THE AMERICAN JOURNAL OF PSYCHIATRY RESIDENTS’ JOURNAL January 2015 Volume 10 Issue 1 Inside In This Issue 2 The Pharmacologic and Nonpharmacologic Treatment of Opioid Use Disorder Rohit Aiyer, M.D. 5 A Case of New-Onset Schizophrenia With Gilbert’s Syndrome Cody Armstrong, M.D. 7 Pain, Depression, and Delirium: Evaluation of the Complex Consultation-Liaison Patient Joanna Koutros, M.D. 9 Revisiting the Guidelines for Violence Risk Assessment of Patients in the Psychiatric Emergency or Inpatient Setting Swapnil Rath, M.D. This month’s issue of the Residents’ Journal focuses on a variety of topics. Rohit Aiyer, M.D., examines the pharmacologic and nonpharmacologic treatment of opioid use Toward Forging a National 11 disorder and provides discussion of diagnostic criteria, withdrawal symptoms and Policy for Police Mental Health monitoring, relapse prevention, and overdose. In a case report, Cody Armstrong, M.D., Training explores the link between schizophrenia with Gilbert’s syndrome in a patient with Rehan Puri, M.D., M.P.H. changing bilirubin levels. In another case report, Joanna Koutros, M.D., emphasizes 12 Marijuana and Madness, 2nd the effect of depression on a patient’s somatic complaints and the importance of rec- Edition ognizing symptom clusters. Swapnil Rath, M.D., outlines and explains the guidelines Review by Tony Pham, B.A. for violence risk assessment in the psychiatric emergency or inpatient setting. Rehan Puri, M.D., M.P.H., comments on a national policy for police mental health training. 15 Residents’ Resources Lastly, Tony Pham, B.A., reviews the second edition of Marijuana and Madness. Editor-in-Chief Associate Editors Editors Emeriti Misty Richards, M.D., M.S. Ijeoma Chukwu, M.D., M.P.H. Sarah B. Johnson, M.D. Kathleen Mary Patchan, M.D. Molly McVoy, M.D. Senior Deputy Editor Joseph M. Cerimele, M.D. Rajiv Radhakrishnan, M.B.B.S., M.D. Media Editor Holly S. Peek, M.D., M.P.H. Sarah M. Fayad, M.D. Deputy Editor Staff Editor Monifa Seawell, M.D. Tobias Wasser, M.D. Angela Moore Arshya Vahabzadeh, M.D. The Pharmacologic and Nonpharmacologic Treatment of Opioid Use Disorder Rohit Aiyer, M.D. Opioid prescription analgesics are re- Treatment ally assessed and should not be >10 mg sponsible for more deaths than the Methadone is a synthetic, long-acting every few days (8). The literature shows combined number of deaths from both opioid with pharmacologic actions similar that there are several methods to calcu- suicide and motor vehicle accidents (1). to morphine (see Table 1). It is primar- late and convert, and Weschules and Bain In addition, opioid use disorder has a ily a full-receptor agonist and simulates (9) reviewed several of these methods and serious economic impact in the United the action of endogenous opioids and af- concluded that there is no superiority in States, with total costs of prescription fects the release of the neurotransmitters any one conversion protocol. opioid abuse estimated at $55.7 billion glutamate, norepinephrine, dopamine, Buprenorphine maintenance treatment in 2007. Workplace costs accounted for acetylcholine, and serotonin. Methadone doses studied for opioid addiction treat- $25.6 billion (46%), health care costs also competitively inhibits N-methyl-D- ment have ranged from 1 mg–2 mg to 16 accounted for $25.0 billion (45%), and aspartate (4). According to World Health mg–32 mg, depending upon the formu- criminal justice costs accounted for $5.1 Organization (WHO) guidelines, for pa- lation (solution versus tablet), with the billion (9%) (2). Opioid use disorder is an tients using street opioids, such as heroin, duration of treatment lasting from a few epidemic issue in the United States that methadone doses of 20 mg/day will typi- weeks to years. There are three phases in needs to be addressed and taken very seri- cally be adequate to relieve withdrawal buprenorphine maintenance treatment ously by American health care providers, symptoms and retain patients in treat- that should be addressed. The first is the particularly psychiatrists. ment. When it is established that the induction phase, which involves helping initial dose is well tolerated, the metha- Opioid Use Disorder the patient to initiate the process. The done dose should be gradually increased second phase is the stabilization phase, Diagnostic Criteria until the patient is comfortable and not which lasts 1–2 months and is started using heroin or other illicit opioids (5). when the patient is not experiencing In DSM-IV, there were two separate di- Buprenorphine, a partial mu-agonist and withdrawal symptoms. The third phase agnoses: substance abuse and substance antagonist at the kappa opioid receptor, is maintenance, which can last for an in- dependence. In DSM-5, the abuse and has been shown to be effective and safe as definite period and focuses on prevention dependence criteria have been combined a treatment for withdrawal symptoms (see of relapse (10). into one disorder, and the diagnosis has Table 1). Buprenorphine combined with been renamed “substance use disorder.” naloxone is the variation preferred for Buprenorphine/naloxone comprises the DSM-5 states that a patient is considered withdrawal therapy in opioid use disorder partial mu-opioid receptor agonist bu- to have an opioid use disorder if he or she patients (6). Detoxification can also be prenorphine in combination with the has a problematic pattern of opioid use accomplished by symptomatic treatment opioid antagonist naloxone in a 4:1 ratio, leading to clinically significant impair- of opioid withdrawal using medications respectively. When buprenorphine/nal- ment or distress, as manifested by two of such as clonidine (for autonomic hyper- oxone is taken sublingually as prescribed, 11 criteria, which are clustered into the activity), nonsteroidal anti-inflammatory the naloxone exerts no clinically signifi- following four groups: impaired control, drugs (for malaise and myalgias), antidi- cant effect, leaving the opioid agonist social impairment, risky use, and pharma- arrheals and antispasmodics (for diarrhea effects of buprenorphine to predominate. cologic dependence (3). and abdominal cramps), and ondansetron Less frequent dispensing of buprenor- (for nausea) (7). phine/naloxone (e.g., three times per Opioid Withdrawal week) is a major advantage of this in- Maintenance Treatment of tervention and therefore can improve Symptoms and Monitoring Opioid Use Disorder patient satisfaction (11). Opioid withdrawal can be monitored using scales such as the Clinical Opiate For methadone maintenance treatment, Pharmacologic Treatment of Withdrawal Scale. The withdrawal syn- WHO guidelines state that doses in the Opioid Use Disorder drome usually includes symptoms and range of 60 mg–109 mg are the most signs of CNS hyperactivity, such as lac- effective (5). There are many proposed Relapse Prevention rimation, agitation, nausea, rhinorrhea, ratios to convert dosages from mor- Relapse involves use of a substance, such increased respiration rate, insomnia, and phine to methadone, ranging from 4:1 as heroin, following a week or more of ab- stomach cramps (4). to 40:1 (oral morphine:oral methadone). stinence, or one day of heavy use during a The rate of increase should be individu- time when the patient has been drug-free The Residents’ Journal 2 TABLE 1. Pharmacologic Treatments for Opioid Use Disordera Drug Dosage Pharmacokinetics Pharmacodynamics Side Effects Drug-Drug Interactions Methadone 60 mg–110 Rapidly absorbed from Mu-agonist and N-methyl-D- Dizziness, There are additive CNS depres- mg the gastrointestinal tract aspartate antagonist. drowsiness, sive effects. Can potentiate the and can be detected in the nausea, deleterious effects of alcohol. blood within 30 minutes. vomiting, and There is also strong evidence sweating. for QTc prolongation. Buprenorphine 8 mg–32 mg Broken down into A partial agonist at the Headache, CYP3A4 Inhibitors and induc- norbuprenorphine and mu-opioid receptor and an nausea, insom- ers. glucuronidation. antagonist at the kappa- nia, abdomi- opioid receptor. nal pain, and sweating. Buprenorphine 8 mg plus Broken down into Buprenorphine is a partial Headache, Benzodiazepine, erythromycin, plus naloxone 2 mg–16 mg norbuprenorphine and agonist at the mu-opioid pain, insom- itraconazole, an HIV protease plus 4 mg glucuronidation. receptor and an antagonist nia, constipa- inhibitor, rifampin, phenytoin, at the kappa-opioid recep- tion, sweating, carbamazepine, and a barbitu- tor. Naloxone is a potent and nausea. rate such as phenobarbital. antagonist at mu-opioid receptors. Naltrexone 50 mg Subject to significant first- Pure opioid antagonist (mu Blurred vision, Safety is unknown, and the pass metabolism. receptor). tachycardia, concomitant use of two are hallucinations, potentially hepatotoxic medica- nausea, stom- tions. ach pain, and lower fever. Naloxone 0.02 mg, Rapidly distributed in the Pure opioid antagonist (mu Chest pain, Large dosages are required to 0.4 mg, and body. receptor). tachycardia, antagonize buprenorphine. 1.0 mg per mL dry cough, sweating, nausea, headache, and seizures. a Data were obtained from the RxList (http://www.rxlist.com). and is attempting to maintain abstinence. Overdose change in behavior (15). CBT interven- To counter relapse and prevent future Naloxone is a nonselective short-acting tion has been proposed by researchers episodes, Marlatt and Donovan (12) sug- opioid receptor antagonist and is pres- to have great potential, particularly in gested six strategies to help clinicians: ently considered