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Major depressive disorder (MDD) is a debilitating mental disorder that can be treated with a number of different antidepressant therapies, each with its own unique prescribing considerations. Complicating the selection of an appropriate antidepressant for adults with MDD is the heterogeneity of clinical profiles and depression subtypes. Additionally, patient comorbidities, preferences, and likelihood of adhering to treatment must all be considered when selecting an appropriate therapy. With the majority of prescriptions being written by primary care practitioners, it is appropriate to review the unique characteristics of all available antidepressants, including safety considerations. Prior to initiating antidepressant treatment and when patients do not respond adequately to initial therapy and/or exhibit any hypomanic or manic symptoms, bipolar disorder must be ruled out, and evaluation for psychiatric comorbidities must be considered as well. Patients with an inadequate response may then require a treatment switch to another drug with a different mechanism of action, combination, or augmentation strategy. In this narrative review, we propose that careful selection of the most appropriate antidepressant for adult patients with MDD based on their clinical profile and comorbidities is vital for initial treatment selection.Strategies must be considered for addressing partial and inadequate responses as well to help patients achieve full remission and sustained functional recovery. This review also highlights data for MDD clinical outcomes for which gaps in the literature have been identified, including the effects of antidepressants on functional outcomes, sleep disturbances, emotional and cognitive blunting, anxiety, and residual symptoms of depression.

Objective: Effective screening for bipolar I disorder can lead to enhanced assessment, improved diagnosis, and better patient outcomes. The Rapid Mood Screener (RMS), a new bipolar I disorder screening tool, was evaluated in a nationwide survey of health care providers (HCPs)., Methods: Eligible HCPs were asked to describe their opinions/current use of screening tools, assess the RMS, and evaluate the RMS versus the Mood Disorder Questionnaire (MDQ). Results were stratified by primary care and psychiatric specialty. Findings were reported using descriptive statistics; statistical significance was reported at the 95% confidence level., Results: Among respondents (N = 200), 82% used a tool to screen for major depressive disorder (MDD), while 32% used a tool for bipolar disorder. Most HCPs were aware of the MDQ (85%), but only 29% reported current use. According to HCPs, the RMS was significantly better than the MDQ on all screening tool attributes (eg, sensitivity/specificity, brevity, practicality, easy scoring; P  < .05 for all). Significantly more HCPs reported that they would use the RMS versus the MDQ (81% vs 19%, P  < .05); 76% reported that they would screen new patients with depressive symptoms, and 68% indicated they would rescreen patients with a depression diagnosis. Most HCPs (84%) said the RMS would have a positive impact on their practice, with 46% saying they would screen more patients for bipolar disorder., Discussion: In our survey, the RMS was favorably evaluated by HCPs. A large percentage of respondents preferred the RMS over the MDQ and indicated that it would likely have a positive impact on clinicians' screening behavior., (© Copyright 2023 Physicians Postgraduate Press, Inc.)

​​ ​​ When a patient with major depressive disorder experiences inadequate response to an antidepressant, clinicians should employ measurement-based care strategies to improve outcomes. Evidence suggests that adjunctive therapies, such as the FDA-approved atypical antipsychotics, are efficacious when the initial treatment is well tolerated but not improving symptoms. Clinicians should consult guidelines, peer-reviewed journals, CME programs, and other sources to stay up-to-date with current and emerging treatments in this area. They should also be familiar with the available options for psychotherapy, neurostimulation, supplements, and exercise for patients who prefer alternative therapies. ​​., (© Copyright 2020 Physicians Postgraduate Press, Inc.)

​​​​ About 30%-50% of patients experience inadequate response to antidepressant therapy, and treatment choices for these patients include augmenting the antidepressant with another therapy, increasing the dose, switching to a different antidepressant, or combining antidepressants. Clinicians should tailor treatment strategies based on patients' response, tolerability, and disease severity. In this activity, augmentation and adjunctive strategies involving atypical antipsychotics, as well as off-label options including buspirone, stimulants, thyroid hormone, and lithium, are reviewed.​ ​., (© Copyright 2020 Physicians Postgraduate Press, Inc.)

​​ Measurement-based care (MBC) is an important strategy in the treatment of patients with major depressive disorder who have inadequate antidepressant response. The rating scales used in MBC can assist clinicians at critical decision points, such as when to declare a treatment failure, what to do with partial improvement, and how long to continue successful treatment. Measurement has two benefits: it gives the clinician an objective basis for comparison of symptom severity over time, and it helps patients to have insight into their illness course. Further, many of these tools do not add substantially to the length of the clinical visit. MBC can also be used to monitor and address residual symptoms such as fatigue and irritability that impact patients' functioning and quality of life.​ ​., (© Copyright 2020 Physicians Postgraduate Press, Inc.)

​​ ​​ Being able to recognize inadequate response to antidepressant treatment and distinguish it from treatment-resistant depression is key in order for clinicians to provide appropriate therapies. Although definitions vary, nonresponse is often defined as less than 25% improvement on a standardized rating scale, and partial response, as more than 25% but less than 50% improvement. Residual symptoms characteristic of inadequate response (less than 50% improvement) include low mood, anxiety, irritability, guilt, and somatic symptoms. Various factors that may contribute to inadequate response to an antidepressant include inadequate dose or duration, poor adherence, and misdiagnosis. ​., (© Copyright 2020 Physicians Postgraduate Press, Inc.)

Follow the case of Mrs C, a primary care patient with depression who fails to respond to initial antidepressant treatment, and see how measurement-based care helps her clinician confirm her diagnosis, track symptom response, and assess her sense of well-being. Using rating scales such as the 9-item Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder 7-item scale (GAD-7), and Mood Disorder Questionnaire (MDQ) can help clinicians recognize suboptimal response and make treatment adjustments such as optimizing the medication dose, switching to another medication, or augmenting with medications, psychotherapy, or exercise. For Mrs C and other patients with depression, the goal of treatment must go beyond symptom remission to improve quality of life., (© Copyright 2016 Physicians Postgraduate Press, Inc.)

Chronic pain is the leading reason patients see their primary care physician, and the burden of pain and depression in those with medical illness is particularly severe. Improving depressive symptoms can decrease physical symptoms in many patients, but these patients may require a different treatment strategy than those with depression alone. This activity provides guidance on recognizing and accurately diagnosing pain and major depression, managing these conditions using assessment tools and measurement-based care, avoiding unwanted side effects and drug interactions, and properly matching patients to appropriate treatments., (© Copyright 2013 Physicians Postgraduate Press, Inc.)

Background: The treatment of bipolar depression remains problematic. Lamotrigine has been shown in randomized controlled studies to be efficacious in preventing bipolar depression and rapid cycling states., Methods: Twenty-four women with cyclothymic temperament and refractory depression were recruited from four outpatient sites (three primary care and one psychiatric) and treated with lamotrigine in a naturalistic, open-label study. Temperament was determined by responses on the TEMP-A self-rating scale. Eighteen (75%) of these cyclothymic patients also scored high on the depressive temperament. Eighteen (75%) met DSM-IV criteria for bipolar II disorder. In two thirds of the cases, lamotrigine was add-on therapy to an antidepressant. Response to therapy was assessed using the DSM-IV Global Assessment of Functioning (GAF)., Limitations: This study was naturalistic in design, without controls or blinds., Results: Of the 23 patients who remained in the study, 16 (70%) had significant, sustained responses. Of these 16, 12 (75% of responders, 52% of the total) had remissions (GAF > 80) sustained longer than 12 months. Robust, sustained responses to lamotrigine monotherapy were seen in 4 patients (17%). Seven patients (30%) received no apparent benefit from lamotrigine., Conclusions: Lamotrigine induced prolonged illness remissions in a substantial number of female patients whose symptoms were both complex and refractory. Most manifested high scores on the cyclothymic and depressive temperaments, and prior refractoriness to multiple antidepressant and antidepressant/mood stabilizer combinations, before remitting with lamotrigine augmentation or monotherapy.