Response to antidepressants in major depressive disorder with melancholic features: the CRESCEND study

BackgroundThis study aimed to determine whether major depressive disorders with melancholic and without melancholic features differ with respect to their responses to treatment with antidepressants.MethodsFrom a nationwide sample of 18 hospitals in South Korea, 559 presenting patients with major depressive disorder were recruited. The DSM-IV based Structured Clinical Interview was administered for confirmatory diagnoses and depression subtypes with/without melancholic features. After baseline evaluation, they received naturalistic clinician-determined antidepressant interventions. Assessment scales for evaluating depression (HAMD), anxiety (HAMA), global severity (CGI-s), and functioning (SOFAS) were administered at baseline and re-evaluated at 1, 2, 4, 8, and 12 weeks later.ResultsAt baseline, the 243 (43.5%) participants with melancholic features were more likely to have a previous history of depression, and had higher HAMA and lower SOFAS scores. After adjustment for baseline status, participants with melancholic features were more likely to achieve and to experience shorter times to CGI-s remission and associated with an enhanced global symptomatic remission with any antidepressant treatment. They were more likely to achieve and to experience shorter times to CGI-s remission and this difference was strongest in those receiving selective serotonin reuptake inhibitor (SSRI) antidepressants treatment.LimitationsThe study was observational, and the treatment modality was naturalistic.ConclusionsThese findings suggest a faster and more evident global response to pharmacotherapy in melancholia compared to other depressive syndromes, particularly where SSRI agents are used.     

Cross-national epidemiology of DSM-IV major depressive episode

Background

Major depression is one of the leading causes of disability worldwide, yet epidemiologic data are not available for many countries, particularly low- to middle-income countries. In this paper, we present data on the prevalence, impairment and demographic correlates of depression from 18 high and low- to middle-income countries in the World Mental Health Survey Initiative.

Methods

Major depressive episodes (MDE) as defined by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DMS-IV) were evaluated in face-to-face interviews using the World Health Organization Composite International Diagnostic Interview (CIDI). Data from 18 countries were analyzed in this report (n = 89,037). All countries surveyed representative, population-based samples of adults.

Results

The average lifetime and 12-month prevalence estimates of DSM-IV MDE were 14.6% and 5.5% in the ten high-income and 11.1% and 5.9% in the eight low- to middle-income countries. The average age of onset ascertained retrospectively was 25.7 in the high-income and 24.0 in low- to middle-income countries. Functional impairment was associated with recency of MDE. The female: male ratio was about 2:1. In high-income countries, younger age was associated with higher 12-month prevalence; by contrast, in several low- to middle-income countries, older age was associated with greater likelihood of MDE. The strongest demographic correlate in high-income countries was being separated from a partner, and in low- to middle-income countries, was being divorced or widowed.

Conclusions

MDE is a significant public-health concern across all regions of the world and is strongly linked to social conditions. Future research is needed to investigate the combination of demographic risk factors that are most strongly associated with MDE in the specific countries included in the WMH.     

Clinical features and correlates of major depressive disorder in individuals with body dysmorphic disorder

BACKGROUND: Body dysmorphic disorder (BDD) and major depressive disorder (MDD) appear highly comorbid. However, MDD in individuals with BDD has received little investigation. METHODS: The prevalence and characteristics of comorbid MDD were assessed in 178 BDD subjects. BDD subjects with current comorbid MDD (n=68) were compared to BDD subjects without current comorbid MDD (n=96) on demographic and clinical characteristics. Predictors of current MDD were determined using logistic regression. RESULTS: 74.2% of subjects had lifetime MDD, and 38.2% had current MDD. The melancholic subtype was most common, and a majority of depressed subjects had recurrent episodes. Mean onset of BDD occurred at a younger age than MDD. Subjects with current comorbid MDD had many similarities to those without MDD, although those with comorbid MDD had more severe BDD. Subjects with comorbid MDD were also more likely to have an anxiety or personality disorder, as well as a family history of MDD. They also had greater social anxiety, suicidality, and poorer functioning and quality of life. Current MDD was independently predicted by a personality disorder and more severe BDD. LIMITATIONS: It is unclear how generalizable the results are to the community or to subjects ascertained for MDD who have comorbid BDD. The study lacked a comparison group such as MDD subjects without BDD. CONCLUSIONS: MDD is common in individuals with BDD. Individuals with current MDD had greater morbidity in some clinically important domains, including suicidality, functioning, and quality of life. A personality disorder and more severe BDD independently predicted the presence of current MDD.     

An examination of DSM-IV depressive symptoms and risk for suicide completion in major depressive disorder: a psychological autopsy study

BACKGROUND: It is unclear whether certain DSM-IV depressive symptoms are more prevalent among individuals who die in the context of a major depressive episode and those who do not, whether this is associated with proximal or distal suicide risk, and whether depressive symptoms cluster to indicate suicide risk. METHOD: A psychological autopsy method with best informants was used to investigate DSM-IV depressive symptoms among 156 suicides who died in the context of a major depressive episode and 81 major depressive controls. RESULTS: Suicides' depressive symptoms were more likely to include weight or appetite loss, insomnia, feelings of worthlessness or inappropriate guilt as well as recurrent thoughts of death or suicidal ideation. Fatigue and difficulties concentrating or indecisiveness were less prevalent among depressed suicides. These associations were independent of concomitant axis I and II psychopathology. The concomitant presence of (a) fatigue as well as impaired concentration or indecisiveness and (b) weight or appetite gain and hypersomnia was associated with decreased suicide risk. Inter-episode symptom concordance suggests that insomnia is an immediate indicator of suicide risk, while weight or appetite loss and feelings of worthlessness or guilt are not. LIMITATIONS: This study employed proxy-based interviews. CONCLUSIONS: We found that discrete DSM-IV depressive symptoms and clusters of depressive symptoms help differentiate depressed individuals who die by suicide and those who do not. Moreover, some DSM-IV depressive symptoms are associated with an immediate risk for suicide, while others may result from an etiology of depression common to suicide without directly increasing suicide risk.     

The Diagnostic Inventory for Depression: a self-report scale to diagnose DSM-IV major depressive disorder

In this report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, we describe the development and validation of the Diagnostic Inventory for Depression (DID), a new self-report scale designed to assess the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV; American Psychiatric Association, 1994) symptom inclusion criteria for a major depressive episode, assess psychosocial impairment due to depression, and evaluate subjective quality of life. A large sample of 626 psychiatric outpatients completed the DID and were interviewed with the Structured Clinical Interview for DSM-IV (SCID). The measure's test-retest reliability, discriminant and convergent validity, and sensitivity to clinical change were investigated. The DID subscales achieved high levels of internal consistency and test-retest reliability. The DID was more highly correlated with another self-report measure of depression than with measures of anxiety, substance use problems, eating disorders, and somatization, thereby supporting the convergent and discriminant validity of the scale. The DID also was highly correlated with interviewer ratings of the severity of depression and psychosocial functioning, and DID symptom severity scores were significantly different in depressed patients with mild, moderate, and severe levels of depression. The DID was a valid measure of symptom change. Finally, the DID was significantly associated with a diagnosis of major depressive disorder.     

Randomized comparison of selective serotonin reuptake inhibitor (escitalopram) monotherapy and antidepressant combination pharmacotherapy for major depressive disorder with melancholic features: a CO-MED report

Background

The clinical effects of antidepressant combinations vs. monotherapy as initial treatment for major depression with melancholic features (MDD-MF) are unknown.

Methods

Outpatients with chronic or recurrent major depression (MDD) were randomized to initial treatment with escitalopram + placebo (the MONO condition), bupropion-sustained release + escitalopram, or venlafaxine-extended release + mirtazapine (the COMB conditions) in the Combining Medications to Enhance Depression Outcomes (CO-MED) trial. Secondary data analyses were conducted to compare demographic and clinical characteristics, and contrast clinical responses according to drug treatment, in patients with MDD-MF (n = 124) and non-melancholic MDD (n = 481).

Results

While numerically lower, remission rates in MDD-MF did not differ significantly from those with non-melancholic MDD either at 12 (33.1% vs. 41.0%, aOR 1.16, p = 0.58) or 28 (39.5% vs. 46.8%, aOR = 1.02, p = 0.93) weeks of treatment. Remission rates did not differ significantly between combination and monotherapy groups in either MDD-MF or non-melancholic MDD patients at either time point. Similar conclusions were reached for response rates, premature study discontinuation, and self-rated depression symptom severity.

Limitations

This is a secondary analysis of data from the CO-MED trial, which was not designed to address differential treatment response in melancholic and non-melancholic MDD.

Conclusions

We found no evidence of differential remission or response rates to antidepressant combination or monotherapy between melancholic/non-melancholic MDD patients, or according to antidepressant treatment group, after 12 and 28 weeks. Melancholic features may not be a valid predictor of more favorable response to antidepressant combination therapy as initial treatment.     

Interpersonal profiles in major depressive disorder

Although patients with mood disorders report interpersonal difficulties in addition to depression or anxiety, few studies have examined interpersonal patterns in those patients. Here the authors' goals were to (a) identify the interpersonal pattern in patients with major depressive disorder (MDD), (b) determine interpersonal differences between subgroups of MDD patients, and (c) examine the interpersonal patterns of comorbid MDD patients. One- hundred forty-one MDD adults participated in an ongoing randomized clinical trial of treatments for depression. Interpersonal profiles revealed that MDD patients were significantly more distressed by interpersonal problems than normative samples. Furthermore, MDD patients with depressive personality disorder reported more interpersonal distress than MDD-only patients report and were more likely to have interpersonal problems related to dominance and control than submissiveness.     

RSA fluctuation in major depressive disorder

Cardiac vagal control, as measured by indices of respiratory sinus arrhythmia (RSA), has been investigated as a marker of impaired self-regulation in mental disorders, including depression. Past work in depressed samples has focused on deficits in resting RSA levels, with mixed results. This study tested the hypothesis that depression involves abnormal RSA fluctuation. RSA was measured in depressed and healthy control participants during rest and during two reactivity tasks, each followed by a recovery period. Relative to controls, depressed persons exhibited lower resting RSA levels as well as less RSA fluctuation, primarily evidenced by a lack of task-related vagal suppression. Group differences in RSA fluctuation were not accounted for by differences in physical health or respiration, whereas group differences in resting RSA level did not survive covariate analyses. Depression may involve multiple deficits in cardiac vagal control.     

Autobiographical memories in major depressive disorder

The objective of this research was to study the relation between the processing and recall of information in major depressive disorder. An autobiographical memory task was applied to 42 subjects with a diagnosis of major depressive disorder, 28 subjects with a diagnosis of panic disorder and 51 subjects without any psychological disorder. We used clinical scales for the evaluation of depression and anxiety. The results of the three groups, and both assessment periods of depressed subjects, were compared. The results indicate the existence, in severely depressed subjects, of a bias in processing and recalling negative information. We associate this situation to the existence of negative contents in self-schemas and processing and recall of information consistent with these schema contents. Based on the obtained results, we consider that the onset and maintenance of depression is more related to the information encoding and recall processes, controlled by the self's negative schemas, than with negative thoughts.     

Early developmental characteristics and features of major depressive disorder among child psychiatric patients in Hungary

OBJECTIVE: We investigate the relations of early atypical characteristics (perinatal problems, developmental delay, and difficult temperament) and onset-age (as well as severity of) first major depressive disorder (MDD) and first internalizing disorder in a clinical sample of depressed children in Hungary. METHOD: Participants were 371 children (ages 7-14) with MDD, and their biological mothers, recruited through multiple clinical sites. Diagnoses (via DSM-IV criteria) and onset dates of disorders were finalized "best estimate" psychiatrists, and based on multiple information sources. Mothers provided developmental data in a structured interview. RESULTS: Difficult temperament predicted earlier onset of MDD and first internalizing disorder, but its effect was ameliorated if the family was intact during early childhood. Further, the importance of difficult temperament decreased as a function of time. Perinatal problems and developmental delay did not impact onset ages of disorders, and none of the early childhood characteristics associated with MDD episode severity. CONCLUSIONS: Children with MDD may have added disadvantage of earlier onset if they had a difficult temperament in infancy. Because early temperament mirrors physiological reactivity and regulatory capacity, it can affect various areas of functioning related to psychopathology. Early caregiver stability may attenuate some adverse effects of difficult infant temperament.     

Automaticity in anxiety disorders and major depressive disorder

In this paper we examine the nature of automatic cognitive processing in anxiety disorders and Major Depressive Disorder (MDD). Rather than viewing automaticity as a unitary construct, we follow a social cognition perspective (Bargh, 1994) that argues for four theoretically independent features of automaticity: unconscious (processing of emotional stimuli occurs outside awareness), efficient (processing emotional meaning uses minimal attentional resources), unintentional (no goal is needed to engage in processing emotional meaning), and uncontrollable (limited ability to avoid, alter or terminate processing emotional stimuli). Our review of the literature suggests that most anxiety disorders are characterized by uncontrollable, and likely also unconscious and unintentional, biased processing of threat-relevant information. In contrast, MDD is most clearly typified by uncontrollable, but not unconscious or unintentional, processing of negative information. For the anxiety disorders and for MDD, there is no sufficient evidence to draw firm conclusions about efficiency of processing, though early indications are that neither anxiety disorders nor MDD are characterized by this feature. Clinical and theoretical implications of these findings are discussed and directions for future research are offered. In particular, it is clear that paradigms that more directly delineate the different features of automaticity are required to gain a more comprehensive and systematic understanding of the importance of automatic processing in emotion dysregulation.     

Fluoxetine in tricyclic refractory major depressive disorder

Data regarding open-label treatment with fluoxetine following failure to respond to tricyclic antidepressants (TCAs) or intolerance of TCA side effects, suggest a response rate between 51.4% and 62.1%, depending on the definition of TCA refractoriness employed. Double-blind study of this issue would extend these findings. Fluoxetine is well tolerated in patients unable to tolerate TCAs. Within this population, more than 80% of patients unable to tolerate TCAs found fluoxetine acceptable. Fluoxetine, as an alternative to polypharmaceutical augmentation, may represent a logical choice as the next step in therapy for a patient who has initially been treated with a TCA and has proven refractory or intolerant.     

Physical anhedonia in major depressive disorder.

Physical anhedonia, evaluated by the score on the physical anhedonia scale (PAS) of Chapman et al. [J. Abnorm. Psychol. 4 374-382 (1976)] was studied in 61 patients, who met RDC criteria for major depressive disorder and in 61 normal subjects. The depressed patients scored significantly higher than the normal group and presented a continuous distribution. Physical anhedonia of depressed patients seems related to the severity of the depression and does not appear to identify a qualitatively distinct subgroup.     

Delayed mood transitions in major depressive disorder

The hypothesis defended here is that the process of mood-normalizing transitions fails in a significant proportion of patients suffering from major depressive disorder. Such a failure is largely unrelated to the psychological content. Evidence for the hypothesis is provided by the highly variable and unpredictable time-courses of the depressive episodes.     

Cerebellar vermis volume in major depressive disorder

The vermis is located in the midline of the cerebellum and is involved in the regulation of affect and cognitive processes. Although changes in vermis size have been reported in several psychiatric disorders such as schizophrenia and bipolar disorder, no volumetric studies have been conducted on samples of patients with major depressive disorder (MDD). One-hundred and five adult subjects were recruited: 35 patients who were presenting for first treatment (FT; 22 females), 35 patients with known previous treatment (PT; 22 females), and 35 healthy controls (NC; 22 females), matched for age and gender. We compared the volumes of the total vermis, the anterior lobe (V1), the superior–posterior lobe (V2), and the inferior–posterior lobe (V3), among these study groups. Anterior vermis (V1) was larger in patients with MDD with a long history of antidepressant treatment compared to healthy controls. This finding was evident only in men [F(2, 36) = 9.23, p = .001]. Patients in the FT group did not differ from healthy controls in any vermian region. We found no correlations between vermian subregional volumes and clinical variables such as illness duration or age at onset of illness. We speculate that the larger anterior vermis volumes might arise from abnormalities in connectivity or as compensatory responses to the prefrontal dysfunction noted in patients with MDD but confirmation of this hypothesis awaits further studies.     

Prodromal symptoms in primary major depressive disorder

Prodromal symptomatology was investigated, by means of a modified version of Paykel's Clinical Interview for Depression, in 15 outpatients at their first episode of primary major depressive disorder. Compared to normals, generalized anxiety and irritability were significantly more frequent. Impaired work and interests, fatigue, initial and delayed insomnia were also reported. Four patients who relapsed upon discontinuation of antidepressant treatment displayed the same prodromal symptomatology as in the initial episode.