Effect of lamotrigine on depressive symptoms in adult patients with epilepsy

In this investigation, the effects of lamotrigine versus placebo on depressive symptoms in patients with epilepsy were prospectively assessed. This investigation was a secondary analysis of a randomized, double-blind, placebo-controlled, parallel-group study in which adult patients received adjunctive lamotrigine (n=32) or placebo (n=38) for a 7-week dose escalation phase, followed by a 12-week maintenance phase, for primary generalized tonic-clonic (PGTC) seizures. Mood symptoms were assessed with the Beck Depression Inventory, second edition (BDI-II), the Profile of Mood States (POMS), and the Cornell Dysthymia Rating Scale-Self-Report (CDRS). Mean (SD) BDI-II scores at screening reflected mild depressive symptoms and were similar between groups (lamotrigine 18.3 (12.1), placebo 16.8 (12.0)). At the end of the maintenance phase, mean (SD) improvement from baseline was greater with lamotrigine than placebo with respect to BDI-II score (lamotrigine 8.9 (7.6), placebo 1.7 (8.5), P=0.01) and POMS total score (lamotrigine 32.0 (30.4), placebo 6.5 (32.3), P=0.03) and numerically greater with lamotrigine than placebo for CDRS score (lamotrigine 7.3 (7.8), placebo 4.1 (13.9), P=0.50). Among the subset of patients with at least mild depression (BDI-II score10), mean improvement from baseline was numerically, but not statistically significantly, greater with lamotrigine (11.5, n=13) than placebo (3.1, n=18) (P=0.054). Median percentage reductions in seizure frequency were significantly greater with lamotrigine than placebo during the escalation phase, the maintenance phase, and the escalation and maintenance phases combined for PGTC seizures and all generalized seizures. However, improvement in seizure frequency was not correlated with improvement in mood (r=0.1, P=ns). Compared with placebo, lamotrigine improved mood symptoms independently of seizure reduction in patients with generalized seizures. Lamotrigine may be useful in treating patients with epilepsy and comorbid depressive symptoms.     

Comorbid attention-deficit/hyperactivity disorder in adult psychiatric outpatients with depressive or anxiety disorders

Background. There are very few studies reporting on the prevalence and the contribution of not previously diagnosed ADHD in the clinical picture of other psychiatric disorders. The aim of our study is to determine the prevalence and clinical correlates of comorbid attention deficit/hyperactivity disorder (ADHD) in adult psychiatric outpatients with depressive or anxiety disorders. Methods. During a 6-month period, 114 outpatients with depressive or anxiety disorders were evaluated for ADHD diagnosis. Assessment included interviews with both patient and relatives/friends and the use of a daily diary. Moreover, the patients completed the self-report scales Beck Depression Inventory (BDI), Spielberger's Anxiety Inventory (STAI), and the Symptom Checklist-90-R Rating Scale (SCL-90-R). Results. A total of 22 out of 114 patients (19.3%) received an ADHD diagnosis for the first time in their life. Comorbid ADHD compared to non ADHD patients scored significantly higher (p < 0.05) for depression (BDI), state and trait anxiety (STAI) and in the following SCL-90-R factors: Positive Symptoms Distressing Index, Positive Symptoms Index, Somatization, Obsessive Compulsive, Depression, Anxiety, and Hostility. Conclusions. ADHD might go unrecognized among psychiatric outpatients. Patients with depressive or anxiety disorder reporting more severe symptomatology should be carefully screened for possible comorbid adult ADHD.     

Risk of extremity fractures in adult outpatients with epilepsy

PURPOSE: To study the incidence of extremity fractures in a group of adult patients with epilepsy attending an outpatient clinic compared with the incidence of fractures in the general population in the same geographic area. METHODS: We selected 177 consecutive adult patients with epilepsy attending the outpatient clinic at the Department of Neurology at Karolinska Hospital in Stockholm in 1995. This study population was matched with an Injury Registry to identify those epilepsy patients who during 1991 through 1995 attended the emergency department for an extremity fracture. The observed number of fractures in the epilepsy group was compared with the corresponding number of expected cases based on regional fracture rates. Relative-risk estimates for fractures were calculated with respect to the duration of epilepsy, mono- or polytherapy, and history of tonic-clonic seizures. RESULTS: Twenty (11%) of 177 patients sustained 23 fractures that prompted a visit to the emergency department. The incidence of fractures in the epilepsy patients was 23.8/1,000 person-years. The overall Standardized Morbidity Ratio (SMR) was 2.39 (95% CI, 1.52-3.59). A significantly higher risk for fractures was thus found in patients with epilepsy. Risk factors were age 45 years or older, male sex, and occurrence of generalized seizures. It also was found that the relative risk of fractures was higher during the first and second year compared with >or=5 years after diagnosis (RR, 3.71; 95% CI, 1.20-11.48). CONCLUSIONS: Our results highlight the risk of fractures in outpatients with epilepsy. In this patient group, 43% of the fractures were definitely or possibly seizure related. Males 45 years or older are a particular risk group. Special attention is required for this group of patients who are at higher risk for fractures. The risk is apparently higher in the first 2 years after diagnosis, although potential bias in ascertainment of fracture incidents in our study may have underestimated the long-term risk for fractures.     

抑郁症患者首次门诊误诊分析

目的:探讨影响抑郁症首次门诊诊断的相关因素.方法:调查111例经抑郁专科门诊确诊的抑郁症患者按首次诊断分误诊组与确诊组,比较两组的一般资料、临床症状、伴随躯体疾病及诊治医师情况,分析影响诊断的主要因素.结果:111例患者中首次误诊者60例,占54.1%;精神病性症状,焦虑,强迫,伴随躯体疾病及与诊治医师年资在误诊组与确诊组组间差异存在显著性(P＜0.05).结论:精神症状、伴随躯体疾病与医师经验是抑郁症患者首次门诊确诊的主要影响因素.     

Predictors of depressive symptoms at hospital discharge in patients with major depressive disorder

Abstract

Objective. Often patients with major depressive disorder (MDD) leave the hospital with continued significant symptomatology. This study sought to evaluate demographic, clinical, and psychosocial predictors of the presence of clinically significant depressive symptoms, defined as a Modified Hamilton Rating Scale for Depression score of ≥ 14, immediately following hospitalization for MDD. Methods. The study enrolled 135 patients with MDD as part of a larger clinical trial investigating the efficacy of post-hospitalization pharmacologic and psychosocial treatments for depressed inpatients. Structured clinical interview and self-report data were available from 126 patients at hospital admission and discharge. Results. Despite the significant decreases in depressive symptoms over the course of hospitalization, 91 (72%) displayed clinically significant depressive symptoms at discharge. Multivariate logistic regression analysis revealed that female sex, earlier age of onset, and poorer social adjustment were unique predictors of symptom outcome. Conclusions. Results suggest that a large proportion of patients leave the hospital with continued significant symptomatology, and the presence of such symptoms following hospitalization for MDD is likely to be explained by a combination of factors.     

Lamotrigine in patients with epilepsy and comorbid depressive symptoms

PurposeThis open-label study evaluated the antidepressant qualities of lamotrigine (LTG) in people with epilepsy.MethodsEligible patients exhibited low to moderate depressive symptoms and required a change in antiepileptic drug (AED) therapy, but were excluded if they had a major depressive disorder (MDD). Lamotrigine was added onto a stable AED regimen, and self-report instruments were administered to evaluate changes in mood states. Evaluations were conducted at baseline, at the end of 19 weeks of adjunctive treatment, and 36 weeks following conversion to monotherapy.ResultsOne hundred and fifty-eight patients with epilepsy participated; 96 patients completed adjunctive treatment, and 66 patients completed monotherapy. Intent-to-treat analyses for all instruments showed improvement in depression scores after adjunctive LTG treatment. Improvement was maintained for those converted to monotherapy.ConclusionsThese data suggest that LTG may have antidepressant activity for patients with epilepsy and comorbid low to moderate depressive symptoms, and warrant a randomized controlled trial for validation.     

A comparison of fluoxetine and imipramine in the treatment of outpatients with major depressive disorder

A double-blind clinical trial was undertaken to evaluate the clinical efficacy and safety of fluoxetine compared with imipramine in the treatment of 59 outpatients suffering from major depressive disorder. The mean scores of all depression rating scales showed that the drugs had comparable efficacy. The side effect profile of imipramine was found to be mainly anticholinergic, which was not the case for fluoxetine, where it was mainly found to be gastrointestinal, such as nausea and diarrhoea. In both groups the total number of adverse events reported were the same. Fluoxetine treatment resulted in weight loss, whereas imipramine treatment resulted in a slight but significant weight increase.     

Treating depressive symptoms in schoolchildren

Abstract. Although studies on sub-threshold depression in childhood and adolescence havedemonstrated an at risk profile that merits further attention, only few investigators examined the impact of therapy with these children. In this study, twenty elementary schoolchildren (aged 10–12) with moderate depressive symptoms were randomly assigned to an eighteen-session cognitive-behavioural treatment programme or to a waiting list (WL) control group (= Study 1). The key components of the programme Taking Action used in the study were: affective education, problem-solving, cognitive restructuring and engaging in enjoyable activities. Child self-reports and parent reports were used to evaluate the outcome. Paired ttests comparing the 4-months follow-up results with baseline measurements, revealed a significant improvement on the Children Depression Inventory and on the Self-Perception Profile for Children, but only in the treatment group. Afterwards, the WL control group was treated as well. All children were followed in a long-term follow-up study (= Study 2). Analyses at the 12 month stage of the follow-up study showed a further improvement of the scores on the Self-Perception Profile. Moreover, a significant decrease was found on the Children Depression Inventory, the State-Trait Anxiety Inventory and the Child Behaviour Checklist parent measure. It was concluded that the protocol is suitable for European children. The most remarkable findings in this pilot study are discussed.     

Diurnal mood variation in outpatients with major depressive disorder

Background: Diurnal mood variation (DMV) with early morning worsening is considered a classic symptom of melancholic features of major depressive disorder (MDD) according to the Diagnostic and Statistical Manual. This report used data from the sequenced treatment alternatives to relieve depression study to determine whether DMV was associated with treatment outcome to citalopram. Methods: Two thousand eight hundred and seventy‐five outpatients with nonpsychotic MDD were evaluated during a 14‐week trial of the selective serotonin reuptake inhibitor citalopram. Participants were divided into three groups: those with “classic” DMV (early morning worsening), those with any form of DMV (morning, afternoon, or evening worsening), and those with no DMV. Participants with classic DMV and those with any form of DMV were compared to those with no DMV in terms of baseline sociodemographic and clinical characteristics, treatment outcomes, and treatment features. Results: Minor baseline clinical characteristics and treatment feature differences were found between participants with and without DMV. Participants with classic morning DMV had slightly higher response rates than those without DMV. However, no differences were found in response or remission between either group of participants with DMV and those with no DMV. Conclusion: DMV does not appear to be associated with a unique prominent pattern of response to selective serotonin reuptake inhibitor treatment in patients with depression, and does not appear to be a serotonergically modulated process. Further evaluation is necessary to determine if this relationship holds true for dopaminergic and noradrenergic antidepressant agents, such as dual‐acting agents or antidepressant medication combinations. Depression and Anxiety, 2009. © 2009 Wiley‐Liss, Inc.     

The impact of self-reported depressive symptoms on memory function in neurological outpatients

OBJECTIVES: To examine the effect of self-reported depressive symptoms on memory function in a non-psychiatric, non-litigation outpatient sample and to identify which memory tests may be most susceptible for depression-related decline. METHODS: Self-reported depressive symptoms were measured by the Beck Depression Inventory (BDI-II) and memory function was assessed using a wide range of neuropsychological memory tests (digit span, word-list learning, visuospatial learning, incidental memory, story recall). Patients who visited the neurological outpatients clinic and were referred for a neuropsychological examination were included (N=50). RESULTS: Correlation analyses showed that the BDI-II was significantly correlated with immediate story recall, delayed verbal recognition and the digit span. Furthermore, patients with mild or moderate-to-severe depressive symptoms performed worse than non-depressed patients on immediate story recall, but not on any of the other memory tests. DISCUSSION: Memory performance is only minimally disrupted in neurological outpatients with depressive symptoms compared to non-depressed outpatients. These results are discussed in relation to limited mental effort and weak encoding in patients with self-reported depressive symptoms.     

抑郁症门诊患者中未识别出的双相障碍者的临床特征（英文）

背景双相障碍常未被识别或被误诊为单相抑郁。明确未被识别或被误诊的双相障碍者的临床特征有助于减少错误分类。目的调查门诊抑郁症患者中未被识别的双相障碍者的比例,并分析未被识别的双相障碍者的临床特征。方法使用32项轻躁狂症状清单（Hypomania Checklist-32,HCL-32）、心境障碍问卷（Mood Disorder Questionnaire,MDQ）和简明国际神经精神访谈（Mini International Neuropsychiatric Interview,MINI）对目前被诊断为抑郁症的100例门诊患者进行调查。对被重新诊断为双相障碍与仍然被诊断为抑郁症的患者的临床特征进行比较分析。结果共有29例（29%）抑郁症门诊患者被诊断为双相障碍;其中双相Ⅰ型6例,双相Ⅱ型23例。与未更改诊断的抑郁症者相比,被重新诊断为双相障碍者年龄轻、起病早、发病次数多、受教育程度高,多为复发性抑郁且多伴精神病性症状。多因素Logistic回归分析显示年龄（OR=0.55,95%CI=0.34~0.89）和精神病性症状（OR=9.12,95%CI=1.56~53.26）是双相障碍的独立危险因素。结论在门诊抑郁症患者中未被识别的双相障碍比例较高,尤其是双相Ⅱ型。与单相抑郁相比,诊断为抑郁症而为未被识别的双相障碍者年龄轻,更可能伴有精神病性症状。     

Efficacy of quetiapine and risperidone against depressive symptoms in outpatients with psychosis

BACKGROUND: The treatment of psychotic symptoms in patients with mood disorders is a complex challenge. Antipsychotic medications in these individuals may be associated with extrapyramidal symptoms (EPS), worsening of depression, and functional impairment. Atypical antipsychotics such as quetiapine and risperidone are associated with a decreased incidence of adverse events such as EPS. The objective of this study was to compare the efficacy and tolerability of quetiapine and risperidone for the treatment of depressive symptoms in outpatients with psychosis. METHOD: In this 4-month, multicenter, open-label trial, patients were randomly assigned in a 3:1 ratio of quetiapine to risperidone, and both drugs were flexibly dosed. Eligible patients had psychoses and demonstrated 1 of several DSM-IV diagnoses, including schizoaffective disorder, bipolar I disorder, major depressive disorder, delusional disorder, Alzheimer's dementia, schizophreniform disorder, vascular dementia, and substance abuse dementia. Patients were classified as mood disordered if they had bipolar disorder, major depressive disorder, or schizoaffective disorder. Efficacy was assessed using the Positive and Negative Syndrome Scale and the Clinical Global Impressions scale. The Hamilton Rating Scale for Depression (HAM-D) was used to assess the level of depressive symptoms. The primary tolerability assessment was presence or absence of substantial EPS, defined as EPS severe enough to require an alteration in treatment. RESULTS: A total of 554 patients were randomly assigned to quetiapine and 175 to risperidone. Mean doses at 16 weeks were 318 mg for quetiapine and 4.4 mg for risperidone. Although both agents produced improvements in mean HAM-D scores, quetiapine produced a greater improvement than risperidone in all patients (p =.0015). Within the mood-diagnosed population, incidences of both substantial EPS (p =.001) and at least moderate EPS (p =.0373) occurred significantly less frequently among patients taking quetiapine. For patients with non-mood diagnoses, incidences of substantial EPS were fewer for patients taking quetiapine than for those taking risperidone (p =.062); however, this was not statistically significant. CONCLUSION: These results suggest that quetiapine may be a useful agent in the management of depressive symptoms in patients with psychosis.     

Atypical depressive symptoms and clusters in unipolar and bipolar depression

In order to examine differences in the atypical symptoms of depression between unipolar and bipolar patients, we studied 109 depressed patients (79 unipolar and 30 bipolar subjects) diagnosed with DSM-IV criteria. Patients were assessed using the Atypical Depression Diagnostic Scale (ADDS), a semi-structured interview that rates mood reactivity and other atypical depressive symptoms. Although atypical depression was common in this sample (28% of cases with definite atypical depression), no differences were found between the unipolar and bipolar patients in either the atypical symptom profile or the prevalence of an atypical depression diagnosis. The interrelationships between the atypical symptoms were also examined using a hierarchical cluster analysis. A five-cluster solution maximized differences between groups, with results suggesting that atypical depression may be a heterogeneous diagnosis.     

The course of depressive symptoms in early Parkinson's disease

Little is known about the course of depressive symptoms in Parkinson's disease (PD). We studied the course of clinically significant depressive symptoms using data from two clinical trials that followed 413 early, untreated PD subjects for 12 to 18 months. We measured depressive symptoms with the 15‐item geriatric depression scale (GDS‐15); a score of ≥5 indicates clinically significant depressive symptoms. We used a time‐dependent Cox model to examine the association between demographic variables, PD severity, and medication use on the time to resolution of depressive symptoms. One hundred fourteen of 413 (27.6%) subjects were screened positive for depression during the study, with a median GDS‐15 score of 6, indicating mild symptoms. Within 6 months, 47% of subjects experienced remission of clinically significant depressive symptoms. Subjects with mild depressive symptoms were more likely to develop moderate to severe depressive symptoms (GDS ≥ 10) than those without prior symptoms (relative risk = 6.16). Increasing severity of depressive symptoms, older age, and longer PD duration predicted a lower likelihood of symptom resolution (hazard ratios 0.83–0.92). Mild depressive symptoms have a variable course, with remission and development of more sustained and severe symptoms occurring over time. More severe depressive symptoms may herald a protracted course. © 2009 Movement Disorder Society     

抑郁症患者的躯体症状

目的:了解抑郁症患者的躯体症状特征。方法:采用自制调查表对符合中国精神障碍分类与诊断标准第3版抑郁发作的119例门诊及住院患者进行调查。根据汉密尔顿抑郁量表(HAMD)评分,将119例患者分为轻度、重度抑郁症两组,比较两组的一般资料及躯体症状。结果:两组的一般资料差异无显著性,而重度抑郁组躯体症状与轻度抑郁组差异显著。结论:抑郁症的躯体症状非常突出,应引起足够重视。     

Major depressive episodes with hypomanic symptoms are common among depressed outpatients

Depressive mixed states (major depressive episodes [MDE] with some hypomanic symptoms) are not classified in DSM-IV. The aim of the present study was to determine the prevalence of depressive mixed states in depressed outpatients, and to compare bipolar II with unipolar depressive mixed states. Seventy consecutive bipolar II and unipolar depressed outpatients were interviewed using the DSM-IV Structured Clinical Interview (SCID). At least one hypomanic symptom was present in 90% of patients, and three or more in 28.5%. Symptoms of depressive mixed states included irritable mood, distractibility, racing thoughts, and increased talking. Bipolar II subjects had more concurrent hypomanic symptoms (three or more in 48.7% v 3.2%, P = 0.000). Depressive mixed states with three or more hypomanic symptoms correctly classified 70.0% of bipolar II subjects. These findings have important treatment implications, as antidepressants may worsen the symptoms of depressive mixed states, and mood stabilizers can be useful.     

Inflammatory markers in women with postpartum depressive symptoms

Postpartum depression (PPD) is a devastating disorder affecting not only more than 10% of all women giving birth, but also the baby, the family, and the society. Compiling evidence suggests the involvement of the immune system in the pathophysiology of major depression; yet, the immune response in perinatal depression is not as well studied. The aim of this study was to investigate the alterations in peripheral levels of inflammatory biomarkers in 169 Swedish women with and without depressive symptoms according to the Edinburgh postnatal depression scale or the M.I.N.I neuropsychiatric interview at eight weeks postpartum. Among the 70 markers analyzed with multiplex proximity extension assay, five were significantly elevated in women with postpartum depressive symptoms in the adjusted LASSO logistic regression analysis: Tumor necrosis factor ligand superfamily member (TRANCE) (OR-per 1 SD increase = 1.20), Hepatocyte growth factor (HGF) (OR = 1.17) Interleukin (IL)-18 (OR = 1.06), Fibroblast growth factor 23 (FGF-23) (OR = 1.25), and C-X-C motif chemokine 1 (CXCL1) (OR 1.11). These results indicate that women with PPD have elevated levels of some inflammatory biomarkers. It is, therefore, plausible that PPD is associated with a compromised adaptability of the immune system.