25

Determining the Responsiveness of Depression Questionnaires and 

Optimal Treatment Duration for Antidepressant Medications Evidence-based Synthesis Program

APPENDIX A: SEARCH STRATEGIES

Key Question #1

Database: PubMed ® <1950 to February 2, 2009>

1 “Depressive Disorder, Major”[Mesh] OR (major AND depression) 32348

2

PHQ9 OR “Patient Health Questionnaire” OR “Beck Depression Inventory” OR BDI 

OR BDI-II OR GDS OR “Geriatric Depression Scale” OR SDDS-PC OR “symptom 

driven diagnostic system primary care” OR PRIMEMD OR “Primary care evaluation of mental disorders” OR DEPS OR “CESD” OR “CES-D” OR (“Center” AND 

Epidemiologic* AND Stud* AND Depression) OR “CESD-10”

11913

3 (change OR changes OR Improv* OR decreas*) AND (score OR scale* OR scores 

OR responsiv* OR sensitiv*) 447184

4 #1 AND #2 AND #3 522

5

(questionnaire OR psychometrics) AND (“Depressive Disorder, Major”[Mesh] OR 

(major AND depression)) AND (((responsiv*[tw] OR sensitiv*[tw]) AND (change[tw] 

OR changes[tw])) OR (clinical*[tw] AND important[tw] AND (change[tw] OR 

changes[tw])))

126

6 #4 OR #5 626

7 #6 Limits: Humans, English, All Adult: 19+ years 516

Database: PsychInfo <up to February 2, 2009>

1 major depression/ 58084

2 major depression.tw. 16118

3

(PHQ9 or “Patient Health Questionnaire” or “Beck Depression Inventory” or BDI or 

BDI-II or GDS or “Geriatric Depression Scale” OR SDDS-PC or “symptom driven 

diagnostic system primary care” or PRIMEMD or “Primary care evaluation of mental disorders” or DEPS).tw. 9324

4

((change or changes or Improv* or decreas*) and (score or scale* or scores or 

responsiv* or sensitiv*)).tw. 82044

5 #1 or #2 61641

6 #3 and #4 and #5 893

7

limit 6 to ((“followup study” or “longitudinal study” or “prospective study” or “systematic review”) AND “adulthood age 18 yrs AND older” AND “peer-reviewed journal” 

AND English AND human) 157
26

Determining the Responsiveness of Depression Questionnaires and 

Optimal Treatment Duration for Antidepressant Medications Evidence-based Synthesis Program

Key Question #2, Systematic Reviews

Database: PubMed ® <1950 to March 02, 2009>

1 (“Depressive Disorder”[Mesh] OR “major depression”) 63463

2 (antidepress* OR “Antidepressive Agents”[Mesh] OR “Antidepressive Agents 

“[Pharmacological Action]) 114617

3 (recurrence[Mesh] OR relaps* OR recurren*) 410446

4 #1 AND #2 AND #3 2073

5 #4 AND systematic[sb] 106

Key Question #2, Randomized Controlled Trials

Database: PubMed ® <1950 to March 01, 2009>

1 (“Depressive Disorder”[Mesh] OR “major depression”) 63463

2 (antidepress* OR “Antidepressive Agents”[Mesh] OR “Antidepressive Agents 

“[Pharmacological Action]) 114617

3 (recurrence[Mesh] OR relaps* OR recurren*) 410446

4 (randomized controlled trial[Publication Type] OR (randomized[Title/Abstract] AND 

controlled[Title/Abstract] AND trial[Title/Abstract]) 275051

5 #1 AND #2 AND #3 AND #4 428

6 Limits: Publication Date from 2007/01/01 to 2009/03/1, Humans, English, All Adult: 

19+ years 48 
27

Determining the Responsiveness of Depression Questionnaires and 

Optimal Treatment Duration for Antidepressant Medications Evidence-based Synthesis Program

APPENDIX B: FULL TEXT EXCLUSIONS

Inclusion Criteria for Key Question #1, Assessment Tools Responsive to Change

1. One of the specified instruments (PHQ-9, Beck Fast Screen, CESD-10, GDS-15, SDDS-PC, 

DEPS, PRIME MD)

2. Adults with depressive disorder: outpatient setting

3. Comparator: Comparison to an interview-based instrument

4. Study Design: Longitudinal 

5. Study Design: Sample > 50

6. English language article

General Exclusion Criteria*

Author & Ref #

NOT 1. NOT 2.NOT 3.NOT 4.NOT 5.NOT 6.

Ahava, 1998[51] X

Adler, 2004[52] X

Allard, 2004[53] X

Altamura, 1989[54] X

Amsterdam, 2008[55] X

Babyak, 2000[56] X

Baldwin, 2008[57] X

Barbosa, 2003[58] X

Berkman, 2003[59] X

Berlim, 2005[60] X

Berlim, 2007[61] X

Boyer, 1998[62] X

Brody, 2006[63] X

Brown, 2000[64] X

Brown, 2005[65] X

Cassidy, 2005[66] X

Casten, 2000[67] X

Chen, 2006[68] X

Conradi, 2007[69] X

Cook,1999[70] X

Corney, 2005[71] X

Coulehan, 1997[72] X

Dalton, 2000[73] X

Davies, 2003[74] X

DeBattista, 2003[75] X

Dori, 1999[76] X
28

Determining the Responsiveness of Depression Questionnaires and 

Optimal Treatment Duration for Antidepressant Medications Evidence-based Synthesis Program

General Exclusion Criteria*

Author & Ref #

NOT 1. NOT 2.NOT 3.NOT 4.NOT 5.NOT 6.

Dubovsky, 2001[77] X

Dunner, 1987[78] X

Einarson, 2004[79] X

Fava, 1999[80] X

Fawcett, 1987[81] X

George, 1999[82] X

George, 2008[83] X

Goodnick, 1997[84] X

Goodnick, 1998[85] X

Judd, 2004[86] X

Kates, 2002[87] X

Koivumaa-Honkanen, 2008[88] X

Koran, 1995[89] X

Kroenke, 2006[90] X

Lesperance, 2007[91] X

Lett, 2007[92] X

Levitt, 1999[93] X

Liebowitz, 2007[94] X

Lustman, 1998[95] X

Lustman, 2000[96] X

Lydiard, 1997[97] X

Mazeh, 2007[98] X

McIntyre, 2005[99] X

Mohamed, 2006[100] X

Mulrow, 1998[101] X

Mynors-Wallis, 2000[102] X

Patkar, 2006[103] X

Perez, 1999[104] X

Picardi, 2005[105] X

Pollock, 1989[106] X

Posternak, 2001[107] X

Proudfoot, 2003[108] X

Pyne, 2002[109] X

Quilty, 2008[110] X

Raskin, 2003[111] X

Raskin, 2007[112] X

Rollman, 2002[113] X
29

Determining the Responsiveness of Depression Questionnaires and 

Optimal Treatment Duration for Antidepressant Medications Evidence-based Synthesis Program

General Exclusion Criteria*

Author & Ref #

NOT 1. NOT 2.NOT 3.NOT 4.NOT 5.NOT 6.

Rush, 2005[114] X

Rutherford, 2007[115] X

Salkovskis, 2006[116] X

Shelton, 2001[117] X

Singh, 2001[118] X

Skevington, 2001[119] X

Spalletta, 2002[120] X

Stark, 1985[121] X

Szegedi, 2005[122] X

Thase, 1997[123] X

Trivedi, 2004[124] X

Tutty, 2000[125] X

van Gurp, 2002[126] X

van Marwijk, 2008[127] X

Vinkers, 2004[128] X

Wade, 2008[129] X

Wise, 2007[130] X

Items in the table (e.g. Not 1) correspond to the inclusion criteria listed above the table

Inclusion Criteria for Key Question #2, Systematic Reviews

1. Systematic review evaluating anti-depressant vs. placebo. A systematic review contains a 

methods section with search strategy and approach to synthesizing the data

2. Patients: Adults with major depressive disorder who have remitted or improved substantially 

with anti-depressant medication, English language article

3. Outcome: Relapse/recurrence

General Exclusion Criteria*

Author & Ref #

NOT 1. NOT 2.NOT 3. 

Bauer 2009[131] X

Gartlehener 2008[132] X

Quaseem 2008[133] X

Anderson 2008[134] X

Papakostas 2007[135] X

Furukawa 2007[136] X

Zimmerman 2007[137] X

Lam 2004[138] X

Items in the table (e.g. Not 1) correspond to the inclusion criteria listed above the table*
30

Determining the Responsiveness of Depression Questionnaires and 

Optimal Treatment Duration for Antidepressant Medications Evidence-based Synthesis Program

Inclusion Criteria for Key Question #2, Randomized Controlled Trials

1. Study Design: Randomized Controlled Trial

2. Patients: Adults

3. Outcome: Relapse/recurrence

4. Compares anti-depressant vs. placebo

5. Patients: Adults with major depressive disorder who have remitted or improved substantially 

with anti-depressant medication

6. English language article

General Exclusion Criteria*

Author & Ref #

NOT 1. NOT 2.NOT 3.NOT 4.NOT 5.NOT 6.

Dombrovski 2008[139] X

Keller 2007[140] X

*Items in the table (e.g. Not 1) correspond to the inclusion criteria listed above the table
31

Determining the Responsiveness of Depression Questionnaires and 

Optimal Treatment Duration for Antidepressant Medications Evidence-based Synthesis Program

APPENDIX C: QUALITY RATINGS

Quality Rating for Key Question #1, Assessment Tools Responsive

to Change

Was the criterion standard applied and interpreted blinded to the results of the depression 

questionnaire?

Was the depression questionnaire applied and interpreted blinded to the results of the criterion 

standard?

Was the interview-based criterion standard a validated measure of depression severity?

Did follow-up of the enrolled sample exceed 80%?

Was the analysis appropriate to the study question?

Was the study funded by the pharmaceutical industry?

Was a conflict of interest disclosure given? If given, was there a potential conflict of interest?

Quality Rating for Key Question #2, Systematic Reviews

Was a focused clinical question clearly stated?

Was the search for relevant studies detailed and exhaustive?

Were inclusion/exclusion criteria clearly defined and appropriate?

Were primary studies evaluated for quality and appropriateness?

Were assessments of studies reproducible?

Were analyses conducted to measure variability in effect?

Were differences in how outcomes were reported and analyzed across studies were taken into 

consideration?

Was publication bias assessed?

Were clinically important outcomes (harms and benefits) reported?

Were the conclusions supported by the data presented?
32

Determining the Responsiveness of Depression Questionnaires and 

Optimal Treatment Duration for Antidepressant Medications Evidence-based Synthesis Program

Quality Rating for Key Question #2, Randomized Controlled Trials

Were the groups similar at baseline in terms of baseline characteristics and prognostic factors? 

Were depression outcomes assessed using a valid methodology and criteria?

Were subjects and providers blind to the intervention/exposure status of participants?

Were outcome assessors blind to exposure/intervention status?

Were incomplete outcome data adequately addressed?

Was there an important differential loss to follow-up between the compared groups (defined as ≥ 

10%)?

Was there an overall high loss to follow-up ( ≥ 20% for studies <12 months and ≥ 30% for 

studies of 12 month or longer duration)

Was there a conflict of interest?

Were the methods used for randomization adequate?

Was allocation concealment adequate? 
33

Determining the Responsiveness of Depression Questionnaires and 

Optimal Treatment Duration for Antidepressant Medications Evidence-based Synthesis Program

APPENDIX D: PEER REVIEW

Question: Are the objectives, scope, and methods for this review clearly described?

Reviewer Comment Reply

1 YES. The objectives, scope were very clear and appropriate. The methods were transparent and appropriately rigorous for a best evidence 

review, even though the types of studies sought to answer KQ1 and 

KQ2 were very different. It was helpful to have all of the information 

on search strategies, inclusion/exclusion criteria and data extraction in 

the appendices.

Acknowledged

2 The inclusion and exclusion criteria for Key Question 1 greatly diminish the synthesis’s scope. Given this limitation, I know of no additional 

studies that should have been included in the review for Key Question 

1 or 2.

In general, the Synthesis needs a strong editing (e.g. ensuring consistency in abbreviations, defining abbreviations before applying them, 

correcting punctuation and formatting) 

In addition, there were several places within the synthesis where this 

reviewer could not understand the meaning of a sentence. Specifically:

• Page 8, line 11-12 – “For the finding that the MCID is 5” would 

be best to define this as the Mean Change in Depression Score for 

MDD 

• Page 16, line 11 – “the similarity of groups similar at baseline” 

• Page 25, line 2 – “the number needed”...(number of what?)

• The Evidence Tables 1-5 are very difficult to read because of inconsistent formatting and text layout.

The inclusion/exclusion 

criteria were developed 

with the stakeholders to 

focus on the questions of 

interest.

Editing has been completed to ensure consistency

These sentences have 

been edited to clarify the 

meaning.

We did not find the Page 

25, line 2 reference; on 

page 26 we state the 

“number needed to treat 

to prevent one relapse...”

3 Yes, all of these aspects are clearly described. Acknowledged

4 a) Objectives are clearly defined.

b) Scope is also clearly defined, with the exception that the assessment 

tools that are surveyed are those immediately referable to depressive 

disorders and their symptoms (i.e., disease-specific). One could also 

perceive quality of life, functional capacities, health services utilization and costs as relevant outcomes. I agree with focusing on diseasespecific assessment, and this is clear as the manuscript goes on, but I 

would make it absolutely clear up front so as to frame the boundaries of 

this review explicitly.

c) Methods are clearly defined.

Acknowledged

Edits made to clarify 

that focus is limited to 

depression symptom 

questionnaires

Acknowledged
34

Determining the Responsiveness of Depression Questionnaires and 

Optimal Treatment Duration for Antidepressant Medications Evidence-based Synthesis Program

Question: Is there any indication of bias in our synthesis of the evidence? 

Reviewer Comment Reply

1 NO. Appropriate precautions were used to minimize bias including 1) 

having 2 researchers review the titles and/or abstracts of articles for 

potential inclusion, 2) having 1-2 reviewers over-read the data abstraction forms to assure accurate abstraction, 3) using well known criteria to 

assess the quality of the studies that included items about funding source 

and conflict of interest (Appendix C) and strength of evidence (GRADE), 

4) providing readers with enough detail to assure transparency, and 5) 

including comments from outsider reviewers in an Appendix. 

Acknowledged

2 It was not clear how this group of authors was selected to conduct the 

evidence synthesis. Was this a competitive application or were the 

authors selected based on their willingness to conduct the synthesis, their 

expertise in the area of study, or other factors?

This has been addressed 

in the topic refinement 

section

3 No, there is no indication of bias Acknowledged

4 No Acknowledged

Question: Are there any studies on responsiveness of depression questionnaires or relapse prevention trials 

related to this report that we have overlooked?

Reviewer Comment Reply

1 NO. These are difficult studies to do well and get funded appropriately 

since they require a diagnostic interview as a reference standard (KQ1) 

and have a long follow-up period (KQ2). I was not surprised that few 

studies were found.

Acknowledged

2 None

3 No, there are no responsiveness studies missed to include in the analysis. 

However, in the discussion of results, the authors refer to a UK qualitative 

study suggesting clinicians are skeptical of depression questionnaires. If 

this study is cited, the authors should also cite two recent studies showing 

US primary care physicians (Nease et al, 2008) and psychiatrists (Duffy et 

al) found the PHQ-9 clinically useful and continued to use.

Also, the authors did not include the 10-item CES-D short-form (Andresen et al, 1994). There are probably no studies testing its responsiveness, 

but I mention it simply because it does fall within the authors’ 10-item 

inclusion criteria for brief measures.

• Nease DE, Nutting PA, Dickinson WP, Bonham AJ, Graham DG, Gallagher KM, Main DS. Inducing sustainable improvement in depression 

care in primary care practices. Joint Commission Journal on Quality 

and Patient Safety 2008;34:247-255.

• Duffy FF, Chung H, Trivedi M, Rae DS, Regier DA, Katzelnick DJ. 

Systematic use of patient-rated depression severity monitoring: is 

it helpful and feasible in clinical psychiatry? Psychiatric Services 

2008;59:1148–1154.

• Andresen EM, Malmgren JA, Carter WB, Patrick DL. Screening for 

depression in well older adults: evaluation of a short form of the CESD (Center for Epidemiologic Studies Depression Scale). Am J Prev 

Med. 1994; 10: 77–84.

The discussion has been 

revised and the additional 

studies referenced

The CESD-10 was not 

excluded but our search 

did not include terms 

specific to this instrument. We have updated 

the search and results. 49 

additional citations were 

identified but none met 

eligibility criteria

4 None that meet the defined criteria, to my knowledge Acknowledged
35

Determining the Responsiveness of Depression Questionnaires and 

Optimal Treatment Duration for Antidepressant Medications Evidence-based Synthesis Program

Question: Please write additional suggestions or additional comments below for this report. If applicable, 

please indicate the page and line numbers from the draft report. 

Reviewer Comment Reply

1 The target audience for this report includes administrators and policy 

makers. They would benefit from a conclusion section at the end of 

the Executive Summary that simply stated the conclusions followed 

by quality of the evidence supporting the conclusion. This could even 

be 2 bullet points. Administrators and policy makers are likely to start 

with this bottom line and read backwards if they need more detail. For 

example, you could use lines 14-16 on page 24, lines 11-15 on page 

23, and lines 44-46 and 1-4 on pages 24 and 25 after editing them. For 

KQ2, it helps to have both the RR and NNT. 

The results section in the Executive Summary was difficult to follow for KQ1, lines 31-43, page 7. The methods paragraph describes 

the standardized response mean (SRM) then the results start with the 

mean change score. I would list the mean change score and SRM for 3 

months, then for 6 months. Although you save words in the current version, it is harder to read. Also in line 41 define the abbreviation MCID 

since you use it later.

Figure 1 on page 13 is difficult to read in its current size. It would be 

good if it could be enlarged.

In Table 7 on page 26, it would be helpful to include some data in the 

comments section after the summary comment, e.g., mean change score 

expected of responders. Also, I would include the NNT with the RR.

Appendix B is important to document why studies were excluded/

include. Using “not 1,” “not 2,” etc is a bit confusing, but I could not 

think of a better way to concisely describe these criteria for the table 

headers.

In Appendix C, page 37, line 30 has a typo. I think it should read “...

evaluated for quality and appropriateness?”

The evidence tables are dense, but the details are important for transparency.

We have followed this 

suggestion

We have followed this 

suggestion

The figure has been 

enlarged

We have followed this 

suggestion

Modified to improve 

clarity

Thank you. Typo corrected

Acknowledged
36

Determining the Responsiveness of Depression Questionnaires and 

Optimal Treatment Duration for Antidepressant Medications Evidence-based Synthesis Program

2 Key Question 1

In general, this reviewer felt that Key Question 1 was not an “assessment of tools that were responsive to change”, but rather a review of 

the PHQ-9’s (and at times the PHQ-2’s) responsiveness to change. 

This apparent bias first appears in the background section in which the 

synthesis first author’s work (reference 15) concluded that the PHQ9 had better performance characteristics and gave more information 

for depression diagnosis than other instruments. Thus, from the very 

beginning, this reviewer was confused on why Key Question 1 was 

requested for a synthesis review.

Given these issues, the background on Depression Questionnaires either 

1) needs to be expanded to describe the 7 other questionnaires that have 

< 10 items, or 2) for the sake of transparency, the background section 

should clearly state in the text that the work that identified the PHQ-9 

as the optimal self reported primary care depression measure was conducted by the first author of this synthesis. 

The fact that the primary manuscripts reviewed for Key Question 1 

(references 29-32) were all conducted by the same first author (Lowe) 

should be noted in the limitations.

Since the authors note that there has been no work to date measuring 

responsiveness to change in instruments was for the PHQ-9 and was 

applied in a population greater than age 60, the Future Research section 

should also call for additional studies to identify whether or not the 

PHQ-9 (and other measures) respond to change in younger populations.

Key Question 2

Given that the number of prior episodes is a major risk for relapse, 

did any of the RCT’s reviewed for Key Question 2 address this issue? 

Though this is alluded to on page 22, lines 17-20, it should be more 

clearly stated.

We have attempted to 

strengthen the message 

that we searched for ALL 

feasible instruments, but 

only found data for the 

PHQ. The background 

has been modified to 

briefly describe the eligible questionnaires.

Discussion has been 

updated to note this issue.

No change; the PHQ9 

has been evaluated in 

mid-life and older adults

The number of prior depressive episodes was not 

systematically reported in 

the trials

3 Page 6, lines 17-36: In paragraph, authors state “Clinical guidelines 

recommend continuation treatment for 4-6 months ... However, clinical guidelines for longer-term maintenance phase treatment are more 

variable and performance indicators (e.g., HEDIS) do not address 

maintenance phase treatment.” But Key Question #2 is: “What is the 

minimum duration of continuation phase treatment to decrease risk of 

relapse?” Continuation (1st 4-9 months after remission) and maintenance (long-term treatment after continuation) phases of treatment 

have distinct meanings in some guidelines, and the authors’ going back 

and forth between these 2 terms (and in other places the vaguer phrase 

“long-term treatment” leaves the reader confused whether their review 

is focused on evidence for continuation phase treatment, maintenance 

phase, or both. Please clarify for reader.

Page 8, Lines 31-46: This section clarifies the answer to the question 

above (i.e., this review looks at both continuation and maintenance 

treatment) – this should be clarified on p. 6

This comment and the 

following comment have 

been addressed in the revision. The background 

on page 6 clarifies that 

the review addressed 

continuation and maintenance phase treatment

As above
37

Determining the Responsiveness of Depression Questionnaires and 

Optimal Treatment Duration for Antidepressant Medications Evidence-based Synthesis Program

Page 14, Lines 36-37: There is a short-form of the CES-D (10 items). 

The reference is provided under #3 above. The authors might note why 

this was not included in their search.

Page 15, Lines 7-8: The authors might add to their parenthetical examples of measures longer than 10 items the Inventory for Depressive 

Symptoms (since it was used in the landmark STAR*D trial where 40% 

of patients were from primary care) and the CES-D.

Page 18, Lines 7-9: The authors state: “In addition the study team included a biostatistician from Pfizer, and Pfizer funded the current study 

and the PHQ-9 development, suggesting a potential conflict of interest.” 

However, unlike drugs sold for profit, the PHQ-9 always has been made 

available free of charge. Thus, the potential conflict of interest is much 

weaker than if drug trials were being analyzed.

Page 24, Lines 35-42: The authors state: “Qualitative studies show that 

patients favor questionnaires to measure depression severity but general 

practitioners in the UK were cautious about the validity and utility of these 

measures and skeptical about the motives behind their introduction. General practitioners specifically valued clinical judgment more than objective 

assessment. Practitioners were aware of the potential for manipulation of 

indicators for economic reasons. If these findings hold true for VA clinicians, these barriers would need to be addressed for successful implementation of the PHQ-9 (or any other measure) for routine monitoring.”

However, two recent studies in the US showed good uptake of the 

PHQ-9 by primary care physicians (Nease et al 2008) and psychiatry 

(Duffy et al 2008).

Previously addressed

This recommendation 

was followed

This is a valid point 

about the availability 

free of charge. However, 

potential COI still exists 

as increased identification of depression may 

increase sales or related 

for-profit products. No 

change

Previously addressed

Question: Recommendations for future ESP topical areas of interest or programmatic comments may also 

be included at the end of this section. 

Reviewer Comment Reply

1 Topics: 

1. Treatment of chronic obstructive pulmonary disease

2. Palliative chemotherapy for lung, colon, and possibly other cancers

Programmatic Comments:

1. Translating evidence syntheses into policy and organizational decisions will be a difficult step. I assume the ESPs are linked to OQP, 

but there should be outreach to VISNs and medical centers.

Acknowledged

Acknowledged

2 None

3 None at this time

4 If feasible, a review of evidence-based methods and data on suicide risk 

evaluation in primary care settings would be helpful

Acknowledged
38

of Depression Questionnaires and 

Antidepressant Medications Evidence-based Synthesis Program

vidence Tables

stion #2 Systematic Review, Hansen, 2008[35]

haracteresigns

Patient Characteristics Outcomes Assessed Relative risks/other sum- mary effect measures Comments Quality Rating

udies: 23 

ontrolled 

untries:

uded US

UK, France, 

multinational

ervention: 

eneration 

ssant: bu

citalopram, 

e, escit

fluoxetine, 

ine, mir

nefazadone, 

e, sertraline, 

, venla

ettings 

ticles):

ttings: 4

nt”: 12

n: 6

22

Total no. of patients: 8241Age: Mean age range generally 40-50. Two trials w/ range 65-87Gender:Most >60% femaleMany >65% femaleDepressive Disorder:26 required MDD diagnosis, 1 required only QIDS-C-16 > 5.Severity of initial symptoms:Many used HDRS. Some had requirement for # episodes.Race/ethnicity: NG Exclusion:Use of other psychotropics, presence of comorbid psychiatric or medical disease most common

Relapse definition: most used increase in HAMD or MADRS above predefined cutoff pt. Some added clinical criteria.Treatment duration (after acute phase): Continuation: 14-72 weeksMaintenance: 36-100 weeks.12 trials: f/up <1yr (redefined as continuation)11 trials: f/up 1+ yr (redefined as maintenance)Outcomes:1) Continuation phase relapse rate compared to placebo2) Maintenance phase recurrence rate compared to placeboOther Outcomes: 4) Rates of adverse events5) Rates of loss to f/up attributed to adverse events

Relapse re-defined as relapse w/in 

1 yr continuationRecurrence re-defined as relapse w/in 1 yr maintenanceOutcomes:1) Unadjusted frequency of relapse was 22% active treatment, 42% placebo2) Unadjusted frequency of recurrence was 26% for active treatment, 48% placeboOther Outcomes: 3) Adverse events rates given for individual studies when reported (compared w/ acute-phase studies, relative incidence of most common adverse events was lower)5) Loss to f/up attributed to adverse events was 7% for active treatment and 4% for placebo (did not report significance) 

Comments: -In meta-regression, duration of follow-up did not impact effect size -Authors reported fair quality of studies included-Moderate grade evidence

Quality Rating: highFocused clinical question? YesDetailed & exhaustive search? YesInclusion/exclusion criteria clearly defined & appropriate? YesStudies evaluated for quality & appropriately? YesAssessments of studies reproducible? YesMeasured variability in effect? YesDifferences in how outcomes were reported and analyzed across studies considered? YesPublication bias assessed? Yes,Clinically important outcomes (harms & benefits) reported? YesConclusions supported by data presented? Yes
39

of Depression Questionnaires and 

Antidepressant Medications Evidence-based Synthesis Program

stion #2 Randomized Controlled Trials

ve

Patient Baseline Characteristics

Inclusion/Exclusion Criteria Outcome

Results 

Adverse Events (%) Analysis

Quality Rating 

ve:

 

s

ne 

:

ne 

y

Mean Age:Venlafaxine ER 42.0 Placebo 42.6 Sex (% female):Venlafaxine ER 69%Placebo 67%Race (% white):Venlafaxine ER 81%Placebo 88%Baseline (HDRS)Venlafaxine ER 4.3Placebo 4.9

Inclusion Criteria:

• ≥ 18 years old• MDD by DSM-IV• Depression symptoms for ≥ 1 month• ≥3 prior depressive episodes, 2 in the past 5 

years

• Two months between episodes • HDRS-17 score ≥ 20 at screening and ≥18 at 

randomization

• Response or remission of intake episode at 

end of continuation phase

Exclusion Criteria:

• Failed trial of study medications• Treatment resistant, defined as failure of 

three med trials, ECT, or psychotherapy

• Hypersensitivity to study medications• Alcohol or illicit drug use within 6 months• Seizure disorder• Other serious medical diseases• Other mental illnesses • Pregnant or lactating• ECT within 3 months• Fluoxetine or MAO-I within 30 days• Other antidepressant within 14 days• Any other psychotropic drug 7 days

Venlafaxine ER was associated with significantly lower risk of recurrence in comparison to placebo.Probability of recurrence:Month 6: Venlafaxine ER: 18.8%Placebo: 28.4%Month 12:Venlafaxine ER: 23.1%Placebo: 42%

Headache:Venlafaxine ER 25Placebo 24Upper Respiratory Infection:Venlafaxine ER 17Placebo 12Dry Mouth: Venlafaxine ER 15Placebo 11Insomnia:Venlafaxine ER 14Placebo 13Sweating:Venlafaxine ER 14Placebo 12Weight Gain:Venlafaxine ER 12Placebo 7Dizziness:Venlafaxine ER 11Placebo 21Nausea:Venlafaxine ER 11Placebo 10Sexual Problems:Venlafaxine ER 11Placebo 7

Overall Attrition Rate:Venlafaxine = 50%Placebo = 73%(p<.001)ITT Analysis:YesQuality Rating: fair?Grps similar at baseline? YesOutcomes used valid methodology & criteria?Yes, HDRS-17Subjects & providers blind to intervention status of participants? Yes

Outcome assessors blind? YesIncomplete outcome data adequately addressed? Yes, ITT>10% differential loss to f/up between grps? YesOverall >30% loss to f/up? Yes, 40%Conflict of interest? Funded by venlafaxine manufacturerAdequate randomization methods? NGAllocation concealment adequate? NG
40

of Depression Questionnaires and 

Antidepressant Medications Evidence-based Synthesis Program

stion #2 Randomized Controlled Trials

ve

Patient Baseline Characteristics

Inclusion/Exclusion Criteria Outcome

Results 

Adverse Effects Analysis

Quality Rating 

ve:

erm 

xine 

in 

ent 

:

Mean Age:Venlafaxine ER 41Placebo 43.1Sex (% female):Venlafaxine ER 73Placebo 63Race (% white):NGBaseline (HDRS)Venlafaxine 3.2Placebo 4.5

Inclusion Criteria:

• ≥18 years old• MDD by DSM-IV• Depression symptoms for ≥ 1 month• ≥ 3 prior depressive episodes, 2 in the 

past 5 years

• Two months between episodes • HDRS-17 score ≥20 at screening and 

≥18 at randomization

• Response or remission of intake episode 

at end of continuation phase

Exclusion Criteria:

• Failed trial of study medications• Treatment resistant, defined as failure of 

three med trials, ECT, or psychotherapy

• Hypersensitivity to study medications• Alcohol or illicit drug use within 6 

months

• Seizure Disorder• Others serious medical diseases• Other mental illnesses • Pregnant or Lactating• ECT within 3 months• Fluoxetine or MAO-I within 30 days• Other antidepressant within 14 days• Any other psychotropic drug 7 days

Kaplan-Meier probability estimate for not experiencing recurrence OR increasing dose to 300mg/day:67% for venlafaxine ER =< 225 mg 41% for placeboNNT of 4.5Estimated probability of not having recurrence greater in venlafaxine ER group vs. placebo (76% versus 58%) but did not reach level of statistical significance 

Not reported Overall Attrition Rate:

NGITT Analysis:Not doneQuality Rating: fair or poor?Grps similar at baseline? YesOutcomes used valid methodology & criteria?Partial, HDRS-17 & dose increase of antidepressantSubjects & providers blind to intervention status of participants? YesOutcome assessors blind? YesIncomplete outcome data adequately addressed? No, reasons not reported>10% differential loss to f/up between grps? NoOverall >30% loss to f/up? NoConflict of interest? Funded by venlafaxine manufacturerAdequate randomization methods? NGAllocation concealment adequate? NG
41

of Depression Questionnaires and 

Antidepressant Medications Evidence-based Synthesis Program

stion #2 Randomized Controlled Trials

ve

Patient Baseline Characteristics

Inclusion/Exclusion Criteria Outcome

Results 

Adverse Events (%) Analysis 

Quality Rating 

ve:

sis that 

s will 

pram 

:

nce 

ram 

 weeks 

ment

am 10-

Mean Age:Escitalopram 73Placebo 72Sex (% female):Escitalopram 78%Placebo 79% Race (% white):Escitalopram 99.7%Placebo 100%Baseline (MADRS):Escitalopram 5.1Placebo 5.1

Inclusion Criteria:

• >= 65 years old• MDD by MINI• Response to a 12 week trial of escitalopram• MADRS score >= 22• Duration of t index episode of at least 4 

weeks

• MMSE score >= 24 •Exclusion Criteria:• Current or past history of manic or hypomanic episode, psychotic disorder (including MDD with psychotic features), 

MR, or mental disorders resulting from a general medical condition

• Any substance abuse disorder, presence or history of a clinically significant 

neurologic disorder, neurodegenerative disorder, and any personality disorder.

• Significant suicide risk• Recent receipt prior to screening of the 

following treatments:

antipsychotic drugs, ECT, lithium, carbamazepine, valproate, or valpromide antidepressants, benzodiazepines, nonbenzodiazepine anxiolytics or hypnotics 

(other than zolpidem, zopiclone, or zaleplon); serotonin agonists (for example, triptans), psychotherapy

hypersensitivity to citalopram and/or 

escitalopram

resistance to two trials of antidepressants 

or resistance to citalopram or escitalopram 

Escitalopram wasfour times as effective as placebo in preventing relapse over 24 weeks in older patients with MDD who had achieved full remission Percentage who relapsed:Escitalopram: 9% (13 patients)Placebo: 33% (50 patients)

Any adverse event:Escitalopram 35.3Placebo 34.9Diarrhea:Escitalopram 3.3Placebo 2.6Dizziness:Escitalopram 4.6Placebo 3.3Nausea:Escitalopram 0Placebo 0Headache:Escitalopram 2.6Placebo 3.3

Overall Attrition Rate:Escitalopram = 15%Placebo = 8.5%(excluding relapsers)ITT Analysis:Yes

Quality Rating:

Grps similar at baseline? YesOutcomes used valid methodology & criteria?Yes, MADRSSubjects & providers blind to intervention status of participants? YesOutcome assessors blind? Yes

Incomplete outcome data adequately addressed? Yes, ITT

>10% differential loss to f/up between grps? NoOverall >30% loss to f/up? NoConflict of interest? Funded by escitalopram manufacturerAdequate randomization methods? YesAllocation concealment adequate? Yes
42

of Depression Questionnaires and 

Antidepressant Medications Evidence-based Synthesis Program

stion #2 Randomized Controlled Trials

ve

Patient Baseline Characteristics

Inclusion/Exclusion Criteria Outcome

Results 

Adverse Events (%) Analysis

Quality Rating 

ve:

e 

on, 

rapy, 

 

) to 

y:

p af

phase 

e all 

DM 

ne 

21)

Baseline characteristics of those randomized to ADM and placebo in the maintenance phase were not separately reported.For all subjects randomized to AMD or placebo:Female 78.2%Caucasian 80.0%Minority 20.0%Married 36.3%Have children 43.6%College education 63.8%

Inclusion Criteria:

• response to acute phase treatment 

for depression with 16 weeks of paroxetine

• diagnosis of MDD for index 

episode on the basis of diagnostic interviews

• 20 or above on the Beck Depression Inventory II and scores of 14 

or above on the 17-item version of the HDRS

Exclusion Criteria:Not explicitly stated in this report

Rates of relapse after 1 year follow up from Cox regression analysis:paroxetine: 53%placebo: 59%(not statistically significantly different)

Not reported Overall Attrition Rate:

ADM = 7%Placebo = 19%ITT Analysis:UnclearQuality Rating: Poor - Fair?Grps similar at baseline? NGOutcomes used valid methodology & criteria?Yes, HRSDSubjects & providers blind to intervention status of participants? YesOutcome assessors blind? YesIncomplete outcome data adequately addressed? No, reasons not reported>10% differential loss to f/up between grps? YesOverall >30% loss to f/up? NoConflict of interest? No, funded by NIMHAdequate randomization methods? YesAllocation concealment adequate? Yes
43

Determining the Responsiveness of Depression Questionnaires and 

Optimal Treatment Duration for Antidepressant Medications Evidence-based Synthesis Program

REFERENCES (TEXT AND APPENDICES)

1. Murray, C.J. and A.D. Lopez, Alternative projections of mortality and disability by cause 

1990-2020: Global Burden of Disease Study. Lancet, 1997. 349(9064): p. 1498-504.

2. Katon, W. and H. Schulberg, Epidemiology of depression in primary care. Gen Hosp Psychiatry, 1992. 14(4): p. 237-47.

3. Ormel, J., et al., Recognition, management, and course of anxiety and depression in general 

practice. Arch Gen Psychiatry, 1991. 48(8): p. 700-6.

4. Simon, G.E. and M. VonKorff, Recognition, management, and outcomes of depression in 

primary care. Archives of Family Medicine, 1995. 4(2): p. 99-105.

5. Gilbody, S., et al., Collaborative cares for depression: a cumulative meta-analysis and review of longer-term outcomes. Arch Intern Med, 2006. 166(21): p. 2314-21.

6. Gilbody, S., P. Bower, and P. Whitty, Costs and consequences of enhanced primary care for 

depression: systematic review of randomized economic evaluations. Br J Psychiatry, 2006. 

189: p. 297-308.

7. Williams, J.W., Jr., et al., Systematic review of multifaceted interventions to improve depression care. Gen Hosp Psychiatry, 2007. 29(2): p. 91-116.

8. Rubenstein, L.V., et al., Determining key features of effective depression interventions., 

V.A.H.S.R.D.S.E.-B.S. Program, Editor. 2009: Washington, DC.

9. Anonymous, Depression: Management in Primary and Secondary Care. Clinical Guideline 

23. National Institute for Health and Clinical Excellence: London. 2007.

10. Anonymous, Health Care Guideline: Major Depression in Adults in Primary Care. 11th 

edition. Institute for Clinical Systems Improvement. Available at: www.icsi.org. 2008.

11. Dalton, S.O., et al., Use of selective serotonin reuptake inhibitors and risk of upper gastrointestinal tract bleeding: a population-based cohort study. Arch Intern Med, 2003. 163(1): 

p. 59-64.

12. Richards, J.B., et al., Effect of selective serotonin reuptake inhibitors on the risk of fracture.

Arch Intern Med, 2007. 167(2): p. 188-94.

13. Diem, S.J., et al., Use of antidepressants and rates of hip bone loss in older women: the 

study of osteoporotic fractures. Arch Intern Med, 2007. 167(12): p. 1240-5.

14. Williams, J.W., Jr., et al., Is this patient clinically depressed? JAMA, 2002. 287(9): p. 1160-

70.

15. Williams, J.W., Jr., Is this patient clinically depressed?, in The Rational Clinical Examination: Evidence-Based Clinical Diagnosis, S.D.L.a. Rennie, Editor. 2009, McGraw Hill. p. 

247-264.

16. Gilbody, S., et al., Screening for depression in medical settings with the Patient Health 

Questionnaire (PHQ): a diagnostic meta-analysis. J Gen Intern Med, 2007. 22(11): p. 1596-

602.

17. Faries, D., et al., The responsiveness of the Hamilton Depression Rating Scale. J Psychiatr 

Res, 2000. 34(1): p. 3-10.

18. Liang, M.H., A.H. Fossel, and M.G. Larson, Comparisons of five health status instruments 

for orthopedic evaluation. Med Care, 1990. 28(7): p. 632-42.

19. Deyo, R.A., P. Diehr, and D.L. Patrick, Reproducibility and responsiveness of health status 

measures. Statistics and strategies for evaluation. Control Clin Trials, 1991. 12(4 Suppl): p. 

142S-158S.
44

Determining the Responsiveness of Depression Questionnaires and 

Optimal Treatment Duration for Antidepressant Medications Evidence-based Synthesis Program

20. Guyatt, G., S. Walter, and G. Norman, Measuring change over time: assessing the usefulness of evaluative instruments. J Chronic Dis, 1987. 40(2): p. 171-8.

21. Deyo, R.A. and R.M. Centor, Assessing the responsiveness of functional scales to clinical 

change: an analogy to diagnostic test performance. J Chronic Dis, 1986. 39(11): p. 897-

906.

22. Frank, E., et al., Conceptualization and rationale for consensus definitions of terms in major 

depressive disorder. Remission, recovery, relapse, and recurrence. Arch Gen Psychiatry, 

1991. 48(9): p. 851-5.

23. Panel, D.G., Depression in Primary Care: Volume 2. Treatment of Major Depression. Clinical Practice Guideline, Number 5., P.H.S. U.S. Department of Health and Human Services, 

Agency for Health Care Policy and Research., Editor. April 1993: Rockville, MD.

24. Beck, A., R. Steer, and G. Brown, BDI-II fast screen for medical patients manual. 2000, 

London: The Psychological Corporation.

25. Andresen, E.M., et al., Screening for depression in well older adults: evaluation of a short 

form of the CES-D (Center for Epidemiologic Studies Depression Scale). Am J Prev Med, 

1994. 10(2): p. 77-84.

26. Salokangas, R.K., O. Poutanen, and E. Stengard, Screening for depression in primary care. 

Development and validation of the Depression Scale, a screening instrument for depression.

Acta Psychiatr Scand, 1995. 92(1): p. 10-6.

27. D’Ath, P., et al., Screening, detection and management of depression in elderly primary care 

attenders. I: The acceptability and performance of the 15 item Geriatric Depression Scale 

(GDS15) and the development of short versions. Fam Pract, 1994. 11(3): p. 260-6.

28. Spitzer, R.L., K. Kroenke, and J.B. Williams, Validation and utility of a self-report version 

of PRIME-MD: the PHQ primary care study. Primary Care Evaluation of Mental Disorders. Patient Health Questionnaire. JAMA, 1999. 282(18): p. 1737-44.

29. Broadhead, W.E., et al., Development and validation of the SDDS-PC screen for multiple 

mental disorders in primary care. Arch Fam Med, 1995. 4(3): p. 211-9.

30. Atkins, D., et al., Grading quality of evidence and strength of recommendations. Bmj, 2004. 

328(7454): p. 1490.

31. Lowe, B., K. Kroenke, and K. Grafe, Detecting and monitoring depression with a two-item 

questionnaire (PHQ-2). Journal of Psychosomatic Research, 2005. 58(2): p. 163-71.

32. Lowe, B., et al., Measuring depression outcome with a brief self-report instrument: sensitivity to change of the Patient Health Questionnaire (PHQ-9). Journal of Affective Disorders, 

2004. 81(1): p. 61-6.

33. Lowe, B., et al., Responsiveness of the PHQ-9 to psychopharmacological depression treatment. Psychosomatics: Journal of Consultation Liaison Psychiatry, 2006. 47(1): p. 62-67.

34. Lowe, B., et al., Monitoring depression treatment outcomes with the patient health questionnaire-9. Medical Care, 2004. 42(12): p. 1194-201.

35. Hansen, R., et al., Meta-analysis of major depressive disorder relapse and recurrence with 

second-generation antidepressants. Psychiatric Services, 2008. 59(10): p. 1121-30.

36. Dobson, K.S., et al., Randomized trial of behavioral activation, cognitive therapy, and 

antidepressant medication in the prevention of relapse and recurrence in major depression.

Journal of Consulting and Clinical Psychology, 2008. 76(3): p. 468-77.

37. Kocsis, J.H., et al., Prevention of recurrent episodes of depression with venlafaxine ER in a 

1-year maintenance phase from the PREVENT Study. Journal of Clinical Psychiatry, 2007. 
45

Determining the Responsiveness of Depression Questionnaires and 

Optimal Treatment Duration for Antidepressant Medications Evidence-based Synthesis Program

68(7): p. 1014-23.

38. Gorwood, P., et al., Escitalopram prevents relapse in older patients with major depressive 

disorder. American Journal of Geriatric Psychiatry, 2007. 15(7): p. 581-93.

39. Kornstein, S.G., et al., Assessing the efficacy of 2 years of maintenance treatment with 

venlafaxine extended release 75-225 mg/day in patients with recurrent major depression: a 

secondary analysis of data from the PREVENT study. International Clinical Psychopharmacology, 2008. 23(6): p. 357-63.

40. Kazis, L.E., J.J. Anderson, and R.F. Meenan, Effect sizes for interpreting changes in health 

status. Med Care, 1989. 27(3 Suppl): p. S178-89.

41. Kroenke, K., R.L. Spitzer, and J.B. Williams, The PHQ-9: validity of a brief depression 

severity measure. Journal of General Internal Medicine, 2001. 16(9): p. 606-13.

42. Kornstein, S.G., et al., Escitalopram maintenance treatment for prevention of recurrent depression: a randomized, placebo-controlled trial. J Clin Psychiatry, 2006. 67(11): p. 1767-

75.

43. Lepine, J.P., et al., A randomized, placebo-controlled trial of sertraline for prophylactic 

treatment of highly recurrent major depressive disorder. Am J Psychiatry, 2004. 161(5): p. 

836-42.

44. Reimherr, F.W., et al., Optimal length of continuation therapy in depression: a prospective 

assessment during long-term fluoxetine treatment. Am J Psychiatry, 1998. 155(9): p. 1247-

53.

45. Oslin, D.W., et al., Screening, assessment, and management of depression in VA primary 

care clinics. The Behavioral Health Laboratory. J Gen Intern Med, 2006. 21(1): p. 46-50.

46. Dowrick, C., et al., Patients’ and doctors’ views on depression severity questionnaires 

incentivized in UK quality and outcomes framework: qualitative study. BMJ, 2009. 338: p. 

b663.

47. Nease, D.E., Jr., et al., Inducing sustainable improvement in depression care in primary care 

practices. Jt Comm J Qual Patient Saf, 2008. 34(5): p. 247-55.

48. Duffy, F.F., et al., Systematic use of patient-rated depression severity monitoring: is it helpful and feasible in clinical psychiatry? Psychiatr Serv, 2008. 59(10): p. 1148-54.

49. Dietrich, A.J., et al., Re-engineering systems for the treatment of depression in primary 

care: cluster randomized controlled trial. Bmj, 2004. 329(7466): p. 602.

50. Unutzer, J., et al., Collaborative care management of late-life depression in the primary 

care setting: a randomized controlled trial. JAMA, 2002. 288(22): p. 2836-45.

51. Ahava, G.W., et al., Is the Beck Depression Inventory reliable over time? An evaluation of 

multiple test-retest reliability in a nonclinical college student sample. Journal of Personality 

Assessment, 1998. 70(2): p. 222-31.

52. Adler, D.A., et al., The impact of a pharmacist intervention on 6-month outcomes in depressed primary care patients. General Hospital Psychiatry, 2004. 26(3): p. 199-209.

53. Allard, P., et al., Efficacy and tolerability of venlafaxine in geriatric outpatients with major 

depression: a double-blind, randomized 6-month comparative trial with citalopram. International Journal of Geriatric Psychiatry, 2004. 19(12): p. 1123-30.

54. Altamura, A.C., et al., Clinical activity and tolerability of trazodone, mianserin, and amitriptyline in elderly subjects with major depression: a controlled multicenter trial. Clinical 

Neuropharmacology, 1989. 12 Suppl 1: p. S25-33; S34-7.

55. Amsterdam, J.D., J. Shults, and N. Rutherford, Open-label study of s-citalopram therapy 
46

Determining the Responsiveness of Depression Questionnaires and 

Optimal Treatment Duration for Antidepressant Medications Evidence-based Synthesis Program

of chronic fatigue syndrome and co-morbid major depressive disorder. Progress in NeuroPsychopharmacology and Biological Psychiatry, 2008. 32(1): p. 100-6.

56. Babyak, M., et al., Exercise treatment for major depression: maintenance of therapeutic 

benefit at 10 months. Psychosomatic Medicine, 2000. 62(5): p. 633-8.

57. Baldwin, D., R.A. Moreno, and M. Briley, Resolution of sexual dysfunction during acute 

treatment of major depression with milnacipran. Hum Psychopharmacol, 2008. 23(6): p. 

527-32.

58. Barbosa, L., M. Berk, and M. Vorster, A double-blind, randomized, placebo-controlled trial 

of augmentation with lamotrigine or placebo in patients concomitantly treated with fluoxetine for resistant major depressive episodes. Journal of Clinical Psychiatry, 2003. 64(4): p. 

403-7.

59. Berkman, L.F., et al., Effects of treating depression and low perceived social support on 

clinical events after myocardial infarction: the Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) Randomized Trial. JAMA, 2003. 289(23): p. 3106-16.

60. Berlim, M.T., et al., Reliability and validity of the WHOQOL BREF in a sample of Brazilian 

outpatients with major depression. Quality of Life Research, 2005. 14(2): p. 561-4.

61. Berlim, M.T., et al., Significant improvement in the quality of life of Brazilian depressed outpatients 12 weeks following the start of antidepressants. Psychiatry Research, 2007. 153(3): 

p. 253-9.

62. Boyer, P., et al., Clinical and economic comparison of sertraline and fluoxetine in the treatment of depression. A 6-month double-blind study in a primary-care setting in France.

Pharmacoeconomics, 1998. 13(1 Pt 2): p. 157-69.

63. Brody, B.L., et al., Age-related macular degeneration: self-management and reduction of 

depressive symptoms in a randomized, controlled study. Journal of the American Geriatrics 

Society, 2006. 54(10): p. 1557-62.

64. Brown, C., H.C. Schulberg, and H.G. Prigerson, Factors associated with symptomatic improvement and recovery from major depression in primary care patients. General Hospital 

Psychiatry, 2000. 22(4): p. 242-50.

65. Brown, E.S., et al., A randomized trial of citalopram versus placebo in outpatients with 

asthma and major depressive disorder: a proof of concept study. Biological Psychiatry, 

2005. 58(11): p. 865-70.

66. Cassidy, E.L., S. Lauderdale, and J.I. Sheikh, Mixed anxiety and depression in older adults: 

clinical characteristics and management. Journal of Geriatric Psychiatry and Neurology, 

2005. 18(2): p. 83-8.

67. Casten, R.J., et al., A comparison of self-reported function assessed before and after depression treatment among depressed geriatric patients. International Journal of Geriatric Psychiatry, 2000. 15(9): p. 813-818.

68. Chen, T.M., et al., Using the PHQ-9 for depression screening and treatment monitoring for 

Chinese Americans in primary care. Psychiatric Services, 2006. 57(7): p. 976-81.

69. Conradi, H.J., et al., Enhanced treatment for depression in primary care: long-term outcomes of a psycho-educational prevention program alone and enriched with psychiatric 

consultation or cognitive behavioral therapy. Psychological Medicine, 2007. 37(6): p. 849-

62.

70. Cook, I.A., et al., Neurophysiologic predictors of treatment response to fluoxetine in major 

depression. Psychiatry Research, 1999. 85(3): p. 263-73.
47

Determining the Responsiveness of Depression Questionnaires and 

Optimal Treatment Duration for Antidepressant Medications Evidence-based Synthesis Program

71. Corney, R. and S. Simpson, Thirty-six month outcome data from a trial of counseling with 

chronically depressed patients in a general practice setting. Psychology and Psychotherapy: 

Theory, Research and Practice, 2005. 78(1): p. 127-138.

72. Coulehan, J.L., et al., Treating depressed primary care patients improves their physical, 

mental, and social functioning. Archives of Internal Medicine, 1997. 157(10): p. 1113-20.

73. Dalton, E.J., et al., Use of slow-release melatonin in treatment-resistant depression. Journal 

of Psychiatry and Neuroscience, 2000. 25(1): p. 48-52.

74. Davies, J., et al., Changes in regional cerebral blood flow with venlafaxine in the treatment 

of major depression. American Journal of Psychiatry, 2003. 160(2): p. 374-6.

75. DeBattista, C., et al., A prospective trial of bupropion SR augmentation of partial and nonresponders to serotonergic antidepressants. Journal of Clinical Psychopharmacology, 2003. 

23(1): p. 27-30.

76. Dori, G.A. and J.C. Overholser, Evaluating depression severity and remission with a modified Beck Depression Inventory. Personality and Individual Differences, 2000. 28(6): p. 

1045-1061.

77. Dubovsky, S.L., et al., Nicardipine improves the antidepressant action of ECT but does not 

improve cognition. Journal of ECT, 2001. 17(1): p. 3-10.

78. Dunner, D., et al., Adinazolam--a new antidepressant: findings of a placebo-controlled, 

double-blind study in outpatients with major depression. Journal of Clinical Psychopharmacology, 1987. 7(3): p. 170-2.

79. Einarson, T.R., Evidence based review of escitalopram in treating major depressive disorder 

in primary care. International Clinical Psychopharmacology, 2004. 19(5): p. 305-10.

80. Fava, M., et al., Open study of the catechol-O-methyltransferase inhibitor tolcapone in major depressive disorder. Journal of Clinical Psychopharmacology, 1999. 19(4): p. 329-35.

81. Fawcett, J., et al., Alprazolam: an antidepressant? Alprazolam, desipramine, and an alprazolam-desipramine combination in the treatment of adult depressed outpatients. Journal of 

Clinical Psychopharmacology, 1987. 7(5): p. 295-310.

82. George, T., et al., An open study of sertraline in patients with major depression who failed 

to respond to moclobemide. Australian and New Zealand Journal of Psychiatry, 1999. 33(6): 

p. 889-95.

83. George, T.P., et al., Nicotinic antagonist augmentation of selective serotonin reuptake 

inhibitor-refractory major depressive disorder: a preliminary study. Journal of Clinical Psychopharmacology, 2008. 28(3): p. 340-4.

84. Goodnick, P.J., et al., Sertraline in coexisting major depression and diabetes mellitus. Psychopharmacology Bulletin, 1997. 33(2): p. 261-4.

85. Goodnick, P.J., et al., Bupropion slow-release response in depression: diagnosis and biochemistry. Biological Psychiatry, 1998. 44(7): p. 629-32.

86. Judd, L.L., et al., Randomized, placebo-controlled trial of fluoxetine for acute treatment of 

minor depressive disorder. American Journal of Psychiatry, 2004. 161(10): p. 1864-71.

87. Kates, N., et al., Counselors in primary care: benefits and lessons learned. Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie, 2002. 47(9): p. 857-62.

88. Koivumaa-Honkanen, H., et al., Mental health and well-being in a 6-year follow-up of patients with depression: assessments of patients and clinicians. Social Psychiatry and Psychiatric Epidemiology, 2008. 43(9): p. 688-96.

89. Koran, L.M., et al., Predicting response to fluoxetine in geriatric patients with major de-
48

Determining the Responsiveness of Depression Questionnaires and 

Optimal Treatment Duration for Antidepressant Medications Evidence-based Synthesis Program

pression. Journal of Clinical Psychopharmacology, 1995. 15(6): p. 421-7.

90. Kroenke, K., et al., Venlafaxine extended release in the short-term treatment of depressed 

and anxious primary care patients with multisomatoform disorder. Journal of Clinical Psychiatry, 2006. 67(1): p. 72-80.

91. Lesperance, F., et al., Effects of citalopram and interpersonal psychotherapy on depression 

in patients with coronary artery disease: the Canadian Cardiac Randomized Evaluation of 

Antidepressant and Psychotherapy Efficacy (CREATE) trial. JAMA, 2007. 297(4): p. 367-

79.

92. Lett, H.S., et al., Social support and prognosis in patients at increased psychosocial risk 

recovering from myocardial infarction. Health Psychology, 2007. 26(4): p. 418-427.

93. Levitt, A.J., et al., Do depressed subjects who have failed both fluoxetine and a tricyclic 

antidepressant respond to the combination? Journal of Clinical Psychiatry, 1999. 60(9): p. 

613-6.

94. Liebowitz, M.R., P.P. Yeung, and R. Entsuah, A randomized, double-blind, placebo-controlled trial of desvenlafaxine succinate in adult outpatients with major depressive disorder.

Journal of Clinical Psychiatry, 2007. 68(11): p. 1663-72.

95. Lustman, P.J., et al., Cognitive behavior therapy for depression in type 2 diabetes mellitus. A 

randomized, controlled trial. Annals of Internal Medicine, 1998. 129(8): p. 613-21.

96. Lustman, P.J., et al., Fluoxetine for depression in diabetes: a randomized double-blind 

placebo-controlled trial. Diabetes Care, 2000. 23(5): p. 618-23.

97. Lydiard, R.B., et al., A double-blind, placebo-controlled study comparing the effects of sertraline versus amitriptyline in the treatment of major depression. Journal of Clinical Psychiatry, 1997. 58(11): p. 484-91.

98. Mazeh, D., et al., A randomized, single-blind, comparison of venlafaxine with paroxetine in 

elderly patients suffering from resistant depression. International Clinical Psychopharmacology, 2007. 22(6): p. 371-5.

99. McIntyre, R.S., et al., Measuring the severity of depression and remission in primary care: 

validation of the HAMD-7 scale. CMAJ, 2005. 173(11): p. 1327-34.

100. Mohamed, S., et al., Escitalopram for comorbid depression and anxiety in elderly patients: 

A 12-week, open-label, flexible-dose, pilot trial. Am J Geriatr Pharmacother, 2006. 4(3): p. 

201-9.

101. Mulrow, C.D., et al., Treatment of depression--newer pharmacotherapies. Psychopharmacology Bulletin, 1998. 34(4): p. 409-795.

102. Mynors-Wallis, L.M., et al., Randomized controlled trial of problem solving treatment, antidepressant medication, and combined treatment for major depression in primary care. BMJ, 

2000. 320(7226): p. 26-30.

103. Patkar, A.A., et al., A randomized, double-blind, placebo-controlled trial of augmentation 

with an extended release formulation of methylphenidate in outpatients with treatment-resistant depression. Journal of Clinical Psychopharmacology, 2006. 26(6): p. 653-6.

104. Perez, V., et al., A double-blind, randomized, placebo-controlled trial of pindolol augmentation in depressive patients resistant to serotonin reuptake inhibitors. Grup de Recerca en 

Trastorns Afectius. Archives of General Psychiatry, 1999. 56(4): p. 375-9.

105. Picardi, A., et al., Screening for depressive disorders in patients with skin diseases: a comparison of three screeners. Acta Dermato-Venereologica, 2005. 85(5): p. 414-9.

106. Pollock, B.G., et al., Acute antidepressant effect following pulse loading with intravenous 
49

Determining the Responsiveness of Depression Questionnaires and 

Optimal Treatment Duration for Antidepressant Medications Evidence-based Synthesis Program

and oral clomipramine. Archives of General Psychiatry, 1989. 46(1): p. 29-35.

107. Posternak, M.A. and I. Miller, Untreated short-term course of major depression: a metaanalysis of outcomes from studies using wait-list control groups. Journal of Affective Disorders, 2001. 66(2-3): p. 139-46.

108. Proudfoot, J., et al., Computerized, interactive, multimedia cognitive-behavioral program 

for anxiety and depression in general practice. Psychological Medicine, 2003. 33(2): p. 

217-27.

109. Pyne, J.M., et al., Use of the quality of well-being self-administered version (QWB-SA) in 

assessing health-related quality of life in depressed patients. Journal of Affective Disorders, 

2003. 76(1-3): p. 237-47.

110. Quilty, L.C., L.A. Meusel, and R.M. Bagby, Neuroticism as a mediator of treatment response to SSRIs in major depressive disorder. Journal of Affective Disorders, 2008. 111(1): 

p. 67-73.

111. Raskin, J., et al., Duloxetine in the long-term treatment of major depressive disorder. Journal of Clinical Psychiatry, 2003. 64(10): p. 1237-44.

112. Raskin, J., et al., Efficacy of duloxetine on cognition, depression, and pain in elderly patients with major depressive disorder: an 8-week, double-blind, placebo-controlled trial.

American Journal of Psychiatry, 2007. 164(6): p. 900-9.

113. Rollman, B.L., et al., A randomized trial using computerized decision support to improve 

treatment of major depression in primary care. Journal of General Internal Medicine, 2002. 

17(7): p. 493-503.

114. Rush, A.J. and A. Bose, Escitalopram in clinical practice: results of an open-label trial in a 

naturalistic setting. Depression and Anxiety, 2005. 21(1): p. 26-32.

115. Rutherford, B., et al., An open trial of aripiprazole augmentation for SSRI non-remitters 

with late-life depression. International Journal of Geriatric Psychiatry, 2007. 22(10): p. 986-

91.

116. Salkovskis, P., et al., A randomized controlled trial of the use of self-help materials in addition to standard general practice treatment of depression compared to standard treatment 

alone. Psychological Medicine, 2006. 36(3): p. 325-33.

117. Shelton, R.C., et al., Effectiveness of St John’s wort in major depression: a randomized controlled trial. JAMA, 2001. 285(15): p. 1978-86.

118. Singh, N.A., K.M. Clements, and M.A. Singh, The efficacy of exercise as a long-term 

antidepressant in elderly subjects: a randomized, controlled trial. Journals of Gerontology. 

Series A, Biological Sciences and Medical Sciences, 2001. 56(8): p. M497-504.

119. Skevington, S.M. and A. Wright, Changes in the quality of life of patients receiving antidepressant medication in primary care: Validation of the WHOQOL-100. British Journal of 

Psychiatry, 2001. 178: p. 261-267.

120. Spalletta, G., A. Pasini, and C. Caltagirone, Fluoxetine alone in the treatment of first episode anxious-depression: an open clinical trial. Journal of Clinical Psychopharmacology, 

2002. 22(3): p. 263-6.

121. Stark, P. and C.D. Hardison, A review of multicenter controlled studies of fluoxetine vs. 

imipramine and placebo in outpatients with major depressive disorder. Journal of Clinical 

Psychiatry, 1985. 46(3 Pt 2): p. 53-8.

122. Szegedi, A., et al., Acute treatment of moderate to severe depression with hypericum extract 

WS 5570 (St John’s wort): randomized controlled double blind non-inferiority trial versus 
50

Determining the Responsiveness of Depression Questionnaires and 

Optimal Treatment Duration for Antidepressant Medications Evidence-based Synthesis Program

paroxetine. BMJ, 2005. 330(7490): p. 503.

123. Thase, M.E., Efficacy and tolerability of once-daily venlafaxine extended release (XR) in 

outpatients with major depression. The Venlafaxine XR 209 Study Group. Journal of Clinical 

Psychiatry, 1997. 58(9): p. 393-8.

124. Trivedi, M.H., et al., Clinical results for patients with major depressive disorder in the 

Texas Medication Algorithm Project. Archives of General Psychiatry, 2004. 61(7): p. 669-

80.

125. Tutty, S., G. Simon, and E. Ludman, Telephone counseling as an adjunct to antidepressant 

treatment in the primary care system. A pilot study. Effective Clinical Practice, 2000. 3(4): 

p. 170-8.

126. van Gurp, G., et al., St John’s wort or sertraline? Randomized controlled trial in primary 

care. Canadian Family Physician, 2002. 48: p. 905-12.

127. van Marwijk, H.W., et al., Primary care management of major depression in patients aged 

> or =55 years: outcome of a randomized clinical trial. British Journal of General Practice, 

2008. 58(555): p. 680-6, I-II; discussion 687.

128. Vinkers, D.J., et al., The 15-item Geriatric Depression Scale (GDS-15) detects changes in 

depressive symptoms after a major negative life event. The Leiden 85-plus Study. International Journal of Geriatric Psychiatry, 2004. 19(1): p. 80-4.

129. Wade, A.G., et al., Escitalopram and duloxetine in major depressive disorder: a pharmacoeconomic comparison using UK cost data. Pharmacoeconomics, 2008. 26(11): p. 969-81.

130. Wise, T.N., et al., The safety and tolerability of duloxetine in depressed elderly patients with 

and without medical comorbidity. International Journal of Clinical Practice, 2007. 61(8): p. 

1283-93.

131. Bauer, M., et al., The effect of venlafaxine compared with other antidepressants and placebo 

in the treatment of major depression: A meta-analysis. European Archives of Psychiatry and 

Clinical Neuroscience, 2009.

132. Gartlehner, G., et al., Comparative benefits and harms of second-generation antidepressants: background paper for the American College of Physicians. Annals of Internal Medicine, 2008. 149(10): p. 734-50.

133. Qaseem, A., et al., Using second-generation antidepressants to treat depressive disorders: 

a clinical practice guideline from the American College of Physicians. Annals of Internal 

Medicine, 2008. 149(10): p. 725-33.

134. Anderson, I.M., et al., Evidence-based guidelines for treating depressive disorders with 

antidepressants: a revision of the 2000 British Association for Psychopharmacology guidelines. J Psychopharmacol, 2008. 22(4): p. 343-96.

135. Papakostas, G.I., et al., Antidepressant dose reduction and the risk of relapse in major depressive disorder. Psychotherapy and Psychosomatics, 2007. 76(5): p. 266-70.

136. Furukawa, T.A., et al., Long-term treatment of depression with antidepressants: a systematic 

narrative review. Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie, 2007. 

52(9): p. 545-52.

137. Zimmerman, M., M.A. Posternak, and C.J. Ruggero, Impact of study design on the results 

of continuation studies of antidepressants. Journal of Clinical Psychopharmacology, 2007. 

27(2): p. 177-81.

138. Lam, R.W. and S.H. Kennedy, Evidence-based strategies for achieving and sustaining full 

remission in depression: focus on metaanalyses. Canadian Journal of Psychiatry. Revue 
51

Determining the Responsiveness of Depression Questionnaires and 

Optimal Treatment Duration for Antidepressant Medications Evidence-based Synthesis Program

Canadienne de Psychiatrie, 2004. 49(3 Suppl 1): p. 17S-26S.

139. Dombrovski, A.Y., et al., Maintenance treatment for old-age depression preserves healthrelated quality of life: a randomized, controlled trial of paroxetine and interpersonal psychotherapy. Journal of the American Geriatrics Society, 2007. 55(9): p. 1325-32.

140. Keller, M.B., et al., The Prevention of Recurrent Episodes of Depression with Venlafaxine 

for Two Years (PREVENT) Study: Outcomes from the 2-year and combined maintenance 

phases. Journal of Clinical Psychiatry, 2007. 68(8): p. 1246-56.

141. Doogan, D.P. and V. Caillard, Sertraline in the prevention of depression. Br J Psychiatry, 

1992. 160: p. 217-22.

142. Feiger, A.D., et al., Double-blind, placebo-substitution study of nefazodone in the prevention of relapse during continuation treatment of outpatients with major depression. Int Clin 

Psychopharmacol, 1999. 14(1): p. 19-28.

143. Gelenberg, A.J., et al., Randomized, placebo-controlled trial of nefazodone maintenance 

treatment in preventing recurrence in chronic depression. Biol Psychiatry, 2003. 54(8): p. 

806-17.

144. Gilaberte, I., et al., Fluoxetine in the prevention of depressive recurrences: a double-blind 

study. J Clin Psychopharmacol, 2001. 21(4): p. 417-24.

145. Hochstrasser, B., et al., Prophylactic effect of citalopram in unipolar, recurrent depression: 

placebo-controlled study of maintenance therapy. Br J Psychiatry, 2001. 178: p. 304-10.

146. Keller, M.B., et al., Maintenance phase efficacy of sertraline for chronic depression: a randomized controlled trial. JAMA, 1998. 280(19): p. 1665-72.

147. Klysner, R., et al., Efficacy of citalopram in the prevention of recurrent depression in elderly 

patients: placebo-controlled study of maintenance therapy. Br J Psychiatry, 2002. 181: p. 

29-35.

148. Lustman, P.J., et al., Sertraline for prevention of depression recurrence in diabetes mellitus: 

a randomized, double-blind, placebo-controlled trial. Arch Gen Psychiatry, 2006. 63(5): p. 

521-9.

149. Montgomery, S.A., J.G. Rasmussen, and P. Tanghoj, A 24-week study of 20 mg citalopram, 

40 mg citalopram, and placebo in the prevention of relapse of major depression. Int Clin 

Psychopharmacol, 1993. 8(3): p. 181-8.

150. Montgomery, S.A., et al., Venlafaxine versus placebo in the preventive treatment of recurrent major depression. J Clin Psychiatry, 2004. 65(3): p. 328-36.

151. Montgomery, S.A. and G. Dunbar, Paroxetine is better than placebo in relapse prevention 

and the prophylaxis of recurrent depression. Int Clin Psychopharmacol, 1993. 8(3): p. 189-

95.

152. Reynolds, C.F., 3rd, et al., Maintenance treatment of major depression in old age. N Engl J 

Med, 2006. 354(11): p. 1130-8.

153. Robert, P. and S.A. Montgomery, Citalopram in doses of 20-60 mg is effective in depression 

relapse prevention: a placebo-controlled 6 month study. Int Clin Psychopharmacol, 1995. 

10 Suppl 1: p. 29-35.

154. Schmidt, M.E., et al., The efficacy and safety of a new enteric-coated formulation of fluoxetine given once weekly during the continuation treatment of major depressive disorder. J 

Clin Psychiatry, 2000. 61(11): p. 851-7.

155. Simon, J.S., et al., Extended-release venlafaxine in relapse prevention for patients with major depressive disorder. J Psychiatr Res, 2004. 38(3): p. 249-57.
52

Determining the Responsiveness of Depression Questionnaires and 

Optimal Treatment Duration for Antidepressant Medications Evidence-based Synthesis Program

156. Terra, J.L. and S.A. Montgomery, Fluvoxamine prevents recurrence of depression: results 

of a long-term, double-blind, placebo-controlled study. Int Clin Psychopharmacol, 1998. 

13(2): p. 55-62.

157. Thase, M.E., et al., Efficacy of mirtazapine for prevention of depressive relapse: a placebocontrolled double-blind trial of recently remitted high-risk patients. J Clin Psychiatry, 2001. 

62(10): p. 782-8.

158. Weihs, K.L., et al., Continuation phase treatment with bupropion SR effectively decreases 

the risk for relapse of depression. Biol Psychiatry, 2002. 51(9): p. 753-61.

159. Wilson, K.C., et al., Older community residents with depression: long-term treatment with 

sertraline. Randomized, double-blind, placebo-controlled study. Br J Psychiatry, 2003. 182: 

p. 492-7.