Asim A Shah

Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial

OBJECTIVE Ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist, has shown rapid antidepressant effects, but small study groups and inadequate control conditions in prior studies have precluded a definitive conclusion. The authors evaluated the rapid antidepressant efficacy of ketamine in a large group of patients with treatment-resistant major depression. METHOD This was a two-site, parallel-arm, randomized controlled trial of a single infusion of ketamine compared to an active placebo control condition, the anesthetic midazolam. Patients with treatment-resistant major depression experiencing a major depressive episode were randomly assigned under double-blind conditions to receive a single intravenous infusion of ketamine or midazolam in a 2:1 ratio (N=73). The primary outcome was change in depression severity 24 hours after drug administration, as assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS The ketamine group had greater improvement in the MADRS score than the midazolam group 24 hours after treatment. After adjustment for baseline scores and site, the MADRS score was lower in the ketamine group than in the midazolam group by 7.95 points (95% confidence interval [CI], 3.20 to 12.71). The likelihood of response at 24 hours was greater with ketamine than with midazolam (odds ratio, 2.18; 95% CI, 1.21 to 4.14), with response rates of 64% and 28%, respectively. CONCLUSIONS Ketamine demonstrated rapid antidepressant effects in an optimized study design, further supporting NMDA receptor modulation as a novel mechanism for accelerated improvement in severe and chronic forms of depression. More information on response durability and safety is required before implementation in clinical practice.

Ketamine for treatment-resistant unipolar depression: current evidence.

Currently available drugs for unipolar major depressive disorder (MDD), which target monoaminergic systems, have a delayed onset of action andsignificant limitations in efficacy. Antidepressants with primary pharmacological targets outside the monoamine system may offer the potential for more rapid activity with improved therapeutic benefit. The glutamate system has been scrutinized as a target for antidepressant drug discovery. The purpose of this article is to review emerging literature on the potential rapid-onset antidepressant properties of the glutamate NMDA receptor antagonist ketamine, an established anaesthetic agent. The pharmacology of ketamine and its enantiomer S-ketamine is reviewed, followed by examples of its clinical application in chronic, refractory pain conditions, which are commonly co-morbid with depression. The first generation of studies in patients with treatment-resistant depression (TRD) reported the safety and acute efficacy of a single subanaesthetic dose (0.5 mg/kg) of intravenous ketamine. A second generation of ketamine studies is focused on testing alternate routes of drug delivery, identifying methods to prevent relapse following resolution of depressive symptoms and understanding the neural basis for the putative antidepressant actions of ketamine. In addition to traditional depression rating endpoints, ongoing research is examining the impact of ketamine on neurocognition. Although the first clinical report in MDD was published in 2000, there is a paucity of adequately controlled double-blind trials, and limited clinical experience outside of research settings. Given the potential risks of ketamine, safety considerations will ultimately determine whether this old drug is successfully repositioned as a new therapy for TRD.

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)

Depression and the Suicidal Patient

Depression is the most common psychiatric illness in the general community, with 3% to 4% of depressives dying by suicide today. Studies have shown that depression has considerable morbidity and mortality. This article focuses on depressed patients and their management within the emergency department. Understanding the intricacies of the interview process and identifying which patients need immediate attention are important skills for the emergency physician.

Psychiatric Emergencies in Pregnant Women

Psychiatric emergencies in pregnancy can be difficult to manage. The authors (both practicing psychiatrists and emergency clinicians) review the evaluation and treatment of common mental health diagnoses in pregnancy.

Stabilization and Management of the Acutely Agitated or Psychotic Patient

Acutely agitated or psychotic patients are particularly challenging to manage in the emergency department. Often these patients present with little or no history, and an adequate assessment may initially be difficult because of the condition of the patient. This article discusses basic concepts regarding agitation, and the related management goals and strategies.

Sexual Side Effects of Antipsychotic Drugs

The use of antipsychotic drugs carries a difficult balance between the benefit of relieving psychotic symptoms and the risk of suffering from some of troubling adverse effect. Sexual dysfunction is very common among the patients taking antipsychotic drugs, but this area has been relatively neglected to date. This review article will summarize our current understanding of sexual dysfunction caused by the use of antipsychotic drugs. Sexual dysfunction is considered by many schizophrenia patients to be more troublesome than most other symptoms and adverse drug effects [1,2] and is a major cause of poor quality of life [3], negative attitude to therapy and treatment noncompliance [2].

Health Policy Considerations in Treating Mental and Behavioral Health Emergencies in the United States

In recent years, health care providers have sounded the call that the US mental health system is in crisis. With decreases in funding and eroding access to care, the availability of psychiatric services has become increasingly limited, failing to meet growing needs. This article provides a brief history of mental health services in the United States and describes the current landscape of US psychiatric care; it touches upon some of the most important policy considerations, describing some of the glaring issues in US mental health care today. Last, it offers some potential remedies to improve care in acute behavioral emergencies.

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.

Epic Fail! Poor Neuropsychiatric Documentation Practices in Emergency Psychiatric Patients

Background: There is a strong association between mental illness and poor physical health. However, research indicates that the standard of physical examinations performed on patients with psychiatric illnesses is sub-optimal, falling short of recommended/expected assessments. Objective: This study aimed to assess the completeness of the neurological and psychiatric examinations performed by emergency physicians in a level 1 trauma centre with a dedicated psychiatric emergency centre. Methods: A retrospective chart review of 50 consecutive emergency psychiatric patients was performed. Each of the 50 patients had been “medically cleared” and deemed stable for transfer to inpatient psychiatry. Results: The documented neurologic and psychiatric examinations were generally poor. Mood and affect were documented in less than 50% of cases. Suicidality was documented in less than 1/3 of the patients who presented with a chief complaint of suicidal ideation. Only one patient had a documented a mini-mental status examination. 16% of patients did not have their orientation status documented. More than half did not have a cranial nerve examination. Less than 25% had their gait or reflexes tested. 28% of patients had their strength tested and 12% had a sensory examination performed. Conclusions: Most psychiatric patients are not receiving a thorough neuropsychiatric physical examination by emergency providers, an alarming finding deserving more scrutiny. Additional research is needed to ascertain which components of the neurological and psychiatric examination are the highest yield and would have the greatest impact patient care outcomes and disposition. Interdisciplinary consensus must also be reached on what constitutes an adequate examination for patients with varying severity of neuropsychiatric presentations (e.g., suicidal ideation, altered mental status, frank psychosis).