Duloxetine in treatment of anxiety symptoms associated with depression

Most patients with major depressive disorder (MDD) have symptoms of anxiety associated with their depression. Duloxetine, a potent and balanced dual serotonin and norepinephrine reuptake inhibitor, is effective in the treatmentof depression. We investigated its effects in treating the symptoms of anxiety in depressed patients. This investigation includes all the placebo-controlled studies of duloxetine in MDD but focuses on four trials in which duloxetine was superior to placebo on the primary outcome measure of the 17-item Hamilton Depression Rating Scale (HAMD(17)) total score. Studies 1 and 2 included duloxetine at 60 mg/d (the recommended starting and therapeutic dose) and placebo. Study 3 included duloxetine 120 mg/d (administered as 60 mg b.i.d.), fluoxetine 20 mg/d, and placebo. Study 4 included duloxetine 40 mg/d (administered as 20 mg b.i.d.), duloxetine 80 mg/d (administered as 40 mg b.i.d.), paroxetine 20 mg/d, and placebo. Anxiety was assessed in all studies using the HAMD anxiety/somatization subfactor and the anxiety-psychic item (HAMD Item 10). Studies 3 and 4 also included the Hamilton Anxiety Rating Scale (HAMA). Across the four studies, duloxetine at doses of >/=60 mg was compared with placebo on 10 outcomes and with either paroxetine or fluoxetine on 6 outcomes. In 8 comparisons, mean improvement for duloxetine was significantly greater than placebo at the last study visit and/or across all study visits. In 3 comparisons, the mean improvement for duloxetine was significantly greater than paroxetine or fluoxetine. In these studies, duloxetine provided rapid relief of anxiety symptoms associated with depression. Previous reports have summarized duloxetine's efficacy in treating the core emotional symptoms and painful physical symptoms associated with depression. Duloxetine's efficacy in treating a broad spectrum of symptoms associated with depression, including mood, anxiety, and painful physical symptoms, may be attributed to dual reuptake inhibition of both serotonin and norepinephrine. Efficacy in these three key symptom domains may in turn explain the high probabilities of remission (43-57%) observed in these studies.     

Escitalopram in the treatment of anxiety symptoms associated with depression

Most patients with depression have symptoms of anxiety associated with their illness. Our aim in this study was to investigate the efficacy of escitalopram, a proven antidepressant, on symptoms of anxiety in patients with major depressive disorder (MDD). Data from five placebo-controlled escitalopram studies in MDD were analyzed. Three of the studies also included a comparison with citalopram. In all studies, anxiety was assessed using the Inner Tension item (item 3) of the Montgomery-Asberg Depression Rating Scale (MADRS). In three studies, anxiety symptoms were also specifically assessed, either continuously over time or at baseline and end point, by using the Hamilton Rating Scale for Anxiety (HAM-A), the Anxious Mood item of the HAM-A (item 1), the Psychic Anxiety subscale of the HAM-A (items 1-6 and 14), the Anxiety Psychic item (item 10) of the Hamilton Rating Scale for Depression (HAM-D-24), and the Anxiety/Somatization subfactor (items 10-13, 15, and 17) of the HAM-D-24. Escitalopram was significantly superior to placebo in all comparisons. Citalopram was also consistently better than placebo in all comparisons, except in the HAM-D-24 Anxiety/Somatization subfactor. In some comparisons with placebo, escitalopram showed a significantly earlier onset of action or an earlier separation. Escitalopram was significantly more effective compared to placebo in treating both anxiety symptoms and the entire depression in the total depressive population, as well as in depressive patients with a high degree of anxiety.     

Effect of levetiracetam on depression and anxiety in adult epileptic patients

BACKGROUND: Interictal depression is common in patients with epilepsy and it significantly impacts quality of life. Some studies indicate that levetiracetam (LEV) may have mood stabilizing properties. METHODS: Twenty-five adults with uncontrolled partial seizures and concomitant depressive symptoms were treated with LEV. Patients were evaluated for depression and anxiety with several psychometric measures, including: Montgomery and Asberg Depression Rating Scale (MADRS), Hamilton Depression Rating Scale (HDRS), Zung Self-rating Scale for Depression (Z-SDS), Hamilton Anxiety Rating Scale (HARS), Zung Self-rating Scale for Anxiety (Z-SAS). RESULTS: Evaluations after 5 weeks and after 3 months of LEV treatment demonstrated significant improvement in depression and anxiety. CONCLUSIONS: This uncontrolled study suggests that treatment with LEV may also improve depression and anxiety in patients with partial seizures. However, the sample of patients is limited and the possibility of a placebo effect cannot be excluded. These findings must be considered preliminary and should be replicated under placebo-controlled conditions.     

The effect of lamotrigine on platelet monoamine oxidase type B activity in patients with bipolar depression

Lamotrigine is an anticonvulsant drug effective in the treatment of epilepsy and bipolar depression. Preclinical data showed that lamotrigine inhibited monoamine oxidase (MAO) activity in vitro. The aim of the study was to determine the effects of 6-weeks lamotrigine treatment on platelet MAO type B (MAO-B) activity in patient with bipolar depression. The study included 26 female patients with bipolar I disorder in depressive episode (DSM-IV criteria, Hamilton Depression Rating Scale (HAMD) and Young Mania Rating Scale). Platelet MAO-B activity was determined spectrofluorimetrically before and after 6 weeks of the treatment with a relatively low dose of lamotrigine (100 mg/day). Six weeks of treatment with lamotrigine significantly decreased platelet MAO-B activity in bipolar depressed patients. This inhibitory effect was not related to smoking status and was independent of the treatment combinations (lamotrigine alone or in combination with either lithium or antipsychotics). Lamotrigine treatment induced a decrease in total HAMD scores in bipolar depressed patients, which was not significantly correlated with reduction of platelet MAO-B activity. These findings provide in vivo insight of lamotrigine effect on platelet MAO-B activity in patients with bipolar depression. Its in vivo MAO-B inhibiting effect might have contributed in part to its antidepressant activity.     

Sensitivity of the six-item Hamilton Depression Rating Scale

We studied the sensitivity in detecting changes of the 6-item version of the original 17-item Hamilton Depression Rating Scale (HAM-D) and compared it with the more widely used versions among 164 depressed outpatients with and without atypical features before and after treatment with fluoxetine. The 6-item HAM-D was shown to be as sensitive as the 17-, 21-and 24-item versions of this scale. In addition, the different versions of the HAM-D were strongly correlated with each other at baseline and at the endpoint. It appears that the 6-item version of the HAM-D allows the assessment of severity of depression with comparable sensitivity to the standard and more elaborate versions of the same scale.     

Clinical response of quetiapine in rapid cycling manic bipolar patients and lactate level changes in proton magnetic resonance spectroscopy

The aim of the current study was to evaluate the relationship between quetiapine's effect on the improvement of mood symptoms in bipolar patients and brain metabolite level changes as measured by proton magnetic resonance spectroscopy ((1)H-MRS). Rapid cycling bipolar patients in the manic state were recruited and treated with quetiapine for 12 weeks. Clinical assessment was performed using the Young Mania Rating Scale (YMRS), the 17-item Hamilton Depression Rating Scale (HDRS) and the Clinical Global Impression-Severity scale (CGI-S) at baseline and weekly intervals during the 12-week period. In order to evaluate metabolite level changes over time, (1)H-MRS scans were acquired at baseline and week 12. There were significant reductions in YMRS scores (by 43.0%), HDRS scores (by 27.5%) and CGI-S score (by 44.6%) over the 12 week-period. Lactate levels significantly decreased over the 12-week study period (22.4%). This change in lactate levels was more prominent in quetiapine responders than in non-responders. Additionally, there was a positive correlation between changes in lactate levels and those in YMRS scores (r=0.52, p=0.003). Our findings suggest that quetiapine's antimanic and antidepressant efficacy in patients with rapid cycling bipolar disorder may potentially be related to decreased lactate levels in frontal regions of the brain.     

Assessment of depression in Parkinson's disease: The contribution of somatic symptoms to the clinimetric performance of the Hamilton and Montgomery–Åsberg rating scales

Objective

To assess the influence of somatic symptoms of the Hamilton Depression Rating Scale (HAMD) and Montgomery–Åsberg Depression Rating Scale (MADRS) on the clinimetric performance of these scales in patients with Parkinson's disease (PD).

Methods

A total of 224 patients underwent a protocolized mental status examination, consisting of the Structured Clinical Interview for DSM-IV depressive disorder (SCID-D), as well as the HAMD and MADRS. Sensitivity, specificity, positive, and negative predictive values for a range of cut-off scores were calculated for both rating scales and for modified versions of these scales in which all somatic items were eliminated. In addition, receiver operating characteristic (ROC) curves were obtained for both the modified and unmodified scales.

Results

Elimination of the somatic items of depression from the HAMD and MADRS resulted in a reduced specificity of both the HAMD and the MADRS, and an increased sensitivity of the MADRS.

Conclusion

The authors recommend the full version of the HAMD and MADRS if used for diagnostic purposes; for screening purposes, the abbreviated version without somatic items can be used. Additional advantages of using full rating scales, with somatic items included, are that these provide more information on the severity of depression and allow for easier comparison across studies.     

Depression and anxiety in amyotrophic lateral sclerosis: Correlations between the distress of patients and caregivers

Introduction: Depression and anxiety are common in amyotrophic lateral sclerosis (ALS) patients and caregivers. Methods: In this study we investigated 93 ALS patients and their 93 caregivers. Depression and anxiety were quantified by the Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale, respectively. Results: Very strong correlations between depression and anxiety were found among patients and their caregivers. The severity of depression and anxiety of patients correlated moderately with that of their caregivers. No correlations were found between the severity of depression and anxiety and ALS Functional Rating Scale–Revised (ALSFRS‐R) score or for disease duration among patients and caregivers. However, severity of depression and anxiety in caregivers correlated with their age. Conclusions: Depression and anxiety in ALS patients and their caregivers were associated closely with each other but not with physical disability or disease duration in our Chinese population. Muscle Nerve 51: 353–357, 2015     

HF-rTMS treatment decreases psychomotor retardation in medication-resistant melancholic depression

Repetitive Transcranial Magnetic Stimulation (rTMS) applied to the left dorsolateral prefrontal cortex (DLPFC) might be a promising treatment strategy for depression. As one of the key features of melancholic depression is disturbances in psychomotor activity, we wanted to evaluate whether HF-rTMS treatment could influence psychomotor symptoms. Twenty antidepressant-free unipolar melancholic depressed patients, all at least stage III medication-resistant, were studied. All were treated with 10 sessions of High-Frequency (HF)-rTMS applied to the left dorsolateral prefrontal cortex (DLPFC) under MRI guidance. Forty percent of the patients showed a reduction of at least 50% on their initial 17-item Hamilton Depression Rating Score (HDRS) scale and were defined as clinical responders. Regardless of clinical outcome HF-rTMS treatment resulted in significant decreases on the Depressive Retardation Rating Scale (DRRS) scores. Although this was an open study in a relatively small sample, our results suggest that HF-rTMS might act on the ‘psychomotor’ level and these findings could add some further information as to why this kind of treatment can be beneficial for severely depressed patients of the melancholic subtype.     

未用药抑郁症自杀者的临床特征与HPA轴功能分析

目的探讨首发未用药的抑郁症自杀者与抑郁症非自杀者的临床特征和下丘脑—垂体—肾上腺轴功能状况。方法对112例首次发作未用药的抑郁症患者,按是否存在自杀(含自杀观念或行为)分为抑郁症自杀组(49例)和抑郁症非自杀组(63例),采用自编问卷调查患者社会人口学资料和早期抑郁发作的临床特征,包括首发年龄、抑郁程度、强迫和焦虑症状、有无自杀观念或行为等,患者治疗前均进行17项汉密尔顿抑郁量表(17-item Hamilton depression scale,HAMD-l7)、汉密尔顿焦虑量表(Hamilton anxiety scale,HAMA)、Yale-Brown强迫量表(Yale-Brown obsessive compulsive scale,Y-BOCS)和自杀评估量表评定,并采用电化学发光法检测血清皮质醇(cortisol,CORT)和促肾上腺素皮质激素(adrenocorticotropic hormone,ACTH)水平。结果两组间就诊年龄、首发年龄、病程均无统计学差异(P0.05)。早期临床症状中,仅见抑郁症自杀组绝望感和性欲下降多于抑郁症非自杀组(P0.05)。抑郁症自杀组HAMD总分及认知障碍因子分和绝望感因子分高于抑郁症非自杀组(P0.01);HAMA总分、Y-BOCS总分和CORT与ACTH水平在两组间差异均无统计学意义(P0.05)。抑郁症自杀组自杀得分与早期临床特征、各量表总分、CORT和ACTH水平的相关性均无统计学意义(P0.05)。结论抑郁症自杀者相对无自杀者早期症状中性欲下降更明显,且认知障碍和绝望感等抑郁症状的程度更重。但早期临床特征和HPA轴功能状况尚不能为抑郁症患者发生自杀观念或行为提供佐证。     

Hjernebeskadigelse og sexuel abnormitet En oversigt og et tilfælde

Abstract

Background: Rating scales used to assess the severity of depression e.g. the Hamilton Depression Rating Scale 17-item (HDRS-17) partly rely on the patient's subjective experience and reporting. Such subjective measures tend to have low reliability and adding objective measures to complement the assessment of depression severity would be a major step forward. Aims: To investigate correlations between electronic monitoring of psychomotor activity and severity of depression according to HDRS-17. Methods: A total of 36 patients with unipolar disorder (n = 18) or bipolar disorder (n = 18) and 31 healthy control persons aged 18–60 years were included. Psychomotor activity was measured using a combined heart rate and movement sensor device (Actiheart) for 3 consecutive days, 24 h a day. Results: We found that sleeping heart rate (beats/min) correlated with HDRS-17 in both patients with unipolar disorder and bipolar disorder (unadjusted model: B = 0.46, 95% CI 0.037–0.89, P = 0.034). In contrast, correlations between activity energy expenditure (kJ/kg/day), cardio-respiratory fitness (mlO₂/min/kg) and HDRS-17 were non-significant. Conclusions: These results suggest that measuring sleeping heart rate in non-experimental daily life could be an objective supplementary method to measure the severity of depression and perhaps indicate presence of insomnia.     

Association between serotonin-related gene polymorphisms and suicidal behavior in depressive patients

BACKGROUND: Several studies have suggested that there is a substantial genetic contribution to suicidal behavior. Genes encoding proteins involved in serotonergic transmission are major candidates in association studies of suicidal behavior. In this study, we aimed to investigate the 5-HT2A receptor (5HTR2A) and tryptophan hydroxylase (TPH) genes for association with suicidal behavior in depressive patients. METHODS: Patients with major depression who had recently attempted suicide (n=191) and control subjects (n=193) were genotyped for 5HTR2A 102T/C, and TPH 218A/C. The lethality of the suicide attempt was measured using the Risk-Rescue Rating (RRR) and Lethality Suicide Attempt Rating Scale (LSARS). The severity of depression was measured using the Hamilton Depression Rating Scale (HDRS). RESULTS: There were no significant differences in the genotype distributions or allelic frequencies in the two serotonergic polymorphisms between suicide attempters and normal controls. None of the two serotonergic polymorphisms was correlated with lethality. CONCLUSIONS: We concluded that these polymorphisms may not be associated with susceptibility to suicidal behavior in our Korean population. Our results were in line with most previous studies. More work is needed to replicate these findings. Our future studies aim at identifying other genetic associations.     

CLINICAL PREDICTORS OF SOMATIC AND PSYCHOLOGICAL SYMPTOMS OF DEPRESSION IN ALZHEIMER'S DISEASE

The Hamilton Rating Scale for Depression was employed to assess the severity of somatic and psychological symptoms of depression in 42 outpatients with dementia of the Alzheimer type. The severity of somatic symptoms increased in the more severe stages of dementia whereas the severity of psychological symptoms did not vary. Psychological symptoms were more severe in female patients and in patients with a better awareness of cognitive decline. In contrast, the degree of cognitive dysfunction was the only significant predictor of the severity of somatic symptoms. These results suggest that, in Alzheimer's disease, somatic symptoms are secondary to dementia rather than manifestations of a coexistent depressive disorder and point to the limited value of the Hamilton scale for detecting depression in demented patients.     

Comparative analysis of observer depression scales

The Hamilton Depression Scale (HAMD), Bech Rafaelsen Melancholia Scale (BRMS) and Montgomery Asberg Depression Rating Scale (MADRS) are analyzed according to mean discriminatory power, internal consistency, homogeneity and transferability. The analysis was done separately in different samples of patients with depressive syndromes: a) operationally defined depressive syndrome; b) Major Depressive Disorder (RDC); c) Major Depressive Disorder, endogenous type (RDC). BRMS and MADRS were superior to HAMD in all evaluated aspects. Further, the BRMS was superior to MADRS according to the criteria of homogeneity and transferability.     

Persistent cognitive impairment in depression: the role of psychopathology and altered hypothalamic-pituitary-adrenocortical (HPA) system regulation.

BACKGROUND: Dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) system and cognitive impairment are consistent findings in depression. This study examines the associations between HPA system regulation, cognitive functioning, and psychopathology in depressed inpatients on admission and at discharge. METHODS: The HPA system dysregulation was evaluated with the dexamethasone (DEX)/corticotropin-releasing hormone (CRH) test. Cognitive assessment included speed of information processing, divided and selective attention, as well as short-term and working memory. Psychopathology was evaluated with the Hamilton Rating Scale for Depression (HAMD). Data from 75 depressed inpatients are reported, 51 (68%) of them achieved remission. RESULTS: Despite a significant reduction of depressive symptoms between admission and discharge, a high rate of patients remained cognitively impaired. Selective attention improved significantly in remitters and nonremitters, while speed of information processing increased only in remitters. The cortisol response to the DEX/CRH test decreased significantly only in remitters, which was uncorrelated with cognitive performance. In nonremitters, severity of depression was significantly correlated with information processing time while improvement in short-term memory was negatively associated with the cortisol response at discharge. CONCLUSIONS: Our data support the assumption that psychopathological symptoms and the HPA system dysregulation can be dissociated in their impact on cognitive functioning in depressed patients.     

FACTOR STRUCTURE OF THE HAMILTON RATING SCALE FOR DEPRESSION IN A COHORT OF COMMUNITY-DWELLING ELDERLY

We examined the factor structure of the 17-item Hamilton Rating Scale for Depression (HRS-D) in 206 community-dwelling elderly patients. Using principal components analysis and quartimax rotation, a four-factor structure involving all 17 items and accounting for 57.7% of the variance was derived. The factors represented the following dimensions of depressive symptomatology and illness: depressed affect, vegetative symptoms, anxiety, and agitation/insight. This factor structure reflects the presentation of depressive symptomatology and depressive illness in this population. Findings suggest that the HRS-D can be used for clinical assessment of depressive symptomatology along major dimensions of depressive illness in community-dwelling elderly. © 1997 John Wiley & Sons, Ltd.     

脑卒中后抑郁与部位的相关性研究

目的：探讨急性期脑卒中患者影像学改变在脑卒中后抑郁（PSD）患者中的相关性和临床意义,期望早期发现PSD患者并为及时干预提供帮助。方法：对329例急性脑卒中后1个月内患者采用系统的神经心理评估和MRI检查。所有患者均常规行汉密尔顿抑郁量表（HAMD）评分,根据头颅MRJ结果分析病变部位。结果：PSD的发病率以左侧半球脑卒中患者明显高于双侧和右侧半球脑卒中患者,且左侧额叶和基底节尤为突出。不同病灶数目组间比较,PSD的发生率以多灶患者明显高于单灶患者（P〈0．01）。结论：急性脑卒中后PSD与病变部位在左侧半球尤其是左侧额叶、颞叶和基底节区具有显著相关性。完全前循环梗死也是易患PSD的危险因素。     

Comparison of the efficacy between paroxetine and sertraline augmented with aripiprazole in patients with refractory major depressive disorder

Objective

Only two-thirds of depressive patients respond to antidepressant treatment. In recent years, addition of an atypical antipsychotic drug to ongoing treatment with an antidepressant has been considered effective and well-tolerated. In the present study, we compared the efficacy between paroxetine and sertraline augmented with aripiprazole in patients with refractory major depression.

Subjects and methods

Twenty-four patients who met the DSM-IV criteria for major depressive disorder who did not at least two different classes of antidepressants were enrolled in the study. Nine were male and thirteen were female, and their ages ranged from 28 to 66 (mean ± SD = 39 ± 12) years. Patients were prescribed paroxetine (n = 11) or sertraline (n = 13) for 4 weeks. Then, those whose scores on the 17-item Hamilton Rating Scale for Depression (HAMD17) decreased below 50% received adjunctive therapy of aripiprazole for 4 weeks.

Results

Although the use of either combination treatment decreased the HAMD17 scores compared to the respective monotherapy, there was no significant difference in HAMD17 scores between the paroxetine plus aripiprazole group and sertraline plus aripiprazole group.

Conclusion

Aripiprazole augmentation therapy with paroxetine or sertraline was equally effective and tolerated in patients with refractory major depressive order.     

Corticotropin-releasing factor test in melancholic patients in depressed state versus recovery: a comparative study

PURPOSE: Basal adrenocorticotropin hormone (ACTH) and cortisol levels and their response to corticotropin-releasing factor (CRF) test were studied in melancholic depressive patients in depressed state and recovery, and compared with healthy controls. METHODS: Fifty-four outpatients diagnosed with unipolar depressive disorder with melancholic features according to DSM-IV and 23 healthy controls were included in the study. The Structured Clinical Interview for DSM-IV (SCID-IV) was used for diagnosis. Twenty-nine patients were in recovery, while 25 were in depressed state at the moment of the administration of the CRF test. FINDINGS: No differences were found between the recovered and depressed groups with respect to CRF test. Lower ACTH and higher cortisol levels with significant differences were shown in the neuroendocrine variables at 15, 30, and 60 min, and in peak response and increase, in the ACTH and cortisol response curves to CRF challenge between the groups of melancholic patients, both recovered and depressed, compared with the healthy control subjects. Moreover, recovered and depressed melancholic patients had a higher whole cortisol area under the curve with significant differences than the healthy control subjects. CONCLUSIONS: The crossover clinical status at the moment of the CRF test doesn't differentiate changes in the HPA axis in melancholic patients, while we did find significant differences in the group of healthy controls in comparison with the groups of melancholic patients both in depressive state and recovery. This supports the hypothesis that hypothalamic pituitary adrenal (HPA) axis shows alterations that remain in depressive patients even after recovery.     

Endocrine responses to growth hormone-releasing hormone, thyrotropin-releasing hormone and corticotropin-releasing hormone in depression

To explore and to compare hypothalamic-pituitary-somatotropic (HPS), hypothalamic-pituitary-thyroid (HPT) and hypothalamic-pituitary-adrenocortical (HPA) axis function in depression, 30 subjects (15 patients with a major depressive episode and individually matched controls) received 50 micrograms growth hormone-releasing hormone-44 amide at 9:00, 200 micrograms thyrotropin-releasing hormone (TRH) at 9:00 and 100 micrograms human corticotropin-releasing hormone (CRH) at 18:00 on consecutive days as an i.v. bolus dose. Compared with controls, depressed patients showed blunted growth hormone (GH) responses to GHRH, decreased TRH-induced thyrotropin (TSH) release and reduced corticotropin (ACTH) but normal cortisol secretion following CRH. ACTH secretion following CRH and TRH-induced TSH release were positively correlated across depressed patients and controls but no significant correlations between GH responses to GHRH and TRH-induced TSH release or ACTH and cortisol secretion following CRH administration were demonstrated. Our findings suggest that altered HPT and HPA axis function associated with depression are triggered by factors that are at least partly different from those that cause HPS system dysfunction. We conclude that the pathophysiological process resulting in aberrant neuroendocrine secretory dynamics associated with depression may primarily occur at a suprapituitary site, and that HPS, HPT and HPA axis dysfunction may be precipitated by complex central and peripheral regulatory mechanisms involving largely independent factors.