Act early to improve outcomes in schizophrenia and major depressive disorder

At the 35th ECNP Congress in Vienna, Austria (15th−18th Oct), in a symposium entitled ‘Overcoming barriers in major depressive disorder and schizophrenia: what are we waiting for?’ a distinguished faculty discussed the importance of timely diagnosis and early implementation of management strategies. There are barriers to providing effective therapy that may be overcome by establishing a strong patient-physician relationship and by delivering integrated care. Various approaches to treatment-resistant depression, including augmentation strategies, were also discussed. What is clear is that in both schizophrenia and major depressive disorder, early intervention, complete symptom management and uninterrupted care offer patients the best opportunity for remission and full functional recovery.

Early and integrated intervention improves outcomes

As Dr Charlotte Emborg Mafi (Aarhus University Hospital, Denmark) explained, “the first psychotic episode provides a unique opportunity to intervene to avoid a relapsing course of illness and loss of functional level”. Early intervention starts with psychoeducation and personalized antipsychotic treatment, and can improve the course of illness.

“The first psychotic episode provides a unique opportunity to intervene to avoid a relapsing course of illness and loss of functional level.” – Dr Charlotte Emborg Mafi, Copenhagen, Denmark

Patients are afraid of relapse because they know it can diminish personal autonomy, cause distress to family members, jeopardize relationships and disrupt education and employment.1,2 An integrated approach to care, including assertive community treatment, programs for family involvement and social skills training, is shown to improve clinical outcomes and treatment adherence.3

 

Fixing the ‘broken brain’

Professor Robin Emsley (Stellenbosch University, South Africa) considered that the underlying fundamental disorder must be adequately treated to achieve full functional recovery. In schizophrenia, the way to fix the ‘broken brain’ is to provide uninterrupted stabilization of dopamine D2 receptors.4 This can be achieved by providing effective, continuous treatment in the early stages of illness.

“Stopping antipsychotic treatment is the strongest predictor of relapse and there is mounting evidence that each relapse may be the critical factor in emergent treatment-refractoriness.” – Professor Robin Emsley, Cape Town, South Africa

“Stopping antipsychotic treatment is the strongest predictor of relapse and there is mounting evidence that each relapse may be the critical factor in emergent treatment-refractoriness”, said Professor Emsley.5 He considered that “the most appropriate use of long-acting injectable antipsychotics is in the early stages of schizophrenia”, for which there is evidence of illness stabilization and improvement in symptomatic and functional remission.6,7

 

Defining inadequate response in MDD

Turning attention to depression, Assistant Professor Diane McIntosh (University of British Columbia, Canada) considered that many patients with depression have inadequate response (partial/minimal response) to treatment which is less easy to define compared to treatment-resistant depression (TRD).8 What is not in doubt is that inadequate response is a powerful predictor of relapse. She added that “If residual symptoms are left behind, that patient is at a massive risk of having another episode of depression, with ongoing functional impairment and impaired quality of life.” The best chance of achieving remission with treatment is within 6 months of onset of major depressive disorder.9

“If residual symptoms are left behind, a patient is at a massive risk of having another episode of depression, with ongoing functional impairment and impaired quality of life.” – Assistant Professor Diane McIntosh, British Columbia, Canada

 

Augmentation strategies in MDD

Although effective, Professor Anthony Cleare (Kings College London, UK) identified that very few patients with TRD are given augmentation strategies in clinical practice. However, evidence suggests that augmentation is at least as effective as switching strategies.10,11 “When deciding whether to augment or to switch, building on a partial response is a good strategy” he said. "Consideration of other factors present that may respond well to augmentation therapies include psychoses or bipolar spectrum, and symptoms of anxiety, fatigue and sleep interruption. Patients who have an early response to augmentation treatment, within the first 2 weeks, go on to have a good treatment outcome", he added.12

“Patients who have an early response to augmentation treatment, within the first 2 weeks, go on to have a good treatment outcome.” – Professor Anthony Cleare, London, UK

 

Educational financial support for this Satellite symposium was provided by Otsuka Pharmaceutical Development and Commercialization Inc., and Lundbeck A/S.

 

ECNP : European College of Neuropsychopharmacology 
MDD : Major Depressive Disorder 
TRD : treatment resistant depression
UK : United Kingdom

BE-NOTPR-0235, approval date : 01.2023

Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.

References
  1. Emsley R, et al. The evidence for illness progression after relapse in schizophrenia. Schizophr Res. 2013;148(1-3):117-21.
  2. Kane JM. Treatment strategies to prevent relapse and encourage remission. J Clin Psychiatry. 2007;68(Suppl 14):27-30.
  3. Petersen L, et al. A randomized multicenter trial of integrated versus standard treatment for patients with a first episode of psychotic illness. BMJ 2005;331(7517):602.
  4. Emsley R, et al. The nature of relapse in schizophrenia. BMC Psychiatry 2013;13:50.
  5. Takeuchi H, et al. Does relapse contribute to treatment resistance? Antipsychotic response in first- vs. second-episode schizophrenia. Neuropsychopharmacology 2019;44(6):1036–42.
  6. Kane JM, et al. Effect of long-acting injectable antipsychotics vs usual care on time to first hospitalization in early-phase schizophrenia: a randomized clinical trial. JAMA Psychiatry. 2020;77(12):1217–24.
  7. Phahladira L, et al. Early recovery in the first 24 months of treatment in first-episode schizophrenia-spectrum disorders. NPJ Schizophr 2020;6(1):2.
  8. McAllister-Williams RH, et al. The identification, assessment and management of difficult-to-treat depression: An international consensus statement. J Affect Disord 2020;264:264-282.
  9. Bukh JD, et al. The effect of prolonged duration of untreated depression on antidepressant treatment outcome. J Affect Disord 2013;145:42–48.
  10. Mohamed S, et al. Effect of antidepressant switching vs augmentation on remission among patients with major depressive disorder unresponsive to antidepressant treatment: The VAST-D randomized clinical trial. JAMA 2017;318:132–145.
  11. Carter B, et al. Relative effectiveness of augmentation treatments for treatment-resistant depression: a systematic review and network meta-analysis. Int Rev Psychiatry 2020;32:477–490.
  12. Taylor RW, et al. Predictors of response to augmentation treatment in patients with treatment-resistant depression: A systematic review. J Psychopharmacol 2019;33:1323–39.
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