Halifax Treatment Refractory Depression Trial
Condition: Depression
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant
Study type: Interventional

Summary: 
      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: 
      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.
    

Intervention name(s): Intensive Short-term Dynamic Psychotherapy; Secondary Care Treatment as Usual
Intervention type(s): Behavioral; Behavioral
Intervention description(s): 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.; 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.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: depression; treatment-resistance; psychodynamic psychotherapy; Treatment refractory depression