Halifax Treatment Refractory Depression Trial

NCT ID: NCT01141426

Last Updated: 2022-08-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-09-30

Study Completion Date

2017-10-31

Brief Summary

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This study will use a randomized parallel group design to examine the effects of Intensive Short-term Dynamic Psychotherapy (ISTDP) for depressed patients non-remitting following at least one course of antidepressants. The effects of ISTDP will be judged through comparison against secondary care treatment as usual. The aim is to establish the clinical and cost effectiveness of ISTDP treatment.

Detailed Description

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Major depression is a common morbid condition resulting in chronicity, recurrent disability, loss of physical health, and in many cases, death through suicide or medical conditions. By 2020, depression is projected to account for 4.4% of global disease burden (1) and the loss of 65 million disability-adjusted life years (2). A United Kingdom study (3) estimated direct treatment costs would reach three billion pounds by 2026 and indirect costs have been found to be 23 times larger (4).

Anti-depressant treatment is considered a bona fide first line agent for major depression. In some real-world studies, however, anti-depressant medications have not fared well. A large scale report, including the STAR-D study, reports remission rates that are disappointing: the percentage of patients attaining remission in first line and second line trials was 37% and 31% with relapse rates of 40% and 55%, respectively (5). Studies show that when depression does not remit with first line medication, it is more common to consider medication changes rather than commencing psychotherapy (6, 7). For treatment refractory depression (TRD), this situation may be due to insufficient empirical evidence demonstrating the efficacy of psychotherapy.

Current Canadian guidelines for depression (8) recommend psychodynamic psychotherapy as a third-line individual psychotherapy treatment option for major depressive disorder. However, two systematic reviews (9, 10) failed to identify any controlled trial data for any psychodynamic therapy for TRD and only three good quality randomized controlled trials (RCT) for other psychotherapy approaches. Although the empirical evidence for psychotherapy was described as limited, the authors concluded that it appears to be an effective option for TRD (10). Practitioners continue to provide psychodynamic therapies in routine clinical practice despite the shortage of empirical evidence; this suggests that formal study of psychodynamic therapies for TRD are urgently needed.

Within this broad treatment rubric, Short-Term Psychodynamic Psychotherapy (STPP) is a category of treatments derived from psychoanalytic theories but by definition distinguishable by the time-limited focus and emphasis on symptom reduction, in comparison to longer-term models where treatment is less structured and the therapist is typically less active. Interventions used in STPPs can be understood on a continuum between 'supportive' and 'expressive' techniques (11). More expressive therapies (e.g., ISTDP) emphasize greater attention to defences and anxiety that block the experiencing of underlying emotions. These emotional factors are understood to culminate in the exacerbation and perpetuation of depression. A meta-analysis found STPPs to be superior to control modalities in studies of major depression (Cohen's d = 0.69) but that further high-quality, randomized control trials are required (12). Of paramount importance however, the gains obtained with STPPs were maintained in long-term follow-up. Three studies have demonstrated direct treatment intervention outcome relationships between STPP and subsequent improvements in depressive symptoms (13-15).

One subtype of STPP is a method called Intensive Short Term Dynamic Psychotherapy (ISTDP). ISTDP has been studied in 18 published clinical studies. Randomized controlled trials have demonstrated its beneficial effects in patients with personality disorders, panic disorder and somatoform disorders (16-18). In a single case series of patients with treatment resistant depression, patients fared well with ISTDP with 8 of 10 achieving complete remission (19). These patients responded to a relatively short course of treatment with reduction and stoppage of the majority of medications. At the Centre for Emotions \& Health (CEH), data were collected from a naturalistic sample of non-psychotic patients presenting with depression. The number of sessions varied from 2 to 62, with a mean (SD) of 8(11). Self-report scores on the Brief Symptom Inventory (BSI) (20) (N = 95) and Inventory of Interpersonal Problems (IIP) (21) (N = 84) were collected at time of intake and termination of ISTDP. The severity of clinical symptoms was markedly and significantly reduced after treatment.

Eight published studies have evaluated the cost-effectiveness of ISTDP (16, 19, 22-26). Two studies included patients with major depression. In one study of treatment-resistant depression (n = 10), we saw major drops in disability cost as 4 of 5 disabled patients returned to work and medications were stopped or reduced (19). In the second study of 231 patients with major depression now being analyzed (Abbass, in preparation), there was a $4,400 hospital and physician cost saving maintained year over year, while waiting list controls had no significant change over time. The post treatment cost savings in the subsequent 3 years were $5000, $5900 and $5100 per patient, thus supporting the concept of lasting cost reductions after treatment with ISTDP.

In summary, based on these preliminary empirical data highlighting the effectiveness of ISTDP, coupled with the current paucity of empirical support for all psychotherapies with this population, formal study of the efficacy of this approach for treatment refractory depression is warranted in the setting of a controlled efficacy trial. As a relatively brief and non-invasive treatment option, should research demonstrate evidence of cost effectiveness and clinical efficacy, this would support the call for this treatment to be made more readily available.

Conditions

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Depression

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Secondary Care Treatment as Usual

At the four secondary health care sites, treatment as usual will consist of a multidisciplinary team approach including pharmacotherapy and clinical management, supportive or structured activities focused around symptom management and in some cases, individual or group psychotherapy. Pharmacotherapy treatment strategies will be individualized regimes informed by evidence-based recommendations. TAU will not be regulated in order to get a naturalistic assessment of standard secondary care treatment delivery with the exception that trial participants not be offered a psychodynamic / psychoanalytic based psychotherapy treatment during the course of the trial. Therapeutic interventions are likely to be heterogeneous therefore the trial coordinator will document in detail the dose and approaches delivered to each participant in order to account for this heterogeneity.

Group Type ACTIVE_COMPARATOR

Secondary Care Treatment as Usual

Intervention Type BEHAVIORAL

At the four secondary health care sites, treatment as usual will consist of a multidisciplinary team approach including pharmacotherapy and clinical management, supportive or structured activities focused around symptom management and in some cases, individual or group psychotherapy. Pharmacotherapy treatment strategies will be individualized regimes informed by evidence-based recommendations. TAU will not be regulated in order to get a naturalistic assessment of standard secondary care treatment delivery with the exception that trial participants not be offered a psychodynamic / psychoanalytic based psychotherapy treatment during the course of the trial. Therapeutic interventions are likely to be heterogeneous therefore the trial coordinator will document in detail the dose and approaches delivered to each participant in order to account for this heterogeneity.

Intensive Short-Term Dynamic Psychotherapy (ISTDP) Group

The ISTDP model is an emotion focused brief format of psychotherapy that helps the patients identify and address emotional factors that culminate into exacerbation of depression and perpetuation of depression. The emphasis is on awareness of emotions and how they affect the person's behavioral patterns and mood. The research protocol calls for the treatment to be delivered according to a 20-session time-limited format. The first session is an extended 2-3 hour appointment (21), then sessions are planned to occur on a weekly basis lasting 60 minutes in duration. Termination in fewer sessions is based upon agreement between therapist and patient.

Group Type EXPERIMENTAL

Intensive Short-term Dynamic Psychotherapy

Intervention Type BEHAVIORAL

The ISTDP model is an emotion focused brief format of psychotherapy that helps the patients identify and address emotional factors that culminate into exacerbation of depression and perpetuation of depression. The emphasis is on awareness of emotions and how they affect the person's behavioral patterns and mood. The research protocol calls for the treatment to be delivered according to a 20-session time-limited format. The first session is an extended 2-3 hour appointment (21), then sessions are planned to occur on a weekly basis lasting 60 minutes in duration. Termination in fewer sessions is based upon agreement between therapist and patient.

Interventions

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Intensive Short-term Dynamic Psychotherapy

The ISTDP model is an emotion focused brief format of psychotherapy that helps the patients identify and address emotional factors that culminate into exacerbation of depression and perpetuation of depression. The emphasis is on awareness of emotions and how they affect the person's behavioral patterns and mood. The research protocol calls for the treatment to be delivered according to a 20-session time-limited format. The first session is an extended 2-3 hour appointment (21), then sessions are planned to occur on a weekly basis lasting 60 minutes in duration. Termination in fewer sessions is based upon agreement between therapist and patient.

Intervention Type BEHAVIORAL

Secondary Care Treatment as Usual

At the four secondary health care sites, treatment as usual will consist of a multidisciplinary team approach including pharmacotherapy and clinical management, supportive or structured activities focused around symptom management and in some cases, individual or group psychotherapy. Pharmacotherapy treatment strategies will be individualized regimes informed by evidence-based recommendations. TAU will not be regulated in order to get a naturalistic assessment of standard secondary care treatment delivery with the exception that trial participants not be offered a psychodynamic / psychoanalytic based psychotherapy treatment during the course of the trial. Therapeutic interventions are likely to be heterogeneous therefore the trial coordinator will document in detail the dose and approaches delivered to each participant in order to account for this heterogeneity.

Intervention Type BEHAVIORAL

Eligibility Criteria

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Inclusion Criteria

* Patients aged 18 - 65 years.
* Patients must identify depression as their primary problem (rather than being secondary to other mental health diagnosis).
* Any DSM-IV diagnosis of Major Depression as assessed by the Mini Neuropsychiatric Interview plus (M.I.N.I. plus) at time of research intake interview.
* Patients will have had at least one treatment trial of antidepressants at an acceptable therapeutic dose (length ≥ 6 weeks) for the current depressive episode without adequate response (score on the Hamilton Rating Scale for Depression ≥ 16 ) at time of screening interview.
* Patients will not have started new medications in the previous ≥ 6 weeks, or have received psychotherapy treatment in the 12 months prior to being invited to participate in the study.
* Participants will agree to video-taped sessions and will consent to the investigator accessing their information in clinical files and hospital database (e.g., medications, number of visits to health care professionals).

Exclusion Criteria

* Psychotic depression, bipolar depression, substance dependence, severe cluster A or B personality disorders, active suicidality, or cognitive impairment: such that patients require an intervention other than psychotherapy (as per the current protocol for the experimental treatment arm) or patients unable to give consent to treatment.
* Patients with depression due to a general medical condition or secondary to a comorbid mental health or psychosocial condition will be excluded.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Nova Scotia Health Authority

OTHER

Sponsor Role collaborator

Joel Town

OTHER

Sponsor Role lead

Responsible Party

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Joel Town

Dr. Joel Town

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Joel Town

Role: PRINCIPAL_INVESTIGATOR

Capital District Health Authority and Dalhousie University

Locations

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Capital District Health Authority

Halifax, Nova Scotia, Canada

Site Status

Countries

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Canada

References

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Guilbert JJ. The world health report 2002 - reducing risks, promoting healthy life. Educ Health (Abingdon). 2003 Jul;16(2):230. doi: 10.1080/1357628031000116808. No abstract available.

Reference Type BACKGROUND
PMID: 14741909 (View on PubMed)

2. Murray CJL, Lopez AD. The Global Burden of Disease. A Comprehensive Assessment of Mortality and Disability from Diseases, Injuries and Risk Factors in 1990 and Projected to 2020. Cambridge, Massachussetts: Harvard University Press; 1997.

Reference Type BACKGROUND

3. McCrone P, Dhanasiri S, Patel A, Knapp M, Lawton-Smith S. Paying the Price: The Cost of Mental Health Care in England to 2026. London: King's Fund; 2008.

Reference Type BACKGROUND

Thomas CM, Morris S. Cost of depression among adults in England in 2000. Br J Psychiatry. 2003 Dec;183:514-9. doi: 10.1192/bjp.183.6.514.

Reference Type BACKGROUND
PMID: 14645022 (View on PubMed)

Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, Niederehe G, Thase ME, Lavori PW, Lebowitz BD, McGrath PJ, Rosenbaum JF, Sackeim HA, Kupfer DJ, Luther J, Fava M. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006 Nov;163(11):1905-17. doi: 10.1176/ajp.2006.163.11.1905.

Reference Type BACKGROUND
PMID: 17074942 (View on PubMed)

Markowitz JC. When should psychotherapy be the treatment of choice for major depressive disorder? Curr Psychiatry Rep. 2008 Dec;10(6):452-7. doi: 10.1007/s11920-008-0073-7.

Reference Type BACKGROUND
PMID: 18980727 (View on PubMed)

Simon GE, Ludman E, Unutzer J, Bauer MS. Design and implementation of a randomized trial evaluating systematic care for bipolar disorder. Bipolar Disord. 2002 Aug;4(4):226-36. doi: 10.1034/j.1399-5618.2002.01190.x.

Reference Type BACKGROUND
PMID: 12190711 (View on PubMed)

Parikh SV, Segal ZV, Grigoriadis S, Ravindran AV, Kennedy SH, Lam RW, Patten SB; Canadian Network for Mood and Anxiety Treatments (CANMAT). Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical guidelines for the management of major depressive disorder in adults. II. Psychotherapy alone or in combination with antidepressant medication. J Affect Disord. 2009 Oct;117 Suppl 1:S15-25. doi: 10.1016/j.jad.2009.06.042. Epub 2009 Aug 13.

Reference Type BACKGROUND
PMID: 19682749 (View on PubMed)

Stimpson N, Agrawal N, Lewis G. Randomised controlled trials investigating pharmacological and psychological interventions for treatment-refractory depression. Systematic review. Br J Psychiatry. 2002 Oct;181:284-94. doi: 10.1192/bjp.181.4.284.

Reference Type BACKGROUND
PMID: 12356654 (View on PubMed)

Trivedi RB, Nieuwsma JA, Williams JW Jr. Examination of the utility of psychotherapy for patients with treatment resistant depression: a systematic review. J Gen Intern Med. 2011 Jun;26(6):643-50. doi: 10.1007/s11606-010-1608-2. Epub 2010 Dec 24.

Reference Type BACKGROUND
PMID: 21184287 (View on PubMed)

11. Luborsky L. Principles of psychoanalytic psychotherapy: A manual for supportive/expressive treatment New York: Basic Books; 1984.

Reference Type BACKGROUND

Driessen E, Cuijpers P, de Maat SC, Abbass AA, de Jonghe F, Dekker JJ. The efficacy of short-term psychodynamic psychotherapy for depression: a meta-analysis. Clin Psychol Rev. 2010 Feb;30(1):25-36. doi: 10.1016/j.cpr.2009.08.010.

Reference Type BACKGROUND
PMID: 19766369 (View on PubMed)

Barber JP, Crits-Christoph P, Luborsky L. Effects of therapist adherence and competence on patient outcome in brief dynamic therapy. J Consult Clin Psychol. 1996 Jun;64(3):619-22. doi: 10.1037//0022-006x.64.3.619.

Reference Type BACKGROUND
PMID: 8698958 (View on PubMed)

14. Gaston L, Thompson L, Gallagher D, Cournoyer L-G, Gagnon R. Alliance, technique, and their interactions in predicting outcome of behavioral, cognitive, and brief dynamic therapy. Psychotherapy Research. 1998;8(2):190-209.

Reference Type BACKGROUND

Hilsenroth MJ, Ackerman SJ, Blagys MD, Baity MR, Mooney MA. Short-term psychodynamic psychotherapy for depression: an examination of statistical, clinically significant, and technique-specific change. J Nerv Ment Dis. 2003 Jun;191(6):349-57. doi: 10.1097/01.NMD.0000071582.11781.67.

Reference Type BACKGROUND
PMID: 12826915 (View on PubMed)

Abbass A, Sheldon A, Gyra J, Kalpin A. Intensive short-term dynamic psychotherapy for DSM-IV personality disorders: a randomized controlled trial. J Nerv Ment Dis. 2008 Mar;196(3):211-6. doi: 10.1097/NMD.0b013e3181662ff0.

Reference Type BACKGROUND
PMID: 18340256 (View on PubMed)

Abbass A, Kisely S, Kroenke K. Short-term psychodynamic psychotherapy for somatic disorders. Systematic review and meta-analysis of clinical trials. Psychother Psychosom. 2009;78(5):265-74. doi: 10.1159/000228247. Epub 2009 Jul 11.

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PMID: 19602915 (View on PubMed)

Abbass A, Town J, Driessen E. Intensive short-term dynamic psychotherapy: a systematic review and meta-analysis of outcome research. Harv Rev Psychiatry. 2012 Mar-Apr;20(2):97-108. doi: 10.3109/10673229.2012.677347.

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PMID: 22512743 (View on PubMed)

Abbass AA. Intensive Short-Term Dynamic Psychotherapy of treatment-resistant depression: a pilot study. Depress Anxiety. 2006;23(7):449-52. doi: 10.1002/da.20203.

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PMID: 16845654 (View on PubMed)

Town JM, Falkenstrom F, Abbass A, Stride C. The anger-depression mechanism in dynamic therapy: Experiencing previously avoided anger positively predicts reduction in depression via working alliance and insight. J Couns Psychol. 2022 Apr;69(3):326-336. doi: 10.1037/cou0000581. Epub 2021 Sep 30.

Reference Type DERIVED
PMID: 34591500 (View on PubMed)

Related Links

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http://www.istdp.ca

website of centre conducting research

Other Identifiers

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AA002

Identifier Type: -

Identifier Source: org_study_id

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