Depressive symptoms and antidepressant use in a random community sample of ethnically diverse, urban elder persons

BACKGROUND: There are limited data on depressive symptoms and antidepressant use in ethnically diverse, urban elderly. METHODS: Analysis of depressive symptom and antidepressant use data from an epidemiological survey of dementia in an ethnically diverse, urban, elderly community. RESULTS: 21.5% (N=566) reported clinically significant depressive symptoms. Severity was inversely associated with socioeconomic status. 7.5% (N=194) reported antidepressant medication use. Multiple logistic regression analysis adjusting for severity and other covariates showed that men and African Americans had nearly half the odds of using antidepressants. Antidepressant use was more frequent among Hispanics, those with more severe depression and more medical illness. LIMITATIONS: Combined sample; CES-D not validated in Hispanics and inner-city African Americans; depressive symptoms assessed at one time-point; lack of complete income data; geographically restricted. CONCLUSIONS: In this elder sample, taking into account depressive symptom severity and other confounds, antidepressant use is nearly half as likely among men and African Americans.     

The association among depressive symptoms,smoking status and antidepressant use in cardiac outpatients

Both depression and smoking are highly prevalent and related to poorer outcomes in cardiac patients. In this study, the authors examined the association between depressive symptoms and smoking status, described the frequency and type of antidepressant use, and prospectively tested the effects of antidepressant use in smokers on smoking status and psychosocial outcomes. Participants comprised 1,498 coronary artery disease (CAD) outpatients who completed a baseline survey which assessed depressive symptoms, current medications, and smoking status. A second survey was mailed 9 months later that assessed depressive symptoms, anxiety, insomnia and smoking status. Results showed that current and former-smokers had significantly greater depressive symptoms than non-smokers. Ten percent of patients were taking antidepressants, most frequently SSRIs, with significantly more smokers on antidepressants than former and non-smokers. At follow-up, smokers on antidepressants were less likely to have quit, had greater anxiety, depressive symptoms and insomnia than smokers not using antidepressants. This study demonstrated that smokers and quitters with CAD had greater depressive symptoms and use of antidepressants than non-smokers, but that the antidepressants utilized may not be optimizing outcomes.     

功能性消化不良患者伴抑郁障碍的诊断和治疗

目的：探讨功能性不良（FD）患者的抑郁障碍及抗抑郁药对其疗效。方法：以CCMD－2－R为标准诊断抑郁障碍。将伴抑郁的FD随机分为3组：文拉法新组，多塞平组和对照组（常规内科治疗）。以治疗前，治疗2周和8周FD症状积分及Zung抑郁自评量表（SDS）积分变化评定疗效。结果：（1）FD中抑郁障碍的发生率为32．28％。（2）FD症状积分在文拉法新组和多塞平组于治疗2周时即明显减少（P＜0．05），于治疗8周时非常明显低于对照组（P＜0．05）；SDS只分在文拉法新组于治疗2周时即明显减少（P＜0．05），文拉法新组和多塞平组于治疗8周时均明显低于对照组（P＜0．05）；（3）文拉法新组不良反应明显低于多塞平组。结论：FD伴发的抑郁障碍发生率高，抗抑郁治疗能有效改善消化不良和抑郁症状，文拉法新作用迅速且优于多塞平。     

维生素B〈sub〉12〈/sub〉对抑郁症的辅助治疗

目的观察抑郁症患者血清维生素B12水平,探讨抗抑郁剂合并维生素B12治疗维生素B12缺乏抑郁症的疗效及安全性。方法对400名抑郁症患者进行血清维生素B12浓度测查,将筛查出的维生素B12缺乏的抑郁症患者70例,随机分为两组,各35例。对照组根据病情口服西酞普兰20～40 mg/次,每日1次,治疗8周;研究组根据病情口服西酞普兰20～40 mg/次,每日1次,同时合并使用维生素B12,治疗8周。研究组及对照组治疗前后1,2,4,8周末分别进行汉密尔顿抑郁量表（HAMD）评定;治疗后1,2,4,8周末分别评定副反应量表（TESS）;治疗前及治疗后4,8周末分别查血清维生素B12浓度。结果抑郁症患者血清维生素B12平均水平（359.7±183.2）pg/ml,维生素B12缺乏发生率为19.5%,研究组与对照组第1周末汉密尔顿抑郁量表评分差异无显著性（P＞0.05）,治疗第2,4、8周末有显著性差异（P〈0.01）,研究组有效率为94.3%,对照组为74.3%,两组差异有显著性（P〈0.01）,血清维生素B12浓度治疗后4,8周末有显著性差异（P〈0.01）,且研究组汉密尔顿抑郁量表评分与血清维生素B12浓度负相关。两组不良反应均较轻微,TESS评分比较差异无显著性（P＞0.05）。结论抑郁症患者血清维生素B12平均水平较正常明显降低,维生素B12缺乏发生率高,维生素B12辅助抗抑郁剂治疗可明显提高疗效,且不增加不良反应。     

Antidepressant response and well-being in pre-, peri- and postmenopausal women with major depressive disorder treated with fluoxetine

BACKGROUND: We assessed the impact of menopausal status on treatment response and well-being in a cohort of outpatient women with major depressive disorder (DSM-III-R criteria), who received treatment with fluoxetine (20 mg/day for 8 weeks). METHODS: Menopausal status was defined based on age, presence of menstrual irregularity or amenorrhea and vasomotor symptoms. Remission and response of depression were defined as a 17-item Hamilton Depression Rating Scale (HAM-D-17) score or=50%, respectively. Well-being was assessed by self-rating with the Symptom Questionnaire. Remitters were followed up for 28 additional weeks. RESULTS: No differences in rates of response and remission as well as in levels of well-being were observed among pre- (n = 121), peri- (n = 28) and postmenopausal (n = 35) women at the endpoint of the acute phase, even after adjustment for baseline depression severity. Residual symptoms, however, were significantly more common in postmenopausal women, except for the continuation phase endpoint. Differences in residual symptoms during the acute phase subsided after adjustment for baseline depression severity. CONCLUSIONS: Overall, menopausal status did not significantly affect the response to fluoxetine treatment and the degree of posttreatment well-being among major depressive disorder patients.     

The association of serum C-reactive protein with the occurrence and course of postpartum depression

CRP has been positively correlated with depressive symptomatology but this has received less study in postpartum depression (PPD). In this secondary analysis of a trial of PPD treatment, depressive symptoms (Structured Interview Guide for the Hamilton Depression Rating Scale—Atypical Depression Symptoms (SIGH-ADS₂₉)) and serum CRP levels were assessed and associations between CRP and SIGH-ADS₂₉ scores evaluated. The associations between baseline log CRP and depression response and remission were also assessed. Of the 35 women included, neither baseline log CRP nor exit log CRP was significantly associated with SIGH-ADS₂₉ score. Baseline CRP was not associated with response or remission. In this sample of women with PPD, CRP was not associated with depressive symptoms nor response to treatment.

     

Serum levels of interleukin-6 and interleukin-10 in relation to depression scores in patients with cardiovascular risk factors

It is currently unknown whether elevated cytokine levels in depression are confined to any specific subgroup of depressive patients. In this study, medical out-patients presenting with cardiovascular risk factors (N = 356) were assessed for both cognitive-affective and physical symptoms of depression using the Hospital Anxiety and Depression Scale (HADS) and the Maastricht questionnaire (MQ), respectively. In study participants assigned to the highest (≥21) and lowest (≤5) quartile for the MQ score, serum levels of cytokines were measured. We found highly significant associations between cognitive-affective symptoms of depression and elevated serum levels of interleukin-6 (IL-6; ρ = .231; p = .002) and interleukin-10 (IL-10; ρ = .370; p < .001), respectively. In multiple regression models elevated IL-10 serum concentration was independently related to cognitive-affective symptoms of depression (ρ = .165; p = .002). When all cytokines were included in one model, elevated IL-10 serum concentrations remained a significant predictor for depressive mood (ρ = .157; p = .009). In patients with cardiovascular risk factors and extreme scores for vital exhaustion, elevated serum IL-6 and even more IL-10 concentrations are linked to the presence of depressive mood. Future studies will have to test whether the so far unreported association of IL-10 with depressive mood represents a causal pathway involved in the pathogenesis or in the prognostic effect of depressive mood in cardiac patients.     

Plasma and serum brain-derived neurotrophic factor (BDNF) in depressed patients during 1 year of antidepressant treatments

BACKGROUND: Brain-derived neurotrophic factor (BDNF) has been hypothesized to be involved in the neurobiology of major depression. The aim of this study was to assess the possible relationships between depressive symptoms and serum and/or plasma BDNF levels during 1 year of antidepressant treatment. METHODS: Plasma and serum BDNF levels were assayed in 15 drug-free depressed patients and in 15 healthy control subjects at baseline and the 1st, 3rd, 6th and 12th month of antidepressant treatment. RESULTS: At baseline, patients' serum and plasma BDNF levels were significantly lower (p<.001 and p=.004, respectively) than those found in healthy control subjects. However, while from the 1st month of treatment patients' plasma BDNF levels did not differ significantly from those observed in healthy control subjects, serum BDNF levels in patients remained significantly lower at all times. LIMITATIONS: The main limitations of the current study are represented by the small sample size and the high discontinuation rate. CONCLUSIONS: Untreated depressed patients showed reduced baseline serum and plasma BDNF levels, as compared with control subjects. The clinical improvement paralleled the normalization of plasma BDNF after 1 month of treatment, while, at every assessment time, patients' serum BDNF levels were lower than those of control subjects. This would suggest that serum BDNF might represent a non-specific trait marker of depression.     

Faster response in depressive patients treated with fluoxetine alone than in combination with buspirone

BACKGROUND: The aim of this study was to compare the antidepressant efficacy of standard dose, dose optimization of antidepressant drug and buspirone augmentation strategies. METHODS: 120 outpatients with a DSM-IV diagnosis of unipolar depression were randomised to 12-weeks of open label treatment with fluoxetine 20 (flx20) or 40 mg (flx40) daily or fluoxetine 20 mg plus buspirone 20 mg daily (flx20-plus-buspirone). The severity of depression was assessed by Hamilton Depression Rating Scale (HDRS). Response was defined as a 50% or greater reduction of the baseline HDRS total score. A response, which began at any time of the study and was maintained until the last visit, was defined as a sustained response. RESULTS: The proportion of responders was not significantly different among the treatment groups at the endpoint. Survival analysis showed, however, a significant faster response in the patients treated with flx20 or flx40 alone than flx20-plus-buspirone. The mean times to onset of a sustained response were 33, 24 and 40 days, respectively. LIMITATIONS: The lack of treatment-resistant group is a methodological limitation of this study. CONCLUSIONS: Adding buspirone to fluoxetine in the treatment of major depressive disorder may delay the time to onset of antidepressant efficacy. In order to accelerate and maximise the clinical response in depressive patients, clinician should prefer to optimize the fluoxetine dose instead of in combination with buspirone.     

Inflammatory Markers in Acute Myocardial Infarction Patients: Preliminary Evidence of a Prospective Association With Depressive Symptoms

Inflammatory activity has been associated with both coronary disease and depressive symptoms. We sought to determine whether inflammatory markers in myocardial infarction (MI) patients are prospectively associated with depressive symptomatology. Participants were a convenience sample of MI patients. Depressive symptoms were assessed soon after the MI and again 7 months postdischarge. Inflammatory markers examined were interleukin-6 (IL-6) and interleukin-1β. Results suggest no significant cross-sectional association between inflammatory markers and depressive symptoms at baseline. However, bivariate and multiple regression analyses revealed a significant positive prospective association between baseline IL-6 and depressive symptoms 7 months later ( β  = .57, p  < .01). The results suggest that temporal considerations are important in understanding relationships between inflammation and depressive symptoms following MI.     

Partial sleep deprivation therapy combined with sertraline induces more rapid improvements in quality of life items in major depressive disorder

BACKGROUND: Total or partial sleep deprivation was showed to have rapid antidepressive effects in depression. Sleep deprivation therapy in major depression constitutes insufficient antidepressive treatment response and depressive symptoms reoccur after one night of recovery. Combination of antidepressant medication with sleep deprivation therapy is generally indicated. These combination therapies were found more favorable overall therapeutic effect than antidepressive monotherapy. METHODS: In this study, we examined the Quality of Life changes with the antidepressive therapy using partial sleep deprivation plus sertraline and sertraline monotherapy in patients with major depressive disorder. Thirteen patients received six partial sleep deprivation therapies in addition to sertraline, that sleep schedule in deprivation nights started at 11:00-12:00 p.m. to 03:00 a.m. and 11 patients treated with sertraline monotherapy as a control group. Quality of Life was evaluated with the WHOQOL-100, depression and the accompanying anxiety were also assessed at baseline and at the end of the 4th week. RESULTS: Patients treated with combination therapy improved significantly and more rapidly. Rapid improvement in quality of life in major depressive disorder was showed in patients treated with combination of late partial sleep deprivation and sertraline. LIMITATIONS: Small sample size, the lack of placebo group and short duration of the study are the main limitations. CONCLUSIONS: In clinical practice, QOL improvement can be accelerated using combination of partial sleep deprivation with the sertraline therapy.     

Effect of medical comorbidity on response to fluoxetine augmentation or dose increase in outpatients with treatment-resistant depression

This study assessed the effect of general medical comorbidity on response to next-step antidepressant treatments among subjects with major depressive disorder whose depression failed to respond to an 8-week open trial of 20 mg/day of fluoxetine. Of the 386 outpatients in the open trial, 101 who remained depressed were randomly assigned to double-blind treatment with either an increased dose of fluoxetine or lithium or desipramine augmentation for 4 weeks. The Cumulative Illness Rating Scale (CIRS) was used to assess baseline general medical comorbidity, and the Hamilton Depression Rating Scale was used to assess depressive symptoms. Logistic regression analysis showed that CIRS score was not associated with likelihood of remission or premature study discontinuation. Medical comorbidity thus does not appear to be associated with significantly poorer outcome among patients whose major depressive disorder failed initially to respond to an initial trial of 20 mg/day of fluoxetine.     

Promoter polymorphisms of SERPINE1 are associated with the antidepressant response to depression in Alzheimer's disease

Depression is one of the most frequent neuropsychiatric symptoms in Alzheimer's disease (AD). As the main regulator of the tissue plasminogen activator/brain-derived neurotrophic factor axis, plasminogen activator inhibitor-1 (PAI-1) is involved in the pathogenesis of both AD and depression. This suggests a potential role of the PAI-1 gene SERPINE1 in the development of AD-related depression and its response to antidepressant treatment. The purpose of this study was to explore the association between the SERPINE1 promoter polymorphisms (rs1799889 and rs2227631) and the risk of depression in AD and to determine the relationship between these 2 polymorphisms and the response to paroxetine treatment in AD patients with depressive symptoms. A total of 423 AD patients, all of which were inpatients, including 161 patients with obvious depressive symptoms, were recruited into this study, and the MassARRAY system was used for genotyping. We failed to detect any significant associations of these 2 polymorphisms with AD-related depression in the Chinese population (p>0.05). However, for the depressive symptoms in AD, the frequency of the 5G allele of rs1799889 was significantly higher (p=0.009 after Bonferroni correction) in responders than in non-responders to an 8-week paroxetine treatment. Our preliminary results suggest that the SERPINE1 promoter polymorphisms may be associated with antidepressant treatment, but not with the increased susceptibility to the depressive symptoms in AD.     

Long-term naturalistic treatment of depressive symptoms in bipolar illness with divalproex vs. lithium in the setting of minimal antidepressant use

OBJECTIVE: Risks have been associated with the long-term use of antidepressant in the treatment of bipolar disorder. We review our naturalistic experience with divalproex versus lithium in treating depressive symptoms of bipolar illness. METHOD: All patients with bipolar disorder treated with lithium or divalproex were identified in a university outpatient psychiatry clinic sample over one year (n=38 patients, 41 treatment trials). Treatment response was based on standard prospective symptom rating scales. Mean duration of follow-up was 90 weeks. RESULTS: Lithium and divalproex were equally effective and tolerated in the total sample. Antidepressant effects were noted despite sparing use of standard antidepressant agents (19% received them). Lithium non-responders responded well to divalproex (50%), and vice versa (44%). Divalproex monotherapy (24%) was more common than lithium monotherapy (7%, P=0.07) and was notably effective in treating depressive symptoms, with a 7/10 response on the CGI-BP and improvement on the HDRS (14.8+/-9.2 to 7.6+/-7.8, P=0.003, duration of prospective follow up 26.7 weeks). CONCLUSIONS: Lithium and divalproex were equally effective and tolerated in this naturalistic sample, but responders may represent distinct subgroups. Both agents, but particularly divalproex, demonstrated long-term antidepressant effects, with limited adjunctive standard antidepressant use.     

Treatment-resistant depression and Axis II comorbidity

BACKGROUND: Researchers of unipolar depression have speculated that personality disturbance is a contributing factor in the development of treatment resistance. The purpose of this study was to compare the prevalence of Axis II disorders between a sample of rigorously defined, treatment-resistant depressed outpatients and a sample of depressed outpatients not having experienced treatment resistance. METHODS: 53 patients with treatment-resistant depression (TRD) and 105 patients with non-treatment-resistant depression (non-TRD) were recruited through respective outpatient clinical trials at the Massachusetts General Hospital's Depression Clinical and Research Program. Diagnosis of Major Depressive Disorder was made using the Structured Clinical Interview for the DSM-III-R, personality disorders were assessed using the Structured Clinical Interview for DSM-III-R Personality Disorders, and antidepressant treatment resistance was defined using the McLean Hospital Antidepressant Treatment Record. Participants from both studies were matched for baseline HAM-D-17 total score and gender. Multiple chi-square analysis was used to compare frequencies of Axis II disorders between TRD and non-TRD patients as well as to compare categorical baseline demographic variables. Unpaired t tests were used to compare baseline demographic and clinical variables measured in a continuous manner. RESULTS: Non-TRD patients had a higher rate of obsessive-compulsive personality disorder than TRD patients, but this difference was not statistically significant after adjusting for multiple comparisons. No other differences were found to be statistically significant. Range of Axis II comorbidity was 0.0-30.2% for TRD patients and 2.9-37.1% for non-TRD patients. CONCLUSIONS: In this sample, treatment resistance in a current major depressive episode was not associated with an increased rate of Axis II disorders. Strengths of this study include the use of structured interview instruments to assess Axis I and II conditions, and having the two study groups matched for gender and baseline severity of depression. Limitations of this study include a modest sample size and reliance on DSM personality constructs.     

Serotonin transporter mRNA expression in peripheral leukocytes of patients with major depression before and after treatment with paroxetine

Serotonin transporter (5HTT) is thought to be involved in the pathophysiology of major depression and the target of antidepressants. We hypothesized that 5HTT mRNA levels in peripheral leukocytes may be associated with depressive states and the therapeutic response to antidepressant treatments. Fifteen patients with major depression and age-, sex-matched control subjects were studied. 5HTT mRNA levels were determined with quantitative real-time PCR method. 5HTT mRNA levels in leukocytes were significantly higher in depressive patients at baseline (before medication) than in control subjects. 5HTT mRNA levels were decreased significantly after 8 weeks of paroxetine medication compared with those at baseline. Our investigation suggested that the increased expression of 5HTT mRNA in peripheral leukocytes may be related with the pathophysiology of depression and its reduction after treatment may reflect the adaptive change induced by the antidepressant.     

Neurophysiologic changes during estrogen augmentation in perimenopausal depression

BACKGROUND: Estrogen augmentation of antidepressant medication has been an effective treatment in a subgroup of women experiencing affective symptoms during perimenopause. It has been suggested that estrogen facilitates serotonergic transmission in brain regions involved in mood disorders. We investigated differences in physiologic brain changes with estrogen augmentation in women with perimenopausal depression who reached remission compared to those who did not reach remission. We also assessed whether such changes were correlated with serum hormone levels. METHODS: Quantitative electroencephalography (QEEG) was used to examine neurophysiologic brain changes in remission and non-remission of depressive symptoms. Women with major depressive disorder (MDD) in partial remission who were taking antidepressant medication for a minimum of 8 weeks and were experiencing two or more perimenopausal symptoms (hot flashes, night sweats, irregular periods, memory impairment, vaginal dryness) were recruited from the community. Absolute power, relative power, and QEEG cordance, a measure that has moderately strong associations with cerebral perfusion, were obtained before and after 6 weeks of treatment with 0.625 mg of conjugated estrogen per day. RESULTS: Women who experienced remission of depressive symptoms (Ham-D< or =7) had a significant decrease in right frontal QEEG cordance (p=0.008, t((8))=-3.54) which was not present in non-remitters. No significant correlations were found between hormone levels and QEEG cordance. CONCLUSION: In women with perimenopausal depression, physiologic brain changes in the right frontal region during estrogen augmentation were associated with remission of depression.     

A 3.5-year naturalistic follow-up study of depressed out-patients

Outcome studies of patients suffering from depression indicate high relapse rates and a tendency towards chronicity. The present study describes the long-term outcome of 95 depressed outpatients in a third-level referral centre. and examines the relationship between baseline-variables (age, sex, level of psychopathology, age at onset of first psychiatric disorder, duration of illness at baseline, diagnosis) and outcome variables. After 3.5 years, 34 patients (36%) had a chronic course, 24 patients (25%) had at least one recurrence and 37 patients (39%) had a non-recurrent course. Chronicity was significantly correlated with an early age of onset of the first psychiatric disorder, a high level of psychopathology and a high level of depressive symptoms at baseline. The duration of depression at index did not differentiate chronic course from recurrent or non-recurrent course. After 1 year of follow-up, patients with recurrence were significantly more likely to stop antidepressant treatment. The results confirm the great chance for chronicity and recurrence in depression and the need to develop long-term treatment programs to prevent relapse.     

Clinical response augments NK cell activity independent of treatment modality: a randomized double-blind placebo controlled antidepressant trial

BACKGROUND: Major depressive disorder (MDD) has been associated with alterations in immune function. Suppression of natural killer (NK) cell activity (NKCA) reliably characterizes immunological alterations observed in MDD. Antidepressant pharmacotherapy has been associated with modulation of NKCA. Previous investigations into antidepressant modulation of NKCA have not employed randomized double-blind placebo controlled designs. Thus, it is unknown whether treatment-associated changes in immune function are due to drug, placebo, or spontaneous remission effects. The present investigation examined the effect of antidepressant treatment on NKCA utilizing a randomized double-blind placebo controlled experimental design. METHOD: Patients (N = 16) met DSM-IV criteria for MDD and were randomly assigned to drug (N = 8; citalopram, 20 mg/day) or placebo (N = 8) under double-blind conditions. Severity and pattern of depressive symptoms were assessed by the Hamilton Depression Rating Scale (HDRS). NK cell function was measured using a standard chromium-release assay and NK cell number assessed by flow cytometry. HDRS scores, NK cell function, and NK cell numbers were collected at 0, 1, 2 and 4 weeks of treatment. RESULTS: Clinical response was associated with augmented NKCA independent of treatment condition. Failure to respond to treatment resulted in significantly reduced NKCA over treatment interval. CONCLUSIONS: The present results suggest that alterations in the depressive syndrome, regardless of therapeutic modality, may be sufficient to modulate NKCA during antidepressant trials and thus may significantly impact on co-morbid health outcomes in MDD.     

Longitudinal relations between employment and depressive symptoms in low-income, suicidal African American women

Unemployment and depression are problematic at both individual and societal levels, and research suggests that the two phenomena are related. More thorough and longitudinal analyses, particularly ones within low-income minority populations, are needed to guide the development of programs to increase employment in persons with mental health problems. The current study aimed to specify the relations over time between depressive symptoms and employment status within a sample of 46 low-income African American women participating in an intervention study for intimate partner violence and suicidal behavior. Hierarchical logistic regression analysis indicated that baseline levels of depressive symptoms predicted employment status at the end of a 10-week intervention period, controlling for baseline employment status. Chi-square analysis and qualitative analyses of trends in depression scores showed that changes in employment status during the 10-week intervention period predicted 6-month and one-year follow-up levels of depressive symptoms. Results imply that, for women in the currently sampled population, depressive symptoms create vulnerability for job loss, but the ability to gain employment despite high levels of depressive symptoms is linked to lowered depression levels over the long term. Community programs assisting such women could therefore not just lower the vulnerability to job loss by treating depressive symptoms, but they could potentially lower long-term depression levels through interventions that enhance employability and motivation to pursue work.