Methamphetamine use disorder: current trends and treatmentAnn Watson, MD

Swedish First Hill Family Medicine

May 28, 2021

Financial disclosures

•none

Objectives

• Describe current trends in WA state

• Describe complications of short and long term use

• Review treatment strategies

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?

What is methamphetamine?

Methamphetamine Use in WA State

Ref: Stoner SA 2018

Deaths by county2

0

0

3

-

2

0

0

4

2015-2016

Ref: Stoner SA 2018

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

Mechanism of actionIncreases synapse of monoamine neurotransmitters including dopamine, norepinephrine

and serotonin

Ref: UTD 2021, Bloom K 2021

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

Short-term effects

Ref: Verywell / Joshua Seong

Sympathetic nervous system activation

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

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

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

Withdrawal Timeline

Withdrawal symptoms

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)

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

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

Medications• None FDA approved

• Lots of research on antidepressants, antipsychotics, substitution/replacement therapy

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

Mirtazapine• Proposed mechanism of action

(MOA):

Noradrenergic and specific serotonergic antidepressant

Mixed monoamine agonist/antagonist -> release of norepinephrine, serotonin and dopamine in the CNS

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

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

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

Bupropion + Naltrexone

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

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

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

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

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

Questions?

https://www.123rf.com/clipart-vector/methamphetamine.html

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