6/6/2018. Conflict of Interest Statement. Emerging Data on Non-opioid Prescription Drug Abuse

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1 Emerging Data on Non-opioid Prescription Drug Abuse Richard Dart, MD, PhD Director, Rocky Mountain Poison and Drug Center Professor, University of Colorado School of Medicine Conflict of Interest Statement Most manufacturers of prescription opioids or stimulants subscribe to RADARS System. RADARS System is the property of Denver Health and Hospital Authority, a political subdivision of the State of Colorado. Subscribers receive information, but do not participate in developing the System, data collection, or analysis. They do not have access to the raw data. Employees are prohibited from personal financial relationships with any company. 2 Artist: Jason Mecier 3 1

2 Evolution of Substance Abuse Alcohol Marijuana Polysubstance Abuse Heroin (Fentanyl) Opioid Abuser Availability Cost Setting Other Drugs IR Rx Opioid ER Rx Opioid 4 Why Abuse Non-Opioid Prescription Drugs? Potentiate effects of opioids Smooth out effects of other drugs Substitution or replacement of drug of choice Treat early withdrawal 5 National Poison Data System, Generic Code Intentional Abuse Benzodiazepines Dextromethorphan Amphetamines Carisoprodol 8633 Atypical Antipsychotics 8556 Other Sedative/Hypnotic/Anxiety/Anti- Psychotic 8150 Diphenhydramine 5927 Other SSRI 5185 Other Antihistamines 5155 Other Anticonvulsant (Excluding Barbiturates) 3931 Methylphenidate 3662 Other Antidepressant 3173 Cyclobenzaprine 2948 Gabapentin 1373 Clonidine

3 Prevalence (95%CI) 6/6/2018 National Survey of Drug Use and Health Lifetime Nonmedical Use GABA Analogs Gabapentin, pregabalin Misuse common in opioid use disorders (15% -28%) Increased mortality when combined with opioids o Synergistic respiratory depression US Poison Centers, Diversion of GABA Analogs is Increasing Buttram ME, et al. Pharmacoepidemiol Drug Saf. 2017;

4 Use of Gabapentin Increases Mortality Risk Gomes et al. PLoS Med Oct; 14(10): e Other Anticonvulsants Nearly all have been reported both in polysubstance abuse cases Levetiracetam abuse emerging Synergistic CNS depression with opioids Cardiac effects also possible

5 Loperamide Antidiarrheal, Rx and OTC Intestinal mu agonist Poor systemic absorption due to p-glycoprotein BUT often co-used with inhibitors Abused alone or in combination with opioids 13 Slide on Loperamide Deaths Eggleston W, et al. Ann Emerg Med 2017;69: Loperamide National Poison Data System, No significant change in rate of exposures, but behavior and reasons are changing Increased proportion of intentional abuse cases 8% 34% RADARS System 15 5

6 Loperamide Abuse Miller H et al. JAPHA 2017, 57(2): S45 S

7 Antidepressants Reports of abuse of all classes May have higher rates with SNRI Stimulant effects due to norepinepherine reuptake inhibition When used with opioids, pharmaceutical speedball effect Adverse effects include seizures and dysrhythmias 19 Bupropion National Poison Data System, Increased single substance exposures compared to total mentions Used as a primary drug Increased proportion of intentional exposures Markedly increased use in teenage population

8 Antipsychotics Atypical antipsychotics commonly abused both alone and in combination with other drugs Especially popular in incarcerated population Quetiapine often drug of choice 22 Antipsychotic Abuse 429 patients from detox and rehab units 73 (17%) abuse atypical antipsychotics with: Alcohol, opioids, cocaine/crack, methamphetamine, cannabis Quetiapine most common (84.9%) Olanzapine (17.8%) Risperidone (24.7%) Aripiprazole (20.5%) Ziprasidone (8.1%) Asenapine (2.9%) Goals: "getting mellow, "slowing down, or enhancing effects of other drugs American Academy of Addiction Psychiatry (AAAP) 24th Annual Meeting & Symposium 23 Quetiapine DAWN ED visits Mattson et al. Subst Abuse May 24;9: doi: /SART.S ecollection

9 25 Benzodiazepines GABA-A agonists Single agent and polysubstance exposures CNS depression Synergistic with EtOH and opioids Respiratory depression rare with isolated oral exposure BUT also synergistic 26 Benzodiazepines / Opioids National Poison Data System, BDZ alone Opioid alone BDZ + Opioid Calcaterra S et al,

10 Benzodiazepines / Opioids National Poison Data System, Calcaterra S et al, Stimulants Used as single substance or polysubstance Pharmaceutical speedball effect Highest rates in teenage and young adult population Rates of intentional abuse stable, but diversion increasing 30 10

11 per 100,000 population /6/2018 Diversion of Rx Stimulants is Increasing Methylphenidat e RADARS PC 3Q2017, intentional abuse cases 31 Poison Center Program Route of Administration, 3Q 2017 % Int. Abuse Cases References: RADARS PC 3Q2017, intentional abuse cases

12 Cyclobenzaprine Few studies of misuse/abuse Anticholinergic effects Structural similarity to tricyclic antidepressants Synergistic CNS and respiratory depression with opioids Increasing rates in poison centers Summary Nonopioid pharmaceutical drug abuse is increasing Many likely to be co-abused with opioids Synergistic CNS and respiratory depression most common interaction Need methods for surveillance and early warning 36 12

13 Questions? 37 13