First Annual Alzheimer’s Disease Summit Targeted Recent Advances in Diagnosis and Management
Alzheimer’s disease (AD) is expected to increase dramatically in the coming decades as a consequence of global aging. In response to the growing public health need for recognition and optimal treatment of dementia and cognitive impairment associated with AD, leading experts in the field established The Alzheimer’s Disease Summit (ADS). The inaugural convocation of the ADS, themed Translating Research Advances Into Clinical Practice, was held on May 3, 2008, in Washington, DC.
The ADS provided a comprehensive update of cutting-edge research and addressed application of knowledge to day-to-day practice. Led by co-chairs Jeffrey L. Cummings, MD, of the University of California at Los Angeles, and Pierre N. Tariot, MD, of the Banner Alzheimer’s Institute, a team of 13 internationally recognized experts in the field presented to an audience of geriatric psychiatrists, neurologists, geriatricians, and primary care physicians. Key topics were grouped into four educational sessions: Advances in Clinical Assessment; Advances in Neuroimaging and Biomarkers; Current AD Therapy; and The Future of AD Therapeutics. In a concluding panel discussion, guest panelist Russell Katz, MD, Director of Neurology Products at the Food and Drug Administration, gave perspective on disease-modifying agents.
“This program was both practical and forward-looking, providing a terrific update on how advances in the science of Alzheimer’s disease can be applied in practice, showing how best to use the currently available medications, and describing advances in the emergence of disease-modifying treatments” noted Dr. Cummings.
Approximately 84% of attendees reported enhanced knowledge of AD and approximately 75% found the information convincing and applicable enough to implement significant changes to their practice in the form of new screening techniques for MCI, changes to treatment protocol, and discussion of new treatment options with patients. Among the more specific topics addressed were new office-based techniques to simplify the detection of cognitive impairment and AD; imaging techniques for diagnosis of dementia and assessment of MCI in the earliest phases of AD; characterization of dementia syndromes using magnetic resonance imaging, FDG positron emission tomography, and amyloid imaging; new treatment targets; and compounds with therapeutic promise, such as anti-amyloid and neuroprotective agents.
This educational event was jointly accredited by the Mount Sinai School of Medicine and MBL Communications, Inc. The ADS proceedings will be available as a CME supplement to CNS Spectrums and Primary Psychiatry as well as a series of podcasts in October 2008 (http://cmepsychcast.mblcommunications.com). The next ADS will convene in 2009.
For more information, please visit www.mblcommunications.com/aspx/meetings.aspx.
This activity was supported in part by educational grants from Forest Pharmaceuticals, Inc., Eisai Inc., Medivation, Inc., and Elan Pharmaceuticals, Inc. –DH
Cognitive Remediation Improves Psychological Functioning in TBI Patients
Traumatic brain injury (TBI) occurs when sudden trauma causes damage to the brain, ie, when the head suddenly and violently hits an objects or when an object pierces the skill, thus entering the brain tissue. TBI patients suffer from impaired physical, cognitive, and psychological functioning that can impede their progress for the remainder their lives. Keith Ganci, BS, and Amy Rosenbaum, PhD, from the Park Terrace Care Center in Rego Park, NY, studied 94 patients between 17–80 years of age with an average length of treatment of 12.42 (SD=10.73) months. Patients were treated within 6 months of their initial injury and received intensive interdisciplinary treatment, including cognitive remediation and psychotherapeutic services. Patient brain injuries had focal and diffuse injuries in all areas of the brain.
“We were interested in the association between cognitive functioning and psychological status,” said Ganci. “We believe that much more research needs to be done with respect to recovery curves in TBI in order to provide the most comprehensive rehabilitation possible.”
The researchers used the Functional Independence Measure and the Functional Assessment Measure (FIM/FAM) to assess patients improvements in functioning. By using the cognitive and psychological adjustment subscales FIM/FAM, Ganci and Rosenbaum were able to test the patients memory, orientation, attention, safety judgment, and problem solving skills, and social interaction, emotional status, adjustment to limitations, and employability, respectively.
“What we did was create a variable called change scores. These scores were the individual patient’s discharge scores minus admission scores for both cognitive functioning and psych adjustment. Thus, we compared change in cognitive functioning to change in psych adjustment,” said Ganci.
Ganci and Rosenbaum believe that cognitive remediation helps to further facilitate psychological adjustment after brain injury.
“I was pleased with the findings because I believe that they illustrate the importance of cognitive remediation in TBI rehabilitation programs,” said Ganci. “In many cases, it is the cognitive deficits that preclude patients from returning to the community independently, not the physical deficits. Cognitive remediation is as important as physical therapy, occupational therapy, and speech therapy in TBI rehabilitation.”
Ganci and Rosenbaum also found that psychological functioning at discharge and patients that made greater improvements in cognitive functioning made greater improvements in psychological functioning.
“Much more research needs to be done in the field,” Ganci concluded. “Specifically, more studies need to look at what else we can do to help individuals with TBI return to their normal lives as safely and independently as possible.” (2008 Eastern Psychological Association Conference). –CN
Recent Drug Approvals from the Food and Drug Administration
The United States Food and Drug Administration recently approved several medications for various disease states. The Table outlines the new indications and dosage ranges as well as the side effects most commonly seen during clinical trials. For more information, please consult each medication’s respective prescribing information. –CN
Higher Risk of PTSD in Patients with History of Mood and Anxiety Disorders
Posttraumatic stress disorder (PTSD) is a comorbid condition affecting approximately 7.7 million American adults. Statistically, women are more likely to develop PTSD than men. According to a study by Barbara Andersen, PhD, and colleagues, women with a history of mood and anxiety disorders are at higher risk of suffering PTSD.
The study involved 74 breast cancer patients who were screened for cancer-related PTSD with diagnostic interviews over an 18-month period after cancer diagnosis or surgery. The researchers used the data to form three patient groups, including PTSD (n=12; ie, full diagnosis), subsyndromal PTSD (n=5; ie, show PTSD symptoms, but not to the extent of the full diagnosis), and no symptoms (n=47). Results revealed that women with PTSD were more than twice as likely as breast cancer patients without the condition to have had previous mood disorders and more than three times likely to have suffered anxiety disorders. In addition, past alcohol and substance abuse was linked to symptoms of PTSD in approximately 33% of women with PTSD, 20% of subsyndromal women, and 10% of women with no PTSD. A history of traumatic life events such as physical abuse was linked to 50% of PTSD patients and <17% of women in the other patient cohorts as well.
With 63.51% of cancer patients showing no symptoms of PTSD, the study reveals that breast cancer patients are not at risk for PTSD. However, women in the PTSD and subsyndromal groups were approximately four times more likely than breast cancer patients without the disorder to claim they were unable to work due to emotional distress. This suggests the importance of screening newly diagnosed breast cancer patients for past mood an anxiety disorders, as PTSD symptoms impact everyday life.
Research for this study was provided by grants from the American Cancer Society, Longaberger Company-American Cancer Society Grant for Breast Cancer Research, National Cancer Institute, National Institute of Mental Health, Ohio State Comprehensive Center, United States Army Medical Research Institute, and the Walther Cancer Institute. (J Trauma Stress. 2008;21(2):165-172.) –ML
Childhood Sexual Abuse Is a Risk Factor for Development of Bulimia Nervosa in Young Adulthood
Prior studies have shown that childhood incidence of sexual abuse is linked to a variety of mental health disorders and behavioral problems, including major depressive disorder, panic disorder, posttraumatic stress disorder, substance abuse (alcohol and drugs), and suicide. Eating disorders, such as anorexia and bulimia nervosa, have also been linked to childhood sexual abuse although data have been conflicting as to the association of each disorder to prior sexual abuse. Researchers at the Department of General Practice at the University of Melbourne in Australia sought to determine the relationship between childhood sexual abuse among females ≤16 years of age and the later development of anorexia and/or bulimia nervosa.
Lena Sanci, MBBS, PhD, FRACGP, and colleagues studied 1,936 female students from 44 public, private, and Catholic schools in Victoria, Australia from 1992 to 2008 to determine if a link between sexual abuse and development of an eating disorder exists. Among the 1,936 students (average age=15 years) who took part in at least one portion of the study, 999 continued the study through follow-up evaluation (average age of participants at follow-up=24 years).
All participants were assessed for anorexia or bulimia using the Branch Eating Disorders Test and identified with either disorder following Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. Childhood sexual abuse that occurred ≤16 years of age was identified via self-report measures at follow-up. Childhood sexual abuse was measured at follow up due to the increased willingness among young adult participants to divulge incidents of abuse rather than children, and the duration between possible incident and follow-up being a shorter duration.
Thirty-five participants developed bulimia and 32 participants developed anorexia during the study period. Ninety-six participants reported one episode of childhood sexual abuse and 70 participants reported ≥2 episodes of abuse. When investigating the link between sexual abuse and eating disorder development, the incidence of bulimia was 2.5 times higher for those who reported one episode of sexual abuse and 4.9 times higher for those who reported ≥2 episodes of abuse, when compared to female students who did not report any episodes of sexual abuse.
There was no link between the development of anorexia and childhood sexual abuse. Sanci and colleagues adjusted for mediating or confounding factors including age, psychiatric morbidity, dieting behavior, and background factors, such as parental divorce. The authors concluded that childhood sexual abuse appears to be a risk factor for the development of bulimia nervosa in young adulthood and is not mediated by other psychiatric disorders. These findings are also similar to other studies that show both disorders related to childhood sexual abuse, although the link for bulimia is stronger.
Sanci and colleagues stated that these findings illustrate that the emotional style of patients with bulimia is similar to those who experience childhood sexual abuse, including feelings of emotional stress and secrecy. These patterns may be an important focus of interest to clinicians treating patients with bulimia.
Funding for this research was provided by the Australian Center for Excellence in Eating Disorders, the Australian National Depression Initative, and the Australian National Health and Medical Research Council. (Arch Pediatr Adolesc Med. 2008;162(3):261-267.) —CP
Amitriptyline in Low Doses Can Improve Quality of Life for Adolescents with IBS
Irritable bowel syndrome (IBS) is a comorbid functional disorder wherein the large intestine operates abnormally, resulting in abdominal pain, bloating, and diarrhea. As there is no cure for IBS, existing treatments only mitigate its symptoms. Past research suggests that the antidepressant amitriptyline is effective for the treatment of IBS in adults. However, a study by Ron J. Bahar, MD, and colleagues, suggests that low doses of amitriptyline can similarly and substantially improve the overall quality of life (QOL) for adolescents with IBS.
The double blind, placebo-controlled study involved 33 IBS patients (24 girls, 9 boys) between 12–18 years of age. It consisted of three phases, including 2 weeks of enrollment and symptom scoring, 8 weeks of therapy with either amitriptyline or placebo, and 3 weeks of post-medication washout and symptom scoring. Doses of amitriptyline were given according to the patient’s body mass; ie, 30–50 kg (one 10-mg capsule), 50–80 kg (two 10-mg capsules), and 80 kg (three 10-mg capsules). At 2, 6, 10, and 13 weeks, patient response to treatment was assessed using a symptom checklist, pain-rating scale, visual analog scale, and IBS-QOL questionnaire. The results found that patients receiving amitriptyline were more likely to experience improvement in QOL as well as reduction in right lower quadrant pain of the lower abdomen at 6, 10, and 13 weeks; reduction in IBS-associated diarrhea at 6 and 10 weeks; and reduction in periumbilical pain at 10 weeks.
“Most surprisingly, we were able to obtain statistically significant results with a relatively small number of subjects,” Dr. Bahar said. “Similarly, the biggest limitation to the study was the subject size, which did not allow us to stratify by sex.”
Greater than 50% of adolescents with IBS, or their parents or guardians, were deterred from enrolling in the study. They cited negative reports in the media and Food and Drug Administration warnings that discussed increased suicidal behavior in children using antidepressants. However, the researchers argue that such concerns are irrelevant as the dose in the study was lower than the dose used to treat depressive disorders. In this study, AMI is considered a treatment for neuropathic pain complemented by chronic pain symptoms, not an antidepressant.
Future research will determine who continues to stay well on amitriptyline, whose symptoms yield completely, and which medications can be substituted for amitriptyline so adolescents with IBS may safely use them.
Funding for this study was provided by AstraZeneca and the James L. Brooks and Diane Brooks Medical Research Foundation of the California Community Foundation. (J Pediatr. 2008;152(5):685-689.) –ML
Antidepressant Use Shown Not to be Cause for Suicide Rate Decline in Older Adults
Although 815,000 people die by suicide worldwide each year, in industrialized countries, the rate of suicide has progressively declined in recent years. Researchers in the psychiatric community have attributed the decline to the increased identification of mental health disorders such as major depressive disorder, and the increased use of antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs). However, contrary to this claim, additional studies have not found an effect on suicide risk among patients taking SSRIs. Thus, the effect of patients taking SSRIs and/or other medications on the overall suicide rate has yet to be clearly determined.
Annette Erlangsen, PhD, of the National Centre for Register-based Research at the University of Aarhus in Denmark, and colleagues, studied the suicide and antidepressant use rate among people ≥50 years of age living in Denmark from 1996 to 2000 in order to determine if the decline in suicide rate (from 52.2 to 22.1 per 100,00 people between 1980 and 2000) was due to increased antidepressant use (from 8.4 to 52.2 per 1,000 people between 1990 and 2000). In Denmark, older adults receive antidepressants at higher rates than younger age groups and also have higher suicide rates than other age groups. Researchers evaluated suicide and antidepressant use rates for 2,100,808 adults.
Data were gathered from the Centralised Civil Register, the Register of Medical Product Statistics, and the Registry of Causes of Death. Antidepressants included in the analysis included SSRIs, such as citalopram and fluoxetine; tricyclic antidepressants (TCAs), such as clomipramine and nortriptyline; and other antidepressants, such as mirtazapine and nefazodone. Among all study participants, 299,440 filled ≥1 antidepressant prescriptions during the study period and were considered as “in treatment.” During the study period, 2,136 participants died by suicide.
Suicide rates for men fell by 9.7 per 100,000 people and rates for women fell 3.7 per 100,00 people during the study period. Regarding this decline in suicide rates among participants taking antidepressants, .94 suicides per 100,000 people were accounted for by men and .40 suicides per 100,000 people were accounted for by women taking antidepressants, which are approximately <10% of the total decline in suicide rates during the study time frame. Although rates were not significantly different among types of antidepressants taken, the authors found that men taking SSRIs had higher suicide rates than those taking TCAs.
Erlangsen and colleagues concluded that only a small portion of older adults who commit suicide are being treated with antidepressants at the time of death. According to the authors, this ratio was expected to be higher given the large reductions in treatment-specific suicide rates. The authors recommend that suicide prevention programs for older adults not only focus on the increased use of antidepressants. Study limitations included the potential influence on findings due to the method of defining “in treatment” as well as lack of information regarding prescription rates and actual drug administration and the possible influence of antidepressants taken without a prescription.
Funding for this research was provided by the American Foundation for Suicide Prevention, the Danish Velux Foundation, and the National Institute of Aging. (J Epidemiol Community Health. 2008;62(5):448-454.) —CP
Psychiatric dispatches is written by Deborah Hughes, Michelisa Lanche, Christopher Naccari, and Carlos Perkins, Jr.