Drug treatment in depressed elderly in the Dutch community

OBJECTIVES: In older people, a diagnosis of depression is frequently missed, and proper treatment is subsequently hampered. We investigated antidepressant and benzodiazepine use in an older community sample, and assessed possible risk factors associated with non-treatment in depressed elderly. METHODS: Data were used from the baseline measurements of the Longitudinal Aging Study Amsterdam (LASA). In a random, age and sex stratified community sample of 3107 older Dutch people (55 to 85 years), respondents were screened on depression with the Center for Epidemiologic Studies Depression Scale (CES-D). In the depressed subsample depressive disorder according to DSM-III was assessed using the Diagnostic Interview Schedule (DIS). The use of antidepressants and anxiolytics (benzodiazepines) in the depressed subsample was measured, and associations with age, sex, cognitive impairment, physical health and anxiety symptoms were investigated. RESULTS: Only 16% of the respondents with a major depressive disorder used antidepressants. More than half of them used non-therapeutic dosages. Lower antidepressant use was associated with cognitive impairment. Benzodiazepine use was more likely than antidepressant use, which was especially evident in females in the major depressive disorder group. CONCLUSIONS: Depressed older people were undertreated, particularly when they were cognitively impaired. A high rate of benzodiazepine use was found, particularly in females.     

Factors associated with antidepressant use in depressed and non-depressed community-dwelling elderly: the three-city study

OBJECTIVES: The aim of this study was to identify factors associated with antidepressant use in non-depressed and depressed elderly persons, assuming that they varied according to clinical status. METHODS: We studied 7,868 French community-dwelling subjects aged 65 years and over. The Center for Epidemiological Studies-Depression scale and the Mini International Neuropsychiatric Interview were used to define three groups: non-depressed, high depressive symptoms and current major depressive disorder. Separate analyses were performed to identify the factors which were associated with antidepressant use in each group. RESULTS: Antidepressant use (55% selective serotonin re-uptake inhibitors, 25% tricyclic antidepressants, 20% other types) increased from 4.9% in non-depressed subjects to 17.3% in subjects with high depressive symptoms (HDS) and 33.6% of in those with current major depressive disorder (MDD). The factors associated with antidepressant use varied according to depression status. In particular, men with current MDD were more often treated with antidepressants than women whereas, in both the HDS and the non-depressed groups, antidepressant use was, as has been observed elsewhere, more frequent in women. Gender also had a strong modifying effect on the relationship between antidepressant use and history of major depression. Finally, the direction of the association between antidepressant use and cognitive performance varied according to depression status. CONCLUSIONS: This study showed that the direction and strength of the association between antidepressant use and demographic and health-related factors varied according to the severity of depression symptoms. Further studies are needed to clarify the relationship between gender and cognition and antidepressant use.     

Effects of antenatal depression and antidepressant treatment on gestational age at birth and risk of preterm birth

OBJECTIVE: The authors evaluated the effects of prenatal antidepressant exposure and maternal depression on infant gestational age at birth and risk of preterm birth. METHOD: Ninety women were followed in a prospective, naturalistic design through pregnancy with monthly assessments of symptoms of depression and anxiety using the Structured Clinical Interview for DSM-IV mood module for depression, the Hamilton Depression Rating Scale, the Beck Depression Inventory, and the Perceived Stress Scale. Participants included 49 women with major depressive disorder who were treated with antidepressants during pregnancy (group 1), 22 women with major depressive disorder who were either not treated with antidepressants or had limited exposure to them during pregnancy (group 2), and 19 healthy comparison subjects (group 3). The primary outcome variables were the infants' gestational age at birth, birth weight, 1- and 5-minute Apgar scores, and admission to the special care nursery. RESULTS: Groups 1, 2, and 3 differed significantly in gestational age at birth (38.5 weeks, 39.4 weeks, 39.7 weeks, respectively), rates of preterm birth (14.3%, 0%, 5.3%, respectively), and rates of admission to the special care nursery (21%, 9%, 0%, respectively). Birth weight and Apgar scores did not differ significantly between groups. Mild to moderate depression during pregnancy did not affect outcome measures. CONCLUSIONS: Prenatal antidepressant use was associated with lower gestational age at birth and an increased risk of preterm birth. Presence of depressive symptoms was not associated with this risk. These results suggest that medication status, rather than depression, is a predictor of gestational age at birth.     

The role of provider attitudes in prescribing antidepressants to older adults: leverage points for effective provider education

OBJECTIVES: The purpose of this study was to determine if primary care provider knowledge of late-life depression, attitudes about treatment of depression in late life, and experience treating late-life depression affect the likelihood internists would prescribe antidepressants to older patients. METHODS: This study was a primary care provider survey study. From a pool of 456 eligible mailed surveys, 253 providers completed (55% response rate) a survey assessing provider self-reported knowledge about treating late-life depression with antidepressants, their attitudes about older patients' acceptance and response to antidepressant medications, their professional and personal experience with antidepressant medication, and their comfort with prescribing antidepressants to older patients was created for this study. RESULTS: Univariate analyses indicated that 75% of primary care providers were knowledgeable about the use of antidepressant treatment in older people, and 86% said they felt comfortable treating depression in older patients. Multivariate analyses indicated that the decision to treat older patients with antidepressants was largely influenced by time to treat patients, provider belief that antidepressants could treat late-life depression, their comfort with treating late-life depression, and having had older patients respond to antidepressant treatment in the past (R2 = .52, p < .001). CONCLUSIONS: This study shows that attitudinal and experiential factors play an important role in the likelihood that a provider will treat an older, depressed patient with an antidepressant, more so than knowledge about how to prescribe an antidepressant to older patients. Residency programs for primary care practitioners should include education about the efficacy of antidepressant treatment in older people and should involve hands-on experience in treating late-life depression.     

Adjunctive antidepressant use and symptomatic recovery among bipolar depressed patients with concomitant manic symptoms: findings from the STEP-BD

OBJECTIVE: Practice guidelines have advised against treating patients with antidepressants during bipolar mixed states or dysphoric manias. However, few studies have examined the outcomes of patients with co-occurring manic and depressive symptoms who are treated with antidepressants plus mood stabilizing drugs. METHOD: The authors compared outcomes in patients with bipolar disorder who received a mood stabilizing agent with versus without an antidepressant for a bipolar depressive episode accompanied by > or = 2 concurrent manic symptoms. The 335 participants were drawn from the first 2,000 enrollees in the National Institute of Mental Health (NIMH) Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Kaplan-Meier survival curves and Cox regression models were used to compare time to recovery. General linear models examined the relationship between antidepressant use or mania symptom load at the study entry and mania or depression symptom severity at the 3-month follow-up. RESULTS: Adjunctive antidepressant use was associated with significantly higher mania symptom severity at the 3-month follow-up. The probability of recovery at 3 months was lower among patients with higher baseline depression severity. Antidepressant use neither hastened nor prolonged time to recovery once potential confounding factors were covaried in a Cox regression model. CONCLUSIONS: In bipolar depression accompanied by manic symptoms, antidepressants do not hasten time to recovery relative to treatment with mood stabilizers alone, and treatment with antidepressants may lead to greater manic symptom severity. These findings are consistent with those from the STEP-BD randomized trial for pure bipolar depression, in which adjunctive antidepressants did not yield higher recovery rates than did mood stabilizer monotherapy.     

Risk factors for major depression in older medical inpatients: a prospective study.

OBJECTIVE: To determine risk factors for major depression in older medical inpatients. METHOD: In a prospective cohort study, 86 older medical inpatients without depression or antidepressant medication were assessed 3, 6, and 12 months after enrollment. Incident major depression was diagnosed using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. Potential predictive variables included sociodemographic variables, physical state, cognition, depressive symptoms, medication use, prior depressive episode, social network, support, and bereavement. Cox proportional hazards analysis (with backward variable elimination) was used to determine the best set of predictors. RESULTS: Twenty-six patients (30.2%) met criteria for incident major depression. Predictors of major depression included the following: prior depressive episode, birth outside Canada, low comorbidity, inadequate emotional support, fewer children seen, depressed mood, and diurnal variation. The risk of depression increased with the number of risk factors present. CONCLUSION: The seven identified risk factors may guide efforts to prevent major depression in older medical inpatients.     

Impact of antidepressant discontinuation after acute bipolar depression remission on rates of depressive relapse at 1-year follow-up

OBJECTIVE: While guidelines for treating patients with bipolar depression recommend discontinuing antidepressants within 6 months after remission, few studies have assessed the implications of this strategy on the risk for depressive relapse. This study examined the effect of antidepressant discontinuation or continuation on depressive relapse risk among bipolar subjects successfully treated for an acute depressive episode. METHOD: Eighty-four subjects with bipolar disorder who achieved remission from a depressive episode with the addition of an antidepressant to an ongoing mood stabilizer regimen were followed prospectively for 1 year. The risk of depressive relapse among 43 subjects who stopped antidepressant treatment within 6 months after remission ("discontinuation group") was compared with the risk among 41 subjects who continued taking antidepressants beyond 6 months ("continuation group"). RESULTS: A Cox proportional hazards regression analysis indicated that shorter antidepressant exposure time following successful treatment was associated with a significantly shorter time to depressive relapse. Furthermore, patients who discontinued antidepressant treatment within the first 6 months after remission experienced a significantly shorter period of euthymia before depressive relapse over the length of 1-year follow-up. One year after successful antidepressant response, 70% of the antidepressant discontinuation group experienced a depressive relapse compared with 36% of the continuation group. By the 1-year follow-up evaluation, 15 (18%) of the 84 subjects had experienced a manic relapse; only six of these subjects were taking an antidepressant at the time of manic relapse. CONCLUSIONS: The risk of depressive relapse in patients with bipolar illness was significantly associated with discontinuing antidepressants soon after remission. The risk of manic relapse was not significantly associated with continuing use of antidepressant medication and, overall, was substantially less than the risk of depressive relapse. Maintenance of antidepressant treatment in combination with a mood stabilizer may be warranted in some patients with bipolar disorder.     

Mediating roles of adherence attitude and patient education on antidepressant use in patients with depression

PURPOSE. The purpose of this study was to examine the roles of adherence attitude to antidepressants and patient education as mediators in mediating patients' attitudes toward antidepressant use. DESIGN AND METHODS. A sample of 201 outpatients, 50 years of age or older, with major depressive disorder, completed a drug use questionnaire, attitudes toward and patient education about antidepressants questionnaire, and Adherence Attitude Inventory. FINDINGS. Attitudes toward antidepressants were positively associated to antidepressant use, an association explained by the mediating variable, patient education about antidepressants. Adherence attitudes to antidepressants were a mediator that accounted to a significant degree for the causal relationship between attitudes toward antidepressants and antidepressant use. PRACTICE IMPLICATIONS. Adequate patient education and an understanding of patients' adherence attitude to antidepressant use are needed in nursing practice to reduce patients' uncertainty about treatment and increase successful treatment.     

Antidepressant treatment of co-occurring depression and alcohol dependence.

The use of antidepressant pharmacotherapy to treat patients with co-occurring depression and alcohol dependence is controversial. There is a stigma attached to giving medications to alcohol-dependent persons. Also, empirical evidence is sparse and inconsistent, which discourages the use of antidepressants in these patients. Historically, it has been a challenge to accurately diagnose a depressive disorder in the presence of alcohol dependence. In addition, early clinical studies were fraught with methodological problems; however, improved diagnostic assessments are now available, and in the last decade, results from well-controlled trials appear to support the use of antidepressants in this patient population in the specific role of relieving depressive symptoms. The majority of these trials also demonstrate that antidepressants have relatively little impact on reducing heavy drinking in this patient population, even though the medications reduce depressive symptoms. Newer approaches to treating patients with co-occurring depression and alcohol dependence suggest adding to the antidepressant a pharmacotherapy that directly impacts drinking. The findings from this review better define the action of antidepressants in patients with co-occurring depression and alcohol dependence as specific to reducing depressive symptoms, and these medications and their action on mood have little impact on treating the co-occurring alcohol dependence.     

Treatment of depression associated with the menstrual cycle: premenstrual dysphoria, postpartum depression, and the perimenopause

Several forms of depression are unique to women because of their apparent association with changes in gonadal hormones, which in turn modulate neuroregulatory systems associated with mood and behavior. This review examines the evaluation and treatment of depression that occurs premenstrually, postpartum, or in the perimenopause on the basis of current literature. The serotonergic antidepressants consistently show efficacy for severe premenstrual syndromes (PMSs) and premenstrual dysphoric disorder (PMDD), and are the first-line treatment for these disorders. The use of antidepressants for postpartum depression is compromised by concerns for effects in the infants of breast-feeding mothers, but increasing evidence suggests the relative safety of the antidepressant medications, and the risk calculation should be made on an individual basis. Estradiol may be effective for postpartum depression and for moderate-to-severe major depression in the perimenopause. In spite of its frequent use, progesterone is not effective for the mood and behavioral symptoms of PMS/PMDD, postpartum depression, or perimenopausal depressive symptoms.     

Depression in Asthma: Prevalence and Clinical Implications

BACKGROUND: Asthma and depression are both common illnesses. Data suggest that the prevalence of asthma and asthma-related morbidity and mortality has increased in the past 2 decades. Asthma has long been considered an illness in which mood and emotions contribute to symptom exacerbation. Therefore, we reviewed the recent literature on depression in persons with asthma. DATA SOURCES: The MEDLINE (1966-1999) and PSYCHINFO (1967-1999) databases were used to find English-language articles on asthma and depression. Search terms included asthma, depression, dysthymia, and mood. DATA SYNTHESIS: This literature suggests depressive symptoms are more common in asthma patients than in the general population and perhaps even more common than in some other general medical conditions. Depression may be associated with asthma morbidity and mortality. Limited data suggest the older tricyclic antidepressants may improve both depression and asthma symptoms. However, no studies have examined the use of second-generation antidepressants in asthma patients. CONCLUSION: Depressive symptoms are common in asthma patients. However, the prevalence of depressive disorders in this population is not well determined. Future studies should focus on determining the prevalence of major depressive disorder in this population and the effect of antidepressants on mood and asthma symptoms.     

Depression in the medical setting: biopsychological interactions and treatment considerations

This article examines depression in 6 medical conditions: coronary artery disease (CAD), cancer, human immunodeficiency virus (HIV) infection, Parkinson's disease, pain, and the sex hormone changes of aging. Research is beginning to define specific biological and psychological mechanisms underlying the adverse interactions between depression and these medical conditions. Antidepressant medications, psychosocial therapies, and hormonal manipulations are effective in reducing depressive symptoms. Specific psychosocial interventions may increase longevity in CAD and cancer and may enhance quality of life in HIV infection. Newer antidepressants appear to be safer and better tolerated than older agents for medically ill patients, but do not appear to be as effective for neuropathic pain. Dopamine agonists may benefit depression associated with Parkinson's disease. Hormone replacement therapy may improve subsyndromal depressive symptoms in postmenopausal women and may enhance antidepressant response for older women with major depression.     

Marital status, depressive episodes, and short-term prognosis of patients with acute coronary syndrome: Greek study of acute coronary syndrome (GREECS)

The association between marital status and short-term prognosis of patients hospitalized for acute coronary syndrome (ACS) was evaluated. From October 2003 to September 2004, a sample of 6 hospitals located in Greek regions was selected, and almost all survivors after an ACS were enrolled into the study (2172 patients were included in the study; 76% were men). The in-hospital mortality rate was 3.2% in male patients and 5.7% in female patients (p = 0.009). Never-married patients had 2.8-times higher risk of dying during hospitalization compared with married, after adjusting for various confounders (p < 0.01, attributable risk = 64%). Furthermore, never-married had 2.7-times higher risk of dying during the first 30-days following hospitalization compared with married (p < 0.01, attributable risk = 62%). Moderate depressive symptoms 3.26-fold (95% CI 1.40-7.11) the risk of recurrent events, while severe depressive symptoms were associated with 8.2-fold (95% CI 3.98-17.1) higher risk of events. No interaction was observed between marital status and depression on 30-day prognosis of ACS patients (p > 0.5). People who were not-married and depressed at the time of an acute cardiac episode were at higher risk of fatal events than people who were married, irrespective of depression status and other characteristics.     

The impact of antidepressant discontinuation versus antidepressant continuation on 1-year risk for relapse of bipolar depression: a retrospective chart review

BACKGROUND: Current treatment guidelines recommend discontinuation of an antidepressant within 3 to 6 months after remission of depression in patients with bipolar illness. Yet few studies directly compare the impact of antidepressant discontinuation versus antidepressant continuation on the risk for depressive relapse in patients with bipolar disorder who have been successfully treated for a depressive episode. METHOD: In a retrospective chart review, patients with DSM-IV bipolar disorder who were treated for an index episode of depression by adding antidepressant medication to ongoing mood stabilizer medications were identified. The risk of depressive relapse in 25 subjects who stopped antidepressant medications after improvement was compared with the risk of depressive relapse in 19 subjects who continued antidepressants after improvement. RESULTS: Termination of antidepressant medication significantly increased the risk of a depressive relapse. Antidepressant continuation was not significantly associated with an increased risk of mania. CONCLUSION: While this study may have been limited by the retrospective nature of the chart review, nonrandomized assignment of treatment, and reliance on unstructured progress notes, it suggests that antidepressant discontinuation may increase the risk of depressive relapse in some patients with bipolar disorder. Further research is needed to clarify whether maintenance antidepressant treatment may be warranted in some patients with bipolar disorder, especially in those with frequent recurrent depressive episodes.     

Safety and efficacy of testosterone gel 1% augmentation in depressed men with partial response to antidepressant therapy

The current study evaluates the efficacy and safety of testosterone (T) gel 1% augmentation on depressive symptoms and quality of life in treatment-resistant, depressed, hypogonadal men older than 50 years of age who are receiving antidepressants. The authors hypothesized that T augmentation would improve depressive symptoms and quality of life. Eighteen hypogonadal men entered the study who had had an adequate trial of antidepressant therapy and had significant depressive symptoms. Participants were continued on their antidepressant and were randomized to receive either placebo or active T gel (5 g) to be applied once a day. Participants were tested on 6 occasions: screening visit, an initial session (pretreatment), at 6 and 12 weeks during the first treatment condition, and at 18 and 24 weeks during the crossover condition. The authors found a significant improvement in depressive symptoms from baseline to 12 weeks of testosterone treatment. However, a statistical difference between placebo and testosterone treatment phases was not demonstrated. The limitations of the study, including the chronicity and severity of patients' depression, variability in T levels, and a small sample size, probably influenced the ability to detect a discernable difference. Nevertheless, the study shows that T gel augmentation may be helpful in hypogonadal males with depression.     

Medication use and nonadherence to psychoactive medication for mental health problems by community-living canadian seniors with depression

Objectives: To determine the relation between level of depression and psychoactive medication use and nonadherence in Canadian seniors, given that late-life depression is a common, serious mental health problem in Canada. Methods: Canadian Community Health Survey-Mental Health and Well-Being respondents aged 65 years and older (n = 7736) comprised the study sample. Using the Composite International Diagnostic Interview to assess depressive symptoms, we created 4 depression levels to capture a spectrum of depressive disorders and (or) symptoms: major depression, comorbid major depression, depressive symptoms, and no depressive symptoms. Psychoactive medications assessed included sleep aids, anxiolytics, and mood stabilizers and (or) antidepressants (AD). Nonadherence was defined as either not taking medication as recommended or taking medication at a lower dosage than prescribed. Results: In total, 22.5% of respondents took psychoactive medication for a mental health problem in the previous 12 months. Psychoactive medication use was 46.8% for major depression, 43.1% for comorbid major depression, 34.0% for depressive symptoms, and 17.6% for no depressive symptoms. Rates of psychoactive medication use ranged from 46.5% of those with major depression, to 17.6% of those with no depressive symptoms. Overall, the rate of nonadherence to psychoactive medication was 31%; rates were highest among those with depressive symptoms (37.4%) and lowest among those with no depressive symptoms (27.4%). All 3 depressive categories were associated with greater odds of use and nonadherence. Conclusion: All 3 depression categories were associated with increased use of and nonadherence to psychoactive medication; however, rates of AD and (or) mood stabilizer use for clinically significant depression were low.     

Efficacy of atypical antipsychotics in depressive syndromes

Depression is a frequent symptom in psychiatry, either isolated (major depression) or entangled with other psychiatric symptoms (psychotic depression, depression of bipolar disorders). Many antidepressant drugs are available with different pharmacological profiles from different classes: tricyclic antidepressants, monoamine oxydase inhibitors, selective serotonin reuptake inhibitors (SSRI). However, there are some limitations with these drugs because there is a long delay before relief for symptoms, some patients with major depression are resistant to treatment, there is a risk to induce manic symptoms in patients with bipolar disorders and these drugs have no effect on the psychotic symptoms frequently associated to major depression. The leading hypothesis for the search of more efficient new antidepressants has been the amine deficit hypothesis: noradrenaline and/or serotonin deficit and more recently dopamine deficit. Moreover, a dopamine deficit has been also hypothesized as the central mechanism explaining the negative symptoms of schizophrenia. These symptoms are the consequence of a deficit of normal behaviours and include affective flattening, alogia, apathy, avolition and social withdrawal. There is thus a great overlap between symptoms of depression and negative symptoms of schizophrenia. Atypical antipsychotics, in contrast with conventional neuroleptics, have been shown to decrease negative symptoms, most probably through the release of dopamine in prefrontal cortex, thus improving psychomotor activity, motivation, pleasure, appetite, etc. The dopamine deficit in cortical prefrontal areas was thus an unifying hypothesis to explain both some symptoms of depression and negative symptoms of schizophrenia. Studies in animal confirm this view and show that the association of an atypical antipsychotic drug and an SSRI (olanzapine plus fluoxetine) increases synergistically the release of dopamine in prefrontal areas. Moreover, most of the atypical antipsychotics have a large action spectrum, beyond the only dopamine receptors: their effects on the serotonin receptors--particularly the 5-HT2A and 5-HT2C receptors--suggest that their association to SSRI could be a promising treatment for depression. Indeed, SSRI act mainly by increasing the serotonin level in the synapse, thus leading to a non specific activation of all pre- and post-synaptic serotonin receptors. Among them, 5-HT2A/2C receptors have been involved in some of the unwanted effects of SSRI: agitation, anxiety, insomnia, sexual disorders, etc. The inhibition of these receptors could be thus beneficial for patients treated with SSRI. Amisulpride is an unique atypical antipsychotic that selectively blocks dopamine receptors presynaptically in the frontal cortex, possibly enhancing dopaminergic transmission. The antidepressant effect of amisulpride was shown in dysthymia in many clinical studies versus placebo, tricyclic antidepressants, SSRI or others. However, a shorter delay for symptom relief was not demonstrated for amisulpride as compared to comparative antidepressants. Other atypical antipsychotics (clozapine, olanzapine), which act on a large variety of receptors, have shown antidepressant effects--mainly in association with SSRI--in different psychiatric diseases: treatment-resistant major depression, major depression with psychotic symptoms and depression of bipolar disorders, with no increase of manic symptoms in this latter case. Moreover, the delay for symptom relief was greatly shortened. More comparative double-blind studies are required to confirm and to precise the antidepressant effects of atypical antipsychotics. Nevertheless, these studies suggest that atypical anti-psychotics could be of great value in depressive conditions reputed for their resistance to treatment with usual antidepressants. Particularly, new strategies emerge that combine atypical antipsychotics and antidepressants for greater efficacy and more rapid relief of depression symptoms.