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 2. Know the characteristics of 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 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 • (Valium), (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 New Users 2008 NSDUH

2500000

2000000

1500000

1000000

500000

0 M P TranquilizersMDMA Inhala C S L Se H PCP arijuana ain P o timulantsSD er c dativ o aine in n ills ts e s

Number of new users in 2008

CRIT 2010 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 Age at First Use 2008 NSDUH

30 25 20 15 10 5 0 P In M L Cocaine M Pain pillsS S Hero T CP halants arijuana SD D timulantse ranq MA dativ in ui e lizers s

Age in Years

CRIT 2010 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