Thomas M. Penders

Hallucinatory delirium following use of MDPV: “Bath Salts”

Generally used to describe analogues of the amphetamine molecule, the term “designer drug” was first applied to synthetically modified natural opiates [1]. By chemical alteration of the structure of another natural stimulant, cathinone, agents have been introduced to the drug-using public for sale in convenience stores and over the internet [2]. Methylmethcathinone (mephedrone) and its analogs have made their appearance worldwide marketed as “legal highs” or “synthetic cocaine” [3]. Sold as “Bath Salts”, medical facilities and poison control centers across the United States have encountered an epidemic of reactions over the past year [4,5]. Labeled and promoted as “not for human consumption” and widely available in convenience stores, these stimulant agents can be sold openly to anyone who can afford the nominal cost. The substances are identified as “Bath Salts” for the apparent purpose of avoiding regulation under laws governing use of psychostimulants. They are then marketed as such on internet sites. Use of methylenedioxypyrovalerone (MDPV), a synthetic beta-ketone with similar structure and having a rapid onset of action in the central nervous system, has led to multiple hospitalizations and emergency department visits [6]. We describe three cases of a paranoid psychotic delirium following use of “Bath Salts”.

Intoxication Delirium following Use of Synthetic Cathinone Derivatives

Background: In published reports of hallucinatory delirium following use of “bath salts” analytic laboratory testing has demonstrated the synthetic cathinone derivative methylenedioxypyrovalerone (MDPV). MDPV can cause a false-positive screening immunoassay result for phencyclidine (PCP). Patients using MDPV are prone to development of the syndrome of excited delirium (ExD), a condition also described with PCP. Objective: This review summarize reports from several series of cases of delirium associated with MDPV emphasizing the features of both intoxication and excited delirium. Methods: Literature review and clinical description of a series of patients from Eastern North Carolina. Conclusion: MDPV is likely the responsible agent in production of both toxic and excited delirium syndromes identified with the recreational use of “bath salts” in the United States over the past two years. Scientific significance: Patients using MDPV are prone to the development of toxic delirum with some developing ExD. a condition associated with considerable risk for serious medical morbidity. Commonly used interventions directed at extreme agitation and paranoia may exacerbate the pathophysiology of ExD.

Bright Light Therapy as Augmentation of Pharmacotherapy for Treatment of Depression: A Systematic Review and Meta-Analysis

Background Bright light therapy has demonstrated efficacy and is an accepted treatment for seasonal depression. It has been suggested that bright light therapy may have efficacy in nonseasonal depressions. Also, there is evidence that bright light therapy may improve responsiveness to antidepressant pharmacotherapy. Data Sources We searched PubMed/MEDLINE, PsycINFO, PsycARTICLES, CINAHL, EMBASE, Scopus, and Academic OneFile for English-language literature published between January 1998 and April 2016, using the keywords bright light therapy AND major depression, bright light therapy AND depress*, bright light therapy AND bipolar depression, bright light therapy AND affective disorders, circadian rhythm AND major depression, circadian rhythm AND depress*, and circadian rhythm AND affective disorder. Study Selection and Data Extraction Studies that reported randomized trials comparing antidepressant pharmacotherapy with bright light therapy ≥ 5,000 lux for ≥ 30 minutes to antidepressant pharmacotherapy without bright light therapy for the treatment of nonseasonal depression were included. Studies of seasonal depression were excluded. Following review of the initial 112 returns, 2 of the authors independently judged each trial, applying the inclusionary and exclusionary criteria. Ten studies were selected as meeting these criteria. Subjects in these studies were pooled using standard techniques of meta-analysis. Results Ten studies involving 458 patients showed improvement using bright light therapy augmentation versus antidepressant pharmacotherapy alone. The effect size was similar to that of other accepted augmentation strategies, roughly 0.5. Conclusions Analysis of pooled data from randomized trials provides evidence for the efficacy of use of bright light therapy ≥ 5,000 lux for periods ≥ 30 minutes when used as augmentation to standard antidepressant pharmacotherapy in the treatment of major depressive disorder and bipolar depression without a seasonal pattern.

Delusional infestation following misuse of prescription stimulants.

Received February 19, 2014; revised March 17, 2014; accepted March 17, 2014. From Department of Psychiatric Medicine, Brody School of Medicine, East Carolina University, Greenville, NC. Send correspondence and reprint requests to Thomas M. Penders, M.D., Department of Psychiatric Medicine, Brody School of Medicine, East Carolina University, 600 Moye Boulevard, Suite 400E, Greenville, NC 27834; e-mail: penderst@ecu.edu & 2014TheAcademy of PsychosomaticMedicine. Published by Elsevier Inc. All rights reserved. Introduction

Use of Buprenorphine in treatment of refractory depression—A review of current literature

OBJECTIVE Current treatment strategies for depressive disorders have limited efficacy, leaving many patients unimproved or with significant residual symptoms. The development of additional treatments represent a significant unmet need for providers. Several lines of evidence suggest that the opioid system may be involved in regulation of mood and incentives salience. Intervention based on modifying central opioid receptors may represent a novel approach to treatment of depressive disorders among those unresponsive to accepted treatments. DATA SOURCES We searched the English language literature using keywords: Buprenorphine AND Major Depression; Buprenorphine AND Bipolar Depression; Buprenorphine AND Affective Disorders. RESULTS Use of low dose buprenorphine as augmentation of pharmacotherapy for depression has shown promise in several reported studies. Effect size of available randomized controlled studies is comparable if not greater than most accepted augmentation strategies. CONCLUSION Review of available literature on the use of buprenorphine in individuals with treatment resistant depression demonstrated efficacy in the treatment of depressive disorders. Further prospective randomized controlled trials should be undertaken to evaluate the efficacy of buprenorphine as an adjunct for depression refractory to current pharmacotherapies.

Adverse life events, psychiatric history, and biological predictors of postpartum depression in an ethnically diverse sample of postpartum women

BACKGROUND Race, psychiatric history, and adverse life events have all been independently associated with postpartum depression (PPD). However, the role these play together in Black and Latina women remains inadequately studied. Therefore, we performed a case-control study of PPD, including comprehensive assessments of symptoms and biomarkers, while examining the effects of genetic ancestry. METHODS We recruited our sample (549 cases, 968 controls) at 6 weeks postpartum from obstetrical clinics in North Carolina. PPD status was determined using the MINI-plus. Psychiatric history was extracted from medical records. Participants were administered self-report instruments to assess depression (Edinburgh Postnatal Depression Scale) and adverse life events. Levels of estradiol, progesterone, brain-derived neurotrophic factor, oxytocin, and allopregnanalone were assayed. Principal components from genotype data were used to estimate genetic ancestry and logistic regression was used to identify predictors of PPD. RESULTS This population was racially diverse (68% Black, 13% Latina, 18% European). Genetic ancestry was not a predictor of PPD. Case status was predicted by a history of major depression (p = 4.01E-14), lifetime anxiety disorder diagnosis (p = 1.25E-34), and adverse life events (p = 6.06E-06). There were no significant differences between groups in any hormones or neurosteroids. CONCLUSIONS Psychiatric history and multiple exposures to adverse life events were significant predictors of PPD in a population of minority and low-income women. Genetic ancestry and hormone levels were not predictive of case status. Increased genetic vulnerability in conjunction with risk factors may predict the onset of PPD, whereas genetic ancestry does not appear predictive.

The Behavioral Profile of Methylenedioxypyrovalerone (MDPV) and α– pyrrolidinopentiophenone (PVP) - A Systematic Review

The article entitled, “The Behavioral Profile of Methylenedioxypyrovalerone (MDPV) and α– pyrrolidinopentiophenone (PVP) - A Systematic Review”, submitted in Current Drug Abuse Reviews (CDAR) by Dr. Cornel N Stanciu has been withdrawn from the journal in accordance with BSP Editorial Policies.

Underutilization of Pharmacotherapy for Treatment of Alcohol Use Disorders Part II-Results from a Survey of Practices among North Carolina Mental Health Providers and Brief Review of Efficacy of Available Pharmacotherapies

Introduction: Alcohol is the third leading cause of preventable death worldwide. There is substantial risk for development of alcohol use disorder among those with psychiatric disorders, complicating their care. Despite extensive evidence in support from controlled trials and from expert opinion, medication-assisted treatment has had low levels of penetration in practice. Only 3% of sufferers receive FDA-approved treatment. The goal of this survey is to explore potential causes of underutilization of evidence-based pharmacotherapeutical agents in the treatment of alcohol use. Secondary, we analyze differences in practice patterns between different academic institutions, facilities specializing in chemical dependence treatment, and general community practitioners. We are aware of no prior study that has attempted to evaluate these factors. Methods: An online questionnaire was designed in Qualtrics and distributed through the use of an anonymous link. Target participants were members of the Psychiatry departments of four academic institutions in NC, community mental health providers, prescribers from chemical dependence treatment facilities, and Veteran Affairs psychiatrists. A total of 170 participated, an 85% response rate. Data was analyzed using Qualtrics software as well as by a statistician. Results: A significant portion of psychiatric patients have comorbid alcohol use, and despite patient interest, medications are rarely utilized in both academic as well as chemical dependence facilities-20% of respondents never prescribed any. Reasons mainly include lack of provider knowledge of available medications (r=-0.277, n=136, p=0.001), prescribing guidelines (r=-0.265, n=136, p=0.002) and dosing (r=-0.245, n=136, p=0.004). Provider’s attitude towards substance use treatment also affects prescribing (r=-0.21, n=136, p=0.014). Those who do prescribe seem to favor off-label medications and avoid Naltrexone IM formulation. Providers acknowledge that the majority of those with alcohol use disorders have medical conditions caused or affected by the ongoing use. Instituting medications leads to positive experiences: patients maintain sobriety longer, have less legal problems and are better able to engage in their care. Conclusion: In the treatment of alcohol use, guidelines recommend FDA approved medications in conjunction with bio psychosocial interventions. Global assessment indicates prescribers mainly avoid pharmacotherapy due to lack of comfort and knowledge. There may also be financial barriers in a current alcohol treatment system that is traditionally non-medically oriented. Although it is recommended to start with FDA approved medications, off-label use is high. Despite positive implications noted when medications are instituted, providers’ ambivalence continues. As part of our daily practices, general psychiatrists should gain confidence in using evidence-based, FDA approved, medications in treatment of alcohol use disorders.

Letter to the Editor—Methylenedioxypyrovalerone as a Cause of Excited Delirium

Sir, Kesha et al. (1) recently report in this Journal on a fatal case involving a patient hospitalized following use of methylenedioxypyrovalerone (MDPV), one of the many new psychoactive substances that have appeared worldwide over the past 5 years as a part of a flourishing market facilitated by the expansion of Internet communications. As described in this report, and others, MDPV has the capacity to produce a hallucinatory delirium as well as the constellation of findings described with other stimulant drugs as the syndrome of excited delirium (2,3). Treatment of patients presenting with such symptoms represents a challenge as very high levels of agitation and violent behavior occur together with disturbances of thermoregulation, rhabdomyolysis, dehydration, and cardiac dysrhythmias requiring intensive medical management. Many interventions used to manage agitated and violent behaviors, such as use of antipsychotic agents and restraints, may serve to worsen the underlying pathophysiology of this condition. An awareness by clinicians of the associated consequences of intoxication from these substances is essential to minimizing treatment-related morbidity. After observing an increased number of urine immunoassay screens positive for PCP during a time that we were witnessing increased use of MDPV in the community, we were able to demonstrate that the addition of MDPV to control urine samples resulted in a positive test for PCP as exemplified by the patient described in this report (4). Baumann (5) has demonstrated convincingly that MDPV has actions on the CNS that mimic those of cocaine with more potent facility to block central dopamine uptake, a property that explains its proclivity for producing excited delirium as well as its highly addictive potential. Patients who have used the drug describe cravings during periods of abstinence that are experienced as much stronger than those of cocaine. The alarming increase in appearance of new psychoactive substances is currently overwhelming attempts at regulation. The number of newly marketed psychoactive substances globally has increased from 166 in 2009 to 251 by the middle of 2012. The number of substances targeting the recreational drug market during this period exceeds the 234 that are currently controlled through international treaties. The alarming toxicities of some of these agents, such as MDPV, and the relative lack of understanding of their effects in humans represent a global public health problem (6). Recent rapid assays for MDPV are now available through several commercial laboratories. We join with Dr. Kesha et al. in emphasizing the need for specific identification of these molecules as characteristic toxidromes have important implications for treatment (7).

Persistent akathisia masquerading as agitated depression after use of ziprasidone in the treatment of bipolar depression.

There has been increasing recognition that the second-generation antipsychotic drugs can produce extrapyramidal side effects. This case reports the development of severe akathisia in a patient being treated with ziprasidone for bipolar depression. The case illustrates that this symptom can be easily mistaken for worsening agitated depression. Akathisia may produce considerable distress and elevate suicide risk. Such symptoms may persist for weeks and be refractory to discontinuation of the offending agent or to pharmacological interventions commonly used to mitigate this reaction.