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The Massachusetts General Hospital Guide to Depression pp 3–19Cite as

Treatment-Resistant Depression

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Part of the book series: Current Clinical Psychiatry ((CCPSY))

Abstract

Major depression is one of the most common psychiatric disorders, and it often presents in combination with other medical and psychiatric illnesses. In almost one third of cases, it manifests as “difficult-to-treat depression” or “treatment-resistant depression” (TRD). In this chapter we will present an overview of this complex clinical problem, including epidemiology and challenges with definition and classification. We will discuss challenges with the differential diagnosis of TRD and steps for its treatment, including optimization, augmentation, and combination of pharmacologic agents. Finally, we will review briefly the use of somatic therapies or “neuromodulation” in the treatment of TRD.

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Authors and Affiliations

  1. Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Cristina Cusin

  2. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

    Stefan Peyda

Authors
  1. Cristina Cusin
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  2. Stefan Peyda
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Correspondence to Cristina Cusin .

Editor information

Editors and Affiliations

  1. Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Benjamin G. Shapero

  2. Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    David Mischoulon

  3. Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Cristina Cusin

FAQs: Common Questions and Answers

FAQs: Common Questions and Answers

  • Q1. When should TRD be diagnosed in a patient with depression?

  • A1. From clinical trials, the most common definition of TRD requires the lack of response to at least two adequate treatments for depression, including medications, talk therapy, or ECT, in the current episode. However this definition is of limited value in the clinical setting because it does not consider lack of response to antidepressant treatments in previous episodes, or the phenomenon of tachyphylaxis; the loss of effect of a medication after the initial benefit was sustained for a period of time, which probably has different underlying mechanisms.

  • Q2. What are the best steps when a depressed patient does not respond to a first-line treatment?

  • A2. The first recommendation is always to reevaluate the main diagnosis and all comorbidities, both from the medical and psychiatric point of view, in addition to the presence of concomitant medications that may affect mood or change the metabolism of the antidepressant. Bipolar depression, comorbid alcohol or substance use disorder, severe anxiety disorder, PTSD or OCD, and autoimmune disorders may significantly affect the likelihood of response to treatment. Psychiatry is lagging behind other disciplines in the habit of quantifying the severity of symptoms of depression over time, for example, with a self-administered or clinician-administered scale, to help with clinical decision making.

  • Q3. For how long should an antidepressant be tried before implementing changes?

  • A3. Most clinical trials to determine efficacy of a drug last 8 weeks, although if a patient does not show any clinical improvement after 4–6 weeks at an adequate dose, it is reasonable to modify the treatment with augmentation or combination.

  • Q4. When should ECT be considered in a patient with treatment-resistant depression?

  • A4. A clinician should consider multiple factors, including the severity and duration of depressive episode, the presence of suicidal ideation or behaviors, the number of past treatments failed, the presence of intolerable side effects from medications, potential medical contraindications, and patient wishes. ECT should be considered earlier in the algorithm in severe cases where the patient is at significant risk of harming self or others, is requiring physical restraint, and is acutely psychotic or catatonic or when the symptoms are life-threatening (e.g., refusal of food and water).

  • Q5. Could the label “TRD” have implications for subsequent response? Should we tell patients they are diagnosed with TRD?

  • A5. We know from research studies and from clinical practice that expectations on treatment outcome may directly influence the likelihood of the outcome itself (e.g., an enthusiastic endorsement from the clinician can increase the response rate to a treatment – even to a placebo – and conversely a tepid support may decrease it); however no study has specifically investigated whether the label “TRD” has a possible negative impact on subsequent outcome. Given the fact that patients with TRD are often experiencing hopelessness, it is important for the clinician to be aware of the existence of multiple modalities of treatment, to express positive expectations in the context of prescribing an intervention, and finally to consider expert consultation as another tool to help care for a patient.

  • Q6. How should we consider non-pharmacological and non-device-based therapies in the classification of TRD?

  • A6. The currently available classifications of TRD do not include other efficacious treatments. Part of the reason for excluding non-pharmacological and non-device-based interventions in the definitional criteria may be due to the difficulty in defining a failed trial. For example, how would a “failure to respond to an adequate course of CBT” be defined (a course of adequate duration and with adequate attendance and participation of the patient)? This is an important consideration because in controlled studies no antidepressant treatment has been shown to be clearly superior to another, even though different patients may respond to one medication and not to another. Similarly, a patient may experience poor response to medications but excellent response to individual therapy. The goal for the clinician is to match the best possible treatment to the patient. The chances of success are increased with the number of different options available for patients who do not improve with a first-line approach.

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Cusin, C., Peyda, S. (2019). Treatment-Resistant Depression. In: Shapero, B., Mischoulon, D., Cusin, C. (eds) The Massachusetts General Hospital Guide to Depression. Current Clinical Psychiatry. Humana Press, Cham. https://doi.org/10.1007/978-3-319-97241-1_1

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  • DOI: https://doi.org/10.1007/978-3-319-97241-1_1

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