Montgomery-Asberg Depression Rating Scale Scores Research Articles

A Placebo-Controlled Trial of Acetyl-L-Carnitine and α-Lipoic Acid in the Treatment of Bipolar Depression

Bipolar disorder may be associated with mitochondrial dysfunction. Therefore, agents that enhance mitochondrial functioning may be efficacious in bipolar disorder. We performed a randomized placebo-controlled trial of the mitochondrial enhancers acetyl-L-carnitine (ALCAR) and α-lipoic acid (ALA) in patients with bipolar depression, and assessed markers of cerebral energy metabolism using phosphorus magnetic resonance spectroscopy. We administered ALCAR (1000-3000 mg daily) plus ALA (600-1800 mg daily) or placebo for 12 weeks to 40 patients with bipolar depression and obtained imaging data at baseline, week 1, and week 12 of treatment in 20 patients using phosphorus 3-dimensional chemical-shift imaging at 4 T. Statistical analysis used random effects mixed models. We found no significant difference between ALCAR/ALA and placebo on change from baseline in the Montgomery-Asberg Depression Rating Scale in both the longitudinal (mean difference [95% confidence interval], -1.4 [-6.2 to 3.4], P = 0.58) and last-observation-carried-forward (-3.2 [-7.2 to 0.9], P = 0.12) analyses. ALCAR/ALA treatment significantly reduced phosphocreatine levels in the parieto-occipital cortex at week 12 (P = 0.002). Reduction in whole brain total nucleoside triphosphate levels from baseline to week 1 was associated with reduction in Montgomery-Asberg Depression Rating Scale scores (P = 0.02) in patients treated with ALCAR/ALA. However, this was likely a chance finding attributable to multiple statistical comparisons. Treatment with ALCAR and ALA at the dose and duration used in this study does not have antidepressant effects in depressed bipolar patients and does not significantly enhance mitochondrial functioning in this patient group.

Efficacy and tolerability of asenapine for acute mania in bipolar I disorder

The aim of this study was to quantitatively review, using a meta-analytic approach, randomized-controlled trials analyzing the efficacy and safety profiles of asenapine in the treatment of bipolar disorder (BD). MEDLINE (1966 to August 2012) and EMBASE (1980 to August 2012) databases were systematically searched to identify relevant papers. Data from four randomized-controlled trials were analyzed. For continuous data (Young Mania Rating Scale, Clinical Global Impression Scale for Bipolar Disorder, and Montgomery-Asberg Depression Rating Scale scores), the Hedges g was adopted as a measure of the effect size; for dichotomous outcome measures (discontinuation and rates of adverse events), the risk ratio was calculated. In short-term trials, asenapine was found to be significantly superior to placebo in the treatment of manic symptoms of BD. There is also evidence of the positive effects of asenapine compared with placebo on depressive symptoms in mixed bipolar states. In the medium-term and long-term studies, asenapine showed comparable efficacy with the well-established comparator olanzapine in the treatment of manic and depressive symptoms of BD. Adverse events such as somnolence, weight gain, and extrapyramidal symptom, which have an impact on treatment adherence, are scarcely or moderately elicited by asenapine, which shows a better profile than olanzapine on metabolic parameters. On the basis of these results, asenapine can be considered as an effective and tolerable treatment for manic and mixed episodes of BD.

Homocysteine, depression and cognitive function in older adults

BackgroundDepression and high total plasma homocysteine (tHcy) are independently associated with cognitive impairment in older adults. We designed this study to determine if high tHcy is a mediator of cognitive performance in older adults with major depression. MethodsWe recruited 358 community-dwelling older adults experiencing depressive symptoms, 236 (65.9%) of who met DSM-IV-TR criteria for major depression. Assessment included the Montgomery Asberg Depression Rating Scale (MADRS), fasting tHcy and the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery. ResultsIndividuals with major depression and high tHcy had significantly worse immediate verbal and delayed visual recall. Non-depressed participants with high tHcy had lower MMSE, immediate and delayed recall scores than those with normal tHcy. The odds of cognitive inefficiency for those with high tHcy was nearly doubled for the MMSE (OR 1.9, 95%CI 1.1–3.3), immediate (OR 1.9, 95%CI 1.1–3.5) and delayed (OR 1.9, 95%CI 1.1–3.4) word recall after adjusting for age, gender, IHD and MADRS score. LimitationsThe presence of sub-syndromal depressive symptoms in our non-depressed group and exclusion of participants with established cognitive impairment may limit the generalizability of this study. ConclusionsElevated tHcy was associated with weaker performance in tests of immediate and delayed memory and global cognitive performance when compared to those with normal tHcy independent of the presence of major depression or the severity of depressive symptoms. Homocysteine lowering B-vitamin supplementation may offer a potential therapeutic target to try and mitigate the often-disabling impact of cognitive deficits found in this population.

Comparison of Brain Structural Variables, Neuropsychological Factors, and Treatment Outcome in Early-Onset Versus Late-Onset Late-Life Depression

To compare differences in gray matter volumes, white matter and subcortical gray matter hyperintensities, neuropsychological factors, and treatment outcome between early- and late-onset late-life depressed (LLD) subjects. We conducted a prospective, nonrandomized, controlled trial at the outpatient clinics at Washington University and Duke University on 126 subjects, aged 60 years or older, who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depression, scored 20 or more on the Montgomery-Asberg Depression Rating Scale (MADRS), and received neuropsychological testing and magnetic resonance imaging. Subjects were excluded for cognitive impairment or severe medical disorders. After 12 weeks of sertraline treatment, subjects' MADRS scores over time and neuropsychological factors were studied. Left anterior cingulate thickness was significantly smaller in the late-onset depressed group than in the early-onset LLD subjects. The late-onset group also had more hyperintensities than the early-onset LLD subjects. No differences were found in neuropsychological factor scores or treatment outcome between early-onset and late-onset LLD subjects. Age at onset of depressive symptoms in LLD subjects are associated with differences in cortical thickness and white matter and subcortical gray matter hyperintensities, but age at onset did not affect neuropsychological factors or treatment outcome.

Aripiprazole as augmentation therapy in bipolar patients with current minor or subsyndromal mood symptoms.

BackgroundThis study aims to evaluate the effectiveness of aripiprazole augmentation of maintenance treatment for bipolar disorder in patients with minor or subsyndromal mood episodes while on a stable dose of a mood stabiliser and/or antidepressant.MethodsAll subjects had a diagnosis of bipolar I or II disorder (Diagnostic and Statistical Manual of Mental Disorders-4th Edition, Text Revision). Open-label aripiprazole was given over 8 weeks initially. The starting dose was 5 to 15 mg/day with a mean final dose of 11.5 mg (±4.6). Patients were assessed at weeks 0, 2, 4 and 8 with the Montgomery-Asberg Depression Rating Scale (MADRS), Young Mania Rating Scale (YMRS) and Clinical Global Impression of Severity (CGI-S).Results and discussionSeventeen of 20 (85%) patients completed week 4, while 14 (70%) patients completed 8 weeks. For intention-to-treat data, there was a significant decrease in MADRS scores over the course of treatment, with a reduction of 6.40 points at endpoint (p < 0.0005). Improvement from baseline was significant at week 2 and remained through to week 8. Similarly, CGI-S scores significantly decreased over the course of study, but not YMRS scores. Aripiprazole was shown to be a modestly effective augmentation therapy for depressive symptoms in bipolar I and II in this small open-label study.

The Sertraline vs Electrical Current Therapy for Treating Depression Clinical Study

Transcranial direct current stimulation (tDCS) trials for major depressive disorder (MDD) have shown positive but mixed results. To assess the combined safety and efficacy of tDCS vs a common pharmacological treatment (sertraline hydrochloride, 50 mg/d). Double-blind, controlled trial. Participants were randomized using a 2 × 2 factorial design to sertraline/placebo and active/sham tDCS. Outpatient, single-center academic setting in São Paulo, Brazil. One hundred twenty antidepressant-free patients with moderate to severe, nonpsychotic, unipolar MDD. Six-week treatment of 2-mA anodal left/cathodal right prefrontal tDCS (twelve 30-minute sessions: 10 consecutive sessions once daily from Monday to Friday plus 2 extra sessions every other week) and sertraline hydrochloride (50 mg/d). MAIN OUTCOME MEASURES In this intention-to-treat analysis, the primary outcome measure was the change in Montgomery-Asberg depression rating scale score at 6 weeks (end point). We considered a difference of at least 3 points to be clinically relevant. The analysis plan was previously published. Safety was measured with an adverse effects questionnaire, the young mania rating scale, and cognitive assessment. Secondary measures were rates of clinical response and remission and scores on other scales. At the main end point, there was a significant difference in Montgomery-Asberg depression rating scale scores when comparing the combined treatment group (sertraline/active tDCS) vs sertraline only (mean difference, 8.5 points; 95% CI, 2.96 to 14.03; P = .002), tDCS only (mean difference, 5.9 points; 95% CI, 0.36 to 11.43; P = .03), and placebo/sham tDCS (mean difference, 11.5 points; 95% CI, 6.03 to 17.10; P < .001). Analysis of tDCS only vs sertraline only presented comparable efficacies (mean difference, 2.6 points; 95% CI, -2.90 to 8.13; P = .35). Use of tDCS only (but not sertraline only) was superior to placebo/sham tDCS. Common adverse effects did not differ between interventions, except for skin redness on the scalp in active tDCS (P = .03). There were 7 episodes of treatment-emergent mania or hypomania, 5 occurring in the combined treatment group. In MDD, the combination of tDCS and sertraline increases the efficacy of each treatment. The efficacy and safety of tDCS and sertraline did not differ. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01033084.

Efficacy of quetiapine in patients with bipolar I and II depression: a multicenter, prospective, open-label, observational study

PurposeTo evaluate and compare the therapeutic efficacy of quetiapine in bipolar I and II depression patients in the clinical setting.Patients and methodsThis was an 8-week, multicenter, open-label, observational study for bipolar depression. The dosage of quetiapine was flexible, and concomitant medications were permitted on clinician’s judgments. A total of 1097 patients were enrolled, and 764 bipolar depression patients who exhibited good therapeutic compliance (>75% compliance rate) were analyzed.ResultsClinical Global Impression – Bipolar scale and Montgomery–Asberg Depression Rating Scale scores were significantly improved at weeks four and eight compared with the baseline scores. At the end of the 8-week study, the response rate was 58.9%, and the remission rate was 42.1%. However, there were no significant differences in the response and remission rates between bipolar I and II disorder (BD-I and BD-II) patients (response rate 60.1% versus 56.3%; remission rate 44.5% versus 37.0%). Montgomery–Asberg Depression Rating Scale score at baseline (β = 0.612, P < 0.001), duration of current episode (β = −0.152, P = 0.001), and presence of remission on previous episode (β = 0.111, P = 0.012) were significantly associated with improvements in depressive symptoms. Fatigue (16.0%), somnolence (14.9%), and manic/hypomanic switching (0.6% at week four, 0.3% at week eight) were observed throughout the study period.ConclusionThe results of this study suggest that quetiapine improves depressive symptoms in BD-I and BD-II patients with a minimal incidence of manic switching. The therapeutic efficacy of quetiapine increased with time. Quetiapine could be an effective and safe modality for the treatment of BD-I and BD-II.

Antidepressant Prophylaxis Reduces Depression Risk but Does Not Improve Sustained Virological Response in Hepatitis C Patients Receiving Interferon Without Depression at Baseline: A Systematic Review and Meta-Analysis

Depression complicates interferon-based hepatitis C virus (HCV) antiviral therapy in 10% to 40% of cases, and diminishes patient well-being and ability to complete a full course of therapy. As a consequence, the likelihood of achieving a sustained virological response (SVR [ie, permanent viral eradication]) is reduced. To systematically review the evidence of whether pre-emptive antidepressant prophylaxis started before HCV antiviral initiation is beneficial. Inclusion was restricted to randomized controlled trials in which prophylactic antidepressant therapy was started at least two weeks before the initiation of HCV antiviral treatment. Studies pertaining to patients with active or recent depressive symptoms before commencing HCV antiviral therapy were excluded. English language articles from 1946 to July 2012 were included. The MEDLINE, Embase and Cochrane Central databases were searched. Where possible, meta-analyses were conducted evaluating the effect of antidepressant prophylaxis on SVR and major depression as well as on Montgomery-Asberg Depression Rating Scale and Beck Depression Index scores at four, 12 and 24 weeks. The Cochrane Collaboration tool was used to assess bias risk. Six randomized clinical trials involving 522 patients met the inclusion criteria. Although the frequency of on-treatment clinical depression was decreased with antidepressant prophylaxis (risk ratio 0.60 [95% CI 0.38 to 0.93]; P=0.02; I2=24%), no benefit to SVR was identified (risk ratio 1.08 [95% CI 0.74 to 1.57]; P=0.69; I2=58%). This practice is not justified to improve SVR in populations free of active depressive symptoms leading up to HCV antiviral therapy.

Efficacy of an adjunctive brief psychodynamic psychotherapy to usual inpatient treatment of depression: rationale and design of a randomized controlled trial

BackgroundA few recent studies have found indications of the effectiveness of inpatient psychotherapy for depression, usually of an extended duration. However, there is a lack of controlled studies in this area and to date no study of adequate quality on brief psychodynamic psychotherapy for depression during short inpatient stay exists. The present article describes the protocol of a study that will examine the relative efficacy, the cost-effectiveness and the cost-utility of adding an Inpatient Brief Psychodynamic Psychotherapy to pharmacotherapy and treatment-as-usual for inpatients with unipolar depression.Methods/DesignThe study is a one-month randomized controlled trial with a two parallel group design and a 12-month naturalistic follow-up. A sample of 130 consecutive adult inpatients with unipolar depression and Montgomery-Asberg Depression Rating Scale score over 18 will be recruited. The study is carried out in the university hospital section for mood disorders in Lausanne, Switzerland. Patients are assessed upon admission, and at 1-, 3- and 12- month follow-ups. Inpatient therapy is a manualized brief intervention, combining the virtues of inpatient setting and of time-limited dynamic therapies (focal orientation, fixed duration, resource-oriented interventions). Treatment-as-usual represents the best level of practice for a minimal treatment condition usually proposed to inpatients. Final analyses will follow an intention–to-treat strategy. Depressive symptomatology is the primary outcome and secondary outcome includes measures of psychiatric symptomatology, psychosocial role functioning, and psychodynamic-emotional functioning. The mediating role of the therapeutic alliance is also examined. Allocation to treatment groups uses a stratified block randomization method with permuted block. To guarantee allocation concealment, randomization is done by an independent researcher.DiscussionDespite the large number of studies on treatment of depression, there is a clear lack of controlled research in inpatient psychotherapy during the acute phase of a major depressive episode. Research on brief therapy is important to take into account current short lengths of stay in psychiatry. The current study has the potential to scientifically inform appropriate inpatient treatment. This study is the first to address the issue of the economic evaluation of inpatient psychotherapy.Trial registrationAustralian New Zealand Clinical Trial Registry (ACTRN12612000909820)

The Vasopressin V1bReceptor Antagonist SSR149415 in the Treatment of Major Depressive and Generalized Anxiety Disorders

These studies were designed to evaluate the efficacy and tolerability of the first nonpeptide vasopressin V(1b) receptor antagonist, SSR149415, in the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD). Studies were randomized 8-week, double-blind, placebo-controlled trials evaluating 100- and 250-mg twice daily doses of SSR149415, placebo, and escitalopram 10 mg/day or paroxetine 20 mg/day, conducted from August 2006 through February 2008. Participants met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria for MDD or GAD. Baseline Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale (HDRS) total scores were ≥ 24 and 18, respectively, and in the GAD trial baseline Hamilton Anxiety Rating Scale (HARS) score was ≥ 22. Primary efficacy variables included changes from baseline in total score on HDRS or HARS and MADRS, and the secondary variable included changes in the Clinical Global Impressions-Severity of Illness score (CGI-S). A 4-week, double-blind, placebo-controlled study evaluating the effect of 100- and 250-mg twice daily doses of SSR149415 on the hypothalamic-pituitary-adrenal (HPA) axis in MDD patients was also conducted. In the GAD trial, SSR149415 did not separate from placebo on the primary (HARS-100 mg: P = .29; 250 mg: P = .21) and secondary (CGI-S-100 mg: P = .18; 250 mg: P = .24) outcome measures, while paroxetine demonstrated efficacy (HARS: P = .003; CGI-S: P = .01). In 2 MDD trials, SSR149415-treated patients did not show significant improvement from baseline on any outcome measure compared with placebo-treated patients (HDRS-100 mg: P = .21 and .48, respectively; 250 mg: P = .22 and P = .46, respectively; CGI-S-100 mg: P = .64 and P = .82, respectively; 250 mg: P = .33 and P = .08, respectively). In the third MDD study, SSR149415 250 mg (P = .04), but not escitalopram (P = .15), demonstrated significant improvement compared to placebo on the HDRS total score at week 8. SSR149415 had no deleterious effects on the HPA axis. These studies demonstrate that SSR149415 may not be useful for the treatment of GAD and that its antidepressant potential needs to be further evaluated. ClinicalTrials.gov identifiers: NCT00374166 (Sanofi ID number: DFI5880), NCT00361491 (Sanofi ID number: DFI5879), NCT00358631 (Sanofi ID number: DFI5878), NCT01606384 (Sanofi ID number: PDY5467).

A Randomized, Double-Blind, Placebo-Controlled 8-Week Trial of the Efficacy and Tolerability of Multiple Doses of Lu AA21004 in Adults With Major Depressive Disorder

Lu AA21004 is an investigational multimodal antidepressant. This randomized controlled trial evaluated the efficacy and tolerability of multiple doses of Lu AA21004 versus placebo in adults with major depressive disorder (MDD). Adults diagnosed with MDD (based on DSM-IV-TR criteria) with a Montgomery-Asberg Depression Rating Scale (MADRS) score ≥ 26 were randomly assigned (1:1:1:1) to receive Lu AA21004 1 mg, 5 mg, or 10 mg or placebo for 8 weeks (between August 2008 and August 2009). The primary endpoint was reduction in 24-Item Hamilton Depression Rating Scale (HDRS-24) total score after 8 weeks of treatment compared with placebo for Lu AA21004 10 mg. Additional outcomes included response and remission rates, Sheehan Disability Scale (SDS), Clinical Global Impressions-Global Improvement scale (CGI-I), MADRS total score, and HDRS-24 total score in subjects with baseline Hamilton Anxiety Rating Scale (HARS) score ≥ 20. Adverse events were assessed throughout the study. A total of 560 subjects (mean age = 46.4 years) were randomized. There was a statistically significant reduction from baseline in HDRS-24 total score at week 8 for Lu AA21004 10 mg vs placebo (P < .001). There were improvements (nominal P values < .05 with no adjustment for multiplicity) in HDRS-24 total score, response and remission rates, CGI-I score, MADRS total score, and HDRS-24 total score in subjects with baseline HARS score ≥ 20 at week 8 for all Lu AA21004 treatment groups vs placebo. No significant differences were seen in SDS scores between any dose of Lu AA21004 and placebo. The most common adverse events were nausea, headache, and dizziness. After 8 weeks of treatment with Lu AA21004 10 mg, there was a significant reduction in HDRS-24 total score compared with placebo in adults with MDD. Lu AA21004 was well tolerated in this study. ClinicalTrials.gov identifier: NCT00735709.

Lamotrigine vs. lamotrigine plus divalproex in randomized, placebo‐controlled maintenance treatment for bipolar depression

To compare the maintenance efficacy of lamotrigine (Lam) to combination therapy of Lam+divalproex ER (Div) in recently depressed patients with bipolar disorder (BD). We randomized 86 BD I or II patients in a major depressive episode to 8 months of double-blind treatment with Lam+placebo or Lam+Div. To be eligible for randomization, patients had to achieve control of both depressive and manic symptoms during an open phase that included both Lam and Div. Time to depressive episode did not differ significantly by Kaplan-Maier survival analysis (χ2=1.82, df=1, P=0.18). However, several secondary outcomes did show significant differences. The proportion of Lam+placebo patients who had at least one Montgomery-Asberg Depression Rating Scale (MADRS) score≥15 during the maintenance phase was 67% (30/45) compared with 44% (18/41) for the Lam+Div group (χ2=4.51, P=0.03). Among BD I patients assigned to Lam+placebo, 71.4% (25/35) had at least one visit with MADRS score≥15 compared with 36.7% (11/30) among Lam+Div patients (χ2=7.89, df=1, P=0.005). Lam+Div generally provided greater maintenance efficacy than Lam alone for depressive indices in recently depressed BD patients.

Female Sexual Dysfunction in Patients Treated with Antidepressant—Comparison between Escitalopram and Fluoxetine

Selective serotonin reuptake inhibitor is one of the most widely used antidepressant and commonly associated with female sexual dysfunction (FSD). This study compares the prevalence of FSD between patients on escitalopram and fluoxetine. The risk factors for FSD were also examined. A cross-sectional study involved 112 female depressed patients (56 each group) who were in remission (as defined in the fourth edition of Diagnostic and Statistical Manual of Mental Disorders [DSM-IV] during the past 2 months with no significant signs or symptoms of the disturbance and Montgomery-Asberg Depression Rating Scale score of ≤10) from the psychiatric clinic in a university hospital. The rates of sexual dysfunction between the two groups were compared. The subjects were interviewed by using Structured Clinical Interview for DSM-IV. Sexual dysfunction was assessed with the Malay Version of the Female Sexual Function Index. The prevalence of FSD was 44.6% for all patients, 55.4% for the fluoxetine group, and 33.9% for the escitalopram group. Multivariate logistic regression analysis showed no significant difference in the risk of FSD between the two groups. Moderate to high dosing was the only significant associated factor for FSD (odds ratio = 4.89, 95% confidence interval = 1.94-12.33). There was no significant difference in the risk of having FSD between patients treated with fluoxetine or escitalopram. Patients on higher dosage of antidepressant have higher risk of having FSD.

Update on the development of lurasidone as a treatment for patients with acute schizophrenia

Lurasidone is a novel benzisothiazole antipsychotic drug for the treatment of schizophrenia. Of the antipsychotic drugs, lurasidone has the highest affinity for the 5-hydroxytryptamine (5-HT)7 receptor. Lurasidone also has high affinities for the dopamine D2, 5HT2A, 5-HT1A and α2C adrenergic receptors. Moreover, lurasidone has low affinities for the α1 adrenergic, histamine H1 and muscarinic M1 receptors. The involvement of 5-HT7 receptors in cognitive processes has been suggested by both pharmacological and molecular investigations. Chronic treatment with lurasidone increases neurotrophin BDNF mRNA levels in both the hippocampus (ventral and dorsal) and prefrontal cortex under basal conditions or in response to an acute swim stress. Lurasidone may potentiate N-methyl-D-aspartate receptor (NMDAR) function through antagonistic action on 5-HT7 receptors without a direct affinity for NMDARs. These results suggest that lurasidone treatment may be a novel approach for the prevention of the development of cognitive impairment in individuals who are at risk for schizophrenia or related disorders involving cognitive impairment. In clinical trials, treatment with lurasidone was associated with significantly greater endpoint improvement versus placebo on the Positive and Negative Syndrome Scale total score after 6 weeks among subjects receiving 80 or 160 mg. The most frequent side effects of lurasidone were akathisia, nausea, parkinsonism, dizziness and somnolence. Once-daily treatment with lurasidone at 160 mg was superior to placebo based on the composite cognitive functioning measure. Lurasidone treatment produced improvements in Montgomery–Asberg Depression Rating Scale scores at 6 weeks that were significantly greater than placebo. A limitation of this review is that the majority of the data were obtained from abstracts and posters. These sources have not been subjected to the peer review processes of medical journals; thus, the results presented in these forums may require further quality review and subsequent revision prior to final publication.

Accurately Predicting Bipolar Disorder Mood Outcomes

Monitoring mental health treatment outcomes for populations requires an understanding as to which patient information is needed in electronic format and is feasible to obtain in routine care. To examine whether bipolar disorder outcomes can be accurately predicted and how much clinical detail is needed to do so. RESEARCH DESIGN, DATA SOURCES, AND PARTICIPANTS: Longitudinal study of bipolar disorder patients treated during 2000 to 2004 in the 19-site Systematic Treatment Enhancement Program for Bipolar Disorder observational study arm (N=3168). Clinical data were obtained at baseline and quarterly for over 1 year. We fit a "gold standard" longitudinal random-effects regression model using a detailed clinical information and estimated the area under the receiver operating characteristic curve (AUC) to predict accuracy using a validation sample. The model was then modified to include patient characteristics feasible in routinely collected electronic data (eg, administrative data). We compared the AUCs for the "limited-detail" and gold standard models, testing for differences between the AUCs using the validation sample. Remission, defined as Montgomery-Asberg Depression Rating Scale score <5 and Young Mania Rating Scale score <4. The gold standard models had baseline AUC=0.80 (95% confidence interval=0.74 to 0.86) and 0.75(0.64 to 0.86) at 1-year follow-up. The predicted accuracies of the limited-detail model were lower at baseline [AUC=0.67(0.60 to 0.75)]; correlated test χ=14.25, P=0.002] and not statistically different from the gold standard model at 1 year [AUC=0.67(0.54-0.80); correlated test χ=2.88, P=0.090]. Future work is needed to develop clinically accurate and feasible models to predict bipolar disorder outcomes. Clinically detailed and limited models performed similarly for shorter-term prediction at 1-year; however, there is room for improvement in prediction accuracy.

Cognitive-Behavioral Therapy for the Treatment of Depression and Adherence in Patients With Type 1 Diabetes

Depression is one of the most common psychological problems affecting individuals with type 1 diabetes, and it is associated with treatment nonadherence and worse clinical outcomes. The research on treating depression or nonadherence in adults with type 1 diabetes is limited. We adapted an evidence-supported treatment, individual cognitive-behavioral therapy for adherence and depression (CBT-AD), for type 1 diabetes and examined its feasibility, acceptability, and potential for an effect. The pilot study included 9 patients with a DSM-IV diagnosis of major depression, dysthymia, or residual depressive symptoms despite treatment with an antidepressant; a diagnosis of type 1 diabetes per patient self-report; and a glycosylated hemoglobin A1c (HbA1c) level of 8.0% or greater. Patients were referred by their diabetes care providers to a behavioral medicine specialty setting and received 10 to 12 sessions of CBT-AD. Main outcome measures included percent of eligible participants who enrolled in the study, session attendance, independently-rated Montgomery-Asberg Depression Rating Scale (MADRS) score, self-reported adherence to diabetes care activities, and adherence to self-monitoring of blood glucose levels. Data were collected from June 27, 2008, through March 31, 2010. There was a clinically meaningful decrease in depression severity (mean [SD] MADRS score decrease from 26.0 [4.73] to 12.3 [7.37], Cohen d = 2.90), demonstrated improvements in diabetes self-care (increase in blood glucose monitoring from 65.0 [26.72] to 82.7 [22.75], Cohen d = -0.66, and a difference in self-reported percent insulin doses in the past 2 weeks from 77.1 [29.84] to 87.1 [23.6], Cohen d = -0.34), and possible improvement in glycemic control (decrease in HbA1c levels from 9.6 [1.32] to 9.0 [1.04], Cohen d = 0.45). These preliminary results provide evidence for the acceptability, feasibility, and potential utility of CBT-AD for patients with type 1 diabetes and depression. clinicaltrials.gov Identifier: NCT01527981.

Brain-Volume Increase With Sustained Remission in Patients With Treatment-Resistant Unipolar Depression

Previous magnetic resonance imaging (MRI) studies have demonstrated brain-volume reductions in unipolar major depressive disorder (MDD). It is not clear whether these atrophic changes can be stabilized with antidepressant treatment and/or reversed with remission. The objective of this study was to prospectively examine brain-volume changes in patients with treatment-resistant depression, comparing those who achieved sustained remission with those who did not remit. This prospective observational cohort study investigated the roles of clinical responsiveness and antidepressant treatment in lessening brain atrophy in depression. Data were collected between October 2004 and December 2008. Baseline MRI scans were obtained from 28 outpatients with treatment-resistant MDD (diagnosed according to DSM-IV criteria) who were recruited from the Mood Disorders Research Unit at the Royal Ottawa Mental Health Centre, Ottawa, Ontario, Canada. Twenty-seven patients underwent follow-up scanning after either 6 months of sustained remission (Montgomery-Asberg Depression Rating Scale score ≤ 12) or 12 months of failure to remit. Longitudinal whole-brain and voxel-based gray- and white-matter volume changes were estimated. Twelve patients (mean age at baseline = 47.5 years) achieved sustained 6-month remission. In contrast to nonremitters (n = 15; mean age at baseline = 44.3 years), remitted patients demonstrated a significant mean increase in whole-brain volume during follow-up (F(1,27) = 9.51, P = .005). Within-subject voxel-based morphometry analyses identified increased gray-matter volume in remitters in the right orbitofrontal cortex (t(11) = 7.61, P = .006) and the right inferior temporal gyrus (t(11) = 6.65, P = .004). Nonremitters showed decreased white-matter volume in the left anterior limb of the internal capsule (t(13) = 3.86, P = .04). Given that remitters exhibited a mean increase in brain volume while nonremitters lost volume, pharmacotherapy in the absence of sustained remission is most likely insufficient to elicit brain-volume increase in MDD. The findings suggest that clinical remission rather than pharmacotherapy may be the key factor involved in driving volumetric recovery in treatment-resistant depression.

Garden rehabilitation stabilises INF-gamma and IL-2 levels but does not relieve depressive-symptoms

Introduction: Based on theories on the impact of an enriched environment on stress regulation, we conducted a small-scale study on psychiatric patients to examine the effect of add-on garden rehabilitation on illness and inflammatory state. Materials and methods: Patients suffering from a moodor an anxiety disorder were recruited while hospitalized, or from an outpatient psychiatric facility. Before entering the study, they were randomized to participate in an 8-week garden rehabilitation and treatment as usual (TAU) or to TAU only. Before start of the study, after 4 weeks and 8 weeks all patients were subjected to blood sampling. Their psychopathology was rated according to the Comprehensive Psychopathological Rating Scale, from which e.g. the Montgomery Asberg Depression Rating Scale (MADRS) was retrieved. Levels of inflammatory factors in blood plasma were measured using high sensitivity photon-emission based ELISA (Mesoscale). Results: At baseline and before randomization, there was no significant difference in inflammatory factors between rehabilitation patients and TAU controls when controlling for ECT, age and sex neither were any differences in plasma levels found between diagnostic groups. Repeated measures ANOVAs showed that the MADRS scores, as well as the levels of interleukin (IL)-6, decreased sig-

Asenapine as Adjunctive Treatment for Acute Mania Associated With Bipolar Disorder

In a 12-week randomized, placebo-controlled study evaluating the efficacy and safety of adjunctive asenapine, bipolar I disorder patients experiencing manic or mixed episodes despite pretreatment with lithium or valproate monotherapy were treated with flexible-dose, twice-daily asenapine 5 or 10 mg (n = 158) or placebo (n = 166). The primary efficacy end point was change from baseline Young Mania Rating Scale (YMRS) total score at week 3. Secondary outcomes included YMRS response and remission and Clinical Global Impression for Bipolar Disorder and Montgomery-Asberg Depression Rating Scale score changes. Patients completing the core study were eligible for a 40-week double-blind extension assessing safety and tolerability. Adjunctive asenapine significantly improved mania versus placebo at week 3 (primary end point) and weeks 2 to 12. The YMRS response rates were similar at week 3 but significantly better with asenapine at week 12. The YMRS remission rates and changes from baseline on Clinical Global Impression for Bipolar Disorder for mania and overall illness were significantly better with asenapine at weeks 3 and 12. No other statistically significant differences on secondary outcomes were observed. Only a small number of patients entered the extension, making firm statistical conclusions on efficacy difficult. Treatment-emergent adverse events reported by 5% or more of asenapine patients and at twice the incidence of placebo were sedation, somnolence, depression/depressive symptoms, oral hypoesthesia, and increased weight in the 12-week core study. Adjunctive asenapine to lithium or valproate was more effective than mood stabilizer monotherapy in the core study and was well tolerated for up to 52 weeks.

Course of Improvement in Depressive Symptoms to a Single Intravenous Infusion of Ketamine vs Add-on Riluzole: Results from a 4-Week, Double-Blind, Placebo-Controlled Study

The N-methyl-D-aspartate antagonist ketamine has rapid antidepressant effects in patients with treatment-resistant major depression (TRD); these effects have been reported to last for 1 week in some patients. However, the extent and duration of this antidepressant effect over longer periods has not been well characterized under controlled conditions. Riluzole, a glutamatergic modulator with antidepressant and synaptic plasticity-enhancing effects, could conceivably be used to promote the antidepressant effects of ketamine. This study sought to determine the extent and time course of antidepressant improvement to a single-ketamine infusion over 4 weeks, comparing the addition of riluzole vs placebo after the infusion. Forty-two subjects (18-65) with TRD and a Montgomery-Asberg Depression Rating Scale (MADRS) score of ≥ 22 received a single intravenous infusion of ketamine (0.5 mg/kg). Four to six hours post-infusion, subjects were randomized to double-blind treatment with either riluzole (100-200 mg/day; n=21) or placebo (n=21) for 4 weeks. Depressive symptoms were rated daily. A significant improvement (P<0.001) in MADRS scores from baseline was found. The effect size of improvement with ketamine was initially large and remained moderate throughout the 28-day trial. Overall, 27% of ketamine responders had not relapsed by 4 weeks following a single ketamine infusion. The average time to relapse was 13.2 days (SE=2.2). However, the difference between the riluzole and placebo treatment groups was not significant, suggesting that the combination of riluzole with ketamine treatment did not significantly alter the course of antidepressant response to ketamine alone.