Recurrent Depressive Episodes Research Articles

Eye Movement Desensitization and Reprocessing as an Adjunctive Treatment of Unipolar Depression: A Controlled Study

Depression is a severe mental disorder that challenges mental health systems worldwide. About 30% of treated patients do not experience a full remission after treatment, and more than 75% of patients suffer from recurrent depressive episodes. Although psychotherapy and medication can improve remission rates, the success rates of current treatments are limited. In this nonrandomized controlled exploratory study, 21 patients with unipolar primary depression were treated with a mean of 44.5 sessions of Cognitive Behavioural Therapy (CBT) including an average 6.9 adjunctive sessions of Eye Movement Desensitization and Reprocessing (EMDR). A control group (n= 21) was treated with an average of 47.1 sessions of CBT sessions alone. The main outcome measure was the Beck Depression Inventory II (BDI-II). The treatment groups did not differ in their BDI-II scores before treatment, and both treatments resulted in significant improvement. There was an additional benefit for patients treated with adjunctive EMDR (p= .029). Also the number of remissions at posttreatment, as measured by a symptom level below a BDI-II score of 12, was significantly better in the adjunctive EMDR group, the group showing more remissions (n= 18) than the control group (n= 8;p< .001). This potential effect of EMDR in patients with primary depression should be examined further in larger randomized controlled studies.

EPA-0023 – Diabetes and major depressive disorder interaction: no effect of baseline diabetic control on six month depression outcomes

Prior studies have demonstrated an inter-relationship between the diagnosis of diabetes, obesity and depression. Our prior studies have shown that the diagnosis of diabetes or baseline body mass index (BMI) did not impact six month depression remission rates. Our hypothesis was that level of control of diabetes (hemoglobulin A1c < 8.0%) in depressed diabetic patients would have no effect on depression remission rates six months after diagnosis. This study was retrospective analysis of 451 diabetic primary care patients diagnosed with Major Depressive Disorder or Dysthymia with a PHQ-9 score of 10 or greater. ▪ Outcome variable was clinical remission (PHQ-9 < 5) at six months. ▪ Logistic regression modeling included the demographic variables of age, gender, marital status, the clinical variables of BMI, baseline PHQ-9 score, hemoglobin A1c level (at date of diagnosis of depression) and clinical diagnosis (recurrent or first episode of depression, or dysthymia). 78.5% (354) of depressed diabetics were in good control of diabetes (hemoglobin A1c< 8%) at enrollment. Obesity (BMI≥ 30) at baseline was not different between the controlled and uncontrolled diabetic patients at baseline (approximately 70%), p=0.36. Figure 1 Odds ratio for clinical remission (PHQ-9<5) at six months in diabetic primary care patients, by variable (N=451). Controlling for age, gender, marital status, race, clinical diagnosis and clinical site. ▪ Baseline control of diabetes was not an independent predictor for depression outcome at six months. This data suggests that poor diabetic control was not associated worsening clinical outcomes in depression management.

EPA-0021 – Initial depression severity: impact of obesity and diagnosis of diabetes of depressed primary care patients

Introduction Prior studies have demonstrated an inter-relationship between the diagnosis of diabetes, obesity and depression. Our data has demonstrated that baseline body mass index (BMI) was not predictive for clinical outcomes (remission at six months). Does either obesity or diabetes impact initial depression severity? Objectives/Aims Our hypothesis was that obesity and the diagnosis of diabetes in depressed primary patients would have no effect on initial depression severity at the time of diagnosis of depression. Methods This study was retrospective analysis of 4,310 primary care patients diagnosed with Major Depressive Disorder or Dysthymia with a PHQ-9 score of 10 or greater. ▪ Outcome variable was initial depression severity at the time of diagnosis (as measured by PHQ-9). ▪ Logistic regression modeling included the demographic variables of age, gender, marital status, the clinical variables of BMI, diagnosis of diabetes (yes/no) and clinical diagnosis (recurrent or first episode of depression, or dysthymia). Results Download : Download full-size image Figure 1 . Odds ratio for severe depression (PHQ-9≥20) at diagnosis in depressed primary care patients, by variable (N=4,310). Conclusions ▪ Baseline obesity was not an independent predictor for severe depression. ▪ Diagnosis of diabetes was an independent predictor for as protective for severe depression at diagnosis. This data suggests that obesity was not associated with worsening depression severity; diabetes may be seen as protective if patients were being seen sooner and diagnosed earlier in their disease course.

EPA-0022 – Diagnosis of diabetes and obesity have no impact on six month remission rates for depressed primary care patients

Prior studies have demonstrated an inter-relationship between the diagnosis of diabetes, obesity and depression. Our data has demonstrated that baseline body mass index (BMI) was not predictive for clinical outcomes (remission at six months). Our hypothesis was that obesity (BMI ≥30) and the diagnosis of diabetes in depressed primary patients would have no effect on depression remission rates six months after diagnosis. This study was retrospective analysis of 1, 894 primary care patients diagnosed with Major Depressive Disorder or Dysthymia with a PHQ-9 score of 10 or greater. Outcome variable was clinical remission (PHQ-9 < 5) at six months. Logistic regression modeling included the demographic variables of age, gender, marital status, the clinical variables of BMI, baseline PHQ-9 score, diagnosis of diabetes (yes/no) and clinical diagnosis (recurrent or first episode of depression, or dysthymia). Download : Download full-size imageFigure 1. Odds ratio for clinical remission (PHQ-9<5) at six months in depressed primary care patients, by variable (N=1,894). Figure 1. Odds ratio for clinical remission (PHQ-9<5) at six months in depressed primary care patients, by variable (N=1,894). Controlling for age, gender, marital status, race, clinical diagnosis and clinical site with logistic regression modeling. Baseline obesity was not an independent predictor for depression outcome at six months. Diagnosis of diabetes was not an independent predictor for depression outcome at six months. This data suggests that obesity and diabetes were not associated with worsening clinical outcomes in depression management.

Neuroprotective and antioxidant effects of curcumin in a ketamine-induced model of mania in rats

Bipolar disorder (BD) is a chronic and debilitating illness characterized by recurrent manic and depressive episodes. Our research investigates the protective effects of curcumin, the main curcuminoid of the Indian spice turmeric, in a model of mania induced by ketamine administration in rats. Our results indicated that ketamine treatment (25mg/kg, for 8 days) induced hyperlocomotion in the open-field test and oxidative damage in prefrontal cortex (PFC) and hippocampus (HP), evaluated by increased lipid peroxidation and decreased total thiol content. Moreover, ketamine treatment reduced the activity of the antioxidant enzymes superoxide dismutase and catalase in the HP. Pretreatment of rats with curcumin (20 and 50mg/kg, for 14 days) or with lithium chloride (45mg/kg, positive control) prevented behavioral and pro-oxidant effects induced by ketamine. These findings suggest that curcumin might be a good compound for preventive intervention in BD, reducing the episode relapse and the oxidative damage associated with the manic phase of this disorder.

Influence of Sex and Menopausal Status on Response, Remission, and Recurrence in Patients With Recurrent Major Depressive Disorder Treated With Venlafaxine Extended Release or Fluoxetine

To evaluate the effects of sex and menopausal status on acute-, continuation-, and maintenance-phase treatment outcomes in patients with recurrent major depressive disorder (MDD). This was a secondary analysis of data from the Prevention of Recurrent Episodes of Depression With Venlafaxine for Two Years (PREVENT) trial, a multiphase, multicenter, double-blind study in which adult outpatients with recurrent MDD (by DSM-IV criteria) were randomly assigned to 10 weeks of acute-phase venlafaxine extended release (ER) (75-300 mg/d) or fluoxetine (20-60 mg/d). Patients achieving response or remission had 6 months of continuation-phase treatment. Responding or remitting patients in the venlafaxine ER group were randomly assigned to venlafaxine ER or placebo for 2 consecutive 12-month maintenance phases; fluoxetine-treated patients continued receiving fluoxetine. The outcome measures for this analysis were acute- and continuation-phase response and remission rates (as measured by the 17-item Hamilton Depression Rating Scale) and time to depression recurrence in the maintenance phases according to sex and menopausal status at baseline. The intent-to-treat population comprised 781 patients in the venlafaxine ER group (65% women) and 266 patients in the fluoxetine group (61% women); 64% of all women were premenopausal, and 25% were postmenopausal (5% perimenopausal; not analyzed). At acute-phase end, remission rates in the venlafaxine ER vs fluoxetine groups were 44% vs 47% in men, 51% vs 52% in women, 50% vs 52% in premenopausal women, and 52% vs 55% in postmenopausal women. At continuation-phase end, remission rates in the venlafaxine ER vs fluoxetine groups were 71% vs 74% in men, 72% vs 67% in women, 72% vs 69% in premenopausal women and 71% vs 63% in postmenopausal women. Response rates were consistent with these findings. Based on a Cox proportional hazards model, sex was not a significant predictor of recurrence during the first or second maintenance phase (hazard ratio [HR] = 1.233; P = .3712 and HR = 1.103; P = .8075, respectively), and neither was menopausal status at acute-phase baseline (HR = 0.941; P = .8234 and HR = 0.531; P = .2065, respectively). In this study of patients with recurrent MDD, treatment outcomes with venlafaxine ER and fluoxetine did not differ on the basis of sex or menopausal status. Our confidence in these findings is limited by the lack of a placebo arm during the acute and continuation phases and by the small sample sizes for subgroup analyses in the maintenance phases. ClinicalTrials.gov identifier: NCT00046020.

Maintenance electroconvulsive therapy up to 12 years

BackgroundMaintenance electroconvulsive therapy (m-ECT) is effective in preventing recurrences of depressive episodes. There is little information on long-term m-ECT extending over several years and its impact on cognitive functions. This study was an attempt to determine the efficacy and side effects of long-term m-ECT. MethodDepressive episodes and admissions before m-ECT for a period equal to the duration of m-ECT and during m-ECT were compared using medical records. Cognitive functions assessed by Mini-Mental State Examination (MMSE) before and after m-ECT were compared along with the review of Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG). Results17 patients had m-ECT that extended from 6 to 153 months (mean 39, SD=44.46). The average number of episodes before and during m-ECT was 2.47 (SD=2.23) and 0.88 (SD=1.31) respectively (Wilcoxon ranked test Z=3.06, r=0.55, two-tailed p=0.002). Average number of admissions dropped from 2.05 (SD=1.88) to 0.23 (SD=0.43) during m-ECT (Z=3.471, r=0.71, p=0.001). The average time to recurrence was 24.24 months (SD=25.20) with longest depression free survival of 105 months. There was no significant difference in MMSE score before and after the commencement m-ECT or progressive deterioration in NUCOG score. LimitationsThis study was limited by retrospective nature of data collection, small sample size, confounding effects of antidepressants along with m-ECT and absence of a highly sensitive cognitive screening tool that can capture all types of cognitive impairments following m-ECT. ConclusionsIn a naturalistic setting the efficacy of m-ECT may extend over several years while cognitive functions remain largely unaffected.

Hidden scars in depression? Implicit and explicit self-associations following recurrent depressive episodes.

To help explain the recurrent nature of major depressive disorder, we tested the hypothesis that depressive episodes and/or the duration of depressive symptoms may give rise to persistent dysfunctional implicit and/or more explicit self-associations, which in turn may place people at risk for the recurrence of symptoms. We therefore examined, in the context of the Netherlands Study of Depression and Anxiety, whether the strength of self-depressed associations at baseline was related to the number of past episodes (retrospective analysis; n = 666), and whether the duration of symptoms between baseline and follow-up predicted self-depressed associations at 2-year follow-up (prospective analysis; n = 726). The lifetime Composite International Diagnostic Interviews and Life Chart Interview were used to index the number of depressive episodes; the Implicit Association Test and its explicit equivalent were used to index self-associations. Consistent with the hypothesis that self-depressed associations strengthen following prolonged activation of negative self-associations during depressive episodes, individuals' implicit and explicit self-depressed associations correlated positively both with the number of prior depressive episodes at baseline and with the duration of depressive symptoms between baseline and 2-year follow-up. There was evidence that these relationships held, particularly in the prospective study, even when controlling for neuroticism and current depressive symptoms, whereas the retrospective relationship between number of episodes and implicit self-associations fell just short of significance.

Vortioxetine: Atypical antidepressant

Although its mechanism of action is not fully understood, vortioxetine is an inhibitor of serotonin (5-hydroxytryptamine [5-HT]) reuptake and an agonist at 5-HT1A receptors; a partial agonist at 5-HT1B receptors; and an antagonist at 5-HT3, 5-HT1D, and 5-HT7 receptors. According to Takeda, it is the fi rst and only antidepressant that increases the availability of serotonin by this unique combination of pharmacodynamic activity. The contribution of each of these mechanisms of action to vortioxetine’s antidepressant effect has not been established; however, they may represent an improvement over other antidepressants currently on the market, said Takeda.

The effects of recurrent episodes of depression on startle responses: a longitudinal population-representative study

The effects of recurrent episodes of depression on startle responses: a longitudinal population-representative study

Personalized medicine in bipolar disorder: how can we overcome the barriers to clinical translation?

Bipolar disorder (BD) is a complex mood disorder characterized by recurrent episodes of mania and depression, affecting 1–4% of the general population [1]. The phenotypic representation of BD is highly heterogeneous, a characteristic that is reflected in the variability in response to mood-stabilizing drugs observed in bipolar patients. Mood stabilizers are a class of drugs that includes anticonvulsants, second-generation antipsychotics and lithium, with the latter being the mainstay in BD treatment. In 1949, John Cade described, for the first time, lithium’s antimanic effect [2]. In the following years, many trials demonstrated lithium’s efficacy in shortterm and prophylactic treatment of BD [3]. The choice of lithium as the first treatment in BD patients has also been influenced by its welldescribed antisuicidal effect – suicide being one of the leading causes of death in BD patients [4]. For these reasons, the vast majority of studies on response to drugs used in BD have thus far been focused on lithium more than any other mood stabilizer. While a significant proportion of patients chronically treated with lithium show full remission with stabilization of mood alterations, approximately 70% of subjects present partial or complete nonresponse [5]. This significant rate of insufficient response, together with the potentially serious adverse effects of lithium treatment, has stimulated a growing body of research aimed at the identification of predicting factors and new drug targets. The first step for the design of targeted therapies should consist of the identification of predictive markers of response. Nevertheless, with the exception of clinical factors, findings have so far provided weak evidence for specific predictors of lithium response. The main barriers

The effects of recurrent episodes of depression on startle responses

Prior work suggests that major depression is associated with abnormal startle blink responses; however, only chronic or recurrent depression appears to be associated with this effect. The current study tested this hypothesis directly by examining whether recurrent major depression accounted for the anomalous startle seen in major depression using a sample of 515 female twins from the Minnesota Twin Family Study. Blink responses recorded at the age of 20 were examined in relation to number of episodes of depression prospectively assessed from ages 11 to 20. Results showed that only subjects who had experienced multiple episodes of depression showed abnormal startle responses. Subjects who had experienced just one episode of depression in their lifetime did not differ from controls. This lends additional support to the idea that recurrent depression may have a different etiological basis than nonrecurrent depression.

P.1.j.002 Memory impairment in old mice is differentially sensitive to different classes of antidepressants

test (p = 0.008), word list recognition test (p = 0.032), constructional recall (p = 0.025) than normal control elderly group. Boston naming test (p = 0.006) and Construction praxis (p = 0.04) were significant lower in recurrent episode group than single episode group. Word list memory test (p = 0.033) and Word list recognition (p = 0.025) had significant negative correlation with months from first episode onset. GDS has significant positive correlation (R2 Linear=0.152) with trail making test A. There were no significant differences in cognitive functions between recovered geriatric depressive patients who had been confirmed as melancholic type (n = 11) and normal elderly group (p = 0.09–0.532). Conclusion: The findings of this study suggest the correlation between geriatric depression and executive function decline. Cognitive deficits overall appear to be more common among remitted geriatric depression patients. And recurrent episode of depression could impair the executive function in elderly patients. The findings also suggest when elderly people gets in longer duration of depressive state memory impairment could occur. More studies are necessary to examine cognitive dysfunction in remitted psychotic, melancholic and bipolar spectrum MDD.

The association between the disruption of motor imagery and the number of depressive episodes of major depression

BackgroundMental rotation performance may be used as an index of mental slowing or bradyphrenia, and may reflect, in particular, speed of motor preparation. Previous studies suggest depressive patients present the correlates of impaired behavioural performance for mental rotation and psychomotor disturbance. The aim of this study is to compare the mental rotation abilities of patients with a first episode of depression, recurrent depression and healthy control subjects with regard to hand tasks. MethodsWe tested 32 first episode of depression, 38 recurrent depression and 36 healthy control subjects by evaluating the performance of depressed patients with regard to the hand mental rotation tasks. ResultsFirst, the first episode and recurrent depression subjects were significantly slower and made more errors than controls in mentally rotating hands. Second, the first depressive episode but not the recurrent depression displayed the same pattern of response times to stimuli at various orientations relative to control subjects in the hand task. Third, in particular, recurrent depression subjects were significantly slower and made more errors during the mental transformation of hands than first depressive episode relative to control subjects and the differences were significantly larger in female than male subjects in the mental rotation hand task. LimitationsPatients were on antidepressant medication. ConclusionsThese results suggest that the impaired behavioural performance for mental representation processing are related to the number of previous episodes. Moreover, the recurrent major depressive episodes may contribute to the reinforcement of cognitive impairments and further the development or maintenance of mental representation dysfunctions, especially in female patients. A deficit on mental rotation in the depressive patients may be potential biomarkers for recurrence chronically.

One-year outcomes of unipolar depression patients with manic or hypomanic switch during acute antidepressant treatment

Objective. The aim of the study was to investigate one-year outcomes of unipolar depression patients with manic or hypomanic switch during acute antidepressant treatment. Methods. A review of medical records revealed 37 consecutive patients admitted from 1997 to 2002 who underwent an antidepressant-induced manic or hypomanic switch fulfilling DSM-IV criteria. Their clinical courses were retrospectively investigated after discharge. Results. Of the 37 patients, 33 (89.2%) were followed up for 1 year after discharge. None developed a manic episode, while seven developed a hypomanic episode, including 1 patient who was lost after emerging from a hypomanic episode within 6 months after discharge. Only one of those seven patients developed hypomania during acute antidepressant treatment for a recurrent depressive episode under maintenance mood stabilizer treatment. Furthermore, bipolar conversion occurred in four patients within the first 6 months and in another two patients, including 1 with rapid cycling, over the subsequent 6 months after discharge. Of these 33 patients, 28 received continuous maintenance treatment with mood stabilizers for the one-year period after discharge. Conclusions. The subjects were considered to have a bipolar nature according to the prevalence rate of bipolar conversion over a one-year period. Longer follow-up studies appear warranted determine the diagnostic issues of antidepressant-induced switch in unipolar depression.

Stressful life events severity in patients with first and recurrent depressive episodes

Stressful life events are associated with depression and their role in first onset and recurrences is a promising but controversial perspective of research. The objective is to analyze the role of number of previous episodes and life events exposure in a large sample of primary care depressive patients taking into account life events severity. 10,257 patients with DSM-IV criteria for a current single or recurrent major depressive episode were recruited by 2,056 general practitioners in a cross-sectional epidemiological study. Patients answered the Montgomery-Asberg Depression Rating Scale, the Patient Health Questionnaire and the Social Readjustment Rating Scale (SRRS). Stressful life events were categorized into three levels of severity (severe, moderate and mild). All relevant confounding variables were analyzed: age, gender, depression severity, somatic symptoms severity and length of episode. We found a significant positive correlation with number of episodes and depression severity. There was no significant correlation of SRRS scores with age, gender and length of episode. ANOVA exploring life events severity with regard to number of episodes showed statistically differences in SRRS total score, moderate life events and mild life events (F=15.14, p<0.001) but not for severe life events. Prevention and treatment strategies for recurrent depression need to manage life stressful events during mild and long-term periods and not just in the initial recurrences of the disease.

Practical considerations for the development of a psychoeducation programme: lessons from the Cardiff experience

Bipolar disorder is characterised by episodes of depression and mania or hypomania. Most patients tend to experience predominantly chronic depressive symptoms or recurrent depressive episodes with the result that bipolar depression can be misdiagnosed as major depressive disorder. This can lead to inappropriate medication choices and increased healthcare costs (1, 2). Psychoeducational interventions for bipolar disorder – particularly group interventions – that are delivered alongside medication, are known to be effective in reducing rates of relapse and can have a positive impact by helping patients to develop a range of long-term, self-management skills

Sexual Functioning in Patients With Recurrent Major Depressive Disorder Enrolled in the PREVENT Study

The incidence of treatment-emergent sexual dysfunction in the acute and continuation phases of the prevention of recurrent episodes of depression with venlafaxine ER for two years (PREVENT) study was assessed. Adult outpatients with recurrent major depressive disorder were randomly assigned to receive venlafaxine extended release (ER; 75-300 mg/day) or fluoxetine (20-60 mg/day). Sexual dysfunction was assessed using items from the 17-item Hamilton Rating Scale for Depression (HAM-D(17)) and the Inventory of Depressive Symptomatology-Self-Report (IDS-SR). The baseline rates of sexual dysfunction based on the HAM-D(17) and IDS-SR items were 57.9% and 48.8%, respectively. The rates of new-onset sexual dysfunction for the venlafaxine ER-treated (44.8%, HAM-D(17); 38.4%, IDS-SR) and fluoxetine-treated patients (52.9%, HAM-D(17); 50.0%, IDS-SR) were similar; approximately 80% of the cases resolved during treatment. Treatment response was associated with lower rates of new-onset sexual dysfunction compared with nonresponse. The patients who remitted were the least likely to experience sexual dysfunction during antidepressant treatment.

Prevention of Relapse With Maintenance Electroconvulsive Therapy in Elderly Patients With Major Depressive Episode

To evaluate the effectiveness and safety of maintenance electroconvulsive therapy (mECT) in elderly patients with treatment-resistant Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition major depressive episode. Seven elderly patients with treatment-resistant major depressive episode were treated with a complete ECT cycle. Thereafter, they received one monthly ECT session as maintenance for 1 year. Response to treatment was defined as at least a 50% drop from baseline on the Hamilton Depression Rating Scale (HamD) and remission as not meeting criteria for major depression, a HamD score of 7 or less, and Clinical Global Impressions-Severity of Illness score of 1. We compared their response with the response of 7 elderly patients with treatment-resistant major depression who were treated with a full cycle of ECT but did not receive mECT (non-mECT). We compared the 2 groups for the number of relapses or recurrences of major depressive episodes after remission was achieved; a relapse or a recurrence occurred when HamD scores were 14 or higher, or when Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision major depressive episode criteria were met, or when Clinical Global Impressions-Severity of Illness score was 3 or higher and increased by at least 2 points from response/remission. The mECT group (4 women and 3 men; mean age, 73 years) had significantly less mean relapses/recurrences (0 vs 1.57) and hospitalizations (0 vs 1) and received less drug treatment than the nonMECT group (similar for age and sex composition) during the 12-month follow-up period. All patients with mECT improved during treatment and did not relapse. Maintenance ECT protected elderly patients from recurrent depressive episodes from relapsing/recurring more than standard ECT.

A multi-state model to improve the design of an automated system to monitor the activity patterns of patients with bipolar disorder

This paper describes the role of mathematical modelling in the design and evaluation of an automated system of wearable and environmental sensors called PAM (Personalised Ambient Monitoring) to monitor the activity patterns of patients with bipolar disorder (BD). The modelling work was part of an EPSRC-funded project, also involving biomedical engineers and computer scientists, to develop a prototype PAM system. BD is a chronic, disabling mental illness associated with recurrent severe episodes of mania and depression, interspersed with periods of remission. Early detection of the onset of an acute episode is crucial for effective treatment and control. The aim of PAM is to enable patients with BD to self-manage their condition, by identifying the person's normal ‘activity signature’ and thus automatically detecting tiny changes in behaviour patterns which could herald the possible onset of an acute episode. PAM then alerts the patient to take appropriate action in time to prevent further deterioration and possible hospitalisation. A disease state transition model for BD was developed, using data from the clinical literature, and then used stochastically in a Monte Carlo simulation to test a wide range of monitoring scenarios. The minimum best set of sensors suitable to detect the onset of acute episodes (of both mania and depression) is identified, and the performance of the PAM system evaluated for a range of personalised choices of sensors.