_______________________________________________________________________ Depression and Suicide
From a clinical perspective, it is unrealistic to expect patients with MDD and minimal treatment response to continue with their antidepressant beyond two to four weeks. Integrating best evidence with pragmatism, intervention is recommended with insufficient outcome (symptom reduction ≤20%) after two to four weeks of treatment [62; 150]. With minimal improvement by two to four weeks, the recommended approach is to increase the dose, if the initial antidepressant is tolerated, or switch to another antidepressant if side effects are problematic [158]. Comparative Discontinuation Rates Due to Side Effects A meta-analysis of randomized controlled trials involving second-generation antidepressants found that overall discon- tinuation rates did not differ significantly between SSRIs as a class and bupropion, mirtazapine, nefazodone, trazodone, and venlafaxine. The higher discontinuation rate of venlafaxine versus SSRIs due to side effects (11.5% vs. 8.5%) was balanced by lower discontinuation rates due to lack of efficacy (3.5% vs. 4.4%) [122]. Collaboration with Mental Health Professionals Primary care providers should consider collaborating with behavioral healthcare providers when caring for patients with depression, especially in the following situations [21]: • Patient request for psychotherapy • Severe symptoms and impairment in patient • High suicide risk • The presence of other psychiatric condition (e.g., per- sonality disorder, history of mania) • Suspicion or history of substance abuse • Clinician discomfort with the case • Medication advice (psychiatrist or other mental health prescriber) • Patient request for more specialized treatment Integrate Measurements into Monitoring and Follow-Up Measurement-based care refers to the systematic use of mea- surement tools, such as validated rating scales, to monitor the trajectory of disease course and treatment response and support clinical decision-making. Using simple rating scales for measurement-based care of depression can improve outcomes such as symptom remission and adherence [62]. Many of the same instruments previously mentioned in this course can be used for this purpose. Among the most widely used instru- ments are the Inventory of Depressive Symptoms (IDS), the HAM-D, the MADRS, the PHQ-9, and the BDI [22]. Routine monitoring of patient outcomes should go beyond assessing depression symptoms by including the ongoing evalu- ation of functional impairment and quality of life. These out- comes are more important and relevant to patients, and each may vary independently of symptoms. Assessing functionality should include evaluating social and occupational/educational functioning. Quality-of-life assessments offer the opportunity
to more broadly evaluate patient well-being and overall health satisfaction [62]. The use of measurement tools should supple- ment and not replace clinician judgment [206; 207]. HERBAL MEDICATIONS, DIETARY SUPPLEMENTS, AND ALTERNATIVE THERAPIES Up to 50% of patients with depression use complementary therapies [208]. Herbal medications, dietary supplements, and alternative therapies for depression are appealing to many patients because they are perceived as being natural, helpful, and free of the potentially troubling side effects associated with pharmaceutical antidepressant treatment. Patients ambivalent about taking psychiatric medication are also likely to gravitate to these therapy approaches [209]. All patients should be asked if they are taking over-the-counter dietary supplements or herbal medications, to avoid adverse drug-drug interactions. Because many patients use comple- mentary/alternative therapies, clinicians should have a clear understanding of the most common modalities and potential impact on treatment course and outcomes. Acupuncture Acupuncture treatment of depression has shown mixed results, with some randomized controlled trials showing a significant treatment effect and others showing no significant difference from controls. Acupuncture may be an option for those who reject conventional treatments, for patients with milder depres- sion, or for pregnant or nursing women for whom the risks of pharmacotherapy are greater [21]. S-adenosylethionine (SAMe or Sam-E) S-adenosylethionine (SAMe) is a naturally occurring com- pound that is present in most parts of the human body and is involved in immune processes and the metabolism of dopa- mine, serotonin, and melatonin. Several studies have found that compared with placebo, SAMe is efficacious in oral doses of 800–1,600 mg/day, with side effects that were mild and transient. Overall, parenteral and oral formulations of SAMe are comparable to TCAs in efficacy in the treatment of MDD and are better tolerated. SAMe may also have comparable efficacy to TCAs in subgroups such as postpartum women and patients with HIV [22]. Hypericum perforatum (St. John’s Wort) St. John’s wort possesses an SSRI-like mechanism, and although considered a first-line antidepressant in many Euro- pean countries for mild-to-moderate depression, there is no consensus on its efficacy in MDD. Overall, the data suggest that St. John’s wort has efficacy comparable to low-dose TCAs in mild-to-moderate depression but is better tolerated by patients. However, St. John’s wort interacts with many drugs, including other antidepressants, warfarin, oral contraceptives, and antiretroviral, anticancer, and antirejection drugs. With numerous potential drug interactions, St. John’s wort cannot be considered a benign agent, and further studies are needed [175; 210; 211; 212; 213; 214; 215].
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