Nonpsychotic Major Depression Research Articles

Getting Better, Getting Well

In general, the pharmacological treatment of non-psychotic major depressive disorder in old age is only partially successful, with only approximately 50% of older depressed adults improving with initial antidepressant monotherapy. Many factors may predict a more difficult-to-treat depression, including coexisting anxiety, low self-esteem, poor sleep and a high coexisting medical burden. Being aware of these and other predictors of a difficult-to-treat depression gives the clinician more reasonable expectations about a patient's likely treatment course. If an initial antidepressant trial fails, the clinician has two pharmacological options: switch or augment/combine antidepressant therapies. About 50% of patients who do not improve after initial antidepressant therapy will respond to either strategy. Switching has several advantages including fewer adverse effects, improved treatment adherence and reduced expense. However, as a general guideline, if patients are partial responders at 6 weeks, they will likely be full responders by 12 weeks. Thus, changing medication is not indicated in this context. However, if patients are partial responders at 12 weeks, switching to a new agent is advised. If the clinician treats vigorously and if the patient and clinician persevere, up to 90% of older depressed patients will respond to pharmacological treatment. Furthermore, electroconvulsive therapy is a safe and effective non-pharmacological strategy for non-psychotic major depression that fails to respond to pharmacotherapy. Getting well and staying well is the goal; thus, clinicians should treat to remission, not merely to response. Subsequently, maintenance treatment with the same regimen that has been successful in relieving the depression strongly improves the patient's chances of remaining depression free.

Aripiprazole augmentation for treatment of patients with inadequate antidepressants response

This study evaluated whether or not augmentation with aripiprzazole is beneficial and tolerable to patients with an inadequate response to antidepressants (ADs). Thirteen patients with nonpsychotic major depression, who had failed to respond to an adequate trial of at least one AD, were prescribed aripiprazole (dose, 5-30 mg) for 8 weeks. The dose of their preexisting ADs was not changed. The treatment response was defined as the mean changes in the scores of the Hamilton Depression Rating Scale (HAM-D) from the baseline to the end of treatment. Eleven (84.6%) patients returned for at least one follow-up visit, and 7 (53.8%) patients completed the study. The HAM-D and Clinical Global Impression-Severity (CGI-S) scores decreased significantly from the baseline to the end of treatment by 53.8% and 56.0%, respectively (Z = -2.937, P =.003; Z = -2.961, P =.003). Seven (63.6%) patients showed a > or = 50% reduction in the HAM-D score at the end of treatment. Three (27.3%) patients met the remission criteria at the end of treatment. There were no serious side effects. Despite the high dropout rate in this open study, aripiprazole appears to be reasonably effective and tolerated as an augmentation strategy in conjunction with conventional ADs treatment in patients with an inadequate AD response. These results highlight the potential benefits of aripiprazole for these patients. However, adequately powered, randomized, controlled trials are needed to confirm these results.

Serum creatine kinase level in unmedicated nonpsychotic, psychotic, bipolar and schizoaffective depressed patients

Creatine kinase (CK) level was previously found to be increased in the majority of hospitalized acute psychotic patients. We aimed to asses the possible differences in CK level in various forms of depression: major with and without psychotic symptoms, of bipolar depression and schizoaffective depression. Unmedicated hospitalized patients participated: nonpsychotic major depression ( n = 39), psychotic major depression ( n = 23), bipolar depression ( n = 23) and schizoaffective depression ( n = 24). The severity of depression was assessed by the Hamilton Depression Rating Scale (Ham-D) and blood samples were collected in the morning of admission day, prior to any treatment. Ham-D yielded a significantly higher score for psychotic major depression group, compared with all other groups which showed similar score. CK serum level was significantly higher in nonpsychotic major depression than in all other forms of depression. The results indicate a biological difference between the nonpsychotic major depression and the “psychotic” cluster of depressive syndromes.

STAR☆D: The Results Begin to Roll in

As clinicians, we all recognize that many of the depressed patients we see do not adequately respond to our first treatment. What to do next for these individuals remains unclear, as there are few data from well-controlled replicated trials to guide us. In the absence of clear guidance from empirical research, we use what evidence is available, as well as case reports, our own clinical experience, and recommendations from experts. This lack of evidence-based guidance was the primary motivation behind the development of The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. This large study, funded at considerable cost by the National Institute of Mental Health and years in the making, has begun to yield results. Available clinical trials, many sponsored by the pharmaceutical industry and conducted in research centers (academic or private), generally focus on uncomplicated, nonchronic major depression; in this respect, they often do not reflect the clinical “real world.” STAR*D was designed to be relevant to clinicians by including patients more typical of outpatient practice. The patients are drawn from psychiatric and primary care “real world” settings, and the exclusion criteria are much less restrictive than usual. Patients with chronic depression and other psychiatric and medical comorbidities are included, and outcomes focus on remission (a Hamilton Depression Rating Scale score of 7 or less) rather than just a decrease in symptom severity. In this issue of the Journal, Fava and colleagues detail the Level 3 results of STAR*D. Their article follows an article published in the January issue of the Journal on the Level 1 results (1), and two articles published in the New England Journal of Medicine in March detailing the Level 2 results (2, 3). We can now begin to put STAR*D into context and examine what clinical guidance these results provide. First, a brief overview of the study is worthwhile. In Level 1, over 4,000 patients with nonpsychotic major depression were entered into the study and given citalopram at doses of up to 60 mg. The primary outcome was remission, a relatively asymptomatic threshold. This first level approximates typical clinical practice in that the initial intervention was a selective serotonin reuptake inhibitor (SSRI). Level 2 included those patients who did not remit or could not tolerate citalopram. They were offered the option of switching to another treatment, or augmentation of the citalopram that they were taking. The switching options were sustainedrelease bupropion, sertraline or venlafaxine extended-release, and the augmentation options were bupropion sustained-release, buspirone, or cognitive behavior therapy (the cognitive behavior therapy results have not yet been published). Again, this level approximates clinical practice in that patients were able to express a preference for switching or for continuing citalopram and adding an augmenter. Level 3 included patients who did not achieve remission or could not tolerate the treatment that they received at Level 2. These patients were randomly assigned to mirtazapine or nortriptyline. This is the study conducted by Fava and colleagues, presented in this issue of the Journal. It is worthwhile to read each study in the order of publication, as there are many details not covered in this editorial that may affect how one interprets the importance of the data. So what were the results, and what have we learned that we did not already know? The overall remission rate in Level 1 (all patients taking openlabel citalopram) was 27.5%. No surprise here, as clinical trials with antidepressants typically report remission rates of 30% or less (4). “What have we learned that we did not already know?” At Level 2, remission rates did not differ significantly among the three antidepressant switch strategies: 21.3% with bupropion sustained-release, 18.1% with sertraline, and 24.4% with venlafaxine extended-release. Level 2 remission rates were also similar across drug augmentation strategies: 29.7% achieved remission with citalopram plus bupropion sustained-release, and 30.2% achieved remission with citalopram plus buspirone, but buspirone was not tolerated as well as bupropion. Here, we do have some surprises and, perhaps, new clinical guidance. In clinical practice today, it is popular to target our second-tier approaches at specific neurotransmitters (5). That is, if an SSRI does not help, try a

STAR*D: The Results Begin to Roll in

STAR*D: The Results Begin to Roll in

STAR*D: The Results Begin to Roll in

As clinicians, we all recognize that many of the depressed patients we see do not adequately respond to our first treatment. What to do next for these individuals remains unclear, as there are few data from well-controlled replicated trials to guide us. In the absence of clear guidance from empirical research, we use what evidence is available, as well as case reports, our own clinical experience, and recommendations from experts. This lack of evidence-based guidance was the primary motivation behind the development of The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. This large study, funded at considerable cost by the National Institute of Mental Health and years in the making, has begun to yield results. Available clinical trials, many sponsored by the pharmaceutical industry and conducted in research centers (academic or private), generally focus on uncomplicated, nonchronic major depression; in this respect, they often do not reflect the clinical “real world.” STAR*D was designed to be relevant to clinicians by including patients more typical of outpatient practice. The patients are drawn from psychiatric and primary care “real world” settings, and the exclusion criteria are much less restrictive than usual. Patients with chronic depression and other psychiatric and medical comorbidities are included, and outcomes focus on remission (a Hamilton Depression Rating Scale score of 7 or less) rather than just a decrease in symptom severity. In this issue of the Journal, Fava and colleagues detail the Level 3 results of STAR*D. Their article follows an article published in the January issue of the Journal on the Level 1 results (1), and two articles published in the New England Journal of Medicine in March detailing the Level 2 results (2, 3). We can now begin to put STAR*D into context and examine what clinical guidance these results provide. First, a brief overview of the study is worthwhile. In Level 1, over 4,000 patients with nonpsychotic major depression were entered into the study and given citalopram at doses of up to 60 mg. The primary outcome was remission, a relatively asymptomatic threshold. This first level approximates typical clinical practice in that the initial intervention was a selective serotonin reuptake inhibitor (SSRI). Level 2 included those patients who did not remit or could not tolerate citalopram. They were offered the option of switching to another treatment, or augmentation of the citalopram that they were taking. The switching options were sustainedrelease bupropion, sertraline or venlafaxine extended-release, and the augmentation options were bupropion sustained-release, buspirone, or cognitive behavior therapy (the cognitive behavior therapy results have not yet been published). Again, this level approximates clinical practice in that patients were able to express a preference for switching or for continuing citalopram and adding an augmenter. Level 3 included patients who did not achieve remission or could not tolerate the treatment that they received at Level 2. These patients were randomly assigned to mirtazapine or nortriptyline. This is the study conducted by Fava and colleagues, presented in this issue of the Journal. It is worthwhile to read each study in the order of publication, as there are many details not covered in this editorial that may affect how one interprets the importance of the data. So what were the results, and what have we learned that we did not already know? The overall remission rate in Level 1 (all patients taking openlabel citalopram) was 27.5%. No surprise here, as clinical trials with antidepressants typically report remission rates of 30% or less (4). “What have we learned that we did not already know?” At Level 2, remission rates did not differ significantly among the three antidepressant switch strategies: 21.3% with bupropion sustained-release, 18.1% with sertraline, and 24.4% with venlafaxine extended-release. Level 2 remission rates were also similar across drug augmentation strategies: 29.7% achieved remission with citalopram plus bupropion sustained-release, and 30.2% achieved remission with citalopram plus buspirone, but buspirone was not tolerated as well as bupropion. Here, we do have some surprises and, perhaps, new clinical guidance. In clinical practice today, it is popular to target our second-tier approaches at specific neurotransmitters (5). That is, if an SSRI does not help, try a

The Montgomery Äsberg and the Hamilton ratings of depression: A comparison of measures

The 17-item Hamilton Rating Scale for Depression (HRSD17) and the Montgomery Äsberg Depression Rating Scale (MADRS) are two widely used clinician-rated symptom scales. A 6-item version of the HRSD (HRSD6) was created by Bech to address the psychometric limitations of the HRSD17. The psychometric properties of these measures were compared using classical test theory (CTT) and item response theory (IRT) methods. IRT methods were used to equate total scores on any two scales. Data from two distinctly different outpatient studies of nonpsychotic major depression: a 12-month study of highly treatment-resistant patients (n=233) and an 8-week acute phase drug treatment trial (n=985) were used for robustness of results.MADRS and HRSD6 items generally contributed more to the measurement of depression than HRSD17 items as shown by higher item-total correlations and higher IRT slope parameters. The MADRS and HRSD6 were unifactorial while the HRSD17 contained 2 factors. The MADRS showed about twice the precision in estimating depression as either the HRSD17 or HRSD6 for average severity of depression. An HRSD17 of 7 corresponded to an 8 or 9 on the MADRS and 4 on the HRSD6.The MADRS would be superior to the HRSD17 in the conduct of clinical trials.

Clinical and Demographic Factors Associated With DSM-IV Melancholic Depression

The purpose of this paper is to use demographic and clinical data from a large diverse group of outpatients diagnosed with non-psychotic major depression to investigate the validity of the DSM-IV concept of melancholic depression. Baseline clinical and demographic data were collected on 1500 outpatients (1456 of whom melancholia could be determined) with non-psychotic major depressive disorder (MDD) participating in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Depressive symptom severity was assessed by clinical telephone interview using the 17-item Hamilton Rating Scale for Depression (HRS-D17) and the 30-item Inventory of Depressive Symptomatology (IDS-C30). The types and degrees of concurrent psychiatric symptoms were measured using a self report, the Psychiatric Diagnostic Screening Questionnaire (PDSQ), by recording the number of items relevant to each diagnostic category endorsed by study participants. Adjusting for severity of depression (as measured by the total HRS-D17 scores), no differences were found in the rate of melancholic depression by race, marital status, education, employment status, family history of depression, primary care versus specialty care, monthly income, and degree of psychiatric and medical co-morbidity. Melancholic depression was significantly more likely in men than women. Melancholic depression after adjustment for severity was associated with a slightly younger age at study entry, as well as with greater illness severity, and slightly shorter duration of current episode. Hispanic ethnicity was associated with lower melancholic depression rates at the .06 level of significance. Among outpatients with MDD, melancholic features were less likely in Hispanic patients, but more likely in slightly younger patients and in men. Melancholic features were also related to a slightly shorter current episode. These findings are consistent with the notion that external socio-demographic factors do not play an important role in the pathophysiology of melancholic depression.

Persistence of Neuropsychologic Deficits in the Remitted State of Late-Life Depression

Cognitive impairment in late-life depression (LLD) is prevalent, disabling, and persists despite the remission of depressive symptoms. This article characterizes neuropsychologic functioning during remission in LLD. The authors examined longitudinal performance on a comprehensive neuropsychologic battery in 56 nondemented subjects age 60 or older who initially presented with an episode of nonpsychotic unipolar major depression and 40 nondemented, age- and education-equated comparison subjects with no history of depression. Subjects were assessed at baseline (in a depressed state) and one year later (when remitted). After one year, 45% of the LLD subjects were cognitively impaired despite remission of depression. Visuospatial ability, information-processing speed, and delayed memory were most frequently impaired; 94% of the patients who were impaired at baseline remained impaired one year later. Twenty-three percent of the patients who were cognitively normal while depressed developed impairment one year later. Most older individuals who are cognitively impaired during a depressive episode remain impaired when their depression remits. In addition, a substantial proportion of older depressed individuals who are cognitively intact when depressed are likely to be impaired one year later, although their depression has remitted.

Treating Depression During Pregnancy and the Postpartum: A Preliminary Meta-Analysis

Objectives: This meta-analysis evaluates treatment effects for nonpsychotic major depression during pregnancy and postpartum comparing interventions by type and timing. Methods: Studies for decreasing depressive severity during pregnancy and postpartum applying treatment trials and standardized measures were included. Standardized mean differences were calculated for continuous variable outcome data. Results: Thirteen interventions reported positive effect sizes, one reported marginally positive effect size, one reported no effect, and the remaining reported marginally negative effect size. By type of treatment, medication with cognitive behavioral therapy (CBT; 3.871, p < .001) and medication alone (3.048, p < .001) reported largest effect size, followed by group therapy (CBT, educational, and transactional analysis; 2.045, p < .001), interpersonal psychotherapy (1.260, p < .001), CBT (.642, p < .001), psychodynamic (.526, p = .014), counseling (.418, p = .014), and educational (.100, p = .457). Postpartum implementation produced larger effect size (.837, p < .001) than implementation during pregnancy (.377, p = .002). When medication interventions are excluded, postpartum effect size is .704 (p < .001). Conclusions: Preliminary findings suggest medication, alone or with CBT; group therapy with CBT, educational, and transactional analysis components; interpersonal psychotherapy; and CBT produce largest effect sizes in this population among interventions tested.

The Neuropsychological Profile of Psychotic Major Depression and its Relation to Cortisol

Our study described the neuropsychological profile of psychotic major depression (PMD) compared to nonpsychotic major depression (NPMD) patients and psychiatrically healthy controls (HC). We predicted that higher cortisol levels would be associated with greater cognitive deficits. Twenty-nine PMDs, 24 NPMDs, and 26 HCs were recruited at Stanford University Medical Center. Psychiatric ratings, cortisol levels from 1800-0900 hours, and neuropsychological test data were obtained. PMDs had more severe cognitive impairments compared with NPMDs and HCs with the exception of simple verbal attention. PMDs had elevated mean cortisol levels from 1800 to 0100 hours which were significantly correlated with poorer verbal memory and psychomotor speed performance. Cortisol slopes from 1800 to 0100 hours were also significantly correlated with verbal memory and working memory. While PMDs' ability to attend passively to information appears intact, they have more difficulty processing, manipulating, and encoding new information. Elevated cortisol levels, as seen in PMD patients, are associated with poorer cognitive performance especially related to verbal memory for lists of words and working memory.

T3 augmentation of SSRI resistant depression

Purpose of study To investigate whether the addition of triiodothyronine (T3) helps relieve depressive symptoms in non-hypothyroid major depressive disorder patients who failed to respond to an adequate course of standard SSRI antidepressant treatments. Methods Patients who fulfilled the DSM-IV criteria for non-psychotic major depression, able to give informed consent, and failed to show satisfactory antidepressant response after a minimum of six weeks adequate treatment were recruited. To enter the study their Hamilton Depression (17-item HAMD) score had to be 18 or more, thyroid-stimulating hormone (TSH) value within the normal range, and a normal thyrotropin releasing hormone-stimulation test (TRH-ST). All patients continued taking the same SSRI which they had been taking before they entered the study. At the completion of TRH-SH they were all started on 25 μg of T3 and the dose was increased to 50 μg within a week when tolerated; they continued the combination of T3 and the SSRI for a minimum of three weeks. Results Twelve patients, comprising eight females and four males, entered the study. One female patient withdrew during the first week of side effects, eleven patients completed the trial. The patients ranged from 26 to 77 years of age, with the mean age for males and females being 52.3 and 45.1 years, respectively. Five patients were taking sertraline (mean dose = 130 mg/day) and 4 were taking citalopram (mean dose = 50 mg/day), two were on fluvoxamine (150 mg/day) and one patient was on 40 mg of paroxetine. The women took a mean daily dose of 40.6 μg of T3 for a mean duration of 3.75 weeks, while the men were on a mean daily dose of 43.8 μg of T3 for 3.5 weeks. T3 augmentation was associated with a statistically significant drop ( p < .003) in the mean HAMD at end of the three weeks compared to baseline scores. Five patients (42%) showed ≥ 50% improvement on HAMD scores, with three achieving full remission (HAMD scores ≤ 7) at the end of the study. There were no reliable differences between responders and non-responders in baseline HAMD scores, number of previous antidepressant trials, gender or Δmax TSH. Conclusion T3 augmentation resulted in improvement of mood scores. The responders' rate of 42% in our study is comparable to the response rates reported using T3 or lithium to augment tricyclic antidepressants or other combination strategies used to treat resistant depression. Even though one patient withdrew prematurely due to side effects, the remaining 11 patients tolerated the addition of T3 very well. With the availability of T3, a viable, safe, inexpensive and effective augmentation treatment, the recent trend of replacing T3 with other novel strategies appears unwarranted.

The Clinical Significance of Psychotic Depression

&lt;P&gt;As reviewed by Rothschild et al. in this issue, studies published during the past 2 decades have demonstrated that major depression associated with psychotic features (MD-Psy), particularly delusions, is associated with poor outcomes, including a greater mortality rate, an increased risk for suicide, and poorer functional outcomes than occur with nonpsychotic major depression. Nevertheless, our knowledge about the pathogenesis and long-term management of MD-Psy remains limited. Greater awareness of this disorder and more accurate diagnoses are required to optimize the treatment response and prognosis of MD-Psy.&lt;/P&gt; &lt;H4&gt;ABOUT THE AUTHOR&lt;/H4&gt; &lt;P&gt;Dr. Feldman is psychiatry resident, New York Presbyterian Hospital, Weill Medical College of Cornell University, New York, NY.&lt;/P&gt; &lt;P&gt;Address reprint requests to: Diana Feldman, MD, New York Presbyterian Hospital, 525 E. 68th St., Box 140, New York, NY 10021.&lt;/P&gt;

Research Assessment of Patients With Psychotic Depression: The STOP-PD Approach

&lt;P&gt;Major depression with psychotic features (psychotic depression) is a severe, disabling disorder. Compared with nonpsychotic major depression, psychotic depression has been associated with greater severity of depressive symptoms, greater functional impairment, increased risk of suicide, lower rate of recovery, increased risk of depressive relapse and recurrence, and more frequent hospital admissions. There are significant challenges in conducting a treatment study of psychotic depression, including the recruitment, retention, and assessment of patients.&lt;/P&gt; &lt;H4&gt;ABOUT THE AUTHORS&lt;/H4&gt; &lt;P&gt;Dr. Flint is professor, Department of Psychiatry, University of Toronto, and head, Geriatric Psychiatry Program, University Health Network, Toronto, Ontario, Canada; the Geriatric Program and Research Institute, Toronto Rehabilitation Institute, Toronto; and the Toronto General Research Institute, Toronto. Dr. Schaffer is assistant professor, Department of Psychiatry, University of Toronto, and Head, Mood Disorders Program, Sunnybrook and Women’s College Health Sciences Centre, Toronto. Dr. Meyers is professor of psychiatry, Department of Psychiatry, Weill Medical College of Cornell University and New York Presbyterian Hospital, Westchester, NY Dr. Rothschild is Irving S. and Betty Brudnick Professor of Psychiatry, Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA. Dr. Mulsant is professor of psychiatry, Western Psychiatric Institute and Clinic, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA; clinical director, Geriatric Mental Health Program, Centre for Addiction and Mental Health, Toronto, and professor, Department of Psychiatry, University of Toronto.&lt;/P&gt; &lt;P&gt;Address reprint requests to: Alastair J. Flint, MB, FRCPC, FRANZCP, Toronto General Hospital, 200 Elizabeth Street, 8 Eaton North, Room 238, Toronto, Ontario, Canada, M5G 2C4; or e-mail &lt;a href="mailto:alastair.flint@uhn.on.ca"&gt;alastair.flint@uhn.on.ca&lt;/a&gt;.&lt;/P&gt; &lt;P&gt;Dr. Flint disclosed a relevant financial relationship with Pfizer Canada. Dr. Schaffer disclosed a relevant financial relationship with Eli Lilly Canada. Dr. Rothschild disclosed relevant financial relationships with Lilly and Pfizer. Dr. Mulsant disclosed relevant financial relationships with Pfizer, Eli Lilly, Forest/Lundbeck, AstraZeneca, Janssen, and Alkermes. Dr. Meyers disclosed no relevant financial relationships.&lt;/P&gt; &lt;P&gt;This article was supported by United States Public Health Service grants MH 62446, MH 62518, MH 62565, and MH 62624 from the National Institute of Mental Health.&lt;/P&gt;

Residual Symptoms in Depressed Patients After Treatment With Fluoxetine or Reboxetine

Residual symptoms are common and have a variety of consequences in depressed patients who respond to treatment, but seldom have specific residual symptoms been assessed. We examined the frequency and severity of residual depressive symptoms in 2 studies comparing the selective serotonin reuptake inhibitor (SSRI) fluoxetine with the norepinephrine reuptake inhibitor (NRI) reboxetine. Data from two 8-week, previously published, double-blind, random-assignment studies comparing fluoxetine and reboxetine were obtained. Both studies included men and women who met DSM-III-R criteria for unipolar nonpsychotic major depression. Symptoms were assessed with the 21-item Hamilton Rating Scale for Depression (HAM-D). The frequency and severity of residual symptoms were determined in the patients who completed treatment and responded (had at least 50% improvement on the HAM-D). In study 1, 117 patients completed treatment and responded. In study 2, 113 patients completed treatment and responded. The most frequent symptoms present after treatment were psychic anxiety, lack of interest, somatic anxiety, and depressed mood. No residual symptom differed significantly between treatment groups in both samples. Ordinal logistic regression, used to control for baseline symptom severity, revealed no other differences between drug groups except that decreased libido was significantly greater with fluoxetine in study 1 and study 2. Three composite scores for residual anxiety, sleep disturbance, and reduced drive did not differ between drug groups. This study found no differences in residual symptoms in depressed patients who responded to treatment with the SSRI fluoxetine and the NRI reboxetine, with the exception that the fluoxetine group had a greater decrease in sexual interest, a likely side effect of that drug.

Presenting characteristics of depressed outpatients as a function of recurrence: Preliminary findings from the STAR*D clinical trial

Objectives Recurrent depression predicts risk for subsequent episodes, but it is unclear how it relates to demographic features, course of illness, and clinical presentation. Methods We report on the baseline data for the first 1500 patients enrolled in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study ( www.star-d.org). Patients were required to have a DSM-IV diagnosis of nonpsychotic major depression and to score ⩾ 14 on the 17-item Hamilton rating scale for depression. Status with respect to recurrent depression and other aspects of illness course and demographic features were ascertained at intake, along with measures of depression and concurrent general medical illness. Results Patients with recurrent depression were older, had an earlier age of onset, and were more likely to have a positive family history of depression than first episode patients. However, recurrent patients were less likely to be chronic and reported shorter current episodes than first episode patients, something that was largely confined to females. Recurrent patients were more likely than first episode patients to report non-essential aspects of mood, cognition, and somatic symptoms, although largely as a consequence of greater overall depressive symptom severity. Conclusions As compared to single episode depressions, recurrent depression was associated with greater symptom severity and illness characteristics suggestive of greater underlying risk, but not other demographic characteristics than age. Risk for recurrence appeared to be distinct from chronic depression. A subset of chronic first episode patients may lack the capacity to remit and may therefore be distinct from those with recurrent episodes.

Differential Response to Combined Treatment in Patients With Psychotic Versus Nonpsychotic Major Depression

Research has demonstrated that depressed patients with psychotic features show poorer outcomes when treated with pharmacotherapy alone compared with those without psychotic features. However, research has not investigated whether this differential response also applies to combined treatment that includes pharmacotherapy and psychotherapy. In the current study, data were pooled from two clinical trials in which patients diagnosed with major depressive disorder with or without psychotic features were treated with combined treatment. Although similar in severity at pretreatment, results indicated that patients with psychotic depression showed a poorer response in terms of depression severity at postoutpatient treatment and at 6-month follow-up compared with those with nonpsychotic depression. Following treatment, patients with psychotic depression were over four times as likely to exhibit high levels of depression and suicidal ideation. Current state-of-the-art combined treatments have poorer efficacy in depressed patients with psychotic symptoms, and adapted treatment approaches are needed.

Distinctive neurocognitive effects of repetitive transcranial magnetic stimulation and electroconvulsive therapy in major depression

Studies have compared electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS) with regard to clinical efficacy in the treatment of depression, but no study has yet addressed the differential impact on cognition. To compare the neurocognitive effects of unilateral ECT and rTMS. Thirty patients with treatment-refractory non-psychotic major depression received an average of ten treatments with either unilateral ECT or left prefrontal rTMS and were assessed for objective and subjective cognitive impairments before and about a week after treatment. Treatment response was comparable (46% of the ECT group and 44% of the rTMS group showed a reduction of 50% or more in Hamilton Rating Scale for Depression scores). In patients treated with rTMS, cognitive performance remained constant or improved and memory complaints alleviated, whereas in the ECT group memory recall deficits emerged and memory complaints remained. In contrast to unilateral ECT, rTMS has no adverse memory effects.

A dimensional approach to personality in atypical depression

The current study addresses the relationship of personality and atypical depression using the Five-Factor Model (FFM), a dimensional approach to personality. The aim of the study was to help clarify which personality traits are more characteristic of atypical depression than of other depressive subtypes. Outpatients ( n = 160) with non-psychotic major depression were characterized as having atypical ( n = 26), or non-atypical depression ( n = 134) based on DSM-IV criteria. To limit the effect of state depression, personality was assessed after subjects received a minimum of 14 weeks of antidepressant treatment. The Revised NEO Personality Inventory, which generates data based on the FFM, was the primary assessment measure. Post-treatment, relative to the non-atypical comparison group, the atypical group had significantly higher scores on the dimension of Neuroticism, the facets of Impulsivity and Anger–Hostility, and a significantly lower score on the facet of Deliberation. In sum, the FFM provides a new understanding of which unique personality characteristics may be associated with atypical depression.

What moderator characteristics are associated with better prognosis for depression?

A retrospective data analysis was conducted to evaluate the usefulness of baseline characteristics in predicting treatment response to antidepressant medication in 97 outpatients with nonpsychotic major depression treated for up to sixteen weeks with nefazodone. Baseline demographics (gender), illness features (symptom severity, length of illness, length of current episode, number of episodes, age of onset, longitudinal subtype, endogenicity, melancholia, family history of mood disorders), and social features (living status) were evaluated. Response to treatment was defined as a >/= 50% reduction in the 17-item Hamilton Rating Scale for Depression (HRSD(17)) score. The results of a survival analysis indicated that patients with shorter histories of illness (< 4 years), a negative family history of depression, and those who were either married or were living with someone were more likely to have a positive outcome during the acute phase treatment of depression. The main findings are consistent with extensive previous literature indicating a better short-term outcome of depression where illness is shorter, where there is no family history, and where there is better social support.