sign in sign up
<<
Home , H1 antagonist

Virginia Addiction ECHO*Clinic February 21, 2020

*ECHO: Extension of Community Healthcare Outcomes Helpful Reminders

Rename

• Rename your Zoom screen, with your name and organization Helpful Reminders

• You are all on mute please unmute to talk

• If joining by telephone audio only, *6 to mute and unmute Unmute Helpful Reminders

• Please type your full name and organization into the chat box

Chat Box • Use the chat function to speak with IT or ask questions VCU Opioid Addiction ECHO Clinics

• Bi-Weekly 1.5 hour tele-ECHO Clinics • Every tele-ECHO clinic includes a 30 minute didactic presentation followed by case discussions • Didactic presentations are developed and delivered by inter-professional experts • Website Link: www.vcuhealth.org/echo Hub Introductions

VCU Team

Clinical Director Gerard Moeller, MD Administrative Medical Director ECHO Hub and Principal Vimal Mishra, MD, MMCi Investigator

Clinical Expert Lori Keyser-Marcus, PhD Courtney Holmes, PhD Albert Arias, MD

Didactic Presentation Gerard Moeller, MD

Program Manager Bhakti Dave, MPH

Practice Administrator David Collins, MHA

IT Support Vladimir Lavrentyev, MBA Introductions:

• Name • Organization

Reminder: Mute and Unmute to talk *6 for phone audio Use chat function for Introduction What to Expect

I. Didactic Presentation I. Gerry Moeller, MD

II. Case presentations I. Case 1 I. Case summary II. Clarifying questions III. Recommendations

II. Case 2 I. Case summary II. Clarifying questions III. Recommendations Lets get started! III. Closing and questions Didactic Presentation Pharmacotherapy for Methamphetamine

F. Gerard Moeller, M.D. Professor and Division Chair: Addictions Department of Psychiatry VCU School of Medicine

9 Disclosures

• I have received grant funding from Indivior pharmaceuticals and Nektar Therapeutics for research unrelated to this talk

10 Meth vs. Cocaine Methamphetamine Cocaine Stimulant and local

Man-made Plant-derived

Smoking produces a long-lasting high Smoking produces a brief high

50% of the drug is removed from the 50% of the drug is removed from the body in 12 hours body in 1 hour

Increases dopamine release and Blocks dopamine re-uptake blocks dopamine re-uptake

Limited medical use for ADHD, Limited medical use as a local narcolepsy, and weight loss anesthetic in some surgical procedures

11 Methamphetamine Brain Effects • Methamphetamine metabolized in the liver to amphetamine • Methamphetamine and amphetamine reverse the transport direction of the dopamine, norepinephrine, and serotonin transporters, increasing the levels of monamines in the synapse • Also inhibit the vesicular monoamine transporter (VMAT) increasing monoamines in the cytoplasm and inability to make monoamine vesicles for normal process for neurotransmission • Methamphetamine has been shown to cause neurotoxicity characterized by long lasting depletion of dopamine and changes in striatal and nerve terminals in preclinical studies

12 Structure of

MDMA

Pseudoephedrine Sulfate

13 Treatment of Stimulant Abuse

• Treatment of Psychiatric complications • Depression - warranted if symptoms persist after drug withdrawal • - Amphetamine induced psychosis very similar in appearance to Schizophrenia. Treatment with effective.

14 No FDA Approved for Methamphetamine

Challenges Opportunities  Medication Compliance • Administer in clinic  Treatment Retention • Contingency Management • Inclusion Criteria  Subject Heterogeneity  Subject Recruitment

15 Medications Have Been Assessed for Amphetamine and Methamphetamine Use Disorders

Treatments Agents Mechanisms Outcome & Inhibits DA via monoamine Methylphenidate Some evidence of benefit in reduction of use, but also negative trials Stimulants transporter Amphetamines Induce DA release and inhibits DAT No clear evidence of benefit Overall no significant effect, some evidence for response in subgroups of Neuroadaptations Inhibits DA and NE reuptake methamphetamine users Disulfiram Inhibits dopamine β-hydroxylase No clear evidence of benefit Acts through both dopaminergic and Modafinil Inconsistent results. Some evidence that compliant patients benefit glutaminergic pathways Atomoxetine NE No clear evidence of benefit Ibudilast Phosphodiesterase inhibitor No clear evidence of benefit in clinical trial with 125 participants Reduces glutamate by enhancing the N-acetylcysteine Large trial underway in Australia glutamate transporter Vigabatrin Inhibits GABA transaminase No clear evidence of benefit Some evidence of benefit in reduction of use, but primary outcome Topiramate Enhances GABA activity partly negative in trial of 140 participants increases NE, DA, and serotonin levels No clear evidence of benefit in clinical trial with 104 participants

Varenecline Nicotinic partial No clear evidence of benefit Other , Inhibit monoamine reuptake, other Reduction in use in small trial in MSM treated with mirtazapine which was Antidepressants Sertraline mechanisms confirmed with larger trial Inconsistent findings. One study with reduced positive urine drug screens, Naltrexone Antagonist at mu opioid receptor others negative Antipsychotics / No clear evidence of benefit, possibility of increased harm GABA, Voltage Dependent Calcium Baclofen, gabapentin No clear evidence of benefit and Channels Anti- Monoclonal to neutralize methamphetamine Phase 1 study underway methamphetamine activities antibody Note. DAT = dopamine transporter; GABA = γ-aminobutyric acid; BBB = brain barrier; MSM = cis or transgender men who have sex with men; NE = norepinephrine; TCA = antidepressants; CUD = cocaine use disorder.

16 Recent Reviews

• Chan B, Freeman M, Kondo K, et al. Pharmacotherapy for methamphetamine/amphetamine use disorder-a systematic review and meta-analysis. Addiction. 2019;114(12):2122-2136 • Lee NK, Jenner L, Harney A, Cameron J. Pharmacotherapy for amphetamine dependence: A systematic review. Drug Depend. 2018;191:309-337.

17 Methylphenidate • Stimulant that blocks reuptake of DA, NE • Has abuse/diversion potential • Hypertension/cardiac effects limit use • Five randomized clinical trials studying effects of methylphenidate for MUD have been reported • Based on randomized trials completed to date, there is low strength evidence supporting methylphenidate reducing methamphetamine use (based on systematic reviews)

18 Methylphenidate

• Ling et al., 2014: 110 methamphetamine dependent participants – sustained release methylphenidate vs. placebo showed no difference in the primary outcome measure of self-reported days of methamphetamine use in the last 30 days of active treatment – planned secondary analyses there were fewer self-reported methamphetamine use days from baseline through the active phase of treatment and lower craving scores compared to placebo (MPH-SR (Concerta®) 18 mg daily for week 1, 36 mg for week 2 and 54 mg for weeks 3–10) DOSE TITRATION IMPORTANT • Miles et al., 2013: Trial of sustained release methylphenidate vs. placebo in 79 methamphetamine/amphetamine users – No difference from placebo in positive urine drug screens – Better retention in methylphenidate treated participants

19 Topiramate

• • Sodium, Calcium channel and GABA effects • No abuse potential. Cognitive side effects limit use. • Two recent reviews (above) conclude there is some evidence to support topiramate for methamphetamine use • Evidence is limited to a few clinical trials

20 Topiramate • Elkashef 2012: 140 MUD participants treated with slow titration over 35 days to target dose of 200mg per day of topiramate – No difference in abstinence from methamphetamine in weeks 6-12 of the 13-week study, – Secondary analysis showed reduced weekly median urine methamphetamine levels and observer rated severity of dependence • Rezaie et al., 2016: 62 MUD participants with target dose of 200mg topiramate – Reduction in positive methamphetamine urine drug screen results at week 6 of a 10 week study compared to placebo (but no significant difference at all other weeks)

21 Bupropion

• • Weak DA reuptake inhibition, antagonist at nicotinic receptors • Seizure risk at higher doses • Several clinical trials • Some evidence of subgroup effects

22 

 

(From Elkashef et al., 2009) 23 Bupropion

• Elkashef 2008: 151 MUD participants treated 150 mg bupropion twice daily – No significant difference in abstinence from methamphetamine overall – Subgroup analysis showed male patients with lower levels of methamphetamine use responded better to bupropion • Anderson et al., 2015: 204 MUD participants who used less than daily 150mg sustained release bupropion daily – No difference with bupropion – Medication compliance poor

24 Mirtazapine

• Antidepressant • 5-HT2, NE, H1 antagonist • Sedation significant side effect • Two studies showing potential

25 Mirtazapine

• Colfax et al., 2011: 60 MUD participants treated 30 mg mirtazapine once daily (titrated up from 15mg daily after one week) – Sexually active; men who had sex with men and had methamphetamine use disorder – Participants were randomized to receive the study drug or placebo for 12 weeks – Mirtazapine group had fewer methamphetamine-positive urine test results compared with participants assigned to the placebo group. – Risky sexual behavior reduced in mirtazapine treated group

26 Mirtazapine

• Coffin et al., 2019: 120 MUD participants treated 30 mg mirtazapine once daily – Sexually active; cisgender men, transgender men, and transgender women who had sex with men and had methamphetamine use disorder – Participants were randomized to receive the study drug or placebo for 24 weeks – By week 12, the rate of methamphetamine-positive urine test results significantly declined among participants randomized to mirtazapine vs placebo. Mirtazapine resulted in reductions in positive urine test results at 24 weeks and 36 weeks vs placebo. – Depression and reduced in mirtazapine treated group – Medication compliance poor

27 Mirtazapine Stopped

Coffin et al., 2019

28 Modafinil

• Wakefulness promoting medication • Weak DA reuptake inhibition • Inconsistent results • Some evidence that compliant patients benefit

29 Modafinil

• Anderson et al., 2012: 210 treatment seeking MUD participants randomized to two doses of modafinil (200 or 400mg) – Overall no significant change in weekly percentage of participants having a methamphetamine non-use week – Participants that were compliant with modafinil treatment based on urine screens did show a greater maximum duration of methamphetamine abstinence • Similar findings in Shearer et al., 2009

30 Take Home Messages

• Overall, no large-scale trial has shown consistent results • Compliance has been a major problem in trials • Some medications did show effects in at least some patients, so may be an option (mirtazapine in patients who are not sleeping, etc.) • All medications have side effects. Need to be weighed against possible benefits • Since off-label, insurance may not cover prescriptions • Counseling/behavioral therapy still gold standard

31 Future Directions

• Could medications be more beneficial as relapse prevention treatments? • How can compliance be improved in studies? • What about combination treatments?

32 Questions? Case Presentation #1 Manhal Saleeby, MD • 12:35-12:55 [20 min] • 5 min: Presentation • 2 min: Clarifying questions- Spokes • 2 min: Clarifying questions – Hub • 2 min: Recommendations – Spokes • 2 min: Recommendations – Hub • 5 min: Summary - Hub

Reminder: Mute and Unmute to talk *6 for phone audio Use chat function for questions Reminder: Mute and Unmute to talk *6 for phone audio Use chat function for questions Reminder: Mute and Unmute to talk *6 for phone audio Use chat function for questions Main Question:

Reminder: Mute and Unmute to talk *6 for phone audio Use chat function for questions Case Presentation #2 Jen Phelps, LPN • 12:55pm-1:25pm [20 min] • 5 min: Presentation • 2 min: Clarifying questions- Spokes (participants) • 2 min: Clarifying questions – Hub • 2 min: Recommendations – Spokes (participants) • 2 min: Recommendations – Hub • 5 min: Summary - Hub

Reminder: Mute and Unmute to talk *6 for phone audio Use chat function for questions Reminder: Mute and Unmute to talk *6 for phone audio Use chat function for questions Reminder: Mute and Unmute to talk *6 for phone audio Use chat function for questions Reminder: Mute and Unmute to talk *6 for phone audio Use chat function for questions Main Question:

Reminder: Mute and Unmute to talk *6 for phone audio Use chat function for questions Case Studies

• Case studies • Submit: www.vcuhealth.org/echo • Receive feedback from participants and content experts • Earn $100 for presenting

Claim Your CME and Provide Feedback

• www.vcuhealth.org/echo

• To claim CME credit for today's session • Feedback • Overall feedback related to session content and flow? • Ideas for guest speakers? Access Your Evaluation and Claim Your CME Access Your Evaluation and Claim Your CME Access Your Evaluation and Claim Your CME

• www.vcuhealth.org/echo

• To view previously recorded clinics and claim credit Access Your Evaluation and Claim Your CME Access Your Evaluation and Claim Your CME VCU Virginia Opioid Addiction TeleECHO Clinics

Bi-Weekly Fridays - 12-1:30 pm

Mark Your Calendar --- Upcoming Sessions

March 6: Enhanced Recovery After Surgery: Opioid Reducing Program Nirav Patel, MD

March 20: : Are Patients Suffering or Are We Doing the Right Thing? Andrew Chapman, MD

April 3: Hep C and Opioids Richard Sterling, MD

Please refer and register at vcuhealth.org/echo THANK YOU!

Reminder: Mute and Unmute to talk *6 for phone audio Use chat function for questions