Integrating Pharmacotherapy and Behavioral Therapy for Substance Use Disorders

I

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Dr. Weiss has previously consulted to

Alkermes, which manufactures extended-

release naltrexone (Vivitrol)

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•

Medication adherence

•

Define and attain SUD goals:

abstinence or reduction

•

Deal with other problems: mental

and physical health, interpersonal,

work/school, housing, etc.

3

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

Medications only work if you

take them.



 Many people don

’

t take them.

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

Perceived or real ineffectiveness



Intolerable side effects



Cost



Overly complex regimen

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

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

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

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

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

Denial of disorder



Poor/no plan for treatment adherence



Lack of understanding of the need for

consistent dosing



Misconceptions or fears about the

medications



Forgetfulness (perhaps in part due to the

disorder or the medication)

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

Desire to get high with the medication, e.g., taking

too much



Medication interferes with or blocks drug high



Patient does not want to mix alcohol/drugs with

medications



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

Family/friends/peer support group members

discourage use of medication



Perceived stigma attached to taking the medication

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

Clinician unsure about treatment’s effectiveness



Poor communication about rationale, risks/benefits,

and how to use the medication



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

Severe depression/pessimism about treatment



Anxiety about side effects



Impatience waiting for medication to work (taking too

much)

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

The approach to the patient



External reinforcement, e.g., family



Prescribing patterns

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

Actively discuss adherence issues



Are you taking your meds? 

How much 

are you taking?



Illness education (why patient needs medication)



Ask about obstacles to adherence (e.g.,

comprehension, emotions, complexity, cost)



Behavioral aids (Post-its, alarm on phone/watch)

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

Family education



Family support, e.g., disulfiram contract



Contingency management, e.g.,

rewards for taking medication

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

Simple regimens



Pill boxes



Longer-acting or “forgiving” medications



Depot medications (e.g., injectable

buprenorphine or naltrexone)

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Disulfiram

•

Naltrexone

•

Acamprosate

15

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•

Inhibits aldehyde dehydrogenase, an enzyme in

the metabolism of alcohol

•

Acetaldehyde poisoning when alcohol ingested

•

Reaction occurs 10-15 min. after drinking

•

Non-adherence very common

•

Only suitable for patients seeking 

abstinence

16

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•

Incorporated as part of behavioral couples therapy

•

Spousal monitoring

•

Mutual thanking

–

“Thanks for taking your disulfiram.”

–

“Thanks for reminding me and watching me.”

•

No discussion of past or future drinking outside of

meetings with therapist

17

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•

Reduced drinking

•

Greater marital satisfaction

•

Less intimate partner violence

•

Better functioning in children

18

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•

Mechanism of action: May reduce alcohol-induced

craving (

priming response

) and alcohol reward

•

Does not reduce likelihood of 

any 

drinking, but

reduces likelihood of 

heavy

 drinking; helps contain

a slip (lapse) rather than leading to relapse

•

Comes in oral and extended-release (4-week) IM

injectable form

•

Like with disulfiram, non-adherence is very

common, with resultant poor outcomes

19

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CBT includes discussion of 

abstinence violation

effect

•

Distinguishing between lapse (slip) and full-blown

relapse

•

Similar to mechanism of action of naltrexone

20

N

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+

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•

Anton et al. (2005)

•

160 pts on naltrexone or placebo randomized to

12 CBT or 4 motivational enhancement therapy

(MET) sessions over 12 weeks

•

Naltrexone (ntx) patients had longer time to

relapse than placebo

•

Ntx + CBT patients had best outcomes, better

than ntx + MET

•

Some conflicting studies on specific value of CBT

with ntx

21

A

c

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m

p

r

o

s

a

t

e

•

Mechanism of action: interacts with glutamate

and GABA neurotransmitters systems

•

May reduce protracted withdrawal symptoms

22

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:

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•

Requires 3x a day dosing

•

The ‘tid’ method

23

NIAAA COMBINE Study

•

Studied optimal combinations of medications,

behavioral Tx for alcohol use disorder (N=1,383)

•

Patients receive naltrexone, acamprosate, both, or

neither; all pts receiving pills received Medical Mgmt

•

Half of the patients received specialized

psychotherapy (the Combined Behavioral

Intervention, or CBI), in addition to Medical

Management (MM)

•

Results: Naltrexone, CBI both effective, but no

combinations improved outcomes

•

One cohort received CBI alone, no pills or MM:

enabled an examination of placebo effect (CBI vs.

CBI + placebo pills + MM)

         Anton et al., 2006

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Weiss et al., 2008

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

Overall health check



Advice to abstain from drinking



Check on medication: efficacy,

tolerability, 

adherence



Advice to attend mutual-help groups,

e.g., AA

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Chi-square = 7.38, df = 2, p < 0.03

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Partially

•

AA attendance during treatment was a

significant predictor of % days abstinent

during treatment (p=.03)

But

•

When the overall analysis was adjusted for

AA attendance during treatment, the

differences remained significant (p<0.001)

Pill-Taking

•

A daily reminder of the reason for

      the pill-taking

•

Reinforces recovery efforts

•

An additional benefit of medication adherence

Pharmacotherapy of

Opioid Use Disorder

I

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31

Buprenorphine and

Behavioral Interventions

D

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“Physicians must attest that they

have the capacity to refer

addiction treatment patients for

appropriate counseling”

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•

Largest study of treatment of prescription opioid

dependence (N=653 at 10 U.S. sites)

•

Studied different lengths of buprenorphine-

naloxone (bup-nx) + different intensities of

counseling

•

‘Success’: abstinence or near-abstinence from

opioids



7% success with 4-week taper



49% success while stable on bup-nx x 12 wks



9% success after 2nd taper after 12-wk bup-nx

•

Adding counseling to bup-nx and weekly medical

management did 

not

 improve outcome

                 Weiss et al. 2011

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t



4 major studies have shown that adding

counseling to buprenorphine + medical

management (MM) is not superior to

buprenorphine + MM alone

Carroll & Weiss, 2017

K

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y

q

u

e

s

t

i

o

n

s

1.

Is buprenorphine that effective?

2.

Is MM that effective?

3.

Is counseling that ineffective for this

population?

4.

Are there subgroups of patients who benefit

from additional counseling, including those

with co-occurring psychiatric disorders?

Wei

Q

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s

t

i

o

n

#

1

:

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f

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?



Compared to what?



Yes-- but room for improvement

Wei

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n

#

2

:

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M

M



Overall health check



Urine monitoring



Check on medication: efficacy,

adherence, tolerability



Monitor craving



Advice to abstain



Advice to attend mutual-help groups



But, MM in these studies more intensive

than community standard

Wei

Q

u

e

s

t

i

o

n

#

3

:

A

r

e

b

e

h

a

v

i

o

r

a

l

t

r

e

a

t

m

e

n

t

s

t

h

a

t

i

n

e

f

f

e

c

t

i

v

e

w

i

t

h

t

h

i

s

p

o

p

u

l

a

t

i

o

n

?

A

r

e

a

l

l

b

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h

a

v

i

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a

l

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v

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p

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p

u

l

a

t

i

o

n

?

    No

A

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f

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c

t

i

v

e

?



3 RCTs show 

benefit 

of behavioral tx



All had either contingency

management, computerized treatment,

or both



App-based interventions currently in

use, some of them offering contingency

management within the app

Bickel et al., 2000

Schottenfeld et al., 2005

Christensen et al., 2014

R

C

T

s

v

s

.

R

e

a

l

-

w

o

r

l

d

R

e

s

u

l

t

s



Non-randomized observational and

database studies may yield different

results from RCTs



Different level of patient motivation



No research infrastructure support

A

r

e

b

e

h

a

v

i

o

r

a

l

i

n

t

e

r

v

e

n

t

i

o

n

s

t

h

a

t

i

n

e

f

f

e

c

t

i

v

e

?

Samples., 2022



Retrospective study of Medicaid data

base, 2013-18 in ~5,000 pts with OUD



74% of pts had no or few (<1

day/month) psychosocial services



17% had low-intensity services (avg. <2

days/month)



9% had high-intensity services (avg. 7

days/month)

A

r

e

b

e

h

a

v

i

o

r

a

l

i

n

t

e

r

v

e

n

t

i

o

n

s

t

h

a

t

i

n

e

f

f

e

c

t

i

v

e

?

Samples., 2022



Buprenorphine retention was higher in

the 2 groups receiving psychosocial

services



Median days retained:136 vs.145 vs. 84

for high, low, and no services



>

 180 days retained: 42% vs. 43% vs.

32% 

for high, low, and no services



Some

 patients do well with bupe and MM

and no other psychosocial services

A

r

e

b

e

h

a

v

i

o

r

a

l

i

n

t

e

r

v

e

n

t

i

o

n

s

t

h

a

t

i

n

e

f

f

e

c

t

i

v

e

?

Samples., 2022



Distinctions between data base studies

vs. RCTs



Non-randomized studies: high-intensity tx

can reflect poor initial outcomes



MM in RCTs could approximate low or

even high-intensity services in database

studies

Wei

Q

u

e

s

t

i

o

n

#

4

:

A

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b

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a

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n

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s

?

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a

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l

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r

v

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n

t

i

o

n

s

?

POATS analysis compared outcomes of

patients with and without additional

counseling among those pts with



More severe drug problems



Co-occurring psychiatric illness

D

i

d

d

r

u

g

c

o

u

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l

i

n

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s

?

(

n

=

2

6

6

w

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e

(

>

6

0

%

)

Interaction between heroin & treatment p=.03                               

Weiss et al., 2014

D

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19% of POATS pts had PTSD



Those 

with

 PTSD had more successful

outcomes if they received drug counseling

(67% successful with MM + counseling vs.

36% successful with MM alone)



No difference between conditions for those

without

 PTSD



Interaction significant (p<0.05)

McHugh et al., 2021

W

h

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:

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•

Agonist treatment 

had by far the best correlation with

opioid abstinence over time, with odds ratios = 3-5

•

Mutual-help 

group attendance also correlated with

abstinence, with odds ratios = 2-3

Weiss et al.,  2019

W

h

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t

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S

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.

,

2

0

1

8

)



Shared medical visit



Group-based OUD treatment



Both models seem feasible, well-accepted



Lower-cost



No rigorous randomized controlled trials vs.

individual therapy or vs. MM alone



Research needed on this model, though

group therapy research is daunting

methodologically

W

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a

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a

b

o

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t

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s



Case management



Recovery coaches/peer navigators



Mindfulness



Exercise



Yoga



Acupuncture



Telehealth

H

o

w

t

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p

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o

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d

?

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s

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r

p

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e



Many patients do well with buprenorphine

and MM alone, but we’re not good at

predicting who will and who won’t do well



Limited resources for MM, behavioral tx



Some patients 

don’t 

want 

counseling



Understanding the importance of 

early

treatment response

 may help our decision-

making

D

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R

a

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i

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a

l

e

1)

 Some medications, e.g., antidepressants, may

take a number of weeks to work optimally.

Therefore, waiting several weeks to examine

treatment response may be helpful.

2)  What about the typical time course of treatment

response to buprenorphine in treatment of OUD?

3)  Knowing this could help guide clinical practice

early in the treatment of this population.

M

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)

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y

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x

r

e

s

p

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n

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e

(

c

o

n

t

.

)

Luo et al., 2023

•

Harmonized data from 3 large studies of OUD

treatment

•

First 3 weeks were critical predictors of relapse

   (4 consecutive weeks of use)

•

Negative urine tests in weeks 1-3: 13% relapsed

•

Positive or missing urines in weeks 1-3: 85% relapsed

C

o

n

c

l

u

s

i

o

n

s

:

t

h

e

i

m

p

o

r

t

a

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c

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f

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a

r

l

y

t

x

r

e

s

p

o

n

s

e

1)

The 

first 2-3 weeks 

of treatment with buprenorphine yield

important information

2) Patients who abstain from opioids in the first 2-3 weeks have a

good-to-excellent 

chance of good 12-week outcome

3) However, those who use opioids in each of the first 2-3 weeks

(even in week 1 alone) are far less likely to have a good 12-

week outcome

4) Although not possible in POATS, increasing intensity of

psychosocial treatment should be considered

           McDermott et al., 2015

N

a

l

t

r

e

x

o

n

e

a

n

d

B

e

h

a

v

i

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r

a

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t

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v

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p

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d

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e

D

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s

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v

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x

o

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t

o

f

o

p

i

o

i

d

u

s

e

d

i

s

o

r

d

e

r



Adherence to oral naltrexone in OUD is

poor; oral naltrexone ineffective for most

OUD patients



This was a major reason for development

of XR-naltrexone



Some positive results for behavioral Rx,

but limited



Contingency management: rewarding taking

medication and/or negative urine tests



Behavioral family therapy/observed Rx-taking

Carroll 2001, Nunes 2006, Sullivan 2018

C

o

n

c

l

u

s

i

o

n

•

Many factors influence the interaction

between meds and behavioral Rx

–

Efficacy of medication

–

Severity of the SUD and associated

conditions (e.g., psychiatric illness)

–

Mechanism of action of medication

–

Tx goal: abstinence vs. reduction

–

Who is delivering the behavioral Rx

–

Intensity and context of treatment

70

Thank you to NIDA for research

support and to my colleagues at

McLean Hospital and the NIDA

Clinical Trials Network

Thank you to NIDA for research

support and to my colleagues at

McLean Hospital and the NIDA

Clinical Trials Network

Questions?