Management of Treatment-Resistant Depression _ _________________________________________________
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In addition to augmentation strategies, a diverse and growing range of interventions are available as options for treatment- resistant depression. Most engage novel therapeutic targets.
ADJUST THE TREATMENT Options for patients lacking benefit from their initial antide- pressant include switching antidepressants, switching to or adding psychotherapy, and adjunctive strategies (i.e., adding a second medication). The decisions to switch or add medica- tions should be individualized and based on clinical factors [8]. Clinicians may consider switching to another antidepres- sant when [8]: • It is the first antidepressant trial. • Side effects are poorly tolerated. • Minimal or no response (i.e., <25% improvement). • There is more time to wait for a response (e.g., less severe, less functional impairment). • Patient prefers switching to another antidepressant. Lack of response to one first-line antidepressant does not preclude potential benefits from other antidepressants, but the value of switching between classes or within classes of antidepressants is debatable. An adjunctive medication may be added when [8]: • There have been two or more antidepressant trials. • The initial antidepressant is well tolerated. • There is partial response (i.e., >25% improvement). • There are specific residual symptoms or side effects to the initial antidepressant that can be targeted. • There is less time to wait for a response (e.g., more severe, more functional impairment). • Patient prefers to add on another medication. Patients with MDD often prefer augmentation (add-on) to switching if partial improvement is achieved with the initial agent [71]. Standard antidepressants are frequently used as add-on therapy to enhance efficacy. For example, combining a TCA and an SSRI may be helpful for some patients, but the TCA dose should be adjusted because SSRIs may increase TCA levels [72; 73]. Combining an SSRI, SNRI, or TCA with a presynaptic a2-autoreceptor antagonist (e.g., mirtazapine, trazodone) has shown significantly greater benefit than other combinations, with dosage differences accounting for about 50% of the total difference in treatment effect. Tolerability, as measured in patient dropout, was lower than expected with this combination [74].
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so you may determine the validity or relevance of the information. These sections may be used in conjunction with the course material for better application to your daily practice.
INTRODUCTION Treatment-resistant depression is a problem increasingly encountered by primary care and mental health providers. Most definitions of treatment response compare changes in depression rating scale scores between pre-treatment and follow-up. Standardized rating scales such as the MADRS and HAM-D are widely used to quantify treatment response [1]. The definition of antidepressant response falls into four categories [2; 3]: • Remission: The absence of depressive symptoms or minimal symptoms (HAM-D score ≤7) • Response: A 50% or greater reduction in symptoms • Partial response: A 25% to 50% reduction in symptoms • Nonresponse: The absence of meaningful response (symptom reduction ≤25%) Standard antidepressants fail to produce adequate response in 30% to 50% and remission in up to 70% of patients with major depressive disorder (MDD) [4; 5; 6]. Partial response, instead of full remission, leaves patients with impairing residual symptoms and high risk of relapse. Each relapse increases symptom severity, decreases treatment response, and heightens risk of treatment-resistant MDD [7]. Contributors to treatment-resistant depression include ill- ness severity, medical and psychiatric comorbidity, and the limitations of FDA-approved drug options. The definition of treatment resistance lacks consensus, but the most common definition is inadequate response to two or more antidepres- sants. This does not consider adjunctive strategies or distin- guish patients with partial versus non-response [8; 9].
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