Residual Depressive Symptoms Research Articles

How does MBCT for depression work? studying cognitive and affective mediation pathways.

Mindfulness based cognitive therapy (MBCT) is a non-pharmacological intervention to reduce current symptoms and to prevent recurrence of major depressive disorder. At present, it is not well understood which underlying mechanisms during MBCT are associated with its efficacy. The current study (n = 130) was designed to examine the roles of mindfulness skills, rumination, worry and affect, and the interplay between those factors, in the mechanisms of change in MBCT for residual depressive symptoms. An exploratory but systematic approach was chosen using Sobel-Goodman mediation analyses to identify mediators on the pathway from MBCT to reduction in depressive symptoms. We replicated earlier findings that therapeutic effects of MBCT are mediated by changes in mindfulness skills and worry. Second, results showed that changes in momentary positive and negative affect significantly mediated the efficacy of MBCT, and also mediated the effect of worry on depressive symptoms. Third, within the group of patients with a prior history of ≤ 2 episodes of MDD, predominantly changes in cognitive and to a lesser extent affective processes mediated the effect of MBCT. However, within the group of patients with a prior history of ≥ 3 episodes of MDD, only changes in affect were significant mediators for the effect of MBCT.Trail Registration: Nederlands Trial Register NTR1084

A Randomized Controlled Trial of the Efficacy and Safety of Lisdexamfetamine Dimesylate as Augmentation Therapy in Adults With Residual Symptoms of Major Depressive Disorder After Treatment With Escitalopram

Evaluate the efficacy and safety of lisdexamfetamine dimesylate augmentation for major depressive disorder (MDD) in escitalopram nonremitters. In this proof-of-concept study (conducted from July 2009-August 2010) with a prespecified critical α = .10, adults with nonpsychotic MDD (DSM-IV-TR criteria) and residual depressive symptoms (17-item Hamilton Depression Rating Scale score ≥ 4) after 8 weeks of open-label escitalopram were randomized to 6 weeks of lisdexamfetamine dimesylate (20-50 mg/d) or placebo augmentation. The primary endpoint, Montgomery-Asberg Depression Rating Scale (MADRS) total score change in escitalopram nonremitters (MADRS total score > 10) from week 8 (augmentation baseline) to week 14/end of study, was assessed using analysis of covariance, with last observation carried forward. For nonremitters (placebo, n = 64; lisdexamfetamine dimesylate, n = 65), the least squares (LS) mean (90% CI) treatment difference for MADRS total score reduction at week 14/end of study (-2.3 [-4.5 to -0.1]; P = .0902) met the prespecified criterion for lisdexamfetamine dimesylate superiority (adjusted effect size, -0.3); the number needed to treat for MADRS remission (MADRS total score ≤ 10) was 6.7. The LS mean treatment difference in remitters was not statistically significant (1.2 [-1.6 to 4.0]; P = .4726). Among randomized participants, 49.4% (42/85) receiving placebo and 60.2% (53/88) receiving lisdexamfetamine dimesylate had ≥ 1 treatment-emergent adverse event, the most frequent with lisdexamfetamine dimesylate being dry mouth and headache (both 11.4%). Mean (SD) vital sign and electrocardiogram changes (placebo vs lisdexamfetamine dimesylate) were 0.5 (8.98) versus 2.3 (9.04) mm Hg (systolic blood pressure), -1.0 (7.19) versus 0.9 (6.61) mm Hg (diastolic blood pressure), -0.4 (7.39) versus 4.8 (8.64) beats per minute (heart rate), and -1.6 (11.23) versus -4.9 (11.84) milliseconds (Fridericia-adjusted QTc). Lisdexamfetamine dimesylate augmentation reduced depressive symptoms in participants with inadequate escitalopram response. ClinicalTrials.gov identifier: NCT00905424.

EEG correlates and possible predictors of the efficacy of the treatment of endogenous depression

An analysis of EEG spectral power values and of quantitative clinical scores of depressive conditions has been carried out in dynamics of treatment in 40 patients with endogenous depression with the main goal to study neurophysiologic correlates and to search possible predictors of therapeutic outcome. The reduction of depressive symptoms by the end of the treatment course was associated with EEG signs of improvement of brain functional state. Significant correlations have been revealed between the EEG narrow-band spectral power values and clinical scores. As well, significant correlations have been revealed between some initial (before beginning of treatment) EEG parameters and quantitative clinical scores at the stage of remission establishing. The values of EEG beta-1 and beta-2 spectral power appeared to be such predictors, while initially larger values of EEG beta activity spectral power were associated with higher pronounce of residual depressive symptoms after the treatment course. The data obtained allow to justify basic views on brain mechanisms of various aspects of depressive disorders, and to reveal possible neurophysiological predictors of efficacy of treatment of endogenous depression.

Biological rhythm disturbance in remitted bipolar patients.

BackgroundBiological rhythm disturbance is common in bipolar patients and seems to affect the course and prognosis of the illness negatively. The main aim of the current study was to assess biological rhythms in remitted bipolar patients. We also assessed whether there was an association between clinical variables or functioning and biological rhythms in remitted bipolar participants.MethodsThe Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) was used to assess biological rhythm disturbance. It is an 18-item interviewer-administered instrument which allows us to investigate the main areas related to circadian rhythm disturbance (sleep/social, activities, and eating pattern) in bipolar disorder.Results and discussionBipolar patients (n = 107) experienced greater biological rhythm alterations than the control group (n = 100) (BRIAN total scores 35.36 ± 7.11 vs. 32.48 ± 6.10, t = 6.912, p = 0.002, Cohen's d = 0.43, r = 0.21). In particular, patients were more impaired than the control group with regard to sleep/social (14.67 ± 4.14 vs. 13.49 ± 2.91, t = 10.61, p = 0.018, Cohen's d = 0.33, r = 0.16) and activity (8.49 ± 2.51 vs. 7.07 ± 2.13, t = 3.90, p = 0.001, Cohen's d = 0.61, r = 0.29) domains. Furthermore, a significant correlation was found between biological rhythms with residual depressive symptoms (r = 0.459, p < 0.001) and functioning (r = 0.432, p < 0.001). These findings suggest a potential link between biological rhythms and the pathophysiology of bipolar disorder. It highlights the importance of novel instruments (e.g., BRIAN) which allow us to assess biological rhythm disturbance in psychiatry. Finally, specific psychosocial interventions focused on lifestyle regularity may be considered as a supplemental treatment of bipolar illness episodes.Electronic supplementary materialThe online version of this article (doi:10.1186/2194-7511-1-6) contains supplementary material, which is available to authorized users.

Social adjustment among treatment responder patients with mood disorders

BackgroundPatients with major depression (MD) show reduced social adjustment when compared with healthy controls. However, even among treatment responders, significant differences in social adjustment occur. The main aim of the present work is to study several socio-demographic and clinical variables possibly influencing social adjustment in MD patients who responded to treatment. MethodsTwo hundred and eleven MD patients experiencing a depressive episode who responded to their current treatment were recruited within the context of a large European multicentre project. Our primary outcome measure was the association between 19 socio-demographic and clinical variables and total social adjustment scores, as measured with the Social Adjustment Scale (SAS). Secondary outcome measures included the associations between the same variables and SAS sub-scales, and the associations between these variables and self-esteem, as measured with the Rosenberg Self-Esteem Scale. ResultsA co-morbidity with anxiety disorders and the severity of residual depression symptoms were the strongest independent factors associated with poorer social adjustment, in terms of total and most sub-areas' SAS scores. Other variables associated with total and sub-areas' SAS scores were identified as well, although some variations across different areas were observed. LimitationsThe cross-sectional design, the retrospective assessment of data and the lack of a placebo control group. ConclusionsOur results confirm that a co-morbidity with anxiety disorders and higher residual depression symptoms could reduce social adjustment among responder MD patients. Further longitudinal studies are needed to confirm our results.

Relationship of changes in cognitive and depressive symptoms during antidepressant treatment of individuals with geriatric depression and their relationship to the APOE epsilon 4 allele.

BackgroundCo-occurring cognitive impairment in geriatric depression may not improve with antidepressant treatment and it may progress to dementia.AimAssess the relationship between changes in cognitive and depressive symptoms among patients with geriatric depression and their association with the APOE epsilon 4 allele before and after antidepressant treatment.MethodsThe presence of the APOE epsilon 4 allele was assessed in 64 incident cases of geriatric depression and 31 elderly individuals without depression and the Geriatric Depression Scale (GDS), Mini-Mental State Examination (MMSE), digit span test, and Trail Making Tests A and B (TMT-A, TMT-B) were administered to these subjects at baseline and 12 months after baseline, during which time the depressed group received standardized treatment with selective serotonin reuptake inhibitors (SSRIs).ResultsPrior to treatment patients with geriatric depression had significantly worse cognitive functioning than control subjects and 31 (48%) met criteria for mild cognitive impairment (MCI). After treatment depressed patients with and without comorbid MCI both had significant improvements in their depressive and cognitive symptoms, but those with MCI had more residual symptoms. The severity of cognitive symptoms was not associated with the severity of depressive symptoms at baseline, but they were positively correlated at the 12-month follow-up. The APOE epsilon 4 allele was identified in 14% (9/64) of the patients and in 3% (1/31) of the controls (Fisher's Exact Test, p=0.158). Compared to depressed patients without the allele, depressed patients with the allele had more severe cognitive deficits both before and after treatment, though only some of these differences were statistically significant.ConclusionsThere is substantial cognitive impairment in elderly individuals with geriatric depression. Both the depressive and cognitive symptoms improve with standard SSRI treatment, but individuals with comorbid MCI have more residual depressive and cognitive symptoms after treatment. The APOE epsilon 4 allele is associated with greater cognitive impairment in geriatric depressed patients and may be associated with less responsiveness of cognitive symptoms to antidepressant treatment.

Validity and reliability of a rating scale on subjective cognitive deficits in bipolar disorder (COBRA)

BackgroundDiscrepancies between bipolar patients' reports and neuropsychological testing have been described and replicated. Unfortunately, no valid, specific, user-friendly, brief instrument is available to measure cognitive deficits as reported by these patients. The main aim of this study was to validate a novel instrument named the “cognitive complaints in bipolar disorder rating assessment” (COBRA). Second, we investigated the relationship between the COBRA, objective cognitive measures and illness course variables. MethodThe total sample (N=215) included 91 bipolar disorder patients and 124 healthy controls. The psychometric properties of the COBRA (e.g. internal consistency, concurrent validity, discriminative validity, factorial analyses, ROC curve and feasibility) were analyzed. A complete neuropsychological battery was used as objective cognitive assessment. ResultsThe COBRA had one-factor structure with very high internal consistency (Cronbach's alpha=0.913). A high convergent validity was indicated by a strong correlation with the Frankfurt Complaint Questionnaire (ro=0.888, p<0.001). Bipolar patients experienced greater cognitive complaints compared to control group suggesting a discriminative validity of the instrument. Significant correlations were found between the COBRA and some objective cognitive measures. Furthermore, higher COBRA scores were associated with bipolar II subtype, residual depressive symptoms, hypomanic episodes and total episodes. LimitationsThe cross-sectional design of the study, the influence of medication and severity of patients included. ConclusionsThe COBRA showed to be a useful instrument to assess overall cognitive complaints in bipolar disorder with very satisfactory psychometric properties. Cognitive complaints were partially correlated with memory and executive function measures and with issues that may increase the subjective perception of cognitive deficits, such as subthreshold depressive symptoms and number of episodes.

The effect of residual symptoms on clinical characteristics and functioning of patients with bipolar disorder in remission

Objective: The objective of this study was to investigate the relationship between the residual symptoms of patients with Bipolar Disorder (BD) in remission and their sociodemographic, clinical and treatment-related characteristics and their effect on functioning. Methods: The study group consisted of BD patients who were in remission and met the inclusion criteria of the study. The patients were assessed in a single cross-sectional interview. Results: A total of 120 patients (54.2% women) were included in the study. Those who never got married had significantly more manic residual symptoms than those who were married and divorced/widowed. The Global Assessment of Functioning (GAF) scores of the married group were significantly higher than those of the patients who never got married and were divorced/widowed. The GAF scores of those employed came out to be significantly higher than those of the unemployed, housewives and retired. Depressive residual symptoms and having the disease at a younger age had more prominent negative effects on functioning, the last attack experienced had an impact on the residual depressive symptoms and the accompanying anxiety symptoms, and the reasons that made the patients to come to regular doctor monitoring were mostly depressive symptoms and the decline in general functioning. Only 23.4% of the patients were monitored with a single mood stabilizer and 75% of them used at least 2 medications, but no statistically significant relationship was found between the treatment received by the patients and their residual symptoms and functioning. Conclusion: Since BD affects psychosocial functioning to a large extent, it is becoming increasingly important today to identify the characteristics of the disease, to monitor patients regularly and continuously, and to plan their treatment. Many variables that determine the nature of residual symptoms and contribute to functioning alongside residual symptoms are factors that prevent BD patients from forming a homogeneous group and demonstrating a similar prognosis. This makes it important to develop a different treatment strategy specific to each BD patient.

The Efficacy of Daily Naikan Therapy on the Residual Symptoms of Major Depression：A Randomized Controlled Study

The Efficacy of Daily Naikan Therapy on the Residual Symptoms of Major Depression：A Randomized Controlled Study

Can an Integrative Approach to the Management of Depression Help Patients Achieve Functional Recovery? A Review of Current Literature

The neurobiology of emotion regulation is complex and multifactorial. Current models suggest that connections between information processing by the brain and its communications with the mind and body are impaired by chronic stress and the system is dysregulated in Major Depressive Disorder (MDD). Despite the high prevalence of MDD, the condition remains poorly managed with current treatment approaches, which have traditionally been aimed at correcting a single level of dysfunction, notably in neurotransmitters. A substantial proportion of patients who achieve symptomatic improvement with conventional therapy continue to report residual depressive symptoms and/or poor psychosocial functioning. Few clinical trials have been powered to detect changes in measures of functioning, resulting in a lack of evidence-based guidance for clinicians. The present paper reviews the evidence for an integrated, multipronged approach to the management of depression that may involve pharmacotherapy, psychotherapy, Complementary and Alternative Medicine (CAM) approaches such as yoga/meditation, exercise, diet and dietary supplements, and social support groups. The author advocates for the use of a patient-centric approach founded on a strong patientprovider alliance for the management of MDD. A shared decision-making approach should consider the potential role of pharmacotherapy, psychotherapy and CAM, which may enhance symptomatic remission and functional recovery in patients with MDD. These results may be mediated, at least in part, through improved regulation of the Hypothalamic- Pituitary-Adrenal (HPA) axis, and reduced allostatic stress load.

2993 – Is mindfullness an evidence-based treatment?

Derived from ancient Buddhist and Yoga practices, mindfulness is a mental state characterized by nonjudgmental awareness of the present moment experience while encouraging openness, curiosity, and acceptance. This skill can be learned through practice, and has be integrated in different clinical approaches. Mindfulness-Based Stress Reduction (MBSR) is a structured group programme conceived to alleviate suffering associated with physical, psychosomatic and psychiatric disorders. A systematic review of RCTs on MBSR supports that this approach improves mental health in non-clinical and clinical populations. In clinical populations with psychiatric disorders, MBSR has some benefit as it reduces symptoms of distress, anxiety and depression or teaches patients coping skills to handle these symptoms. Mindfulness-Based Cognitive Therapy (MBCT), which is an adaptation of the MBSR programme, incorporates elements of cognitive therapy to prevent depressive relapse. Meta-analysis indicate that MBCT is an effective intervention for relapse prevention in patients with recurrent major depressive disorder in remission, at least in case of three or more previous episodes. Moreover, in two studies, MBCT was at least as effective as maintenance antidepressant medication. While MBCT is a relapse prevention programme for patients in full remission, recent data suggest that it may be indicated also for people in partial remission, including those with quite significant residual depressive symptoms.

Cognitive Training for Psychiatric Disorders

Psychiatric disorders are associated with impairments in neural system activity and connectivity across distributed networks that underlie cognition and social–emotional processes. Increasing evidence indicates that these neural system dysfunctions are not immutably fixed, but instead may be amenable to well-designed cognitive training interventions that target restoration of neural system operations (Browning et al, 2012; Klingberg et al, 2005; Subramaniam et al, 2012). An explicitly ‘systems neuroplasticity'-based approach to cognitive training is founded on the premise that during successful skill learning, disproportionately larger and better-coordinated neuronal populations represent the salient inputs and action outputs of the trained skill, resulting in an increased feed-forward signal strength from sensory regions as well as greater task-relevant feedback-inhibitory control from the prefrontal cortex to enhance representations of relevant stimuli, and to enable more efficient and accurate associative memory processes (Vinogradov et al, 2012). Effective cognitive training must target the underlying neural impairments associated with a specific pathophysiology. For children with ADD, for example, Klingberg et al 2005 found that computerized visual working memory (WM) exercises drove improvements in non-trained visuospatial and executive tasks, indicating generalization of training. This group also found that WM training improved WM capacity, which was correlated with neural changes in D1 receptor density, indicating increased dopaminergic release during training (Klingberg, 2010; McNab et al, 2009). Browning et al (2012) investigated attentional bias modification (ABM) training in remitted patients with depression, and found that ABM reduced residual depressive symptoms and normalized the cortisol awakening response, suggesting that it may be a ‘cognitive vaccine' that reduces the neurobehavioral risk for future depression episodes. Our group recently performed a double-blind randomized controlled trial of a set of computerized exercises that focused on early auditory and visual processing, WM and basic social cognition (vs computer games control condition) in individuals with schizophrenia. Our rationale was that schizophrenia is characterized by deficits in both early pre-attentive perceptual processes as well as higher-order attention and WM operations (Vinogradov et al, 2012). We found that the schizophrenia participants who received the targeted training showed behavioral improvements on (untrained) neuropsychological measures of verbal memory and on reality-monitoring tasks, thus indicating generalization of training effects. Further, after the intervention, neural activation patterns during reality monitoring, which were abnormal in these patients at baseline, began to resemble the patterns observed in healthy participants (Figures 1a and c), and predicted better social functioning 6 months later (Subramaniam et al, 2012). Figure 1 Whole-brain fMRI analysis of reality-monitoring activity reveals signal increase within: (a) the medial prefrontal cortex (mPFC) in 15 healthy comparison (HC) subjects, (b) the posterior cingulate cortex, rather than the mPFC, in patients with schizophrenia ... Together, these emerging data suggest that people with a range of neuropsychiatric illnesses can benefit from targeted cognitive training; that this type of training can ‘restore' aspects of behavior and neural system functioning; and that this training can be generalized to enduring improvements in real-world functioning (Browning et al, 2012; Klingberg et al, 2005; Subramaniam et al, 2012). Future studies must examine the specific intervention methods that promote maximal cognitive and neural system ‘restoration' in the neuropsychiatrically impaired brain—likely by combining targeted cognitive training approaches with cognitive enhancing medications and neuromodulation techniques such as transcranial direct current stimulation.

Dépression en médecine générale

Identification of Major Depressive Disorder (MDD) can be easily done by asking systematically the following questions. During the last month: "Did you lose interest and pleasure for the things that you usually like and enjoy?" "Have you lost energy, or do you feel abnormally tired or depressed?" Physical symptoms of MDD are more frequent for patients supported by general practitioner. Patients suffering from a general medical affection are more likely to present a risk of MDD. Treatment of MDD for patients suffering from a general medical affection must be identical to that of patients not suffering from a medical affection. Objective of the antidepressant treatment is the complete remission and not only the response. Evaluating precisely the symptoms of depression in pretherapetical phase allows to facilitate distinction of side effects of a treatment versus residual symptoms of depression. Treatment must be taken during a sufficient period: 6to 9months for a first Major depressive episode up to entire life for the most serious cases of recurrent MDD. Making the patient aware of the main side effects of the treatment that he will face rapidly (digestion troubles essentially) is a simple way to reduce the risks of early abandon of the treatment.

Effectiveness of Abbreviated CBT for Insomnia in Psychiatric Outpatients: Sleep and Depression Outcomes

To test the efficacy of cogntive-behavioral therapy for insomnia (CBT-I) as a supplement treatment for psychiatric outpatients. Comorbid insomnia is prevalent among individuals with varied psychiatric disorders and evidence indicates that CBT-I may be effective for reducing insomnia and other psychiatric symptoms. The present study randomly assigned 30 psychiatric outpatients (mean duration of treatment = 3.6 years) with low sleep quality and residual depressive symptoms to two sessions of CBT-I or a treatment as usual control group. Assessment included the Pittsburgh Sleep Quality Index (PSQI) for insomnia and the Patient Health Questionnaire (PHQ-9) for depression at pretreatment and 4 and 8 weeks posttreatment. Patients who received CBT-I demonstrated within group changes in PSQI and the PHQ-9 scores at both 4 and 8 weeks posttreatment, but did not show between-group differences. Additionally, 38% of the treatment participants achieved normal sleep at follow-up compared with none in the control condition. This study provides preliminary evidence that abbreviated behavioral treatment has beneficial effects on residual insomnia and depression in long-term psychiatric outpatients.

Efficacy of mindfulness-based cognitive therapy in relation to prior history of depression: randomised controlled trial

There appears to be consensus that patients with only one or two prior depressive episodes do not benefit from treatment with mindfulness-based cognitive therapy (MBCT). To investigate whether the effect of MBCT on residual depressive symptoms is contingent on the number of previous depressive episodes (trial number NTR1084). Currently non-depressed adults with residual depressive symptoms and a history of depression (≤2 prior episodes: n = 71; ≥3 episodes: n = 59) were randomised to MBCT (n = 64) or a waiting list (control: n = 66) in an open-label, randomised controlled trial. The main outcome measured was the reduction in residual depressive symptoms (Hamilton Rating Scale for Depression, HRSD-17). Mindfulness-based cognitive therapy was superior to the control condition across subgroups (β = -0.56, P<0.001). The interaction between treatment and subgroup was not significant (β = 0.45, P = 0.16). Mindfulness-based cognitive therapy reduces residual depressive symptoms irrespective of the number of previous episodes of major depression.

Distinguishing subclinical (subthreshold) depression from the residual symptoms of major depression.

The terms ‘sub-clinical’ or ‘subthreshold’ are widely used in medicine to label individuals who are in the early stages of a disease process (e.g., cancer, hypertension, etc.) and to identify high-risk populations that need to be monitored or provided with specific preventative interventions or treatments. Because the pathophysiological changes that occur in the sub-clinical stages of a condition are similar to those that occur during the full-blown disease, sub-clinical states are usually considered prodromal versions of the disease under consideration. Based on this usage, subclinical or subthreshold depression should refer to an individual who has not previously met full criteria for major depression who currently experiences depressive symptoms that are not severe enough or persistent enough to merit a diagnosis of major depression. Using this concept, a recent two-year follow-up study found that subthreshold depression can predict the subsequent occurrence of depressive disorders (OR=6.23, 95% CI=3.31-11.74) or anxiety disorders (OR=3.47, 95% CI= 1.78-6.78).[1] Unlike other medical disciplines, in clinical psychiatry the sub-clinical and subthreshold labels are also used to describe residual clinical states after the partial remission of a full episode of a condition. For example, ‘sub-clinical depression’ is often used to describe the clinical state of a patient who has not entered full remission and still has residual symptoms after treatment with antidepressants.[2],[3] I believe it important to distinguish these two situations. Prodromal depressive symptoms prior to the onset of a full-criteria major depression and the residual depressive symptoms after the partial resolution of a major depressive episode may be symptomatically similar but they are clinically distinct conditions that require different interventions so it is inappropriate to combine them under a single label. Residuals symptoms following a major depressive illness require continued pharmacological and/or psychotherapeutic treatment but sub-clinical depressive symptoms prior to the first occurrence of a major depressive illness usually only require observation and follow-up. More active treatment for sub-clinical depressive symptoms is usually only justified if they persist for two years or longer (in which case the diagnosis of Dysthymic Disorder is usually applied) or if the individual has had full-criteria major depressive illness in the past and thus is at a high risk of progressing to a full-criteria episode of illness. Collapsing these different situations under a single rubric is both inaccurate and could potentially lead to inappropriate treatment. I recommend that persistent depressive symptoms following a major depressive illness that do not meet the full criteria of the disorder be labeled ‘residual symptoms’ (not sub-clinical or subthreshold symptoms) and that the ‘sub-clinical depression’ or ‘subthreshold depression’ labels be limited to depressive symptoms that occur prior to the first onset of a full depressive episode. But depressive affect is part of the normal human condition so we must also avoid the inappropriate overuse of the sub-clinical and subthreshold labels by, for example, labeling the depressive symptoms identified in screening programs of healthy community members as ‘subthreshold depression’. Depressive symptoms in individuals without prior episodes of full-criteria depressive illness should only be given the sub-clinical or subthreshold labels if the symptoms are ‘clinically significant’, that is, when they result in significant distress or significant social or occupational dysfunction.

Efficacy, tolerability, compliance, and quality of life of patients with mood disorders switched from Quetiapine immediate release to extended release

The present study aimed to assess switch from immediate-release (IR) to extended-release (XR) quetiapine in terms of efficacy, tolerability, compliance, and quality of life in a sample of patients with mood disorders. Thirty patients, 10 with major depressive disorder and 20 with bipolar disorder, with residual depressive symptoms, who had switched from quetiapine IR (mean 365 mg/day) to XR (mean 373 mg/day), were recruited and evaluated using different psychometric scales, administered at T0 (switch), T1, and T2 (1 and 6 weeks after the switch, respectively). A significant reduction from T0 to T2 of the total scores on the Hamilton depression rating scale (t=2.15; P=0.04), Hamilton anxiety scale (t=3.04; P=0.006), and clinical global impression-severity item (t=2.8; P=0.01) was found. No differences were found in terms of compliance and quality of life. The switch was well tolerated by 2/3 of patients. Most reported side effects were early/central insomnia with day drowsiness (16.7%), increased appetite and weight (8.4%), mild asthenia (4.2%), and constipation (4.2%), which, in two cases, led to switch interruption. Strategies to relieve side effects, including gradual cross-switch, improved switch feasibility. Switch from quetiapine IR to XR seems to be associated with clinical improvement in major depressives with residual symptoms, although some patients may report side effects because of the different pharmacokinetics.

Cognitive deficits in the remitted state of unipolar depressive disorder.

Patients with unipolar depressive disorder may present with cognitive deficits in the remitted state, and the aim of the present study was to investigate whether cognitive deficits within specific cognitive domains are present. Via the Danish registers (Civil Person Register, Danish Psychiatric Register) we identified individuals between 40 and 80 years of age with a diagnosis of unipolar disorder at their first discharge from a psychiatric hospital, and a gender- and age-matched control group. Particular emphasis was placed on assuring that patients were in a remitted state. Cognitive function was assessed with a broad range of neuropsychological tests. A total of 88 patients and 50 controls were included in the study. In multiple linear regression analyses with simultaneous adjustment for age, gender, education level, premorbid IQ, and residual depressive symptoms, a diagnosis of unipolar disorder predicted lower performance on the Trail Making Test, the Symbol Digit Modalities Test, and on the Stroop test. Cognitive deficits are present in patients with unipolar disorder in the remitted state. The deficits seem to reside more within the cognitive domain of attention than within other domains, and may be characterized by impairment of processing speed and cognitive flexibility.

The cumulative load of depressive illness is associated with cognitive function in the remitted state of unipolar depressive disorder

ObjectiveTo investigate whether the cumulative number, duration and subtypes (severity and presence of psychotic features) of previous episodes of depression in patients with unipolar depressive disorder in a remitted state are associated with decreased global cognitive function. MethodsVia the Danish registers individuals between 40 and 80 years of age were identified: (1) patients with a diagnosis of unipolar disorder at their first discharge from a psychiatric hospital in the period 1994 to 2002, and (2) gender and age matched control individuals. The participants were assessed with the Cambridge Cognitive Examination (CAMCOG), which provides a composite measure of global cognitive function. ResultsA total of 88 patients and 50 controls accepted our invitation to participate, fulfilled the selection criteria and were included in the study. The cumulative duration of depressive episodes was associated with a decreased CAMCOG score adjusted for age, gender, education, premorbid IQ and residual depressive symptoms (B=−0.14, 95% C.I. (−0.26, −0.02), R2adj=0.31, P=.02). Significant associations were also found between CAMCOG score and the cumulative duration and total number of depressive episodes with psychotic features, respectively. ConclusionOur findings suggest that cognitive dysfunction is associated with the cumulative duration of depressive episodes, and that, in particular, depressive episodes with psychotic features in the course of illness may be a significant predictor of future impairment of cognitive function.

A longitudinal study of differences in late- and early-onset geriatric depression: Depressive symptoms and psychosocial, cognitive, and neurological functioning

Objectives: Studies suggest early-onset depression (EOD) is associated with a more severe course of the depressive disorder, while late-onset depression (LOD) is associated with more cognitive and neuroimaging changes. This study examined if older adults with EOD, compared with those with LOD, would exhibit more severe symptoms of depression and, consistent with the glucocorticoid cascade hypothesis, have more hippocampal volume loss. A second goal was to determine if LOD, compared with EOD, would demonstrate more cognitive and neuroimaging changes. Method: At regular intervals over a four-year period non-demented, older, depressed adults were assessed on the Mini-Mental Status Examination and the Montgomery–Asberg Depression Rating Scale. They were also assessed on magnetic resonance imaging. Results: Compared with LOD, EOD had more depressive symptoms, more suicidal thoughts, and less social support. Growth curve analyses indicated that EOD demonstrated higher levels of residual depressive symptoms over time. The LOD group exhibited a greater decrement in cognitive scores. Contrary to the glucocorticoid cascade hypothesis, participants with EOD lost right hippocampal volume at a slower rate than did participants with LOD. Right cerebrum gray matter was initially smaller among participants with LOD. Conclusions: EOD is associated with greater severity of depressive illness. LOD is associated with more severe cognitive and neurological changes. These differences are relevant to understanding cognitive impairment in geriatric depression.