in ECT, the oldest form of brain-stimulation treatment for depression. Dr. O’Reardon pointed out that because VNS works as an automatic delivery system, compliance is automatic, as compared to the 30 percent noncompliance rate with prescribed medications. Patients can, however, adjust their dosage, and can shut off and restart the device if necessary. VNS has few of the side effects of other treatments, such as memory loss, sexual dysfunction or weight gain, and can be used in combination with other treatments. The downside, at present, Dr. O’Reardon said, is cost: VNS requires surgical implantation, and insurance companies often deny coverage despite VNS’s FDA approval In assessing effectiveness, Dr. O’Reardon emphasized that the patients with whom VNS has been tried typify the most treatment resistant. On average, they have been depressed for 25 years and have failed 16 medication treatments, four of which were administered during the most recent depression (a protocol requirement), which in most cases had been ongoing for two years or more. Half the patients failed to improve with ECT. With VNS, instead of the 10 to 15 percent improvement rate that would have been expected with conventional treatment, Dr. O’Reardon reported that 40 to 45 percent are doing well a year or two into treatment, and 80 to 85 percent still have the device implanted since even those who have not achieved complete remission have experienced improvement in symptoms. In transcranial magnetic stimulation (TMS), which Dr. O’Reardon next described, a magnetic coil is positioned on the scalp over the frontal part of the brain. Brain circuits in that area are stimulated with pulses of about the same strength as those of an MRI. TMS is noninvasive, requires no anesthesia and can be done as an office procedure lasting about half an hour. It does, however, require 15 to 20 sessions to achieve antidepressant effect, and it must be maintained. Dr. O’Reardon said that his patients come for treatment on average once a week or twice a month. TMS effectiveness has been under study for a decade, Dr. O’Reardon said, and in five of six studies comparing it to ECT, which has been the gold standard for severe, refractory depression, TMS has shown equal efficacy, but did not cause memory loss, a common ECT side effect. TMS carries some risk of seizure, estimated at one in 1,000 to 10,000, as compared to one in 1,000 for Prozac, one in 250 for Wellbutrin, and one in 100 for the tricyclic antidepressants. (Dr. O’Reardon reported no incidence of seizure in some 10,000 TMS sessions he has conducted.) TMS is approved for use in Canada, Europe, Australia and Israel, but not yet in the US. A multicenter trial in which Dr. O’Reardon is participating is reaching conclusion. If the results are positive, TMS will be submitted to the FDA for approval. Additionally, Dr. O’Reardon stated, there has been a study, recently published, in which TMS was used to treat post-stroke depression, and another showing TMS as beneficial in suppressing hallucinations in schizophrenia; these leads, he said, will be followed up in future studies. Dr. Wade Berrettini-Nicotine Addiction in the Mentally Ill Mental illness imposes a spectrum of related health hazards. Dr. Berrettini, the final speaker at the Sarasota and Palm Beach symposia, stated that people with schizophrenia, depression, bipolar disorder and other psychiatric disorders bear most of the burden in this country for nicotine dependency, a problem he said is too often overlooked by psychiatrists and other health professionals. Twenty percent of American adults are daily smokers. By comparison, Dr. Berrettini cited a survey by the National Institute on Alcoholism and Alcohol Abuse in which, of 43,000 people interviewed, a third of the respondents with recurring depression reported smoking a pack of cigarettes a day. For those with bipolar disorder the percentage was somewhat higher, and for those with schizophrenia, panic disorder and alcoholism it was a lot higher. Smoking makes people with psychiatric illnesses feel better: it reduces anxiety and improves attention. Conversely, nicotine withdrawal worsens symptoms. Nicotine achieves its effects, Dr. Berrettini explained, by binding to brain-cell receptors that activate dopamine-containing cells, one of the major ways the brain signals reward. This reward-system sensitization causes long-term adaptive changes in the brain. There are currently two FDA-approved treatments for nicotine addiction. One is nicotine replacement therapy, principally the nicotine patch, which works by delivering progressively lower doses of nicotine over a six-week period, reducing withdrawal symptoms and cravings. But, Dr. Berrettini said, the relief is short lived. Generally, nicotine craving reasserts itself after treatment stops, and he suggested that some people might have to use nicotine replacement as long-term therapy. The other FDA-approved treatment is the antidepressant Bupropion. Like the patch, it doubles the odds of being able to quit for those who are motivated, but his message here, too, was that it may have to be used long term. On a note of hope, Dr. Berrettini reported that two new medicines are on the horizon, awaiting FDA approval. One, Varenicline, works by binding to the same brain receptor that binds to nicotine, and has tested more effective than Bupropion. The second, Rimonabant, binds to the receptor that binds the active component in marijuana. Dr. Berrettini’s interest in nicotine addiction, the predisposition to which has been shown to be largely genetic, grew out of his major research into the genetics of psychiatric illness. In concluding his remarks, he announced two new, large-scale projects by the National Institute of Mental Health to create national repositories of DNA and clinical data from people with schizophrenia and bipolar disorder, which will be made available to research scientists all over the world, and he said that enrollees are currently being recruited. |
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