What’s the Harm? Prescribing Buprenorphine and Benzodiazepines Sherry Nykiel, M.D. Act ing Medical Direct or Chief of Addict ion Psychiat ry
Obj ectives By the end of the presentation, participants will: Understand the hazards associated with the prescribing of benzodiazepines in general Know the risks of combining benzodiazepines and buprenorphine Recognize the dangers of denying treatment with buprenorphine to taking prescribed or illicit benzodiazepines Identify appropriate treatment plans for patients on buprenorphine and benzodiazepines
Benzodiazepines –A Brief History 1955 – Leo S ternbach synthesizes chlordiazepoxide while working on tranquilizer development at Hoffman-LaRoche He initially found the results disappointing and abandoned the results 1957 - co-worker, Earl Reeder, was spring cleaning the lab and rediscovered the compound and submitted it for animal testing Rather than being negative as expected, it showed strong sedative, anticonvulsant and muscle relaxant properties 1960 – Librium is introduced to the world 1963 – Diazepam (Valium) is marketed by the same company 1970’s – these two medications largely replace barbiturates due to their improved safety profile
Benzodiazepines –A Brief History 1965 – oxazepam released 1975 – clonazepam released 1977 – lorazepam released 1981 – temazepam released 1982 – triazolam released 1985 – midazolam released Today: 35 benzodiazepine derivatives exist 21 of these are approved internationally
Benzodiazepines –A Brief History 1980’s – risk of dependence becomes evident • Benzodiazepines were the subj ect of the largest class action suit (at that time) against drug manufacturers in Great 1965 – oxazepam released Britain 1975 – clonazepam released • 14,000 patients using 1800 law firms alleged that the pharmaceutical company 1977 – lorazepam released was aware of the dependence potential but withheld this information from 1981 – temazepam released physicians 1982 – triazolam released • Lack of funding and concerns re: expert witnesses (psychiatrists) had a conflict of 1985 – midazolam released interest Today: 35 benzodiazepine derivatives exist 21 of these are approved internationally
Why prescribe? All BZD have anxiolytic, hypnotic, muscle relaxant, anticonvulsant and amnesic effects Most common indications for new BZD prescriptions are insomnia and anxiety BZDs are prescribed at greater rates than antidepressants for the treatment of depression and anxiety, despite evidence that supports antidepressants as first line medications The maj ority of these prescriptions are written by general practitioners Between 1996 and 2013: The number of people prescribed a benzodiazepine increased 67% and continues to rise The total quantity more than tripled Generally considered safe when prescribed for short term use (2-4 weeks) S oyka, 2019
Why prescribe? ht t ps:/ / vaww.portal2.va.gov/ sit es/ ad
Why prescribe? ht t ps:/ / vaww.portal2.va.gov/ sit es/ ad
Why prescribe? 25-76% of those newly prescribed a BZD will remain on it long-term Long term is considered more than 4-8 weeks, which is when one will begin to have some physiologic dependence The maj ority of those taking BZD for more than 8 weeks will have some withdrawal Most of those who are on long-term will have difficulty tapering off Many long term patients will never successfully taper off The goal for these patients is tapering to the lowest possible dose
Long-term BZD use ht t ps:/ / vaww.portal2.va.gov/ sit es/ ad
Long-term BZD use Most patients prescribed BZDs long-term remain within recommended dosage levels A small percentage will develop “ high dose dependence” Long-term prescription abuse (more than 2 times the prescribed dose) following treatment of an underlying condition A consequence of BZD use for recreational purposes High dose dependent users: S uffer more frequently from co-occurring mental disorders Are less likely to tolerate current discontinuation and withdrawal strategies Have a higher risk of inj ury or impairment as a result of use
BZD withdrawal syndrome Has been documented to occur following attempts to withdrawal from even low dose BZD S ymptoms generally occur between 2-3 days (for shorter acting BZDs) and 5-10 days (for longer acting BZDs) and may include: Anxiety Muscle spasms Panic attacks Depersonalization S Hallucinations/ psychosis leep disorders Cognitive impairment S eizures
BZD withdrawal syndrome Not unlike opioids, fear of BZD withdrawal symptoms often deters patients from attempts to discontinue their use
Re-evaluating the Use of Benzodiazepines
Re-evaluating the Use of Benzodiazepines The overdose death rate involving benzodiazepine from 2001– 2014 increased five fold ht t ps:/ / vaww.portal2.va.gov/ sit es/ ad
Re-evaluating the Use of Benzodiazepines ht t ps:/ / vaww.portal2.va.gov/ sit es/ ad
Re-evaluating the Use of Benzodiazepines The overdose death rate involving benzodiazepine from 2001– 2014 increased five fold, with opioids involved in 75% of these deaths After opioids, benzodiazepines are the drug class most commonly involved in intentional and unintentional pharmaceutical OD deaths (29.4% ) Rate of co-prescribing benzodiazepines and opioids has nearly doubled between 2001-2013 ht t ps:/ / vaww.portal2.va.gov/ sit es/ ad
S ubstances Abused with Benzodiazepines
The Opioid Epidemic
The Opioid Epidemic
The Opioid Epidemic ht t ps:/ / www.legit script .com/ blog/ 2018/ 09/ nsduh-report -opioid-abuse/
The Opioid Epidemic
The Opioid Epidemic Family medicine (32% ), internal medicine (23% ), and orthopedics (11% ) were the most common high- volume prescribing specialties Across specialties, hydrocodone and oxycodone were the most- frequently prescribed opioid types Nataraj N, et.al., 2019
The Opioid Epidemic Family medicine (32% ), internal medicine (23% ), and orthopedics (11% ) were the most common high- volume prescribing specialties Across specialties, hydrocodone and oxycodone were the most- frequently prescribed opioid types In 2010, enough prescription opioids were prescribed to medicate every American adult around the clock for a month
The Opioid Epidemic Family medicine (32% ), internal medicine (23% ), and orthopedics (11% ) were the most common high- volume prescribing specialties Across specialties, hydrocodone and oxycodone were the most- frequently prescribed opioid types In 2010, enough prescription In 2015, enough prescription opioids were prescribed to opioids were prescribed to medicate every American adult medicate every American adult around the clock for a month around the clock for three weeks https:/ / www.cdc.gov/ drugoverdose/ pdf/ pubs/ 2018-cdc-drug-surveillance-report.pdf
The Opioid Epidemic
The Opioid Epidemic
The Opioid Epidemic
The Opioid Epidemic
The Opioid Epidemic https:/ / www.drugabuse.gov/ drugs-abuse/ opioids/ benzodiazepines-opioids
Treatment
Withdrawal management vs. “ maintenance”
Goals of Withdrawal Management Reduce discomfort S how empathy Link with aftercare (on-going) services
Goals of Withdrawal Management Reduce discomfort S how empathy Link with aftercare (on-going) services It is unrealistic to think that successful withdrawal management will lead to continuous abstinence
Buprenorphine Treatment Formally known as “ maintenance”
Buprenorphine Treatment Benefits of treatment include: Reduced illicit use Improved social functioning Increased retention in treatment Decreased morbidity and mortality Reduced risk of infectious disease transmission Reduced engagement in criminal activity ht t ps:/ / www.drugabuse.gov/ publicat ions/ research-reports/ medicat ions-to-treat -opioid-addict ion/ efficacy-medicat ions-opioid-use-disorder
Buprenorphine Treatment ht t ps:/ / www.researchgat e.net / figure/ mu-Recept or-Pharmacology_fig1_258857065
Buprenorphine Treatment
Buprenorphine and Benzodiazepines U.S . Treatment outcomes Prospective S tudy (TOPS ) 74% of heroin users entering treatment reported BZD within the past year 25% were found to be using daily Lavie et. al., 2009 showed that among buprenorphine treated patients in France: 67% reported lifetime prevalence of BZD use 54% reported use within the last month Methadone patients have similar prevalence rates of benzo use Estimates of problematic BZD use in these groups ranges from 18-50% Not all opioid users will experience harm or develop BZD use disorder (Lintzeris et.al., 2009)
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