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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.

​​ ​​ 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. ​​.

​​​​ 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.​ ​.

​​ 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.​ ​.

​​ ​​ 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. ​.

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.

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.

Remember the mid-1980s? Many psychiatric researchers were very surprised to find a large burden of depression in primary care patients. Of course, with the advent of the SSRIs (selective serotonin reuptake inhibitors) and other safe and effective antidepressants, we in primary care were reassured that we could, indeed, adequately treat these patients, reducing morbidity (and mortality!) with expedition and ease. Twenty years on, and the plot has thickened. In our offices and for our patients, the high prevalence of treatment-resistant depression, the confusion involving differential diagnoses (including bipolar depression and substance abuse disorder), and the interplay of Axis II disorders with Axis I pathology have laid bare some of the halcyon assumptions regarding easy efficacy that marked primary care affective medicine 2 decades ago. If the past informs the present, and is truly prologue to the future, then we could use a history lesson. Callahan and Berrios provide the very best kind—well-written, informative, clearly referenced, and lucidly conceptualized—to tell a story of how we came to approach mental illness in primary care as we do. Their central thesis states that the current model of depression is deterministic and too narrowly defined, overemphasizing the biomedical and failing to take fully into account the contributions of psychosocio-spiritual factors to the patient's experience of emotional suffering. They contend that this narrow model, developed by specialty psychiatry and later endorsed by primary care physicians, prevents many patients from receiving adequate diagnoses and treatment. In addition, it neglects many of the multidisciplinary strengths of the generalist physician and thus lowers the quality of care. To begin, the authors explode 2 favorite myths of modern medicine: that of the old-time doctor (who saw fewer patients, had more time, and was happier with the practice) and that of the old-time patient (who complained less, appreciated the doctor more, and was reluctant to accept medical treatment for emotional suffering). Next, they portray the realities of midcentury primary care and subsequent changes in generalist practices. They then trace the emergence of specialty psychiatry, the development of effective medications for psychiatric disorders, and the rise of criteria-based psychiatric diagnoses. Following the development of fluoxetine as penicillin for the blues, the authors describe the consequences of marketing in a vacuum—the interaction of pharmaceutical companies with physicians or patients in the absence of robust regulatory and academic relationships. The book closes by arguing that only a broader model of mental health and illness will bring to bear the particular strengths of primary care in reducing the overall burden of morbidity and mortality (in a manner similar to the mass strategy associated with such multifactorial illnesses as coronary artery disease and diabetes mellitus). In other words, we don't necessarily need to become better psycho-pharmacologists; we might better serve our patients as better listeners, or counselors, or in some other capacity. As an intriguing aside, the authors propose that the confusion that reigns with regard to the treatment of affective illness in primary care is symptomatic of a more fundamental problem—the failure of generalists to posit and practice a comprehensive vision of their relationship to patients and to society as a whole. Having yielded to the allure of becoming Everydoctor for Everypatient, will generalists suffer a dilution of skills and focus that will ultimately devalue the enterprise entirely? The authors believe this may be the case and argue that the emotionally suffering patient is the canary in the coal mine that signals this unraveling of a coherent role for the generalist in modern medicine. Now and again, a book or paper appears that seems to part the fog, not only showing things as they are but explaining how they arrived to be that way. Reinventing Depression is that kind of book. In a manner reminiscent of Starr's classic The Social Transformation of American Medicine,1 it points the ways to a workable postmodern model of primary care affective medicine by thoroughly illuminating past and present conditions, with all their inconsistencies and serendipities. Serious students of the sociology of medicine, the evolution of primary care as a practice and as a discipline, and the treatment of mental illness will find it time well spent.

I grant that it is uncommon for reviewers to share their thoughts on books that have been in print for 4 years. However, I also confess that it is not uncommon for this reviewer to sometimes attend to the tyranny of the urgent, while the seductive book slides further and further beneath a pile of unread journals, personal correspondence, scattered bills and professional letters, and yes, the occasional parking violation. Thus it was that, a full 2 years from the intended season, I read this anthology—and fell so hopelessly for its variety and subtlety of expression of the untellable, the incomprehensible experience of mental illness, that I bring you this summation. Unholy Ghost is a collection of 23 essays by persons who are writers by trade and depressives (or family members of depressives) by fate. In the manner of (and containing an excerpt from) Styron's classic memoir Darkness Visible, the book comprises pieces that are unrelated, but not disjointed, as each offers a unique perspective on what the inner life of depression truly is. I have pored over research articles, labored over textbooks, and memorized sections (yes) of the DSM-IV, but never have I encountered documents that framed the stories of my own patients so well as some found here. Consider the title phrase, borrowed from Jane Kenyon's “Credo”: “Pharmaceutical wonders are at work/but I believe only in this moment/of well-being. Unholy ghost,/you are certain to come again.”1 For the clinician, this book is a mine containing rich ore, and much of the work has been done in helping him or her to grasp the patient's inner life. The interplay between medical illness (heart surgery) and depression, the struggle of a pregnant mother with the risk of teratogenicity of pharmaceutical therapy, the relation between pain and depression, the special characteristics of unipolar versus bipolar depression, ethnic and cultural contextualization of mental illness, the experience of hospitalization and electroconvulsive therapy, the influence of childhood events on adult psychiatric health and illness—they're all here and faithfully rendered. To hear Darcey Steinke say, “I felt like I'd been found incompetent and fired from my own life” (p. 64) or listen to David Karp report that “my mind made a choice each day about how to torment my body” (p. 143) is to be granted a special window into the soul of depression by those unfortunate enough to have lived it, gifted enough to report it, and courageous enough to undertake such an enterprise. The sections are modular, and thus, each demands little of the busy practitioner's time. Woe to the reader, however, who starts this book without adequate time. He or she will soon be drawn inexorably to it, and it will be the journals, the letters, and yes, the traffic violation, which end at the bottom of the heap.

In this memoir, Michael Rowe recounts the life, illness, and death of his son, who succumbed to complications of a liver transplant at the age of 19. The focus of the book is Jesse's final 3 months in hospital in 1995, but Rowe supplements the chronological accounts of the hospitalization with flashbacks to Jesse's childhood. Each of the 14 chapters also contains an original sketch by Jesse, who was an aspiring artist. The sketches serve as points of departure for Rowe, first as a frightened father looking for windows into the mind of his gravely ill son, then as a grieving father hoping to capture glimpses of meaning after his son is gone. The author is honest, perceptive, and forthcoming in his tale. Readers expecting a well-choreographed story, with the stock characters of the bravely suffering patient, the quietly grieving parents, and the magnanimously hovering medical staff will be disappointed. This is no Death Be Not Proud, a lyrical, majestic elegy to a fallen son. This is a postmodern story, where coherence is fleeting, events are chaotic, and interactions are truncated by unspoken thoughts and demanding schedules. There is beauty here, and heroism too. But it is of an unpredictable and ephemeral kind. Rowe's guilt at leaving work to be with Jesse, or vice versa, is a vivid portrait of a father in conflict, frustrated at his impotence. When Jesse becomes violently nauseous, and no one can seem to find an emesis basin, it is his stepmother who cups her hands underneath his chin so that his vomitus won't soil his clothes. Each of Jesse's 4 parents finds a way to remain family, pooling resources to try to rise to an occasion that is unthinkable—the death of a child. For all its poignant snapshots, I found the book to be deeply frustrating. The author's jolting style, a stream-of-consciousness more akin to the frenetic pace of MTV than to Faulkner's flowing run-ons, prevents the reader from grasping any real sense of the direction of the story. As a character, Jesse is presented as aloof, mysterious, and unknown. He is not easy to root for, and the reader is ever wary of the shifting teams of physicians and surgeons, who alternately seem to hold omnipotence and powerlessness in one collective, imperfect conglomerate of human foible. The conclusion of the book is unsatisfying, and not just because the hero doesn't win. We feel we never knew the hero at all. Despite this sense of incompletion, or perhaps because of it, I feel that clinicians who care for pediatric patients or for patients who have ill children would benefit greatly from reading The Book of Jesse. Rowe said that most of all, he wanted to “tell Jesse's story.” I think that he accomplished just that—he tells a contemporary tale, where good doesn't necessarily win the day, where fathers long to know their sons but feel they must keep their distance, and where families struggle to find meaning in a world that sometimes has no immanently discernible pattern. Having never faced serious illness in one of my children, I cannot quibble with Rowe because he did not give me an uplifting and inspirational book. I must praise him for giving me a true one.

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.

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.

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.

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.

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.

The wisdom of the adage about books and their covers is often lost on this self-confessed bibliophile. Little books, big books, paperbacks, leather-bound behemoths—I am easily seduced. So I was surprised (and embarrassed) to find that I delayed this review for 2 months for none but the shallowest of reasons: I didn't like the feel of it. A wire-bound softcover, its title states it is intended to be a manual (literally, a book for the hand). But at a size of 75 cubic inches and a weight of 1 lb 8 oz, that's some hand. The spiral binding is impractical in a book this large; after a few uses, it invariably becomes bent, rendering the pages difficult to turn. The end result is predictable, and it seems the pages central to the discussion always tear loose first. Enough ranting about mundane practicality; on to the content. Try as I might to resist this book, I could not. The organization of the material is prosaic and not conducive to quick reference. The information presented is 5 years old (a virtual eternity in postmodern medicine). The DSM nosology is a hybrid between III-R and IV, offering a nice time capsule, but not anticipating the next generation of nomenclature. Despite these weaknesses, Pies' writing is superb. Underneath the casual, conversational tone lies a profound understanding of the disorders discussed that is communicated with aplomb. Seven chapters cover most of the usual topics in good depth; notable exceptions are impulse disorders and eating disorders. Most of the clinical syndromes are treated systematically via a refreshingly clear schema; sections are titled “The Central Concept,” “Historical Development of the Disorder,” “The Biopsychosocial Perspective,” “Pitfalls in the Differential Diagnosis,” “Adjunctive Testing,” “Treatment Directions and Goals,” and “Integrated Case History.” In particular, the sections on the bipolar spectrum and unipolar depression flow easily and resonate well with the experience of mood disorders in primary care. The historical information and smattering of clever quotes help keep the reader's interest in lively fashion. The real strength of the book, however, is in Pies' treatment of the integrated, Engelian model of illness. Unlike most authors, he does more than lip service to the idea that elements of a patient's medical, psychologic, and social milieu may intertwine. He demonstrates these facts by case histories, showing how ignoring any 1 of the 3 spheres may lead to gross errors in diagnosis and treatment, owing to the oft-neglected fact that identical symptoms may spring from vastly different etiologies. His brief descriptions of the various psychological tests available are the most useful for generalist physicians that I have found to date. Finally, his discussion of biomedical disorders having an impact on (or presenting as) psychiatric disturbances is outstanding. In sum, the layout of this book stifles Pies' penetrating insights and his gift for prose. It is too bulky to reliably serve his target audience (upper-level residents in psychiatry) or generalist physicians as a handy guide. It is too sketchy to serve as a comprehensive reference. Still, it earns a place on my shelf, until Pies fleshes out his ideas in a full-scale text.

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.

The recent defeat of a referendum to legalize physician-assisted suicide in Michigan (not to mention the performance of euthanasia on national television by a prominent pathologist) has underscored continued public interest in issues surrounding medical care delivered at the end of life. In a manner similar to its relative silence during the abortion debate in the 1980s, the medical community has been generally reticent to forward cogent arguments supporting viable models of end-of-life care. The group of essays compiled by Steinberg and Youngner are a welcome aberration to this disturbing trend.

Depression commonly co-occurs with medical illnesses and chronic pain, which can contribute to the somatic symptoms of depression, complicate diagnosis and treatment, worsen patients' prognosis, and hinder recovery. Many therapies are available to treat depression, but patients with depression and pain or medical conditions may require a different treatment strategy than those with depression alone. This activity focuses on the best methods for recognizing and diagnosing these conditions, selecting appropriate therapies to create comprehensive treatment plans, and monitoring and educating patients to improve their quality of life.

For patients with depression, antidepressant response rates are generally low and residual symptoms can increase the risk of relapse. Poor response may be linked to increased inflammatory cytokines and obesity. Specifically targeting inflammation with adjunct l-methylfolate treatment may help patients with depression finally achieve remission. In this Webcast, experts examine the multi-directional relationship between obesity, inflammation, and depression, consider preliminary data on genetic alleles, and review evidence using l-methylfolate as a targeted therapy.

Treatment goals for patients with bipolar disorder differ depending on the phase in which the patient presents. During maintenance treatment, the goal of therapy should be for patients to become stable and improve their quality of life. However, the most challenging barrier to effective treatment of bipolar disorder is patient nonadherence with clinician-recommended therapy. A strong treatment alliance between patients and clinicians to provide good social support can help patients adhere to treatment.

I am not really a fan of case-based learning, but I did enjoy this book. The authors present the information with an opening case followed by a question-and-answer style discussion, concluding summary points, and references with each issue-based chapter. I found the question-and-answer style text easy to read and practical as well as comprehensive enough to cover the subject without being too long and drawn out. The book was penned by obviously very knowledgeable pharmacists from the United Kingdom. Therefore, they discuss the use of some medications that are not available in the United States. There is the rare reference to “best use of the UK medical system,” but not enough to be distracting. I found the advice to be concise and practical. The discussions are well founded in the scientific literature, and the authors always point out when they had to use experience or limited science to provide guidance in therapy. This book is strictly about pharmacologic treatment and does not stray into biosociomedical theory of causation or psychotherapy. There is some mention of psychotherapy where appropriate, but no attempt is made to discuss the details, which is consistent with the title and goal of the text. In a nutshell, I think this book would be very useful for those who take care of patients who have complicated mental health disorders. I do not think that most primary care physicians would find the types of patients discussed in the text in their practices. While well written, I believe this book is for the small audience of psychopharmacologists and not the general population of physicians.