Methamphetamine use disorder: current trends and treatment
Transcript of Methamphetamine use disorder: current trends and treatment
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Methamphetamine use disorder: current trends and treatmentAnn Watson, MD
Swedish First Hill Family Medicine
May 28, 2021
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Financial disclosures
•none
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Objectives
• Describe current trends in WA state
• Describe complications of short and long term use
• Review treatment strategies
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Case: John• 37yo man with history of HTN, polysubstance use disorder (primary
methamphetamine), depression, PTSD, schizoaffective d/o
• Relevant medications:
Suboxone 8mg daily
Bupropion XR 150mg q24h
Buspar 50mg TID
Seroquel 50mg QD
Geodon 40mg qAM + 60mg qPM
• Can I have a prescription for Adderall for methamphetamine replacement?
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What is methamphetamine?
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Methamphetamine Use in WA State
Ref: Stoner SA 2018
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Deaths by county2
0
0
3
-
2
0
0
4
2015-2016
Ref: Stoner SA 2018
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Concomitant substances
Ref: Stoner SA 2018
Bottom line:
• ~1/2 of meth overdose deaths involve an opioid
• Treat underlying OUD
• Primary meth users should carry naloxone
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Mechanism of actionIncreases synapse of monoamine neurotransmitters including dopamine, norepinephrine
and serotonin
Ref: UTD 2021, Bloom K 2021
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Mode of administration
Time to brain
circulation
Smoking 6-8 sec
Injecting 10-15 sec
Snorting 3-5 min
Ingesting (PO) 180 minRef: Gisborneherald.co.nz
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Short-term effects
Ref: Verywell / Joshua Seong
Sympathetic nervous system activation
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Long-term effects
• Addiction
• Increased risk HIV, Hep B/C
• Extreme weight loss
• Intense itching, formication, skin sores
• Severe dental decay
Ref: https://facesofmeth.us/
Ref: CBS news, 2011
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Long term cognitive changes
• Anxiety
• Psychosis paranoia, persecutory delusions,
auditory, visual, and tactile hallucinations
• Moderate Cognitive Deficits
• Neurotoxicity
• Increased risk of Parkinson’s dementia
Blum K 2021
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Effects in Pregnancy• Low birth weight
• Premature birth
• Postpartum hemorrhage
• Retained placenta
• Poor nutrition, sleep, inattention to prenatal care
• Possible increase in anxiety and impulse control in children
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Withdrawal Timeline
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Withdrawal symptoms
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Behavioral/Psychosocial treatments
Matrix Model
Cognitive behavioral therapy (CBT)
Contingency management (CM)
Motivational interviewing (MI)
Brief intervention
Residential rehab programs
Exercise
Repetitive transcranial stimulation (rTMS) and Transcranial Direct Current Stimulations (tDCS)
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Matrix model• 16 week behavioral health intervention
• Group CBT (36 sessions), individual counseling (4 sessions), family education groups (12 sessions), group social support (4 sessions) and urine and weekly breath alcohol testing.
• Encourages attendance at 12-step meetings like Crystal Meth Anonymous
• 4 studies 2004-2018 showed positive result
• Conclusions: Decreased risky behaviors, days of meth use
Effect lasted 18 months
Ref: Siefried KJ 2020, AshaRani P 2020
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Contingency Management (CM)• Encourages positive behavior change by providing positive
reinforcement
• Positive reinforcement: vouchers exchangeable for money or prizes
• Consequences: withholding vouchers
Resetting earned vouchers to 0
punishment by making an unfavorable report to a parole officer
• 7 studies 2006-2019 showing positive outcomes
• Conclusions: CM associated with decreased positive utox
Ref: Siefried KJ 2020, AshaRani P 2020
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Medications• None FDA approved
• Lots of research on antidepressants, antipsychotics, substitution/replacement therapy
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Research on Pharmacotherapies • Antidepressants: Amineptine,
Mirtazapine, Bupropion, Bupropion+ naltrexone, Sertraline, Atomoxetine
• TCAs: Imipramine
• Atypical antipsychotics; Aripiprazole, Aripiprazole + methylphenidate
• Anticonvulsants: Topiramate
• CNS stimulants: Dextroamphetamine/dexamphetamine, methylphenidate
• Other CNS agents: Modafinil
• GABA agonist/GABAergic agents: Baclofen, gabapentin
• Opioid agonists: Buprenorphine, Buprenorphine + methadone
• Partial cholinergic nicotinic agonist: Varenicline
• Glutamatergic agents: N-acetyl cysteine, N-acetyl cysteine + naltrexone, Riluzole
• CRF1 antagonist: Pexacerfont
• Benzodiazepine antagonist/GABA agonist/H1 histamine receptor: Flumazenil + gabapentin + hydroxyzine
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Mirtazapine• Proposed mechanism of action
(MOA):
Noradrenergic and specific serotonergic antidepressant
Mixed monoamine agonist/antagonist -> release of norepinephrine, serotonin and dopamine in the CNS
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Mirtazapine• Kongsakon, 2005: n= 20, mirtazapine 15-60mg PO QD
Improvement in withdrawal symptoms
Cruickshank, 2008: n=31, mitrazapine 30mg PO QD No difference in retention or withdrawal symptoms
Colfax, 2011: n= 60, mirtazapine 30mg QD in MSM Reduction in use, reduction in high-risk sexual behaviors
Conclusion: Conflicting results
May improve withdrawal symptoms
Reduction in use, reduction in high risk behaviors
Ref: Kongsakon R 2005, Cruickshank CC 2008, Colfax GN 2011, Siefried KJ 2020
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Buprenorphine• Proposed MOA:
μ-opioid receptor partial agonist, κ-opioid receptor antagonist
• 2015: buprenorphine 6mg PO QD for 16 weeks, n=40 Decreased MA cravings while taking buprenorphine, benefit stopped when off
medication
• 2017: buprenorphine 8 mg vs. methadone 40 mg OD over 17 days, n=40 Reduced cravings in both groups
No control
No UDS
• Conclusions: May help with cravings while taking Use to treat co-occurring OUD
Ref: Salehi M 2015, Ahmadi J 2017, Siefried KJ 2020
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Agonist therapy• Proposed MOA: replacement with alterative CNS
stimulant
• Cochrane review, 2013: 4 randomized trials, total n=162
• 2013, 2014, 2015, 2020: 3 randomized trials, total n=307 Examined dexamphetamine, methylphenidate
• Conclusions:
No reduction in use
No increase in sustained abstinence
Possible reduction in severity of withdrawal symptoms
Ref: Perez-Man a 2013, Miles 2013, Ling 2014, Rezaei 2015, Stoner SA 2018, Akhondzadeh 2020
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Bupropion + Naltrexone
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Bupropion + Naltrexone: proposed MOA• Bupropion:
inhibits reuptake of NE and dopamine
minimal effect on the reuptake of serotonin
no inhibitory effect on monoamine oxidase; nicotinic acetylcholine receptor agonist
• Naltrexone: Opioid receptor antagonist
Trivedi MH 2021 Texas
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Bupropion + Naltrexone• Trivedi, 2021: n=403
Stage 1: naltrexone ER 380mg q3wks IM + bupropion ER 450 mg per day QD vs placebo x 6 weeks
Stage 2: non-responders in stage 1 randomized to additional 6 weeks
Primary outcome = at least ¾ methamphetamine-negative urine samples
Trivedi MH 2021 Texas
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Bupropion + Naltrexone
Trivedi MH 2021
• Primary outcome:
2 stages over 12 weeks: treatment effect of 11.1%
• Secondary outcomes:
Reduction in negative utox-6.8%
Decreased cravings -9.7%
Decreased PHQ9 score: -1.1
Treatment Effectiveness Assessment: -4.0%
• Conclusion: small but statistically significant response
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Case: John• 37yo man with history of HTN, polysubstance use disorder (primary
methamphetamine), depression, PTSD, schizoaffective d/o
• Can you prescribe me Adderall?
• Relevant medications:
Suboxone 8mg daily
Bupropion XR 150mg q24h
Buspar 50mg TID
Seroquel 50mg QD
Geodon 40mg qAM + 60mg qPM
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Summary• Greatly increasing methamphetamine use in WA state over last several
years
• >50% deadly overdoses associated with co-occurring use with opiates Treat underlying OUD
Consider prescribing naloxone to patients who use methamphetamines
• First line treatment: behavioral health interventions (matrix model, contingency management)
• Consider mirtazapine 30mg PO QD, mixed results in studies
• Consider bupropion PO + naltrexone IM for patients without contraindications
• Amphetamine replacement not effective
• Further research needed on pharmacotherapies
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Questions?
https://www.123rf.com/clipart-vector/methamphetamine.html
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