Improving depression severity assessment--I. Reliability, internal validity and sensitivity to change of three observer depression scales

The Hamilton Depression Scale (HAMD) is the most commonly used scale for depression severity assessment and for antidepressant treatment evaluation. Alternative scales have been proposed by Bech and Rafaelsen (BRMS) and by Montgomery and Asberg (MADRS) to try to overcome the shortcomings of HAMD: they are based on different concepts of severity and different scaling procedures. Comparisons with respect to reliability, validity and ability to detect change have been performed using these scales in different samples. The BRMS proved superior. This result makes it necessary to question the usual procedure of testing the efficacy of antidepressants by means of HAMD alone. Problems in defining the severity of depression and in testing the validity of severity scales are discussed.     

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 rating scales in Parkinson's disease: critique and recommendations.

Depression is a common comorbid condition in Parkinson's disease (PD) and a major contributor to poor quality of life and disability. However, depression can be difficult to assess in patients with PD due to overlapping symptoms and difficulties in the assessment of depression in cognitively impaired patients. As several rating scales have been used to assess depression in PD (dPD), the Movement Disorder Society commissioned a task force to assess their clinimetric properties and make clinical recommendations regarding their use. A systematic literature review was conducted to explore the use of depression scales in PD and determine which scales should be selected for this review. The scales reviewed were the Beck Depression Inventory (BDI), Hamilton Depression Scale (Ham-D), Hospital Anxiety and Depression Scale (HADS), Zung Self-Rating Depression Scale (SDS), Geriatric Depression Scale (GDS), Montgomery-Asberg Depression Rating Scale (MADRS), Unified Parkinson's Disease Rating Scale (UPDRS) Part I, Cornell Scale for the Assessment of Depression in Dementia (CSDD), and the Center for Epidemiologic Studies Depression Scale (CES-D). Seven clinical researchers with clinical and research experience in the assessment of dPD were assigned to review the scales using a structured format. The most appropriate scale is dependent on the clinical or research goal. However, observer-rated scales are preferred if the study or clinical situation permits. For screening purposes, the HAM-D, BDI, HADS, MADRS, and GDS are valid in dPD. The CES-D and CSDD are alternative instruments that need validation in dPD. For measurement of severity of depressive symptoms, the Ham-D, MADRS, BDI, and SDS scales are recommended. Further studies are needed to validate the CSDD, which could be particularly useful for the assessment of severity of dPD in patients with comorbid dementia. To account for overlapping motor and nonmotor symptoms of depression, adjusted instrument cutoff scores may be needed for dPD, and scales to assess severity of motor symptoms (e.g., UPDRS) should also be included to help adjust for confounding factors. The HADS and the GDS include limited motor symptom assessment and may, therefore, be most useful in rating depression severity across a range of PD severity; however, these scales appear insensitive in severe depression. The complex and time-consuming task of developing a new scale to measure depression specifically for patients with PD is currently not warranted.     

Methodological aspects in the assessment of severity of depression by the Hamilton Depression Scale

Observer-rating scales are used for the evaluation of drug trials in depression. One of the most widely used depression rating scales is still the Hamilton Depression Scale (HAMD), which was developed at the time when the first antidepressants were becoming available. Due to its construction it seems to have a specific focus on drug effects of classical antidepressants. As a result of different methodological analyses such as principal component analysis, the Rasch model and facet analysis, a differentiation between core symptoms reflecting the severity of depression and additional symptoms describing other aspects of the symptomatology of depression seems meaningful. The use of the HAMD 6-item score, described primarily by Bech, as the main efficacy criterion in antidepressant drug trials gives a fair estimation of drug-induced changes of severity of depression and avoids bias such as the well-known bias of the HAMD total score in favour of tricyclic antidepressants. This is demonstrated by the evaluation of two sertraline-amitriptyline comparative studies.     

Methodological aspects in the assessment of severity of depression by the Hamilton Depression Scale

Observer-rating scales are used for the evaluation of drug trials in depression. One of the most widely used depression rating scales is still the Hamilton Depression Scale (HAMD), which was developed at the time when the first antidepressants were becoming available. Due to its construction it seems to have a specific focus on drug effects of classical antidepressants. As a result of different methodological analyses such as principal component analysis, the Rasch model and facet analysis, a differentiation between core symptoms reflecting the severity of depression and additional symptoms describing other aspects of the symptomatology of depression seems meaningful. The use of the HAMD 6-item score, described primarily by Bech, as the main efficacy criterion in antidepressant drug trials gives a fair estimation of drug-induced changes of severity of depression and avoids bias such as the well-known bias of the HAMD total score in favour of tricyclic antidepressants. This is demonstrated by the evaluation of two sertraline-amitriptyline comparative studies.

     

The Bipolar Depression Rating Scale (BDRS): its development, validation and utility

OBJECTIVES: Unipolar and bipolar depression differ neurobiologically and in clinical presentation. Existing depression rating instruments, used in bipolar depression, fail to capture the necessary phenomenological nuances, as they are based on and skewed towards the characteristics of unipolar depression. Both clinically and in research there is a growing need for a new observer-rated scale that is specifically designed to assess bipolar depression. METHODS: An instrument reflecting the characteristics of bipolar depression was drafted by the authors, and administered to 122 participants aged 18-65 (44 males and 78 females) with a diagnosis of DSM-IV bipolar disorder, who were currently experiencing symptoms of depression. The Bipolar Depression Rating Scale (BDRS) was administered together with the Hamilton Depression Rating Scale (HAM-D), Montgomery Asberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS). RESULTS: The BDRS has strong internal consistency (Cronbach's alpha = 0.917), and robust correlation coefficients with the MADRS (r = 0.906) and HAM-D (r = 0.744), and the mixed subscale correlated with the YMRS (r = 0.757). Exploratory factor analysis showed a three-factor solution gave the best account of the data. These factors corresponded to depression (somatic), depression (psychological) and mixed symptom clusters. CONCLUSIONS: This study provides evidence for the validity of the BDRS for the measurement of depression in bipolar disorder. These results suggest good internal validity, provisional evidence of inter-rater reliability and strong correlations with other depression rating scales.     

Sensitivity of the Montgomery Asberg Depression Rating Scale to response and its consequences for the assessment of efficacy

An increasing body of evidence is available suggesting that the Hamilton Depression Rating Scale (HAMD) is not a sensitive measure of treatment effect. In this investigation, we explore the sensitivity of the individual items of the Montgomery Asberg Depression Rating Scale (MADRS) and compare the consequences of selecting a different scale as primary endpoint in the analysis of efficacy. A graphical approach is proposed for the evaluation of the sensitivity of individual items to response, using data from randomised, placebo-controlled clinical trials in which HAMD and MADRS were measured concurrently. Subsequently, we illustrate the impact of differences in the sensitivity of the primary endpoint for the detection of statistical significance in treatment effect. In contrast to the HAMD, our item-by-item analysis of the MADRS reveals that all individual items are sensitive to response, irrespective of treatment type. However, some HAMD subscales still outperform MADRS in the detection of treatment effect. The selection of these subscales as primary endpoints in clinical trials could save over 1/3 in patients compared to the full HAMD whilst keeping the same statistical power.     

Development and reliability of the HAM-D/MADRS interview: an integrated depression symptom rating scale

The Hamilton Rating Scale for Depression (HAM-D) and the Montgomery-Asberg Depression Rating Scale (MADRS), two widely used depression scales, each have unique advantages and limitations for research. The HAM-D's limited sensitivity and multidimensionality have been criticized, despite the scale's popularity. The MADRS, designed to be sensitive to treatment changes, is briefer and more uniform. A limitation of the MADRS is the lack of a structured interview, which may affect reliability. The HAM-D and the MADRS are often used conjointly as endpoints in depression trials. We designed a hybrid questionnaire that allows administration of MADRS and 31 HAM-D items simultaneously. Seventy mood disorder patients (60 bipolar I, 10 major depressive disorder) were administered the HAM-D/MADRS Interview (HMI) as part of a larger study. Interrater reliability for 50 patients was excellent for the HAM-D and the MADRS (ICC=0.97-0.98). MADRS item reliabilities (ICC=0.86-0.97) were higher than obtained in studies that did not use a structured interview. Reliability coefficients for seven HAM-D(31) 'atypical' symptoms ranged from 0.77 to 0.95. HMI was highly correlated with the Global Clinical Impressions Scale. This is the first study we know of to investigate the reliability of a structured interview of either the MADRS or of the HAM-D(31). The HMI provides an easily administered, reliable method of rating depression severity which may improve consistency and validity of study findings.     

A clinical monitoring form for mood disorders

Objective:  The Clinical Monitoring Form (CMF) for mood disorders was developed as a time efficient record keeping tool for routine clinical use. This report presents preliminary data evaluating the correlation between the CMF's dimensional subscales for depression and mood elevation and formal mood rating scales across a wide spectrum of mood states.
Methods:  To harvest data for 500 follow-up visits required collection of data from consecutive records accumulated during the conduct of seven double blind clinical trials involving a total of 58 participants. These trials utilized the CMF as a source document in conjunction with formal study outcome scales, e.g. Hamilton Rating Scale for Depression (HRSD), the Montgomery-Asberg Depression Rating Scale (MADRS), the Young Mania Rating Scale (YMRS) and the Mania Rating Scale (MRS) from the Schedule of Affective Disorders-Current (SUM-C). Correlation coefficients were calculated to examine the relationship between the formal rating scales, Clinical Global Impression and the depression (SUM-D) and mood elevation (SUM-ME) subscales of the CMF.
Results:  Robust correlations were observed between SUM-D and the formal depression scales, HRSD and MADRS, r =0.79, r =0.88, respectively. Similar robust correlations were also found between the SUM-ME and the formal mood elevation scales, YMRS and the MRS, r =0.84, r =0.86, respectively.
Conclusion:  The CMF appears to offer a reasonable alternative to the formal rating scales typically used in research studies.     

卒中后抑郁的评估进展

卒中后抑郁发病率较高,准确的评估有利于临床诊疗。目前,对卒中后抑郁的评估多依赖 量表。对于不影响语言表达的卒中患者,汉密尔顿抑郁量表、卒中后抑郁分级量表和蒙哥马利抑郁 量表应用最为广泛,且其信度和效度均较高。对于失语患者的卒中后抑郁评价量表虽然开发的比较 多,但临床应用相对较局限,其中卒中失语抑郁问卷和失语抑郁评估量表应用相对较多。目前针对卒 中后抑郁评估量表的应用人群、评估指标有所差异,在应用这些量表时,相比原发疾病,评估者更重 视抑郁情绪的问题,这可能会造成患者的不配合和排斥,从而影响量表评价的准确性,这些局限性 有待进一步研究解决。     

老年与非老年抑郁症的临床特征差异

目的:探讨老年期抑郁症的临床特征。方法:以60例老年期抑郁症患者作老年组,选60例非老年期抑郁症患者为非老年组。对两组分别用汉密尔顿抑郁量表和汉密尔顿焦虑量表进行评定。结果:老年组抑郁症状中激越和疑病症状显著高于非老年组(P<0.01),老年组的躯体症状中自主神经系统症状、心血管系统症状和消化系统症状显著高于非老年组(P<0.05或P<0.01);躯体性焦虑和认知障碍、焦虑/躯体化和睡眠障碍的严重程度均显著高于非老年组(P<0.05或P<0.01)。结论:老年期抑郁症激越、疑病、躯体症状、焦虑、睡眠障碍及认知障碍等更加突出。     

French adaptation, concurrent validation and factorial analysis of the Bech and Rafaelsen melancholia scale

33 depressive patients diagnosed major depressive episode (DSM III) have been assessed by the French translation of the melancholia scale of Bech and Rafaelsen and the following scales: scale of depressive retardation (ERD) (Widlocher), Hamilton depression rating scale with 26 items (HDS 26), Montgomery and Asberg depression rating scale (MADRS). A concurrent validation shows that Bech-Rafaelsen melancholia scale is valid. A principal components analysis with VARIMAX rotation found 4 principal components: retardation and blunted affect, asthenia, anxiety, suicidal impulses.     

氯氮平撤药症状调查

目的：了解氯氮平的撤药症状。方法：对31例服用氯氮平治疗的精神分裂症患者停药1周，分别于停药前后予简明精神病评定量表(BPRS)、副反应量表(TESS)、汉密尔顿抑郁量表(HAMD)、汉密尔顿焦虑量表(HAMA)评定疗效及不良反应。结果：停药后BPRS、TESS、HAMD、HAMA总分均明显高于停药前，停药后有25例(80％)精神症状恶化。结论：氯氮平的撤药症状发生频率高，症状多样。     

Validation of the Hamilton Depression Rating Scale and Montgommery and Asberg Rating Scales in terms of AGECAT depression cases

OBJECTIVE. To validate the Hamilton Depression (17) and Montgommery and Asberg Depression Scales as research instruments in older depressed community residents. DESIGN. External validation against GMS/AGECAT case level in the recruitment of older community residents for an antidepressant trial. ANALYSES. Receiver operator curves were generated for each rating scale, using GMS/AGECAT case level in external criterion. The sensitivity, specificity, positive and negative predictive values of both rating instruments were examined in the whole sample and age and gender subgroups. MADRS and HAM-D cut-off scores differentiating GMS/AGECAT cases from subcases were identified. RESULTS. HAM-D cut-off score of 16 and MADRS score of 21 were identified as differentiating case from sub-case. Diagnostic accuracy of both instruments was good, reflecting good sensitivity and specificity across both genders and sub-age groups. CONCLUSIONS. Both scales performed well in this population. These scores provide researchers with externally validated and clinically relevant cut-off scores in designing trials in the management of older depressed community residents.     

Psychiatric assessment in medical long-term care facilities: Reliability of commonly used rating scales

Clinical assessment of psychopathology includes quantifying symptoms on rating scales. Caution must be used in applying standardized instruments to new populations because their reliability may alter considerably. This study assesses the interrater reliability of six well-known rating scales when applied to patients residing in a medical long-term care facility. The scales include measures of depression, psychosis and cognitive impairment. The specific scales used were: Hamilton Depression Scale; Brief Psychiatric Rating Scale; Mini-Mental State Examination; Mental Status Questionnaire; Global Deterioration Scale; and Brief Cognitive Rating Scale.     

Improving depression severity assessment--II. Content, concurrent and external validity of three observer depression scales

The Hamilton Depression Scale (HAMD), the Montgomery-Asberg Depression Rating Scale (MADRS) and the Bech-Rafaelsen Melancholia Scale (BRMS) were compared with respect to content, concurrent and external validity in sample of 130 patients with a major depressive episode. The three scales did equally well in concurrent and external validity. The HAMD showed some deficiencies in content validity. The consequences for depression severity assessment are discussed.     

抑郁症的增效治疗（二）——齐拉西酮对伴有精神病性症状抑郁症的治疗作用

目的：探讨齐拉西酮治疗伴有精神病性症状抑郁症的临床疗效。方法：60例伴有精神病性症状的抑郁症患者随机分为合用组28例（齐拉西酮联合帕罗西汀治疗）和单用组32例（单用帕罗西汀治疗）,疗程6周。采用汉密尔顿抑郁量表（HAMD）、简明精神病评定量表（BPRS）、临床疗效总评量表（CGI）和治疗中出现的症状量表（TESS）评定临床疗效和不良反应。结果：治疗后两组HAMD、BPRS及CGI评分均较治疗前明显下降（P〈0.05或P〈0.01）;两组比较,以合用组降低更为显著（P〈0.05或P〈0.01）。合用组TESS评分（2.11±1.20）分和单用组TESS评分（1.9±0.16）分差异无统计学意义（P〉0.05）。结论：齐拉西酮联合帕罗西汀治疗伴有精神病性症状的抑郁症临床疗效优于单用帕罗西汀。     

Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial.

BACKGROUND: We tested whether transcranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (DLPFC) is effective and safe in the acute treatment of major depression. METHODS: In a double-blind, multisite study, 301 medication-free patients with major depression who had not benefited from prior treatment were randomized to active (n = 155) or sham TMS (n = 146) conditions. Sessions were conducted five times per week with TMS at 10 pulses/sec, 120% of motor threshold, 3000 pulses/session, for 4-6 weeks. Primary outcome was the symptom score change as assessed at week 4 with the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes included changes on the 17- and 24-item Hamilton Depression Rating Scale (HAMD) and response and remission rates with the MADRS and HAMD. RESULTS: Active TMS was significantly superior to sham TMS on the MADRS at week 4 (with a post hoc correction for inequality in symptom severity between groups at baseline), as well as on the HAMD17 and HAMD24 scales at weeks 4 and 6. Response rates were significantly higher with active TMS on all three scales at weeks 4 and 6. Remission rates were approximately twofold higher with active TMS at week 6 and significant on the MADRS and HAMD24 scales (but not the HAMD17 scale). Active TMS was well tolerated with a low dropout rate for adverse events (4.5%) that were generally mild and limited to transient scalp discomfort or pain. CONCLUSIONS: Transcranial magnetic stimulation was effective in treating major depression with minimal side effects reported. It offers clinicians a novel alternative for the treatment of this disorder.     

The validity of the depression rating scales in discriminating between citalopram and placebo in depression recurrence in the maintenance therapy of elderly unipolar patients with major depression

The World Federation of Societies of Biological Psychiatry guidelines for treatment of unipolar major depression has recommended three depression rating scales for evaluating outcome: The Hamilton Depression Rating Scale (HAM-D), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Bech-Rafaelsen Melancholia Scale (MES). In this study we evaluated the ability of these scales to differentiate between citalopram and placebo in the recurrence prevention of unipolar depression. The study is a psychometric reexamination of a trial on the efficacy of citalopram versus placebo in the maintenance therapy of elderly patients with unipolar depression. Internal validity (the Cronbach coefficient alpha, the Loevinger coefficient of homogeneity, and factor analysis) of the three scales has been examined to evaluate their unidimensionality. In the outcome analysis for depression recurrence, the conventional cutoff scores of the three scales are used. In total, 60 patients received citalopram and 61 patients received placebo in the maintenance phase of 48 weeks. The results showed that the internal validity was higher for MES and MADRS than for HAM-D. Using the MADRS, 67.2 % of the patients on placebo and 31.6 % of the patients on citalopram developed a depression recurrence (ratio 2.12); using HAM-D17, 42.6 % on placebo and 13.3 % on citalopram developed a depression recurrence (ratio 3.20); and using the MES, 34.4 % on placebo and 11.7 % on citalopram developed a depression recurrence (ratio 2.94). The conventional cutoff scores of HAM-D17 and MES for depression recurrence indicated a ratio between citalopram and placebo of around 3, while the conventional cutoff scores of MADRS for depression recurrence indicated a ratio of only around 2. In future trials on the recurrence prevention of unipolar depression, a cutoff score of 25 rather than 22 on the MADRS is recommended.     

度洛西汀与西酞普兰治疗老年抑郁症对照研究

目的探讨度洛西汀与西酞普兰治疗老年抑郁症的疗效及安全性。方法 58例老年抑郁症患者随机分为度洛西汀组（n=29）和西酞普兰组（n=29）。治疗8周后用汉密顿抑郁量表（HAMD）和副反应量表（TESS）评定疗效及不良反应。结果两组疗效相仿（P〉0.05）;两组不良反应差异无统计学意义（P〉0.05）。结论度洛西汀治疗老年抑郁症是安全有效的。