Mark J. Rapoport

Efficacy and Safety of Antidepressants for Treatment of Depression in Alzheimer's Disease: A Metaanalysis

Objective: Depression in patients with Alzheimers disease (AD) is common (15% to 63%) and is associated with significant morbidity and increased mortality. Our objective was to quantitatively summarize the data on the efficacy and safety of antidepressant treatment for depression complicating AD. Method: We performed a metaanalysis of randomized, double-blind, placebo-controlled trials of antidepressants with a database search of the English literature (up to 2006) and a manual search of references in the retrieved articles. We extracted the proportion of subjects who responded and remitted, experienced adverse events (AEs), discontinued treatment due to AEs, or discontinued treatment for any reason. Cognition scores were also extracted. Results: We included 5 studies, which involved 82 subjects treated with antidepressants and 83 subjects who received placebo treatment. Antidepressants were superior to placebo for both treatment response (odds ratio [OR] 2.32; 95% confidence interval [CI], 1.04 to 5.16) and remission of depression (OR 2.75; 95%CI, 1.13 to 6.65). There were no significant differences between the 2 groups for change in cognition (weighted mean difference –0.71, 95%CI, –3.20 to 1.79), overall dropouts (OR 0.70; 95%CI, 0.29 to 1.66) or dropout due to AEs (OR 1.41; 95%CI 0.36 to 5.54). The numbers needed to treat for one additional AD patient to respond to antidepressant treatment were 5 (95%CI, 3 to 59) and 5 (95%CI, 2 to 24) for remission of depression. Conclusions: Antidepressant treatment for depression in AD is efficacious, with rates of discontinuation that are comparable to placebo. Nonetheless, clinicians must be vigilant regarding the potential side effects of antidepressants in this population.

Efficacy and Feasibility of Nonpharmacological Interventions for Neuropsychiatric Symptoms of Dementia in Long Term Care: A Systematic Review

BACKGROUND Nonpharmacological therapies are often recommended as a first-line treatment for neuropsychiatric symptoms (NPS) of dementia in long term care (LTC); however, little is known about which nonpharmacological interventions are most effective for NPS in LTC or the feasibility of interventions, given the availability of resources in typical LTC environments. METHODS We searched the electronic databases MEDLINE, EMBASE, PsychINFO (1980-2010), the Cochrane Library, and Google Scholar using keywords and medical subject headings for randomized, controlled trials evaluating nonpharmacological interventions for NPS conducted in LTC settings. Change in severity of NPS symptoms was evaluated through the NPS outcomes measures reported in studies. We assessed study quality and described the feasibility of interventions based on various aspects of study design. RESULTS A total of 40 studies met inclusion criteria. Sixteen (40%) of 40 included studies reported statistically significant results in favor of nonpharmacological interventions on at least one measure of NPS. These interventions included staff training in NPS management strategies, mental health consultation and treatment planning, exercise, recreational activities, and music therapy or other forms of sensory stimulation. Many of the studies had methodological limitations that placed them at potential risk of bias. Most interventions (n = 30, 75%) required significant resources from services outside of LTC or significant time commitments from LTC nursing staff for implementation. CONCLUSIONS There are several nonpharmacological interventions that may be effective for NPS in LTC, although there are a limited number of large-scale, high-quality studies in this area. The feasibility of some interventions will be limited in many LTC settings and further research into practical and sustainable interventions for NPS in LTC is required to improve usage of these important treatments.

Pharmacological treatments for neuropsychiatric symptoms of dementia in long-term care: a systematic review.

Background: Medications are frequently prescribed for neuropsychiatric symptoms (NPS) associated with dementia, although information on the efficacy and safety of medications for NPS specifically in long-term care (LTC) settings is limited. The objective of this study was to provide a current review of the efficacy and safety of pharmacological treatments for NPS in LTC. Methods: We searched MEDLINE, EMBASE, PsychINFO, and the Cochrane Library for randomized controlled trials comparing medications with either placebo or other interventions in LTC. Study quality was described using the Cochrane collaboration risk of bias tool. The efficacy of medications was evaluated using NPS symptom rating scales. Safety was evaluated through rates of trial withdrawals, trial withdrawals due to adverse events, and mortality. Results: A total of 29 studies met inclusion criteria. The most common medications evaluated in studies were atypical antipsychotics (N = 15), typical antipsychotics (N = 7), anticonvulsants (N = 4), and cholinesterase inhibitors (N = 3). Statistically significant improvements in NPS were noted in some studies evaluating risperidone, olanzapine, and single studies of aripiprazole, carbamazepine, estrogen, cyproterone, propranolol, and prazosin. Study quality was difficult to rate in many cases due to incomplete reporting of details. Some studies reported higher rates of trial withdrawals, adverse events, and mortality associated with medications. Conclusions: We conclude that there is limited evidence to support the use of some atypical antipsychotics and other medications for NPS in LTC populations. However, the generally modest efficacy and risks of adverse events highlight the need for the development of safe and effective pharmacological and non-pharmacological interventions for this population.

Predictors of driving cessation in mild-to-moderate dementia

Background: Although physicians in most provinces are mandated to report patients whose driving ability is impaired by illness, little is known about dementia-related factors associated with driving cessation. The purpose of our study was to explore factors that may affect the likelihood of driving cessation in a sample of elderly, community-dwelling patients with dementia. Methods: A 3-year prospective study, the Canadian Outcomes Study in Dementia (COSID) has enrolled 883 patients with mild-to-moderate dementia at 32 centres across Canada. Assessment tools included the Mini-Mental State Examination (MMSE) for cognition, the Global Deterioration Scale (GDS) for staging (severity), the Functional Autonomy Measurement System (SMAF) for function, and the Neuropsychiatric Inventory (NPI) for behaviour. Factors associated with the decision to quit driving after the baseline assessment were tested with Cox survival analysis. Results: Of 719 subjects who were or had been drivers, 203 (28.2%) were still driving at baseline. Over an observation period that averaged 23 months, 97 (48.5%) of 200 patients quit driving. Factors predictive of driving cessation included GDS (hazard ratio [HR] 1.68, 95% confidence interval [CI] 1.15–2.45), MMSE score (HR 0.90, 95% CI 0.83–0.97) and NPI findings (HR 1.63 for presence of ≥ 3 behaviours, 95% CI 1.01–2.62). Among the NPI behaviours, when they were analyzed separately, agitation led to a decreased likelihood of driving cessation (p = 0.019), whereas apathy (p = 0.031) and hallucinations (p = 0.050) led to an increased likelihood. Interpretation: Cognitive impairment and behaviours such as agitation, apathy and hallucinations were significant predictors of driving cessation in patients with a mild to moderate degree of dementia. These findings should be considered when one counsels patients and their families.

Relationship of psychosis to aggression, apathy and function in dementia.

Psychosis has been associated with aggression in dementia, but the nature of this relationship has been unclear. There has been very little research into the relations between apathy and functional status to psychosis in dementia. The purpose of this study is to investigate the relationship between psychosis and aggression, apathy, and functional status in outpatients with dementia.

Depression following traumatic brain injury: epidemiology, risk factors and management.

It is important for clinicians to recognize major depression following traumatic brain injury (TBI) because of its association with poor global and psychosocial outcome, postconcussive symptoms and cognitive deficits. The purpose of this review is to provide an up-to-date selective review of the current understanding of epidemiology, risk factors and management of major depression following TBI. Many studies of prevalence of depression following TBI have not used accepted structured criteria for the diagnoses, but those that did found wide ranges of rates, from 17% to 61%. The risk factors for development of depression following TBI are poorly understood, but past psychiatric history, frontal lesions and atrophy, and family dysfunction have been shown in more than one study to play important roles. There are few controlled trials of the treatment of major depression in patients with TBI using accepted diagnostic criteria for major depression, as well as defined criteria for response and remission. As such, it is important for clinicians to use best practice guidelines for the treatment of major depression in the absence of TBI.

Outcome following traumatic brain injury in the elderly: a critical review.

Background: The elderly are at risk for traumatic brain injury (TBI), but their outcome following these injuries remains unclear. Objective: This paper critically reviews research done to date on cognitive and functional outcome following TBI in the elderly. Methods: MEDLINE and PSYCHLIT databases going back to 1965 were searched. Results: Studies suggest that TBI results in adverse cognitive and functional outcomes in the elderly. There is uncertainty as to whether TBI is a significant risk factor for Alzheimers disease (AD). Methodological problems in these studies include selection bias, small samples, retrospective analyses, and, particularly, the failure to address the role of pre-morbid functioning. These problems limit the strength of the outcome studies, and may account for the equivocal findings on AD risk. Conclusions: It is premature to conclude from the published research to date that the elderly have a uniformly poor outcome following TBI. Directions for further research are suggested.BACKGROUND The elderly are at risk for traumatic brain injury (TBI), but their outcome following these injuries remains unclear. OBJECTIVE This paper critically reviews research done to date on cognitive and functional outcome following TBI in the elderly. METHODS MEDLINE and PSYCHLIT databases going back to 1965 were searched. RESULTS Studies suggest that TBI results in adverse cognitive and functional outcomes in the elderly. There is uncertainty as to whether TBI is a significant risk factor for Alzheimers disease (AD). Methodological problems in these studies include selection bias, small samples, retrospective analyses, and, particularly, the failure to address the role of pre-morbid functioning. These problems limit the strength of the outcome studies, and may account for the equivocal findings on AD risk. CONCLUSIONS It is premature to conclude from the published research to date that the elderly have a uniformly poor outcome following TBI. Directions for further research are suggested.

Age and Major Depression After Mild Traumatic Brain Injury

OBJECTIVE The authors investigated the relationship between age and major depression in the acute period following mild traumatic brain injury (TBI). METHODS Patients with mild TBI (N=210) were assessed for the presence of major depression with the Structured Clinical Interview for DSM-IV. RESULTS Older patients (age 60-plus) had lower rates of major depression than younger patients. CONCLUSION Older patients seem to be relatively resilient to major depression shortly after mild TBI.

An open-label study of citalopram for major depression following traumatic brain injury.

Major depression is associated with substantial psychosocial dysfunction and post-concussive symptomatology following traumatic brain injury (TBI). Studies to date of anti—depressant treatment for major depression post-TBI have been limited by small sample size. The goal of the present study is to examine the rates of response and remission associated with citalopram treatment for major depression following traumatic brain injury. Subjects with major depression following mild-to moderate TBI were treated with open-label citalopram with a starting dose of 20 mg/day to a maximum of 50 mg/day for either 6 weeks (n = 54) or 10 weeks (n = 26). The Hamilton Depression Rating Scale (HAMD) was used to assess depression severity. Response was defined by a 50% reduction in HAMD score, and remission was defined by a HAMD score of ≤7. The mean HAMD at baseline and 6 weeks were 23.66 (SD 6.8) and 16.30 (SD 9.3), respectively (t[53] = 7.157, p < 0.0001). The mean HAMD at 10 weeks was 12.96 (SD 7.9) (t[25] = 7.323, p < 0.0001). At 6 weeks, 54 subjects were assessed and 27.7% responded with 24.1% in remission. At 10 weeks, 26 subjects were assessed and 46.2% responded with 26.9% in remission. The response rate in the present sample was substantially lower than previously reported for patients with TBI, but comparable to the results of the largest effectiveness trial of citalopram for general out-patients with major depression in the absence of TBI.

Diagnosis and management of pathological laughter and crying.

Patients with various neurologic disorders exhibit exaggerated or inappropriate episodes of laughter, crying, or both without an apparent motivating stimulus or in response to stimuli that would not have elicited such an emotional response before the onset of the underlying disease. During these episodes, patients have difficulty controlling their emotional expression according to the contextual information. In contrast, patients with mood disorders have a pervasive and sustained change in their emotional experience and thus exhibit spells of laughter or crying because of an underlying mania or depression. This article focuses on the clinical presentation, diagnosis, prevalence, and proposed pathophysiological mechanisms of and available treatment options for this clinical phenomenon.