Nonpsychotic Major Depressive Disorder Research Articles

Atypical Antipsychotic Augmentation Strategies in the Context of Guideline-based Care for the Treatment of Major Depressive Disorder

There is a growing body of evidence that supports the use of atypical antipsychotics as augmentation agents for nonpsychotic unipolar major depressive disorder (MDD) in adults. Unfortunately, varying definitions of treatment-resistant depression, the limited evidence available for interventions after two or more treatment failures, and when and whether to use medications from nonantidepressant classes, remain a key gap in the knowledge base for clinicians. We identified and reviewed the following guidelines to discuss the status of augmentation therapy with atypical antipsychotic agents in MDD: American Psychiatric Association practice guidelines for treatment of patients with MDD; Canadian Network for Mood and Anxiety Treatments clinical guidelines for the management of MDD in adults; National Institute for Health and Clinical Excellence guidelines for treatment and management of depression in adults; British Association of Psychopharmacology guidelines for treatment of depressive disorders; Institute for Clinical Systems Improvement healthcare guideline for MDD in adults in primary care; clinical practice recommendations for depression; international consensus statement on MDD; German Society of Psychiatry, Psychotherapy and Neurology guidelines for unipolar depression; and World Federation of Societies of Biological Psychiatry guidelines for biological treatment of unipolar depressive disorders in primary care. Reflecting the cumulative evidence in the past decade, augmentation strategies including atypical antipsychotic augmentation are recommended in most guidelines for partial or nonresponders, at the same stage as switching or combination strategies. However, there are few direct comparisons of different augmentation strategies and little information about the optimal duration of augmentation strategies or use in special populations. Clinicians should note that guidelines are derived from an evolving database of evidence and cannot take into account the myriad of clinical variables that differ between individual patients. Therefore, they are intended to provide a useful framework for the management of depression and should be used in conjunction with other recognized sources of patient information and the application of clinical wisdom.

Psychotic versus non-psychotic major depressive disorder: A comparative naturalistic study

ObjectivePsychotic depressed patients were found to have more severe cognitive deficits, poorer treatment response and higher suicidal risk respect to non-psychotic depressives. Aim of the present research was to compare clinical variables and outcome between psychotic and non-psychotic major depressive patients. MethodA sample of 36 major depressed patients was divided into two groups according to the presence of psychotic symptoms. Structured Clinical Interview for DSM (SCID-I) and Hamilton Depression Rating Scale (HAM-D) were administered to the patients at baseline by trained raters. One-way analysis of variance (ANOVAs) and chi-square tests were performed to compare the two groups. Binary logistic regression was performed to assess the risk of lack of response/remission in patients with psychotic symptoms and the risk of developing psychotic symptoms in major depressives with a family history of schizophrenia or bipolar disorder. ResultsPsychotic major depressives presented more severe illness as showed by HAM-D baseline scores (F=17.20, p<0.001), a longer duration of hospitalization (F=7.64, p=0.009) and they were more frequently treated with clomipramine (χ2=16.22, p=0.027). Psychotic symptoms were predictive of lack of remission (OR=4.09, p=0.05) and family history of schizophrenia/psychotic bipolar disorder was associated with psychotic major depression (OR=10.81, p=0.04). ConclusionsPatients with psychotic symptoms present a more severe course of illness as showed by long hospitalizations and lower rates of remission. Psychotic depressives show more frequently a family history of “major psychoses” suggesting a continuum in psychotic disorders and a genetic association of major psychotic depression with bipolar disorder and schizophrenia.

Confounding control in a nonexperimental study of STAR*D data: logistic regression balanced covariates better than boosted CART

PurposePropensity scores (PSs), a powerful bias-reduction tool, can balance treatment groups on measured covariates in nonexperimental studies. We demonstrate the use of multiple PS estimation methods to optimize covariate balance. MethodsWe used secondary data from 1292 adults with nonpsychotic major depressive disorder in the Sequenced Treatment Alternatives to Relieve Depression trial (2001–2004). After initial citalopram treatment failed, patient preference influenced assignment to medication augmentation (n = 565) or switch (n = 727). To reduce selection bias, we used boosted classification and regression trees (BCART) and logistic regression iteratively to identify two potentially optimal PSs. We assessed and compared covariate balance. ResultsAfter iterative selection of interaction terms to minimize imbalance, logistic regression yielded better balance than BCART (average standardized absolute mean difference across 47 covariates: 0.03 vs. 0.08, matching; 0.02 vs. 0.05, weighting). ConclusionsComparing multiple PS estimates is a pragmatic way to optimize balance. Logistic regression remains valuable for this purpose. Simulation studies are needed to compare PS models under varying conditions. Such studies should consider more flexible estimation methods, such as logistic models with automated selection of interactions or hybrid models using main effects logistic regression instead of a constant log-odds as the initial model for BCART.

Brain Morphology Changes in a Remitted Patient With Late-Onset, Drug-Naïve, Non-Psychotic Major Depressive Disorder After Amisulpride Monotherapy

Brain Morphology Changes in a Remitted Patient With Late-Onset, Drug-Naïve, Non-Psychotic Major Depressive Disorder After Amisulpride Monotherapy

Improving metabolic parameters of antipsychotic child treatment (IMPACT) study: rationale, design, and methods.

BackgroundYouth with serious mental illness may experience improved psychiatric stability with second generation antipsychotic (SGA) medication treatment, but unfortunately may also experience unhealthy weight gain adverse events. Research on weight loss strategies for youth who require ongoing antipsychotic treatment is quite limited. The purpose of this paper is to present the design, methods, and rationale of the Improving Metabolic Parameters in Antipsychotic Child Treatment (IMPACT) study, a federally funded, randomized trial comparing two pharmacologic strategies against a control condition to manage SGA-related weight gain.MethodsThe design and methodology considerations of the IMPACT trial are described and embedded in a description of health risks associated with antipsychotic-related weight gain and the limitations of currently available research.ResultsThe IMPACT study is a 4-site, six month, randomized, open-label, clinical trial of overweight/obese youth ages 8–19 years with pediatric schizophrenia-spectrum and bipolar-spectrum disorders, psychotic or non-psychotic major depressive disorder, or irritability associated with autistic disorder. Youth who have experienced clinically significant weight gain during antipsychotic treatment in the past 3 years are randomized to either (1) switch antipsychotic plus healthy lifestyle education (HLE); (2) add metformin plus HLE; or (3) HLE with no medication change. The primary aim is to compare weight change (body mass index z-scores) for each pharmacologic intervention with the control condition. Key secondary assessments include percentage body fat, insulin resistance, lipid profile, psychiatric symptom stability (monitored independently by the pharmacotherapist and a blinded evaluator), and all-cause and specific cause discontinuation. This study is ongoing, and the targeted sample size is 132 youth.ConclusionAntipsychotic-related weight gain is an important public health issue for youth requiring ongoing antipsychotic treatment to maintain psychiatric stability. The IMPACT study provides a model for pediatric research on adverse event management using state-of-the art methods. The results of this study will provide needed data on risks and benefits of two pharmacologic interventions that are already being used in pediatric clinical settings but that have not yet been compared directly in randomized trials.Trial registrationClinical Trials.gov NCT00806234

Regional cerebral blood flow changes and performance deficit during a sustained attention task in schizophrenia: 15O‐water positron emission tomography

Attention deficit has been reported in both schizophrenia patients and patients with major depressive disorder (MDD). The aim of this study was to elucidate the deficits in sustained attention and associated neural network dysfunctions in schizophrenia patients and MDD patients, and to investigate the difference between the two patient groups. Twelve schizophrenia patients, 12 patients with non-psychotic MDD, and 12 healthy control subjects participated in this study. A sustained attention to response task (SART) was used to measure attention capacity. Cerebral blood flow (CBF) during attention tasks was measured using H(2) (15) O positron emission tomography. Statistical parametric mapping and analysis of covariance were performed to compare the behavioral performance and CBF changes during SART among three groups. Behavioral performances were not significantly different among the three groups except for an increased commission error rate in the schizophrenia group. Regional CBF during SART was significantly reduced in the left inferior frontal gyrus, the left cuneus, and the right superior parietal lobule and increased in the right superior frontal gyrus and the right cuneus in the schizophrenia group compared to the healthy control group. In the MDD group, neither significant regional CBF difference nor behavioral deficit was found compared to the healthy control group. Behavioral performance deficit and perfusion changes in the prefrontal and parietal cortices during SART were observed only in the schizophrenia group. Prefrontal and parietal network dysfunction for sustained attention may be involved in the pathophysiology of schizophrenia.

Predictors of remission in depression to individual and combined treatments (PReDICT): study protocol for a randomized controlled trial.

BackgroundLimited controlled data exist to guide treatment choices for clinicians caring for patients with major depressive disorder (MDD). Although many putative predictors of treatment response have been reported, most were identified through retrospective analyses of existing datasets and very few have been replicated in a manner that can impact clinical practice. One major confound in previous studies examining predictors of treatment response is the patient’s treatment history, which may affect both the predictor of interest and treatment outcomes. Moreover, prior treatment history provides an important source of selection bias, thereby limiting generalizability. Consequently, we initiated a randomized clinical trial designed to identify factors that moderate response to three treatments for MDD among patients never treated previously for the condition.Methods/designTreatment-naïve adults aged 18 to 65 years with moderate-to-severe, non-psychotic MDD are randomized equally to one of three 12-week treatment arms: (1) cognitive behavior therapy (CBT, 16 sessions); (2) duloxetine (30–60 mg/d); or (3) escitalopram (10–20 mg/d). Prior to randomization, patients undergo multiple assessments, including resting state functional magnetic resonance imaging (fMRI), immune markers, DNA and gene expression products, and dexamethasone-corticotropin-releasing hormone (Dex/CRH) testing. Prior to or shortly after randomization, patients also complete a comprehensive personality assessment. Repeat assessment of the biological measures (fMRI, immune markers, and gene expression products) occurs at an early time-point in treatment, and upon completion of 12-week treatment, when a second Dex/CRH test is also conducted. Patients remitting by the end of this acute treatment phase are then eligible to enter a 21-month follow-up phase, with quarterly visits to monitor for recurrence. Non-remitters are offered augmentation treatment for a second 12-week course of treatment, during which they receive a combination of CBT and antidepressant medication. Predictors of the primary outcome, remission, will be identified for overall and treatment-specific effects, and a statistical model incorporating multiple predictors will be developed to predict outcomes.DiscussionThe PReDICT study’s evaluation of biological, psychological, and clinical factors that may differentially impact treatment outcomes represents a sizeable step toward developing personalized treatments for MDD. Identified predictors should help guide the selection of initial treatments, and identify those patients most vulnerable to recurrence, who thus warrant maintenance or combination treatments to achieve and maintain wellness.Trial registrationClinicaltrials.gov Identifier: NCT00360399. Registered 02 AUG 2006. First patient randomized 09 FEB 2007.

Aripiprazole Monotherapy-Related Gray-Matter Growth in a Patient With First-Episode Drug-Naïve Non-Psychotic Major Depressive Disorder

Back to table of contents Previous article Next article LettersFull AccessAripiprazole Monotherapy-Related Gray-Matter Growth in a Patient With First-Episode Drug-Naïve Non-Psychotic Major Depressive DisorderChien-Han Lai, M.D.Chien-Han LaiDepartment of Psychiatry, Buddhist Tzu-Chi General Hospital, Taipei Branch, Taipei, TaiwanSearch for more papers by this author, M.D.Published Online:1 Jul 2012https://doi.org/10.1176/appi.neuropsych.11080198AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Aripiprazole, a kind of D2 partial agonist antipsychotic, is approved for major depressive disorder (MDD) add-on therapy. It is believed to be related to its 5-HT1A partial agonist, 5-HT2C antagonist and 5-HT2A antagonist property. Here I want to present a case of first-episode drug-naïve nonpsychotic MDD with improvements of symptoms after 6-week treatment. Magnetic resonance imaging (MRI) structural analysis also revealed gray matter (GM) growth and brain volume (BV) increase within 6 weeks.Case ReportMiss L is a 47-year-old female patient with first-episode drug-naïve MDD for 1-2 months. No specific physical illness, psychotic features, past manic episodes, nonpsychiatric medication use and substance abuse were mentioned. The symptoms of typical depression were mentioned, such as distinct depressed mood, suicide ideation, lack of interest, lack of energy, psychomotor agitation and sleep disturbances [Hamilton Rating Scale for Depression (HRSD): 32]. After visiting my clinic, she started to receive aripiprazole monotherapy as 2.5 mg/day and then the dose was titrated to 5 mg within 1 week without any significant side effects except mild headache and dizziness. No significant extrapyramidal side effects were mentioned. After 6 weeks of therapy, her MDD symptoms improved (HRSD: 13).Structural brain magnetic resonance imaging (MRI) scans were obtained with 3T Siemens version scanner housed at MR Center, National Yang Ming University. Scans with three-dimensional fast spoiled gradient-echo recovery (3D-FSPGR) T1W1 (TR 2530ms; TE 3.03ms; slice thickness=1mm (no gap);192slices; matrix = 224×256; field of view: 256mm; number of excitation=1) were performed at first visit and 6th week visit. Her body weight was 71.2 kg at baseline and 71.7 kg at 6th week. Structural MRI was preprocessed with Structural Image Evaluation, using Normalization, of Atrophy (SIENAX) function of FSL (FMRIB Software Library) to calculate single time point GM, WM, and BV after registering and normalizing to template. The brain morphology change was estimated by SIENA function to calculate percentage BV change (PBVC). After analyzing brain MRI structure by SIENAX, GM increased from 750145.59 to 790751.54 within 6 weeks and PBVC is 0.0352900, which suggested BV increase after aripiprazole treatment (Figure 1).FIGURE 1. BV Increased After Aripiprazole (5 mg/day) 6-week TherapyBlue color represented atrophy and red color represented growth of BV. A positive estimated PBVC value represented BV increase.DiscussionAccording to study of Frodl et al., MDD is associated with GM deficits over amygdala, hippocampus, prefrontal cortex, and anterior cingulate cortex.1 These regional GM deficits are related to their symptoms severity and even represent a kind of “trait marker” for MDD.2 GM growth effects might be related to the following reasons, such as synaptic remodeling and neurogenesis3 from the stimulation of neutrophic factors by antipsychotics,4 prevention of oxidative stress or 6-OH-dopamine lesioning and with subsequent increased glial cell proliferation in frontal cortex.5Department of Psychiatry, Buddhist Tzu-Chi General Hospital, Taipei Branch, Taipei, TaiwanThis case study was approved by the institute of review board of Buddhist Tzu Chi Hospital, Taipei Branch. The author thanks Miss Wang (MR Center, National Yang Ming University) for MRI acquisition help and technique assistance and also acknowledges MR support from National Yang-Ming University, Taiwan, which is in part supported by the MOE plan for the top university.References1 Frodl TS, Koutsouleris N, Bottlender R, et al.: Depression-related variation in brain morphology over 3 years: effects of stress? Arch Gen Psychiatry 2008; 65:1156–1165Crossref, Medline, Google Scholar2 Lai CH, Hsu YY, Wu YT: First episode drug-naïve major depressive disorder with panic disorder: gray matter deficits in limbic and default network structures. Eur Neuropsychopharmacol 2010; 20:676–682Crossref, Medline, Google Scholar3 Konradi C, Heckers S: Antipsychotic drugs and neuroplasticity: insights into the treatment and neurobiology of schizophrenia. Biol Psychiatry 2001; 50:729–742Crossref, Medline, Google Scholar4 Parikh V, Khan MM, Mahadik SP: Olanzapine counteracts reduction of brain-derived neurotrophic factor and TrkB receptors in rat hippocampus produced by haloperidol. Neurosci Lett 2004; 356:135–139Crossref, Medline, Google Scholar5 Wang HD, Dunnavant FD, Jarman T, et al.: Effects of antipsychotic drugs on neurogenesis in the forebrain of the adult rat. Neuropsychopharmacology 2004; 29:1230–1238Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited ByPsychiatry and Clinical Neurosciences, Vol. 72, No. 5Gray matter increases in fronto-parietal regions of depression patients with aripiprazole monotherapyMedicine, Vol. 95, No. 34 Volume 24Issue 3 Summer 2012Pages E49-E50 Metrics PDF download History Published online 1 July 2012 Published in print 1 July 2012

Neuropsychological performance in a sample of 13–25year olds with a history of non-psychotic major depressive disorder

There is evidence for neuropsychological dysfunction in depression among adult and elderly participants but little research has been conducted on the neuropsychological functioning of youth with depression. The aim of the present study was to investigate the neuropsychological functioning of outpatient young participants with depression. Computerised neuropsychological tests requiring executive functioning, working memory, attention, verbal memory and learning, planning, and visuospatial skills were carried out in a sample of 13-25year-olds with a lifetime history of non-psychotic major depression (n=32) and in healthy age balanced controls (n=65). Psychiatric diagnoses were ascertained using the MINI International Neuropsychiatric Interview. Participants with current or previous major depressive disorder demonstrated impairments in executive function tasks requiring conceptual skills and set-shifting, attention and working memory. However, planning skills were found to be largely intact. Positive affect was associated to better attention, working memory and verbal learning in depressed participants, independently from gender and education. The results may be affected by the small sample size and heterogeneity of the sample. The findings from this study indicate, and are one of the first to identify, that young subjects aged between 13 and 25, with a lifetime history of depression, have impaired executive and working memory functioning.

Distressing Adverse Events After Antidepressant Switch in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Trial: Influence of Adverse Events During Initial Treatment with Citalopram on Development of Subsequent Adverse Events with an Alternative Antidepressant

To determine whether distressing adverse events (DAEs) experienced during initial antidepressant treatment are associated with subsequent DAEs after switching to a second antidepressant. Secondary analysis of data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. Primary care and psychiatric care facilities. A total of 727 outpatients aged 18-75 years with nonpsychotic major depressive disorder who failed first-step therapy with citalopram and were switched to second-step monotherapy with an alternative antidepressant. In the STAR*D trial, patient-reported DAEs were entered into the Patient-Rated Inventory of Side Effects (PRISE). In this secondary analysis, data from PRISE were used to determine the incidence of DAEs during first-step treatment with citalopram and second-step treatment with sustained-release bupropion, sertraline, or extended-release venlafaxine. Regression models were used to compare the risk of adverse events during second-step treatment between those who reported similar adverse events during first-step treatment and those who did not, while controlling for potential confounders. Of the 727 patients analyzed, DAEs were reported by 514 patients (70.7%) during first-step treatment and 626 (86.1%) during second-step treatment; no significant differences were observed among the three second-step treatment groups. Overall, patients reporting DAEs during first-step treatment were more likely to report DAEs during second-step treatment (risk ratio [RR] 1.11, 95% confidence interval [CI] 1.03-1.20). After controlling for confounders, patients were significantly more likely to report DAEs specific to a body function or organ system, such as those involving the genitourinary system (RR 3.39, 95% CI 2.41-4.78) or sexual functioning (RR 2.75, 95% CI 2.29-3.29), if the patients had reported similar events during initial treatment. Patients who experienced DAEs with initial antidepressant treatment were likely to report similar adverse events after switching to an alternative antidepressant, even when subsequent treatment is from a different class of antidepressants.

An open-label study of adjunctive repetitive transcranial magnetic stimulation (rTMS) for partial remission in major depressive disorder

Objective. This study aimed to evaluate the effect of adjunctive treatment with rTMS in patients with partial remission major depressive disorder. Method. Subjects were patients meeting DSM-IV-TR criteria for non-psychotic major depressive disorder who responded to 8 weeks of medication treatment but still had residual symptoms (HAM-D score between 7 and 18). All patients were assigned to receive 10 daily sessions (total of 12,500 magnetic pulses) of rTMS applied at the left dorsolateral prefrontal cortex as adjunctive treatment. The antidepressant effect was measured repeatedly at 6 days, and at 4 and 8 weeks after treatment with the Thai version of HAM-D scale as a primary outcome scale. Results. Seven of nine patients (78%) reached the stage of remission (HAM-D < 8) after being treated with adjunctive rTMS. There was a statistically significant difference in decreasing of the HAM-D score during the treatment, χ2 (df 3) = 17.929, P < 0.001. There was no severe adverse event. One patient had vertigo after the first session of treatment and one patient had a scalp contraction feeling during treatment but full recovered in half an hour with no medical intervention. Conclusion. For patients with a major depressive disorder in partial remission, high frequency rTMS may provide benefits in adjunctive treatment which are tolerated well. However, the long term effects should be observed.

Pre-adult onset and patterns of suicidality in patients with a history of recurrent depression

BackgroundThis report assesses the association between age of onset of major depression and later suicidality in a sample of 276 recurrently depressed patients recruited for the Oxford/Bangor Staying Well after Depression (SWAD) Trial, and interviewed when in remission.MethodsThe study enrolled adult patients with a history of at least three episodes of non-psychotic major depressive disorder from primary care and psychiatric care practices and through community advertisements. At study entry, all participants estimated the age of their first onset of a major depressive episode and completed both self-report and interview-based assessments of past and current suicidal ideation and behavior. Participants were divided into pre-adult and adult onset groups using a cut-off age of 18.ResultsForty-eight percent of the sample reported a pre-adult age of onset. Pre-adult age of onset was significantly associated with suicidality, both from self-report and from interviewer assessment even when adjusting for differences in age, gender, employment status, length of the disorder and early adversity.LimitationsRelevant variables were all assessed through retrospective reports.ConclusionsPre-adult age of onset is closely associated with risk for and severity of later suicidality, replicating, in a sample of patients assessed when in remission, findings from studies that assessed patients when currently depressed. The association of pre-adult age of onset with suicidality is not due to differences in sociodemographic variables, length of the disorder and early adversity.

P-539 - A meta-analysis of executive dysfunctions in unipolar major depressive disorder (MDD) without psychotic symptoms and their changes during antidepressant treatment

In patients with MDD, empirical evidence supports the existence of moderate but significant neuropsychological deficits as compared to non-depressed controls. With respect to cognitive domains, impairment has been reported for executive functioning in particular, whereas less significant deficits have been found for psychomotor speed, attention and memory. Additionally, studies reported a substantial improvement in neuropsychological functioning during the course of an antidepressant treatment in patients with MDD. Nevertheless, the effect size of executive dysfunctions in unipolar, non-psychotic MDD as well as their relationship to antidepressant treatment is ambiguous. Meta-analytic methods were used to assess the severity of executive dysfunctions in unipolar, non-psychotic MDD as compared to healthy controls and to investigate their course during antidepressant treatment. 15 studies comparing the executive functions of 375 patients with DSM-IV MDD and 481 healthy controls were analysed. Furthermore, in 3 studies including 122 MDD patients the Stroop test performance was examined before and after antidepressant treatment. MDD patients performed 0.439 up to 1.18 (p < 0.0001) standard mean differences worse than healthy controls. The Stroop performance improved during the course of treatment (p = 0.0001). We revealed significant executive dysfunctions in unipolar, non-psychotic MDD patients compared to healthy controls and an improvement of the Stroop performance during the course of treatment. However, the results of our longitudinal analysis are not transferable to other components of executive functioning. Future studies with different test procedures are needed to further investigate the influence of antidepressant treatment on executive functions.

Twelve-month, prospective, open-label study of repetitive transcranial magnetic stimulation for major depressive disorder in partial remission

BackgroundThe purpose of this study was to evaluate the long-term effect of repetitive transcranial magnetic stimulation (rTMS) as adjunctive treatment in patients with partial remission of major depressive disorder.MethodsThis was a 12-month, prospective, open-label study in patients meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria for nonpsychotic major depressive disorder who responded to 8 weeks of medication treatment but did not reach remission. All patients were assigned to receive 10 sessions of rTMS applied at the left dorsolateral prefrontal cortex. During the course of rTMS, the patients were still taking their usual medication. Patients were followed up for 12 months to determine the long-term antidepressant effect.ResultsThere were nine patients (seven women and two men) who met the inclusion criteria and agreed to receive rTMS. The mean Hamilton rating scale for depression (HAM-D) score prior to treatment with rTMS was 12.89 ± 2.15. At 12 months after treatment, the mean HAM-D score was 6.45 ± 1.67 using a Friedman test, and in patients with partial remission of major depressive disorder, the HAM-D score significantly decreased after treatment with rTMS at 12 months (P = 0.001). Seven patients (77.78%) had reached the stage of remission (HAM-D < 8) after treating with rTMS at 12 months. There were no serious adverse events. One patient had vertigo after the first session of treatment and one patient felt scalp contractions during treatment, and both fully recovered within half an hour with no medical intervention.ConclusionFor patients with major depressive disorder in partial remission, high frequency rTMS at the left dorsolateral prefrontal cortex may provide benefits in adjunctive treatment with well tolerability. Also, follow-up findings show a long duration of benefit.

What are the clinical implications of new onset or worsening anxiety during the first two weeks of SSRI treatment for depression?

To evaluate the prevalence of new onset or worsening of anxiety symptoms, as well as their clinical implications, during the first 2 weeks of Selective Serotonin Reuptake Inhibitor (SSRI) pharmacotherapy for depression. Adult outpatients with nonpsychotic major depressive disorder were enrolled in an 8-week acute phase SSRI treatment trial at 15 clinical sites across the United States. Worsening anxiety was defined as a greater than 2-point increase on the Beck Anxiety Inventory (BAI) between baseline and Week 2. New onset of anxiety symptoms was ascribed when the BAI baseline rating was 0 and the Week 2 value was greater or equal to 2 points on the BAI. Overall, after 2 weeks of treatment, 48.8% (98 of 201 participants) reported improvement in anxiety symptoms, 36.3% (73 of 201) reported minimal symptom change, and 14.9% (30 of 201) reported worsening of anxiety symptoms. No association was found between change in anxiety symptoms within the first 2 weeks and change in depressive symptoms or remission at the end of 8 weeks of treatment. For participants with clinically meaningful anxiety symptoms at baseline, however, worsening of anxiety during the first 2 weeks of treatment was associated with worsening depressive symptoms by 8 weeks (P = .054). The trajectory of anxiety symptom change early in SSRI treatment is an important indicator of eventual outcome for outpatients with major depression and baseline anxiety symptoms.

Assessing anxious features in depressed outpatients

Both the 17-item Hamilton Rating Scale for Depression (HRSD(17)) and 30-item Inventory of Depressive Symptomatology - Clinician-rated (IDS-C(30) ) contain a subscale that assesses anxious symptoms. We used classical test theory and item response theory methods to assess and compare the psychometric properties of the two anxiety subscales (HRSD(ANX) and IDS-C(ANX)) in a large sample (N = 3453) of outpatients with non-psychotic major depressive disorder in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Approximately 48% of evaluable participants had at least one concurrent anxiety disorder by the self-report Psychiatric Diagnostic Screening Questionnaire (PDSQ). The HRSD(ANX) and IDS-C(ANX) were highly correlated (r = 0.75) and both had moderate internal consistency given their limited number of items (HRSD(ANX) Cronbach's alpha = 0.48; IDS-C(ANX) Cronbach's alpha = 0.58). The optimal threshold for ascribing the presence/absence of anxious features was found at a total score of eight or nine for the HRSD(ANX) and seven or eight for the IDS-C(ANX) . It would seem beneficial to delete item 17 (loss of insight) from the HRSD(ANX) as it negatively correlated with the scale's total score. Both the HRSD(ANX) and IDS-C(ANX) subscales have acceptable psychometric properties and can be used to identify anxious features for clinical or research purposes.

A meta‐analysis of executive dysfunctions in unipolar major depressive disorder without psychotic symptoms and their changes during antidepressant treatment

Empirical evidence supports the existence of significant executive deficits in patients with major depressive disorder (MDD) as compared to non-depressed controls. Nevertheless, the effect size of executive dysfunctions in unipolar, non-psychotic MDD as well as their relationship to antidepressant treatment is ambiguous. Meta-analytic methods were used to assess the severity of executive dysfunctions in unipolar, non-psychotic MDD as compared to healthy controls and to investigate their course during antidepressant treatment. Fifteen studies comparing the executive functions of 375 patients with DSM-IV MDD and 481 healthy controls were analysed. Furthermore, in three studies, including 122 patients with MDD, the Stroop test performance was examined before and after antidepressant treatment. Patients with MDD performed 0.439 up to 1.18 (P < 0.0001) standard mean differences worse than healthy controls. The Stroop performance improved during the course of treatment (P = 0.0001). We revealed significant executive dysfunctions in patients with unipolar, non-psychotic MDD compared with healthy controls and an improvement of the Stroop performance during the course of treatment. Future studies with different test procedures are needed to further investigate the influence of antidepressant treatment on executive functions.

Concise Health Risk Tracking Scale

Monitoring suicidality and risk following initiation of antidepressant treatment is an essential component of clinical care, but few brief, reliable ratings of suicidal ideation and behavior in adults are available. This report evaluates the psychometric properties of a brief self- and clinician-rated measure of factors related to the risk of suicide attempt or completion. Adult outpatients with nonpsychotic major depressive disorder (MDD) (n = 240) were enrolled from July 2007 through February 2008 and treated in an 8-week, open-label trial with the clinician's choice of a selective serotonin reuptake inhibitor at 6 primary care and 9 psychiatric clinical care settings in the National Institute of Mental Health-funded Depression Trials Network. Diagnosis of MDD was determined by the Psychiatric Diagnostic Screening Questionnaire and an MDD checklist based on DSM-IV-TR criteria. Suicidal ideation and behavior are 1 of 9 symptoms of MDD (depressed mood, loss of interest, appetite or weight change, sleep disturbance, reduced concentration or indecisiveness, fatigue or decreased energy, psychomotor agitation or retardation, feelings of worthlessness, or excessive guilt). The newly developed Concise Health Risk Tracking (CHRT) scale was administered both as the CHRT Self-Report (CHRT-SR) and Clinician Rating (CHRT-C) scales. Psychometric evaluations were conducted on both scales. The internal consistency (Cronbach α) was .77 for the 7-item CHRT-C and .78 for the 7-item CHRT-SR with a consistent factor structure, and 3 independent factors (current suicidal thoughts and plans, perceived lack of social support, and hopelessness) for both versions. The 7-item CHRT-C and the 7-item CHRT-SR have excellent psychometric properties and can be used to monitor suicidal risk in clinical practice and research settings. Whether either scale will predict suicide attempts or completions in actual practice would require a very large prospective study sample. Clinicaltrials.gov Identifier: NCT00532103.

Adjunctive Medication Strategies for Treatment- Resistant Depression

Abbreviations AD antidepressant CANMAT Canadian Network for Mood and Anxiety Treatments MDD major depressive disorder TRD treatment-resistant depression Depression is a serious illness. Numerous studies show that major depressive disorder (MDD) is associated with significant personal distress and burden of disability.1 The good news is that there are many effective treatments available to treat MDD. The bad news is that not everyone experiences a full response to treatment. For example, the Sequenced Treatment Alternatives to Relieve Depression (commonly known by its acronym, STAR*D) effectiveness study found that, in the real world, remission outcomes are modest, with only 33% of patients with MDD achieving full remission of symptoms after the first antidepressant (AD) and only 67% after 1 year of treatment involving up to 4 treatment steps.2 Thus a significant percentage of patients will have a treatment-resistant depression (TRD), regardless of how treatment-resistant is defined.3 It is also clear that TRD is associated with poor outcomes and a disproportionate amount of the burden associated with MDD.4,5 Although TRD is often used in the literature as if it were a distinct entity, there is considerable variability in how TRD is defined and there is no consensus definition.6 For example, a commonly applied definition for TRD is failure of 2 or more ADs, preferably from different classes. However, some studies define resistant depression as failure of one AD, while others attempt to stage resistance by incorporating responses to other treatments (including older medications, such as tricyclic ADs or monoamine oxidase inhibitors, and somatic treatments, such as electroconvulsive therapy).7 Moreover, the definition of failure also varies considerably from study to study. Some TRD studies include patients with treatment failure by history, while others define failure prospectively. These diagnostic issues contribute to significant heterogeneity in TRD samples, which makes it difficult to compare treatment studies of TRD. In the context of modest success rates with AD monotherapy for MDD, how can we optimize outcomes for the large proportion of patients with TRD? We practice in an evidence-based medicine climate, so it is important to first consider evidence-based treatment approaches. However, we need to remember to differentiate between evidence of lack of efficacy and lack of evidence of efficacy. The latter is much more representative of the evidence landscape in psychiatry than the former. While there is reasonable evidence to support choices for initial pharmacotherapy of MDD, there is still only limited evidence for many important clinical questions, including how to manage poor or incomplete response to an initial AD. To further complicate the issue, the terminology for treatment strategies for TRD is changing. Augmentation and combination have been used in the literature to describe distinct strategies when adding another medication to an AD. Augmentation referred to adding a medication that was not considered an AD (for example, lithium or triiodothyronine), while combination referred to the practice of adding a second AD (for example, desipramine or bupropion). However, the definition of an AD is blurring and some medications that were considered augmentation agents may be effective ADs on their own. For example, older studies indicated that lithium may have acute AD effects for unipolar depression,8 and more recent studies show that some atypical antipsychotics (for example, quetiapine extended release9) are effective as monotherapy for nonpsychotic MDD. For this reason, some authors have suggested that the terms augmentation and combination be replaced by add-on or adjunctive, which do not infer the type of medication added.10 The 2009 revision of the Canadian Network for Mood and Anxiety Treatments (CANMAT) depression guidelines summarizes the evidence for pharmacologic strategies for TRD. …

Residual Symptoms in Depressed Outpatients Who Respond by 50% But Do Not Remit to Antidepressant Medication

Little is known about the quantity or quality of residual depressive symptoms in patients with major depressive disorder (MDD) who have responded but not remitted with antidepressant treatment. This report describes the residual symptom domains and individual depressive symptoms in a large representative sample of outpatients with nonpsychotic MDD who responded without remitting after up to 12 weeks of citalopram treatment in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Response was defined as 50% or greater reduction in baseline 16-item Quick Inventory of Depressive Symptomatology--Self-Report (QIDS-SR₁₆) by treatment exit, and remission as a final QIDS-SR₁₆ of less than 6. Residual symptom domains and individual symptoms were based on the QIDS-SR₁₆ and classified as either persisting from baseline or emerging during treatment. Most responders who did not remit endorsed approximately 5 residual symptom domains and 6 to 7 residual depressive symptoms. The most common domains were insomnia (94.6%), sad mood (70.8%), and decreased concentration (69.6%). The most common individual symptoms were midnocturnal insomnia (79.0%), sad mood (70.8%), and decreased concentration/decision making (69.6%). The most common treatment-emergent symptoms were midnocturnal insomnia (51.4%) and decreased general interest (40.0%). The most common persistent symptoms were midnocturnal insomnia (81.6%), sad mood (70.8%), and decreased concentration/decision making (70.6%). Suicidal ideation was the least common treatment-emergent symptom (0.7%) and the least common persistent residual symptom (17.1%). These findings suggest that depressed outpatients who respond by 50% without remitting to citalopram treatment have a broad range of residual symptoms. Individualized treatments are warranted to specifically address each patient's residual depressive symptoms.