Remission Of Major Depressive Disorder Research Articles

Treating to target in major depressive disorder: response to remission to functional recovery.

Treating to target in chronic diseases [e.g. Major Depressive Disorder (MDD)] fosters precision, consistency, and appropriateness of treatment selection and sequencing. Therapeutic target definitions/endpoints in MDD should satisfy patient-, provider-, and societal expectations. Functional recovery in depression and return to both physical and mental health are the overarching therapeutic objectives. Treating to target in MDD implies multidimensional symptomatic remission, with a particular emphasis on cognitive function and aspects of positive mental health. Several atypical antipsychotic agents (i.e. brexpiprazole, aripiprazole, quetiapine) are FDA-approved as augmentation agents in MDD. Vortioxetine, duloxetine, and psychostimulants have evidence of independent, direct, and robust effects on cognitive function in MDD. Vortioxetine is the only agent that demonstrates efficacy across multiple cognitive domains in MDD associated with functional recovery. Measurement-based care, health information technology/systems, and integrated care models (e.g. medical homes) provide requisite tools and health environments for optimal health outcomes in MDD. Achieving remission in MDD does not equate to health. Return to positive mental health as well as full functioning provide the impetus to pivot away from traditional provider-defined outcomes toward an inclusive perspective involving patient- and society-defined outcomes (i.e. optimization of human capital). As in other chronic diseases, treating to target (e.g. cognitive function) further increases the probability of achieving optimal health outcomes.

Generalized Anxiety Disorder and Major Depressive Disorder in Pregnant and Postpartum Women: Maternal Quality of Life and Treatment Outcomes

Comorbid generalized anxiety disorder (GAD) and major depressive disorder (MDD) in perinatal women is often under-diagnosed, resulting in suboptimal treatment and leading to significant maternal dysfunction. We describe a prospective, longitudinal study of the course, treatment outcomes, and quality of life (QoL) in pregnant and postpartum women with MDD and anxiety disorders. Two separate cohorts of women were recruited through the Reproductive Mental Health Program, Women's and Children's Hospital, Vancouver, British Columbia, for pharmacotherapy of depressed mood. One cohort was recruited during pregnancy and followed to one month postpartum; the other cohort was recruited postpartum and followed for 12 weeks. All women met the DSM-5 criteria for MDD and anxiety disorders. This non-lactating perinatal population completed measures of depression, anxiety, worry symptoms, and QoL at multiple study visits. Depressed women with GAD or excessive worry were compared to those without GAD in each cohort. Analysis revealed that despite the majority of women with MDD having remission of symptoms with treatment, those with postpartum GAD displayed a poorer quality of life, with persistent worry symptoms, and their illness was slower to remit. Pregnant depressed women with uncontrollable worry (a GAD indicator) showed a lower probability of achieving remission of symptoms with treatment than those without uncontrollable worry. All pregnant and postpartum women with GAD and MDD responded to pharmacotherapy, and the majority attained complete remission of MDD. However, their GAD symptoms persisted, and their QoL was compromised. Given the chronic debilitating course of concomitant MDD and GAD in the perinatal population, it is essential to focus on adjunctive therapies to aim for full recovery.

Correlates of residual fatigue in patients with major depressive disorder: The role of psychotropic medication

ObjectiveFatigue is not only a core symptom of major depressive disorder (MDD), but also a common residual symptom. We determined the sociodemographic, clinical, and pharmacologic factors that were associated with fatigue in patients with remission or partial remission of MDD. MethodsData was derived from a randomized controlled trial of acupuncture in 137 MDD patients with residual symptoms. Fatigue was measured by Multidimensional Fatigue Inventory (MFI-20). Self-report and clinician-rated scales were used to assess psychopathology. 17-item Hamilton Depression Rating Scale (HDRS17) score≤7 denoted MDD remission. ResultsParticipants’ average HDRS17 score was 10.5; 29.2% were in remission. The average MFI-20 score was 71.8; 83.2% had severe fatigue, defined as MFI-20 score≥60. Fifty-two of 137 participants (38%) were using sedating psychotropic medications. Antidepressant dosage ranged from 1–90mg fluoxetine equivalent and sedatives/hypnotics from 1–60mg diazepam equivalent. There were significant correlations between MFI-20 score and HDRS17 depression and anxiety subscores, Hospital Anxiety and Depression Scale (HADS) depression and anxiety subscores, and Pain Catastrophizing Scale score, but insomnia and daytime sleepiness, sociodemographics, current medical conditions, and psychotropic medication use were not significant correlates. Upon multiple regression, HADS and HDRS17 depression scores independently predicted MFI-20 score. In remission and partial remission subgroups, HADS depression score was an independent predictor. LimitationParticipants were recruited from specialty psychiatric units; hence the findings may not be applicable in non-specialized settings. ConclusionFatigue was predicted by depression severity in remitted or partially remitted MDD. Psychotropic medication and higher dosage were not associated with greater fatigue.

Predictors of impaired work functioning in employees with major depression in remission

ObjectivesThis study aims to (i) assess work functioning in employees returning to work with a major depression in remission, (ii) study the predictors of impaired work functioning. MethodsParticipants diagnosed with major depressive disorder (MDD), on long term sick leave (mean 27 weeks) and treated in a specialized mental healthcare setting, were selected from an intervention study sample. They were eligible for this study if they were remitted from their depression and had returned to work for at least 50% of their contract hours at 18 month follow-up. Work functioning was assessed with the Work Limitations Questionnaire (WLQ) and the Need For Recovery scale (NFR). Potential predictors of impaired work functioning were demographic characteristics (assessed at baseline), health characteristics (assessed at baseline, six and twelve month follow-up), and personality- and work characteristics (assessed at 18 month follow-up). ResultsAfter their return to work with MDD in remission, employees were on average still impaired in their work functioning. Personality characteristics were the strongest predictor of this impaired work functioning, followed by health and work characteristics. In the final prediction model, only a passive reaction coping style remained as predictor. LimitationsWe used self-report data with respect to work functioning and work characteristics and not an assessment by a supervisor. ConclusionsPersonality trait, coping style, and ability to manage the work environment should be addressed in mental health and return-to-work interventions. Subsequent improved work functioning may be beneficial for mental health and may reduce societal costs.

Impaired insight into delusions predicts treatment outcome during a randomized controlled trial for Psychotic Depression (STOP-PD study).

Insight into delusional beliefs varies in patients with major depressive disorder (MDD) with psychotic features ("psychotic depression"). The relationship between impaired insight and illness severity and its impact on treatment outcomes has not been studied in psychotic depression. As such, the aim of this analysis was to explore the relationship among impaired insight, patient characteristics (ie, illness severity, cognition, suicidality, and social functioning), and treatment outcome (ie, remission) during acute treatment of psychotic depression. This secondary analysis is based on the data from the Study of Pharmacotherapy for Psychotic Depression (STOP-PD) in which 259 participants meeting DSM-IV criteria for MDD with psychotic features enrolled between December 2002 and June 2007 (including 142 aged ≥ 60 years) in a 4-center, 12- week, double-blind, randomized controlled trial funded by the US National Institutes of Health. Insight into delusions was assessed using the Delusion Assessment Scale (DAS). The primary outcomes were the predictive utility of insight into illness (ie, Hamilton Depression Rating Scale [HDRS] insight item) and insight into delusions (conviction factor derived from the DAS) on final treatment outcome at 12 weeks of treatment (ie, full remission, partial remission, and nonremission). At baseline, impaired insight into delusions was positively associated with illness severity (HDRS-16 which excluded the insight item, r = 0.15, P = .016) and negatively correlated with measures of cognition (P < .05). Improvement in insight was not associated with changes in cognition, suicidality, or social functioning after adjusting for covariates. Independent of the severity of depression or psychosis, impaired insight into delusions at baseline (χ² = 11.65, P = .020) and after 3 (χ² = 9.62, P = .047), 6 (χ² = 6.97, P = .031), and 8 (χ² = 9.08, P = .011) weeks of treatment predicted remission at the end of the trial. Impaired insight into delusions appears to be an independent predictor of remission in MDD with psychotic features during acute treatment, suggesting that more attention should be paid to this symptom. Longitudinal studies are required to determine the impact of impaired insight into delusions on long-term outcomes, including relapse. ClinicalTrials.gov identifier: NCT00056472.

Altered anatomical patterns of depression in relation to antidepressant treatment: Evidence from a pattern recognition analysis on the topological organization of brain networks

BackgroundAccumulated evidence has illuminated the topological infrastructure of major depressive disorder (MDD). However, the changes of topological properties of anatomical brain networks in remitted major depressive disorder patients (rMDD) remain an open question. The present study provides an exploratory examination of pattern changes among current major depressive disorder patients (cMDD), rMDD patients and healthy controls (HC) by means of a pattern recognition analysis. MethodsTwenty-eight cMDD patients (age range: 22–54, mean age: 39.57), 15 rMDD patients (age range: 23–53, mean age: 38.40) and 30 HC (23–54, mean age: 35.57) were enrolled. For each subject, we computed five kinds of weighted white matter (WM) networks via employing five physiological parameters (i.e. fractional anisotropy, mean diffusivity, λ1, λ2 and λ3) and then calculated three network measures of these weighted networks. We treated these measures as features and fed into a feature selection mechanism to choose the most discriminative features for linear support vector machine (SVM) classifiers. ResultsLinear SVM could excellently distinguish the three groups with the 100% classification accuracy of recognizing cMDD/rMDD from HC, and 97.67% classification accuracy of recognizing cMDD from rMDD. The further pattern analysis found two types of discriminative patterns among cMDD, rMDD and HC. (i) Compared with HC, both cMDD and rMDD exhibited the similar deficit patterns of node strength primarily involving the salience network (SN), default mode network (DMN) and frontoparietal network (FPN). (ii) Compared with cMDD and rMDD showed the altered pattern of intra-communicability within DMN and inter-communicability between DMN and the other sub-networks including the visual recognition network (VRN) and SN. LimitationsThe present study had a limited sample size and a lack of larger independent data set to validate the methods and confirm the findings. ConclusionsThese findings implied that the impairment of MDD was closely associated with the alterations of connections within SN, DMN and FPN, whereas the remission of MDD was benefitted from the network compensatory of intra-communication within DMN and inter-communication between DMN and the other sub-networks (i.e., VRN and SN).

The First Published Case Report of an Adult Woman Who Developed Suicidal Ideation as an Adverse Event Related to Methylphenidate Use.

To the Editor: Recent attention has been paid to suicidal ideation as an adverse event associated with drugs targeting the central nervous system.1 We report the case of a patient with past history of major depressive disorder in remission for 5 months who attempted suicide shortly after beginning extended-release methylphenidate for untreated attention-deficit/hyperactivity disorder (ADHD). Although the methylphenidate package insert contains data regarding the risk of drug dependence, exacerbation of preexisting psychosis, aggression, and induction of manic/mixed episodes, the drug’s label does not contain a warning regarding increased risk of suicidality.2 Case report. Ms A, a 24-year old white woman, was initially seen at our clinic for depression and anxiety related to family stress and was diagnosed with major depressive disorder (DSM-IV-TR). She was treated with citalopram (20 mg daily) and clonazepam (up to 1 mg at bedtime), and her depression was in remission for a period of 5 months before she complained of ongoing and lifelong inattention and poor concentration. In February 2014, Ms A was diagnosed with ADHD, inattentive type (DSM-IV-TR) using the Adult ADHD Self-Report Scale and was prescribed extended-release methylphenidate at a dose of 18 mg/d. Six days after starting the medication, Ms A’s mother reported that the patient had suddenly become hopeless and attempted suicide by shooting herself in the neck with a BB gun. Ms A was then admitted to the local psychiatric hospital for further evaluation. During the hospitalization, Ms A reported that she began to feel “very down” and “negative” within days of starting the extended-release methylphenidate. She reported no new stressors, and there were no precipitating events noted. She was devoid of manic or psychotic symptoms at the time of admission and did not use alcohol or illicit drugs. While in the hospital, Ms A did not meet criteria for a major depressive episode, and the extended-release methylphenidate was discontinued. She continued taking citalopram, and her depression was still in remission at her next clinic visit, and she was devoid of suicidal ideation. Methylphenidate products do not contain package labeling regarding the development of suicidality during treatment. We searched the medical literature using stimulants AND suicide as search terms on September 18, 2014 and found 2 reported cases of suicidality associated with methylphenidate, both of which occurred in adolescent girls with depressive symptoms. This report presents the first published case of suicidal ideation associated with methylphenidate in an adult female patient whose depression had been in remission for 5 months. The patient developed suicidality after taking 5 doses of extended-release methylphenidate in the absence of new life stressors or a relapse of her depression. Prescription medications are not “one size fits all,” and interindividual differences in neurobiology and metabolism can result in unique efficacy and safety issues. As we advance into the age of “personalized medicine,” these interindividual differences may be better understood, which could lead to more precise medication choice based on the unique biological variants of individual patients.

Reduced default mode network suppression during a working memory task in remitted major depression

Insufficient default mode network (DMN) suppression was linked to increased rumination in symptomatic Major Depressive Disorder (MDD). Since rumination is known to predict relapse and a more severe course of MDD, we hypothesized that similar DMN alterations might also exist during full remission of MDD (rMDD), a condition known to be associated with increased relapse rates specifically in patients with adolescent onset. Within a cross-sectional functional magnetic resonance imaging study activation and functional connectivity (FC) were investigated in 120 adults comprising 78 drug-free rMDD patients with adolescent- (n = 42) and adult-onset (n = 36) as well as 42 healthy controls (HC), while performing the n-back task. Compared to HC, rMDD patients showed diminished DMN deactivation with strongest differences in the anterior-medial prefrontal cortex (amPFC), which was further linked to increased rumination response style. On a brain systems level, rMDD patients showed an increased FC between the amPFC and the dorsolateral prefrontal cortex, which constitutes a key region of the antagonistic working-memory network. Both whole-brain analyses revealed significant differences between adolescent-onset rMDD patients and HC, while adult-onset rMDD patients showed no significant effects. Results of this study demonstrate that reduced DMN suppression exists even after full recovery of depressive symptoms, which appears to be specifically pronounced in adolescent-onset MDD patients. Our results encourage the investigation of DMN suppression as a putative predictor of relapse in clinical trials, which might eventually lead to important implications for antidepressant maintenance treatment.

Clinical Factors Associated with Response to Treatment in a Population of Depressed Patients Treated in General Practice: the Hedonie Study

Introduction In major depressive disorder (MDD), response and remission are the goals of treatment strategies. Aim To describe factors associated with response and remission in MDD, we conducted a longitudinal study exploring response to treatment in a large sample of depressed patients in general practice. Method General practitioners (GPs) recruited depressed patients consecutively and evaluated them using the QIDS-SR and the Snaith-Hamilton Pleasure Scale. Patients were treated with agomelatine and evaluated after 6 to 8 weeks. Response was identified as a 50% improvement in QIDS score and remission as a QIDS score below 5 at endpoint. We conducted a logistic regression to identify the variables associated with response and remission. Results 1752 patients were included (62.4% women, 37.6% men). Average QIDS-SR score was 15.7 (SD=4.3). The average duration of the current episode was 6.1 weeks (SD=6.2) and it was the first episode for 65.7% of the patients. In 91.15% of the patients, anhedonia was considered as severe (score above 5). Level of anhedonia, duration of the episode and recurrence were associated with a higher probability of response to treatment (respectively p Conclusion Level of anhedonia and the characteristics of the episode are associated with the probability of achieving a response. Taking into account these parameters in order to specify treatment strategies is one way to improve the course of MDD.

Effects of remission speed and improvement of cognitive functions of depressed patients

Major depressive disorder (MDD) presents neuropsychological alterations which improve after the treatment, but it might be mediated by clinical variables. Our goal is to study whether the speed of remission of MDD bears any relation to the improvement of the patients׳ cognitive functioning after a successful treatment. We carried out clinical and neuropsychological assessments of 51 patients with MDD. After these procedures they underwent a 24-week treatment with fluoxetine, and were assessed again with the same battery used prior to treatment. They were arranged into three groups according to how rapid their symptoms remitted. The patients with a rapid remission presented improvements in working memory, speed of information processing, and some executive functions, unlike the other groups. Rapid remitters also improved in episodic memory and executive functions more than the other patients.

Increased cortisol awakening response was associated with time to recurrence of major depressive disorder.

Although HPA-axis activity has been studied extensively in relation to depression, there is no consensus whether HPA-axis parameters predicts major depressive disorder (MDD) recurrence. We investigated whether HPA-axis parameters (cortisol awakening response (CAR), the dexamethasone suppression test (DST) and evening cortisol) predict time to recurrence in remitted subjects with a history of MDD and whether childhood trauma and life events interact with HPA-axis parameters in increasing the risk for recurrence. Data were derived from 549 subjects with a lifetime diagnosis of MDD in remission for at least six months preceding the baseline assessment of the Netherlands Study of Depression and Anxiety (NESDA). Subjects were followed up with two interviews over the course of four years to assess recurrence. DSM-IV based diagnostic interviews were used to assess time to recurrence of MDD. Seven salivary cortisol samples collected at baseline with information on CAR, evening cortisol and the DST. Hazard ratios were calculated using Cox regression analysis, adjusted for covariates. A higher CAR was associated with time to recurrence of MDD (HR=1.03, 95%CI 1.003-1.060, p=0.03) whereas evening cortisol and DST were not. No interactions between HPA-axis parameters and stress-related factors were found. Our data support previous studies reporting that subjects with a higher CAR are more vulnerable to recurrence of MDD.

Comparação entre SNRI e SSRI na indução da remissão da perturbação depressiva major: uma revisão baseada na evidência

Aim: To evaluate the effectiveness of serotonin-norepinephrine reuptake inhibitors (SNRI) compared to selective serotonin reuptake inhibitors (SSRI) for induction of remission in major depressive disorder. Data sources: PubMed, evidence-based medicine databases and Index de Revistas Medicas Portuguesas. Review methods: We searched guidelines, systematic reviews and meta-analyses published before 13th January 2013 and randomized clinical trials published between 1st January 2011 and 13th January 2013, using the MeSH terms depressive disorder, major; venlafaxine; duloxetine. Portuguese descriptors depressao and antidepressivos de segunda geracao were also used. We used the Strength of Recommendation Taxonomy (SORT) from the American Family Physician for classifying the levels of evidence and the strength of recommendations. Results: 223 articles were found. Three guidelines, nine systematic reviews and meta-analyses were selected. No RCT were found meeting the inclusion criteria. Both SNRI and SSRI are considered first-line therapeutic choices (level of evidence [LE] 1) and there is no clear evidence for the superiority of SNRI over SSRI (LE 2). There is consistent evidence for the higher efficacy of venlafaxine over fluoxetine and paroxetine (LE 2). Guidelines highlight the importance of choosing an antidepressant by considering tolerability and patient-related aspects (LE 1). Conclusions: SNRI and SSRI are both evidence-based choices for induction of remission in depression (strength of recommendation [SOR] A). Drug and patient characteristics must be taken into account when choosing the antidepressant (SOR A). In a patient without co-morbidities, some SNRI show higher efficacy in remission of depression, but we cannot talk about a class effect. The choice of a SNRI over a SSRI to achieve remission of depression is not supported by the current evidence (SOR B).

Nystagmus as a discontinuation symptom after antidepressant therapy: a case report.

To the Editor: I present a patient with recurrent depression who experienced remission on a fixed daily dose of 150 mg of venlafaxine in the first episode and 15 mg of escitalopram in the second episode. Postural nystagmus appeared after discontinuation of treatment in each episode. Case report. Mr A, a 56-year-old married man, had a 6-year history of recurrent major depressive disorder (MDD) according to the DSM-5. His first episode had begun by January 2007 when he was 50 years old. His depressive symptoms began to appear slowly and were characterized by depressed mood, irritability, diminished interest and pleasure in his everyday activities, loss of appetite, lack of energy, poor concentration, early morning waking, and recurrent thoughts such as, “It is not interesting being alive.” These symptoms led to impaired work and social functioning. His parents and sister had a history of symptoms of depression. Extended-release venlafaxine was started with 37.5 mg/d and was increased gradually to 150 mg/d in 4 weeks with no adverse effects. The patient experienced important symptomatic relief by week 4 and reached remission in 8 weeks. Functionality was completely restored by August 2007. For the next 18 months, Mr A was on the same treatment regimen with full MDD remission. Remarkably, 10 days after completion of slow antidepressant discontinuation (ie, taper for 2 months), Mr A, who had no medical history of eye problems, started experiencing position vertical and lateral nystagmus, usually at its worst in the morning. The symptom was ameliorated during the day, almost disappearing by night. No other visual problem was related by the patient or detected. The symptom persisted for 3 weeks but disappeared slowly at the end of the fifth week. In January 2010, MDD reappeared, characterized by similar symptoms as previously described but with the emergence of symptoms of anxiety and fatigue (both severely worsening in the morning) and serious impairment of social functioning. Escitalopram was administered at 5 mg/d, reaching 15 mg/d in 3 weeks with no unwanted effects. After 6 weeks, depression had remitted. During follow-up (18 months), there was no relapse. After slow discontinuation of escitalopram for 6 weeks, the patient experienced nystagmus with the same characteristics as described earlier, disappearing by 4 to 5 weeks. The literature includes only 1 report of positional nystagmus associated with amitriptyline withdrawal.1 There is another case report of a patient who manifested signs of serotonin syndrome during an intravenous anesthetic with remifentanil and propofol. The patient displayed nystagmus, lower extremity clonus, and diaphoresis. At the time of surgery, the patient was being treated with 60 mg of fluoxetine for severe MDD. His symptoms resolved in the surgical care unit without incident. Investigators have shown that fluoxetine2,3 and sertraline4 can induce oculomotor abnormalities during sleep in depressed patients. It is suggested that these abnormalities are likely to be the result of increased availability of serotonin5,6 and secondary dopaminergic effects.7–9 As the use of antidepressants continues to increase, the incidence of withdrawal symptoms is also likely to increase. Patients treated with antidepressants should be questioned specifically during the discontinuation phase about the presence of this unwanted effect. It is important to recognize its clinical features as well as the benign course after a few weeks of follow-up.

Plasma dehydroepiandrosterone sulfate levels in patients with major depressive disorder correlate with remission during treatment with antidepressants.

We attempted to investigate whether dehydroepiandrosterone sulfate (DHEA-S) levels are associated with remission of major depressive disorder by assessing scores on the 17-Item Structured Interview Guide for the Hamilton Depression before and after antidepressant treatment. Plasma DHEA-S levels in 24 patients diagnosed with major depressive disorder on the basis of Diagnostic and Statistical Manual of Mental Disorders, fourth edition (text revision) before and after antidepressant treatment, and 24 healthy, gender-matched, and age-matched controls were measured using a radioimmunoassay kit. Plasma DHEA-S levels in patients were significantly higher than those in healthy controls. In patients who achieved remission after antidepressant treatment, plasma DHEA-S levels significantly declined compared with the levels before treatment. A significant correlation was observed between changes in DHEA-S levels and Absence of Depressive and Anxious Mood scores, which are calculated from the 2-Item Structured Interview Guide for the Hamilton Depression rating as follows: severity of depressive mood and anxiety in patients before and after antidepressant treatment. These findings suggest that plasma DHEA-S levels can be used as a putative indicator of the state of remission in patients with major depressive disorder. Copyright © 2014 John Wiley & Sons, Ltd.

Does Early Improvement in Anxiety Symptoms in Patients with Major Depressive Disorder Affect Remission Rates? A Post-Hoc Analysis of Pooled Duloxetine Clinic Trials

Objectives: Patients with major depressive disorder (MDD) and a comorbid anxiety disorder or significant anxiety symptoms have decreased functioning, increased risk of suicidality, and worse post-treatment outcomes. This pooled analysis of 8 duloxetine MDD trials was designed to determine whether early improvement in anxiety symptoms predicts MDD remission. Methods: Eight trials were pooled. Patients with a baseline 17-item Hamilton Rating Scale for Depression (HA-MD17) anxiety/somatization factor score ≥7 were considered to have anxious depression. Early response on the HAMD17 total score was defined as a 20% reduction at weeks 2 or 4, a 30% reduction at weeks 2 or 4, or a 50% reduction at weeks 2 or 4 in the HAMD17 anxiety subscale. Each category was analyzed separately for all patients. MDD remission is a score of ≤7 on the HAMD17 total score at study endpoint. Results: The early responder group in each analysis showed greater numerical improvement at endpoint on the HAMD17 total score than the nonresponder group. Duloxetine showed statistically significantly greater improvement than placebo in most nonresponder and responder subgroups. There were no statistically significant interaction effects for the difference between duloxetine and placebo for any of the anxious categories. Conclusion: Although patients who responded in the various response categories had greater numerical improvement and greater remission rates than nonresponding patients, the response and nonresponse groups did not differ statistically regarding the treatment effect of duloxetine. Therefore, early improvement in anxiety symptoms was not a predictor of greater endpoint remission of depressive symptoms for duloxetine treatment.

Lisdexamfetamine Dimesylate Augmentation in Adults With Persistent Executive Dysfunction After Partial or Full Remission of Major Depressive Disorder

Evaluate lisdexamfetamine dimesylate (LDX) augmentation of antidepressant monotherapy for executive dysfunction in partially or fully remitted major depressive disorder (MDD). This randomized, placebo-controlled study (NCT00985725) enrolled 143 adults (18-55 years) with mild MDD (Montgomery-Åsberg Depression Rating Scale (MADRS) score ≤ 18) and executive dysfunction (Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Self-Report Global Executive Composite (GEC) T score ≥ 60) on stable antidepressant monotherapy for ≥ 8 weeks. After 2 weeks of screening, participants were randomized to 9 weeks of double-blind LDX (20-70 mg/day) or placebo augmentation, followed by 2 weeks of single-blind placebo. The primary end point was change from baseline to week 9/end of study (EOS) in BRIEF-A Self-Report GEC T score; secondary assessments included the BRIEF-A Informant Report, MADRS, and treatment-emergent adverse events (TEAEs). Of 143 randomized participants, 119 completed double-blind treatment (placebo, n=59; LDX, n=60). Mean ± standard deviation (SD) BRIEF-A GEC T scores decreased from baseline (placebo, 74.2 ± 8.88; LDX, 76.8 ± 9.66) to week 9/EOS (placebo, 61.4 ± 14.61; LDX, 55.2 ± 16.15); the LS mean (95% CI) treatment difference significantly favored LDX (-8.0 (-12.7, -3.3); P=0.0009). The LS mean (95% CI) treatment difference for MADRS total score also significantly favored LDX (-1.9 (-3.7, 0.0); P=0.0465). TEAE rates were 73.6% with placebo and 78.9% with LDX; serious TEAE rates were 4.2 and 2.8%. In this trial, LDX augmentation significantly improved executive dysfunction and depressive symptoms in participants with mild MDD. The safety profile of LDX was consistent with prior studies in adults with attention-deficit/hyperactivity disorder.

Repetitive transcranial magnetic stimulation enhances sleep quality of patients with comorbid major depressive disorder and insomnia

Insomnia impacts the course of major depressive disorder (MDD), obstructs response to treatment, and raises risk of depression relapse. This study approached how repetitive transcranial magnetic stimulation (rTMS) relieves depression and enhances sleep quality of patients with comorbid major depressive disorder and insomnia. A randomized, controlled, pilot study was conducted in our hospital. The study was approved by local Ethics Committee. All subjects signed informed consents. 30 patients, conforming to meet the Diagnostic and Statistical Manual of Mental Disorders (DSM–IV–TR) criteria for MDD, and Montgomery–Asberg Depression Scale (MADRS) score between 12 and 29 were randomly chosen as the MDD group. Another 30 patients, meeting the DSM–IV–TR criteria for MDD and insomnia, MADRS score between 12 and 29, and Pitts-burgh Sleep Quality Index (PSQI) scores >7, were randomly selected as the MDD and insomnia group. Both groups received rTMS (10 Hz for 4 weeks) once per day. After treatment, patients’ depression was assessed with MADRS, and their sleep quality was evaluated by PSQI. Raters were masked to treatment assignment. There were 30 subjects in MDD group (60% female, mean age 38.56¡‘À12.13 s.d. mean course of disease 11.35¡‘À7.53 months). MDD and insomnia group consisted of 30 subjects (66.67% female, mean age 32.72¡‘À14.69 s.d. mean course of disease 9.23¡‘À4.81 months). Although the rate of depression remission in MDD and insomnia group (59.36%) was higher than MDD group (57.21%), this difference was not significant. After 4 weeks treatment, both MDD group (12.56¡‘À6.73) and MDD insomnia group (11.38¡‘À7.16 s.d.) were significantly improved in MADRS scores (P<0.05). MDD and insomnia group was significantly improved (P<0.05) in PSQI sleep quality (1.40¡‘À0.41), time for falling asleep (1.73¡‘À1.21), sleep time (1.90¡‘À1.28), sleep efficiency (0.90¡‘À1.52), Function during the daytime (1.87¡‘À0.84), total score (8.57 ¡‘À3.74). This pilot study offers the evidence that rTMS improves depression and sleep quality of patients with comorbid major depressive disorder and insomnia. This research was supported by Fund Projects of International Cooperation and Exchanges of Ministry of Science and Technology of China. Grant No. 2011DFA30960.

P.2.f.026 An open clinical trial of adjunctive therapy with aripiprazole in patients with partial remission of major depressive disorder

P.2.f.026 An open clinical trial of adjunctive therapy with aripiprazole in patients with partial remission of major depressive disorder

HPA-axis hormone modulation of stress response circuitry activity in women with remitted major depression

Decades of clinical and basic research indicate significant links between altered hypothalamic–pituitary–adrenal (HPA)-axis hormone dynamics and major depressive disorder (MDD). Recent neuroimaging studies of MDD highlight abnormalities in stress response circuitry regions which play a role in the regulation of the HPA-axes. However, there is a dearth of research examining these systems in parallel, especially as related to potential trait characteristics. The current study addresses this gap by investigating neural responses to a mild visual stress challenge with real-time assessment of adrenal hormones in women with MDD in remission and controls. Fifteen women with recurrent MDD in remission (rMDD) and 15 healthy control women were scanned on a 3T Siemens MR scanner while viewing neutral and negative (stress-evoking) stimuli. Blood samples were obtained before, during, and after scanning for the measurement of HPA-axis hormone levels. Compared to controls, rMDD women demonstrated higher anxiety ratings, increased cortisol levels, and hyperactivation in the amygdala and hippocampus, p<0.05, family-wise error (FWE)-corrected in response to the stress challenge. Among rMDD women, amygdala activation was negatively related to cortisol changes and positively associated with the duration of remission. Findings presented here provide evidence for differential effects of altered HPA-axis hormone dynamics on hyperactivity in stress response circuitry regions elicited by a well-validated stress paradigm in women with recurrent MDD in remission.

Reduced thalamic volumes in major depressive disorder

Altered function in the limbic–cortical–striatial–pallidal–thalamic (LCSPT) circuit has been implicated in the pathophysiology of major depressive disorder (MDD). This study evaluated volumetric differences in subcortical volumes between depressed subjects with MDD (N=142), subjects with MDD in remission (N=72), and healthy controls (N=169). Participants underwent magnetic resonance imaging (MRI) scanning, and subcortical volumes were extracted using FMRIB's Integrated Registration and Segmentation Tool (FIRST), University of Oxford, UK. The depressed MDD subjects exhibited significantly smaller volumes in the bilateral thalamus and hippocampus compared to control subjects, and the differences in the bilateral thalamus remained significant after controlling for total intracranial volume. In a smaller subset of healthy controls and depressed MDD subjects matched to the remitted MDD subjects, significant differences in volume were observed across groups in the bilateral thalamus, as well as the right lateralized caudate, hippocampus, and pallidum; these were primarily accounted for by differences between the depressed MDD subjects versus both the remitted and healthy subjects, though none of these changes remained significant after controlling for total intracranial volume (TIV). Volumetric reductions in the thalamus and hippocampus may contribute to dysfunction within subcortical–cortical networks, consistent with previous evidence of metabolic and hemodynamic abnormalities in these regions in MDD.