Treatment of Drug Addiction PDF

Treatment and Rehabilitation of Drug Addiction Adapted from: Steve Batki, MD (UCSF) PHARMACOTHERA PY to Consider Pharmacotherapy? When Assess patients for:  Severity of Concomitant Medical Illness: Patient’s ability to tolerate medication?  Pregnancy: opioid therapy...

Treatment and Rehabilitation of Drug Addiction Adapted from: Steve Batki, MD (UCSF) PHARMACOTHERA PY to Consider Pharmacotherapy? When Assess patients for:  Severity of Concomitant Medical Illness: Patient’s ability to tolerate medication?  Pregnancy: opioid therapy should be offered to pregnant opioid/heroin addicts; medications that can be associated with adverse physical effects should be avoided (e.g.: disulfiram (Antabuse)  Phase of Recovery: Medications for medical withdrawal or medication to assist with maintenance of abstinence following withdrawal Those with moderate to severe consequences of their substance abuse are good candidates for a pharmacotherapy if, upon assessment, you believe that: 1. They have no medical conditions that would contraindicate use of a medication 2. They are able to understand and adhere to medication use. 3. They are willing to go to psychosocial treatment for their substance abuse (pharmacotherapy alone will not be sufficient to address the aberrant behaviors of addiction) 4. They are fully medically withdrawn from substances and can safely take a maintenance medication. 5. They are vulnerable to relapse without a medication to assist with maintaining abstinence. Phases of Substance Use that are Targets for Pharmacotherapy  intoxication/overdose  withdrawal/detoxification  abstinence initiation/use reduction  relapse prevention  sequelae (psychosis, agitation, etc.) Some Pharmacological Treatment Strategies for SUDs  agonist (replacement/substitution)  antagonist (blockade)  aversive (negative reinforcement)  correction of underlying/associated disorders (such as depression, etc.) 5 Substances for which Substances for Pharmacotherapy which is Available Pharmacotherapy  is not Available  Opioids Cocaine   Methamphetamine Alcohol   Hallucinogens Benzodiazepines   Cannabis Tobacco (nicotine dependence)  Solvents/Inhalants 6 Alcohol Dependence Pharmacothera py Two Phases of Alcohol Dependence: 1. Acute Alcohol Withdrawal 2. Relapse Prevention: Maintenance medications to prevent relapse to alcohol use  Disulfiram  Naltrexone (oral and injectable)  Acamprosate  Benzodiazepines and non-benzodiazepines Note: monitor any patient being treated for a SUD for emergence of depression/anxiety/ suicidality as this can occur in the course of treatment  Disulfiram (Antabuse) How it Works: Blocks alcohol metabolism leading to increase in blood acetaldehyde levels; aims to motivate individual not to drink because they know they will become ill if they do (Goodman and Gilman, 2001) Alcohol Relapse Prevention Meds: Disulfiram (Antabuse) Antabuse reaction: flushing, weakness, nausea, tachycardia, hypotension  Treatment of alcohol/disulfiram reaction is supportive (fluids, oxygen) Side Effects:  Common: metallic taste, sulfur-like odor  Rare: hepatotoxicity, neuropathy, psychosis  Contraindications: cardiac disease, esophageal varices, pregnancy, impulsivity, psychotic disorders, severe cardiovascular, respiratory, or renal disease, severe hepatic dysfunction Patients should avoid alcohol containing foods Clinical Dose: 250 mg daily (range: 125-500 mg/d)  Naltrexone  Oral Naltrexone Hydrochloride  Dose: 50 mg per day  Extended-Release Injectable Naltrexone (Vivitrol) (Garbutt et al, JAMA 2005)  1 injection per month Naltrexone Pharmacology  Similar structure to naloxone (Narcan)  Potent inhibitor of miu opioid receptor binding  may explain reduction of relapse because endogenous opioids involved in the reinforcing (pleasure) effects of alcohol  May explain reduced craving for alcohol because endogenous opioids may be involved in craving for alcohol from Littleton & Zieglgansberger, (2003) Am J Addict 12[Suppl1]:S3-S11  Naltrexone Safety Issues  Can cause hepatocellular injury in very high doses (e.g. 5-10 times higher than normal)  Contraindicated in acute hepatitis or liver failure  Check liver function before, q1 month for 3 months, then q 3 months  Caution about ibuprofen (Motrin, Advil, etc) and other non-steroidal anti-inflammatory agents  may have additive hepatic effects VA/DoD CPG SUDs, www.oqp.med.va.gov/cpg/SUD/SUD_Vase.htm Other safety issues Contraindications:  concomitant opioid analgesics (naltrexone will block analgesic effect)  opioid dependence or withdrawal  hypersensitivity to naltrexone  Medical conditions requiring opioid analgesics  pregnancy (Category C) Naltrexone for Alcohol Dependence  Cochrane Review of NTX decreased relapse to heavy drinking [RR = 0.64] decreased return to any drinking [RR = 0.87 ] NTX increased the time to first drink NTX reduced craving NTX was superior to acamprosate in reducing relapses, drinks and craving. Srisurapanont & Jarusuraisin (2005) Cochrane Database Syst Rev. 2005 Jan 25;(1):CD001867 Naltrexone Delays the Onset of Relapse to Alcohol Benzodiazepines and Non- BZD for Alcohol Dependence Benzodiazepines for the Treatment of Alcohol Withdrawal  BZD produce cross-tolerance with alcohol  BZD has lower abuse potential  However, BZD still remain the drugs of choice for effective treatment of alcohol- withdrawal syndrome - wide margin of safety and low potential to produce physical dependence and tolerance in short-course therapy  Note:Combined use of alcohol and prescribed BZD can be very impairing and produce significant toxicity therefore not suitable for the treatment of alcohol dependence Acamprosate  is thought to stabilize the chemical balance in the brain that would otherwise be disrupted by alcohol withdrawal  works to best advantage in combination with psychosocial support and can help facilitate reduced consumption as well as full abstinence  The mechanism of action is unknown but there’s evidence of inhibition of glutamate receptor- activated responses Opioid Dependence Pharmacothera py Pharmacotherapies for Opiate/Opioid Dependence  Methadone  Naltrexone  Buprenorphine  Opioid Dependence Therapy: Agonist Treatment What is agonist therapy? Use of a long acting medication in the same class as the abused drug (once daily dosing)  Prevention of Withdrawal Syndrome  Induction of Tolerance  What agonist therapy is not:  Substitution of “one addiction for another” Who is appropriate for methadone therapy?  > 18 years (exceptions for 16-17 y.o. with parental consent and special methadone treatment programs)  Greater than 1 year of opioid dependence  Medical compromise  Infectious disease  Pregnancy (CSAT 2005)  Opioid Dependence Maintenance Therapy Determine opioid dependence History (including previous records) Signs of dependence (withdrawal symptoms, tracks) Urine toxicology ECG: determine if pre-existing prolonged QT interval, ECG after 30 days to compare to baseline; methadone prolongs QT in approx. 2% Naloxone challenge can be given if unsure of opioid dependence Clinical Opiate Withdrawal Scale can be used to determine extent of opiate withdrawal symptoms  Opioid Dependence Maintenance Therapy Methadone (must be administered through a registered narcotic treatment program) Characteristics  Long acting mu agonist  Duration of action: 24-36 h  Dose: important issue and philosophical issue for many programs  30-40 mg will block withdrawal, but not craving  Illicit opiate use decreases with increasing methadone dose  80-100 mg is more effective at reducing opioid use than lower doses (e.g.: 40-50 mg/d) Strain et al. 1999  Opioid Dependence Maintenance Therapy Methadone Can interact with many commonly used medications Decreased methadone concentrations:  Pentazocine  Phenytoin  Carbamazepine  Rifampin  Efavirenz  Nevirapine  Lopinavir (Kaletra) Opiate withdrawal syndrome Increased methadone concentrations: Ciprofloxacin Fluvoxamine Discontinuation of inducing drug  Cognitive impairment  Respiratory depression  QTc prolongation; Torsade de Pointes McCance-Katz et al. 2009 Opioid Dependence Maintenance Therapy Methadone Benefits:  Lifestyle stabilization  Improved health and nutritional status  Decrease in criminal behavior  Employment  Decrease in injection drug use/shared needles CSAT, 2005  Opioid Dependence Therapy: Antagonist Treatment Naltrexone Why antagonist therapy?  a pure opioid antagonist and works by blocking the activity of opioids (Walsh et al. 1996)  Prevent impulsive use of drug  Blocks agonist effects  Opioid Dependence Therapy: Antagonist Treatment Naltrexone however:  Relapse rates high (90%) following detoxification with no medication treatment  Side effects: hepatotoxicity, monitor liver function tests every 3 months  Biggest issue is lack of compliance; but those who “test” naltrexone by taking a dose of opioid and experiencing no effect do better with the medication (Cornish JW, et al. 1997)  Naltrexone has in general been better studied for alcoholism than for opioids thus more frequently used for alcoholism  Opioid Dependence Therapy: Antagonist Treatment Buprenorphine  mixed partial agonist opioid receptor (partial μ agonist and it is a weak κ-opioid receptor antagonist)  Compared to methadone, it has the advantage of being only a partial agonist; hence negating the potential for life- threatening respiratory depression in cases of abuse  Given in combination with naloxone, an opioid antagonist to decrease the risk of misuse (naloxone is poorly absorbed when taken by mouth, when taken orally, just the opioid has an effect, but if misused by injecting, the naloxone blocks the effect of the opioid) Epidemiology: Mental Illness in SUDs  Among those with an alcohol disorder, 37% had a comorbid mental disorder.  Among those with non-alcohol drug disorders, more than half (53%) were found to have a mental disorder, with an odds ratio of 4.5 (Regier 1990 JAMA)  SUDS in Mental Illness  Among those with a mental disorder, the odds ratio of an addictive disorder was 2.7, with a lifetime prevalence of about 29%  including an overlapping 22% with an alcohol use disorder,  and 15% with another drug disorder (Regier 1990 JAMA) Why Use Psychiatric Medications in Patients with SUD Comorbidity? 1. To treat psychiatric disorders 2. To attempt to treat substance use disorders  directly or indirectly HARM REDUCTION  As opposed to Abstinence / “curing”  WHO defines Harm reduction as a concept to prevent or reduce negative health consequences associated with certain behaviours  Concerns about transmission of HIV; epidemics in >110 countries; relapsing nature of Addiction  Focuses on minimising health, personal and social harms associated with drug use - the spread of blood-borne diseases, overdoses etc  Ongoing interventions, not short term, as a way to improve health of drug users, their families and society  Marginalised groups Interventions include  Information, education, communication  Education about STD’s +safer sex, family planning ; injection techniques  Health care in relation to infectious diseases; screening, immunisation  Substitution with oral drugs  Needle exchange programmes  Linking with other services – e.g. medical, psychiatric, obstetric, dental ; social and forensic  others COGNITIVE & BEHAVIOURAL STRATEGIES A central element of CBT is anticipating likely problems and enhancing patients’ self-control by helping them develop effective coping strategies Cognitive & behavioural strategies  By identifying triggers for relapse – neg/pos mood states - poor coping skills - social isolation - craving - family issues And developing global self management strategies in areas of cognitive restructuring, skills training, lifestyle changes Cognitive & behavioural strategies Behavioral approaches help: engage people in drug abuse treatment provide incentives for them to remain abstinent modify their attitudes and behaviors related to drug abuse increase their life skills to handle stressful circumstances and environmental cues that may trigger intense craving for drugs and prompt another cycle of compulsive abuse "Cold Turkey"  "Cold turkey" - abrupt cessation of a substance dependence and the resulting unpleasant experience, as opposed to gradually easing the process through reduction over time or by using replacement medication  Advantage – by not actively using supplemental methods, the addict avoids thinking about the habit and its temptation, and avoids further feeding the addiction  Disadvantages - unbearable withdrawal symptoms from the total abstinence, which may cause tremendous stress on the heart and blood vessels (and, in a worst-case scenario, death). Take Home Points  Three medications have been FDA-approved for the maintenance treatment of alcoholism: disulfiram, naltrexone (oral daily or injectable once monthly), and acamprosate  Three medications are FDA-approved for treatment of opioid addiction: naltrexone (an opioid antagonist best for highly motivated patients), methadone (must be given through a licensed narcotic treatment program), and buprenorphine/naloxone (available by prescription from qualified providers).  Some meds are appropriate adjuncts in primary care and should be considered part of the “toolbox” for treating addictions.  Non-pharmacological interventions also play a role in effective management of SUD