Do you want to buy antibiotics online without prescription? https://buyantibiotics24h.net/ - This is pharmacy online for you!
Nmd21310 807.810
Changes in Depressive Symptoms and Social Functioning in the
Sequenced Treatment Alternatives to Relieve Depression Study
John W. Denninger, MD, PhD,* Adrienne O. van Nieuwenhuizen, MSc,* Stephen R. Wisniewski, PhD,Þ
James F. Luther, MSc,Þ Madhukar H. Trivedi, MD,þ A. John Rush, MD,§ Jackie K. Gollan, PhD,||
Diego A. Pizzagalli, PhD,¶ and Maurizio Fava, MD*
antidepressants, social functioning often does not return to baseline
Abstract: Major depressive disorder (MDD) profoundly affects social func-
(Weissman, 2000). A small number of studies have investigated long-
tioning, including the ability to enjoy social activities with peers, friends, and
term social functioning impairments during or after treatment using
family members. We sought to compare changes in social functioning and
antidepressants; these suggest that long-term impairments in social
depressive symptoms in the first level of the Sequenced Treatment Alterna-
functioning may persist even in patients whose depression is deter-
tives to Relieve Depression (STAR*D) study. Adult outpatients (N = 2876)
mined to be in clinical remission (Kennedy et al., 2007). In level 1 of
with diagnoses of MDD were treated using flexible doses of citalopram for
the STAR*D trial, greater baseline symptom severity was associated
up to 14 weeks. We compared the change over the course of treatment in the
with lower health-related quality of life as assessed across multiple
social activities item of the Work and Social Adjustment Scale to the change
domains (Trivedi et al., 2006b). Interestingly, Rapaport et al. (2005)
in individual items of the Quick Inventory of Depressive SymptomsYSelf-
found that symptom measures in mood and anxiety disorders were
Rated (QIDS-SR). Improvement in social functioning was modestly positively
associated with baseline quality of life; however, the symptom mea-
correlated with improvement in sad mood, concentration/decision making, in-
sures accounted for only a small proportion of the variance in quality
volvement, and energy/fatigability. Only 16% to 22% of the variance in the
change in social functioning was accounted for by these symptoms, and only
We sought to make a similar comparison for social function-
32% was accounted for by the total QIDS-SR score. In this large real-world
ing in a large sample of patients with MDD before and after selective
sample of outpatients treated using citalopram, changes in depressive symptoms
serotonin reuptake inhibitor treatment. To this end, we compared
do not entirely explain improvements in social functioning.
changes in social functioning as measured by the social leisure activ-
Key Words: Major depressive disorder, citalopram, social adjustment.
ities item of the Work and Social Adjustment Scale (WSAS), withchanges in depression symptoms in level 1 of STAR*D trial (Mundt
et al., 2002). We hypothesized that changes in symptom measuresduring citalopram treatment would be associated with changes in so-cial functioning measures but would account for only a small propor-
Psychosocial and functional impairments are common in major tion of thevariance in the improvements in social functioning.
depressive disorder (MDD) and are likely to result in negative
psychosocial outcomes, including unemployment and decreased so-cial contacts (Hirschfeld et al., 2002; Weissman, 2000). However, the
exact nature of the relationship between MDD symptoms and defi-
The rationale, design, and detailed methods for the first level
cits in psychosocial functioning remains to be established. Although
of STAR*D have been previously described (Rush et al., 2004;
there is a modest association between decreases in clinical symptoms
Trivedi et al., 2006a). The study protocol was approved by individual
and improvements in social functioning during acute treatment using
institutional review boards, and all patients provided written informedconsent. The generalizability of our results was increased by limitingeligibility to patients who sought care as part of routine medical orpsychiatric treatment (i.e., patients were not recruited through ad-
*Depression Clinical and Research Program, Massachusetts General Hospital,
vertising) and by having broad inclusion and minimal exclusion cri-
Boston, MA; †Epidemiology Data Center, Graduate School of Public Health,
teria. Outpatients aged 18 to 75 years diagnosed with nonpsychotic
University of Pittsburgh, Pittsburgh, PA; ‡Department of Psychiatry, University
MDD with a baseline 17-item Hamilton Depression Rating Scale
of Texas Southwestern Medical Center, Dallas, TX; §Office of Clinical Sci-ences, Duke-National University of Singapore, Singapore; ||Department of
(Hamilton, 1960; Hamilton, 1967) score of 14 or greater were eligi-
Psychiatry and Behavioral Sciences, Northwestern University Feinberg School
ble. Eligible patients (n = 2876) were treated with the selective se-
of Medicine, Chicago, IL; and ¶Department of Psychology, Harvard University,
rotonin reuptake inhibitor citalopram for up to 14 weeks. Citalopram
was started at 20 mg/day and titrated to a target dose of 60 mg/day
The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study
was supported by the NIMH through the N01 MH-90003 contract. The content
by week 6, with flexibility to titrate more slowly if necessary.
of this publication does not necessarily reflect the views or policies of the
The WSAS is a five-item scale used to assess work, home
Department of Health and Human Services, nor does the mention of trade
management, social leisure activities, private leisure activities, and
names, commercial products, or organizations imply endorsement by the US
This report represents secondary analyses of the STAR*D trial. The STAR*D study
the scale ranges from 0.70 to 0.94, and test-retest correlation is 0.73
is registered at Clinical Trials as Sequenced Treatment Alternatives to Relieve
(Mundt et al., 2002). In STAR*D, the WSAS was administered using
Depression (STAR*D; http://clinicaltrials.gov/ct2/home; NCT00021528).
an interactive voice response (IVR) system, which has been shown
Preliminary results were previously presented in poster form at NCDEU: New Research
Approaches for Mental Health Interventions, Phoenix, AZ, May 28, 2008.
Y0.86) with the clinician-administered ver-
Send reprint requests to John W. Denninger, MD, PhD, Massachusetts General
sion (Mundt et al., 2002). The current analysis focused on the social
Hospital, 151 Merrimac St, Ste. 400, Boston, MA 02114-4717.
activities item: ‘‘3. Because of my [disorder], my social leisure ac-
tivities (with other people, such as parties, bars, clubs, outings, visits,
Copyright * 2011 by Lippincott Williams & Wilkins
dating, home entertainment) are impaired,’’ which was rated using
ISSN: 0022-3018/11/19910-0807DOI: 10.1097/NMD.0b013e31822fcbe2
a scale ranging from 0 (‘‘not at all’’) to 8 (‘‘very severely impaired’’).
The Journal of Nervous and Mental Disease & Volume 199, Number 10, October 2011
Copyright 2011 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
The Journal of Nervous and Mental Disease & Volume 199, Number 10, October 2011
The QIDS-SR is a well-validated 16-item self-rated scale of depres-sive symptoms (Rush et al., 2003), which captures the nine criteria
TABLE 2. Pearson Product Moment Correlation (r) andProportion of Variance Accounted for (R2) Between Change
used to diagnose major depressive episode in the DSM-IV. It was
in WSAS Item 3 and Individual QIDS-SR Items or Total QIDS-SR
also administered using the IVR system. Scores for individual items
range from 0 to 3; the score for the entire instrument ranges from0 to 27.
Patients who had QIDS-SR and WSAS scores for entry and exit
(n = 1846) were included in this post hoc analysis. We compared
the change (exitYentry) in the social activities item of the WSAS (item
3) to the change in individual items of the QIDS-SR. The Pearson
product-moment correlation was computed between the change inWSAS item 3 and the change in each QIDS-SR item (for a total of
16 separate correlations); for these correlations, > was adjusted using
the Bonferroni correction, yielding an > of 0.003 (= 0.05/16). In
addition, the Pearson product-moment correlation was computed be-
tween the change in WSAS Item 3 and the change in total QIDS-SR
score. Proportion of variance was calculated as the square of Pearson r.
The STAR*D level 1 analyzable sample of 2876 has been
reported elsewhere (Trivedi et al., 2006a). Of these 2876 patients,
1846 had both baseline and exit assessments of the WSAS. Table 1
shows the baseline characteristics of the 1846 patients included in this
analysis; these were not significantly different from the characteristics
QIDS-SR indicates Quick Inventory of Depressive SymptomatologyYSelf-report;
WSAS, Work and Social Adjustment Scale.
For WSAS Item 3, mean change (exitYentry) was j1.9 T 2.8
(n = 1846, p G 0.0001), with change values ranging from j8 (im-provement) to 8 (worsening). For the 16-item QIDS-SR, total meanchange (exitYentry) was j6.3 T 6.7 (n = 1846, p G 0.0001), with
was modestly correlated with 4 of the 14 individual QIDS-SR items:
change values ranging from j25 (improvement) to 13 (worsening).
sad mood (r = 0.48, p G 0.001), concentration/decision making (r =
Table 2 shows Pearson product moment correlation (r) and the
0.44, p G 0.001), involvement (r = 0.42, p G 0.001) and energy/
proportion of the variance (r2) in WSAS item 3 accounted for by the
fatigability (r = 0.40, p G 0.001). As Table 2 shows, however, only
change in individual QIDS-SR items. Change in social functioning
16% to 23% of the variance in the change in social functioningwas accounted for by each of these items individually. The remain-der of the items each explained 10% or less of the variance in thechange in social functioning. Although the change in the WSAS so-
TABLE 1. Patient Sample Descriptive Characteristics
cial activities item was more highly correlated with the change intotal QIDS-SR score (r = 0.58, p G 0.001), the change in depressive
symptoms overall only accounted for 34% of the variance in the
Rapaport et al. (2005) compared baseline symptom measures
with baseline quality of life measures in an array of mood and anxiety
disorders and found that ‘‘illness-specific symptoms’’ accounted for
only a small to modest proportion of the variance in quality of life,
leading them to conclude that quality of life is a ‘‘related but semi-
independent component of DSM-IV syndromes’’ (p. 1176). In thisstudy, we sought to determine the extent to which improvements in
social functioning, as opposed to the broader concept of quality of
life, were related to improvements in MDD symptoms.
In this large (n = 1846), real-world sample of outpatients,
all QIDS-SR items (except for the infrequently reported increased
appetite and weight gain) were significantly correlated (Bonferroni-
corrected > = 0.003) with change in the social activities item of the
WSAS (Table 2). However, even the most highly correlated items
(sad mood, concentration/decision making, involvement, and energy/
fatigability) individually account for only 16% to 23% of the variance
in social functioning. The less highly correlated items (sleep onsetinsomnia, self-outlook, suicidal ideation, psychomotor slowing, mid-
nocturnal insomnia, decreased appetite, psychomotor agitation, early
morning insomnia, hypersomnia, decreased weight, and increased
appetite) individually account for only 1% to 10% of the variance.
Even the change in total QIDS-SR score accounted for only 34%
Copyright 2011 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
The Journal of Nervous and Mental Disease & Volume 199, Number 10, October 2011
of the variance in the change in WSAS item 3. It should be noted,
Bristol-Myers Squibb Company, Cephalon Inc, Cyberonics Inc, Eli Lilly
as well, that the wording of the WSAS instructions (which explicitly
& Company, Evotec, Fabre-Kramer Pharmaceuticals Inc, Forest
ask subjects to evaluate the effect of their disorder on their social
Pharmaceuticals, GlaxoSmithKline, Janssen Pharmaceutica Products,
functioning) would be expected to bias subjects into linking social
LP, Johnson & Johnson PRD, Meade Johnson, Medtronic, Neuronetics,
functioning and depression symptoms. As such, the proportion of
Otsuka Pharmaceuticals, Parke-Davis Pharmaceuticals Inc, Pfizer Inc,
variance in social functioning accounted for by depression symp-
Sepracor, SHIRE Development, Solvay Pharmaceuticals, VantagePoint,
toms, which we report here, is likely to be an overestimate.
and Wyeth-Ayerst Laboratories. He receives research support from
Similar to the results here, our analysis of changes in social
the Agency for Healthcare Research and Quality (AHRQ), Corcept
functioning and depression symptoms in a double-blind, randomized,
Therapeutics Inc, Cyberonics Inc, Merck, National Alliance for Re-
placebo-controlled trial comparing Hypericum perforatum to sertra-
search in Schizophrenia and Depression, NIMH, National Institute on
line showed that only 25% of the variance in the change in social
Drug Abuse, Novartis, Pharmacia & Upjohn, Predix Pharmaceuticals
functioning, measured using the Sheehan Disability Scale (Sheehan
(Epix), Solvay Pharmaceuticals Inc, and Targacept. A. John Rush
et al., 1996), was accounted for by the variance in the change in
reports receiving royalties from UT Southwestern, speaking fees from
depression symptoms during the 8-week acute phase (Denninger
Otsuka Pharamaceuticals, and consultant fees from Best Practices.
et al., 2008). These and our current results seem to support the con-
Jackie Gollan has received research support from NIMH, National
clusion by Rapaport et al. (2005) that quality of life measures cap-
Alliance for Research in Schizophrenia and Depression, and Amer-
ture a component of mood and anxiety disorders partially distinct
ican Foundation of Suicide Prevention. She has received royalties
from American Psychological Association and Guilford Press. She
Our study has several limitations. First, our use of WSAS item
has owned shares of Pfizer and Bristol-Myers Squibb stock. She has
3 as a proxy measure of social functioning may define social func-
received a speaker honoria from AstraZeneca. She is a consultant for
tioning too narrowly, given that item 3 refers only to social leisure
Prevail Inc. Diego Pizzagalli has received consulting fees from ANT
activities. Second, there are no studies, to our knowledge, correlating
North America Inc (Advanced Neuro Technology) and AstraZeneca
WSAS item 3 scores to total scores on other validated social func-
and honoraria from AstraZeneca. Maurizio Fava has received re-
tioning scales. Finally, we have not controlled for comorbid anxiety
search support from Abbott Laboratories, Alkermes Inc, Aspect
disorders, symptoms of which can also contribute to deficits in so-
Medical Systems, AstraZeneca, BioResearch, BrainCells Inc, Bristol-
cial functioning and quality of life (Rapaport et al., 2005).
Myers Squibb, Cephalon Inc, Clinical Trials Solutions LLC, Covidien,Eli Lilly and Company, EnVivo Pharmaceuticals Inc, Forest Pharma-ceuticals Inc, Ganeden Biotech Inc, GlaxoSmithKline, Johnson &Johnson Pharmaceutical Research & Development, Lichtwer Pharma
GmbH, Lorex Pharmaceuticals, Novartis AG, Organon Pharmaceu-
In sum, the current results support the idea that social func-
ticals, PamLab LLC, Pfizer Inc, Pharmavite LLC, Roche, RTC Logic
tioning measures capture a component of MDD that is distinct from
LLC, Sanofi-Aventis US LLC, Shire, Solvay Pharmaceuticals Inc,
symptom-based measures. Social functioning measures may provide a
Synthelabo, and Wyeth-Ayerst Laboratories. Dr. Fava has received
window into patients’ recovery that incompletely overlaps with mea-
advisory/consulting fees from Abbott Laboratories, Affectis Pharma-
sures of depression symptoms. Further research is needed to deter-
ceuticals AG, Amarin Pharma Inc, Aspect Medical Systems,
mine the optimal way to track and directly remediate quality of life
AstraZeneca, Auspex Pharmaceuticals, Bayer AG, Best Practice
Project Management Inc, BioMarin Pharmaceuticals Inc, BiovailCorporation, BrainCells Inc, Bristol-Myers Squibb, CeNeRx Bio-Pharma, Cephalon Inc, Clinical Trials Solutions LLC, CNS Response
Inc, Compellis Pharmaceuticals, Cypress Pharmaceutical Inc, Dov
John Denninger has received or is receiving salary support
Pharmaceuticals Inc, Eisai Inc, Eli Lilly and Company, EPIX Phar-
from the National Institutes of Health, the Centers for Disease Con-
maceuticals Inc, Euthymics Bioscience Inc, Fabre-Kramer Pharma-
trol, the Kaplen Foundation, Massachusetts General Hospital, and
the Massachusetts General Hospital Physicians Organization, as
GlaxoSmithKline, Gruenthal GmbH, Janssen Pharmaceutica, Jazz
well as (through fellowships funded by unrestricted educational
Pharmaceuticals Inc, Johnson & Johnson Pharmaceutical Research &
grants) from AstraZeneca, Bristol-Meyers Squibb, Cephalon, Janssen,
Development LLC., Knoll Pharmaceuticals Corp., Labopharm Inc,
Lilly, Merck, Pfizer, and Wyeth. Dr. Denninger has also received hon-
Lorex Pharmaceuticals, Lundbeck Inc, MedAvante Inc, Merck & Co.
oraria (through unrestricted educational grants) from AstraZeneca,
Inc, Methylation Sciences, Neuronetics Inc, Novartis AG, Nutrition 21,
Bristol-Meyers Squibb, Cephalon, Eli Lilly, Janssen, Pfizer, and Wyeth.
Organon Pharmaceuticals, PamLab LLC, Pfizer Inc, PharmaStar,
Dr. Denninger and/or the Depression Clinical and Research Program
Pharmavite LLC, Precision Human Biolaboratory, Prexa Pharmaceu-
of Massachusetts General Hospital have received or are receiving
ticals Inc, PsychoGenics, Psylin Neurosciences Inc, Ridge Diagnostics
research support from Abbott, Alkermes, Aspect Medical Systems,
Inc, Roche, RCT Logic LLC, Sanofi-Aventis US LLC., Sepracor Inc,
AstraZeneca, Bristol-Myers Squibb, Cephalon, Eli Lilly, Forest Labo-
Schering-Plough Corporation, Solvay Pharmaceuticals Inc, Somaxon
ratories, GlaxoSmithKline, Johnson & Johnson, Lichtwer Pharma
Pharmaceuticals Inc, Somerset Pharmaceuticals Inc, Synthelabo,
GmbH, Lorex Pharmaceuticals, Novartis, Organon, Pamlab, Pfizer,
Takeda Pharmaceutical Company Limited, Tetragenex Pharmaceu-
Pharmavite, Roche, Sanofi-Synthelabo, Solvay, and Wyeth. Adrienne
ticals Inc, TransForm Pharmaceuticals Inc, Transcept Pharmaceuticals
van Nieuwenhuizen reported no biomedical financial interests or po-
Inc, Vanda Pharmaceuticals Inc, and Wyeth-Ayerst Laboratories.
tential conflicts of interest. Stephen Wisniewski reports having received
Dr. Fava also reports receiving speaking/publishing fees from Adamed
consulting fees from Cyberonic Inc (2005Y2009), ImaRx Therapeutics,
Co, Advanced Meeting Partners, American Psychiatric Association,
Inc (2006), Bristol-Myers Squibb Company (2007Y2008), Organon
American Society of Clinical Psychopharmacology, AstraZeneca,
(2007), Case-Western University (2007), and the Singapore Clinical
Belvoir Media Group, Boehringer Ingelheim GmbH, Bristol-Myers
Research Institute (2009). James Luther reported no biomedical fi-
Squibb, Cephalon Inc, Eli Lilly and Company, Forest Pharmaceuticals
nancial interests or potential conflicts of interest. Madhukar Trivedi is a
Inc, GlaxoSmithKline, Imedex LLC, MGH Psychiatry Reed/Primedia,
consultant to or is on a speakers’ bureau for Abbott Laboratories Inc,
MGH Psychiatry Academy/Reed Elsevier, Novartis AG, Organon
Abdi Ibrahim, Akzo (Organon Pharmaceuticals Inc), AstraZeneca,
Pharmaceuticals, Pfizer Inc, PharmaStar, United BioSource Corp, and
Copyright 2011 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
The Journal of Nervous and Mental Disease & Volume 199, Number 10, October 2011
Wyeth-Ayerst Laboratories. Dr. Fava has equity holdings in Compellis,
Mundt JC, Marks IM, Shear MK, Greist JH (2002) The Work and Social Adjustment
and receives royalty/patent or other income from the following: patent
Scale: A simple measure of impairment in functioning. Br J Psychiatry. 180:461Y464.
for the Sequential Parallel Comparison Design and patent applicationfor a combination of azapirones and bupropion in MDD, copyright
Rapaport MH, Clary C, Fayyad R, Endicott J (2005) Quality-of-life impairment in
depressive and anxiety disorders. Am J Psychiatry. 162:1171Y1178.
royalties for the Massachusetts General Hospital Cognitive andPhysical Functioning Questionnaire, Sexual Functioning Inventory,
Rush AJ, Fava M, Wisniewski SR, Lavori PW, Trivedi MH, Sackeim HA, Thase
ME, Nierenberg AA, Quitkin FM, Kashner TM, Kupfer DJ, Rosenbaum JF,
Antidepressant Treatment Response Questionnaire, Discontinuation
Alpert J, Stewart JW, McGrath PJ, Biggs MM, Shores-Wilson K, Lebowitz BD,
Emergent Signs and Symptoms, and the State vs Trait, Assessability,
Ritz L, Niederehe G; STAR*D Investigators Group (2004) Sequenced treatment
Face Validity, Ecological Validity, and Rule of Three P’s Criteria.
alternatives to relieve depression (STAR*D): Rationale and design. ControlClin Trials. 25:119Y142.
Rush AJ, Trivedi MH, Ibrahim HM, Carmody TJ, Arnow B, Klein DN,
Markowitz JC, Ninan PT, Kornstein S, Manber R, Thase ME, Kocsis JH,
Keller MB (2003) The 16-Item Quick Inventory of Depressive Symptomatology(QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): A psychometric
Denninger JW, van Nieuwenhuizen AO, Mischoulon D, Crawford CM, Clain A,
evaluation in patients with chronic major depression. Biol Psychiatry. 54:
Baer L, Fava M (2008) Social functioning changes in a randomized, placebo-
controlled trial of major depressive disorder treatment with Hypericumperforatum and sertraline. Paper presented at: 161st Annual Meeting of the
Sheehan DV, Harnett-Sheehan K, Raj BA (1996) The measurement of disability.
American Psychiatric Association, Washington, DC. May 5, 2008.
Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatr.
Trivedi MH, Rush AJ, Wisniewski SR, Nierenberg AA, Warden D, Ritz L,
Norquist G, Howland RH, Lebowitz B, McGrath PJ, Shores-Wilson K,
Hamilton M (1967) Development of a rating scale for primary depressive illness.
Biggs MM, Balasubramani GK, Fava M; STAR*D Study Team (2006a)
Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: Implications for clinical practice. Am J Psychiatry.
Hirschfeld RM, Dunner DL, Keitner G, Klein DN, Koran LM, Kornstein SG,
Markowitz JC, Miller I, Nemeroff CB, Ninan PT, Rush AJ, Schatzberg AF,Thase ME, Trivedi MH, Borian FE, Crits-Christoph P, Keller MB (2002) Does
Trivedi MH, Rush AJ, Wisniewski SR, Warden D, McKinney W, Downing M,
psychosocial functioning improve independent of depressive symptoms? A
Berman SR, Farabaugh A, Luther JF, Nierenberg AA, Callan JA, Sackeim HA
comparison of nefazodone, psychotherapy, and their combination. Biol
(2006b) Factors associated with health-related quality of life among outpa-
tients with major depressive disorder: a STAR*D report. J Clin Psychiatry. 67:185Y195.
Kennedy N, Foy K, Sherazi R, McDonough M, McKeon P (2007) Long-term social
functioning after depression treated by psychiatrists: A review. Bipolar Disord.
Weissman MM (2000) Social functioning and the treatment of depression. J Clin
Copyright 2011 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Impressionen aus Mali Von H. Querfurt 12.03.09 „Na, wie war´s in Afrika?“ So höre ich es von überall seit ich wieder zurück bin aus Mali. Wollen sie wirklich etwas hören? Glauben sie wirklich, dass man mit wenigen Worten all das zusammenfassen kann, das uns in den 2 zurückliegenden Wochen bewegt hat? Und kann ich wirklich diese Empfindungen, die wir in Mali hatten in gan
PERSONAL DETAILS (Confidential) Surname:___________________ First Name:______________________ Title:_______ Address:_____________________________________ Suburb: ______________ Postcode: _____ Home Phone: ________________ Mobile Phone:___________________________________ Business Phone:______________ Email:__________________________________________ Date of Birth: / / Occupation