Depression and Suicide _ ______________________________________________________________________
Switch 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. Switching to an antidepressant with evidence of superior efficacy is recommended over switching to a lower-efficacy antidepressant based on it being in a different class [158]. Among switching strategies for poor initial SSRI response or tolerance, switching to venlafaxine seems most effective [110]. Combining or Switching Antidepressants and Psychotherapy Switching from an antidepressant to psychotherapy or vice versa appears useful for non-responders to initial treatment [250]. The addition of CBT or another medication can result in similar rates of improvement, although the addition of medication may result in a more rapid response [251]. Psychotherapy may provide better outcomes on adjustment and functional measures such as mood, suicidal ideation, work, and interests. Medication treatment may be superior on vegetative symptoms such as sleep [252]. Improvement with initial treatment with psychotherapy is typi- cally slower than with pharmacotherapy. A decision regarding progress with psychotherapy and the need to change or aug- ment this treatment modality may require 8 to 10 weeks before evaluation [21; 253]. If a patient has received psychotherapy and not responded, evaluate the treatment and consider another type. Augmentation Patients with MDD often prefer augmentation (add-on) to switching if partial improvement is achieved with the initial agent [254]. 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 [255; 256]. 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 [257]. Adverse effects are higher in combination pharmacotherapy, and combining antidepressants at treatment initiation is not recommended unless the MDD is characterized as severe (i.e., PHQ-0 >20); chronic (duration longer than two years); and recurrent (three or more episodes) [64]. In patients lacking response to their initial or switched standard antidepressant, evidence indicates that standard monoamine antidepressants are not sufficient for many patients and other mechanistic targets are needed [150].
Interventions to improve medication adherence have been found to be effective for up to six months, but the evidence for long-term effectiveness is insufficient and further research is needed [246]. Re-Evaluate the Diagnosis Most patients with MDD have comorbid conditions that can contribute to disease burden and interfere with treatment response [247]. Especially when undiagnosed, MDD with highly anxious features, comorbid panic disorder, social anxiety disorder, or obsessive-compulsive disorder is strongly predictive of poor medication response, side effect intolerance, treatment discontinuation, and worse overall prognosis. Alcohol or sub- stance use disorder contributes to poor treatment response; in these cases, involve addiction specialists as needed [241]. A behavioral health provider should be involved if a person- ality disorder is present [248]. Patients with bipolar disorder may require a different treatment approach, and hypomanic, mixed, or manic histories may not be apparent during the initial evaluation [21]. Patients with chronic subtypes of depression (i.e., chronic MDD, double depression, recurrent MDD) may take longer to respond to treatment; clinicians or patients may assume non-response and prematurely discontinue treatment. Differ- ent depression subtypes may respond preferentially to various antidepressants [249]. 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 [158]. Clinicians may consider switching to another antide- pressant when [158]:
• 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. An adjunctive medication may be added when [158]: • 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.
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