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Biomedical subjects

Charles F Reynolds

Publications and source records attributed to Charles F Reynolds.

At least 19 recordsLinked to original sources

Using trajectories from a bivariate growth curve as predictors in a Cox regression model.

An important research objective in most psychiatric clinical trials of maintenance treatment is to find predictors of recurrence of illness. In those trials, patients are first admitted into an open treatment period also called acute treatment. If they respond to the treatment and are considered to have stable remission from the illness, they enter the second phase of the trial where they are randomized into different arms of the 'maintenance treatments'. Often, more than one response variable is measured longitudinally in the acute treatment phase to monitor treatment responses. Trajectories of these response measures are believed to have predictive ability for recurrences in the maintenance phase of the trial. By using a bivariate growth curve from two such longitudinal measures, we developed a method to use the estimated trajectories of each subject in a Cox regression model to predict recurrence in the maintenance phase. To adjust for the parameter estimation errors, we applied a full likelihood approach based on the conditional expectations of the predictors. Simulation studies indicate that the estimation error corrected estimators for the Cox model parameters are less biased when compared to the naive regression estimators without accounting for these errors. The uniqueness of this method lies in estimating trajectories from bivariate unequally spaced longitudinal response measures. An illustrative example is provided with data from a maintenance treatment trial for major depression in an elderly population. Visual Fortran 90 programs were developed to implement the algorithm.

Aged↗

Expanding the usefulness of Interpersonal Psychotherapy (IPT) for depressed elders with co-morbid cognitive impairment.

BACKGROUND: The utility of Interpersonal Psychotherapy (IPT) has been documented as a maintenance treatment for late life depression as mono-therapy or in combination with antidepressant medication. Late life depression, however, is frequently co-morbid with declining memory or other cognitive abilities such that the usefulness of one-to-one psychotherapies is called into question for this subgroup. Additionally, concerned caregivers often accompany these patients to request help and their role in the presenting symptoms and in their potential resolution must also be addressed by any successful psychotherapy in this population. OBJECTIVES: To explore ways in which IPT could be modified to better serve the particular presentation and needs of depressed elders with cognitive decline along with their caregivers. METHODS: Various modifications of traditional IPT techniques were experimented with and refined in our collaborative late life research center using regular group supervision and feedback from patients and their caregivers. RESULTS: A key component of these modifications involves the integration of the caregiver into the treatment process in flexible ways that recognize their own role transition that is taking place simultaneously with that of the patient's role transition from a greater to a lesser functional state. Other techniques for resolving role conflicts, particularly those directly involving care issues for the patient, are also delineated. These modifications are collectively referred to as IPT-CI for cognitive impairment. A brief case vignette is presented. CONCLUSION: The modifications outlined in this communication reflect an evolving work-in-progress and serve as a framework for the future development of a manual of guidelines to assist healthcare personnel to optimally treat this population and their caregivers.

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Onset of depression in elderly persons after hip fracture: implications for prevention and early intervention of late-life depression.

OBJECTIVES: To identify predictors of onset of major depressive disorder (MDD) and of depressive symptoms in subjects who suffered a hip fracture. DESIGN: Prospective naturalistic study. SETTING: University of Pittsburgh Medical Center-Shadyside, a large urban hospital in Pittsburgh, Pennsylvannia. PARTICIPANTS: One hundred twenty-six elderly patients who received surgical fixation for hip fracture and who were not experiencing a major depressive episode at the time of the fracture; severely cognitively impaired persons were excluded. MEASUREMENTS: Subjects were evaluated at the time of hospital discharge using a battery of clinical measures (including apathy measured using the Apathy Evaluation Scale (AES), delirium, cognitive measures, social support, and disability level). Depression was assessed at the end of the surgical stay, 2 weeks later, and then monthly for 6 months, using the Hamilton Rating Scale for Depression (Ham-D) to evaluate symptomatology and the Primary Care Evaluation of Mental Disorders to evaluate diagnosis of MDD. RESULTS: Eighteen of 126 subjects (14.3%) developed MDD after hip fracture. Of these, 11 developed MDD by the end of the hospitalization, and seven developed MDD between 2 and 10 weeks later. Logistic regression showed that baseline apathy score, as measured using the AES, was the only clinical measure associated with the development of MDD (odds ratio=1.09, 95% confidence interval=1.03-1.16, P=.003); 46.2% of those with high AES scores developed MDD, versus 10.9% of those with lower scores. In contrast, cognitive variables, delirium, disability after hip fracture, and other factors related to the fracture (e.g., fracture type) were not associated with MDD. A repeated-measures analysis with Ham-D over time as a dependent variable generally confirmed these findings; depressive symptoms were highest immediately after the fracture, and apathy and delirium scores were associated with higher depressive symptom levels. CONCLUSION: The onset of MDD is common after hip fracture, and the greatest period of risk is immediately after the fracture. Individuals with clinical evidence of apathy are at high risk for developing MDD, and evaluation and close follow-up of such individuals is warranted. However, further research is needed to examine other candidate variables (e.g., clinical measures or biomarkers) to model adequately the risk for MDD after hip fracture and other disabling medical events.

Affect↗

Use of OSWALD for analyzing longitudinal data with informative dropout.

OSWALD (Object-oriented Software for the Analysis of Longitudinal Data) is flexible and powerful software written for S-PLUS for the analysis of longitudinal data with dropout for which there is little other software available in the public domain. The implementation of OSWALD is described through analysis of a psychiatric clinical trial that compares antidepressant effects in an elderly depressed sample and a simulation study. In the simulation study, three different dropout mechanisms: completely random dropout (CRD), random dropout (RD) and informative dropout (ID), are considered and the results from using OSWALD are compared across mechanisms. The parameter estimates for ID-simulated data show less bias with OSWALD under the ID missing data assumption than under the CRD or RD assumptions. Under an ID mechanism, OSWALD does not provide standard error estimates. We supplement OSWALD with a bootstrap procedure to derive the standard errors. This report illustrates the usage of OSWALD for analyzing longitudinal data with dropouts and how to draw appropriate conclusions based on the analytic results under different assumptions regarding the dropout mechanism.

Humans↗

A fully automated method for quantifying and localizing white matter hyperintensities on MR images.

White matter hyperintensities (WMH), commonly found on T2-weighted FLAIR brain MR images in the elderly, are associated with a number of neuropsychiatric disorders, including vascular dementia, Alzheimer's disease, and late-life depression. Previous MRI studies of WMHs have primarily relied on the subjective and global (i.e., full-brain) ratings of WMH grade. In the current study we implement and validate an automated method for quantifying and localizing WMHs. We adapt a fuzzy-connected algorithm to automate the segmentation of WMHs and use a demons-based image registration to automate the anatomic localization of the WMHs using the Johns Hopkins University White Matter Atlas. The method is validated using the brain MR images acquired from eleven elderly subjects with late-onset late-life depression (LLD) and eight elderly controls. This dataset was chosen because LLD subjects are known to have significant WMH burden. The volumes of WMH identified in our automated method are compared with the accepted gold standard (manual ratings). A significant correlation of the automated method and the manual ratings is found (P<0.0001), thus demonstrating similar WMH quantifications of both methods. As has been shown in other studies (e.g. [Taylor, W.D., MacFall, J.R., Steffens, D.C., Payne, M.E., Provenzale, J.M., Krishnan, K.R., 2003. Localization of age-associated white matter hyperintensities in late-life depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 27 (3), 539-544.]), we found there was a significantly greater WMH burden in the LLD subjects versus the controls for both the manual and automated method. The effect size was greater for the automated method, suggesting that it is a more specific measure. Additionally, we describe the anatomic localization of the WMHs in LLD subjects as well as in the control subjects, and detect the regions of interest (ROIs) specific for the WMH burden of LLD patients. Given the emergence of large NeuroImage databases, techniques, such as that described here, will allow for a better understanding of the relationship between WMHs and neuropsychiatric disorders.

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Statistical analysis of longitudinal psychiatric data with dropouts.

Longitudinal studies are used in psychiatric research to address outcome changes over time within and between individuals. However, because participants may drop out of a study prematurely, ignoring the nature of dropout often leads to biased inference, and in turn, wrongful conclusions. The purpose of the present paper is: (1) to review several dropout processes, corresponding inferential issues and recent methodological advances; (2) to evaluate the impact of assumptions regarding the dropout processes on inference by simulation studies and an illustrative example using psychiatric data; and (3) to provide a general strategy for practitioners to perform analyses of longitudinal data with dropouts, using software available commercially or in the public domain. The statistical methods used in this paper are maximum likelihood, multiple imputation and semi-parametric regression methods for inference, as well as Little's test and index of sensitivity to nonignorability (ISNI) for assessing statistical dropout mechanisms. We show that accounting for the nature of the dropout process influences results and that sensitivity analysis is useful in assessing the robustness of parameter estimates and related uncertainties. We conclude that recording the causes of dropouts should be an integral part of any statistical analysis with longitudinal psychiatric data, and we recommend performing a sensitivity analysis when the exact nature of the dropout process cannot be discerned.

Antidepressive Agents↗

Emergence, persistence, and resolution of suicidal ideation during treatment of depression in old age.

INTRODUCTION: To determine the rate and clinical correlates of emergent, persistent, and resolved suicidal ideation during treatment of major depression in the elderly. METHODS: Based on the course of suicidal ideation before and during 12 weeks of antidepressant treatment, we classified 437 elderly patients (234 treated with paroxetine; 203 with nortriptyline) as either non-suicidal or as having "emergent", "persistent", or "resolved" suicidality. We compared the four groups on pretreatment demographic and clinical measures and with respect to depression, anxiety, and akathisia during treatment. RESULTS: Rates of emergent, persistent, and resolved suicidality were 7.8%, 12.6%, and 15.6%, respectively. Patients with persistent suicidal ideation were more likely to have recurrent depression than non-suicidal patients or patients whose suicidality resolved with treatment. At the start of treatment, patients in all three suicidal groups had lower self-esteem than non-suicidal patients. During the course of treatment, emergent suicidality was not associated with akathisia, nor did rates of emergent suicidality differ between paroxetine- and nortriptyline-treated patients. While at baseline the levels of depression and anxiety and agitation were similar in the four groups, patients with resolved suicidality had a favorable treatment response, while patients with emergent and persistent suicidality were more likely to maintain higher depression scores and had higher levels of anxiety and agitation during treatment. DISCUSSION: Emergence of suicidal ideation is not common but is clinically significant during treatment of late-life depression and may signal more difficult-to-treat-depression.

Affect↗

Outcomes of minor and subsyndromal depression among elderly patients in primary care settings.

BACKGROUND: Although depressive conditions in later life are a major public health problem, the outcomes of minor and subsyndromal depression are largely unknown. OBJECTIVE: To compare outcomes among patients with minor and subsyndromal depression, major depression, and no depression, and to examine putative outcome predictors. DESIGN: Cohort study. SETTING: Patients from primary care practices in greater New York City, and Philadelphia and Pittsburgh, Pennsylvania. PATIENTS: 622 patients who were at least 60 years of age and presented for treatment in primary care practices that provided usual care in a randomized, controlled trial of suicide prevention. Of the 441 (70.9%) patients who completed 1 year of follow-up, 122 had major depression, 205 had minor or subsyndromal depression, and 114 did not have depression at baseline. MEASUREMENTS: One year after a baseline evaluation, data were collected by using the following tools: Hamilton Depression Rating Scale, the depressive disorders section of the Structured Clinical Interview for DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, fourth edition), Charlson Comorbidity Index, Multilevel Assessment Instrument for measuring instrumental activities of daily living, Physical Component Summary of the Medical Outcomes Study Short Form-36, and Duke Social Support Index. RESULTS: Patients with minor or subsyndromal depression had intermediate depressive and functional outcomes. Mean adjusted 1-year Hamilton depression score was 10.9 (95% CI, 9.6 to 12.2) for those with initial major depression, 7.0 (CI, 5.9 to 8.1) for those with minor or subsyndromal depression, and 2.9 (CI, 1.6 to 4.2) for those without depression (P < 0.001 for each paired comparison). Compared with patients who were not depressed, those who had minor or subsyndromal depression had a 5.5-fold risk (CI, 3.1-fold to 10.0-fold) for major depression at 1 year after controlling for demographic characteristics (P < 0.001). Cerebrovascular risk factors were not associated with a diagnosis of depression at 1 year after controlling for overall medical burden. Initial medical burden, self-rated health, and subjective social support were significant independent predictors of depression outcome. LIMITATIONS: Participants received care at practices that had personnel who had been given enhanced education about depression treatment; 29.1% of participants withdrew from the study before completing 1 year of follow-up. CONCLUSIONS: The intermediate outcomes of minor and subsyndromal depression demonstrate the clinical significance of these conditions and suggest that they are part of a spectrum of depressive illness. Greater medical burden, poor subjective health status, and poorer subjective social support confer a higher risk for poor outcome.

Activities of Daily Living↗

Elevation in plasma Abeta42 in geriatric depression: a pilot study.

Elevated plasma amyloid beta 1-42 (Abeta42) level has been linked to increased risk for incident AD in cognitively-intact elderly. However, plasma Abeta levels in individuals with late-life depression (LLMD), especially those with a late age of onset of first depressive episode, who are at a particularly increased risk for Alzheimer's disease, have not been studied. We compared plasma Abeta in 47 elderly with LLMD with 35 controls and examined its relationships to age of onset of first depressive episode, antidepressant treatment (paroxetine or nortriptyline), and indices of platelet activation (platelet factor 4 and beta-thromboglobulin) and brain abnormalities. Results indicated that plasma Abeta42 levels and the Abeta42/40 ratio were elevated in the LLMD group relative to controls in the overall group analyses and in the age- and gender-matched groups. MRI data indicated that higher Abeta42/40 ratio was associated with greater severity of total white matter hyperintensity burden in LLMD. Plasma Abeta levels in LLMD were not influenced by age of onset of first depressive episode or antidepressant treatment and were not related to indices of platelet activation. Our preliminary results suggest that increased plasma Abeta42 and Abeta42/40 ratio are present in geriatric depression, and future studies should be done to confirm these findings and to determine their relationship to cognitive decline and brain abnormalities associated with LLMD.

Aged↗

Maintenance treatment of major depression in old age.

BACKGROUND: Elderly patients with major depression, including those having a first episode, are at high risk for recurrence of depression, disability, and death. METHODS: We tested the efficacy of maintenance paroxetine and monthly interpersonal psychotherapy in patients 70 years of age or older who had depression (55 percent of whom were having a first episode) in a 2-by-2, randomized, double-blind, placebo-controlled trial. Among patients with a response to treatment with paroxetine and psychotherapy, 116 were randomly assigned to one of four maintenance-treatment programs (either paroxetine or placebo combined with either monthly psychotherapy or clinical-management sessions) for two years or until the recurrence of major depression. Clinical-management sessions, conducted by the same nurses, social workers, and psychologists who provided psychotherapy, involved discussion of symptoms. RESULTS: Major depression recurred within two years in 35 percent of the patients receiving paroxetine and psychotherapy, 37 percent of those receiving paroxetine and clinical-management sessions, 68 percent of those receiving placebo and psychotherapy, and 58 percent of those receiving placebo and clinical-management sessions (P=0.02). After adjustment for the effect of psychotherapy, the relative risk of recurrence among those receiving placebo was 2.4 times (95 percent confidence interval, 1.4 to 4.2) that among those receiving paroxetine. The number of patients needed to be treated with paroxetine to prevent one recurrence was 4 (95 percent confidence interval, 2.3 to 10.9). Patients with fewer and less severe coexisting medical conditions (such as hypertension or cardiac disease) received greater benefit from paroxetine (P=0.03 for the interaction between treatment with paroxetine and baseline severity of medical illness). CONCLUSIONS: Patients 70 years of age or older with major depression who had a response to initial treatment with paroxetine and psychotherapy were less likely to have recurrent depression if they received two years of maintenance therapy with paroxetine. Monthly maintenance psychotherapy did not prevent recurrent depression. (ClinicalTrials.gov number, NCT00178100.).

Aged↗

Social inequalities in response to antidepressant treatment in older adults.

CONTEXT: We examined the relationship between socioeconomic status and response to treatment for depression among older adults. METHODS: Secondary analysis of pooled data from the open-label phase of 2 National Institute of Mental Health-funded clinical trials of nortriptyline hydrochloride or paroxetine combined with interpersonal psychotherapy (N = 248). We used Cox proportional hazards regression analyses to examine the association between socioeconomic status, indexed by census tract median annual household income and the subject's educational attainment, and treatment response and remission according to the Hamilton Depression Rating Scale. The association between socioeconomic status and suicidality or depressed mood reported at each week of treatment was examined using repeated-measures generalized logit models. RESULTS: Subjects residing in middle-income census tracts were significantly more likely to respond to antidepressant treatment than subjects residing in low-income census tracts (adjusted hazard ratio, 1.80; 95% confidence interval [CI], 1.18-2.75]). Throughout the course of antidepressant treatment, subjects in the middle- and high-income census tracts were significantly less likely to report suicidal ideation (adjusted odds ratios, 0.48 [95% CI, 0.27-0.94] and 0.39 [95% CI, 0.16-0.94], respectively). No association was found between socioeconomic status and remission. CONCLUSION: Residence in a low-income census tract is associated with a less favorable course of depression among older adults receiving a combination of pharmacologic and psychosocial treatment.

Age Factors↗

Perspectives on depression, mild cognitive impairment, and cognitive decline.

CONTEXT: The public health implications of depression and cognitive impairment in late life are enormous. Cognitive impairment and late-life depression are associated with increased risk for subsequent dementia; however, investigations of these phenomena appear to be proceeding along separate tracks. OBJECTIVES AND DATA SOURCE: The National Institute of Mental Health organized the conference "Perspectives on Depression, Mild Cognitive Impairment, and Cognitive Decline" to consider how the varied perspectives might be better integrated to examine the associations among depression, mild cognitive impairment, and cognitive decline and to illuminate the common or distinct mechanisms involved in these associations. DATA SYNTHESIS: The following 2 broad questions were addressed: (1) What gaps in our knowledge have the greatest public health significance? (2) Can we more efficiently use our research dollars and participant resources to fill these gaps? Meeting participants included grantees from the National Institute of Mental Health and the National Institute on Aging and program staff from the National Institute of Mental Health, the National Institute on Aging, and the National Institute of Neurological Disorders and Stroke. CONCLUSIONS: One of the most important recommendations to emerge from the meeting discussions is for increased collaboration among clinical and epidemiological investigators whose work focuses in the area of depression with those working primarily in the area of memory disorders. Directions for future research were identified.

Aged↗

CYP2D6 genotype and venlafaxine-XR concentrations in depressed elderly.

INTRODUCTION: The elderly are at increased risk for medication-related adverse events. Recent reports indicate that venlafaxine may put the elderly at increased risk of cardio- and cerebrovascular adverse events. We investigated the relationship between the CYP2D6 polymorphism and steady-state plasma concentration of venlafaxine (VEN) and its primary metabolite o-desmethylvenlafaxine (ODV) in elderly participants receiving venlafaxine-XR for major depression in order to explore the contribution of pharmacogenetics to medication tolerability. METHODS: Forty-six elderly participants received venlafaxine-XR for the treatment of major depression. CYP2D6 genotype and steady-state plasma levels of VEN and ODV were determined. RESULTS: Sixty-five percent of participants were homozygous of the wild type (WT) allele, whereas 35% carried one or more variant alleles associated with intermediate and poor 2D6 metabolizer status. VEN concentration per unit dose was significantly higher and ODV concentration per unit dose was significantly lower in participants who carried one or more variant alleles compared to participants who were homozygous for the WT allele. The VEN and ODV concentrations per unit dose were also correlated with creatinine clearance. CYP2D6 genotype was not associated with medication associated side-effects. CONCLUSIONS: Plasma dose-corrected concentrations of VEN and ODV correlated with genetically determined CYP2D6 enzymatic activity in depressed elders treated with venlafaxine-XR. This relationship was not masked by the effects of age-related illness or polypharmacy. Future clinical application of pharmacogenetics to examine 2D6-dependent medications may help reduce the incidence of medication adverse events particularly in those elders at higher risk for medication adverse events due to impaired renal or cardiac function.

Aged↗

Age-related differences in the lifestyle regularity of seniors experiencing bereavement, care-giving, insomnia, and advancement into old-old age.

Compared to younger adults, seniors (> or = 60 yrs) often adopt a highly regular lifestyle, perhaps as an adaptive response to age-related changes in their sleep and circadian rhythms. At baseline, diary measures of lifestyle regularity (SRM-5) were obtained from 104 seniors of three separate groups. Thirty-three subjects were challenged by spousal bereavement or the need to care for a spouse at home with dementia (Challenged); 33 were suffering from formally diagnosed (DSM-IV) insomnia (Insomnia); and 38 were healthy, well-functioning older seniors in the second half of their eighth decade of life or later (Healthy Older). The objective of this study was to determine whether lifestyle regularity increased as a function of age within each of these three senior groups. Overall, age was significantly correlated with SRM-5 (r=0.41, p<0.001), with the SRM score increasing by 0.67 units/decade. The same was true for the Challenged and Insomnia groups, which also showed a significant correlation between SRM and age (Challenged: r=0.48, p<0.01; Insomnia: r=0.36, p<0.05), though with a slightly faster rate of SRM increase in the Challenged (0.95 units/decade) than Insomnia (0.55 units/decade) group. Perhaps there was no correlation between age and SRM (r=0.07, n.s.) in the Healthy Older group due to the small age range, although this group did have a higher overall SRM score than the other two groups (p<0.01). The study thus confirmed that the previously observed increase in lifestyle regularity over the adult lifespan persists into later life. This may represent an adaptive behavioral response that might be used in future therapeutic approaches.

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Preventing depression after stroke.

Mental health prevention research is an emerging and intriguing field. Preventing mental disorders is attractive as successful prevention, as it could potentially avert both emotional suffering and illness related morbidity and mortality. Several studies have looked at preventing post-stroke depression, a common complication of stroke. In this review article, we will first provide a conceptual overview of mental health prevention research. Then, we will discuss recent research supporting the prevention of depression after stroke and the likely positive effect successful prevention may have on non-psychiatric outcomes.

Depression↗

Making sense of mild cognitive impairment: a qualitative exploration of the patient's experience.

PURPOSE: The proposed dementia precursor state of mild cognitive impairment is emerging as a primary target of aging research. Yet, little is known about the subjective experience of living with a diagnosis of mild cognitive impairment. This study examines, from the patient's perspective, the experience of living with and making sense of the diagnosis. DESIGN AND METHODS: We recruited 12 older adults with amnestic or nonamnestic mild cognitive impairment from a university-based memory disorders clinic. We conducted in-home, semistructured interviews in order to elicit rich descriptions of the personal experience of having mild cognitive impairment. We used the qualitative method of grounded theory to analyze narrative data. RESULTS: Understanding and coming to terms with the syndrome, or assigning meaning, constituted a fundamental aspect of living with a diagnosis of mild cognitive impairment. This process comprised interrelated emotional and cognitive dimensions. Participants employed a range of positive, neutral, and negative phrasing in order to depict their emotional reactions to receiving a diagnosis. Cognitive representations of mild cognitive impairment included both prognosis-focused and face-value appraisals. Expectations of normal aging, personal experience with dementia, and concurrent health problems were key contextual factors that provided the backdrop against which participants assigned meaning to a diagnosis of mild cognitive impairment. IMPLICATIONS: Clinicians who disclose diagnoses of mild cognitive impairment need to be mindful of the potential for varying interpretations of the information that is conveyed. Future research needs to include systematic, longitudinal investigations of illness representation and its impact on health behaviors among individuals with mild cognitive impairment.

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What is the optimal duration of a short-term antidepressant trial when treating geriatric depression?

BACKGROUND: To determine the optimal duration of an antidepressant trial in elderly patients, the authors examined the probability of eventually responding to treatment based on early improvement. METHODS: Four hundred seventy-two elderly patients with major depression (nonpsychotic, nonbipolar) were treated under protocolized conditions for up to 12 weeks and assessed weekly with the Hamilton Rating Scale for Depression. The probability of full response after 12 weeks of treatment was calculated in patients who had not fully responded after periods of treatment that lasted for 4 to 10 weeks. RESULTS: Most of the patients who had shown a partial improvement after 4 weeks of treatment became full responders after 4 or more additional weeks of treatment. By contrast, only a few of those who were nonresponders became full responders even after up to 8 additional weeks of treatment. CONCLUSIONS: After 4 weeks of treatment, it is possible to reliably identify a subgroup of elderly patients with depression who are more likely to benefit from a change in their treatment than from a few additional weeks of treatment with the same agent.

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Methylphenidate-enhanced antidepressant response to citalopram in the elderly: a double-blind, placebo-controlled pilot trial.

OBJECTIVE: The authors evaluated the potential of methylphenidate to accelerate and enhance antidepressant response to citalopram in elderly depressed patients. METHODS: Sixteen outpatients with major depression were treated in a 10-week double-blind trial. Response was defined as a score on the Hamilton Depression Rating Scale (24-item) of less than 10. RESULTS: An accelerated response was observed by week 3 in five subjects receiving citalopram (CIT)+methylphenidate (MPH) and in none of those receiving CIT+placebo (PBO). Subjects receiving citalopram and methylphenidate showed a significant improvement in depressive symptoms compared with those on citalopram and placebo. CONCLUSION: Combined treatment with citalopram and methylphenidate appears to be a viable strategy for accelerating and enhancing antidepressant response in elderly depressed patients limited by tolerability and safety.

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