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Management of treatment resistance in the depressed geriatric patient
Abstract
The treatment of depression in geriatric patients is challenging on all levels. Recognition, compliance, medical comorbidity, tolerance of drug regimens, and accessibility of the patient to therapy all represent major clinical problems. Treating depression in elderly, disabled patients requires patience, keen observation skills, and much flexibility. It is critical that these patients trust their physicians and have ready access if problematic side effects develop. In general, when treating patients with a history of failure to respond, the clinician should choose a medication with a tolerable side-effect profile, and persist with it as long as steady, slow gains are being made. Dosages should be maximized to clinical tolerance prior to considering switching agents or augmentation strategies. It is probably wiser to augment than switch if a partial response has been obtained. Particularly among the medically ill elderly, any "lost ground" may be very difficult to replace. All available psychosocial resources should be assessed and brought to bear productively in the treatment context. We are quite far from a full clinical understanding of "treatment resistance" in elderly depressive patients, but the eminent treatability of depression in elderly patients encourages creative exploration of treatment regimens. Rigorous, placebo-controlled studies of representative samples of elderly patients are needed to clarify the diverse interactions among the many pharmacologic agents available to treat resistant/refractory depression in the elderly.
... A deficit of knowledge on the subject of normal aging is in part reflected by the numbers of those depressed elders who commit suicide (AAGP, 2001;Blazer, 2002;Borson et al., 2001;Butler, 1993;Charney et al., 2003;Garrard et al., 1998;Hirschfeld et al., 1997;Kamholz & Mellow, 1996;Lantz, 2002;Peach et al., 2001;Pearson et al., 1997;Revicki, Simon, Chan, Katon & Heiligenstein, 1998;Roff, 2001;Satcher, 1999;Verma, 1998;Woolley, 1997;Zylstra & Steitz, 2000). The elderly have the highest suicide rates of any age group (Reynolds & Kupfer, 1999) and the rates have been rising (Gallo & Lebowitz, 1999). ...
... Aged patients, like physicians and other health care providers, falsely believe emotional dysfunction is an inevitable consequence of growing old (Blazer, 2002;Butler, 1993;Pearson et al., 1997;Satcher, 1999). These patients therefore are reluctant to initiate this topic with their primary care physicians (Blazer, 2002;Butler, 1993;Kamholz & Mellow, 1996;Woolley, 1997). Typically, the aged depressed individual perceives he is responding normally to a life situation (Hirschfeld et al., 1997;Satcher, 1999). ...
... The elderly patient presents with a complex and dynamic interplay of mental illness, disease process and psychosocial issues, all of which make co-morbidity the rule rather than the exception in geriatric practice (Alessi & Cassel, 1996;Blazer, 2002;Borson et al., 2001;Culpepper, 2002;Culpepper et al., 2003;Kamholz & Mellow, 1996;Kennedy, 2003;Klinkman, 2003;Lieberman, 2002;McLean, 2000;Pearson et al., 1997;Proctor et al., 2003;Reynolds, 2003;Reynolds & Kupfer, 1999;Rosack, 2002;Ryan et al., 2002;Satcher, 1999;Siegal, 1998;Verma, 1998). Advancing age increases the probability of medical illness, functional disability and cognitive impairment, all of which muddy the clinical picture (Alessi & Cassel, 1996;Blazer, 2002;Culpepper, 2002;Greden, 2003;Kennedy, 2003;McLean, 2000;Reynolds & Kupfer, 1999;Siegal, 1998;Verma, 1998). ...
... The APA (1990) advocates that ECT can be used regardless of age. Kamholz and Mellow (1996) recommend it as first-line therapy in the elderly and assume that it poses no special threat to a vulnerable brain, despite the evidence of harmful effects, worse outcomes, and possible increased mortality (Burke, Rubin, Zorumski, & Wetzel, 1987;Kroessler & Fogel, 1993). This recommendation clashes with the generally accepted clinical convention that the elderly are especially sensitive to biopsychiatric interventions, including low-dose medication. ...
This two-part paper exposes in a critical way the background and evidence to enable us to comprenhend the use of electroshock for different psychopathological disorders. Our aim is to find out how and why certain psychiatrists indicate this technique, some patients accept it, the health institutions endorse it, and certain scientific societies attempt to dignify it by promoting favorable attitudes among mental health professionals. The results of the literature review are presented in three areas: conceptual, historical, and scientific. Some ideas related to the use of electroshock favor the medicalization of
mental health and hinder patients’ access to appropriate psychological treatments with strong empirical support, in addition to increasing stigma. Based on data that rigorously question the effectiveness and safety of “electroconvulsive therapy” (ECT), arguments are presented for a critical positioning regarding a therapeutic option that is supposedly underutilized in mental health.
... Thus, there exists a pathway by which the neurohumoral activation secondary to severe SDB may potentiate the impact of mental illness. In individuals with depression, for example, OSAS is associated with resistance to both pharmacological and cognitive behavioral therapy [28,29]. Patients with treatmentresistant depression and Cardiovascular Disease (CVD) have a higher rate of cardiovascular events than those with less severe depression [30], and sleep researchers have wondered whether this is explained in part by the underlying inflammatory cascade from incipient OSA that characterizes all three conditions [21,31,32]. ...
Sleep-disordered breathing is common but under-diagnosed. This is concerning given the emerging empirical relationships between severe forms of sleep-disordered breathing, such as obstructive sleep apnea syndrome, and various forms of psychopathology including major depressive disorder, attention deficit hyperactivity disorder, generalized anxiety disorder, schizophrenia and post-traumatic stress disorder. Inflammatory pathways may mediate part of the relationship between sleep-disordered breathing and psychopathology, but the strength and directionality of these processes and associations remains unknown. It may be appropriate to have a heightened index of suspicion for SDB and psychopathology in individuals at higher baseline risk for their co-morbidity. Further investigation in larger, longitudinal, well-controlled studies is needed to understand the relationship of SDB and psychopathology.
... Similarly, cognitive impairment is a risk factor for depressive symptoms (Biderman, Cwikel, Fried, & Galinsky, 2002;Blazer, Burchett, & Fillenbaum, 2002) and may hinder treatment of depression in older adults (Kamholz & Mellow, 1996). As with physical illness, cognitive impairment may limit the number and type of pleasant events available to individuals. ...
... Later-life depression leads to multiple negative outcomes including increased rates of morbidity and mortality, functional impairments, medical burden, higher health service utilization, longer hospital stays, and disability. [4][5][6][7][8][9] Depression in older adults is also associated with reduced adherence to treatment for other medical conditions, diminished quality of life, and suicide in later-life. 10 -14 Later-life depression is a heterogenous syndrome; its heterogeneity is defined and/or manifested in numerous ways: age of onset, symptom presentations, response to treatment, associated comorbidities, and likely underlying etiologies. ...
... In contrast, the APA report does warn that "some elderly patients may have an increased likelihood of appreciable memory deficits and confusion during the course of treatment", although there is no suggestion that ECT poses a special threat to the vulnerable brain or cardiovascular system of the elderly. 11 In a curious twist, an article by Burke et al. 12 is listed in the bibliography of the APA report but not cited in the actual discussions of the elderly. Burke et al. found a high rate (35%) of complications among the elderly. ...
A 92-year-old woman who suffered from dementia with psychotic feature was admitted to a psychiatric ward. She refused to eat or take any medications. After 0.5 mg i.v. injection haloperidol, prolongation of QTc interval occurred in the electrocardiogram. Therefore two sessions of electroconvulsive therapy (ECT) were performed carefully after informed consent was obtained by her family. Almost no psychotic symptoms were observed after the first ECT. No cognitive side-effects were observed during and after the two ECT sessions. This demonstrates that ECT can be used as an alternative treatment when elderly dementia patients with psychotic feature cannot tolerate medication.
Depressive disorders are fairly common among older adults. These disorders can cause significant morbidity and mortality among older people. Unfortunately, depressive disorders are often misdiagnosed or underdiagnosed in this population. A detailed history, a comprehensive mental status examination, a focused physical examination, screening laboratory studies, and appropriate use of neuropsychological testing can assist with the diagnosis of depression among older adults. Available data indicates that both psychotherapy and pharmacotherapy are beneficial in the treatment of depression among older individuals. Electroconvulsive therapy (ECT) is highly effective in the treatment of depressive disorders with psychotic features, catatonic features, and agitation and among individuals who are refractory to other treatments and in situations where there is urgent need for treatment response either due to suicidal or homicidal behaviors or failure to thrive. Evidence also indicates benefits of ketamine, repetitive transcranial magnetic stimulation (rTMS), and collaborative care approaches for the treatment of depression among older adults.
This two-part paper exposes in a critical way the background and evidence to enable us to comprenhend the use of electroshock for different psychopathological disorders. Our aim is to find out how and why certain psychiatrists indicate this technique, some patients accept it, the health institutions endorse it, and certain scientific societies attempt to dignify it by promoting favorable attitudes among mental health professionals. The results of the literature review are presented in three areas: conceptual, historical, and scientific. Some ideas related to the use of electroshock favor the medicalization of mental health and hinder patients’ access to appropriate psychological treatments with strong empirical support, in addition to increasing stigma. Based on data that rigorously question the effectiveness and safety of “electroconvulsive therapy” (ECT), arguments are presented for a critical positioning regarding a therapeutic option that is supposedly underutilized in mental health
: Treatment resistant depression (TRD) significantly contributes to the morbidity and mortality associated with depression occurring in late life. Yet, depression in the elderly population remains largely under-recognised and under-treated. This paper aims to provide an overview of the contributing factors and current treatment approaches in TRD in late life. Consensus on the operational criteria for TRD is still emerging due to unresolved issues on different criteria of definition and diagnosing TRD. If there is treatment failure, a comprehensive diagnostic evaluation along with the assessment of treatment adequacy should be undertaken. Reasons for the lack of treatment response need to be adequately explored including non-compliance, misdiagnosis and co-morbid physical, psychiatric and cognitive disorders. Stabilising co-existing medical conditions as well as addressing the psychological and social issues may be necessary to achieve optimal outcome. Other strategies including increasing the dose and duration of treatment, switching antidepressant, augmentation and combination treatments, and electroconvulsive therapy (ECT) may be appropriate. There is a growing range of treatment options available including newer agents and treatment strategies that may offer improved efficacy and safety for the elderly depressed patients. However, considerable research into such treatment approaches in TRD in late life is still needed. A systematic consideration of all the treatment options with the associated risks and benefits is recommended, together with close monitoring of symptoms, progress and adverse effects.
Electroconvulsive treatment (ECT) is increasingly used in North America and there are attempts to promote its further use world-wide. However, most controlled studies of efficacy in depression indicate that the treatment is no better than placebo with no positive effect on the rate of suicide. ECT is closed-head electrical injury, typically producing a delirium with global mental dysfunction (an acute organic brain syndrome). Significant irreversible effects from ECT are demonstrated by many studies, including: (1) Inventories of autobio- graphic and current events memories before and after ECT; (2) Retrospective subjective observations on memory; (3) Autopsy studies of animals and some of humans. ECT causes severe and irreversible brain neuropathology, including cell death. It can wipe out vast amounts of retrograde memory while producing permanent cognitive dysfunction. Contemporary ECT is more dangerous since the current doses are larger than those employed in earlier clinical and research studies. Elderly women, an especially vulnerable group, are becoming the most common target of ECT. Because of the lopsided risk/benefit ratio, because it is fundamentally traumatic in nature, because so many of the patients are vulnerable and unable to protect themselves, and because advocates of ECT fail to provide informed consent to patients - ECT should be banned.
Depression and anxiety are the most common psychiatric conditions in late life. Despite their prevalence, we know relatively little about their unique manifestation in older adults. And, Although the most common intervention for late-life depression and anxiety continues to be medication, research on psychosocial interventions for late-life depression and anxiety has burgeoned in the past several years. Unfortunately, this growing body of intervention research has yet to be widely translated into improved systems of care for late-life depression. This article is one step toward synthesizing the knowledge in this growing area of research. The review of literature presents the conclusions of several meta-analyses that have reviewed psychosocial interventions for late-life depression and anxiety. In addition, intervention studies concerning the effectiveness of cognitive behavioral therapy, interpersonal therapy, reminiscence therapy, and alternative therapies with depressed and/or anxious older adults are reviewed. A brief description of various approaches to psychosocial intervention with anxious and/or depressed older adults is also presented.
There have been impressive developments in the pharmacological treatment of mood disorders in the elderly, both acute and long-term, and in the management of treatment-resistant depression. The nihilism that had prevailed previously has been replaced by cautious optimism with regard to the results of controlled trials in naturalistic settings and studies in high-risk groups, including patients with multiple medical conditions and subsyndromal states. Curr Opin Psychiatry 11:441-445. (C) 1998 Lippincott-Raven Publishers.
Depression in old age is an eminently treatable condition, with pharmacological treatments forming an important component of the effective treatment options. The evidence base addressing the effectiveness of antidepressants in older people has increased significantly in the past few years. Overall, it remains clear that antidepressants are effective in the acute treatment of major depression in old age, although some recent acute trials have failed to show superiority of active drug over placebo although there is more consistent evidence for the efficacy of continuation and maintenance antidepressant treatment. There is also reasonably consistent evidence for the use of antidepressants longer-term to prevent relapse and recurrence. More research is needed to refine best practice in the treatment of refractory depression and bipolar depression in old age.
Die klinisch-therapeutische Wahl des Antidepressivums ist nach wie vor nicht standardisiert und hängt von einer Vielzahl von
Faktoren des individuellen Verlaufs und der Präferenz des Behandlers ab. Das früher gängige Kielholz-Schema ist nicht mehr
gebräuchlich, u. a. weil es die neuen Antidepressiva nicht enthält. Nach Eruierung möglicher Ursachen der »Therapieresistenz«
und Ausschluss einer »Pseudo-Therapieresistenz«, z. B. Noncompliance, Unterdosierung, negative Arzneimittelinteraktionen,
zu kurze Therapiedauer, sollte das ausgewählte Antidepressivum möglichst unter Plasmaspiegelkontrolle (therapeutisches Drugmonitoring,
TDM) in der Dosierung optimiert werden. Als besonders potente Antidepressiva können Clomipramin sowie die dual wirksamen Substanzen
Mirtazapin und Venlafaxin gelten, bei sog. atypischen Depressionen besitzen Monoaminoxidasehemmstoffe (MAOH) eine überlegene
Wirksamkeit. Hinweise für eine gute Wirksamkeit von Clomipramin und SSRI gibt es bei zwanghaften Depressionen. Psychotische,
wahnhafte Depressionen erfordern die Kombination mit einem bevorzugt atypischen Antipsychotikum. Die Kombination verschiedener
Antidepressiva wird oft praktiziert, ohne dass hierfür ausreichende wissenschaftliche Evidenz bestünde. Hier sind vor allem
mögliche Arzneimittelinteraktionen zu beachten. Von den Augmentationsstrategien kommt der Behandlung mit Lithium die größte
Bedeutung zu. Zur Klassifizierung der Antidepressiva-Nonresponse wurde ein »Staging« (Stadieneinteilung) vorgeschlagen, aus
dem sich sinnvolle Empfehlungen für den Einsatz der verschiedenen Therapieoptionen ableiten lassen. Anzustreben ist eine Standardisierung
der Behandlungssequenzen durch Algorithmen bzw. Stufenpläne. Die Einhaltung derartiger standardisierter Behandlungsprinzipien
dürfte dazu beitragen, den Prozentsatz sog. therapieresistenter Depressionen zu minimieren.
Evidence from several clinical trials in patients with coronary heart disease suggests that depression that does not respond to treatment is associated with a particularly high risk of adverse cardiac outcomes. The purpose of this study was to determine whether obstructive sleep apnea/hypopnea syndrome (OSAHS) is associated with a poor response to antidepressant medication in patients with coronary heart disease.
This was a secondary analysis of data from a randomized, double-blind, placebo-controlled clinical trial of omega-3 fatty-acid augmentation of sertraline for depression in patients with coronary heart disease. Patients with documented coronary heart disease were recruited between May 2005 and December 2008 from cardiology practices in St Louis, Missouri, and through cardiac diagnostic laboratories affiliated with Washington University School of Medicine, St Louis, Missouri. One hundred five patients (mean age = 58 years) with coronary heart disease and current major depressive disorder (DSM-IV) were randomized to receive sertraline plus either omega-3 or placebo for 10 weeks. Cyclical heart-rate patterns associated with OSAHS were detected via ambulatory electrocardiography prior to treatment. Symptoms of depression were measured at baseline and follow-up with the Beck Depression Inventory-II (BDI-II) and the 17-item Hamilton Depression Rating Scale (HDRS-17). The primary endpoint was the BDI-II score at 10 weeks.
Thirty of the 105 patients (29%) were classified as having probable moderate to severe OSAHS on the basis of nighttime heart-rate patterns. These OSAHS patients had significantly higher scores on both the BDI-II (t = -2.78, P = .01) and the HDRS-17 (t = -2.33, P = .02) at follow-up as compared to the reference group. Adjustment for baseline depression score, treatment arm (omega-3 vs placebo), body mass index, and inflammatory markers did not change the results. Patients with OSAHS reported higher item scores at follow-up on all depressive symptoms measured with the BDI-II compared to those without OSAHS.
Obstructive sleep apnea/hypopnea syndrome is associated with a relatively poor response to sertraline treatment for depression. Future research should determine the contribution of OSAHS to the increased risk of adverse cardiac outcome associated with treatment-resistant depression.
Using a case history to illustrate key points, this article (1) highlights depression criteria, prevalence, and later-life depression presentations; (2) discusses factors contributing to later-life depression; (3) reviews the interplay between heart failure and later-life depression; and (4) suggests screening and treatment recommendations for depression in patients with heart failure.
Depression is the most prevalent functional psychiatric disorder in late life. It is associated with a high risk of mortality from comorbid medical illness and from suicide. Successful antidepressant treatment is one of the most effective ways to reduce disability, prevent morbidity, and improve quality of life in an older depressed patient. Treatment-resistant depression is a common clinical problem, reported to affect up to one-third of older depressed patients. However, published data on this clinically important topic are sparse. Available data and clinical experience indicate that many depressed patients labeled as "treatment resistant" or even "treatment refractory" are so labeled because of variables involving the diagnostic or treatment process, rather than because they suffer from a depression that is truly unresponsive to treatment. Unidentified comorbid medical or psychiatric conditions and misdiagnosis often contribute to treatment resistance. Atypical depressive symptoms, such as somatic and cognitive symptoms, and comorbid medical conditions that can themselves produce depressive symptoms often make it difficult to accurately assess antidepressant response in this age group. This often leads to inadequate pharmacotherapy, another major factor contributing to apparent treatment resistance. In older patients, as in younger patients, the selection of the right antidepressant, the right dose, and the right treatment duration constitute the treatment variables essential in ensuring optimal therapeutic response. Approach to treatment-resistant depression in the elderly involves reconsideration of the diagnosis and use of alternate therapeutic measures in a systematic way, including switching to another agent, combination therapy, and electroconvulsive therapy.
Research on treatment-resistant depression in the elderly has been limited, and recommendations for clinical management have often been extrapolated from studies using nongeriatric patients. This report describes a series of 10 elderly patients with refractory depression who were treated with nortriptyline after failing to respond to an adequate trial of a serotonin reuptake inhibitor. Seven (70%) of the patients responded to the addition or substitution of nortriptyline. All seven of the responders have remained on nortriptyline for maintenance therapy, none of whom have experienced recurrence of their depression after an average treatment duration of 1 year. Response to nortriptyline occurred in about 4 weeks in most patients. The mean daily dose of nortriptyline was 54 mg, and the mean plasma level was 97 ng/mL. Minor side effects occurred in three patients. No patients developed significant electrocardiogram changes. Nortriptyline, possibly due to its different mechanism of action, may be effective as either an adjunctive or replacement antidepressant in some cases of geriatric depression that are resistant to serotonin reuptake inhibitors.
Despite its well-established efficacy and its increasing use, electroconvulsive therapy (ECT) remains a controversial treatment. Lack of clarity in the issues related to its use in special patient populations (for example, in children, in adolescents, in pregnant women, in the elderly, and in the medically ill) often contributes to the debate about the use of ECT.
The literature on ECT use in special patient populations is reviewed, together with the commonly associated high-risk medical conditions in clinical practice. Specific reference is made in each case to the safety, tolerability, and efficacy of the procedure.
Much of the literature surveyed consists of case studies, although a few controlled trials are available. In general, ECT use in special populations is relatively safe and extremely effective. In small case series, ECT use in children and adolescents is effective but requires further systematic study. In pregnant women, ECT is very effective, and with proper medical care, it is relatively safe in all trimesters of pregnancy, as well as in the postpartum period. The frail elderly are particularly good candidates for ECT because they are often unresponsive to or intolerant of psychotropic medication. Medical conditions that should receive particular attention during a course of ECT are disorders of the central nervous system (CNS), cardiovascular, and respiratory system. With modern anesthesia techniques and careful medical management of each high-risk patient, most can successfully complete a course of ECT. The process of obtaining informed consent also requires special consideration in this group of patients because their capacity to consent to treatment may be compromised.
With careful attention to each patient's medical and anesthesia needs, ECT is an effective and relatively safe procedure in high-risk special patient populations.
A computer-based literature search of all antidepressant and electroconvulsive therapy (ECT) treatment studies published between 1995 and September 2001 was conducted. In addition, a review of published chapters, review articles, and metaanalyses was also conducted. Articles were categorized into those reporting comparative studies, those in which the therapeutic agent was not compared with another, articles about ECT, and review articles. These recent publications support the conclusions from prior reviews that antidepressants and ECT are effective and safe treatments for depressed elderly patients. Differences in efficacy and side effects appear to be slight among the various types of antidepressants. Research studies of depressed elderly increased markedly since 1995 compared with all previous years although more studies are still necessary.
Although there is evidence for the efficacy of antidepressants and for some individual and group psychotherapy interventions for depressed older adults, a significant number of these do not respond to treatment. Authors assessed the benefits of augmenting medication with group psychotherapy.
They randomly assigned 34 (largely chronically) depressed individuals age 60 and older to receive 28 weeks of antidepressant medication plus clinical management, either alone (MED) or with the addition of dialectical behavior therapy skills-training and scheduled telephone coaching sessions (MED+DBT).
Only MED+DBT showed significant decreases on mean self-rated depression scores, and both treatment groups demonstrated significant and roughly equivalent decreases on interviewer-rated depression scores. However, on interviewer-rated depression, 71% of MED+DBT patients were in remission at post-treatment, in contrast to 47% of MED patients. At a 6-month follow-up, 75% of MED+DBT patients were in remission, compared with only 31% of MED patients, a significant difference. Only patients receiving MED+DBT showed significant improvements from pre- to post-treatment on dependency and adaptive coping that are proposed to create vulnerability to depression.
Results from this pilot study suggest that DBT skills training and telephone coaching may offer promise to effectively augment the effects of antidepressant medication in depressed older adults.
In contrast to the effects seen in younger adults, depressed elderly subjects have shown more modest antidepressant responses to transcranial magnetic stimulation (TMS). We theorized that higher stimulation intensities in older depressed subjects with prefrontal atrophy might be needed to stimulate underlying cortex. In an open design with patients on stable baseline medications, we treated 18 treatment-resistant elderly depressed subjects (mean age 61.2 +/- 7.3) with 15 rTMS sessions over 3 weeks. We adjusted the delivered TMS intensity to account for MRI measured prefrontal atrophy. The skull to prefrontal cortex distance increased with age, whereas the skull to motor cortex distance did not. All subjects tolerated the higher doses well. The average intensity used was 114% of motor threshold (MT) with a range from 103-141% MT. There was an average 35% decline over the 3 weeks in HRSD scores. After 3 weeks of treatment, 27% (5/18) met response criteria (> 50% improvement), with four of these five also meeting criteria for remission (exit Hamilton Depression Score < 8). These initial pilot findings support the need for blinded studies using prefrontal TMS in an elderly population, testing whether TMS, delivered at stimulation intensities calculated to overcome atrophy, is more effective than TMS without adjusting for atrophy.
Up to a third of elderly patients with major depressive disorder are treatment resistant, yet little objective evidence is available to guide the clinician in managing these patients. We report here our experience with elderly subjects with prospectively defined treatment-resistant depression in 2 separate research studies: one entailing an augmentation strategy, the other a change to venlafaxine extended release (XR).
Fifty-three elderly subjects with major depressive disorder according to DSM-IV criteria who failed treatment with paroxetine plus interpersonal psychotherapy received 1 to 3 trials of augmentation with bupropion sustained release, nortriptyline, or lithium. Successively fewer subjects entered each sequential trial of augmentation. Twelve subjects subsequently received venlafaxine XR monotherapy. Response to treatment was defined as a 17-item Hamilton Rating Scale for Depression score of < 10 for 3 weeks.
Sixty percent of subjects (N = 32) responded to some form of augmentation, with 45% (24/53), 31% (5/16), and 43% (3/7) responding to the first, second, and third augmentation trials, respectively. The mean time to response after starting the first augmentation trial was 6.0 (SD = 5.8) weeks. Forty-two percent (N = 5) of the venlafaxine XR-treated subjects responded with the mean time to response of 6.4 (SE = 0.9) weeks. Adverse effects leading to treatment discontinuation and falls were more common in the augmentation subjects than in the venlafaxine XR subjects.
We observed similar rates and speed of response with an augmentation strategy and a strategy of switching to venlafaxine XR in elderly subjects with prospectively defined treatment-resistant major depressive disorder. Venlafaxine XR was generally better tolerated than the augmentation strategies. Further investigation of venlafaxine XR as a preferred strategy for treatment-resistant geriatric depression is warranted.
• The prognostic importance of delusions in the depressive syndrome had been a major focus of study before somatic therapies were available. Recently, the growing evidence that delusional depressives respond at a significantly lower rate to tricyclic antidepressants than do nondelusional depressives has revived this interest. That evidence is reviewed, and the demographic data and pretreatment clinical phenomenology of a series of hospitalized depressed patients were analyzed to see if differences existed between the delusional and nondelusional groups. Delusional unipolar depressives were less likely to recover while receiving placebo, had significantly more psychomotor retardation, and showed a trend toward fewer previous episodes than nondelusional unipolar depressives.
• Depressive symptoms and disorders were identified by structured psychiatric interview in 130 consecutively admitted male inpatients aged 70 years and over. Major depression was found in 11.5% and other depressive syndromes in 23%. While depressive symptoms and syndromes are common among the medically ill, this study demonstrated the need for careful diagnostic assessment of older patients with depressive symptoms before initiating treatment that may itself convey significant risk. Sociodemographic and health characteristics of older men at higher risk for depression were also identified. Patients more likely to be depressed were over age 75 years, had less formal education, experienced cognitive dysfunction, suffered from more severe medical illness (particularly recent myocardial infarction), and had a history of psychiatric illness. Depressive symptoms were also common among patients with renal or neurologic diseases, those having a family history of psychiatric illness, the unmarried, and the more severely disabled. Given the impact of depression on recovery from medical illness, compliance with medical therapy, and costs of extended hospital stays, detection and treatment of this disorder are imperative.
(Arch Intern Med 1988;148:1929-1936)
DEPRESSION in the aging and the aged is a major public health problem. It causes suffering to many who go undiagnosed, and it burdens families and institutions providing care for the elderly by disabling those who might otherwise be able-bodied. What makes depression in the elderly so insidious is that neither the victim nor the health care provider may recognize its symptoms in the context of the multiple physical problems of many elderly people. Depressed mood, the typical signature of depression, may be less prominent than other depressive symptoms such as loss of appetite, sleeplessness, anergia, and loss of interest in, and enjoyment of, the normal pursuits of life. There is a wide spectrum of depressive symptoms as well as types of available therapies.
Because of the many physical illnesses and social and economic problems of the elderly, individual health care providers often conclude that depression is a normal consequence
Background:
We examined the effect of high-dose selegiline in 16 treatment-resistant older depressive patients. We hypothesized that selegiline, at a dosage of 60 mg/d, would be at least partially effective but that the higher doses would not maintain the monoamine oxidase B selectivity observed with the lower doses of selegiline.Methods:
Sixteen treatment-resistant subjects (mean [±SD] age, 65.6±9.3 years) entered a double-blind, randomized, crossover study of placebo vs 3 weeks of selegiline at a dosage of 60 mg/d. Objective measures of mood and behavior were obtained in all subjects, and 10 of the subjects underwent repeated lumbar punctures for analysis of monoamine metabolites in the cerebrospinal fluid.Results:
Objective measures of mood and behavior revealed significant improvement in the Hamilton Depression Rating Scale score (37.4% decrease), the Global Depression score (22.7% decrease), and the Brief Psychiatric Rating Scale score (19.3% decrease); subjective behavioral measures, however, did not show significant improvement during the 3-week medication trial. Cerebrospinal fluid values revealed a statistically significant drop in 3-methoxy-4-hydroxyphenylglycol (51%) and 5-hydroxyindoleacetic acid (17%) levels, and there was a significant lowering of systolic blood pressure on standing (15%), but these changes were not accompanied by clinical side effects.Conclusions:
Our results suggest that high-dose selegiline can be an effective antidepressant in treatmentresistant older depressive patients. While the selegiline dose required has nonselective monoamine oxidase effects and thus would not be free of possible tyramine interactions, other advantages suggest that further investigations with selegiline are warranted in this population.
The authors studied physical comorbidity and the number of medications prescribed in all psychiatric outpatients over age 60 seen at Loma Linda VA Medical Center over a 1-year period. Psychiatric diagnoses were based on DSM-III-R. The authors used a chart review and computerized profiles of data on 90 patients (86% male) with a mean age of 67. Patients with schizophrenia had the fewest physical illnesses; patients with depression had the most; and patients with bipolar and anxiety disorders were intermediate. The number of nonpsychotropic medications followed the same trend. Frequency of cancer and mean duration of hypertension and cardiac illness were greater inpatients with depression than in those with schizophrenia.
Thirty-three elderly depressed patients who had not responded to either phenelzine or nortriptyline after seven weeks of treatment were given an additional two weeks of treatment. Nearly half of these patients responded during this grace period and the overall response rate increased from 54.0% to 70.0%. Patients on phenelzine did particularly well with the extended trial. The authors conclude that for elderly patients, an antidepressant trial of at least two months may be necessary for optimal response.
To determine the prevalence rates of major depressive disorder and of depressive symptoms and their relationship to mortality in nursing homes, research psychiatrists examined 454 consecutive new admissions and followed them up longitudinally for 1 year. Major depressive disorder occurred in 12.6% and 18.1% had depressive symptoms; the majority of cases were unrecognized by nursing home physicians and were untreated. Major depressive disorder, but not depressive symptoms, was a risk factor for mortality over 1 year independent of selected physical health measures and increased the likelihood of death by 59%. Because depression is a prevalent and treatable condition associated with increased mortality, recognition and treatment in nursing homes is imperative.(JAMA. 1991;265:993-996)
Discusses the impact of antidepressant-medication resistance (AMR) on the likelihood of ECT response. Most findings from controlled studies indicate that AMR before ECT is associated with a reduced rate of ECT response. The magnitude of this effect is clinically relevant, suggesting a response rate that is 20–30% lower in AMR Ss. The general practice of continuing pharmacotherapy after ECT with the same class of antidepressants as before is brought into question. It was reported that AMR Ss who respond to ECT are at especially high risk for early relapse (H. A. Sackeim et al, 1990). Though further research is needed, it is argued that at least 50% of AMR Ss will respond to ECT, certainly enough to justify a course of ECT in such situations. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Explores the relationship between treatment-refractory depression (TRD) and psychosocial correlates and the utility of psychotherapies (PTs) for TRD Ss. Chronic depression has been found to be associated with neurotic personality traits (NPTs), high levels of dysfunctional attitudes (HDAs), and persistent life stress. Nonresponse to pharmacotherapy is correlated to serious personality pathology, NPTs, HDAs, and inadequate social support. Chronicity, single marital status, diagnostic comorbidity, and HDAs have been correlated with poor response to PTs such as cognitive-behavioral therapy (CBT) and interpersonal PT. The studies conducted so far indicate that the newer forms of PT have only limited utility as a primary treatment of TRD (between 25–50% of TRD Ss respond to time-limited treatment with CBT). (PsycINFO Database Record (c) 2012 APA, all rights reserved)
This is a longitudinal study of 65 patients who were 80 years old or older at the time they were hospitalized for depression. Thirty-seven were treated with ECT and 28 with medication. Survival after 1, 2, and 3 years in the ECT group was 73.0%, 54.1%, and 51.4%, respectively. Survival after 1, 2, and 3 years in the non-ECT group was 96.4%, 90.5%, and 75.0%, respectively. The relatively high mortality rate in the ECT group in this study suggests that patients over 80 who undergo ECT have more severe physical illness than those who can be treated successfully with medication. Medical comorbidity is a major determinant of long-term outcome of depression in the oldest old.
Copyright (C) 1993 American Association for Geriatric Psychiatry
Trazodone was well tolerated and reasonably effective in a group of 25 treatment-resistant depressed patients. Three patients dropped out of the study during the first week because of side effects. Of the 22 patients who completed 2 or more weeks on trazodone, 63% showed at least a 50% reduction in Hamilton Rating Scale for Depression (HAM-D) score for at least two consecutive weekly rating periods. The group had significant decreases in HAM-D, Brief Psychiatric Rating Scale, and Profile of Mood States Depression Factor scores by the end of the first week of treatment. A few patients who did not respond during the initial 4 weeks of the study did so after 2 or 3 months (after 4 weeks, ratings were done monthly). Side effects were not generally a problem. Sedation occurred in 46% of the patients but was easily managed. Anticholinergic side effects were absent, and hypotension was present only if patients took large doses on an empty stomach. Perhaps because the trazodone dosage was generally not raised rapidly, three more severely depressed patients did not respond. The three patients on stable maintenance lithium prior to starting trazodone also failed to improve. On the other hand, no exacerbation of psychosis or precipitation of mania or hypomania occurred on trazodone.
(C) Williams & Wilkins 1981. All Rights Reserved.
Research efforts are increasingly being directed toward the development of reliable biologic markers that may assist in the early identification of the potential for TRD.
A 70-year-old man with a history of peripheral vascular disease was treated initially with antidepressants, then bilateral electroconvulsive therapy (ECT) for a depressive illness. Apart from an episode of delirium following ECT he recovered fully. Four years later he relapsed. Low-dose antidepressants caused disorientation and oversedation, as did ECT. Shortly afterwards he developed a multi-infarct state with Parkinsonian symptoms, transient schaemic attacks (TIAs) and cerebrovascular attacks (CVAs). His cognitive deficits implicated pathology in the frontal and subcortical areas of the brain. Postmortem examination confirmed widespread atherosclerotic disease, also cerebrovascular disease. The haemodynamic and cerebral effects of ECT are condidered in the context of vascular disease. It is postulated that ECT given to such patients might cause permanent impairment of cognitive function through ischaemia of an already compromised cerebral circulation. Suggestions are outlined regarding a policy for a more comprehensive assessment of patients with atherosclerotic disease. Deficiencies of ECT procedures are highlighted.
A retrospective study of treatment and outcome is described in 59 consecutive referrals to a catchment psychogeriatric service meeting ICD9 criteria for manic depressive illness or depressive neurosis. Of 22 who failed to respond to tricyclic antidepressants, nine (of whom four had also failed to respond to ECT) were treated by lithium augmentation. Systematic comparisons between lithium-treated subjects, tricyclic responders and others failing to respond to tricyclics revealed no significant demographic differences. Lithium augmentation was successful in 6/9 subjects. Two ‘lithium failures’ were treated with tranylcypromine to good effect. At follow-up (median six months, range 3–20 months) 7/9 subjects in the lithium-treated group were well. This was similar to the follow-up status in tricyclic responders and significantly better than outcome in the other tricyclic non-responders. Lithium augmentation appears to be a relatively well-tolerated treatment manoeuvre in refractory depression in old age, with treatment response similar to that reported in younger subjects, and may be of particular use where ECT has failed.
Eight cases of resistant recurrent depression were treated with a combination of nortriptyline and a new serotonin reuptake inhibitor, with or without concurrent lithium therapy. Significant improvement was seen in all patients where other drug regimes and ECT had been ineffective. No adverse reactions occurred in any of our patients, seven of whom were elderly. The combination treatment was more effective than individual therapies alone.
Early clinical observations and recent systematic studies overwhelmingly document a greater role for psychosocial stressors in association with the first episode of major affective disorder than with subsequent episodes. The author postulates that both sensitization to stressors and episode sensitization occur and become encoded at the level of gene expression. In particular, stressors and the biochemical concomitants of the episodes themselves can induce the protooncogene c-fos and related transcription factors, which then affect the expression of transmitters, receptors, and neuropeptides that alter responsivity in a long-lasting fashion. Thus, both stressors and episodes may leave residual traces and vulnerabilities to further occurrences of affective illness. These data and concepts suggest that the biochemical and anatomical substrates underlying the affective disorders evolve over time as a function of recurrences, as does pharmacological responsivity. This formulation highlights the critical importance of early intervention in the illness in order to prevent malignant transformation to rapid cycling, spontaneous episodes, and refractoriness to drug treatment.
Results from the National Institute of Mental Health (NIMH) Collaborative Study of the Psychobiology of Depression raised serious concerns about the longer-term prognosis for major depressive disorder in younger persons. However, little research has examined the prognosis for major depressive disorder in the elderly despite suggestions that they have poorer clinical outcomes than younger adults. The objective of this study was to 1) document rates of recovery and relapse from major depressive disorder in a large group of inpatient elderly and 2) compare recovery and relapse rates from major depressive disorder in the elderly with those in a mixed-age patient group from the NIMH collaborative study.
The psychiatric status of 127 elderly inpatients diagnosed with major depressive disorder by Research Diagnostic Criteria was evaluated for 1 year. The same diagnostic and follow-up method to assess psychiatric symptoms employed in the NIMH study were used.
One year after study admission, 72% of elderly patients had recovered. Nineteen percent of recovered patients, however, had a subsequent episode of major depressive disorder. Recovery and relapse rates in the elderly did not significantly differ from those reported for the mixed-age group in the NIMH study.
It is erroneous to single out the elderly as being more likely to have poorer longitudinal treatment outcomes than others. Study findings indicate the need for continued refinement of somatic and nonsomatic treatments for the elderly to improve rates of sustained recovery from depression.
One hundred patients with major depression who had discontinued fluoxetine because of side effects were enrolled in a multicenter, open, 8-week study of sertraline. After a washout period of at least 3 weeks following fluoxetine discontinuation and an additional 1-week, single-blind, placebo washout period, patients began treatment with 50 mg sertraline once daily. Based on the clinician's judgment of patient response, doses were titrated upward if necessary. The maximum daily dose of sertraline was 200 mg. Depressive symptoms and adverse events were assessed weekly. An interim analysis was conducted of the first 93 patients who completed the study. Of 91 evaluable patients, 69 sertraline-treated patients (75.8%) experienced significant improvement in depression. Only 8 of 93 patients (8.6%) discontinued sertraline because of side effects.
To assess whether fluoxetine use is associated with significant weight loss or other side effects in depressed elderly patients with concomitant medical illness.
A retrospective chart review.
A tertiary care VA hospital.
Five groups of outpatients were studied: (1) patients greater than 75 years old receiving fluoxetine (n = 15); (2) patients 60 to 71 years old receiving fluoxetine (n = 20); (3) patients greater than 75 years old receiving nortryptiline or desipramine (n = 20); (4) patients greater than 75 years old with a history of depression but on no antidepressant medication (n = 20); and (5) patients greater than 75 years old with no history of depression (n = 28).
Mortality, change in weight, reports of anorexia or nausea, and serum sodium and glucose measurements.
Patients greater than 75 years of age taking fluoxetine experienced significantly greater weight loss (average 4.6 kilograms, P = 0.0062) than the other groups. Both groups of patients taking fluoxetine were significantly more likely to report nausea (P = 0.0095) and anorexia (P = 0.0009). No significant differences were noted in mortality or the frequency of hypoglycemia or hyponatremia between groups.
The frequency and degree of weight loss noted here in medically ill elderly receiving fluoxetine warrants further investigation.
The purpose of this review is to set forth guidelines for the treatment of depression in several special populations: (1) the elderly (both ambulatory and institutionalized); (2) patients with concurrent neurologic disorders (Alzheimer's disease, Parkinson's disease, and stroke) and depression; and (3) patients with bereavement-related depression. This is a selective review of studies published in the past 10 years that have utilized structured psychiatric interviewing, randomized clinical trials, and/or monitoring of plasma antidepressant levels. Published data support specific efficacy and safety claims for both pharmacotherapeutic and psychotherapeutic approaches to the treatment of major depression in elderly ambulatory and institutionalized patients. In the case of depression associated with Alzheimer's, Parkinson's, and stroke, there is also evidence of efficacy for antidepressant medication. Finally, bereavement-related syndromal depression appears to respond to antidepressant medication, but further controlled evaluation is desirable. As emphasized by the 1991 National Institutes of Health Consensus Development Conference on the Diagnosis and Treatment of Depression in Late Life, depression in the elderly should be recognized as treatable and should be treated vigorously. Rather than being dismissed as a normal reaction to the multiple medical and psychosocial burdens of late life, it should be treated appropriately to reduce an important source of excess disability.
Paroxetine is a highly potent and selective inhibitor of serotonin reuptake, being more potent in vitro than fluoxetine, fluvoxamine, and sertraline. In contrast to the tricyclic antidepressants, paroxetine has little affinity for catecholaminergic or histaminergic systems. Paroxetine is well absorbed from the gastrointestinal tract and undergoes first-pass metabolism that is partially saturable. Unlike the metabolites of fluoxetine and sertraline, the metabolites of paroxetine are pharmacologically inactive in vivo. Steady-state paroxetine plasma concentrations are generally achieved within 4 to 14 days of commencing therapy and remain stable thereafter. The pharmacokinetics of paroxetine are also consistent with once-daily dosing. This pharmacologic and pharmacokinetic profile, taken together with extensive clinical data, indicates that paroxetine is a valuable addition to the physician's armamentarium for the treatment of depression.
Side effects remain one of the most important clinical issues in antidepressant therapy. Patients may not be able to take appropriate treatment or may not tolerate their medication in adequate doses or for an adequate length of time to manage their depressive illness. This article reviews the extensive safety data from 6705 patients treated with paroxetine. These data indicate that paroxetine has no significant cardiovascular effects, few significant drug interactions, and no clinically significant effects on the ECG or EEG. Furthermore, paroxetine is relatively safe in overdose and has very little anticholinergic activity. Psychomotor performance is not impaired by paroxetine and there is no evidence of any zimelidine-like hypersensitivity reactions or increase in suicidal ideation. As with other selective serotonin reuptake inhibitors (SSRIs), the most common side effect is gastrointestinal upset, especially nausea. This is usually very well tolerated and rarely leads to drug discontinuation. As with other SSRIs, monoamine oxidase inhibitors should not be prescribed concurrently or soon after discontinuing paroxetine because of the risk of a lethal interaction. Paroxetine may be less likely than currently available SSRIs to cause agitation. In general, paroxetine has a very favorable side effect profile and should be an important alternative in the medical treatment of depressive illness.
Depressive illness among the elderly is an important public health concern. However, treatment of the elderly may be complicated by age-related changes in physiology, general medical status, and susceptibility to side effects. There is therefore a need for improved treatment modalities for depressed elderly patients. Paroxetine is an antidepressant that acts through selective inhibition of serotonin reuptake. It lacks the anticholinergic and cardiovascular side effects of most first- and second-generation antidepressants. The authors present the combined data from two similarly designed comparisons of paroxetine and doxepin in outpatients over 60 years of age with major depression. The results show that paroxetine was an effective as doxepin in alleviating depression as measured on the Hamilton Rating Scale for Depression (HAM-D) total score, the Montgomery and Asberg Depression Rating Scale (MADRS), and the Hopkins Symptom Checklist (SCL) depression factor score. Paroxetine was significantly superior to doxepin on the Clinical Global Impressions (CGI) scale for severity of illness, the HAM-D retardation factor, and the HAM-D depressed mood item. Doxepin produced significantly more anticholinergic effects, sedation, and confusion. Paroxetine was associated with more reports of nausea and headache. These results suggest that paroxetine may be a valuable tool for the treatment of major depression in the elderly.
To evaluate the Center for Epidemiology Surveys-Depression (CES-D) scale for inordinate false positives, due to measurement of non-depression-related somatic complaints.
Cross-sectional correlation of analysis of random multi-cluster samples.
Thirteen counties considered representative of the community-dwelling elderly population of Alabama.
One-thousand-sixty persons aged 55 and older.
None.
Study evaluated the relationship of somatic symptomatology, as measured by the Multi-Level Assessment Instrument's Physical Health Domain Index (PHDI) composite score and its three component indices, with the CES-D and its four component scales, particularly the Somatic scale.
The CES-D total score and the Somatic scale were not related to: age increases in the sample; PHDI composite score or the three index scores; or to subgroups of high and low PHDI composite scores. Among those screened as depressed, the PHDI and the three indices were not related to the CES-D total score or three of the four subscales. The CES-D Somatic scale was positively related to those depressed persons with the highest number of total PHDI somatic complaints. However, among the depressed group there were more persons scoring greater than 1.5 standard deviations above the mean on the CES-D Depressive Affect scale (n = 81) than on the Somatic scale (n = 65).
The CES-D and its Somatic scale were relatively unbiased by the respondent's somatic complaints. The CES-D can continue to be considered valid under these circumstances.
The use of ECT has had a resurgence in the past decade as the promise of more effective and specific pharmacotherapy has been unfulfilled. This has been especially true in the elderly in whom ECT has been frequently demonstrated to be a safe and effective intervention. The decision to use ECT in an elderly patient is a complex one, based on the patient's illness, risks of the treatment compared with alternate or no treatment, and patient and family wishes. The list of dogmatic "absolute contraindications" for ECT has been replaced with a pragmatic philosophy looking at risk/benefit ratios. Such an attitude can only serve to enhance the quality of care clinicians provide their patients.
Only a few of the eight tricyclic antidepressants available today have been studied systematically in the elderly. Tertiary amine tricyclics such as amitriptyline and imipramine have been reported to be effective in depressed geriatric patients, but because of their potential for side effects, it is not advisable to use them in the elderly. Desipramine has a less toxic side effect profile, especially with respect to anticholinergic effects, but its efficacy has not been well studied. This does not mean, however, that it is not an effective drug for the elderly depressed. Nortriptyline is the tricyclic that has been the most studied. The results of those studies show that it should be recommended as an antidepressant for older patients. It is effective in both the acute and continuation treatment of depression in the elderly. As far as its use in maintenance treatment, the results are mixed but at this moment there is nothing with which to compare it. It has a favorable side effect profile: low anticholinergic activity; relatively few cardiac side effects, even in patients with preexisting cardiac disease; and relatively less orthostatic hypotension. Nortriptyline also has the virtue of an established therapeutic range for its steady-state plasma level. The role of its 10-hydroxy metabolite needs to be further explored, but when its contribution to efficacy and toxicity is better understood, it may be possible to use nortriptyline in a more precise and safe way in elderly patients. The bulk of evidence suggests, partly by default, that nortriptyline should probably the tricyclic-of-first-choice in treating an elderly patient with major depression.
Although their extent remains unclear, major and minor depressions are widespread in the nursing home population. This statement appears intuitively to be correct when consideration is given to the inactivity, decline in functional competence, loss of personal autonomy, and unavoidable confrontation with the process of death and dying that are associated with nursing home placement. In addition, some nursing home residents have had previous episodes of depression or are admitted to the facility already dysthymic or with other chronic forms of the illness. Such circumstances provide a favorable culture for the development and persistence of depressive illness. When the high frequency of other psychiatric disorders among nursing home residents is factored in, it is not surprising that long-term health care facilities have come to be regarded as de facto psychiatric hospitals. Nursing homes largely lack the treatment resources of psychiatric hospitals, however. Nursing home physicians are often unprepared to make psychiatric diagnoses, and a perfunctory annual psychiatric evaluation is insufficient to manage the complex depression syndromes of nursing home residents. Because nursing home psychiatrists typically work on a consultation basis, recommendations are not necessarily acted upon by the primary physicians. The consequences of undiagnosed and untreated depression are substantial. From the psychiatric perspective, the possibility that depression increases the risk for eventual development of permanent dementia highlights the importance of early identification for cases of reversible dementia. From the rehabilitation point of view, persistent depression among individuals with physical dependency following a catastrophic illness is associated with failure to improve in physical functioning. Depression can probably be linked to increased medical morbidity in nursing home residents, a relationship that also has been suggested for elderly medical inpatients. If so, the use of nursing time and other health-care facility services would be greater for depressed than nondepressed residents, and financial costs would be higher as well. Finally, recent data point to increased mortality in nursing home residents with major depressive disorder. It is apparent that depression in long-term care facilities is a condition with doubtful prognosis and negative medical, social, and financial consequences. The highest costs of all may be paid by nursing home residents who experience the unrelieved suffering of depressive illness. Only epidemiologic research using standard diagnostic criteria and direct resident assessment will adequately establish the magnitude of the need for intervention among depressed residents in long-term care.(ABSTRACT TRUNCATED AT 400 WORDS)
Recent Epidemiologic Catchment area studies found the prevalence of major depression to be only about 1% in community-dwelling elders; other less severe depressive disorders, however, may be present in over 25% of this population. Furthermore, at least 8000 persons over age 60 commit suicide each year, making up nearly one quarter of the total number reported, a rate much higher than expected given the proportion of elderly in the US population. Bipolar disorder, on the other hand, is much less common than unipolar depression at a rate of about 0.1% in the community; in nursing homes, however, as many as 10% of residents may have this condition. Sociodemographic correlates of depression in late life include female sex, divorced or separated marital status, low income or educational level, inadequate social support, and recent negative and unexpected life events. In particular, physical health has a major impact on mood and well-being; consequently, rates of major depressive disorder in elders hospitalized with medical illness are over 10 times that reported in the community.
This study examined the association between depression and mortality among a group of nursing home and congregate apartment residents (initial n = 898) over a 30-month period. Baseline [Time 1 (T1)] and 1-year follow-up [Time 2 (T2)] assessments yielded research-based diagnoses of possible major, minor, or no depression, along with measures of functional disability, cognitive status, and physician-rated health. Event history analyses were used to assess differential mortality as a function of level of depression after T1 and of change in depressive status from T1 to T2. Significant effects for T1 depression at 6, 12, and 18 months after the interview reflected an increased death rate among possible major depressives as compared with other respondents. An effect of change in depressive status from T1 to T2 appeared to be caused by long-term negative effects of T1 depression. Finally, none of the observed associations remained significant when controlled for effects of physical health, functional disability, and cognitive status. Thus, the effects of depression on mortality among this sample appeared to be attributable strictly to the correlation of depression with ill health. However, cautious interpretation is recommended inasmuch as causal paths between depression, ill health, and death remain unclear.
There have only been a few studies of the role of carbamazepine in the management of treatment-resistant depression.
The response to carbamazepine of 16 melancholic patients, who had been depressed for an extended period despite a number of standard treatments, was studied retrospectively.
Seven patients (44%) had a moderate or marked improvement. The responders included both psychotic and nonpsychotic depressives, and patients with concurrent organic brain disease. There was, however, a high rate of complications, with 5 of these 7 responders (71%) having to discontinue carbamazepine because of adverse effects. This high rate of complications may have reflected the older age of our sample.
These findings suggest the efficacy of carbamazepine in melancholic patients who have not responded to conventional treatments, but indicate that the high rate of significant side effects may limit its long-term usefulness.
Fifty-six consecutively admitted elderly (65 and over) patients with depression were assessed on mental, physical and social states. They were followed up and assessed at home one year later. A group of 24 depressed in-patients aged under 65 years admitted to the same ward during the same period was also assessed. Outcome was different for the two groups, with 68% of the elderly 'well' at one year, against 50% of the younger group. The younger group were more likely to have 'poor' outcome (41%) than the elderly (16%). However, there were more deaths than expected, particularly in the elderly. These findings differ from some previous studies, and indicate an excellent prognosis for depression in the elderly. Outcome in younger patients is less good.
The potentiation of fluoxetine by buspirone is described in three cases of treatment-resistant depression. All three patients improved markedly with very few side-effects from the medication. The possibility of synergy between drugs that affect serotonin reuptake inhibition, 5HT1A receptors and 5HT2 receptors is discussed.
Bupropion is a relatively dopamine-specific antidepressant approved for release by the Food and Drug Administration in 1989. Topics included in this review are pharmacokinetics as related to blood levels and clinical response, bupropion's use in the elderly and in the medically impaired, and drug interactions of note.
The relation of poor health to the onset of depression symptoms in late life is well recognized, but little attention has been given to characteristics that might predict persistence or remission of depressive symptoms. In previous analyses the authors found that increasing disability and declining health preceded the emergence of depressive symptoms in older community residents and accounted for 70% of the variance explained by discriminant analyses. The aim of the present analysis was to examine the relevance of changes in health and disability to the persistence of depressive symptoms.
A representative sample of 1,855 adults aged 65 or older were assessed with the Center for Epidemiologic Studies Depression Scale at baseline. Twenty-four months later, 1,577 individuals were available for a second assessment of depressive symptoms. The characteristics of the 97 community residents whose depressive symptoms persisted over 24 months were compared to those of the 114 whose symptoms remitted.
Changes in health, differences in age, sleep disturbance, and added formal support services accounted for more than 30% of the variance between the persistently depressed and remission groups. Advanced age and worsening health were associated with persistent symptoms, improved health with remission.
Previous studies have indicated that untoward changes in health and disability play a major role in the onset of depressive symptoms. These findings show a substantial contribution to chronicity as well.
Treatment responses were monitored in 101 depressed patients, ranging in age from 64 to 92 years, hospitalized on a geropsychiatry unit. Forty-six percent of the patients received ECT. Medications were used in the majority of patients. Responses were assessed with both depression inventories (Beck Depression Inventory and Geriatric Depression Scale) and physician-rated global improvement scores. Advanced age was not associated with poor outcome. ECT was the most important variable associated with a good response, regardless of age.
This study sought to ascertain the affective and cognitive outcome after tricyclic and electroconvulsive treatment of elderly medical-psychiatric patients meeting diagnostic criteria for major depression, some of whom had normal cognitive functioning and some of whom were cognitively impaired before treatment.
Patients who met criteria for major depression on the basis of a structured diagnostic interview and who scored 17 or more on the Hamilton Rating Scale for Depression were evaluated with the Mattis Dementia Rating Scale. The patients were then treated in a nonrandom manner with either tricyclic antidepressants or ECT (followed by tricyclic maintenance therapy). The majority of the patients treated with ECT had not responded previously to tricyclics. Follow-up psychometric testing was repeated in 6 months.
Among the patients with normal pretreatment cognitive functioning, cognition was generally stable. Among the patients with pretreatment cognitive impairment, a substantial number--including those receiving ECT--demonstrated improvement in cognition. While the majority of patients improved with respect to both their affective and cognitive states, certain treatment-refractory subgroups were nevertheless identified.
The data suggest that cognitive dysfunction associated with depression may improve after treatment in a substantial number of elderly patients, including those receiving ECT. Relapse rates, however, may be relatively high, and residual symptoms may persist, which emphasizes the need for optimal initial and long-term antidepressant strategies for this population.
Recent reports supporting the use of lithium carbonate as an adjunct to tricyclic antidepressants for the treatment of refractory depression have not utilized standardized tricyclic antidepressant therapy, nor have they addressed the efficacy of lithium augmentation in a geriatric population. A 3-week open trial was added to the medication regimen of 15 elderly depressed inpatients who had already failed 4 weeks of therapeutic levels of nortriptyline. Treatment response was determined by the 17-item Hamilton Rating Scale for Depression (HAM-D). Two of 15 partial responders before lithium augmentation became complete responders. Of the remaining 13 "nonresponders" before lithium augmentation, one had a complete response, 7 had a partial response and 5 remained nonresponders. Although there was a mean HAM-D change of 8.3 points after lithium augmentation (24.7 +/- 5.9 to 16.4 +/- 6.8, p less than .001), when considering the previously reported similar efficiency of extended nonaugmented nortriptyline, these data do not strongly support lithium augmentation in elderly subjects who fail to respond after 4 weeks of nortriptyline. Further study is needed to determine what role, if any, lithium augmentation should play in the treatment of geriatric depression.
We examined the extent to which medication resistance during an episode of major depression was related to short-term clinical response to bilateral electroconvulsive therapy (ECT). Strength of pharmacological treatment trials was rated in 53 patients who met Research Diagnostic Criteria for major depressive disorder and were subsequently treated with ECT. Patients who had failed to respond to adequate pre-ECT pharmacotherapy were substantially less likely to respond to ECT than patients who had not received adequate pharmacological trials before ECT. Therefore, medication resistance had predictive value with respect to the therapeutic effects of ECT. The clinical and theoretical implications of this finding are discussed.
To determine the prevalence rates of major depressive disorder and of depressive symptoms and their relationship to mortality in nursing homes, research psychiatrists examined 454 consecutive new admissions and followed them up longitudinally for 1 year. Major depressive disorder occurred in 12.6% and 18.1% had depressive symptoms; the majority of cases were unrecognized by nursing home physicians and were untreated. Major depressive disorder, but not depressive symptoms, was a risk factor for mortality over 1 year independent of selected physical health measures and increased the likelihood of death by 59%. Because depression is a prevalent and treatable condition associated with increased mortality, recognition and treatment in nursing homes is imperative.
Although fluoxetine has been shown to be both efficacious and well tolerated, few data are available on the use of this drug in patients with preexisting heart disease and in the elderly. The authors report a case of an elderly patient in whom atrial fibrillation and bradycardia developed shortly after she began treatment with fluoxetine. The dysrhythmias recurred on rechallenge with the drug. A review of the pertinent literature is presented and possible pathophysiologic mechanisms are discussed.
The purpose of the study was to determine if magnetic resonance imaging (MRI) scans of elderly depressed patients differ from MRI scans of age-matched control subjects and age-matched patients with Alzheimer's disease.
The authors studied 21 patients 60 years or older with major depression, 16 patients with Alzheimer's disease, and 14 age-matched control subjects.
Compared to control subjects, depressed patients had greater cerebral sulcal and temporal sulcal atrophy; larger sylvian fissures, lateral ventricles, third ventricles, and temporal horns; and greater severity of subcortical white matter lesions. Depressed patients also had more basal ganglia lesions but similar levels of periventricular hyperintensity. There were no differences between depressed patients with and without delusions on any MRI measure. Depressed patients who received ECT had more temporal horn atrophy and greater subcortical abnormality summary scores than normal subjects. Cortical sulcal atrophy correlated with age at onset of depression.
The findings suggest that elderly hospitalized depressed patients have greater cortical as well as subcortical atrophy and more basal ganglia lesions than age-matched normal control subjects. The correlation of these abnormalities with outcome remains unknown.
A review of the literature on the serotonin syndrome in animals and human beings was conducted, and 12 reports of 38 cases in human patients were then analyzed to determine the most frequently reported clinical features and drug interactions, as well as the incidence, treatment, and outcome of this syndrome.
The serotonin syndrome is most commonly the result of the interaction between serotonergic agents and monoamine oxidase inhibitors. The most frequent clinical features are changes in mental status, restlessness, myoclonus, hyperreflexia, diaphoresis, shivering, and tremor. The presumed pathophysiological mechanism involves brainstem and spinal cord activation of the 1A form of serotonin (5-hydroxytryptamine, or 5-HT) receptor. The incidence of the syndrome is not known. Both sexes have been affected, and patients' ages have ranged from 20 to 68 years. Discontinuation of the suspected serotonergic agent and institution of supportive measures are the primary treatment, although 5-HT receptor antagonists may also play a role. Once treatment is instituted, the syndrome typically resolves within 24 hours, but confusion can last for days, and death has been reported.
The serotonin syndrome is a toxic condition requiring heightened clinical awareness for prevention, recognition, and prompt treatment. Further work is needed to establish the diagnostic criteria, incidence, and predisposing factors, to identify the role of 5-HT antagonists in treatment, and to differentiate the syndrome from neuroleptic malignant syndrome.
The cognitive function scores and subjective memory complaints of eight patients who had each received more than 100 treatments with bilateral modified since wave ECT were equivalent to those of matched patients who had never received ECT. The results suggest that patients given many ECT treatments over several courses do not manifest measurable cognitive impairment at long-term follow-up.