Pharmacologic treatments effective in both generalized anxiety disorder and major depressive disorder: clinical and theoretical implications

OBJECTIVE: To review the efficacy of anxiolytics (alprazolam and azapirones) in major depressive disorder (MDD) and that of antidepressants in generalized anxiety disorder (GAD), thereby exploring the possible theoretical and clinical implications of this efficacy. METHOD: A Medline literature search was performed for the period January 1980 to September 1997 of randomized, double-blind comparison studies between anxiolytics and antidepressants in the acute treatment of adult patients with either MDD or GAD. RESULTS: Alprazolam, at doses double those generally recommended for anxiety disorders, appears to be as effective as tricyclic antidepressants (TCAs) in the acute treatment of mild to moderate MDD. Alprazolam was also found to have a more rapid onset of action than to TCAs, particularly for the improvement of anxiety, somatization, and insomnia. Two azapirones (buspirone and gepirone) also have demonstrated a modest acute antidepressant effect in preliminary studies, albeit only in a depressed outpatient sample with considerable anxiety at baseline. Finally, various antidepressant drugs (imipramine, trazodone, paroxetine) were shown to have, at the least, comparable efficacy to benzodiazepines (BZDs) in the acute treatment of GAD. CONCLUSIONS: The nonspecificity of treatment response suggests that GAD and MDD are 1) different expressions of a similar disorder with a common neurobiological substrate, 2) discrete diagnostic entities that respond to independent pharmacological effects of the same drugs, or 3) a combination of the two (heterogeneity hypothesis). The most relevant clinical finding is the efficacy of antidepressants in the acute treatment of GAD.     

Comorbidity of unipolar depression: I. Major depression with dysthymia.

The degree of current and lifetime comorbidity between major depressive disorder (MDD) and dysthymia (DY) was examined in large community samples of older adolescents (n?=?1,710) and adults (n?=?2,060). DY was highly comorbid with MDD (lifetime odds ratio of 3.4 for adolescents and 1.6 for adults) and was more likely to precede than to follow MDD, especially in persons who became depressed early in life. MDD was by far the more frequent form of depression: Approximately 80% of the depressed persons experienced only MDD, 10% experienced only DY, and 10% experienced both MDD and DY. The large number of persons who had become depressed twice experienced MDD in the 2nd episode, regardless of the nature of the 1st depression. History of depression was associated with a greater probability for other mental disorders in both adolescents and adults; however, the rates of comorbidity for MDD did not differ from rates for DY or for both MDD and DY. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The trauma patient: open hospital choice?

Mental-health service utilization among elderly people has been shown to be low relative to younger age groups. This study was done to determine the current proportion of elderly persons served in a university-affiliated psychiatry outpatient clinic, and to better characterize elderly patients who receive specialized mental-health care in this setting. The proportion of visits from elderly patients (aged 60 and over) was found to be 16%. Demographic and clinical characteristics of a sample of 140 consecutive geriatric patients evaluated at the clinic were obtained. The data revealed that the patients had a mean age of 74.7+/-7.5 (SD) years, and were mostly female (72.1%) and white (78.6%). Surprisingly, the age distribution was found to be bell shaped, with a small upper tail. The three most prevalent psychiatric diagnoses were depression (56.4%), dementia (35.7%), and substance use disorder (20%). Overall, 59.3% of geriatric patients had a history of prior psychiatric treatment. Females were significantly more likely than males to have a psychiatric history (69.3% vs. 33.3%, P = .0001). Among patients with a psychiatric history, females were more likely to have a current diagnosis of major depression (P = .0006), while males were more likely to have a current substance use disorder (P = .03). The prevalence of dementia increased with each successive decade above 60, while the occurrence of bipolar and adjustment disorders was confined to younger geriatric patients. Elderly patients receiving psychiatric treatment in the clinic thus formed a heterogeneous group. Gender, age, and presence of a psychiatric history were all associated with differences in prevalence and distribution of various mental disorders in this geriatric psychiatry outpatient clinic.     

Psychological dysfunction and physical health among elderly medical inpatients.

One hundred and fifty randomly selected geriatric medical inpatients were evaluated for the presence of psychological dysfunction using the Schedule for Affective Disorders and Schizophrenia (SADS) and Research Diagnostic Criteria (RDC) methodology. Objective and subjective measures of physical health status were independently taken and related to the presence of a RDC diagnosis. Results indicated that a large portion of the sample (27.3%) had at least one psychological disorder and that 15.3% of the total sample had a depressive disorder. Comorbid depression was associated with the greatest level of psychological distress and dysfunction and with the poorest physical health status. Finally, depressed elderly patients were less likely than patients with nondepressive psychopathology and control subjects to receive a diagnosis of mental disorder or to receive antidepressant medications during their admission, suggesting that comorbid depression is underrecognized and undertreated in primary care. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Geriatric assessment in oncology

With the anticipated growth in the numbers of elderly persons, a higher prevalence of cancers among older persons is expected; as a result, oncologists will treat larger numbers of older persons in their practices. Clinicians caring for older persons with cancer must recognize the heterogeneity of the elderly population and focus their assessments and care plans accordingly. The author reviewed literature and drew conclusions regarding geriatric assessment in several key areas: the medical, cognitive, affective, functional economic, and environmental status of patients; social support for patients; and advance directives. They concluded that for younger and healthier seniors, simple probes for the presence of common geriatric problems may suffice, but traditional means of medical assessment should be supplemented by brief screening for common geriatric conditions and nonmedical issues that are of particular relevance to the health of older persons. Assessment instruments can be used to guide these brief evaluations, but results must be interpreted in the context of the limitations of the instruments used. Patients who are frail or at high risk for functional decline or nursing home placement should receive more extensive evaluation by individual practitioners or by a multidisciplinary team of health care professionals who can provide comprehensive geriatric assessment. By broadening their assessment skills to include domains that are beyond traditional internal medicine and oncology training, oncologists can better serve their older cancer patients.     

The effect of gender and age at onset of depression on mortality

BACKGROUND: Depression has a marked negative impact on geriatric patient mortality and morbidity. The risk factors and exact reasons for these effects are not well understood. METHOD: Seeking to better define the factors, we retrospectively analyzed the effects of gender and age at onset of affective disorder in a naturalistic study of 192 geriatric patients consecutively admitted to a large midwestern tertiary care center between 1980 and 1987 for the treatment of unipolar depression. RESULTS: After controlling for age at index admission, patients with an onset of depression before age 40 suffered significantly (p < .05) less mortality in follow-up than those with onset after age 40. When effects of gender are examined, the effects of age at onset are most profound in women, with a threefold increase in the rate of death in the cohort with age at onset of depression after 70 years when compared to those with onset before age 40. CONCLUSION: These results and those of others suggest that depressed elderly women with no previous history of affective disorder are at a markedly increased risk compared with elderly women with a history of affective illness for morbidity and mortality and that a significant proportion of elderly depressed patients are admitted to a psychiatric hospital for a depression that is secondary to serious medical illness.     

Development of a shortened center for epidemiological studies depression scale for assessment of depression in rheumatoid arthritis.

Objective: The purpose was to develop a short-form version of the Center for Epidemiologic Studies Depression Scale (CES-D) for the identification of persons with major depressive disorder (MDD) within a population with rheumatoid arthritis (RA). Study Design: Data were analyzed from 337 persons with RA. Forty-six participants met the diagnostic criteria for MDD; 291 participants were classified in the non-MDD category (including 21 participants with dysthymia and 18 participants with minor depressive disorder). A short-form version of the CES-D was developed, and multiple cutoff scores were examined. Results: A cutoff score of ≥5 from a 9-item, short-form CES-D was found to be generally as efficient as the more commonly used full-scale cutoff score of ≥16 for classifying participants with MDD within an RA population. Although the shortened CES-D scale (cutoff score ≥5) was slightly more sensitive, it also exhibited slightly less specificity than the full-scale cutoff score of ≥16. Conclusion: The results suggest that a short-form CES-D can be used to screen for MDD within an RA sample with a degree of efficiency that is generally comparable to that of the full-scale instrument. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A solution to the problem of jail suicide

In American studies in the sixties and seventies caregivers, including physicians, showed a negative attitude towards the elderly. There are indications that such a negative attitude affects the quality of care and the communication with the elderly. Based on predominantly American literature this article reviews research on medical students' knowledge about and attitudes towards older people as well as the impact of geriatric training on the image of older patients and physician-patient communication. In medical students who did not receive a geriatric training, attitudes improved in the eighties and nineties up till a slightly positive level but general gerontological knowledge displayed as many shortcomings as in former days. A few studies show that instructional modules in geriatrics do not have an impact on the attitude towards the elderly. Several studies show that contact with aged persons has a positive influence. Rather than geriatric residency or work in a nursing home, contact with healthy elderly has favourable effects. Attitude improvement based on interactions with older people is maintained during medical education. A program in gerontology as well as geriatric instructional modules can lead to knowledge improvement. Since significantly positive correlations between knowledge and attitude are sometimes demonstrated, increasing gerontological knowledge may lead to more positive attitudes.     

Streptogramins and their potential role in geriatric medicine

Despite advances in antimicrobial chemotherapy over recent decades, morbidity and mortality secondary to infection continues to rise. In addition, the incidence of infection caused by resistant organisms has also increased. Concurrently, the elderly are living longer than prior generations, often with disabling chronic diseases. The more debilitated of the geriatric population are at greater risk for infection, and more likely to acquire or develop antimicrobial resistant organisms. Gram-positive organisms are a source of resistance and commonly cause infection in older patients. Whereas resistance is a concern in all patients, in the elderly this is magnified by limitations in treatment options because of differences in pharmacokinetics and tolerance as compared with younger counterparts. Pharmacokinetic differences include changes in drug distribution and may arise as a result of diminished end organ function. Age-related decreases in renal function often impact on commonly prescribed antimicrobials. In addition, the elderly are more susceptible to drug-drug interactions because polypharmacy is common in this patient population. Streptogramins may offer a useful alternative in the treatment of infections in the elderly due to their coverage of organisms commonly causing infections in this population and because of their favourable pharmacokinetic profiles. While published experience is limited, streptogramins are not appreciably eliminated by the kidney and, therefore, they are less subject to age-related changes in renal elimination. What is required is multi-dose pharmacokinetic analysis of streptogramins in geriatric populations and subset analysis of patient use data on file. The following will provide the reader with the most recently presented data on streptogramin use and their potential. While focusing on potential use in the elderly, we have cited data and issues which we believe will be relevant in the geriatric population.     

The relationship between panic disorder and major depression. A new family study

OBJECTIVE: The comorbidity between panic disorder and major depression (MDD) in individuals has been amply documented. However, data from family studies to determine whether panic disorder and MDD aggregate separately or together in families have been inconclusive, in part because of the absence of studies with the full range of proband groups. This report presents results from a family study with the necessary mutually exclusive groups: panic disorder without MDD, panic disorder with MDD, MDD without panic disorder, and normal controls. METHODS: Diagnostic information was obtained from 193 probands and 1047 of their adult relatives with the Schedule for Affective Disorders and Schizophrenia--Lifetime Version for Anxiety Disorders by direct interview, and/or from multiple informants, without knowledge of proband diagnoses. Best-estimate diagnoses were based on all available information by clinicians independently of data collection and without knowledge of probands' and other relatives' status. RESULTS: Findings indicated the specific and independent transmission of panic disorder and MDD, the separation of panic disorder from MDD, and the nonfamilial nature of late-onset MDD. The pattern of results was unaffected by the use of different diagnostic criteria, number of informants, interview status of relatives, presence of substance abuse or agoraphobia or the sequence of MDD and panic disorder in probands, or whether probands were selected from treatment clinics or community sample. CONCLUSIONS: We conclude that panic disorder and MDD are separate disorders with substantial co-occurrence in individuals, and that panic comorbid with MDD is not a single, distinct disorder. Finally, we illustrate an approach to examining comorbidity in family data through analysis of mutually exclusive, parallel diagnoses in probands and relatives.     

Posttraumatic stress disorder and major depression in veterans with spinal cord injury.

Objective: To explore the relationship between posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) in veterans with spinal cord injury and to compare those results with results found in veterans who had sustained other traumatic injuries. Method: To investigate the relationship between PTSD and MDD in persons with spinal cord injury, the authors examined whether individuals endorsed overlapping items on measures of both disorders, evaluated the contribution of overlapping items to comorbid diagnosis, and conducted an exploratory factor analysis. Results: The overlapping symptoms between the 2 disorders did not fully explain the high rate of comorbidity, although participants who endorsed a symptom common to MDD and PTSD on 1 measure were likely to endorse the corresponding item on another measure. In both samples, items loaded on separate PTSD and MDD factors. Conclusion: MDD and PTSD appear to represent independent reactions to trauma in those individuals who had experienced either a nonspinal cord injury or a spinal cord injury. This research also provides an initial investigation of some of the possible ways that MDD and PTSD are related by addressing psychometric issues inherent in their measurement. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Functional localization in the Onufrowicz nucleus in man

The rapid increase in persons aged 65 and older will account for 20% of the total United States population by the year 2030. The incidence of malignancy likewise increases with advancing age. These factors are likely to result in an epidemic of geriatric cancer cases. Physicians should become knowledgeable on current issues in geriatric oncology which include: how to appropriately select geriatric patients with malignancies for surgical, medical or radiotherapeutic intervention; age as a bias for treatment selection; toxicities from cancer therapy in the elderly and how they can be modified; cancer screening and prevention measures in the elderly, and the special issues of informed consent and pain control in the geriatric cancer patient.     

Childhood and adolescent depression: a review of the past 10 years. Part I

OBJECTIVE: To qualitatively review the literature of the past decade covering the epidemiology, clinical characteristics, natural course, biology, and other correlates of early-onset major depressive disorder (MDD) and dysthymic disorder (DD). METHOD: A computerized search for articles published during the past 10 years was made and selected studies are presented. RESULTS: Early-onset MDD and DD are frequent, recurrent, and familial disorders that tend to continue into adulthood, and they are frequently accompanied by other psychiatric disorders. These disorders are usually associated with poor psychosocial and academic outcome and increased risk for substance abuse, bipolar disorder, and suicide. In addition, DD increases the risk for MDD. There is a secular increase in the prevalence of MDD, and it appears that MDD is occurring at an earlier age in successive cohorts. Several genetic, familial, demographic, psychosocial, cognitive, and biological correlates of onset and course of early-onset depression have been identified. Few studies, however, have examined the combined effects of these correlates. CONCLUSIONS: Considerable advances have been made in our knowledge of early-onset depression. Nevertheless, further research is needed in understanding the pathogenesis of childhood mood disorders. Toward this end, studies aimed at elucidating mechanisms and interrelationships among the different domains of risk factors are needed.     

Treatment of depression in bipolar disorder: new directions for research

The objective of the study was to review the clinical literature on the acute, somatic treatment of the depressed phase of bipolar disorder. We reviewed all available published studies of "standard" somatic treatments (lithium, antidepressant and anticonvulsant agents, and electroconvulsive therapy [ECT]) reporting three or more depressed bipolar patients who were not psychotic, rapid cycling, or previously treatment refractory. We also reviewed all studies of "nonstandard" pharmacologic treatments involving even a single case of a depressed bipolar patient. Data sources included the MEDLINE database and relevant references from articles obtained in this search and in major reviews. Five of seven studies comparing ECT with antidepressant agents find ECT more efficacious. Eight of nine controlled comparisons find lithium superior to placebo in depressed bipolar patients. Three controlled comparisons of lithium to tricyclic antidepressants suggest that lithium is equivalent to tricyclic drugs in such patients. Three double-blind, controlled studies indicate that carbamazepine is more effective than placebo. Limited data on other antidepressant classes suggest that monoamine oxidase inhibitors, bupropion, and serotonergic agents may offer some advantages over tricyclic antidepressants in this population. Some "nonstandard" treatments also show some potential in bipolar patients. The possibility of switching into a manic episode is an important consideration with many of the agents studied, although little remains known about spontaneous versus treatment-associated mood shifts. In contrast to the extensive literature on the acute treatment of the manic phase of bipolar disorder and on the prophylaxis of manic and depressive episodes, there are few studies of treatment of the depressed phase of bipolar disorder, and their results generally are limited or inconclusive. Lithium generated a revolution in psychiatric treatment, but the treatment of the depressed phase of bipolar disorder remains a relatively neglected corner of the field. Several study designs may help to augment knowledge in the treatment of bipolar depression.     

Noninvasive vascular imaging in the diagnosis and treatment of adventitial cystic disease of the popliteal artery

Depressed geriatric patients show substantial intersubject variability in cognitive performance, which complicates attempts to evaluate the cognitive effects of depression and of antidepressant therapy. This variability may reflect the multiple medications older patients take, many of which have anticholinergic effects. This study examined whether serum anticholinergicity (SA) explained some of the variability in depressed geriatric patients' memory performance. Before starting antidepressant treatment, 36 elderly depressed subjects were given a verbal learning test. At the same time, a blood sample was taken and analyzed by radioreceptor binding assay to determine their SA level. Nineteen of the subjects had detectable levels (mean = 0.28 pmole atropine equivalent). Subjects with an SA of zero showed significantly better delayed recall than did those with a positive SA level. Thus, even very low SA may produce subtle decrements in memory performance, an area of cognition known to be highly sensitive to anticholinergic effects.     

Impact of anesthesia on the cognitive functioning of the elderly

Exposure to general anesthesia has been suggested as a possible cause of long-term cognitive impairment in elderly subjects. The present study reviews the literature in this field in order to describe postoperative cognitive impairment in elderly populations, to determine to what extent this may be attributed to anesthetic agents, and to consider evidence of a causal relationship between anesthesia and onset of senile dementia. A systematic literature search was conducted using five bibliographic databases (PASCAL, Medline, Excerpta Medica, Psychological Abstracts, and Science Citation Index). Significant cognitive dysfunction was found to be common in elderly persons 1 to 3 days after surgery, but reports of longer-term impairment are inconsistent due to the heterogeneity of the procedures used and populations targeted in such studies. Incidence rates vary widely according to type of surgery, suggesting that factors other than anesthesia explain a significant proportion of the observed variance. Anesthesia appears to be associated with longerterm cognitive disorder and the acceleration of senile dementia, but only in a small number of cases, suggesting the existence of other interacting etiological factors.     

Comparative outcomes for individual cognitive-behavior therapy, supportive-expressive group psychotherapy, and sertraline for the treatment of depression in multiple sclerosis.

This study compared the efficacy of 3 16-week treatments for depression in 63 patients with multiple sclerosis (MS) and major depressive disorder (MDD): individual cognitive- behavioral therapy (CBT), supportive expressive group therapy (SEG), and the antidepressant sertraline. Significant reductions were seen from pre- to posttreatment in all measures of depression. Intent-to-treat and completers analyses using the Beck Depression Inventory (BDI; A. T. Beck, C. H. Ward, M. Medelson, J. Mock, & J. Erbaugh, 1961) and MDD diagnosis found that CBT and sertraline were more effective than SEG at reducing depression. These results were largely supported by the BDI-18, which eliminates BDI items confounded with MS. However, the Hamilton Rating Scale for Depression (M. Hamilton, 1960) did not show consistent differences between treatments. Reasons for this inconsistency are discussed. These findings suggest that CBT or sertraline is more likely to be effective in treating MDD in MS compared with supportive group treatments. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Case finding in the elderly: a postal questionnaire

AIMS: To evaluate a postal questionnaire designed to identify elderly persons in need of geriatric evaluation and intervention in the community. METHODS: A sample of elderly persons, over 75 years, was randomly selected from the age-sex register of four general practices in the Auckland area. All respondents filled out postal questionnaires and a blinded assessment was made in their own homes using validated geriatric assessment tools (the reference test). Objective evaluations were compared to self report questionnaire results and sensitivity, specificity, positive and negative predictive values were calculated. RESULTS: Sixty-four persons aged 75-93 were evaluated. Thirty-nine subjects (61%) answered the questionnaire in a way which indicated they had one or more unmet needs. Reference test evaluations showed that 23 persons (36%) had problems in one or more areas. Sensitivity for the questionnaire was 0.78 (18/23 correctly identified) and specificity was 0.49. Positive and negative predictive values were 46% and 80% respectively. CONCLUSIONS: A postal questionnaire may be a useful adjunct to health surveillance of the elderly in general practice in New Zealand.     

Paroxetine. A review of its pharmacology, therapeutic use in depression and therapeutic potential in diabetic neuropathy

Paroxetine is a selective serotonin reuptake inhibitor effective in a once-daily administration regimen in the treatment of depression. In elderly patients (aged > or = 60 years) with major depression, short term (6 weeks) treatment with paroxetine produces clinical improvements significantly superior to those seen with placebo and similar to those with tricyclic antidepressant agents, mianserin and fluoxetine. There is evidence that paroxetine has positive effects on co-existing anxiety and does not precipitate agitation. Paroxetine has also shown potential in the symptomatic treatment of diabetic neuropathy; however, further clinical experience is needed to confirm this preliminary result. Short term paroxetine therapy is associated with fewer anticholinergic and CNS adverse effects, but generally more gastrointestinal disturbances, than tricyclic antidepressants and mianserin. Unlike the tricyclic agents, paroxetine does not significantly affect cardiovascular function or impair psychomotor performance. This tolerability profile should be particularly beneficial in elderly patients, who are generally more susceptible than younger patients to the anticholinergic and CNS adverse events associated with tricyclic antidepressant drugs, and in whom there is a higher prevalence of pre-existing cardiovascular disease. It also suggests an important potential advantage over tricyclic antidepressants in the setting of overdosage. Thus, primarily because of its better tolerability profile and potentially lower toxicity in overdosage and in patients with cardiovascular disease, paroxetine appears to be a more attractive option than tricyclic antidepressants for the treatment of depression in late life. Future research should attempt to define more fully the efficacy of paroxetine as long term prophylactic therapy for recurrent depression and to assess how its overall therapeutic profile compares with other selective serotonin reuptake inhibitors in the elderly.     

Impact of depression on response to comedy: A dynamic facial coding analysis.

Individuals suffering from depression show diminished facial responses to positive stimuli. Recent cognitive research suggests that depressed individuals may appraise emotional stimuli differently than do nondepressed persons. Prior studies do not indicate whether depressed individuals respond differently when they encounter positive stimuli that are difficult to avoid. The authors investigated dynamic responses of individuals varying in both history of major depressive disorder (MDD) and current depressive symptomatology (N = 116) to robust positive stimuli. The Facial Action Coding System (Ekman & Friesen, 1978) was used to measure affect-related responses to a comedy clip. Participants reporting current depressive symptomatology were more likely to evince affect-related shifts in expression following the clip than were those without current symptomatology. This effect of current symptomatology emerged even when the contrast focused only on individuals with a history of MDD. Specifically, persons with current depressive symptomatology were more likely than those without current symptomatology to control their initial smiles with negative affect-related expressions. These findings suggest that integration of emotion science and social cognition may yield important advances for understanding depression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)