Considerations when selecting an antidepressant: a narrative review for primary care providers treating adults with depression.

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.

Major depressive disorder (MDD) is a leading cause of disability worldwide and can affect each patient differently. Antidepressants play a critical role in treatment; however, with multiple antidepressant options available, it is important that providers select the best fit for each patient. Rather than use a "one size fits all" approach, it is important to consider each patient's symptoms, medical and psychiatric comorbidities, as well as their treatment preferences. A clear summary of each antidepressant's distinctive characteristics is essential for providers to select antidepressants to best match each patient's needs.This narrative review aims to discuss the latest information on available antidepressants, including their risks and benefits and how they impact symptoms of MDD such as sleep disturbances, anxiety, emotional blunting, and changes in cognition, as well as different treatment goals, such as the ability to function in everyday life. This information can guide clinical practice recommendations and further enable shared decision-making between the provider and patient, incorporating individual treatment needs and preferences.In addition, many patients do not reach their treatment goals with the first antidepressant or may continue to have symptoms of depression after treatment. This review discusses strategies to increase the likelihood of symptom improvement and creates awareness of patient-specific considerations.Overall, careful, personalized selection of antidepressant treatment is critical for finding the right balance of maximized antidepressant effect with minimized side effects, leading to the best possibility for patients to tolerate the medication and ultimately helping patients reach their treatment goals.

Screening for Bipolar I Disorder and the Rapid Mood Screener: Results of a Nationwide Health Care Provider Survey.

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.

Practical Advice for Primary Care Clinicians on the Safe and Effective Use of Vortioxetine for Patients with Major Depressive Disorder (MDD).

Primary care clinicians have a vital role to play in the diagnosis and management of patients with major depressive disorder (MDD). This includes screening for MDD as well as identifying other possible psychiatric disorders including bipolar disorder and/or other comorbidities. Once MDD is confirmed, partnering with patients in the shared decision-making process while considering different treatment options and best management of MDD over the course of their illness is recommended. Vortioxetine has been approved for the treatment of adults with MDD since 2013, and subsequent US label updates indicate that vortioxetine may be particularly beneficial for specific populations of patients with MDD, including those with treatment-emergent sexual dysfunction and patients experiencing certain cognitive symptoms. Given these recent label updates, this prescribing guide for vortioxetine aims to provide clear and practical guidance for primary care clinicians on the safe and effective use of vortioxetine for the treatment of MDD, including how to identify appropriate patients for treatment.

Implementing Measurement-Based Care to Determine and Treat Inadequate Response.

​​ 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.​ ​.

Recognizing Inadequate Response in Patients With Major Depressive Disorder.

​​ ​​ 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. ​.

Inadequate Response to Treatment in Major Depressive Disorder: Augmentation and Adjunctive Strategies.

​​​​ 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.​ ​.

Overcoming Challenges to Treat Inadequate Response in Major Depressive Disorder.

​​ ​​ 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. ​​.

The benefits of measurement-based care for primary care patients with depression.

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.

Sustained remission with lamotrigine augmentation or monotherapy in female resistant depressives with mixed cyclothymic-dysthymic temperament.

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.

When All Else Is Done: The Challenge of Improving Antemortem Care.

Recent findings from the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT) reveal that Americans are receiving antemortem care that is highly technical and interventional, but poorly consistent with patients' wishes. A growing body of research in palliative medicine describes a manner of care that restores the possibility of a "good death" to the vast majority of patients. By familiarizing themselves with the medical, psychological, legal, and existential aspects of antemortem care, primary care physicians can offer excellent palliative care, changing the landscape of postmodern medicine for the benefit of all patients-including ourselves.

When Patients Are Normal People: Strategies for Managing Dual Relationships.

A significant number of generalist physicians, particularly those in rural areas, often find themselves participating in the care of patients for whom the therapeutic relationship overlaps with another relationship (e.g., social or professional). Although psychiatrists and psychologists are typically advised to avoid such "dual relationships," no such prohibition exists for generalists. Little, if any, guidance exists to aid in the management of such dual relationships for the generalist who provides treatment for psychiatric conditions for his or her patients. The author, a generalist with experience in the treatment of mood disorders, describes potential challenges faced by the generalist who chooses to provide care for "dual relationship" patients and outlines strategies for successfully meeting these challenges.

Retrospective Study of Olanzapine in Depressive and Anxious States in Primary Care.

CONTEXT: Bipolar spectrum and treatment-resistant unipolar mood disorders are increasingly identified in primary care settings. Olanzapine demonstrates efficacy in the treatment of acute mania and bipolar depression and in bipolar maintenance therapy. Olanzapine-fluoxetine combination therapy shows efficacy in treatment-resistant depression. OBJECTIVE: To examine the efficacy and tolerability profile of olanzapine in various difficult-to-treat depressive and/or anxious states in primary care outpatients. METHOD: A retrospective chart review was conducted for all identifiable patients prescribed olanzapine for mood disorders (DSM-IV) during a 3-year period (July 1998-July 2001), utilizing clinician and nurse recall, sampling of general continuity clinic records, and a hand search of mood disorder clinic records. MAIN AND SECONDARY OUTCOME MEASURES: Initial and final scores on the Global Assessment of Functioning (GAF) scale, duration of therapy, and adverse effects. RESULTS: Thirty-seven patients were identified as having received treatment with olanzapine; 3 were referred to the mental health specialty sector at the time of treatment initiation, and 2 were lost to follow-up. Of the 32 patients receiving ongoing treatment by primary care clinicians, most were female (N = 23; 72%) and all were white (100%). Most were diagnosed with a mental illness in the bipolar spectrum (N = 25; 78%) and demonstrated treatment resistance with antidepressants and/or mood stabilizers (mean number of previous psychotropic medications = 3.7). In the group completing therapy (24 patients [75%]; mean duration of treatment = 242 days), GAF scores demonstrated a clinically and statistically significant improvement (mean initial GAF score = 59 +/- 9; mean final GAF score = 76 +/- 11; p < .0001). Twenty (83%) of these 24 patients demonstrated sustained improvement in their GAF scores. In the group that discontinued therapy (8 patients [25%]; mean duration of treatment = 123 days), GAF scores also demonstrated a clinically and statistically significant improvement (mean initial GAF score = 51 +/- 15; mean final GAF score = 70 +/- 11; p < .0001). Six (75%) of these 8 patients demonstrated sustained improvement in their GAF scores. For all patients, observed adverse effects included weight gain (25 patients [86%]; mean = 3.63 kg), sedation (6 patients [19%]), and dry mouth (1 patient [3%]). CONCLUSION: Olanzapine shows promise as an effective pharmacotherapeutic agent for primary care patients with mood disorders that lie along the bipolar spectrum or that are resistant to treatment with antidepressant monotherapies, but is associated with mild-to-moderate weight gain.

Olanzapine for intractable nausea in palliative care patients.

Nausea is a common problem among palliative care patients, which is often undertreated. Olanzapine, an atypical antipsychotic, possesses a unique neurotransmitter binding profile that is similar to methotrimeprazine, an anti-emetic widely used in Europe for recalcitrant nausea. We report a case series of six patients who suffered nausea which was resistant to initial treatment with traditional antiemetics; each patient exhibited marked improvement when treated with olanzapine.

Antemortem care in an afternoon: a successful four-hour curriculum for third-year medical students.

Numerous well-designed studies have shown that patients near the end of life often receive substandard palliative care. Medical students have expressed a strong interest in antemortem care; however, palliative medicine education remains poorly integrated into the overall curriculum at most medical institutions in the United States. In response to this need, a palliative medicine curriculum has been developed for medical students in the required third-year clerkship in family medicine at the University of Tennessee Health Sciences Center The implementation of this curriculum resulted in a statistically significant increase in student competence (as measured by a standardized pretest and post-test) and a significant trend in student confidence (as measured by a single-item Likert scale). The curriculum was popular with students, and encouraged many of them to request hospice clinical experiences during their family medicine clerkship, or to register for the elective fourth-year clerkship in palliative medicine.

Developing a therapeutic plan for treating MS: evidence for new treatments.

Patients with multiple sclerosis (MS) require an individualized treatment plan that will help slow disability progression and reduce the number and duration of relapses. The available disease-modifying therapies are approved for relapsing forms of MS, with one agent also approved for secondary progressive MS. Clinicians must know the benefits and adverse effects associated with these treatments and guide patients to the most appropriate medication tailored to their disease course and presentation, as well as to their preferred administration method. To treat relapses that have not spontaneously remitted, clinicians may use short-term steroids (IV or oral formulations) or, for acute relapses in patients who cannot tolerate steroids, plasma exchange or IV immunoglobulin (IVIG). Patients may also have questions regarding complementary and alternative medicines, so clinicians should know which options are most promising for patients with MS.

Assessing and managing pain and major depression with medical comorbidities.

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.