Cognitive Effects of Atypical Antipsychotic Medications in Patients With Alzheimer's Disease: Outcomes From CATIE-AD
Vigen C.L., Mack W.J., Keefe R.S., Sano M., Sultzer D.L., Stroup T.S., Dagerman K.S., Hsiao J.K., Lebowitz B.D., Lyketsos C.G., Tariot P.N., Zheng L., and Schneider L.S. Am J Psychiatry. 2011 Aug;168(8):831–9.
Objective: The impact of the atypical antipsychotics olanzapine, quetiapine, and risperidone on cognition in patients with Alzheimer's disease is unclear. The authors assessed the effects of time and treatment on neuropsychological functioning during the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease study (CATIE-AD). Method: CATIE-AD included 421 outpatients with Alzheimer's disease and psychosis or agitated/aggressive behavior who were randomly assigned to receive masked, flexible-dose olanzapine, quetiapine, risperidone, or placebo. Based on their clinicians' judgment, patients could discontinue the originally assigned medication and receive another randomly assigned medication. Patients were followed for 36 weeks, and cognitive assessments were obtained at baseline and at 12, 24, and 36 weeks. Outcomes were compared for 357 patients for whom data were available for at least one cognitive measure at baseline and one follow-up assessment that took place after they had been on their prescribed medication or placebo for at least 2 weeks. Results: Overall, patients showed steady, significant declines over time in most cognitive areas, including in scores on the Mini-Mental State Examination (MMSE; -2.4 points over 36 weeks) and the cognitive subscale of the Alzheimer's Disease Assessment Scale (-4.4 points). Cognitive function declined more in patients receiving antipsychotics than in those given placebo on multiple cognitive measures, including the MMSE, the cognitive subscale of the Brief Psychiatric Rating Scale, and a cognitive summary score summarizing change on 18 cognitive tests. Conclusions: In CATIE-AD, atypical antipsychotics were associated with worsening cognitive function at a magnitude consistent with 1 year's deterioration compared with placebo. Further cognitive impairment is an additional risk of treatment with atypical antipsychotics that should be considered when treating patients with Alzheimer's disease.
Divergent Trajectories of Physical, Cognitive, and Psychosocial Aging in Schizophrenia
Jeste D.V., Wolkowitz O.M., and Palmer B.W. Schizophr Bull. 2011 May;37(3):451–5.
Aging is not a uniform process. In the general population, there is a paradox of aging: age-associated decline in physical and some cognitive functions stands in contrast to an enhancement of subjective quality of life and psychosocial functioning. This paradox is even more striking in people with schizophrenia. Compared with the overall population, individuals with schizophrenia have accelerated physical aging (with increased and premature medical comorbidity and mortality) but a normal rate of cognitive aging, although with mild cognitive impairment starting from premorbid period and persisting throughout life. Remarkably, psychosocial function improves with age, with diminished psychotic symptoms, reduced psychiatric relapses requiring hospitalization and better self-management. Many older adults with schizophrenia successfully adapt to the illness, with increased use of positive coping techniques, enhanced self-esteem and increased social support. Although complete remission is uncommon, most individuals with schizophrenia experience significant improvement in their quality of well-being. Cohort effect and survivor bias may provide a partial explanation for this phenomenon. However, the improvement also may reflect some brain changes that are beneficial for the course of schizophrenia along with neuroplasticity of aging. The proposed hypothesis has several implications. As significant medical morbidity in schizophrenia takes years to develop, studies of changes in sensitive biomarkers of aging during the course of illness may point to new treatments aimed at normalizing the rate of biological aging in schizophrenia. At the same time, effective psychotherapeutic interventions can affect brain structure and function and produce lasting positive behavioral changes in aging adults with schizophrenia.
Low Use Of Mental Health Services Among Older Americans With Mood And Anxiety Disorders
Byers A.L., Arean P.A., and Yaffe K. Psychiatr Serv. 2012 Jan;63(1):66–72.
Objective: It is unclear why late-life mood and anxiety disorders are highly undertreated, despite being common among older adults. Thus this study examined prevalence of and key factors associated with nonuse of mental health services among older community-dwelling adults with these disorders. Methods: The sample included 348 participants aged 55 years or older who met 12-month criteria for DSM-IV mood and anxiety disorders and responded to the National Comorbidity Survey Replication (NCS-R), a population-based probability sample. Analyses included frequency measures and logistic regression with weights and complex design-corrected statistical tests. Key factors associated with not using mental health services were determined in a final multivariable model based on a systematic approach that accounted for a comprehensive list of potential predictors. Results: Approximately 70% of older adults with mood and anxiety disorders did not use services. Those who were from racial-ethnic minority groups, were not comfortable with discussing personal problems, were married or cohabitating, and had middle- versus high-income status had increased odds of not using mental health services. In addition, respondents with mild versus serious disorders, no chronic pain complaints, and low versus high perceived cognitive impairment had greater odds of nonuse. Conclusions: Results indicate that improvements are needed in the following areas to combat the very high number of mood and anxiety disorders that go untreated in older Americans: awareness of need, comfort in discussing personal problems with a health care professional, and screening and other prevention efforts.
Management of Frontotemporal Dementia: Targeting Symptom Management in such a Heterogeneous Disease Requires a Wide Range of Therapeutic Options
Jicha G.A. and Nelson P.T. Neurodegener Dis Manag. 2011 Apr;1(2):141–156.
There are no US FDA-approved therapies for the management of frontotemporal dementia (FTD). Evidence-based medicine that would support a FDA indication for the treatment of FTD requires large-scale, randomized, double-blind, placebo-controlled trials that do not currently exist. Progress in obtaining approval and therapeutic indications for FTD has been severely hampered by the heterogeneity of clinical and pathological phenotypes seen in various FTD disease states. These issues are often misinterpreted by clinicians, caregivers and patients suggesting that potential treatment options are nonexistent for this devastating disease. This article discusses these issues in the context of recent studies and publications investigating therapeutic options in FTD, and further suggests a rationale for individualized therapy in FTD. Targeting the myriad of symptoms seen in FTD requires recognition of such symptoms that may play primary or secondary roles in the spectrum of deficits that lead to functional disability in FTD, and the availability of a wide range of therapeutic options that may be helpful in alleviating such symptomatology. Fortunately, agents targeting the many cognitive, behavioral, psychiatric and motor symptoms that can be seen in FTD are readily available, having been previously developed and approved for symptomatic benefit in other disease states. In contrast to the widespread belief that beneficial treatments are not available for FTD today, our therapeutic armament is stocked with pharmacological tools that may improve quality of life for those suffering from this devastating and incurable class of degenerative diseases.
Problem-Solving Therapy and Supportive Therapy in Older Adults With Major Depression and Executive Dysfunction
Areán P.A., Raue P., Mackin R.S., Kanellopoulos D., McCulloch C., and Alexopoulos G.S. Am J Psychiatry. 2010 Nov;167(11):1391–8.
Objective: The purpose of this study was to determine whether problem-solving therapy is an effective treatment in older patients with depression and executive dysfunction, a population likely to be resistant to antidepressant drugs. Method: Participants were adults age 60 and older with major depression and executive dysfunction. Problem-solving therapy was modified to be accessible to this population. Participants were randomly assigned to 12 weekly sessions of problem-solving therapy or supportive therapy and assessed at weeks 3, 6, 9, and 12. Results: Of the 653 individuals referred for this study, 221 met selection criteria and were enrolled in the study. Reduction of depressive symptom severity was comparable for the two treatment groups during the first 6 weeks of treatment, but at weeks 9 and 12 the problem-solving therapy group had a greater reduction in symptom severity, a greater response rate, and a greater remission rate than the supportive therapy group (response rates at week 9: 47.1% and 29.3%; at week 12:56.7% and 34.0%; remission rates at week 9: 37.9% and 21.7%; at week 12: 45.6% and 27.8%). Problem-solving therapy yielded one additional response or remission over supportive therapy for every 4.4–5.6 patients by the end of the trial. Conclusions: These results suggest that problem-solving therapy is effective in reducing depressive symptoms and leading to treatment response and remission in a considerable number of older patients with major depression and executive dysfunction. The clinical value of this finding is that problem-solving therapy may be a treatment alternative in an older patient population likely to be resistant to pharmacotherapy.
Reducing Suicidal Ideation and Depression in Older Primary Care Patients: 24-Month Outcomes of the PROSPECT Study
Alexopoulos G.S., Reynolds C.F. 3rd, Bruce M.L., Katz I.R., Raue P.J., Mulsant B.H., Oslin D.W., and Ten Have T. PROSPECT Group. Am J Psychiatry. 2009 Aug;166(8):882–90.
Objective: The Prevention of Suicide in Primary Care Elderly: Collaborative Trial (PROSPECT) evaluated the impact of a care management intervention on suicidal ideation and depression in older primary care patients. This is the first report of outcomes over a 2-year period. Method: Study participants were patients 60 years of age or older (N=599) with major or minor depression selected after screening 9,072 randomly identified patients of 20 primary care practices randomly assigned to provide either the PROSPECT intervention or usual care. The intervention consisted of services of 15 trained care managers, who offered algorithm-based recommendations to physicians and helped patients with treatment adherence over 24 months. Results: Compared with patients receiving usual care, those receiving the intervention had a higher likelihood of receiving antidepressants and/or psychotherapy (84.9%–89% versus 49%–62%) and had a 2.2 times greater decline in suicidal ideation over 24 months. Treatment response occurred earlier on average in the intervention group and increased from months 18 to 24, while no appreciable increase in treatment response occurred in the usual care group during the same period. Among patients with major depression, a greater number achieved remission in the intervention group than in the usual-care group at 4 months (26.6% versus 15.2%), 8 months (36% versus 22.5%), and 24 months (45.4% versus 31.5%). Patients with minor depression had favorable outcomes regardless of treatment assignment. Conclusions: Sustained collaborative care maintains high utilization of depression treatment, reduces suicidal ideation, and improves the outcomes of major depression over 2 years.