19

Evidence Synthesis for Determining the Efficacy of 

Psychotherapy for Treatment Resistant Depression Evidence-based Synthesis Program

Appendix A: Search Strategy

Question: In primary care patients with major depressive disorder who do not achieve 

remission with acute phase antidepressant treatment, is empirically based psychotherapy 

used as an augmentation or substitution treatment more effective than control for achieving 

remission? Empirically based psychotherapies to be considered are: cognitive behavioral 

therapy, interpersonal therapy, problem-solving therapy, dialectical behavior therapy, and 

acceptance and commitment therapy. 

Inclusion Criteria- Systematic Reviews

Systematic Review

Does psychotherapy benefit patients who have been previously not responded to adequate 

pharmacotherapy?

Search Strategy for Systematic Review: Database: PubMed Medline – 1950 to February 26, 2009

1 “Depressive Disorder”[Mesh] OR (major AND depression) 71993

2 ((problem-solving OR interpersonal OR dialectical behav* OR acceptance 

OR commitment OR mindfulness) AND (therapy OR psychotherapy)) OR 

“Psychotherapy”[Mesh] OR “Behavior Therapy”[Mesh]

229473

3 (“Combined Modality Therapy”[Mesh] OR Drug resistant[Mesh] OR additive OR 

augmentation OR augment* OR relaps* OR recurrent OR refractory OR resistant 

OR persisten* OR treatment failure[Mesh])

1147546

4 #1 AND #2 AND #3 1997

5 Limits: Humans, English, All Adult: 19+ years 1078

6 systematic[sb] 116759

7 #5 AND #6 34

8 Cochrane Database Syst Rev [TA] OR search[Title/Abstract] OR metaanalysis[Publication Type] OR MEDLINE[Title/abstract] OR (systematic[Title/

Abstract] AND review[Title/Abstract])

140388

9 #5 AND #8 24

10 #7 OR #9 41

For Systematic Reviews, the Medline search yielded 41 articles. Title and abstracts were 

reviewed by 2 independent persons who identified 12 articles for full text review. Of the 12 

reviewed, 0 were identified as meeting the inclusion criteria previously established; therefore no 

systematic reviews will be included for this question in the final report. 

Inclusion Criteria- Randomized Controlled Trials

Randomized controlled trials

Outpatient setting

Patients from general population (not special populations)
20

Evidence Synthesis for Determining the Efficacy of 

Psychotherapy for Treatment Resistant Depression Evidence-based Synthesis Program

Adults who have not remised or responded significantly to anti-depressant medication for > 6 

wks and not in therapy (CBT, IPT, Sol. Focused, DBT, ACT, MBT)

If mixed sample, at least 80% must be partial or non-responders or outcomes reported separately 

Exclude: patients with MDD where guidelines recommend mental health specialty care (eg. high 

suicidality, substance abuse, borderline personality d/o)

Relevant comparison

English language articles

Search Strategy for Randomized Controlled Trials: Database: PubMed Medline - 1950 to 

February 26, 2009

1 “Depressive Disorder”[Mesh] OR (major AND depression) 71993

2 ((problem-solving OR interpersonal OR dialectical behav* OR acceptance 

OR commitment OR mindfulness) AND (therapy OR psychotherapy)) OR 

“Psychotherapy”[Mesh] OR “Behavior Therapy”[Mesh] 

229441

3 “Combined Modality Therapy”[Mesh] OR Drug resistant[Mesh] OR additive OR 

augmentation OR augment* OR relaps* OR recurrent OR refractory OR resistant 

OR persisten* OR treatment failure[Mesh]

1147546

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

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

275228

5 #1 AND #2 AND #3 AND #4 422

6 Limits: Humans, English, All Adult: 19+ years 333

For Randomized Control Trials, the Medline search yielded 333 articles. Title and abstracts 

were reviewed by 2 independent persons who identified 43 articles for full text review. Of the 43 

articles reviewed, 12 were identified as meeting the inclusion criteria previously established. 
21

Evidence Synthesis for Determining the Efficacy of 

Psychotherapy for Treatment Resistant Depression Evidence-based Synthesis Program

# citations

41

 # excluded

 29

# full text review

12

 # excluded

 12

# included

0

Figure 1. Systematic Reviews Literature Flow

# citations

333

 # excluded

 290

# full text review

43

 # excluded

 31

# included

12

Figure 2. Randomized Controlled Trials Literature Flow
22

Evidence Synthesis for Determining the Efficacy of 

Psychotherapy for Treatment Resistant Depression Evidence-based Synthesis Program

Appendix B: Peer Review

Question 1: Are the objectives, scope, and methods for this review clearly described?

Reviewer Comment Reply

1 Excellent description of objectives, scope, and methods. This 

review exposes the scarcity of good studies to answer this 

question. The conclusions fit the data.

Acknowledged

2 Clearly described, concisely written, comprehensive, well 

thought out review.

Acknowledged

3 The authors have been particularly thorough in describing clearly 

the objectives, scope, and methods for this review. I don’t believe 

any reader would be left with any question about these.

(As a small matter, on page 15, “solution-focused therapy” 

was listed as one of the empirically-based psychotherapies 

that were considered for purposes of the study. However, in 

Appendix A, this was not listed as one of the search terms; 

“problem-solving” was listed. I think these are both terms of 

art, and are different. Do you want to conform the terms? I 

think the authors likely considered problem solving therapy, but 

not solution-focused therapy.)

Acknowledged

Thank you for pointing out this 

discrepancy. We have now 

changed the term “solution-focused 

therapy” to “problem-solving 

therapy” to reflect terms included in 

the literature search (pg 15, 16).

Question 2: Is there any indication of bias in our synthesis of the evidence? 

Reviewer Comment Reply

1 No indication of bias. This review follows rigorous methods for 

systematic selection and analysis

Acknowledged 

2 No Acknowledged

3 I see no indication of bias in the synthesis of the evidence. 

Indeed, it appears that the authors have gone out of their way 

to eliminate any opportunity for bias.

 Acknowledged

Question 3 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 I don’t know of any others Acknowledged

2 None Acknowledged

3 I don’t know of any studies on the effectiveness of 

psychotherapy as a second step treatment for MDD in patients 

who do not achieve remission after initial treatment with 

antidepressants, per se, that have been overlooked.

 Acknowledged

Question 4: 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 P 6, last line: suggest changing “control” to “comparison 

group,” a term that is more consistent with most patients in this 

group being on some form of treatment.

This review achieves impressive rigor and thoroughness for 

such a limited number of studies. 

We agree with this assertion and 

have attempted to make this point 

throughout the review. However, 

in that specific place, we have 

opted to retain the wording as 

initially developed by VA Central 

Office to avoid confusion regarding 

the question we were originally 

attempting to answer with this review. 
23

Evidence Synthesis for Determining the Efficacy of 

Psychotherapy for Treatment Resistant Depression Evidence-based Synthesis Program

2 4.

a. p. 9 typo, 2nd line from bottom: should be “antidepressant 

medication with CT.

b. p.10. I think the summary and conclusions understate the 

equivalence of CT vs medication as a switch choice. The 

STAR*D data suggested little difference for the between CT 

and meds for the switch arms, and hence for patients who 

would prefer CT it may be a reasonable option. 

c. I’m concerned with the statement: “Based on this sparse 

evidence, we conclude that current trials do not support a 

benefit from adding psychotherapy to antidepressant medication for mid-life adults with treatment resistant MDD”. While it 

is technically correct, I think it is at risk of being mis-interpreted 

too strongly as an indication that there is no role for CT as 

an adjunct in TRD. It seems the evidence is insufficient to 

conclude one way or the other, and I think the wording should 

reflect that the current data do not support a benefit, but that 

the data is insufficient to make a conclusion and that future 

studies may likely change this result. 

d. p.20. Table 1 might benefit from a row that allows a better 

comparison of the level of depressive severity when beginning 

psychotherapy treatment, for e.g., clarifying the BDI or QIDS 

scores as “mild”, “moderate” or “severe”, and a row

that allows comparison of the prior antidepressant treatment 

(e.g.,

antidepressant type, dose, duration). Also, can one report 

the number of prior treatment failures for the current episode?

Finally, the definition of persistent depression (listed in the evidence tables in the appendices) is quite information and would 

be a useful row in Table 1. I realize, however, that some of 

this information may not be available for many studies.

e. Can the authors clarify whether any of the studies directly 

addressed the research question they pose? If not, how might 

they suggest designing a future research project to address 

this question directly? Also, might they suggest a study to 

address the long term risk benefits of a switch to CT (or an 

empirically based psychotherapy) vs medications?

a. Thank you for finding this error. 

The typo has been corrected.

b.& c. We agree with the reviewer 

that our summary and conclusions 

did not emphasize the equivalence 

of the two treatment modalities. We 

have modified the summary statements on pages 9, 10, and 30 to 

reflect the equivalence that we generally observed in studies comparing CT and meds, and to reflect our 

belief that CT remains a reasonable 

treatment option in patients with 

TRD. As we state repeatedly in the 

review, the current evidence is not 

sufficient to determine the superiority of one treatment modality over 

the other. Future research with 

rigorous study designs is necessary 

to definitively answer this question.

d. Per the reviewer’s suggestion, 

we report that that depression 

severity in each study was “moderate.” We agree with the reviewer 

that the number of failures of treatment may be important information 

in evaluating the extent of TRD; 

however, this information was not 

reported in the reviewed studies 

and hence cannot be included. 

We agree that describing persistent 

depression within the text would be 

helpful. We have incorporated this 

suggestion by creating a new table 

(Table 2) that describes the various 

definitions of persistent depression, 

and summarizes antidepressant 

type, dosage, and duration. The 

Additional information about prior 

antidepressant treatment was also 

added to the definitions of persistent depression in the evidence 

tables in the appendices.

e. A sentence was added to the 

discussion on page 30 clarifying 

our position that we do not consider 

the initial key research question 

adequately answered by our review. 

Regarding the reviewer’s suggestion 

of designing a study, our current

(cont’d.)
24

Evidence Synthesis for Determining the Efficacy of 

Psychotherapy for Treatment Resistant Depression Evidence-based Synthesis Program

2 (cont’d) version outlines important components of such a study in the Future 

Research section (pg 35) as well as 

highlights these in the Summary and 

Discussion section. Specifically, we 

highlight the need to study TRD in 

the context of impact on work, medical comorbidities, relapse, and the 

need for cost-effectiveness analysis 

of the different treatments available.

3 This report looked at the condition of treatment resistant major 

depression that failed to respond to an adequate dose of 

antidepressant treatment. I wonder if it would be worth looking 

at individuals who have treatment resistant major depression 

that failed to respond to an adequate dose of antidepressant 

treatment? 

I know of two recent studies that may be worth reviewing:

Watchful waiting for minor depression in primary care: remission rates and predictors of improvement. M.T. Hegel et 

al. General Hospital Psychiatry 28 (2006) 205–212. This 

study suggests that for treatment-seeking samples with minor 

depression in primary care an avoidant coping style seriously interferes with remission, and engaging in regular active 

pleasant events confers an advantage. It further suggests that 

feasible interventions for primary care that promote activity and 

decrease avoidant coping styles may improve outcomes.

Cortico-limbic response to personally challenging emotional 

stimuli after complete recovery from depression. J.M. Hooley 

et al. Psychiatry Research: Neuroimaging 171 (2009) 106–

119. This study suggests that vulnerability to depression may 

be associated with abnormalities in cortico-limbic activation 

that are independent of mood state and that remain even after 

full recovery.

Perhaps there are similar processes at work in those with 

treatment resistant major depression that failed to respond to 

an adequate dose of antidepressant treatment that would not 

respond to traditional psychotherapeutic approaches.

The reviewer makes an interesting 

point. The Hegel study suggests that 

patients with minor depression may 

be successfully treated in primary 

care through pleasant activities and 

by reducing avoidant coping. The 

extensive literature on coping and 

depression supports this conclusion. 

It is likely that patients with minor 

depression may be patients who 

have residual symptoms after an 

MDD episode, in other words, TRD. 

However, it seems that a discussion 

of such interventions is beyond the 

scope of this review because of our 

original goal of comparing CT with 

medications in a treatment resistant 

population. Future reviews may address this issue by incorporating all 

treatments provided in primary care 

settings, and treatments provided to 

patients who may or may not have 

TRD. 

Regarding the Hooley study, it 

would be certainly worthwhile to 

determine the neurological mechanisms that may contribute to TRD 

and/or relapse. Unfortunately, a 

discussion of such mechanisms is 

beyond the scope of this review as 

defined by the VA Central office. 

Question 5: 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 No comment Acknowledged

2 None 

3 I agree wholeheartedly with the statement on page 34 that 

there remains a need for trials of depression treatments to 

inform the specific treatments offered (and to be offered) in 

primary care mental health integration models. This is a pressing need. I would argue that the population of patients that 

could benefit from efficacious and effective treatments in such 

models is far larger than the population of patients who suffer 

from treatment resistant depression.

 Acknowledged
25

Evidence Synthesis for Determining the Efficacy of 

Psychotherapy for Treatment Resistant Depression Evidence-based Synthesis Program

Appendix C: Evidence Tables of RCTs
26

Psychotherapy for Treatment Resistant DepressionEvidence Synthesis for Determining the Efficacy of 

Evidence-based Synthesis Program

Study ID 

TreatmentsDefinition & Persistence Study Information Participants Results Comments/Quality Scoring

al., 2008Harley et 

determined by consentreatment for MDD (as adequate medication Despite stable, Depression:Persistent 

-

sus of 2 senior psychiproviders as usual. psychiatrists and other and meeting with prescribed medications included taking as usual, which continued treatment Pts in this group Wait List (WL) Comparator: minutes each. sessions lasting 90 skills group; 16 weekly DBT based depression Therapy (DBT) Group Dialectical Behavior Psychotherapy: on the SCID-I. met criteria for MDD in MDD), patients still atrists with expertise 

Geographical location: Boston, MA VA sites: referred by outpatient providers.Setting: MHC; participants were 

No

Study design: RCTDuration of follow up: WL: 11DBT: 13Total: 24Number of participants enrolled: 

16 weeks

Inclusion criteria: 

Age 18-65 -Principal diagnosis of MDD on -Have an established treatment 

SCID

-

Stabilized on adequate dose of 

relationship with a psychiatrist

-

entry)for at least 6 weeks before study entering study (no dosage change antidepressant medication before 

Exclusion criteria: 

Bipolar disorder -Psychotic spectrum disorders -Active substance abuse or depen- -Mental retardation

dence

-

Pervasive developmental disorder -Active suicidality -Severe or unstable medical condi- -Patients with previous or current 

tions

-

Borderline Personality Disorder

CBT experience

-

Age: [mean]Sex:Total: 41.8

 [female %]

antidepressant triNumber of lifetime WL: 292.40 (374.94)DBT: 201.00 (131.59)[mean (SD)]episode in days: Duration of current Total: 83%[white (%)] Race/ethnicity:Total: 75%

-

als: [mean (SD)]Number of hospitalWL: 4.27 (2.45)DBT: 3.31 (1.70)

-

izations: [mean (SD)]Engaged in conWL: 25.18 (15.20)DBT: 27.08 (14.23)[mean (SD)]Age at first MDE: WL: 0.27 (0.65) DBT: 0.85 (0.99)

-

Total: 83%individual therapy:current non-CBT 

HAM-D at baseline: severity:1) Interviewer rated depression 

[mean (SD)]

HAM-D at follow-up: WL: 18.64 (4.72)DBT: 16.15 (4.47)

[mean (SD)]

BDI at baseline: severity:2) Self-reported depression p<.05; D=1.45).HAM-D scores than WL (F=4.63; DBT group had significantly lower WL: 17.11 (6.23)DBT: 11.30 (5.31)

[mean (SD)]

BDI at follow-up: WL: 27.44 (11.66)DBT: 27.31 (8.83)

[mean (SD)]

p<.01; D=1.31).BDI scores than WL (F=9.50; DBT group had significantly lower WL: 25.89 (16.30)DBT: 15.10 (12.13)

Small sample sizes, limited inComments:

-

Allocation concealment adRandomization adequate?: YQuality assessment:confound of individual therapy.baseline characteristics, and formation provided on samples’ 

-

Overall quality rating: FairConflict of interest?: Nadequately?: UnknownIncomplete data addressed < 10%?: YDifferential dropout rateDropout rate < 30%?: YOutcomes assessed blind?: Y Subject/providers blind?: NValid outcome assessment?: YBaseline comparability?: Yequate?: Y
27

Psychotherapy for Treatment Resistant DepressionEvidence Synthesis for Determining the Efficacy of 

Evidence-based Synthesis Program

Study ID

TreatmentsDefinition & Persistence Study Information Participants Results Comments/Quality Scoring

2003et al., Kennedy 

after 8-14 weeks of anHAM-D-17≥16 and criteria for MDE with Having initially met depression:Persistent 

-

clinical management.2 weeks for routine Pts were seen every day after 2-4 weeks. increase by 300 mg/which clinicians could lithium carbonate, with 600 mg/day of AD therapy augmented responders” had their considered “partial Pts who were (LA)Lithium Augmentation Comparator:check up.weeks for a medication were also seen every 4 with AD therapy; pts weeks in combination 12 sessions over 8 (CT)Cognitive Therapy Psychotherapy: had HAM-D=8-15.mg/day), patients still venlafaxine (75-225 (50-200 mg/day), or mg/day), sertraline paroxetine (20-40 (300-600 mg/day), with moclobemide tidepressant treatment 

Geographical location: Toronto, Setting: Canada

MHC

VA sites: NoStudy design: RCTDuration of follow up: LA: 21CT: 23Total: 44Number of participants enrolled: 

8 weeks

Inclusion criteria: 

Age 18-65 -Partial response after receiving -

maximum tolerated doses of moor venlafaxine (choice of antide clobemide, paroxetine, sertraline, -weeksthe treating psychiatrist) for 8-14 pressant was at the discretion of 

Initially met criteria for MDE -HAM-D-17≥16 -At least one prior MDE

Exclusion criteria:-

Major medical disorder -Organic brain syndrome -Schizophrenia or schizoaffective -Bipolar disorder

disorder

-

MDD with psychotic features -Substance or alcohol use or -

dependence within past 6 months

Age: [mean (SD)]Sex: LA: 37.7 (11.3)CT: 40.7 (12.5)

[female, n (%)]

Number of prior epiLA: 119.8 (160.8)CT: 126.4 (170.4)[mean (SD)]episode in weeks: Duration of current Not reportedRace/ethnicity:LA: 12 (57%)CT: 12 (52.2%)

-

sodes: [mean (SD)]Comorbid psychiaLA: 24.4 (13.6)CT: 26.3 (13.5)[mean (SD)]Age at first MDE: LA: 2.3 (1.4)CT: 2.1 (1.5)

-

tric diagnoses: [n LA: 4 (19%)CT: 8 (35%)(%)]

med treatment: HAM-D-17 after 8-14 weeks severity:1) Interviewer rated depression 

[mean (SD)]

HAM-D-17 at follow-up: LA: 11.6 (1.9)CT: 12.1 (2.2)

[mean 

BDI after 8-14 weeks med treatseverity:2) Self-reported depression df=42; p=.04; d=.32).in intent-to-treat analysis (t=2.02; HAM-D-17 scores than CT group LA group had significantly lower LA: 9.2 (6.7)CT: 14.8 (9.9)(SD)]

-

ment: [mean (SD)]BDI at follow-up: LA: 22.4 (10.3)CT: 22.7 (8.6)

[mean (SD)]

No significant differences beLA: 15.1 (11.4)CT: 19.9 (10.3)

-

tween groups.

Allocation concealment adRandomization adequate?: Y Quality assessment:excluded non-responders.Only included partial responders; Comments:

-

Incomplete data addressed ad< 10%?: YDifferential dropout rateDropout rate < 30%?: YOutcomes assessed blind?: Y Subject/providers blind?: NValid outcome assessment?: YBaseline comparability?: Y equate?: Y

-

Overall quality rating: GoodConflict of interest?: Nequately?: Y
28

Psychotherapy for Treatment Resistant DepressionEvidence Synthesis for Determining the Efficacy of 

Evidence-based Synthesis Program

Study ID

& TreatmentsPersistence Definition Study Information Participants Results Comments/Quality Scoring

reference.from this extracted primarily *Data were al., 2001Teasdale et 2000*Scott et al., 2003Scott et al., al., 2005Paykel et al., 1999Paykel et 

minutes each.during follow-up for 30 tx and every 8 weeks every 4 weeks during continuation; pts seen Antidepressant (CM)Clinical Management Comparator:received CM.20 weeks. Pts also 16 sessions over Cognitive Therapy (CT)Psychotherapy: BDI≥9.still had HAM-D≥8 & amitriptyline), patients to at least 125 mg of dosage equivalent weeks of minimum weeks (with 4 or more MAOI for at least 8 SSRI, atypical AD, or tricyclic antidepressant, Despite treatment with Persistent depression: Geographical location: Cambridge 

Setting: & Newcastle, England

MHC; Psychiatric OutpaVA sites: tient ClinicsNo

Study design: RCTDuration of follow up: CMT: 78CT: 80Total: 158Number of participants enrolled: 

20 weeks

Inclusion criteria: 

Age 21-65 -DSM-III-R MDD within past 18 -

≥ 9.past 2 months & HRSD ≥ 8 & BDI months but not MDD criteria in 

Exclusion criteria: 

Bipolar disorder -Cyclothymia -Schizoaffective disorder -Drug or alcohol dependence -Antisocial behavior or self-harm -Dysthymia before age 20 -Borderline personality -Learning disability -Organic brain damage -Other primary Axis I disorder -Currently receiving psychotherapy -

than 5 sessionsor previously received CT for more 

Age: [mean Sex:CM: 43.2 (11.2)CT: 43.5 (9.8)(SD)]

 [female, n 

depressive epiDuration of Not reported Race/ethnicity:CM: 41 (53%)CT: 37 (46%)(%)]

-

[median (1sode in months: 

st & 3rd

of MDD: Prior episodes CTM: 13 (9, 21)CT: 14.5 (9, 18)quartiles)]

[median (1st & 3rd

CM: 2 (1, ≥3)CT: 2 (1, ≥3)quartiles)]

trial: HDRS baseline after 8 week drug severity:1) Interviewer rated depression 

[mean (SD)]

HDRS at follow-up: CM=12.2 (2.9)CT=12.1 (2.7)

[mean (SD)]

No significant between group differCM=9.4 (5.3)CT=8.7 (5.3)

-

2) Self-reported depression severp=.14)68 week follow-up (F=2.2; df=1324; over 20 week treatment phase or ences or group x time interactions 

-

trial: BDI baseline after 8 week drug ity:

[mean (SD)]

BDI at follow-up: CM= 22.3 (8.0)CT=21.7 (7.7)

[mean (SD)]

No significant between group differCM= 16.1 (10.0)CT=13.8 (9.6)

-

p=.13)68 week follow-up (F=2.3; df=1293; over 20 week treatment phase or ences or group x time interactions 

remitted but with residual sympNot currently depressed; partially Comments:

-

some dep sx showed sig efIn Scott et al. 2000, found that HDRS and BDIsome depressive symptoms on toms - because not MDD but still 

-

Both CT and CM led to improvesymptomsfects on drug refractory residual 

-

Allocation concealment adRandomization adequate?: YQuality assessment:ment in dep sx

-

Incomplete data addressed ad< 10%?: YDifferential dropout rateDropout rate < 30%?: YOutcomes assessed blind?: Y Subject/providers blind?: N/YValid outcome assessment?: Y Baseline comparability?: Y equate?: Y

-

Overall quality rating: GoodConflict of interest?: Nequately?: Y
29

Psychotherapy for Treatment Resistant DepressionEvidence Synthesis for Determining the Efficacy of 

Evidence-based Synthesis Program

Study ID

& TreatmentsPersistence Definition Study Information Participants Results Comments/Quality Scoring

primarily ex*Data were STAR*Dal., 2007Wisniewski et 2007*Thase et al., 2006Rush et al., 2004Rush et al., 

-

this refertracted from 

-

ence. Switch to CT

for 8 remaining weeks.1-4, then once weekly twice weekly for weeks 16 sessions delivered Cognitive Therapy (CT)Psychotherapy:had HAM-D≥14.14 weeks, patients still mg/day by week 6) for potential dosage of 60 week 4, and maximum to start, 40 mg/day by citalopram (20 mg/day Following treatment with Persistent depression:

: Pts 

Augment CTand began CT.discontinued citalopram 

: Pts 

Switch ADMMedication (ADM)Antidepressant Comparator:and added CT.continued on citalopram 

: 

Augment ADMvenlafaxine.bupropion, sertraline, or citalopram and began Pts discontinued 

: Pts 

buspirone.and added bupropion or continued on citalopram 

Setting: San Diego, NC, IL, MI, VA, TN, ALMA, NY, PA, OK, KS, CA: LA and 14 Regional centers across TX, Geographical location: 

18-Primary Care, 23 MHC 

VA sites: NoStudy design: randomized multiDuration of follow up: Augment ADM=117 Switch ADM=86 Augment CT=65 Switch to CT=36 Total: 304 Number of participants enrolled: step clinical trial 14 weeksInclusion criteria: 

Age 18-75 -Non psychotic MDD -HRSD17≥14

Exclusion criteria:-

Bipolar, schizophrenia, eating d/o, -Hx of intolerability or resistance 

OCD

-

dosageto ≥1 Anti-dep with adequate 

≥7 days Citalopram use prior to -

study enrollment

non-responsive ≥16 session of CT -Medical contraindication

in current MDD episode

-

Pregnant females -Requires psychiatric hospitaliza- -

stabilizerstion, antipsychotics, or mood 

Age: [mean (SD)]Sex: (13.5)Augment ADM=39.7 Switch ADM=41.5 (13.3)(11.5)Augment CT= 40.6 Switch to CT: 43.4 (14.7)

[female, n (%)]

Race/ethnicity:(66.7%)Augment ADM: 78 Switch ADM: 53 (61.6%)Augment CT: 41 (63.1%)Switch to CT: 22 (61.1%)

 [white, 

Number of prior epi(47.5)Augment ADM: 20.0 Switch ADM: 26.5 (54.0)Augment CT: 29.6 (49.4)Switch to CT: 17.4 (31.2)[mean (SD)]episode in months: Duration of depressive (84.6%)Augment ADM: 99 Switch ADM: 63 (73.3%)Augment CT: 52 (80.0%) Switch to CT: 28 (77.8%)n (%)] 

-

sodes of MDD: [mean Augment ADM: 4.6 (5.4)Switch ADM: 8.4 (16.0)Augment CT: 7.3 (14.1)Switch to CT: 8.7 (18.8)(SD)]

1) Interviewer rated depresbetween groups. No significant differences Augment ADM: 8.2 (4.8) Switch ADM: 9.1 (5.0) Augment CT: 8.2 (5.1) Switch to CT: 9.1 (5.4) [mean (SD)] QIDS-C at end of Level 2: Augment ADM: 12.0 (4.6) Switch ADM: 12.1 (4.6) Augment CT: 11.9 (4.3) Switch to CT: 11.2 (4.3) [mean (SD)] QIDS-C at start of Level 2: severity: 2) Self-reported depression between groups. No significant differences Augment ADM: 33.3% Switch ADM: 27.9% Augment CT: 23.1% Switch to CT: 25.0% (HRSD≤7) at end of Level 2: Met remission criteria on Augment ADM: 16.0 (6.7) Switch ADM: 17.7 (6.6) Augment CT: 17.8 (5.7) Switch to CT: 16.4 (6.2) [mean (SD)] HRSD at start of Level 2: sion severity: Numerous pharmaceutical com ADM. to CT lower income than Switch than Augment ADM and Switch CT more impaired & lower QOL Baseline differences in Augment the STAR*D authors. odds with real world experience of psychotherapy acceptability are at randomization. Low rates of randomization, <1/3 agreed to Due to equipoise-stratified Comments: - Allocation concealment ad Randomization adequate?: Y/N Quality assessment: panies supported the project. - Incomplete data addressed ad < 10%?: Y Differential dropout rate Dropout rate < 30%?: Y Outcomes assessed blind?: Y Subject/providers blind?: N Valid outcome assessment?: Y Baseline comparability?: Y/N equate?: Y - Overall quality rating: Good Conflict of interest?: Y equately?: Y
30

Psychotherapy for Treatment Resistant DepressionEvidence Synthesis for Determining the Efficacy of 

Evidence-based Synthesis Program

Study ID

& TreatmentsPersistence Definition Study Information Participants* Results Comments/Quality Scoring

1997& Moore, Blackburn 

1being seen 3 times in over 2 years, with pts 27 sessions delivered Cognitive Therapy (CT) Psychotherapy: on the HAM-D.traditional cut point of 11 the BDI and above the moderate range on symptoms in the to have depressive average continued doses), patients on or above therapeutic choice (prescribed at general practitioner’s medication of the with antidepressant weeks of treatment symptoms over 16 in depressive significant reduction Despite showing Persistent depression:

st month, twice in 2nd

maintenance dose.or above recognized long as prescribed at MAOIs, SSRIs), as choice (tricyclics, of general practitioner’s Maintenance ADM was Medication (ADM)Antidepressant Comparator:thereafter.month, and monthly 

Geographical location: ScotlandSetting: MHC; participants were consultants in a large teaching psyrecruited from outpatient referrals to 

-

VA sites:practices.chiatric hospital and from 2 general 

 No

Study design: RCTDuration of follow up: ADM: 20 (26 initially)CT: 17 (22 initially)Total: 37 (48 initially)Number of participants enrolled:

24 months

Inclusion criteria: 

Age 18-65 -Diagnosis of primary major unipolar -Score of at least 16 on HRSD

depression, non-psychotic

-

Current episode had to be at least -

second MDE

Exclusion criteria:

Having another primary Axis I -Organic brain damage

disorder

-

History of bipolar illness -Alcohol or drug misuse -Could not be prescribed antide- -Unwilling to be randomly allocated 

reasonspressant medication for medical 

-

to treatment

Age: [mean (SD)]Sex:ADM: 40.1 (12.7)CT: 37.8 (13.1)

 [female, n (%)]

Number of prior epiADM: 6.9 (1.3)CT: 7.0 (1.4)[mean (SD)]episode in months: Duration of current Not givenRace/ethnicity:ADM: 17/26 (65%)CT: 17/22 (77%)

-

sodes: [mean (SD)]Number of hospitalADM: 3.2 (2.2)CT: 4.1 (3.4)

-

izations: [mean (SD)]attempts:Number of suicide ADM: 0.8 (2.3)CT: 0.7 (0.9)

 [mean 

initially enrolled par*Data based on ADM: 0.9 (1.9)CT: 0.4 (0.7)(SD)]

-

ticipants.

acute med treatment: HRSD baseline after 16 weeks severity:1) Interviewer rated depression 

[mean 

months follow-up: HRSD interpolated over 24 ADM: 10.6 (6.8)CT: 11.8 (6.3)(SD)]

[mean (SD)]

acute med treatment: BDI baseline after 16 weeks severity:2) Self-reported depression (F=0.31; d.f.=2, 55; NS).difference between treatments ANCOVA showed no significant ADM: 9.3 (7.2)CT: 8.6 (5.6)

[mean 

months follow-up: BDI interpolated over 24 ADM: 19.7 (14.2)CT: 20.4 (11.1)(SD)]

[mean (SD)]

(F=0.72; d.f.=2, 53; NS).difference between treatments ANCOVA showed no significant ADM: 18.1 (13.1)CT: 14.2 (9.9)

Allocation concealment adRandomization adequate?: YQuality assessment:retention for ADM.35% retention for CT and 25% not just the 2 groups of interest.ANCOVAs compared 3 groups, depression.samples met criteria for persistent after 16 weeks of treatment that Reviewers decided based on data Comments:

-

Incomplete data addressed ad< 10%?: NDifferential dropout rateDropout rate < 30%?: NOutcomes assessed blind?: YSubject/providers blind?: NValid outcome assessment?: YBaseline comparability?: Yequate?: Y

-

Overall quality rating: PoorConflict of interest?: Nequately?: Y