BREAKING BAD: WHAT TO DO WHEN YOUR PATIENT IS USING METHAMPHETAMINE - PowerPoint PPT Presentation

BREAKING BAD: WHAT TO DO WHEN YOUR PATIENT IS USING METHAMPHETAMINE

Learning Objectives •Explore patient cases that involve a variety of mental illnesses occurring in the context of previous or current methamphetamine use •Implement strategies to improve differential diagnosis and treatment for patients who have a history of methamphetamine use

Prevalence of Methamphetamine (MA) Use •In 2018, among people aged 12 or older in the United States: • Approximately 1.9 million people (0.7% of the population) used MA in the past year • An estimated 1.1 million people (0.4% of the population) had a MA use disorder •Around 27 million people worldwide (0.5% of the adult population), are estimated to have used amphetamines, including amphetamine, methamphetamine, and pharmaceutical stimulants, in the past year Substance Abuse and Mental Health Services Administration 2019; World Drug Report 2020.

Psychiatric Developments of MA Abuse Proportion of Meth Users 100 90 80 70 60 (%) 50 40 30 20 10 0 *Hypobulia is a lowered ability to make decisions or act Ballester J et al. Expert Rev Clin Pharmacol 2017;10(3):305-14; Javadian S et al. Prim Care Companion CNS Disord 2016;18(6):10.4088/PCC.16m02002; Härtel-Petri R et al. Pharmacopsychiatry 2017;50(3):96-104; Hellem TL. J Subst Abuse Treat 2016;71:16-22; Luo SX, Levin FR. Curr Psychiatry Rep 2017;19(3):14; Warden D et al. Psychiatry Res 2016;246:136-41; Zhong N et al. Prog Neuropsychopharmacol Biol Psychiatry 2016;69:31-7.

MA Use in the Time of COVID-19 • MA causes pulmonary damage, pulmonary hypertension, and cardiomyopathy, which increase risk for COVID-19 infection and associated complications • MA users are at greater risk of overdose, especially in rural areas • Less MA availability (border control) • More availability of MA contaminated with fentanyl • More likely to use alone (social distancing) • Reduced access to health care and recovery services Volkow ND. Ann Intern Med 2020;173(1):61-2; Ostrach B et al. J Rural Health 2020;1-4.

Meth-Gators https://www.nbcnews.com/news/us-news/tennessee-police-warn-locals-not-flush-drugs-fear-meth-gators-n1030291

CASE 1 U ntr ntreated eated S ymptoms mptoms

Attention Deficit Hyperactivity Disorder (ADHD) and Substance Abuse Disorder (SUD) • Comorbidity of ADHD and SUD: • 23.1% of patients with SUD have comorbid ADHD • Lifetime prevalence of ADHD in methamphetamine users is 20.8% • Lifetime prevalence of ADHD in non-users is 6.2% • Treatment of childhood ADHD with a stimulant: • Has not been shown to increase risk of later SUD • May actually DECREASE risk of later SUD • Individuals with a history of MA abuse may have increased tolerance to stimulant medications and may require higher doses Cook J et al. Aust N Z J Psychiatry 2017;51(9):876-85; Bordoloi M et al. Curr Dev Disord Rep 2019;6:224-7; Quinn PD et al. Am J Psychiatry 2017;174(9):877-85.

Malingering? • Falsely or grossly exaggerated medical complaints with the goal of receiving a prescription • As many as 20% of nonmedical stimulant users misrepresent their symptoms to obtain a prescription • Tend to endorse more symptoms of hyperactivity and restlessness • Often give intentionally poor performances on cognitive tests, especially those assessing attention • Important to confirm diagnosis of ADHD • Nonmedical use and diversion of stimulants is commonly low compared with other prescription medications, such as benzodiazepines or opioids Clemow DB, Walker DJ. Postgrad Med 2014;126(5):64-81; Martinez-Raga J et al. Ther Adv Drug Saf 2017;8(3):87-99.

The Rewards of Dopamine • Subjective rewards are due to stimulants increasing synaptic dopamine (DA) levels in the mesocorticolimbic system • Mesocortical circuit includes ventral tegmental area (VTA) projections to nucleus accumbens and prefrontal cortex Ashok AH et al. JAMA Psychiatry 2017;74(5):511-9; Ballester J et al. Expert Rev Clin Pharmacol 2017;10(3):305-14; Levy F. Ther Adv Psychopharmacol 2016;6(6):382-3; Volkow ND, Swanson JM. Am J Psychiatry 2003;160(11):1909-18.

Dopaminergic Synapses Vesicular monoamine transporter-2 (VMAT2) Vesicle containing dopamine Dopamine transporter (DAT) Dopamine Dopamine D2 receptors Stahl SM. Stahl’s essential psychopharmacology 2015.

Dopaminergic Effects of Methylphenidate Methylphenidate inhibits DAT as an allosteric modulator (does not bind to the same spot as Increased synaptic dopamine) dopamine Stahl SM. Stahl’s essential psychopharmacology 2015.

Dopaminergic Effects of Amphetamine (Amph) Amph reverses the Dopamine direction of DAT, displaced from leading to increased synaptic dopamine in synapse vesicles builds up in cytosol Amph competitively inhibits VMAT2 Amph competitively inhibits DAT Increased synaptic dopamine Stahl SM. Stahl’s essential psychopharmacology 2015; Ashok AH et al. JAMA Psychiatry 2017;74(5):511-9; Heal DJ et al. J Psychopharm 2013;27(6):479-96.

Choose Your Poison • Amphetamine (Amph) • Competitively inhibits dopamine transporter (DAT) • Increases DAT-mediated reverse transport of DA from cytoplasm to synapse • Binds to vesicular monoamine transporter (VMAT2), inhibiting uptake of monoamines into synaptic vesicles • Inhibits monoamine oxidase (MOA), the enzyme responsible for monoamine breakdown • Methamphetamine (MA) • Same basic mechanism of action as Amph but… • More addictive than Amph due to greater central nervous system (CNS) penetration and longer duration of action • Euphoria is experienced within 5 minutes and lasts for 8–12 hours • Cocaine • Slower CNS uptake and faster clearance than MA • Acts primarily by blocking DAT • Euphoria lasts for 20–30 minutes Ashok AH et al. JAMA Psychiatry 2017;74(5):511-9; Ballester J et al. Expert Rev Clin Pharmacol 2017;10(3):305-14; Heal DJ et al. J Psychopharm 2013;27(6):479-96; Morais APD et al. CNS Neurosci Ther 2018;24(2):85-97; Thanos PK et al. Beh Brain Res 2017;320:282-90.

Prescription Stimulants vs. Illicit Stimulants • Stimulant “high” depends on how much dopamine is increased AND how fast that increase occurs • Prescribed stimulants : • Have been successfully used to treat ADHD in patients with MA or cocaine addiction • Do not increase risk of substance-related events, even in patients with a history of illicit stimulant use disorders • Methylphenidate and d-amphetamine : • Have a much slower striatal uptake compared to MA or cocaine • When abused, are most often injected • Formulations (extended release, bead technology, osmotic pump, tamper-proof capsules) lower risk of abuse potential based on likability studies • Lisdexamfetamine : • Prodrug of d-amphetamine • Injecting or snorting does not increase drug-positive effects because pharmacokinetic curve is exactly the same Levy F. Ther Adv Psychopharmacol 2016;6(6):382-3; Luo SX, Levin FR. Curr Psychiatry Rep 2017;19(3):14; Heal DJ et al. J Psychopharm 2013;27(6):479-96; Quinn PD et al. Am J Psychiatry 2017;174(9):877-85; Volkow ND, Swanson JM. Am J Psychiatry 2003;160(11):1909-18.

Non-Stimulants • No direct influence on dopaminergic areas linked to stimulant abuse • Guanfacine and clonidine • Influence norepinephrine levels by acting as alpha 2 adrenergic receptor agonists • Atomoxetine • Norepinephrine transporter inhibitor • Less effective for ADHD compared to stimulants? Clemow DB, Walker DJ. Postgrad Med 2014;126(5):64-81; Martinez-Raga J et al. Ther Adv Drug Saf 2017;8(3):87-99; Cortese S et al. Lancet Psychiatry 2018;5(9):727-38.

Abuse Potential of Common ADHD Treatments Treatments Abuse potential Stimulants Amphetamine (XR) High Methylphenidate (XR) High Lisdexamfetamine Low Non-stimulants Atomoxetine None Guanfacine (XR) None Clonidine (XR) Low Bold indicates FDA approval for treatment of adult ADHD; XR=extended release. Stahl SM. The prescriber’s guide. 6th ed. Cambridge University Press 2017.

Untreated Symptoms Summary • MA may be misused to ameliorate untreated psychiatric symptoms associated with ADHD • Stimulant “high” depends on how much dopamine is increased and how fast that increase occurs • Prescribed stimulants may be used to treat ADHD in patients with MA addiction; do not increase risk of substance-related events • Methylphenidate and d-amphetamine have a much slower striatal uptake compared to MA • Lisdexamfetamine has very low abuse potential

CASE 2 Ta rdi rdive ve Dy ski skinesi nesia

Methamphetamine (MA) is Associated with Dysregulated Dopamine and Fine Motor Function • Meta-analyses indicate: • Lower whole striatum, caudate, and putamen dopamine D2/D3 receptor availability and dopamine transporter (DAT) availability in MA users versus non-users • Deficits in fine motor function in adults with a history of MA abuse or dependence versus Fine motor deficits may be associated with striatal non-users DAT availability in detoxified MA abusers (n=15) Proebstl L et al. Eur Psychiatry 2019;59:15-24; Ashok AH et al. JAMA Psychiatry 2017;74(5):511-9; Scott JC et al. Neuropsychol Rev 2007;17(3):275-97; Volkow ND et al. Am J Psychiatry 2001;158(3):377-82.