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Introduction: Patients with Major Depressive Disorder (MDD) referred for electroconvulsive therapy (ECT) have poorer Health Related Quality of Life (HRQOL), compared with other patients with MDD, but ECT is associated with significant and durable improvement in HRQOL. However, no prior research has focused exclusively on elderly patients with MDD receiving ECT., Methods: HRQOL data from 240 depressed patients over the age of 60 was measured with the Medical Outcomes Study Short Form 36 (SF-36). The SF-36 was measured before and after a course of acute ECT. Predictors of change in HRQOL scores were identified by generalized linear modeling., Results: At baseline, participants showed very poor HRQOL. After treatment with ECT, the full sample showed marked and significant improvement across all SF-36 measures, with the largest gains seen in dimensions of mental health. Across all participants, the Physical Component Summary (PCS) score improved by 2.1 standardized points (95% CI, 0.61,3.56), while the Mental Component Summary (MCS) score improved by 12.5 points (95% CI, 7.2,10.8) Compared with non-remitters, remitters showed a trend toward greater improvement in the PCS summary score of 2.7 points (95%CI, -0.45, 5.9), while the improvement in the MCS summary score was significantly greater (8.5 points, 95% CI, 4.6,12.3) in the remitters than non-remitters. Post-ECT SF-36 measurements were consistently and positively related to baseline scores and remitter/non-remitter status or change in depression severity from baseline. Objective measures of cognitive function had no significant relationships to changes in SF-36 scores., Limitations: This study's limitations include that it was an open label study with no comparison group, and generalizability is limited to elderly patients., Discussion: ECT providers and elderly patients with MDD treated with ECT can be confident that ECT will result in improved HRQOL in the short-term. Attaining remission is a key factor in the improvement of HRQOL. Acute changes in select cognitive functions were outweighed by improvement in depressive symptoms in determining the short term HRQOL of the participants treated with ECT., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Aims: To identify baseline clinical factors associated with acute treatment response in depressed older adults with bipolar disorder (BD) receiving lamotrigine., Methods: Secondary analysis of a multisite, 12-week, open-label, uncontrolled study of add-on lamotrigine in 57 adults 60 years and older with BD I or II depression. Measures included the Montgomery Asberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS). Cardiometabolic risk was measured with total serum cholesterol and the Cumulative Illness Rating Scale-Geriatric (CIRS-G) item #13 (endocrine/metabolic burden). Neurocognitive (executive) function was evaluated using the Trail Making Test., Results: Greater reduction in MADRS from baseline was associated with higher baseline cardiometabolic burden at 6 and 9 weeks and lower YMRS scores at 9 weeks. At 12 weeks, improvement in the MADRS from baseline was no longer significantly related to baseline cardiometabolic burden or YMRS scores. A longitudinal mixed model of MADRS scores corroborated these findings with a significant finding of time-by-baseline cholesterol level interaction. In a subset of participants, better baseline executive function was related to greater improvement in the MADRS at 9 weeks but not at 6 or 12 weeks. Among all participants, higher baseline YMRS scores were related to greater likelihood of dropout., Conclusions: Lamotrigine appears to work best in depressed elderly patients with BD who have high cardiometabolic risk and low level of mania. Agents like lamotrigine that act primarily on neuroprogressive pathways involving oxidative stress, neurotrophins, and inflammation may be particularly effective in individuals with BD who have significant cardiometabolic burden because of their effects on shared vulnerability factors in BD and medical illness.

Objective: Given the paucity of information available regarding standardized ratings of depression symptoms in bipolar manic states, and in particular those in older adults, we explored depression ratings in symptomatic participants in a multicenter study of treatment of bipolar I disorder in late life., Methods: Baseline data was obtained from the first 100 patients enrolled in an NIMH-funded, 9-week, randomized, double-blind RCT comparing treatment with lithium or valproate in patients of age 60 years and older with Type I Bipolar mania or hypomania. This multi-site study was conducted at six academic medical centers in the United States and enrolled inpatients and outpatients with a total Young Mania Rating Scale (YMRS) score of 18 or greater. Depressive symptoms were evaluated with the Hamilton Depression Rating Scale (HAM-D) and the Montgomery-Asberg Depression Rating Scale (MADRS). The criterion for at least moderate bipolar depressive symptoms was the European College of Neuropsychopharmacology (ECNP) Consensus Meeting definition of HAM-D 17 total score >20., Results: Eleven percent of patients had mixed symptoms defined by depression scale severity according to ECNP criterion. In the overall sample, total scores on the two depression scales were highly correlated. Total YMRS scores of this mixed symptom group were similar to the remainder of the sample., Conclusions: These preliminary findings suggest that moderate to severe depressive symptoms occur in about one in ten bipolar manic elders. Future studies are needed to further evaluate symptom profiles, clinical correlates, and treatments for bipolar older adults with combined manic and depressive symptoms., (Copyright © 2011 John Wiley & Sons, Ltd.)

Despite the importance of establishing shared scoring conventions and assessing interrater reliability in clinical trials in psychiatry, these elements are often overlooked. Obstacles to rater training and reliability testing include logistic difficulties in providing live training sessions, or mailing videotapes of patients to multiple sites and collecting the data for analysis. To address some of these obstacles, a web-based interactive video system was developed. It uses actors of diverse ages, gender and race to train raters how to score the Hamilton Depression Rating Scale and to assess interrater reliability. This system was tested with a group of experienced and novice raters within a single site. It was subsequently used to train raters of a federally funded multi-center clinical trial on scoring conventions and to test their interrater reliability. The advantages and limitations of using interactive video technology to improve the quality of clinical trials are discussed.

Background: This study investigated the relationship of executive and memory impairment to relapse, recurrence, and course of residual depressive symptoms and signs after remission of geriatric major depression., Methods: Fifty-eight elderly subjects remitted from major depression received continuation nortriptyline treatment (plasma levels 60-150 ng/mL) for 16 weeks and then were randomly assigned to either nortriptyline maintenance therapy or placebo for up to 2 years. Diagnosis was made using the Research Diagnostic Criteria and the DSM-IV criteria after an interview using the Schedule for Affective Disorders and Schizophrenia. Executive dysfunction and memory were assessed with the Dementia Rating Scale, disability and social support were rated with the Philadelphia Multiphasic Instrument, and medical burden was assessed with the Cumulative Illness Rating Scale., Results: Abnormal initiation and perseveration scores, but not memory impairment, were associated with relapse and recurrence of geriatric depression and with fluctuations of depressive symptoms in the whole group and in subjects who never met criteria for relapse or recurrence during the follow-up period. Memory impairment, disability, medical burden, social support, and history of previous episodes did not significantly influence the outcome of depression in this sample., Conclusions: Executive dysfunction was found to be associated with relapse and recurrence of geriatric major depression and with residual depressive symptoms. These observations, if confirmed, will aid clinicians in identifying patients in need of vigilant follow-up. The findings of this study provide the rationale for investigation of the role of specific prefrontal pathways in predisposing or perpetuating depressive syndromes or symptoms in elderly patients.

Serum alpha(1)-acid glycoprotein (AAG) reportedly can increase with age in the normal population, especially among women. In 33 patients with unipolar major depression or bipolar disorder, serum AAG was measured by age. The authors noted a positive association with age, particularly in depressed female patients (n=18; r(s)=0.61; P<0.01). The authors discuss implications for drug pharmacokinetics. Investigation of AAG in mood disorders needs to take age and sex into consideration.

Objective: The purpose of this study was to determine if P300 latency is prolonged in geriatric depression and if longer P300 latency and deficits in initiation and errors of perseveration in depressed elderly patients are related to risk factors for vascular disease., Method: Geriatric patients with unipolar depression (N = 43) and elderly comparison subjects (N = 24) were assessed for depressive symptoms, cognitive functions, risk factors for vascular disease, and P300 latency., Results: Depressed elderly patients had longer P300 latency than normal elderly subjects. In the depressed patients, P300 latency was related to deficits in initiation and errors in perseveration. Risk factors for vascular disease were associated not only with P300 latency but also with deficits in initiation and errors in perseveration., Conclusions: Functional impairment of the cortico-striato-pallido-thalamo-cortical pathways from vascular disease, implicated in late-life depressive disorders, may explain not only deficits in initiation and errors in perseveration but also longer P300 latency in depressed elderly patients. These results are preliminary and need further examination with brain imaging and more sensitive neuropsychological measures.

The authors describe major depression with delusions occurring for the first time in an elderly man receiving metoclopramide and review the literature concerning metoclopramide and depression.

We propose that cerebrovascular disease may predispose, precipitate, or perpetuate some geriatric depressive syndromes. The "vascular depression" hypothesis is supported by the comorbidity of depression, vascular disease, and vascular risk factors and the association of ischemic lesions to distinctive behavioral symptoms. Disruption of prefrontal systems or their modulating pathways by single lesions or by an accumulation of lesions exceeding a threshold are hypothesized to be central mechanisms in vascular depression. The vascular depression concept can generate studies of clinical and heuristic value. Drugs used for the prevention and treatment of cerebrovascular disease may be shown to reduce the risk for vascular depression or improve its outcomes. The choice of antidepressants in vascular depression may depend on their effect on neurologic recovery from ischemic lesions. Research can clarify the pathways to vascular depression by focusing on the site of the lesion, the resultant brain dysfunction, the presentation of depression and time of onset, and the contribution of nonbiological factors.

Objective: The purpose of this study was to examine whether the brainstem evoked responses of geriatric depressed patients with vascular disease show greater changes in wave V latency after increased stimulation than do responses of geriatric depressed patients without vascular disease and elderly comparison subjects with and without vascular disease., Method: Geriatric patients with unipolar depression (N = 53) were recruited from a university psychiatric hospital. Elderly comparison subjects (N = 23) were recruited through advertisements. All subjects were assessed for depressive symptoms, cognitive performance, overall medical burden, vascular disease, and disability. Brainstem evoked response was elicited at stimulation rates of 11.4 and 80.0 clicks/sec., Results: The interaction between depression and vascular disease had a significant effect on change in wave V latency. This effect was synergistic, more than an additive effect. Post hoc comparisons showed that the depressed patients with vascular disease had greater changes in wave V latency that did the depressed patients without vascular disease, comparison subjects with vascular disease, and comparison subjects without vascular disease. Linear discriminant function analysis showed that 82% of the subjects with abnormal changes in wave V latency (sensitivity: 75%, specificity: 81%) could be identified on the basis of ratings for depression and vascular disease., Conclusions: Demyelination afflicting the pons and mesencephalon may explain the greater change in wave V latency for the brainstem evoked response in depressed patients with vascular disease. Further studies combining brainstem evoked response with brain imaging may determine whether depression develops only after vascular disease leads to demyelination.

Objective: The authors' goal was to examine the clinical presentation of a group of depressed elderly patients with clinically defined risk factors for vascular depression compared with a group of elderly depressed patients without such risk factors., Method: Cognitive deficits, disability, and depressive symptoms were examined in 33 consecutively recruited elderly patients defined as having vascular depression and 32 patients defined as having nonvascular depression according to their scores on the Cumulative Illness Rating Scale-Geriatrics., Results: The patients with vascular depression had greater overall cognitive impairment and disability than those with nonvascular depression. Fluency and naming were more impaired in patients with vascular depression, and they had more retardation and less agitation as well as less guilt feelings and greater lack of insight., Conclusions: The symptoms of vascular depression are consistent with lesions that may damage striato-pallido-thalamo-cortical pathways and other areas. The concept of vascular depression can provide the impetus for investigations of prevention and treatment of cerebrovascular disease and for studies of the course of vascular depression and selection of antidepressants.

Objective: The authors' purpose was to identify the relationship of disability to clinical measures that are part of a comprehensive psychiatric examination of depressed elderly patients., Method: The disability of 75 elderly inpatients and outpatients with major depression whose cognitive function ranged from normality to mild dementia was assessed with the Philadelphia Multilevel Assessment Instrument. Age at onset of depression, chronicity of depression, severity of depression, cognitive impairment, medical burden, social support and living environment were assessed with standardized instruments., Results: Impairment in instrumental activities of daily living was significantly associated with advanced age, severity of depression, and medical burden. The relationship of depressive symptoms to impairment in instrumental activities of daily living was not influenced by age or medical burden. Anxiety and depressive ideation as well as retardation and weight loss were significantly associated with impairment in instrumental activities of daily living. Interviewer-rated global disability was associated with advanced age at onset of depression, medical burden, and overall cognitive impairment. Specifically, a disturbance in initiation and perseveration was significantly related to global disability., Conclusions: Impairment in instrumental activities of daily living appears to be a relatively independent dimension of health status that is related to depressive symptoms, particularly anxiety and depressive ideation as well as retardation and weight loss. Global disability may be associated with impairment in initiation and perseveration and with late onset of depression. These findings provide a basis for studies investigating whether psychotherapy aimed at depressive ideation and rehabilitation efforts focused on instrumental activities of daily living can improve the outcome of geriatric depression.

Background: Clinical characteristics of depression, age at illness onset, medical burden, disability, cognitive impairment, lack of social support, and poor living conditions may influence the course of depression. This study investigates the timetable of recovery and the role of the above factors in predicting recovery in elderly patients with major depression., Methods: Recovery was studied in 63 elderly (age >63 years) and 23 younger patients with depression who were followed up for an average of 18.2 months (SD, 13.1 months) under naturalistic treatment conditions. Diagnosis was assigned according to Research Diagnostic Criteria after administration of the Schedule for Affective Disorders and Schizophrenia. The Longitudinal Follow-up Interval Examination was used to identify recovery., Results: The recovery rate of depressed elderly patients was similar to that of younger depressed patients. In the elderly patients, age, antidepressant treatment, age at onset, and chronicity of episode were significantly associated with time to recovery since entry. Among these parameters, late age at onset was the strongest predictor of slow recovery. In younger patients, long time to recovery was predicted by weak social support, younger age, cognitive impairment, and low intensity of antidepressant treatment. In the elderly, the intensity of antidepressant treatment began to decline within 16 weeks from entry and approximately 10 weeks prior to recovery., Conclusions: These findings challenge the view that geriatric depression has a worse outcome than depression in younger adults. However, depressed patients with onset of first episode in late life may be at higher risk for chronicity. Antidepressant treatment prescribed by clinicians may decline prior to recovery despite evidence that high treatment intensity is effective in preventing relapse.

Comorbidity of sensorineural hearing deficits and both depressive states and dementia in late life provided the rationale for this investigation. Cognitively intact geriatric major depressives (n = 43) were assessed for depressive symptoms, cognitive performance, and delusions while symptomatic, and following treatment, when audiometry was performed. Late-onset depressed patients (LOD) had more hearing deficits compared to early-onset depressives (EOD). Age at onset of depression was found to have a significant effect on Pure-Tone Thresholds for 0.5-4.0 kHz and on Word Recognition in Noise in the better ear (0.001 < p < 0.031; ANCOVA). Criteria for neural deficit were met more frequently in LODs compared to EODs, although this was attributable to the older age of LOD. Additional investigations can contribute to our understanding of the relationship between forms of hearing loss and both the course of geriatric depression and its relationship to dementia.

Objective: The goals of this longitudinal investigation were 1) to study the rate of development of irreversible dementia in elderly depressed patients with a dementia syndrome that subsided after improvement of depression and 2) to compare it with that of depressed, never-demented patients., Method: The subjects were 57 elderly patients consecutively hospitalized for major depression. At entry into the study, 23 subjects also met criteria for "reversible dementia," while 34 were without dementia. After a systematic clinical evaluation, the subjects were followed up at approximately yearly intervals for an average of 33.8 months., Results: Irreversible dementia developed significantly more frequently in the depressed group with reversible dementia (43%) than in the group with depression alone (12%). Survival analysis showed that the group with reversible dementia had a 4.69-times higher chance of having developed dementia at follow-up than the patients with depression alone. No clinical characteristics at entry into the study were found to discriminate the subjects who developed irreversible dementia during the follow-up period from those who remained nondemented., Conclusions: These findings suggest that geriatric depression with reversible dementia is a clinical entity that includes a group of patients with early-stage dementing disorders. Therefore, identification of a reversible dementia syndrome is an indication for a thorough diagnostic workup and frequent follow-ups in order to identify treatable neurological disorders.

Brain computed tomography (CT) scans were performed in hospitalized geriatric patients with major depression (n = 45) or primary degenerative dementia (n = 21). Depressed patients with onset of illness at age 60 years or older (n = 32) had greater ventricular size than geriatric depressives with earlier age of illness onset (n = 13). CT parameters of late-onset depressives were comparable to those of patients with primary degenerative dementia. However, early-onset geriatric depressives had significantly smaller ventricles and less sulcal widening than demented patients. The findings suggest that late-onset depression may have a stronger association with neurological dementing disorders than early-onset depression.

Performance on a verbal memory task and affective state were assessed in geriatric major depressives before and during 6 weeks of treatment with nortriptyline (NT) in a fixed-dose design study. Higher plasma NT concentration was associated with poorer free recall but better affective outcome. In contrast, higher plasma Z-10-hydroxynortriptyline (Z-10-OH-NT) concentration was associated with more efficient free recall. Concentration-effect relationships were noted in patients later classified as cognitively unimpaired using the Dementia Rating Scale after optimal treatment, rather than in those with residual cognitive impairment.

Plasma concentrations of nortriptyline (NT) and of unconjugated E-10-hydroxynortriptyline (E-10-OH-NT) were measured under steady-state conditions in elderly (60 yr and older) and young adult (40 yr and younger) patients treated with NT. The two groups received equivalent doses of NT. Plasma NT concentrations of the two groups did not differ, but plasma E-10-OH-NT concentrations were higher in the elderly. The plasma E-10-OH-NT/NT ratios were twice as high in the elderly group. Plasma E-10-OH-NT/NT ratios varied 2000% between individuals in the elderly group but were stable within individuals. Plasma E-10-OH-NT/NT ratios correlated positively but weakly with serum creatinine concentrations.

"I don't know" responses were recorded during administration of the Mini-Mental State Examination in elderly patients with primary degenerative dementia and primary major depression. More "I don't know" responses were given by patients with degenerative dementia; however, demented patients did not differ overall from depressives in the proportion of Not Correct responses consisting of "I don't know" responses. These responses were positively correlated with age and with Hollingshead education and social class scores in depressives but not in demented patients. A higher proportion of Not Correct responses consisting of "I don't know" responses needs to be demonstrated in depressive pseudomentia than in degenerative dementia if this clinical sign is to be used in helping to differentiate the two disorders.

The Cornell Scale for Depression in Dementia is introduced. This is a 19-item clinician-administered instrument that uses information from interviews with both the patient and a nursing staff member, a method suitable for demented patients. The scale has high interrater reliability (kw = 0.67), internal consistency (coefficient alpha: 0.84), and sensitivity. Total Cornell Scale scores correlate (0.83) with depressive subtypes of various intensity classified according to Research Diagnostic Criteria.

Among 18 elderly depressed patients given ECGs before and during nortriptyline treatment, plasma E-10-hydroxynortriptyline and the sum of E-10-hydroxynortriptyline and nortriptyline distinguished the group with conduction/repolarization effects. Plasma nortriptyline, age, drug dose, and baseline cardiovascular status did not.

Despite studies in the early literature showing that ECT may lead to CNS bleeding, it is unclear whether unmodified ECT increases the risk for hemorrhage in patients taking anticoagulants. The authors report two cases of depressed patients who required ECT while on coumarin derivatives. Both patients were switched to heparin. Heparin's short duration of action allowed temporary discontinuation 6-8 hours prior to each ECT with return of coagulation function close to normal when the stimulus was administered. No complications were observed in any of the patients. The authors believe that this technique minimizes any possible risks from ECT in patients on anticoagulants.

Recent advances in the methodology of longitudinal investigations have permitted the identification of predictors of chronicity and relapse of depression. However, findings from mixed-age populations may not be directly applicable to geriatric depression. The effects of medical illness, cognitive dysfunction, and neuroradiological abnormalities on the outcome of geriatric depression merit further evaluation. Late-onset depression requires special attention, since medical and neurological disorders may be particularly important factors in these cases.

The Cornell scale is a 19-item clinician-administered scale of depression that uses information from interviews with both patients and their caregivers. The Cornell scale has been validated in demented patients. In this study, the Cornell scale was psychometically tested in nondemented geriatric subjects by administering it to 15 depressed patients, 15 patients with other psychiatric diagnoses, and 15 normal control subjects. The Cornell scale had high interrater reliability (Cohen's kappa = 0.74), internal consistency (Kuder-Richardson's coefficient = 0.98), and sensitivity, and correlated significantly (Spearman's r = 0.81) with Research Diagnostic Criteria psychiatric diagnoses associated with various intensity of depression. To our knowledge, the Cornell scale is the only depression-rating instrument that has been validated in both demented and nondemented geriatric subjects.

The authors studied platelet MAO activity in psychiatrically hospitalized geriatric patients with depression and dementia. Platelet MAO activity was higher in demented patients with and without depression and in depressed patients with reversible dementia than in nondemented depressed patients. The data suggest that abnormally high platelet MAO activity may reflect a predisposition to the development of a dementia syndrome.

Platelet monoamine oxidase (MAO) activity was assayed in 38 elderly depressed women and 16 matched controls. The depressed women whose illness began at age 55 or earlier (N = 19) had significantly lower MAO activity than patients with later onset (N = 19) or controls.

Depression with reversible dementia occurs frequently in the elderly and may be a diagnostic problem. The 1-mg dexamethasone suppression test (DST) was performed in 175 elderly psychiatric patients. Abnormal DSTs occurred in both patients with primary degenerative dementia (n = 43, 34.9%) and those with major depression without cognitive dysfunction (n = 59, 66.1%). This finding suggests the presence of common hypothalamic abnormalities in these two disorders. There was no difference in the incidence of abnormal DSTs among depressives with a reversible dementia (n = 28, 78.6%), cognitively intact depressives (n = 59, 66.2%), and depressives who also had primary degenerative dementia (n = 24, 70.8%). An abnormal DST is not clinically useful in predicting the outcome of dementia in depressed patients with cognitive dysfunction.

Clinical and biologic studies of geriatric depression are reviewed to evaluate the role of age of onset as a distinguishing parameter. The findings suggest that late-onset depressives have a different presentation, more frequent relapses, and a greater association with medical disorders, dementia, and aging-related biologic changes than early-onset geriatric depressives. Careful clinical evaluation and follow-up of late-onset depressives are suggested. Longitudinal investigations of geriatric depressed patients are needed in order to study the frequency and time of occurrence of various clinical outcomes and identify predictors of outcome in late- and early-onset geriatric depression.

The relationship between personality traits and late-life depression is not well established. The Personality Disorder Examination (PDE), a recently developed structured interview for diagnosing DSM-III-R* personality disorders, has provided a methodological advance for studies in this area. The PDE was administered to 36 cognitively intact elderly individuals. The sample consisted of 21 patients who had recovered from depression and 15 normal volunteers. Two of the patients met DSM-III-R criteria for personality disorder according to the PDE. The patient group received higher scores on PDE items related to each personality diagnosis (P less than .01) except antisocial personality disorder. These preliminary data suggest that elderly patients with a history of major depression have more lifetime personality dysfunction than normal elderly individuals, although no specific pattern could be identified.

In geriatric, depressed inpatients treated with nortriptyline (NT), total unconjugated plasma concentrations of the Z isomer of the 10-hydroxylated metabolite (10-OH-NT) were determined simultaneously with concentrations of the E isomer by high-performance liquid chromatography. Z-10-OH-NT concentrations averaged 14% of E-10-OH-NT concentrations.

Geriatric inpatients with major depression received nortriptyline for 4 weeks. Plasma E-10-hydroxynortriptyline concentrations were correlated positively with residual Hamilton depression ratings and negatively with changes in ratings.

The effect of oral clonidine challenge on cortisol secretion was evaluated in seven patients with primary degenerative dementia and in seven patients with major depression. Postclonidine cortisol levels were decreased in all depressed patients and in demented patients with hypercortisolemia at baseline. Demented patients with normal cortisol levels at baseline developed increased post-clonidine cortisol levels. These preliminary findings suggest differences in noradrenergic regulation of cortisol secretion among patients with primary degenerative dementia.