Abstracts Geriatric Psychiatry
Clinical Symptom Responses to Atypical Antipsychotic Medications in Alzheimer's Disease: Phase 1 Outcomes from the CATIE-AD Effectiveness Trial
Sultzer DL, Davis SM, Tariot PN, Dagerman KS, Lebowitz BD, Lyketsos CG, Rosenheck RA, Hsiao JK, Lieberman JA, Schneider LS; CATIE-AD Study Group.
American Journal of Psychiatry 2008 7; 165( 7): 844– 54
Objective: The study measured the effects of atypical antipsychotics on psychiatric and behavioral symptoms in patients with Alzheimer's disease and psychosis or agitated behavior. Method: The Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) Alzheimer's disease effectiveness study included 421 outpatients with Alzheimer's disease and psychosis or agitated/aggressive behavior. Patients were assigned randomly to masked, flexible-dose treatment with olanzapine, quetiapine, risperidone, or placebo for up to 36 weeks. Patients could be randomly reassigned to a different medication at the clinician's discretion, which ended phase 1. Psychiatric and behavioral symptoms, functioning, cognition, care needs, and quality of life were measured at regular intervals. Results: In relation to placebo, the last observation in phase 1 showed greater improvement with olanzapine or risperidone on the Neuropsychiatric Inventory total score, risperidone on the Clinical Global Impression of Changes, olanzapine and risperidone on the Brief Psychiatric Rating Scale (BPRS) hostile suspiciousness factor, and risperidone on the BPRS psychosis factor. There was worsening with olanzapine on the BPRS withdrawn depression factor. Among patients continuing phase 1 treatment at 12 weeks, there were no significant differences between antipsychotics and placebo on cognition, functioning, care needs or quality of life, except for worsened functioning with olanzapine compared to placebo. Conclusion: In this descriptive analysis of outpatients with Alzheimer's disease in usual care settings, some clinical symptoms improved with atypical antipsychotics. Antipsychotics may be more effective for particular symptoms, such as anger, aggression, and paranoid ideas. They do not appear to improve functioning, care needs, or quality of life.
Elderly Patients with Dementia-Related Symptoms of Severe Agitation and Aggression: Consensus Statement on Treatment Options, Clinical Trials Methodology, and Policy
Salzman C, Jeste DV, Meyer RE, Cohen-Mansfield J, Cummings J, Grossberg GT, Jarvik L, Karemer HC, Lebowitz BD, Maslow K, Pollock BG, Raskind M, Schultz SK, Wang P, Zito JM, Zubenko GS.
The Journal of Clinical Psychiatry 2008 6; 69( 6): 889– 98
Objective: Atypical antipsychotic drugs have been used off label in clinical practice for treatment of serious dementia-associated agitation and aggression. Following reports of cerebrovascular adverse events associated with the use of atypical antipsychotics in elderly patients with dementia, the U.S. Food and Drug Administration (FDA) issued black box warnings for several atypical antipsychotics titled “Cerebrovascular Adverse Events, Including Stroke, in Elderly Patients With Dementia.” Subsequently, the FDA initiated a metaanalysis of safety data from 17 registration trials across 6 antipsychotic drugs (5 atypical antipsychotics and haloperidol). In 2005, the FDA issued a black box warning regarding increased risk of mortality associated with the use of atypical antipsychotic drugs in this patient population. Participants: Geriatric mental health experts participating in a 2006 consensus conference (Bethesda, Md., June 28–29) reviewed evidence on the safety and efficacy of antipsychotics, as well as nonpharmacologic approaches, in treating dementia-related symptoms of agitation and aggression.
Evidence/Consensus Process: The participants concluded that, while problems in clinical trial designs may have been one of the contributors to the failure to find a signal of drug efficacy, the findings related to drug safety should be taken seriously by clinicians in assessing the potential risks and benefits of treatment in a frail population, and in advising families about treatment. Information provided to patients and famiy members should be documented in the patient's chart. Drugs should be used only when nonpharmacologic approaches have failed to adequately control behavioral disruption. Participants also agreed that there is a need for an FDA-approved medication for the treatment of severe, persistent, or recurrent dementia-related symptoms of agitation and aggression (even in the absence of psychosis) that are unresponsive to nonpharmacologic intervention. Conclusions: This article outlines methodological enhancements to better evaluate treatment approaches in future registration trials and provides an algorithm for improving the treatment of these patients in nursing home and non-nursing home settings.
ACNP White Paper: Update on Use of Antipsychotic Drugs in Elderly Persons with Dementia
Jeste DV, Blazer D, Casey D, Meeks T, Salzman C, Schneider L, Tariot P, Yaffe K.
Neuropsychopharmacology 2008 4; 33( 5): 957– 70
In elderly persons, antipsychotic drugs are clinically prescribed off-label for a number of disorders outside of their Food and Drug Administration (FDA)-approved indications (schizophrenia and bipolar disorder). The largest number of antipsychotic prescriptions in older adults is for behavioral disturbances associated with dementia. In April 2005, the FDA, based on a meta-analysis of 17 double-blind randomized placebo-controlled trials among elderly people with dementia, determined that atypical antipsychotics were associated with a significantly (1.6–1.7 times) greater mortality risk compared with placebo, and asked that drug manufacturers add a ‘black box’ warning to prescribing information for these drugs. Most deaths were due to either cardiac or infectious causes, the two most common immediate causes of death in dementia in general. Clinicians, patients, and caregivers are left with unclear choices of treatment for dementia patients with psychosis and/or severe agitation. Not only are psychosis and agitation common in persons with dementia but they also frequently cause considerable caregiver distress and hasten institutionalization of patients. At the same time, there is a paucity of evidence-based treatment alternatives to antipsychotics for this population. Thus, there is insufficient evidence to suggest that psychotropics other than antipsychotics represent an overall effective and safe, let alone better, treatment choice for psychosis or agitation in dementia; currently no such treatment has been approved by the FDA for these symptoms. Similarly, the data on the efficacy of specific psychosocial treatments in patients with dementia are limited and inconclusive. The goal of this White Paper is to review relevant issues and make clinical and research recommendations regarding the treatment of elderly dementia patients with psychosis and/or agitation. The role of shared decision making and caution in using pharmacotherapy for these patients is stressed.
Effectiveness of Cholinesterase Inhibitors and Memantine for Treating Dementia: Evidence Review for a Clinical Practice Guideline
Raina P, Santaguida P, Ismaila A, Patterson C, Cowan D, Levine M, Booker L, Oremus M.
Annals of Internal Medicine 2008 3 4; 148( 5): 379– 97
Background: The effectiveness of the 5 U.S. Food and Drug Administration-approved pharmacologic therapies for dementias in achieving clinically relevant improvements is unclear. Purpose: To review the evidence for the effectiveness of cholinesterase inhibitors (donepezil, galantamine, rivastigmine, and tacrine) and the neuropeptide-modifying agent memantine in achieving clinically relevant improvements, primarily in cognition, global function, behavior, and quality of life, for patients with dementia. Data Sources: Cochrane Central Register of Controlled Trials, MEDLINE, PREMEDLINE, EMBASE, Allied and Complementary Medicine Database, CINAHL, AgeLine, and PsycINFO from January 1986 through November 2006. Study Selection: English-language randomized, controlled trials were included in the review if they evaluated pharmacologic agents for adults with a diagnosis of dementia, did not use a crossover design, and had a quality score of at least 3 on the Jadad scale. Data Extraction: Data were extracted on study characteristics and outcomes, including adverse events. Effect sizes were calculated and data were combined when appropriate. Data Synthesis: 96 publications representing 59 unique studies were eligible for this review. Both cholinesterase inhibitors and memantine had consistent effects in the domains of cognition and global assessment, but summary estimates showed small effect sizes. Outcomes in the domains of behavior and quality of life were evaluated less frequently and showed less consistent effects. Most studies were of short duration (6 months), which limited their ability to detect delay in onset or progression of dementia. Three studies directly compared different cholinesterase inhibitors and found no differences in cognition and behavior. Limitations: Limitations of available studies included short duration, inclusion of only patients with mild to moderate Alzheimer disease, poor reporting of adverse events, lack of clear definitions for statistical significance, limited evaluation of behavior and quality-of-life outcomes, and limited direct comparison of different treatments. Conclusions: Treatment of dementia with cholinesterase inhibitors and memantine can result in statistically significant but clinically marginal improvement in measures of cognition and global assessment of dementia.
Mindfulness Meditation for the Treatment of Chronic Low Back Pain in Older Adults: A Randomized Controlled Pilot Study
Morone NE, Greco CM, Weiner DK.
Pain 2008 2; 134( 3): 310– 9
The objectives of this pilot study were to assess the feasibility of recruitment and adherence to an eight-session mindfulness meditation program for community-dwelling older adults with chronic low back pain (CLBP) and to develop initial estimates of treatment effects. It was designed as a randomized, controlled clinical trial. Participants were 37 community-dwelling older adults aged 65 years and older with CLBP of moderate intensity occurring daily or almost every day. Participants were randomized to an 8-week mindfulness-based meditation program or to a wait-list control group. Baseline, 8-week and 3-month follow-up measures of pain, physical function, and quality of life were assessed. Eighty-nine older adults were screened and 37 found to be eligible and randomized within a 6-month period. The mean age of the sample was 74.9 years, 21/37 (57%) of participants were female and 33/37 (89%) were white. At the end of the intervention 30/37 (81%) participants completed 8-week assessments. Average class attendance of the intervention arm was 6.7 out of 8. They meditated an average of 4.3 days a week and the average minutes per day was 31.6. Compared to the control group, the intervention group displayed significant improvement in the Chronic Pain Acceptance Questionnaire Total Score and Activities Engagement subscale (P = .008, P = .004) and SF-36 Physical Function (P = .03). An 8-week mindfulness-based meditation program is feasible for older adults with CLBP. The program may lead to improvement in pain acceptance and physical function.
Psychotherapeutic Treatments for Older Depressed People
Wilson KC, Mottram PG, Vassilas CA.
Cochrane Database Syst Rev 2008 1 23;( 1): CD004853
Background: Despite a number of reviews advocating psychotherapy for the treatment of depression, there is relatively little evidence based on randomised controlled trials that specifically examines its efficacy in older people. Objectives: To examine the efficacy of psychotherapeutic treatments for depression in older people. Search Strategy: CCDANCTR-Studies and CCDANCTR-References were searched on 11/9/2006. The International Journal of Geriatric Psychiatry and Irish Journal of Psychiatry were handsearched. Reference lists of previous published systematic reviews, included/excluded trial articles and bibliographies were scrutinised. Experts in the field were contacted. Selection Criteria: All randomised controlled trials that included older adults diagnosed as suffering from depression (ICD or DSM criteria) were included. All types of psychotherapeutic treatments were included, categorised into cognitive behavioural therapies (CBT), psychodynamic therapy, interpersonal therapy and supportive therapies. Data Collection and Analysis: Meta-analysis was performed, using odds ratios for dichotomous outcomes and weighted mean differences (WMD) for continuous outcomes, with 95% confidence intervals. Primary outcomes were a reduction in severity of depression, usually measured by clinician rated rating scales. Secondary outcomes, including dropout and life satisfaction, were also analysed. Main Results: The search identified nine trials of cognitive behavioural and psychodynamic therapy approaches, together with a small group of ‘active control’ interventions. No trials relating to other psychotherapeutic approaches and techniques were found. A total of seven trials provided sufficient data for inclusion in the comparison between CBT and controls. No trials compared psychodynamic psychotherapy with controls. Based on five trials (153 participants), cognitive behavioural therapy was more effective than waiting list controls (WMD −9.85, 95% CI −11.97 to −7.73). Only three small trials compared psychodynamic therapy with CBT, with no significant difference in treatment effect indicated between the two types of psychotherapeutic treatment. Based on three trials with usable data, CBT was superior to active control interventions when using the Hamilton Depression Rating Scale (WMD −5.69, 95% CI −11.04 to −0.35), but equivalent when using the Geriatric Depression Scale (WMD −2.00, 95% CI −5.31 to 1.32). Authors' Conclusions: Only a small number of studies and patients were included in the meta-analysis. If taken on their own merit, the findings do not provide strong support for psychotherapeutic treatments in the management of depression in older people. However, the findings do reflect those of a larger meta-analysis that included patients with broader age ranges, suggesting that CBT may be of potential benefit.
Depression and Bipolar Support Alliance Consensus Statement on the Unmet Needs in Diagnosis and Treatment of Mood Disorders in Late Life
Charney DS, Reynolds CF 3rd, Lewis L, Lebowitz BD, Sunderland T, Alexopoulos GS, Blazer DG, Katz IR, Meyers BS, Arean PA, Borson S, Brown C, Bruce ML, Callahan CM, Charlson ME, Conwell Y, Cuthbert BN, Devanand DP, Gibson MJ, Gottlieb GL, Krishnan KR, Laden SK, Lyketsos CG, Mulsant BH, Niederehe G, Olin JT, Oslin DW, Pearson J, Persky T, Pollock BG, Raetzman S, Reynolds M, Salzman C, Schulz R, Schwenk TL, Scolnick E, Unutzer J, Weissman MM, Young RC; Depression and Bipolar Support Alliance.
Archives of General Psychiatry 2003 7; 60( 7): 664– 72
Objectives: To review progress made during the past decade in late-life mood disorders and to identify areas of unmet need in health care delivery and research. Participants: The Consensus Development Panel consisted of experts in late-life mood disorders, geriatrics, primary care, mental health and aging policy research, and advocacy. Evidence: (1) Literature reviews addressing risk factors, prevention, diagnosis, treatment, and delivery of services and (2) opinions and experiences of primary care and mental health care providers, policy analysts, and advocates. Consensus Process: The Consensus Development Panel listened to presentations and participated in discussions. Workgroups considered the evidence and prepared preliminary statements. Workgroup leaders presented drafts for discussion by the Consensus Development Panel. The final document was reviewed and edited to incorporate input from the entire Consensus Development Panel. Conclusions: Despite the availability of safe and efficacious treatments, mood disorders remain a significant health care issue for the elderly and are associated with disability, functional decline, diminished quality of life, mortality from comorbid medical conditions or suicide, demands on caregivers, and increased service utilization. Discriminatory coverage and reimbursement policies for mental health care are a challenge for the elderly, especially those with modest incomes, and for clinicians. Minorities are particularly underserved. Access to mental health care services for most elderly individuals is inadequate, and coordination of services is lacking. There is an immediate need for collaboration among patients, families, researchers, clinicians, governmental agencies, and third-party payers to improve diagnosis, treatment, and delivery of services for elderly persons with mood disorders.
Given space limitations and varying reprint permission policies, not all of the influential publications the editors considered reprinting in this issue could be included. This section contains abstracts from additional articles the editors deemed well worth reviewing.
