Neurocognitive Effects of Combined Electroconvulsive Therapy (ECT) and Venlafaxine in Geriatric Depression: Phase 1 of the PRIDE Study

ObjectiveThere is limited information regarding the tolerability of electroconvulsive therapy (ECT) combined with pharmacotherapy in elderly adults with major depressive disorder (MDD). Addressing this gap, we report acute neurocognitive outcomes from Phase 1 of the Prolonging Remission in Depressed Elderly (PRIDE) study.MethodsElderly adults (age ≥60) with MDD received an acute course of 6 times seizure threshold right unilateral ultrabrief pulse (RUL-UB) ECT. Venlafaxine was initiated during the first treatment week and continued throughout the study. A comprehensive neurocognitive battery was administered at baseline and 72 hours following the last ECT session. Statistical significance was defined as a two-sided p-value of less than 0.05.ResultsA total of 240 elderly adults were enrolled. Neurocognitive performance acutely declined post ECT on measures of psychomotor and verbal processing speed, autobiographical memory consistency, short-term verbal recall and recognition of learned words, phonemic fluency, and complex visual scanning/cognitive flexibility. The magnitude of change from baseline to end for most neurocognitive measures was modest.ConclusionThis is the first study to characterize the neurocognitive effects of combined RUL-UB ECT and venlafaxine in elderly adults with MDD and provides new evidence for the tolerability of RUL-UB ECT in an elderly sample. Of the cognitive domains assessed, only phonemic fluency, complex visual scanning, and cognitive flexibility qualitatively declined from low average to mildly impaired. While some acute changes in neurocognitive performance were statistically significant, the majority of the indices as based on the effect sizes remained relatively stable.     

Atropine Sulfate Premedication and Cardiac Arrhythmia in Electroconvulsive Therapy (ECT)

Prophylactic effects of atropine sulfate as a premedication for cardiac arrhythmia were studied in 44 patients receiving electroconvulsive therapy in a randomized, cross-over, double-blind design. Cardiac rhythms were recorded with Holter monitors during atropine sulfate and placebo treatments. Vagal arrhythmia seemed to be reduced with atropine sulfate premedication, but the frequency of ventricular arrhythmia was not affected.     

Stability of the Subtypes of Major Depressive Disorder in Older Adults and the Influence of Mild Cognitive Impairment on the Stability

ObjectivesTo assess 1) the longitudinal stability of the atypical, melancholic, combined atypical-melancholic and the unspecified subtypes of major depressive disorder (MDD) according to the diagnostic and statistical manual of mental disorders (DSM –IV) specifiers in older adults, and 2) the effect of mild cognitive impairment (MCI) on the stability of these subtypes.DesignProspective cohort study with a 5.1 year-follow-up.SettingPopulation-based cohort from Lausanne, Switzerland.ParticipantsA total of 1,888 participants (mean age: 61.7 years, women: 69.2%) with at least two psychiatric evaluations, one after the age of 65 years.MeasurementsSemistructured diagnostic interview to assess lifetime and 12-month DSM-IV Axis-1 disorders at each investigation and neuro-cognitive tests to identify MCI in participants aged 65 years and over. Associations between lifetime MDD status before and 12-month depression status after the follow-up were assessed using multinomial logistic regression. The effect of MCI on these associations was assessed by testing interactions between MDD subtypes and MCI status.Results1) Associations between depression status before and after the follow-up were observed for atypical (adjusted OR [95% CI] = 7.99 [3.13; 20.44]), combined (5.73 [1.50; 21.90]) and unspecified (2.14 [1.15; 3.98]), but not melancholic MDD (3.36 [0.89; 12.69]). However, there was a certain degree of overlap across the subtypes, particularly between melancholic MDD and the other subtypes. 2) No significant interactions were found between MCI and lifetime MDD subtypes regarding depression status after follow-up.ConclusionThe strong stability of the atypical subtype in particular highlights the need for identifying this subtype in clinical and research settings, given its well-documented links to inflammatory and metabolic markers.     

Methohexital and Succinylcholine Dosing for Electroconvulsive Therapy (ECT): Actual Versus Ideal

ABSTRACT: This report compares the actual doses of methohexital and succinylcholine used for optimal anesthesia and muscle relaxation in electroconvulsive therapy with written guidelines for dosing. The initial doses of methohexital and succinylcholine in milligrams per kilogram were reviewed and compared with subsequent doses of each agent after adjustments were made for individual patient responses during treatment. The dose of methohexital required to induce general anesthesia for most patients is 1.0 mg/kg. The dose of succinylcholine required to provide adequate muscle relaxation during electroconvulsive therapy is 0.9 mg/kg, although there is considerable variability in patient response to this drug.     

Lipopolysaccharide,Immune Biomarkers and Cerebral Amyloid-Beta Deposition in Older Adults With Mild Cognitive Impairment & Major Depressive Disorder

ObjectiveInflammatory activation and increased immune response to lipopolysaccharide occur in both depression and cognitive decline and may link these two conditions. We investigated whether lipopolysaccharide (LPS), LPS binding protein (LBP) and peripheral biomarkers of immune response were associated with increased cerebral deposition of amyloid-beta (Abeta) in older adults with mild cognitive impairment (MCI) and remitted major depressive disorder (rMDD).DesignCross-sectional analysis.SettingFive academic health centers in Toronto.ParticipantsOlder adults with MCI with/without rMDD.MeasurementsWe investigated the associations among serum LPS, LBP, biomarkers of inflammatory activation – Interleukin-6 (IL-6), C-reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1), and cerebral Abeta deposition quantified by positron emission tomography.ResultsAmong 133 study participants (82 with MCI and 51 with MCI+rMDD) there was no association between LPS (beta – 0.17, p = 0.8) or LBP (beta - 0.11, p = 0.12) and global deposition of Abeta following adjustment for age, gender, and APOE genotype in multivariable regression analyses. LBP was positively correlated with CRP (r = 0.5, p <0.001) and IL-6 (r = 0.2, p = 0.02) but no inflammatory biomarker was associated with Abeta deposition; rMDD was not associated with deposition of Abeta (beta -0.09, p = 0.22).ConclusionIn this cross-sectional analysis, we did not find an association among LPS/LBP, immune biomarkers or rMDD and global deposition of Abeta. Future analyses should assess the longitudinal relationships between peripheral and central biomarkers of immune activation, depression and cerebral Abeta deposition.     

Serum Ghrelin Levels and the Effects of Antidepressants in Major Depressive Disorder and Panic Disorder

Background: Two opposing models for the action of ghrelin in the behavioral responses to stress were recently proposed. Some studies suggest that an increase in ghrelin contributes to the mechanisms responsible for the development of stress-induced depression and anxiety, while others suggest that it helps minimize what otherwise would be more severe manifestations of depression and anxiety following stress. Methods: We measured serum ghrelin levels, Profile of Mood States (POMS) scores and State-Trait Anxiety Inventory scores in nonresponders (treatment-resistant patients; 30) and responders (38) with major depressive disorder (MDD), nonresponders (29) and responders (51) with panic disorder and 97 healthy controls. Results: The ghrelin concentration in nonresponders with MDD was higher than that of responders with MDD and normal controls. The ghrelin concentration in nonresponders with panic disorder was higher than that of normal controls. POMS vigor scores in patients with MDD and panic disorder were significantly decreased compared with those in healthy controls. Other POMS scores in patients with MDD and panic disorder were significantly increased compared with those of healthy controls. Trait and state anxiety of the State-Trait Anxiety Inventory in MDD and panic disorder patients were higher than those in healthy controls. Conclusions: These results indicate that decreased serum ghrelin levels might be associated with antidepressant treatment to confer the maximum therapeutic effect in patients with MDD and panic disorder.     

Electroconvulsive therapy (ECT) in the treatment of postpartum psychosis

Postpartum psychosis is one of the most severe manifestations of postpartum mental illness. A psychiatric emergency, the prompt recognition and treatment of postpartum psychosis is essential in insuring maternal and infant well-being and safety. Here, we review the literature on the phenomenology of postpartum psychosis and the prevalence of use, safety, and efficacy of electroconvulsive therapy as a treatment. Studies were searched using CINAHL, EMBASE, MEDLINE, PsycINFO, and PubMed databases. Based on our review, we argue that for some patients, electroconvulsive therapy should be the treatment of choice.     

Neurocognitive differential diagnosis of dementing diseases: Alzheimer's Dementia, Vascular Dementia, Frontotemporal Dementia, and Major Depressive Disorder

Similarities in presentation of Dementia of Alzheimer's Type, Vascular Dementia, Frontotemporal Dementia, and Major Depressive Disorder, pose differential diagnosis challenges. The current study identifies specific neuropsychological patterns of scores for Dementia of Alzheimer's Type, Vascular Dementia, Frontotemporal Dementia, and Major Depressive Disorder. Neuropsychological domains directly assessed in the study included: immediate memory, delayed memory, confrontational naming, verbal fluency, attention, concentration, and executive functioning. The results reveal specific neuropsychological comparative profiles for Dementia of Alzheimer's Type, Vascular Dementia, Frontotemporal Dementia, and Major Depressive Disorder. The identification of these profiles will assist in the differential diagnosis of these disorders and aid in patient treatment.     

Validity of the Depression-Arkansas (D-ARK) Scale: A Tool for Measuring Major Depressive Disorder

The results of 2 validation studies for an assessment tool designed specifically for quality improvement and outcomes assessment efforts in mental healthcare are presented in this paper. The studies evaluated a new tool to assess the patient outcomes for major depressive disorder following treatment in routine clinical settings called the Depression-Arkansas Scale (D-ARK). Study 1 included 54 patients recruited from 3 hospital-based clinics (2 mental health clinics and 1 primary care clinic). Study 2 includes 827 patients from 5 clinical settings including a university based outpatient clinic, a VA based mental health clinic, and a managed-care program. These 2 very different studies provide preliminary evidence that the D-ARK may be a useful tool for quality improvement efforts in the mental healthcare setting. Specifically, they indicate that the D-ARK has strong validity when compared to 2 different research assessments, the Structured Clinical Interview for DSM-III-R, Patient Edition (SCID-P) and the Inventory to Diagnose Depression (IDD), and compared to clinical assessments using both the clinical diagnosis and a clinician checklist     

The Korean Medication Algorithm for Major Depressive Disorder (KMA-MDD): Report of the Korean Society of Depressive and Bipolar Disorders

Objective. There are many differences in biological characteristics, clinical situations, and medical insurance systems with ethnic groups or countries. The Korean Society of Depressive and Bipolar Disorders decided to develop a Korean treatment algorithm for major depressive disorder. Methods. The Korean Medication Algorithm Project for Major Depressive Disorder (KMAP-MDD) was designed with the following principles: (1) to be an ideal algorithm, (2) to be a Korean algorithm, (3) to be a medication algorithm, (4) to be an evidence-based and formal consensus algorithm. After collecting and reviewing many literature citations and reports by evidence-based rule, we constructed a survey questionnaire for formal consensus of Korean experts. By employing panels of experts to review the evidence and survey results thoroughly, we used evidence-based algorithm development as a component of a formal consensus development process. Results. We developed two algorithms for the KMA-MDD: one for major depressive disorder without psychotic feature and the other for major depressive disorder with psychotic features. Clinical guidelines for the implementation of KMA-MDD were also developed. The KMA-MDD provides specific treatment strategies for each stage. Conclusions. The KMA-MDD is the first Korean algorithm for treatment of major depressive disorder. It is based on evidence which supports the efficacy of each treatment, and it has obtained the consensus of Korean experts. We hope that the KMA-MDD will be good practical tool for clinicians who treat major depressive disorder in Korea.     

A Population-Based Longitudinal Study of Recent Stressful Life Events as Risk Factors for Suicidal Behavior in Major Depressive Disorder

The purpose of this study is to investigate whether the type and number of stressful life events (SLEs) will be associated with suicidal behavior in a 3-year follow-up period in persons with major depressive disorder (MDD). Data came from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a nationally representative longitudinal survey of mental health in non-institutionalized adults in the United States. The survey consisted of two waves: Wave 1 (2001-–2002) and Wave 2 (2004–2005), n = 34,653. Twelve past-year SLEs were assessed at baseline. These SLEs were categorized into the following groups based on previous research: Loss or victimization; Relationship, friendship, or interpersonal stress; Financial stress; and Legal problems. Only respondents with MDD at Wave 1 were included (n = 6,004). Several SLEs were strongly associated with suicide attempts, among which, “serious problems with neighbor, friend, or relative” (adjusted odds ratio [AOR] = 2.21; 95% confidence interval [95% CI]: 1.41, 3.45) and “major financial crisis, bankruptcy, or unable to pay bills” (AOR = 2.31; 95% CI: 1.45, 3.66) were the most robust predictors of suicide attempts even after adjusting for sociodemographic variables and any anxiety, substance use, or personality disorder. People with MDD who had been exposed to certain SLEs are at elevated risk for future suicide attempts, even after accounting for the demographic factors and psychiatric comorbidity.     

Letter and Semantic Fluency in Older Adults: Effects of Mild Depressive Symptoms and Age-Stratified Normative Data

Depression induced cognitive impairment, also referred to as the dementia syndrome of depression or pseudodementia, has been well characterized, yet the extent to which the more common mild depressive symptoms influence cognition has not been well studied. We sought to identify the influence of mild depressive symptoms on verbal fluency performance in a large sample of healthy community dwelling older adults. Letter and semantic fluency testing was conducted on 188 participants (ages 60-92 years) with no known history of neurologic or psychiatric disease. Depressive symptoms were assessed with the Geriatric Depression Scale (GDS). A total of 39 subjects obtained GDS scores consistent with mild depressive symptoms (GDS=10-19), and 149 subjects were identified as not depressed (GDS&lt;10). ANOVA indicated that subjects with mild depressive symptoms performed significantly worse than normal controls on letter fluency (p &lt;.05), but there was no significant difference between the groups on semantic fluency. Analysis of the nondepressed group stratified into young-old, middle-old, and oldest-old revealed a significant decline in semantic (p &lt;.001) but not letter fluency with age. The nondepressed young-old showed the expected advantage for word list generation to semantic as compared to letter categories, yet this pattern was reversed in the older age groups, where letter fluency scores exceeded semantic fluency scores. Our results suggest that the presence of even mild depressive symptoms may confound using letter versus category discrepancies in the differential diagnosis of dementia. Further, our findings suggest that the commonly used strategy of examining letter-semantic fluency discrepancies may not be relevant for individuals of advanced age. Age-stratified normative data for fluency testing in older adults is also provided.