Psychosomatics 47:62-67, February 2006
doi: 10.1176/appi.psy.47.1.62
© 2006 Academy of Psychosomatic Medicine
Responsiveness of the PHQ-9 to Psychopharmacological Depression Treatment
Bernd Löwe, M.D., Ph.D.,
Irini Schenkel, M.S.,
Caroline Carney-Doebbeling, M.D., M.S., and
Claus Göbel, M.D.
Received July 20, 2004; revised February 25, 2005; accepted April 6, 2005. From the Dept. of General Internal and Psychosomatic Medicine, Univ. of Heidelberg Medical Center, Heidelberg, Germany (BL); the Regenstrief Institute, Indiana Univ. School of Medicine, Indianapolis, IN, USA (BL, CCD); and Clinical Research, Pfizer GmbH, Karlsruhe, Germany (IS, CG). Address correspondence and reprint requests to Dr. Löwe, Dept. of General Internal and Psychosomatic Medicine, Heidelberg Univ. Medical Center, Im Neuenheimer Feld 410, D-69120, Heidelberg, Germany. e-mail: bernd.loewe{at}med.uni-heidelberg.de
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ABSTRACT
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This is the first study that investigates the responsiveness of the Patient Health Questionnaire-9 (PHQ-9), a standard 9-item self-report depression scale, to antidepressant medication. Authors analyzed data from 1,788 depressed outpatients (66.8% women; mean age, 50.3 years), participating in a prospective, open-label, non-interventional, observational study of sertraline. On the 0–27-point PHQ-9 scale, the total sample gained 10.3 points at 12 weeks, corresponding to a standardized effect size of –1.85. With reference to two independent criterion standards, the PHQ-9 change scores were considerably greater in therapy responders than in nonresponders. The PHQ-9 was equally responsive in men and women. Therefore, the PHQ-9 qualifies as a practical tool for gauging response to pharmacological treatment in depressed patients.
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INTRODUCTION
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Brief, self-administered questionnaires have been advocated to assist with depression case-finding and follow-up in primary care.1–4 Because of its diagnostic validity, brevity, and ease of scoring, the 9-item depression module from the Patient Health Questionnaire (PHQ-9)5,6 has become one of the most frequently used self-report depression scales. In addition to the original English version, several international versions of the PHQ have been tested in primary care and specialized hospital outpatient settings. To date, validated versions of the PHQ exist in Spanish,7 German,8–11 Arabic,12 Chinese,13 and Dutch.14 Internal consistency (r[ ]=0.86, 0.88, and 0.89, respectively)6,9 and test–retest reliability (worst case, r[ICC]=0.81; best case, r[ICC]=0.96)15 of the PHQ-9 are excellent. PHQ-9 depression severity scores correlate substantially with scores of other self-report depression scales, such as the Hospital Anxiety and Depression Scale (HADS; r[tt]=0.74)9,16 or WHO 5-Item Well-Being Index (WBI-5; r[tt]= –0.73).9,17 With reference to the Structured Clinical Interview for DSM–IV (SCID)18 as diagnostic criterion standard, the PHQ-9 has a sensitivity of 95% and a specificity of 84% for major depressive disorder (cutoff  12).9
Results from comparative validation studies suggest that the criterion validity of the PHQ-9 is superior to other brief self-report depression scales.9,10 A change of 5 points on the 0–27-point PHQ-9 scale was suggested as the minimal clinically important difference for individual change in depression severity.15 The fact that the PHQ-9 includes both a categorical algorithm to establish DSM–IV depression diagnosis19 and a continuous score to reflect depression severity, constitutes another advantage of this questionnaire. However, beyond case-finding, the suitability of the PHQ-9 for follow-up assessments and therapeutic monitoring needs to be established.
The PHQ-9’s sensitivity to change has been investigated in two studies: a naturalistic, 1-year follow-up study including 167 medical outpatients20 and a stepped, collaborative-care depression trial, including 434 depressed older adults.15,21 Both studies suggest that the PHQ-9 may be sensitive to change. However, studies investigating the responsiveness of the PHQ-9 to pharmacological depression treatment are lacking. Because existing "gold standard" instruments, like the Hamilton Rating Scale for Depression (Ham-D),22 are time-consuming and require administration by specially-trained interviewers, the qualification of the PHQ-9 to gauge response to antidepressants could greatly unburden patient care and clinical research. Therefore, we aimed to investigate the responsiveness of the PHQ-9 to pharmacological depression treatment.
Using data from a sertraline post-marketing surveillance study, we assessed the responsiveness of the PHQ-9 to antidepressant medication treatment. The efficacy of the selective serotonin reuptake inhibitor (SSRI) sertraline has been shown in multiple studies, including both primary-care and psychiatric patient samples.23–27 Given the proven efficacy of sertraline treatment, we expected that PHQ-9 change scores would reflect the patients’ response to therapy. We also investigated the responsiveness of the PHQ-9 with respect to an independent criterion standard. Finally, we examined the responsiveness of the PHQ-9 in different patient groups, separated by gender, age, level of functional impairment, comorbid physical illness, and type of depressive disorder.
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METHOD
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Study Design and Subjects
The original prospective, open-label, noninterventional, observational, post-marketing surveillance study was performed in order to examine the efficacy, safety, and dosing of sertraline in routine clinical practice. Patients were eligible for this study if they were age 18 years or older, if they were diagnosed with major, minor, or other depressive disorders, and if no contraindications against sertraline were present. Patients were not paid for their participation.
Sertraline was prescribed in the usual manner, in accordance with the terms of the marketing authorization. Because of the "real-world" character of the study, no specific dosing regimens for sertraline were stipulated. However, dosing was to follow the approved German labeling of sertraline: 50 mg once daily, with the possibility of increasing in steps of 50 mg each, to a maximum dose of 200 mg daily. The final examination was to be performed 12 weeks after the beginning of sertraline treatment, with the allowable range being 10 to 14 weeks. Planning, performance, and evaluation followed the recommendations of the German Federal Institute for Pharmaceutical and Medicinal Products.28
The study was conducted by a total of 563 office-based physicians in Germany between January 2001 and May 2003. Sertraline treatment was administered by psychiatrists in about half of the patients (54.3%). Family physicians (39.3%), internists (6.0%), and urologists (0.3%) administered the treatment for the other patients. Sixty-eight percent of the patients were treated by male physicians; 32% were treated by female physicians.
Measures
Baseline and final assessment data were independently collected from the treating physicians and the patients. The physicians entered data in case-report forms. The baseline assessment included sociodemographic patient characteristics, a medical history, clinical depression diagnosis, previous depression treatment, and the physicians’ assessment of depression severity. In order to provide a clinician-based criterion standard for response to antidepressant therapy, treatment response at 12 weeks was defined by the standard criteria of the CGI improvement score.29 In accordance with generally accepted scoring algorithms: 1: very much improved; or 2: much improved on the 7-point CGI improvement scale was defined as treatment response, whereas 3: minimally improved; 4: no change; 5: minimally worse; 6: much worse; or 7: very much worse on the same scale was defined as treatment nonresponse.
Also, the physicians’ assessment of depression severity at baseline and follow-up was evaluated with the Clinical Global Impression (CGI) scale for severity.29 The participating physicians received a single-session individual introduction into the use of the CGI.
The participating patients completed the PHQ-9 depression scale and the PHQ functional impairment item both at baseline and follow-up.5,6,9,30 We used the continuous PHQ-9 score, ranging from 0 to 27, to assess the patients’ self-report of depression severity. With respect to functional impairment, the patient was considered a treatment-responder if his rating on the 4-point PHQ functional impairment scale (0–3) was enhanced by 2 or more points at follow-up, as compared with baseline. Naturally, only the patient subgroup with significant functional limitations at baseline (PHQ functional impairment scale: 2 or 3) was included in these analyses.
Statistical Analyses
Responsiveness refers to the ability of an outcome measure to accurately detect change when it has occurred.20,31 Sensitivity to change is a related construct, which is sometimes used synonymously with responsiveness. However, whereas "sensitivity to change" for an instrument can be assessed without treatment being present,20 the assessment of "responsiveness" requires an intervention, and usually the presence of an additional external criterion for therapeutic response.
Effect-size indices are commonly used to estimate responsiveness because they not only provide a quantitative estimate but also permit comparisons across different instruments as well as patient subgroups. The standardized response mean (difference of mean scores at two assessment-points divided by standard deviation [SD] of score changes) has been advocated as the most adequate effect-size index of responsiveness, because it incorporates the response variance in the denominator.32,33 In order to allow comparisons of PHQ-9 change scores from different patient groups, we computed 95% confidence intervals (CI) around the mean difference scores. For this study, PHQ-9 change scores and the standardized response means were computed for the total sample and the subgroups described below.
The main outcome of this study was the PHQ-9’s responsiveness to treatment in the total sample. Second, we assessed its responsiveness with reference to two external criterion standards: 1) response to therapy, as assessed by the physicians’ rating on the CGI; and 2) response to therapy, as self-report of improvement on functional impairment. Third, we investigated whether response to therapy was adequately reflected by the PHQ-9 in subgroups of 1) patients of both sexes, 2) patient subgroups of different age, 3) patient subgroups with different diagnostic depression status, and 4) patient subgroups with and without comorbid medical illness. Finally, Pearson intercorrelations between scores of the PHQ-9 and the CGI Severity Scale were computed.
One or two missing values on the 9-item PHQ-9 scale were substituted by using the average score of the nonmissing items. Patients with more than two missing values at baseline or follow-up were excluded from the analyses. To investigate whether the noninclusion of patients with more than two missing values on the PHQ-9 influenced the results of our analyses, we performed three different sensitivity analyses: 1) missing values at follow-up were replaced with the observation at baseline carried forward; 2) missing values at follow-up were replaced with the mean item values of the patient sample with complete values; 3) the mean difference score of the 5% of patients with the lowest PHQ-9 difference scores was used to estimate the PHQ-9 sum score of the patients with missing values at follow-up.
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RESULTS
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Baseline Patient Characteristics
A total of 1,878 patients participated in this study; 118 patients (6.3%) prematurely discontinued the study because of adverse events (N=44, 2.3%), lost to follow-up (N=27, 1.4%), insufficient clinical response to sertraline (N=16, 0.9%), or other reasons (N=31, 1.7%). For this study, of the total sample, 90 patients were excluded because of missing values on the PHQ-9 at baseline or follow-up, resulting in the final patient sample of 1,788 patients. Mean patient age was 50.3 (SD: 14.7) years; 1,194 patients (66.8%) were female.
Major depressive disorder was diagnosed in 757 patients (42.3%), minor depression in 543 (30.4%), and other depressive disorders in 438 patients (24.5%). The diagnosis was missing in 50 patients (2.8%). At baseline, 547 patients (32.4%) were currently working, 360 (21.3%) were not in a gainful position, 340 (20.1%) were certified to be unfit for work, 332 (19.6%) were retired, 111 (6.6%) were prematurely retired. Comorbid physical diseases were present in 30% of the patients, most frequently, hypertension (9.5%), musculoskeletal and connective tissue disease (5.0%), diabetes mellitus (2.9%), coronary artery disease (2.1%), gastrointestinal disorders (1.9%), and respiratory and pulmonary disorders (1.5%). The mean sertraline dose was 58.9 (SD: 17.6) mg daily, and the mean treatment duration was 13.9 (SD: 8.6) weeks. Only 10.5% of the patients received other antidepressants in addition to sertraline.
Responsiveness of The PHQ-9
The PHQ-9 scores at baseline and follow-up, PHQ-9 change scores, and the questionnaire’s responsiveness to antidepressant medication treatment are summarized in Table 1. On the 0- to 27-point PHQ-9 scale, the total sample improved by 10.28 (SD: 5.56) points, corresponding to an effect size of –1.85 (standardized response mean). With reference to the clinician’s CGI rating, the patients responding to therapy (87%) improved by an effect size of –2.15, whereas the CGI nonresponders (13%) improved by an effect size of –1.00. Similarly, the change effect size was –2.50 in the patients with functional limitations at baseline who considered their functional status improved at 12 weeks and –0.59 in those who did not. The non-overlap of the confidence intervals around the mean differences of treatment responders and nonresponders gives evidence for the substantial difference of PHQ-9 change scores in the different outcome groups.
The difference score of patients with major depressive disorder was somewhat greater compared with the difference score of patients with major or minor depressive disorder, and patients without comorbid medical conditions showed a greater response to therapy than patients with comorbid physical illness. However, the responsiveness of the PHQ-9 was equivalent for the subgroups of both sexes and different age-groups, respectively.
The results from the three different sensitivity analyses were similar to the results presented in Table 1, suggesting that the noninclusion of the 90 patients with more than two missing values on the PHQ-9 did not result in sampling bias (data available from first author on request). Correlations between scores of the PHQ-9 and the CGI Severity Scale were r=0.44 (p<0.001) and r=0.56 (p<0.001), at baseline and follow-up, respectively.
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DISCUSSION
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This is the first study to demonstrate that the PHQ-9 is responsive to antidepressant medication. On the 0- to 27-point PHQ-9 scale, the mean change of 10.3 (SD: 5.6) points corresponds to a large standardized effect size of –1.9. Given that a 5-point difference in PHQ-9 scores is advocated as the minimal clinically important difference for individual change,15 the PHQ-9 difference score in our study is of substantial size.
Both with respect to a clinician-based and a self-reported criterion standard, the PHQ-9 difference scores were considerably greater in groups of therapy responders than in groups of nonresponders. These findings indicate that the PHQ-9 reflects change in depression severity differentially for patients responding to therapy and those who do not. The PHQ-9 change scores did not only reflect the relatively large differences between treatment responders and nonresponders, but also smaller differences, such as different outcomes of patients with and without comorbid physical illness. This finding is lent support by previous studies indicating that depressed patients with comorbid physical illness tend to have worse depression outcomes than depressed patients without comorbid medical illness.34,35 As evidenced by additional subgroup comparisons, the PHQ-9 is equally responsive in samples of men and women and patient samples of different age, respectively. Correspondingly, the PHQ-9 showed responsiveness in samples with different depression diagnostic status. Consistent with other studies,15,20 even the nonresponder groups showed improvements in depression severity on the PHQ-9. Although this could reflect some modest imprecision of the PHQ-9 or the criterion standard measures, it is also possible that these patients experienced mild improvements during depression treatment, albeit to a degree that was not detected by the 7-point CGI improvement scale or the 4-point PHQ functional impairment scale.
The study findings are consistent with those from our previous naturalistic study, in which the effect sizes of PHQ-9 change, as assessed by standardized response means, were –1.4 in the improved patient group and –0.4 in the unchanged patient group.20 They are also similar to the results from the stepped collaborative-care depression trial, in which, at 3 months, patients with persistent major depression improved by an effect size of –0.6, whereas patients with full remission improved by an effect size of –2.2. In contrast to the above-mentioned studies, in which the PHQ-9 was either completely20 or partially administered as a telephone interview,15 the PHQ-9 was entirely completed as a self-report instrument in the current study.
This study has several limitations. First, our findings primarily apply to the study drug sertraline. Other antidepressants might have led to different indices of responsiveness. Also, the noncontrolled design of the study limits our ability to determine whether the improvement in depression severity was due to sertraline treatment, other co-interventions, placebo effect, or spontaneous improvement. However, given that the PHQ-9 covers the whole range of diagnostic features of major depression, it is likely that it would also be responsive to antidepressants with different modes of action, for example, tricyclic antidepressants. Finally, our study was an open-label, noninterventional, post-marketing surveillance study. This study design has several strengths, such as a large patient sample size, a high number of participating physicians, and real clinical practice conditions. In contrast, weaknesses of this design include the uncontrolled patient selection and dosing of the antidepressant, as well as the limited training of the physicians in assessing depression severity and outcome with the CGI. These factors might have introduced unmeasured selection and measurement biases. However, measurement bias with respect to PHQ-9 is unlikely, given that the PHQ-9 was independently completed by the patients. Even if the physicians’ assessments should be biased, the main outcome of this study, the responsiveness of the PHQ-9 in the total sample, is still valid.
Combined with the two previous studies,15,20 this study supports the conclusion that the PHQ-9 is sensitive to change and responsive both to pharmacological and psychosocial interventions. Future psychometric studies might complement these findings with respect to other psychopharmacological and psychosocial treatment approaches. Also, controlled clinical studies, in which the PHQ-9 is used as a primary or secondary outcome measure, may be used to analyze responsiveness to treatment of the PHQ-9. Finally, a comparison of the responsiveness of the PHQ-9 and standard interview-based measures for depression outcome, for example, the Ham-D,22,36 would help determine whether the PHQ-9 could replace more complex and costly methods for assessing depression outcome. So far, our findings suggest that the PHQ-9 is a practical, valid, and responsive tool for diagnosing and monitoring depression in individual patient care as well as in clinical research.
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ACKNOWLEDGMENTS
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Dr. Löwe received honoraria and grant support from Pfizer Inc., U.S. Pharmaceuticals Group, Germany. Dr. Göbel heads the clinical research department and Ms. Schenkel is the team-leading biostatistician at Pfizer Inc., U.S. Pharmaceuticals Group, Germany.
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REFERENCES
|
- U.S. Preventive Services Task Force: Screening for depression: recommendations and rationale. Ann Intern Med 2002; 136:760–764[Abstract/Free Full Text]
- Williams JW, Noel PH, Cordes JA, et al: Is this patient clinically depressed? JAMA 2002; 287:1160–1170[Abstract/Free Full Text]
- Löwe B, Gräfe K, Kroenke K, et al: Predictors of psychiatric comorbidity in medical outpatients. Psychosom Med 2003; 65:764–770[Abstract/Free Full Text]
- Katon WJ, Unützer J, Simon G: Treatment of depression in primary care: where we are, where we can go. Med Care 2004; 42:1153–1157[CrossRef][Medline]
- Spitzer RL, Kroenke K, Williams JB, Patient Health Questionnaire Primary Care Study Group: Validation and utility of a self-report version of PRIME-MD: The PHQ Primary-Care Study. JAMA 1999; 282:1737–1744[Abstract/Free Full Text]
- Kroenke K, Spitzer RL, Williams JB: The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med 2001; 16:606–613[CrossRef][Medline]
- Diez-Quevedo C, Rangil T, Sanchez-Planell L, et al: Validation and utility of the Patient Health Questionnaire in diagnosing mental disorders in 1,003 general-hospital Spanish inpatients. Psychosom Med 2001; 63:679–686[Abstract/Free Full Text]
- Gräfe K, Zipfel S, Herzog W, et al: Screening for psychiatric disorders with the Patient Health Questionnaire (PHQ): results from the German validation study. Diagnostica 2004; 50:171–181[CrossRef]
- Löwe B, Spitzer RL, Gräfe K, et al: Comparative validity of three screening questionnaires for DSM-IV depressive disorders and physicians’ diagnoses. J Affect Disord 2004; 78:131–140[CrossRef][Medline]
- Löwe B, Gräfe K, Zipfel S, et al: Diagnosing ICD-10 depressive episodes: superior criterion validity of the Patient Health Questionnaire. Psychother Psychosom 2004; 73:386–390[CrossRef][Medline]
- Löwe B, Gräfe K, Zipfel S, et al: Detecting panic disorder in medical and psychosomatic outpatients: comparative validation of the Hospital Anxiety and Depression Scale, the Patient Health Questionnaire, a screening question, and physicians’ diagnosis. J Psychosom Res 2003; 55:515–519[CrossRef][Medline]
- Becker S, Al Zaid K, Al Faris E: Screening for somatization and depression in Saudi Arabia: a validation study of the PHQ in primary care. Int J Psychiatry Med 2002; 32:271–283[CrossRef][Medline]
- Lubetkin EI, Jia H, Gold MR: Depression, anxiety, and associated health status in low-income Chinese patients. Am J Prev Med 2003; 24:354–360[Medline]
- Persoons P, Luyckx K, Desloovere C, et al: Anxiety and mood disorders in otorhinolaryngology outpatients presenting with dizziness: validation of the self-administered PRIME-MD patient health questionnaire and epidemiology. Gen Hosp Psychiatry 2003; 25:316–323[CrossRef][Medline]
- Löwe B, Unützer J, Callahan CM, et al: Monitoring depression treatment outcomes with the Patient Health Questionnaire-9. Med Care 2004; 42:1194–1201[CrossRef][Medline]
- Zigmond AS, Snaith RP: The Hospital Anxiety and Depression Scale. Acta Psychiatr Scand 1983; 67:361–370[Medline]
- World Health Organization Info Package: Mastering depression in primary care, Version 2.2. Copenhagen, Denmark, World Health Organization, Regional Office for Europe, 1998
- First MB, Spitzer RL, Williams JBW, et al: Structured Clinical Interview for DSM-IV (SCID). Washington, DC, American Psychiatric Association, 1995
- American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders. 4th Edition, Text Revision (DSM-IV-TR). Washington, DC, American Psychiatric Association, 2000
- Löwe B, Kroenke K, Herzog W, et al: Measuring depression outcome with a brief self-report instrument: sensitivity to change of the Patient Health Questionnaire (PHQ-9). J Affect Disord 2004; 81:61–66[CrossRef][Medline]
- Unützer J, Katon W, Callahan CM, et al: Collaborative care management of late-life depression in the primary-care setting: a randomized, controlled trial. JAMA 2002; 288:2836–2845[Abstract/Free Full Text]
- Hamilton D: A rating scale for depression. J Neurol Neurosurg Psychiatry 1960; 23:56–62[Medline]
- Glassman AH, O’Connor CM, Califf RM, et al: Sertraline treatment of major depression in patients with acute MI or unstable angina. JAMA 2002; 288:701–709[Abstract/Free Full Text]
- Kroenke K, West SL, Swindle R, et al: Similar effectiveness of paroxetine, fluoxetine, and sertraline in primary care: a randomized trial. JAMA 2001; 286:2947–2955[Abstract/Free Full Text]
- Kocsis JH, Schatzberg A, Rush AJ, et al: Psychosocial outcomes following long-term, double-blind treatment of chronic depression with sertraline vs. placebo. Arch Gen Psychiatry 2002; 59:723–728[Abstract/Free Full Text]
- Sheikh JI, Cassidy EL, Doraiswamy PM, et al: Efficacy, safety, and tolerability of sertraline in patients with late-life depression and comorbid medical illness. J Am Geriatr Soc 2004; 52:86–92[CrossRef][Medline]
- Lépine JP, Caillard V, Bisserbe JC, et al: A randomized, placebo-controlled trial of sertraline for prophylactic treatment of highly recurrent major depressive disorder. Am J Psychiatry 2004; 161:836–842[Abstract/Free Full Text]
- Bundesinstitut für Arzneimittel und Medizinprodukte: Recommendations for planning, performance, and evaluation of post-marketing surveillance studies, Nov. 12, 1998. http://www.bfarm.de/de/Arzneimittel/zul/bekanntm/index.php?more=awbver1.php: 1998
- Guy W: ECDEU: Assessment manual for psychopharmacology. Washington, DC, U.S. Department of Health and Human Services, 1976, pp 218-222
- Löwe B, Spitzer RL, Zipfel S, et al: PRIME MD Patient Health Questionnaire (PHQ), German Version, Manual and Materials, 2nd Edition. Karlsruhe, Pfizer, 2002
- de Bruin AF, Diederiks JP, de Witte LP, et al: Assessing the responsiveness of a functional status measure: the Sickness Impact Profile versus the SIP-68. J Clin Epidemiol 1997; 50:529–540[CrossRef][Medline]
- Katz JN, Larson MG, Phillips CB, et al: Comparative measurement sensitivity of short and longer health status instruments. Med Care 1992; 30:917–925[CrossRef][Medline]
- Wright JG, Young NL: A comparison of different indices of responsiveness. J Clin Epidemiol 1997; 50:239–246[CrossRef][Medline]
- Koike AK, Unützer J, Wells KB: Improving the care for depression in patients with comorbid medical illness. Am J Psychiatry 2002; 159:1738–1745[Abstract/Free Full Text]
- Spijker J, de Graaf R, Bijl RV, et al: Determinants of persistence of major depressive episodes in the general population: results from the Netherlands Mental Health Survey and Incidence Study (NEMESIS). J Affect Disord 2004; 81:231–240[Medline]
- Bagby RM, Ryder AG, Schuller DR, et al: The Hamilton Depression Rating Scale: has the gold standard become a lead weight? Am J Psychiatry 2004; 161:2163–2177[Abstract/Free Full Text]
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ABSTRACT
INTRODUCTION
