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Benzodiazepines Benzodiazepines CRIT program May 2010 Alex Walley, MD, MSc Primary Care Physician HIV Clinic, Boston Medical Center Medical Director, Opioid Treatment Program Boston Public Health Commission Medical Director, Overdose Prevention Pilot Program Massachusetts Department of Public Health CRIT 2010 Learning objectives At the end of this session, participants will be able to: 1. Understand why people use benzodiazepines 2. Know the characteristics of benzodiazepine intoxication and withdrawal syndromes 3. Understand the consequences of these drugs 4. Know the current options for treatment of benzodiazepine dependence CRIT 2010 Roadmap 1. Case and controversies 2. Epidemiology 3. Benzo effects 4. Treatment CRIT 2010 Case • 29 yo man presents for follow-up at methadone clinic after inpatient admission for femur fracture from falling onto subway track from platform. • Treated with clonazepam since age 16 for panic disorder. Takes 6mg in divided doses daily. Missed his afternoon dose day of the accident • Started using heroin at age 23. • On methadone maintenance for 1 year, doing well, about to get his first take home CRIT 2010 Controversies • Are benzodiazepines over-prescribed or under prescribed? • Are they safe in opioid dependent patients? • Why do people buy them off the street? • Why is it so hard to get chronic benzo users off of benzos? CRIT 2010 Why benzos? • Disabling anxiety, insomnia, nausea, seizure disorder • Chronically treated for whom discontinuation is feared • Boosting other sedating medications (opioids) • Euphoria seeking • Self-medication of opioid or alcohol withdrawal or cocaine toxicity CRIT 2010 Prescribers are ambivalent On the one hand On the other hand • Non-medical use of benzos • Rarely the drug of choice very common, esp. in people without previous addiction • Given the amounts prescribed, • Subgroups are particularly benzo abuse is “remarkably concerning low” – Patients on opioids • Benzos work fast with few side • Hard to stop them effects • Early benzo use does not • Benefit maintained over time improve long-term course of PTSD • Benzo may make co-morbid depression worse Stevens, Pollack. J Clin Psychiatry 2005; 66s2:CRIT 2010 21-27 History CRIT 2010 CRIT 2010 Benzodiazepines • Sedative agents • First discovered in 1954 by a Austrian scientist, Leo Sternbach Æ Librium • 1963 Æ Valium • Used for anxiety, seizures, withdrawal, insomnia, drug-associated agitation CRIT 2010 Pharmacology & Kinetics • Acts on GABA receptors by potentiating it’s inhibitory effects on the CNS • Kinetics divided into three groups: – Short acting • Triazolam (Halcion), Oxazepam (Serax), Alprazolam (Xanax) • Midazolam (Versed) Æ but has more active metabolites – Intermediate acting • Lorazepam (Ativan), Temazepam (Restoril) – Long acting • Diazepam (Valium), Chlordiazepoxide (Librium), Clonazepam (Klonopin) • Rapidly absorbed in GI tract, metabolized in liver CRIT 2010 CRIT 2010 Withdrawal Syndrome • Symptoms? – Tremors, anxiety, perceptual disturbances, dysphoria, psychosis, seizures • Onset of symptoms? – Varies, can occur w/in 24-28 hours or weeks afterwards, need to consider how long BZD has been used and rapidity of taper • Treatment? –BZD • Long-acting preferred • Dose reduction 10-25% every 1-2 weeks CRIT 2010 History • Widely available starting in the 1960s • 1980s – high potency benzodiazepiens found to be more effective for panic and anxiety than other drugs – Advantages: rapid onset and less risk of dependence CRIT 2010 Epidemiology CRIT 2010 PCP Heroin Sedatives LSD Stimulants New Users 2008 NSDUH Cocaine Inhalants MDMA 2500000 Tranquilizers 2000000 Pain Pills 1500000 Number ofCRIT new 2010 users in 2008 Marijuana 1000000 0 500000 Past Month Use: 2002-2008 6,000,000 5,000,000 4,000,000 3,000,000 2,000,000 1,000,000 0 2002 2003 2004 2005 2006 2007 2008 Pain Pills Cocaine Tranquilizers Stimulants Heroin CRIT 2010 NSDUH 2008 Tranquilizers Heroin Sedatives Stimulants Pain pills Age at First Use 2008 NSDUHMDMA Cocaine 30 LSD 25 20 Marijuana Age in Years CRIT 2010 15 Inhalants 10 5 PCP 0 Benzodiazepine Effects CRIT 2010 Overdose and oversedation Among 250 opioid dependent subjects with previous methadone or buprenorphine prescriptions, reported the following symptoms when also taking benzos: Symptom Methadone BPN Extreme drowsiness 42% 24% Unconsciousness 7% 3% Overdose 7% 1% CRIT 2010 Nielsen. Addiction 2007; 102: 616-622. Benzos in Methadone Patients Upon MMT entry in Israel • 47% of patients abusing benzos ceased after 1 year • 27% of patients not abusing benzos had started by 1 year • Reasons for abuse included: – 87% to improve emotional state – 41% to boost other drugs – 40% for sleep – 24% to get high on benzos alone – 23% for withdrawal – 19% to reduce the effects of stimulants CRIT 2010 Gelkopf et al. DAD 1999; 55: 63-68. Benzos in Methadone Patients Among 361 cocaine/heroin users enrolled in a contingency management trial in Baltimore, benzodiazepine use was associated with • Increased cocaine use during treatment • Blunted response to contingency management CRIT 2010 Ghitza er al. DAD 2008; 97:150-157. Does the cognitive function of Are they still impaired compared to long-term benzo users controls or normative data? improve following withdrawal? CRIT 2010 Barker. Arch Clinical Neuropsych 19 (2004) 437–454 Withdrawal syndrome Marked decrease or cessation of benzodiazepines after several weeks of regular use and 2 or more … • Autonomic hyperreactivity • Increased hand tremor • Insomnia • Nausea or vomiting • Hallucinations • Psychomotor agitation •Anxiety • Tonic-clonic seizures CRIT 2010 Patient’s perspective on chronic benzo use • Purpose of benzos – Means of coping with stress/anxiety and insomnia “Sometimes my life gets so up in the air that I say to my children, right now I wish I had a wafer-sized Valium.” – Lifeline or life-transforming properties “It makes me want to go on living.” “I think if it weren’t for the chemicals I wouldn’t be chugging along.” “I don’t mentally think I would have survived without it and that’s the truth.” – Lack of awareness, underestimation, disregard for side effects “He wouldn’t have given it to me if he thought it was gonna hurt me.” “It’s just a small, little, tiny white pill.” “It’s the lowest dose that they make.” “My head always feels foggy.” Cook et al. JGIM 2007: 22; 1094-1100. CRIT 2010 Patient’s perspective on chronic benzo use • Attitudes toward taper/ discontinuation – Resistance to taper “I see no reason why I should put myself through hell… We don’t have that long to live and we might as well enjoy ourselves while we’re here.” “On numerous occasions I’ve tried to go off of it. And the reaction is I can’t sleep and I’m totally wired. I’m up all night.” – Rejection of psychological interventions “I just don’t want to. I’m not one of those people who can sit around and talk about my problems with strangers.” – The physician-patient relationship “I have complete faith in Dr. _______. I mean we go back a lot of years. Whatever he says, goes.” Cook et al. JGIM 2007: 22; 1094-1100. CRIT 2010 Treatment CRIT 2010 Treating withdrawal 3 strategies 1. Taper the medication – 10% per day 2. Stabilize with long-acting barbituate (phenobarbital) and taper 30mg per day or slower 3. Substitute an anti-convulsant (carbamazepine or valproic acid Lowinson et al. Substance Abuse: ACRIT Comprehensive 2010 Textbook. 2005. 4th Edition. Lippincott. Thanks! Alex Walley, MD, MSc [email protected] CRIT 2010 Safety • Benzos (unlike barbituates) are believed to be nonlethal unless combined with other types of sedatives CRIT 2010 Prescription Drug Misuse • Higher doses than prescribed • More frequently than prescribed • Without a prescription • Reasons other than intended by the prescriber CRIT 2010.
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