Prevalence and clinical correlates of irritability in major depressive disorder: a preliminary report from the Sequenced Treatment Alternatives to Relieve Depression study

BACKGROUND: Irritability is a common feature of major depressive disorder (MDD), though it is not included in the DSM-IV diagnostic criteria for adult MDD and is not assessed in most standard depression rating scales. Irritability with or without depression has been associated with risk for suicide, violence, and cardiovascular disease. METHOD: The prevalence of significant levels of irritability was examined among the first 1456 outpatients with nonpsychotic MDD entering the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Sociodemographic and clinical features were compared for participants who did and did not report irritability at least 50% of the time during the week preceding study entry. RESULTS: Of 1456 evaluable subjects, 582 (40%) reported irritability more than half the time. These individuals were more likely than nonirritable subjects to be female, to be younger, to be unemployed, and to report a history of at least 1 suicide attempt. Functional status and quality of life were also poorer in this group. Irritability was correlated with overall depressive severity, which accounted for nearly all of the clinical differences noted, with the exception of vascular disease, for which the association persisted after controlling for age, sex, and depressive severity. CONCLUSION: Irritability is prevalent among depressed outpatients and associated with a greater likelihood of suicide attempts, poorer functional status, and greater prevalence of vascular disease. It is correlated with overall depression severity and thus may not represent a distinct depressive subtype per se. The impact of irritability on course and treatment outcome merits further study.     

Sex differences in depression symptoms in treatment-seeking adults: confirmatory analyses from the Sequenced Treatment Alternatives to Relieve Depression study

BACKGROUND: Although epidemiologic research consistently reports greater prevalence of major depressive disorder in women, small sample sizes in many studies do not allow for full elaboration of illness characteristics. This article examines sex differences in terms of illness attributes in a cohort of 2541 outpatients from across the United States who enrolled in the Sequenced Treatment Alternatives to Relieve Depression study. METHODS: Confirmatory analyses were performed in 2541 outpatients comparing men and women with regard to sociodemographic features, comorbid Axis I and Axis III conditions, and illness characteristics. Results were compared with those of our previous report on the initial population of the first 1500 individuals enrolled in Sequenced Treatment Alternatives to Relieve Depression study. RESULTS: In both samples, nearly two thirds of the sample (62.5%) were women. Women had greater symptom severity, but men had more episodes of major depression, despite no difference in the length of illness. No differences in age of onset emerged. As in the first cohort, women showed greater rates of an anxiety disorder, bulimia, and somatoform disorder, as well as more past suicide attempts, whereas men showed more alcohol and substance abuse. Women reported more appetite, weight, hypersomnia, interpersonal sensitivity, gastrointestinal and pain complaints, and less suicidal ideation. Irritability was equally common in men and women. CONCLUSION: This large analysis confirmed most of the clinical features and comorbidities found to be more prevalent in the first cohort of women. In addition, this analysis corroborated previous research suggesting higher rates of atypical and anxious depression in women but refuted the notion of an "irritable depression" found in men. The report confirmed the 1.7:1 ratio for depression seen across sexes in the National Comorbidity Survey.     

Translating Science Into Service: Lessons Learned From the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study

Objective: The purpose of this review is to summarize lessons learned from, and limitations of, the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, focusing on measurement-based care.Data Sources: PubMed and MEDLINE were searched from 1980 through 2006 using terms such as depression, major depressive disorder, augmentation, switching, measurement-based care, and remission. Other relevant articles were identified by checking reference lists of the identified studies.Study Selection: A total of 60 studies were initially identified, which resulted in 34 studies used in this review. The salient criteria used for selection of studies centered on whether results had implications for clinical practice and provided lessons that could be learned and practically applied to real-life settings.Data Extraction: Data were extracted from the STAR*D trial and associated studies that were pertinent to everyday problems encountered by mental health professionals in the community: determination of whether the optimum strategy for a particular patient involves "augmentation" or "switching" of a patient's medication.Data Synthesis: Measurement-based care is essential in order to identify the two thirds of patients who do not achieve remission with the first treatment strategy. Timely changes in antidepressant therapy can improve outcomes.Conclusions: The STAR*D trial underscores the importance of measurement-based care in identifying patients who may not have achieved remission with an initial antidepressant, enabling alternative options such as augmentation or switching to be prescribed to meet this ultimate goal of therapy.     

Treatment outcomes for older depressed patients with earlier versus late onset of first depressive episode: a Sequenced Treatment Alternatives to Relieve Depression (STAR*D) report.

OBJECTIVE: Controversy exists whether age at onset of the first depressive episode predicts chance of response and remission or the timing of such outcome. In this study of older depressed outpatients, the authors evaluated whether the age at onset of the first major depressive episode (MDE) was related to clinical outcomes. DESIGN: Post-hoc dataset analysis for older participants treated with citalopram in the Sequenced Treatment Alternatives to Relieve Depression trial was performed. Side effects, remission rates, and baseline characteristics were compared for participants whose first MDE began at or before age 55 (earlier onset) versus those with their first MDE after age 55 (late onset). SETTING: Participants were enrolled from 23 psychiatric and 18 primary care settings. PARTICIPANTS: There were 574 treatment-seeking outpatients (age range: 55-75 years) with nonpsychotic major depressive disorder who had a baseline 17-item Hamilton Rating Scale for Depression score of > or =14. INTERVENTION: Participants received citalopram treatment for up to 14 weeks. MEASUREMENTS: Remission was defined by a 16-item Quick Inventory of Depressive Symptomatology-Self-Rated score of < or =5 at study exit. Side effects were measured by the Frequency, Intensity, and Burden of Side Effects Rating. RESULTS: Of 574 participants, 72.1% had earlier-onset depression and 27.9% had late-onset depression. Remission rates were not statistically different between earlier-onset (30.8%) and late-onset (31.9%) participants. Time to remission did not differ as well. CONCLUSION: The self-reported age at onset of the first MDE being after age 55 was not related to clinical outcomes for participants 55 to 75 years of age.     

Enrolling research subjects from clinical practice: ethical and procedural issues in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial

The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial is a multi-site effectiveness study funded by the National Institute of Mental Health (NIMH) with the aim of identifying successful, acceptable and cost-effective treatment strategies for outpatients with unremitted depression. With enrollment of 4,041 adults with major depressive disorder (MDD), it is the largest controlled psychiatric treatment study ever undertaken. In the course of developing procedures to ensure that ambitious enrollment goals were met, a number of ethical and practical issues became apparent that underscore the conflicts between effectiveness research and human subject protections. These are delineated as they relate to study design; eligibility criteria; incentives to subjects; investigators and clinical sites; the complementary roles of clinical research coordinators (CRCs) and study clinicians; and recruitment and consent procedures. The STAR*D trial exemplifies the interplay and tension between those strategies that integrate research and clinical aims and roles in the service of enhancing external validity, site participation, and recruitment and retention versus those strategies that differentiate research and clinical treatment in the service of research integrity and human subject protections. We hope that a discussion of these key challenges and dilemmas and how they have been addressed will help inform future discussions concerning design and conduct of ethical effectiveness trials designed to optimize care in real world clinical settings.     

Familiality of major depressive disorder and gender differences in comorbidity

Objective: Gender differences exist in the prevalence and psychiatric comorbidity of major depressive disorder (MDD). This study investigates whether familiality of MDD contributes to observed gender differences in comorbidity. Method: Familial (f‐MDD) and non‐familial (nf‐MDD) MDD cases from a population sample were assessed for comorbid dysthymia, anxiety disorders and alcohol‐related disorders using the Composite International Diagnostic Interview (CIDI). Logistic regression analyses were performed to examine the effect of f‐MDD on gender differences in comorbidity, adjusted for confounders. Results: Women with f‐MDD reported significantly more comorbid dysthymia and generalized anxiety disorder (GAD) than their male counterparts; women with nf‐MDD reported significantly more comorbid simple phobias and agoraphobia than their male counterparts. Gender differences in comorbid panic disorder and alcohol‐related disorders occurred independently of the familial load. Adjustment for age of onset, severity and recurrence of MDD did not change these results. Conclusion: Models to explain comorbidity patterns of MDD differ by gender. Familiality of MDD should be taken into account.     

Current comorbidity of psychiatric disorders among DSM-IV major depressive disorder patients in psychiatric care in the Vantaa Depression Study

BACKGROUND: While numerous studies have documented the high comorbidity of major depressive disorder (MDD) with individual mental disorders, no published study has reported overall current comorbidity with all Axis I and II disorders among psychiatric patients with MDD, nor systematically investigated variations in current comorbidity by sociodemographic factors, inpatient versus outpatient status, and number of lifetime depressive episodes. METHOD: Psychiatric outpatients and inpatients in Vantaa, Finland, were prospectively screened for an episode of DSM-IV MDD, and 269 patients with a new episode of MDD were enrolled in the Vantaa Depression MDD Cohort Study. Axis I and II comorbidity was assessed via semistructured Schedules for Clinical Assessment in Neuropsychiatry, version 2.0, and Structured Clinical Interview for DSM-II-R personality disorders interviews. RESULTS: The great majority (79%) of patients with MDD suffered from 1 or more current comorbid mental disorders, including anxiety disorder (57%), alcohol use disorder (25%), and personality disorder (44%). Several anxiety disorders were associated with specific Axis II clusters, and panic disorder with agoraphobia was associated with inpatient status. The prevalence of personality disorders varied with inpatient versus outpatient status, number of lifetime depressive episodes, and type of residential area, and the prevalence of substance use disorders varied with gender and inpatient versus outpatient status. CONCLUSION: Most psychiatric patients with MDD have at least 1 current comorbid disorder. Comorbid disorders are associated not only with other comorbid disorders, but also with sociodemographic factors, inpatient versus outpatient status, and lifetime number of depressive episodes. The influence of these variations on current comorbidity patterns among MDD patients needs to be taken account of in treatment facilities.     

Fluoxetine: an update of its use in major depressive disorder in adults

The selective serotonin reuptake inhibitors (SSRIs) have emerged as a major therapeutic advance in psychiatry. They have emphasized the pathophysiological role of serotonin (5-HT) in affective disorders. Indeed, SSRIs were developed for inhibition of the neuronal uptake for serotonin (5-HT), a property shared with the TCAs (tricyclic anti-depressants), but without affecting the other various central neuroreceptors (ie, histamine, acetylcholine and adrenergic receptors) that are responsible for many of the safety and tolerability problems with TCAs. In this way, fluoxetine and other SSRIs represent a major advance over tricyclics, because of their lower toxicity. While the position of fluoxetine relative to other selective serotoninergic antidepressants requires further investigation, fluoxetine has a more favorable tolerability profile for a similar efficacy in comparison to tricyclic antidepressants. The pharmacokinetic and pharmacodynamic properties of fluoxetine are well described. After oral administration, fluoxetine is almost completely absorbed. Due to hepatic first-pass metabolism, the oral bioavailability is < 90%. Fluoxetine has a half-life of 2-7 days, whereas the half-life of norfluoxetine ranges between 4 and 15 days. This long half-life of fluoxetine may be advantageous when the patient omits a dose since drug concentrations decrease slightly. On the other hand, in the case of fluoxetine non-response, long washout periods are necessary before switching the patient to a TCA or a MAO inhibitor to avoid drug interactions or the development of a 5-HT syndrome. As a class, SSRIs are considerably more selective in comparison to TCAs in terms of their central nervous system mechanisms, but differ in other clinically relevant aspects. This action affects several specific 5-HT receptors, which, in turn, effects a multitude of neural systems and signalization pathways. However, despite the facilitating serotoninergic neurotransmission, the direct mechanism by which a SSRI exerts its anti-depressant activity remains uncertain. The therapeutic response in major depression for SSRIs (ie 15-20 days) maybe due to a progressive desensitization of somatodendritic 5-HT autoreceptors in the midbrain raphe nucleus. On the other hand, it has also been postulated that 5-HT is a modulator of several neurophysiological pathways, including dopamine, noradrenaline, but also neurotrophic factors, intra-cytoplasmic phosphorylations and nuclear genes expression. Therapeutic activity of SSRIs may finally results in a complex modulation and homeostasis between monoaminergic neurotransmisson and neuronal plasticity. In term of health-care, the introduction of fluoxetine and other SSRIs in the 1980s has radically changed the treatment of depressive disorder worldwide and they have emerged as the first line of treatment for depressive disorders. The efficacy of fluoxetine is now well established in the treatment of major depressive disorder. Indeed, this efficacy has been assessed in numerous clinical controlled trials involving patients with major depressive disorders. Meta-analysis were carried out and confirmed that fluoxetine was as effective as the tricyclic antidepressants, and appeared more effective than placebo in improving the symptoms of depression. However, there is no scientific evidence to suggest that any one SSRI is more effective than another, but not all patients respond to the same agent. Looking to the future, we need further comparative studies of the SSRIs with the next generation of antidepressants such as 5-HT noradrenaline reuptake inhibitors (SNRIs, Venlafaxine). Actually, it is interesting to note that, whereas the emphasis with the SSRIs has been on their selectivity, recent developments have tended to move towards less selective agents, and now to other neurobiological pathways (ie neurotrophic factors). Finally, fluoxetine, in common with other SSRIs, remains today a first-line treatment option for major depressive disorder.     

Posttraumatic stress disorder and major depressive disorder: investigating the role of overlapping symptoms in diagnostic comorbidity

Studies of posttraumatic stress disorder (PTSD) have found high levels of comorbid major depressive disorder (MDD). One reason suggested for the comorbidity is the symptom overlap (contaminated symptoms) between the disorders. The present study investigated the contribution of contaminated symptoms (anhedonia, concentration, and sleep problems) to the comorbidity of PTSD and MDD. PTSD symptoms were subdivided into two groups: the contaminated symptoms and the 14 unique symptoms. It was speculated that if the contaminated symptoms are responsible for the comorbidity, then they will show less specificity than the unique symptoms, will be less highly correlated with a PTSD symptom total count, and be more frequently endorsed in PTSD patients with than without MDD. These hypotheses were tested in a sample (N = 1300) of psychiatric outpatients, 260 of whom had lifetime PTSD. None of the hypotheses were supported, thereby suggesting that the comorbidity between PTSD and MDD is not an artifact of symptom overlap.     

Generalized anxiety disorder in late life: lifetime course and comorbidity with major depressive disorder.

OBJECTIVE: Generalized anxiety disorder (GAD) in elderly persons is highly prevalent, but little is known about its course, age at onset, and relationship to comorbid major depressive disorder (MDD). The authors assessed the course and comorbidity of late-life GAD and MDD. METHODS: Authors assessed elderly subjects in anxiety or depression intervention studies who had a lifetime history of GAD, with current MDD (N=57) or without (N=46). Subjects' lifetime course of illness was charted retrospectively. RESULTS: The 103 subjects had a mean age of 74.1 years, and a mean age at onset of GAD of 48.8 years; 46% were late-onset. GAD episodes were chronic, and 36% were longer than 10 years. Of the comorbid GAD-MDD patients, most had different times of onset and/or offset of the disorders; typically, GAD preceded MDD. CONCLUSIONS: Elderly subjects with GAD tended to have chronic symptoms lasting years-to-decades, without interruption, and many have late onset. Elderly persons with lifetime GAD and MDD tend to have different onset and offset of the two disorders. Findings characterize late-life GAD as a chronic disorder distinct from MDD.     

The impact of medical comorbidity on acute treatment in major depressive disorder

OBJECTIVE: The authors investigated the impact of medical comorbidity on the acute phase of antidepressant treatment in subjects with major depressive disorder. METHOD: A total of 384 outpatients meeting DSM-III-R criteria for major depressive disorder enrolled in 8-week open treatment with fluoxetine, 20 mg/day. The authors used the Cumulative Illness Rating Scale to measure the burden of medical comorbidity and the 17-item Hamilton Rating Scale for Depression to assess changes in depressive symptoms. The outcome measures were response to treatment (>/=50% reduction in score) and clinical remission (score 相似文献   

Psychiatric comorbidity as a predictor of clinical response to nortriptyline in treatment-resistant major depressive disorder

BACKGROUND: A number of studies of major depressive disorder suggest that psychiatric co-morbidity may contribute to treatment resistance. The purpose of this study was to test whether the presence of comorbid Axis I and Axis II disorders predicts clinical response to an open trial of nor-triptyline among patients with treatment-resistant depression. METHOD: Ninety-two outpatients with treatment-resistant DSM-III-R major depressive disorder were enrolled in a 6-week open trial of nor-triptyline (Nov. 1992-Jan. 1999). The presence of comorbid Axis I and Axis II disorders was established at baseline with the use of the Structured Clinical Interview for DSM-III-R. Chi-square analyses were used to test Axis I or Axis II co-morbid conditions as a predictor of clinical response to nortriptyline. RESULTS: Thirty-nine patients (42.4%) responded to nortriptyline. The presence of avoidant personality disorder (p <.01) predicted poorer response to nortriptyline. The response rate was 16.7% for patients with and 48.6% for patients without comorbid avoidant personality disorder. No other comorbid diagnoses were found to predict clinical response in a statistically significant manner. CONCLUSION: The presence of avoidant personality disorder conferred a poorer prognosis in treatment-resistant depression patients treated with nortriptyline.     

Diagnosis of multiple anxiety disorders predicts the concurrent comorbidity of major depressive disorder

Purpose

It has been established that a single anxiety disorder (AD) is more likely to be comorbid with other ADs as well as major depressive disorder (MDD). However, little is known about the comorbidity risks of MDD in patients with double or multiple ADs in comparison with those with a single AD. In this study, we estimated the comorbidity risks of MDD in patients with multiple ADs.

Method

The subjects were 217 consecutive outpatients with any ADs who were comprehensively diagnosed using the Mini International Neuropsychiatric Interview. The comorbidity rates of MDD in subjects with 2 or more ADs were compared with those in subjects with a single AD.

Results

The comorbidity rates of MDD in subjects with a single AD (n = 119), 2 ADs (n = 75), and 3 or more ADs (n = 23) were 20.1%, 45.3%, and 87.0%, respectively. The relative risks of the comorbidity of MDD in subjects with 2 and with 3 or more ADs compared with those with a single AD were 3.3 (95% confidence interval, 1.7-6.3) and 26.4 (95% confidence interval, 8.2-118.7), respectively. Generalized anxiety disorder was associated with a higher comorbidity rate of MDD in subjects with a single AD but not in subjects with 2 or more ADs.

Conclusion

The results showed that the presence of multiple ADs strongly predicts comorbidity with MDD in an exponential manner, suggesting that we should pay attention to the fact that patients with multiple ADs are more likely to be comorbid with MDD.