Neurophysiologic predictors of treatment response to fluoxetine in major depression.

Treatment with antidepressants is marked by heterogeneity of response; predicting individual response to any given agent remains problematic. Neuroimaging studies suggest that response is accompanied by physiologic changes in cerebral energy utilization, but have not provided useful markers at pretreatment baseline. Using quantitative EEG (QEEG) techniques, we investigated pretreatment neurophysiologic features to identify responders and non-responders to fluoxetine. In a double-masked study, 24 adult subjects with current major depression of the unipolar type were studied over 8 weeks while receiving fluoxetine (20 mg QD) or placebo. Neurophysiology was assessed with QEEG cordance, a measure reflecting cerebral energy utilization. Response was determined with rating scales and clinical interview. Subjects were divided into discordant and concordant groups based upon the number of electrodes exhibiting discordance. The concordant group had a more robust response than the discordant group, judged by lower final Hamilton Depression (HAM-D) mean score (8.0+/-7.5 vs. 19.6+/-4.7, P = 0.01) and final Beck Depression Inventory (BDI) mean score (14.0+/-9.4 vs. 27.8+/-3.7, P = 0.015), and by faster reduction in symptoms (HAM-D: 14.0+/-5.0 vs. 23.8+/-4.1, P = 0.004 at 1 week). Groups did not differ on pretreatment clinical or historical features. Response to placebo was not predicted by this physiologic measure. We conclude that cordance distinguishes depressed adults who will respond to treatment with fluoxetine from those who will not. This measure detects a propensity to respond to fluoxetine and may indicate a more general responsiveness to antidepressants.

Dementia caregiver burden: a review of the literature and guidelines for assessment and intervention.

Alzheimer's disease (AD) and other dementias are common degenerative disorders in the elderly. Most AD patients are cared for at home by family members, usually elderly spouses. Although caregiving is associated with significant psychological and physical morbidity, there are wide individual differences among caregivers in how well they adapt to caregiving demands. In addition, recent data suggest that caregiver variables can be important determinants of AD patient institutionalization and that AD patients living with highly distressed caregivers may exhibit higher frequencies of behavioral problems and agitation than those living with less distressed caregivers. Predictors of caregiver outcome, predictors of institutionalization, and the effect of the caregiver on the course and symptomatology of dementia are described. A model of assessment and intervention for the physician, referral processes, and resources for the caregiver are presented.

Brain structure and function and the outcomes of treatment for depression.

BACKGROUND: Depressed patients have a variety of brain structural alterations, the most common being atrophy and deep white-matter lesions. Alterations in brain function also are common, particularly regional decreases in cerebral metabolism and perfusion. METHOD: We review here the evidence that alterations in brain structure and function may explain some of the heterogeneity in outcomes of depression. We also report initial results suggesting that measurement of brain structure and function may help to predict outcomes of treatment for depression. Brain structure was examined using three-dimensional reconstruction and volumetric analysis of magnetic resonance imaging (MRI) scans. Brain function was examined using quantitative electroencephalography (QEEG), performed at baseline and serially during the course of treatment. QEEG measures included coherence (a measure of synchronized activity between brain regions) and cordance (a measure strongly associated with regional cerebral perfusion). RESULTS: Depressed patients have been reported to have larger volumes of white-matter lesions than controls. We have found that some types of white-matter lesions are associated with lower coherence and that subjects with low coherence had significantly poorer outcomes of treatment for depression at 2-year follow-up. Depressed subjects had low cordance at baseline, which decreased further during the course of effective treatment. Subjects who did not improve had little or no change in cordance. Changes in cordance were detected prior to the onset of clinical response, with decreases seen as early as 48 hours after the initiation of treatment in subjects who showed eventual response. CONCLUSION: These preliminary results suggest that functional imaging using QEEG may be useful for assessing, and possibly predicting, outcomes of treatment for depression.