Awais Aftab

QTc prolongation with antipsychotics: is routine ECG monitoring recommended?

Whether or not QTc interval should be routinely monitored in patients receiving antipsychotics is a controversial issue, given logistic and fiscal dilemmas. There is a link between antipsychotic medications and prolongation of QTc interval, which is associated with an increased risk of torsade de pointes (TdP). Our goal is to provide clinically practical guidelines for monitoring QTc intervals in patients being treated with antipsychotics. We provide an overview of the pathophysiology of the QT interval, its relationship to TdP, and a discussion of the QT prolonging effects of antipsychotics. A literature search for articles relevant to the QTc prolonging effects of antipsychotics and TdP was conducted utilizing the databases PubMed and Embase with various combinations of search words. The overall risk of TdP and sudden death associated with antipsychotics has been observed to be low. Medications, genetics, gender, cardiovascular status, pathological conditions, and electrolyte disturbances have been found to be related to prolongation of the QTc interval. We conclude that, while electrocardiogram (ECG) monitoring is useful when administering antipsychotic medications in the presence of co-existing risk factors, it is not mandatory to perform ECG monitoring as a prerequisite in the absence of cardiac risk factors. An ECG should be performed if the initial evaluation suggests increased cardiac risk or if the antipsychotic to be prescribed has been established to have an increased risk of TdP and sudden death. (Journal of Psychiatric Practice 2014;20:196–206)

Flibanserin and its discontents

In August 2015, flibanserin (brand name Addyi) was approved by the Food and Drug Administration (FDA) for treatment of acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. This article summarizes and promotes discussion regarding the numerous controversies that have enclosed flibanserin since the very beginning. This includes questions related to flibanserin’s safety and efficacy and the validity of the clinical trials. Also included are philosophical considerations surrounding the diagnosis of hypoactive sexual desire disorder and pharmacological treatment of low libido. Based on the review of literature, authors judge flibanserin to be modestly effective and reasonably safe, and discuss the differences in philosophical perspectives with less definitive answers.

Behavioral Emergencies: Special Considerations in the Pregnant Patient

This article describes psychiatric emergencies in pregnant women. The perinatal period is a time of psychiatric vulnerability. Up to 1 in 6 pregnant women experience major depressive disorder, and 1 in 4 pregnant women with bipolar disorder experience mood exacerbation. We discuss the management of severe mental illness in pregnancy, risk to mother and child of untreated psychiatric illness in pregnancy, risk of relapse of psychiatric disorders in pregnancy with medication discontinuation, psychopharmacologic considerations of teratogenicity and other fetal adverse effects, acute agitation in the pregnant patient, suicidality in pregnancy, and emergency considerations related to substance use disorders.

Pathophysiological Role of HERV-W in Schizophrenia

Schizophrenia is a neuropsychiatric disorder of complex etiology. Human endogenous retroviruses (HERVs) have been presented as possible candidates explaining the connections between the genetic, infectious, neurodevelopmental, and neuroinflammatory aspects of schizophrenia, with the human endogenous retrovirus type W family (HERV-W) showing the greatest evidence of association. Studies have identified retroviral nucleotide sequences, envelope and capsid proteins, and elevated transcription of HERV-W elements in CSF, blood, and brain samples from individuals with schizophrenia. The HERV-W elements can trigger the immune system in a variety of ways. HERV genetic elements may be activated by various prenatal maternal infections, leading to neuroinflammation and genetic abnormalities, altering the development of the brain, and eventually culminating in the development of schizophrenia. This review presents a concise synthesis of available evidence and theoretical speculation regarding the role of HERV-W in schizophrenia. The need for further investigation is highlighted before any conclusions can be stated with confidence.

Behavioral Emergencies: Special Considerations in the Geriatric Psychiatric Patient

This article reviews psychiatric considerations and common psychiatric emergencies in the elderly. The elderly are vulnerable to medication side-effects because of pharmacokinetic changes from aging, and require lower doses and slower titration. They are a high-risk group for suicide, with more serious intent, fewer warning signs, and more lethality. Prompt diagnosis and treatment of delirium in emergency settings is essential, given association with worse outcomes when undiagnosed. Pharmacologic options with demonstrable efficacy for agitation in dementia are limited to antipsychotics, which are, however, associated with an increased risk of mortality; behavioral interventions are universally recommended as first-line measures.

Nonconvulsive Status Epilepticus After Electroconvulsive Therapy: A Review of Literature

BACKGROUND The clinical presentation and risk factors of nonconvulsive status epilepticus (NCSE) in the context of electroconvulsive therapy (ECT) are poorly understood, and guidance regarding diagnosis and management remains scarce. In this article, we identify case reports of ECT-induced NCSE from literature, and discuss the presentation, diagnosis, and management of these cases in the context of what is known about NCSE from the neurology literature. METHODS A literature search on PubMed for case reports of NCSE after ECT. RESULTS We identified 13 cases for this review. Diagnosis in all cases was based on clinical features and electroencephalogram (EEG) findings. Clinical presentation was altered mental status or unresponsiveness, with subtle motor phenomena in some cases. All cases had nonspecific risk factors that have been associated with prolonged seizures and convulsions, such as recent discontinuation/reduction of benzodiazepines or anticonvulsants, and concurrent use of antipsychotics and antidepressants. All patients were treated with either benzodiazepines or antiepileptic agents. Outcomes in these post-ECT NCSE cases were generally favorable. DISCUSSION Although rare, post-ECT NCSE should be kept in mind by physicians when confusion or unresponsiveness develops and continues after ECT; multilead EEG is gold standard for diagnosis. An intravenous (IV) antiepileptic drug (AED) challenge can help clarify the diagnosis. Initial treatment is recommended with IV benzodiazepines, with a repeat dose if necessary. If seizures persist, IV AEDs are warranted. NCSE refractory to this treatment should be treated with a scheduled IV or oral AED. Serial multilead EEGs should be used to monitor resolution of symptoms. CONCLUSION NCSE after ECT is a rare but recognizable clinical event. A high clinical suspicion and low threshold for EEG is necessary for prompt diagnosis.

The Association Between Leukotriene-Modifying Agents and Suicidality: A Review of Literature

BACKGROUND In 2008 Food and Drug Administration issued a warning regarding a possible association between leukotriene-modifying agents and suicidality. OBJECTIVE The warning remains controversial and this review of literature is an attempt to examine the evidence on the matter. METHODS Literature search on PubMed. RESULTS The data supporting a relationship between leukotriene-modifying agents and suicidality comes primarily from reviews of individual safety reports in adverse event databases; it is subject to considerable reporting bias and does not control for confounding factors. Case-control and cohort studies as well as data from clinical trials do not support an association between leukotriene-modifying agents and suicidality. The data from ecological studies offers strong evidence of a lack of positive association between leukotriene-modifying agents and suicide outcomes (attempts and deaths) at the population level. Furthermore, there is no pharmacological mechanism that would explain an association between the two. CONCLUSION Overall, the weight of higher quality evidence casts doubt on the association (especially at population level), but is not enough to conclusively disprove the association at an individual level.

Associations among comorbid anxiety, psychiatric symptomatology, and diabetic control in a population with serious mental illness and diabetes: Findings from an interventional randomized controlled trial:

Objective Serious mental illness and type II diabetes mellitus have a high comorbidity, and both have a higher prevalence of anxiety disorders compared to the general population. Targeted Training in Illness Management is a group-based self-management training approach which targets serious mental illness and type II diabetes mellitus concurrently. This analysis examines data from a randomized controlled trial of Targeted Training in Illness Management intervention to examine the impact of comorbid anxiety on baseline psychiatric symptomatology and diabetic control, and on longitudinal treatment outcomes. Methods We conducted secondary analyses on data from a prospective, 60-week, randomized controlled trial testing Targeted Training in Illness Management versus treatment as usual in 200 individuals with serious mental illness and diabetes. Primary outcomes included measures related to serious mental illness symptoms, functional status, general health status, and diabetes control. Measures were compared between those participants with anxiety disorders versus those without anxiety at baseline as well as over time using linear mixed effects analyses. Results Forty seven percent of the participants had one or more anxiety disorders. At baseline, those with an anxiety diagnosis had higher illness severity, depressive, and other psychiatric symptomatology and disability. Diabetic control (HbA1c) was not significantly different at baseline. In the longitudinal analyses, no significant mean slope differences over time (group-by-time interaction effect) between those with anxiety diagnoses and those without in treatment as usual group were found for primary outcomes. Within the Targeted Training in Illness Management arm, those with anxiety disorders had significantly greater improvement in mental health functioning. Those with anxiety comorbidity in the Targeted Training in Illness Management group demonstrated significantly lower HbA1c levels compared to no anxiety comorbidity and also demonstrated a greater improvement in HbA1c over the first 30 weeks compared to those without anxiety comorbidity. Conclusion Comorbid anxiety in serious mental illness and type II diabetes mellitus population is associated with increased psychiatric symptomatology and greater disability. Individuals from this population appear to experience greater improvement in functioning from baseline with the Targeted Training in Illness Management intervention. Anxiety comorbidity in the serious mental illness and type II diabetes mellitus population does not appear to have a negative impact on diabetic control. These complex relationships need further study. Clinical Trials Registration ClinicalTrials.gov: Improving outcomes for individuals with serious mental illness and diabetes (NCT01410357).

A Didactic Course on “Philosophy of Psychiatry” for Psychiatry Residents

The intersection of philosophy and psychiatry (also called “philosophy of psychiatry” [1]) has emerged as an important field of study in recent decades. There are many ways in which psychiatric concepts can be subjected to philosophical inquiry. At the core of the field lies the conceptual debate over the meaning and nature of mental disorder, along with its ethical and experiential dimensions. Additionally, philosophers of psychiatry have noted that psychopathological phenomena can help illuminate various philosophical issues in the philosophy of mind. The development of this field can be appraised by the success of the journal Philosophy, Psychiatry, & Psychology [2], the activities of the Association for the Advancement of Philosophy and Psychiatry [3], and the book series by Oxford University Press titled “International Perspectives in Philosophy and Psychiatry.”Despite the relevance of philosophy of psychiatry to practicing psychiatrists, little attempt has been made to incorporate philosophy of psychiatry in the didactic curriculum of US psychiatry residents. Philosophy of psychiatry is not included in the Accreditation Council for Graduate Medical Education (ACGME) psychiatry milestones or in the curriculums of the Psychiatry Resident-In-Training Examination (PRITE) or the American Board of Psychiatry and Neurology (ABPN) exam. In contrast, UK’s Member of the Royal College of Psychiatrists (MRCPsych) exam curriculum [4] includes the category of “philosophy in psychiatry,” and Royal College of Psychiatrists’ competency based curriculum [5] has included “the history and philosophy of science as it relates to concepts of mental disorder” as a component in the past. While many residency programs in the USA have components related to philosophy of psychiatry in their didactics, published reports on these courses are lacking. Among published reports of courses or curricula for psychiatry residents, our literature search led to only one report of a curriculum for child and adolescent psychiatry trainees which incorporated readings from traditional philosophy in domains such as logic, epistemology, ethics, etc. with the aim of improving critical thinking about psychiatric issues [6]. In this educational case report, we describe the development, curriculum, and implementation of a course on philosophy of psychiatry for psychiatry residents at Case Western Reserve University/University Hospitals Cleveland Medical Center (CWRU/UH). Awais Aftab (A.A.) developed and taught the course, Nassir Ghaemi (N.G.) offered guidance through an American Association of Directors of Psychiatric Residency Training (AADPRT) fellowship program, and Susan Stagno (S.S.) served as the institutional faculty mentor. Didactics for psychiatry residents at CWRU/UH are divided into regular mandatory sessions, expected to be attended by all available psychiatry residents, and elective sessions, which are optional to attend for interested PGY2–4 residents. Often there are two or more competing elective options for the same time slot. The didactic course on philosophy of psychiatry, following this model, was also divided into mandatory and elective components. The course was taught from November 2016 to March 2017. * Awais Aftab awaisaftab@gmail.com

The preclinical discovery and development of brexpiprazole for the treatment of major depressive disorder

ABSTRACT Introduction: Brexpiprazole is the most recently approved second-generation antipsychotic, which is used as adjunctive therapy to antidepressants for treating major depressive disorder (MDD) with inadequate response. Brexpiprazole shares pharmacological similarities with other second-generation antipsychotics, especially aripiprazole. Area covered: This review provides a detailed overview of the pre-clinical studies of brexpiprazole, followed by a summary of its clinical studies, and a comparison with other antipsychotics in MDD. Brexpiprazole is superior to placebo in reducing depressive symptoms of patients who have had an inadequate response to a standard antidepressant treatment. The efficacy of brexpiprazole is comparable to aripiprazole and quetiapine-XR, but brexpiprazole has demonstrated a lower risk for akathisia than aripiprazole and a lower risk for somnolence than quetiapine-XR. Expert opinion: Given that different studies have used different criteria to define ‘treatment-resistance’ or ‘inadequate-response’, an accurate comparison of the efficacy and safety of brexpiprazole with other antipsychotics is difficult. Preclinical data supports the premise that the antidepressant-like effects of antipsychotics are mainly due to their ability to modulate/regulate the monoamine system. Therefore, antipsychotics with similar pharmacodynamic properties like brexpiprazole could also take the ‘me too’ approach to treating MDD.