A major challenge in the treatment of major depressive episodes associated with bipolar disorder is differentiating this illness from major depressive episodes associated with major depressive disorder. Mistaking the former for the latter will lead to incorrect treatment and poor outcomes. None of the classic antidepressants, serotonin specific reuptake inhibitors, or serotonin-norepinephrine reuptake inhibitors have ever received regulatory approval as monotherapies for the treatment of bipolar depression. At present, there are only 3 approved medication treatments for bipolar depression: olanzapine/fluoxetine combination, quetiapine (immediate or extended release), and lurasidone (monotherapy or adjunctive to lithium or valproate). All 3 have similar efficacy profiles, but they differ in terms of tolerability. Number needed to treat (NNT) and number needed to harm (NNH) can be used to quantify these similarities and differences. The NNTs for response and remission for each of these interventions vs placebo range from 4 to 7, and 5 to 7, respectively, with overlap in terms of their 95% confidence intervals. NNH values less than 10 (vs placebo) were observed for the spontaneously reported adverse events of weight gain and diarrhea for olanzapine/fluoxetine combination (7 and 9, respectively) and somnolence and dry mouth for quetiapine (3 and 4, respectively). There were no NNH values less than 10 (vs placebo) observed with lurasidone treatment. NNH values vs placebo for weight gain of at least 7% from baseline were 6, 16, 58, and 36, for olanzapine/fluoxetine combination, quetiapine, lurasidone monotherapy, and lurasidone combined with lithium or valproate, respectively. Individualizing treatment decisions will require consideration of the different potential adverse events that are more likely to occur with each medication. The metric of the likelihood to be helped or harmed (LHH) is the ratio of NNH to NNT and can illustrate the tradeoffs inherent in selecting medications. A more favorable LHH was noted for treatment with lurasidone. However, OFC and quetiapine monotherapy may still have utility in high urgency situations, particularly in persons who have demonstrated good outcomes with these interventions in the past, and where a pressing clinical need for efficacy mitigates their potential tolerability shortcomings. In terms of maintenance therapy, adjunctive quetiapine is the only agent where the NNT vs lithium or valproate alone is less than 10 for both the prevention of mania and the prevention of depression.

Irreversible monoamine oxidase inhibitor (MAOI) antidepressants have significant efficacy in treatment-resistant unipolar depression, but in some instances patients may not achieve remission. Among the adjunctive and augmentation strategies, certain second-generation antipsychotics (SGAs) have approval for inadequate responders to antidepressant therapy, including aripiprazole, brexpiprazole, and quetiapine, with lurasidone and the olanzapine/fluoxetine combination indicated for bipolar depression. Clinicians may eschew SGA options in part due to the limited literature on SGA–MAOI combinations, with only one published case involving aripiprazole, and none for olanzapine, lurasidone, or brexpiprazole. In addition to the limited publication history on SGA–MAOI treatment, clinicians may also be deterred by uncertainty regarding SGA mechanisms and the risk of serotonin syndrome or other adverse outcomes. This paper describes the case of a 54-year-old male with a history of psychotic unipolar depression treated with a combination of phenelzine, aripiprazole, and quetiapine, and reviews the 12 published cases of SGA–MAOI combination therapy with a focus on the pharmacological basis for serotonin syndrome, and the SGA mechanisms that should not be associated with a risk for this syndrome.

Responding to the California Supreme Court’s decision and its related legal obligations in Tarasoff v. Regents of Univ. of California over 30 years ago has become a standard part of mental health practice. This case influenced legal requirements governing therapists’ duty to protect third parties in nearly every state in the country. The final ruling in Tarasoff emphasized that therapists have a duty to protect individuals who are being threatened with bodily harm by their patients.

This article will provide a brief overview and update on duty to protect legal requirements. Clinical guidelines for addressing threats and the duty to protect will be discussed, along with risk management approaches. The article will conclude with a sample vignette illustrating these principles.

Emotional difficulties, such as anxiety and depression, are common after acquired brain injury in adults and can influence long-term outcome. Diagnosis in a brain injury context can be difficult. Ideally, rehabilitation approaches should consider the specific treatment of anxiety and depression as well and may include pharmacotherapy, individual psychotherapy, and family interventions. Psychotherapy, especially in regards to longer-term adjustment to brain injury, may have an important adjunctive role in treatment approaches, but adaptations of techniques may be needed. A clinical pathway is described which can help to raise clinicians' awareness, as well as increase detection rates and consideration of the specific role of individual psychotherapy in this clinical population. However, an important caveat is that clinical pathways should not serve as a substitute, but rather a facilitator, for the process of reasoning about individual patients in everyday clinical practice.

Despite relevant evidence of physical illness promoting fibromyalgia syndrome (FMS), some authors claim that it is a psychological illness, or due to “psychological amplification.” Good evi-dence for such views is lacking. Selection processes lead to increased rates of psychological illness in general practice and in specialist practice. The phys-ical distress of FMS can increase both anxiety and depression. Questionable research supported by the insurance industry has tended to provide nega-tive and disparaging views of pain. Current imag-ing studies support the view that central effects connected with FMS relate to the processing of noxious stimulation more than affective disorder.

The management of mood disorders during pregnancy is complex due to risks associated with medication use and risks associated with untreated depression. Antidepressant use during pregnancy is an exposure for the unborn child, and it currently remains unclear what long-term repercussions there might be from this exposure, though available data are reassuring. On the other hand, there are risks for both the mother and child of untreated depression during pregnancy. There is a real need for research into nonpharmacological strategies for the prevention of relapse of mood disorders in pregnant women who are off medications. We have reviewed a number of potential candidate interventions including psychotherapies, exercise, light box therapy (LBT), repetitive transcranial magnetic stimulation (rTMS), electroconvulsive therapy (ECT), holistic strategies, and nutritional and herbal supplements. Currently there is a lack of evidence supporting the use of such strategies in the prevention of depressive relapse during pregnancy, though most of these strategies have at least some support for their use in the treatment of a major depressive episode. Carefully conducted research using one or more of these strategies in women who want to discontinue antidepressants for pregnancy is sorely needed.

Debate continues regarding the relationship between shyness and social phobia. Some have proposed that this relationship is best understood by adopting a spectrum approach where increasing levels of shyness eventually merge into the clinical disorder of social phobia. This paper begins to explore the validity of this spectrum by reviewing similarities and differences between shyness and social phobia and investigating how shyness relates to social phobia subtypes. This paper will also explore precursors to social phobia, namely childhood behavioral inhibition.

A consensus conference on the reasons for the undertreatment of depression was organized by the National Depressive and Manic Depressive Association (NDMDA) on January 17–18,1996. The target audience included health policymakers, clinicians, patients and their families, and the public at large. Six key questions were addressed: (1) Is depression undertreated in the community and in the clinic? (2) What is the economic cost to society of depression? (3) What have been the efforts in the past to redress undertreatment and how successful have they been? (4) What are the reasons for the gap between our knowledge of the diagnosis and treatment of depression and actual treatment received in this country? (5) What can we do to narrow this gap? (6) What can we do immediately to narrow this gap?

Over the last 25 years, the perception of obsessive-compulsive disorder (OCD) has changed; where once it was seen as a rare refractory disorder, it is now viewed as a fairly prevalent, but treatable, medical condition responding to two main therapeutic strategies—serotonin reuptake inhibitors (SRIs) and cognitive-behavioral therapy (CBT). Given the emergence of new results with SRIs, more data on the role of augmentation strategies with second-generation antipsychotics, and recent genetic and neuroimaging findings with potential for advancing the understanding of the pathogenesis of OCD, it was thought appropriate to revisit OCD in order to identify key developments in this field and examine how they might be translated into the clinical arena.This consensus statement is the product of the International Anxiety Disorders Conference that took place in Cape Town in February 2006, and is referred to as the Cape Town Consensus (CTC).

A growing body of evidence documents the value of structured psychotherapeutic interventions for the co-management of bipolar disorder in the context of ongoing medication treatment. This article reviews the rationale, elements, and outcomes for those psychosocial treatments for bipolar disorder that have been emmined in randomized trials. The available evidence suggests that interventions delivered in individual, group, or family settings, can provide significant benefit to patients undergoing pharmaco-theraby for bibolar disorder.

Mixed features specifier (MFS) is a new nosological entity defined and operationalized in the Diagnostic and Statistical Manual of Mental Disorders (DSM), 5th Edition. The impetus to introduce the MFS and supplant mixed states was protean, including the lack of ecological validity, high rates of misdiagnosis, and guideline discordant treatment for mixed states. Mixed features specifier identifies a phenotype in psychiatry with greater illness burden, as evidenced by earlier age at onset, higher episode frequency and chronicity, psychiatric and medical comorbidity, suicidality, and suboptimal response to conventional antidepressants. Mixed features in psychiatry have historical, conceptual, and nosological relevance; MFS according to DSM-5, is inherently neo-Kraepelinian insofar as individuals with either Major Depressive Disorder (MDD) or Bipolar Disorder (BD) may be affected by MFS. Clinicians are encouraged to screen all patients presenting with a major depressive episode (or hypomanic episode) for MFS. Although “overlapping symptoms” were excluded from the diagnostic criteria (eg, agitation, anxiety, irritability, insomnia), clinicians are encouraged to probe for these nonspecific symptoms as a possible proxy of co-existing MFS. In addition to conventional antidepressants, second generation antipsychotics and/or conventional mood stabilizers (eg, lithium) may be considered as first-line therapies for individuals with a depressive episode as part of MDD or BD with mixed features.

Ethnic differences may significantly influence the outcome of psychopharmacological treatment, in terms of prescription, adherence, clinical response, emergence of side effects, as well as pharmacokinetics and pharmacodynamics. The purpose of this review was to explore the available literature in order to provide general suggestions to help clinicians in choosing the best therapeutic option for patients, taking into account ethnicity. Although findings are sometimes controversial, the overall published studies suggest that ethnicities other than Caucasians tend to show a lower response to antidepressants and a reduced compliance. Africans tend to be more prescribed with antipsychotics, probably due to cultural stereotypes, except with clozapine, probably for their chronic benign neutropenia. Asians usually require less antipsychotic dosages than Caucasians. The differential response and side effect profile of antidepressants and antipsychotics have been related to individual intrinsic factors, to genetic make-up, but also to cultural and contextual variables. Interestingly, albeit limited data suggest ethnic-related genetic heterogeneity at the level of the serotonin transporters, the cytochromes and some neuroreceptors. Taken together, no conclusive findings are available about the role and impact of ethnicity in psychopharmacology. One of the main problems is that the majority of the studies in psychopharmacology have been conducted on Caucasians, so that there is an urgent need to have data in other populations. Furthermore, in the era of precision medicine, the role of ethnicity may be also supported by genetic analysis.

Although most patients with depression ultimately respond to antidepressant therapy, >50% have inadequate response to an individual antidepressant trial. The desire to avoid adverse drug reactions is common among patients, and is an important determinant of drug selection among psychiatrists. However, since the major classes of antidepressants and antipsychotics appear to be comparable in efficacy, clinicians have little basis for selecting the most effective agent for an individual patient. Pharmacogenetics, often described as the study of genetic variation that explains differential response to medication, represents an important new avenue toward improving treatment outcomes. Genetic variation in drug-metabolizing enzymes has been recognized for decades. The main focus of current psychiatric pharmacogenetic testing is on the cytochrome P450 (CYP) 2D6 and, to a somewhat lesser extent, on the 2C19 genes. Data suggest that poor metabolizer status can be associated with an increased risk of adverse drug reactions with certain medications, and that ultra-rapid metabolizers may require higher-than-usual doses to achieve a therapeutic response. The importance of CYP enzymes in the metabolism of several antidepressant and antipsychotic drugs suggest that genetic variation may aid in medication selection or dosing. Advances in pharmacogenetic research may facilitate the development of personalized medicine in which genetic information can inform drug selection, leading to optimal drug effectiveness and minimal drug toxicity.

Two decades of research into problematic Internet use have not yielded an established definition, much less an accepted treatment algorithm that is based on the psychopharmacological and psychotherapeutic interventions that have been tested. Meanwhile, technology-mediated tools that purport to curb unnecessary use of Internet-related technologies and the associated negative consequences are gaining in popularity, despite the lack of rigorous clinical trials into their efficacy and safety. Some popular new offerings that vary in browser, operating system and platform compatibility are reviewed. While they share similar goals as “traditional” treatments, they may be more efficient, scalable, and affordable. Using technology against itself may be counter-intuitive, but the popularity of these tools and their potential advantages make them worthy of researchers’ attention. Telepsychiatry platforms, which are gaining a foothold in the treatment of established disorders, may, paradoxically, also prove beneficial for the management of problematic use of Internet-related technologies.