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MDD Treatment Augmentation

CME

Guidelines Overview: Augmentation Therapies in Major Depressive Disorder

Physicians: Maximum of 1.00 AMA PRA Category 1 Credit™

Released: February 26, 2020

Expiration: February 25, 2021

Roger S McIntyre
Roger S McIntyre, MD, FRCPC
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Your patient is a 34-year-old working mother with a 10-year history of MDD. She received 2 successive trials of first-line selective serotonin reuptake inhibitors (SSRIs) and had a partial response to both. She is currently receiving a serotonin and norepinephrine reuptake inhibitor (SNRI); after 4 weeks, however, some symptoms are affecting her performance at work and at home.

Which assessment tool would you recommend to capture changes in her functional impairment during treatment?
Major Depressive Disorder: Common, Costly, Disabling

Roger McIntyre, MD, FRCPC

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Antidepressants: How Effective Are They?

The FDA has approved more than a dozen antidepressants for use in the United States. Approved first‑line antidepressants include SSRIs, SNRIs, multimodal antidepressants such as vortioxetine, norepinephrine, dopamine modulators such as bupropion, and receptor modulators such as mirtazapine.

These agents have all demonstrated efficacy in double‑blind, randomized, placebo‑controlled trials in MDD. Moreover, all of the antidepressants that are considered first-line treatments in the United States have demonstrated their ability to prevent recurrence.

Currently, we do not have sufficient evidence that any single antidepressant agent or class of antidepressant agents is consistently superior to any other agents or classes. The efficacy of antidepressants has been substantiated both in meta‑analyses and network analyses, however. Thus, we can confidently conclude that antidepressants are significantly more effective than placebo in reducing depressive symptoms in adults with MDD.

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STAR*D: Antidepressant Efficacy Decreases With Successive Acute Treatments

The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study was carried out to determine the most effective “next-step” treatment for people with MDD.5 This trial was conducted in community and academic centers in both psychiatric and primary care patients (N = 3671). Between 1 and 4 successive treatments were provided in this study for patents with nonpsychotic MDD. Those who did not achieve remission or did not tolerate any treatment step proceeded to the next treatment step; those with an acceptable benefit from any treatment step remained on that step for 12 months.

The findings from the STAR*D study clearly demonstrate an overall remission rate of approximately 37% for the first‑line agent citalopram. Similarly, second-line therapy with either a switch strategy or an augmentation strategy using additional agents, with or without cognitive–behavioral therapy (CBT), exhibited a mean remission rate of approximately 31%. Strikingly, patients who reached third‑ and fourth-line treatments (as switch or augmentation strategies) experienced a lower remission rate of approximately 13%.

Thus, remission rates are low with first-line and second‑line interventions and decline significantly after the second‑line treatment has failed. This observation clearly demonstrates the need for new augmentation strategies in depression.

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Partial Response and Nonresponse to Antidepressant Treatment

Partial responses and nonresponses to antidepressant therapy are quite common: Only a minority of patients achieves full symptomatic remission.

Remission and response have been defined in various ways, including the following:

  • Remission tacitly implies the full abatement of symptoms. Remission has been characterized by a score of ≤ 7 on the HAM‑D or ≤ 10 on the Montgomery-Asberg Depression Rating Scale (MADRS).6,7
  • Partial response to an antidepressant has been defined as ≥ 50% reduction in overall symptom severity. The patient has had some degree of improvement, but it falls short of remission, which is the desired outcome.
  • Nonresponse to an antidepressant is defined as no improvement whatsoever after an adequate duration of adequately dosed antidepressant therapy.

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Selected MDD Guidelines

The use of point-of-care decision support vehicles, such as evidence‑based practice guidelines, can improve health outcomes in individuals with chronic noncommunicable diseases. Worldwide, more than 150 guidelines have been published regarding the treatment of adults with MDD.

Among the guidelines for MDD that are currently available in North America are those provided by the APA and by CANMAT.8,9

The most current US guidelines are the Florida Best Practices Psychotherapeutic Medication Guidelines, which are updated biannually and were most recently updated in January 2020.10

Clinicians are encouraged to supplement their decision making regarding the selection and sequencing of treatments by using these guidelines. Guideline-based practices improve health outcomes and precision, consistency, and cost effectiveness of caring for adults with MDD.

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Importance of Assessment in MDD

Measurement‑based care—the assessment and quantification of the patient’s depressive symptoms and adverse events of medications—has been identified as an important tactic in chronic disease management. It is crucial for assessing the response to treatment, as well as for screening and diagnostic purposes.

Clinicians should assess the severity of depression in each patient using a clinical metric like the PHQ-9 or the Quick Inventory for Depressive Symptomatology (QIDS). These scores provide the patient and clinician objective, quantifiable information about the severity of the depression.

These measures should be repeated so that clinicians can tailor the treatment to target specific symptoms and both the clinician and patient can obtain objective information about advances toward the treatment goals. The absence of such metrics provides fertile ground for a lack of precision in care outcomes and, in my opinion, sets up the patient for a potentially disappointing outcome.

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Selected Validated MDD Assessment Tools

Many validated depression scales are available. PHQ-9 is the most widely used in primary care and many specialty care settings. It is a self‑administered scale with good face validity, in that the 9 items on the scale represent the 9 criteria for a depressive episode.

Some scales are better known in the research community; these include the HAM‑D and MADRS. Additional tools used in clinical settings include the self‑administered Beck Depression Inventory.

It can also be clinically useful to supplement the assessment of depression with scales that measure functional changes in addition to symptoms of depression. The Generalized Anxiety Disorder 7 scale is commonly used to identify anxiety, the THINC-integrated tool (THINC-it) is used to assess changes in cognition, and the SDS is used to assess function in individuals with depression and evaluate the hazards posed by these conditions in these patients.

Finally, for patients receiving treatment, we should measure adverse events with tools such as the self-report scale, FIBSER.

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Guidelines: Monitoring MDD Treatment Response

There is a consensus across guidelines that monitoring a patient’s response to treatment includes monitoring functioning and adverse events as well as symptoms. This slide provides an overview of how 3 major guidelines can be used to accomplish this.

These scales can be used during the first visit and at follow-up. They are particularly useful when introducing new treatments or modifying ongoing treatments.

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Measurement-Based Care

To summarize, measurement‑based care provides a structured framework for the diagnosis of MDD and to assess and monitor symptoms, function, and adverse events in patients receiving treatment for MDD. Moreover, measurement‑based care is strongly endorsed by multiple guidelines that are used throughout North America and worldwide.

The goals of treatment differ for each phase of treatment. The first phase is the acute phase, where the goals are to achieve remission and begin the process of functional recovery. The second phase is the maintenance phase, during which the goals are to prevent recurrence, consolidate functional gains, and improve measures of wellness, well-being, and positive mental health in our patients.

In both phases, a formal measurement of the patient’s response to treatment is crucial.

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Which assessment tool would you recommend to capture changes in her functional impairment during treatment?
MDD: Integrated Care Model

Individuals with depression often have other physical and psychiatric problems, as well. For example, psychiatric comorbidities such as drug and alcohol use disorders and anxiety disorders are very common in people with depression. Some individuals with depression have interpersonal difficulties because of depression and, perhaps, past events, including trauma. They may also need psychotherapeutic interventions and a more complex psychosocial intervention. Because depression can involve families, it is not uncommon for family involvement and family therapy to be required in some cases.

The care plan must be designed to anticipate that the healthcare needs of an adult with depression can extend to all aspects of physical health, well-being, and interpersonal/social factors that can affect one’s wellbeing.

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