# Presentation: 062946

## Cognitive Behavioral Therapy and Naltrexone for Cocaine Dependence

- Joy M. Schmitz, Ph.D.
- Substance Abuse Research Center
- University of Texas Medical School
- Houston
- Supported by NIDA (DA-09262, DA-6143, DA-15801)

- APA 2004

## Why Combine Behavior Therapy and Medication?

- For the treatment of cocaine dependence, little benefit from pharmacotherapy or psychotherapy alone
- Each form of treatment may address distinct symptom areas, providing broader coverage
- Offset the potential drawbacks associated with either treatment
- Patient heterogeneity leads to differential response to treatment

**Notes:**
It’s not exactly known how txts work together, but in theory, it may be that they address different symptom areas using different mechanisms.  Meds target the biological system while beh therapies target coping strategies and problem-solving.  

So combining txts leads to better coverage of symptoms which, presumably, enhances outcome.

Another advantage of combination txts is that potential drawbacks associated with either txt may be offset by the other.  

Finally, patients are different and respond differently to treatments.  By combining txts you stand a better chance of meeting the diverse needs of the patient. Eventually, this could lead to better matching of patient to specific treatment.  

## Slide 3

**Notes:**
This study was published in 2001.  Coinvestigators included Dr’s Stotts, Rhoades, and Grabowski

## Study Design

**Pharmacotherapy**
**(Naltrexone)**

- 0 mg

- 50 mg

**Psycho-**
**Therapy**

**Drug Counseling**
**        ****(DC)**

**Relapse Prevention**
**        ****(RP)**

**Notes:**
It was set up according to a full 2 x 2 factorial design.

One main IV was NALTREXONE, placebo or 50 mg/d

The second IV was psychotherapy.  Here we compared Drug Counseling and Relapse Prevention therapy.  

We expected to find a MAIN EFFECT for medication, favoring the active condition, as well as a MAIN EFFECT for psychotherapy, favoring the RP condition.

But most importantly, we hypothesized an INTERACTION effect, with the best outcomes expected in the group of patients receiving 50 mg NTX and RP.

## Pharmacotherapy

***Naltrexone***
- Opiate antagonists attenuate cocaine's euphoric effects (Bain & Kornetsky, 1986; Kosten et al., 1992; Hubbell & Reid, 1995; Reid et al., 1993; 1996)** **
- Opiate antagonists decrease cocaine self-administration (DeVry et al., 1989; Mello et al., 1990; Ramsey & vanRee, 1991; Corrigall & Coen, 1991; Reid et al., 1995; 1996; 1997)
- Opiate antagonist treatment associated with lower rates of cocaine use (Kosten et al., 1989; Rosen & Kosten, 1991)

**Notes:**
There were a few reasons why we chose to examine NTX.

There was some indication that the opiate system was involved in the reinforcing effects of cocaine,  And that blocking opiate receptors with an antagonist, like NTX, might affect cocaine administration.

In the preclinical literature several studies demonstrated that pretx with an opiate antagonist 
	attenuated cocaine’s euphoric effects and
	was associated with decreased self-administration of cocaine.

In the clinic setting, two preliminary studies showed less cocaine use in opiate patients who received NTX treatment.

## Psychotherapy

***Relapse Prevention (RP)***
- Coping Skills Relapse Prevention Theory (Marlatt & Gordon, 1985)
- Components include functional analysis of situational factors associated with craving or drug use, self-monitoring and specific home practice exercises, general lifestyle modifications, handling a lapse training.

***Drug Counseling (DC)***
- General education, nondirective support, encouragement for abstinence-oriented behaviors (Woody et al., 1983; Luborsky et al., 1982)
- Components include assessment of problem areas (e.g., health, family, vocation), education about recovery, crisis management.

## Therapy Adherence

## Slide 8

**Notes:**
We enrolled a total of 85 patients.

The four groups did not differ on any baseline characteristics.

They were typical for our cocaine trial.

## Retention

- Log Rank Statistic = 1.72, *df *= 3, *p *= .63.

**Notes:**
So first we compared the groups on retention.  
And saw no differences.
Overall 30% of the patients completed treatment.

## Cocaine Use

**Therapy x Medication x Time:***  F* (2, 60) = 3.69,* p* < 0.03.

- *

**Notes:**
Then we looked at COCIANE USE.  
This slide is set up differently than the others.  Here I’ve plotted the proportion of COCAINE-NEGATIVE urines across time in treatment.

This study differs from other usual RCT in that it was set up as a RELAPSE PREVENTION study.  All subject first completed an initial detoxification phase in which they achieved abstinence before starting the medication trial.  (Abstinence was defined as 5 consecutive cocaine-negative urines).  

So this study focused on RELAPSE PREVENTION.  

So at INTAKE, we had 100% cocaine negative urines, and you can see that patients used again, early in tx, but that over time, those in the NTX-RP condition (LIGHT YELLOW BARS) were more likely to have cocaine-negative urines.  

This was supported statistically by a significant 3-way interaction.  Over time, those in the RP group who received 50 mg NTX used less cocaine than those in the other groups.

## Does homework compliance predict outcome?

- Cognitive-behavioral psychotherapies are based on the premise that clients are more likely to improve if they apply skills learned in treatment to situations outside treatment (i.e., homework).
- The relationship between homework compliance and treatment outcome is reliable and robust across different client problems (Kazantzis et al., 2002).

## CBT Homework

- Examples:
- Self-monitoring
- Trigger sheet
- Recognizing assertiveness
- Goal setting
- Coping records
- Awareness of problem thinking

## Motivation and homework completion on cocaine use during treatment

## Conclusions

- In cocaine-dependent patients, the combination of naltrexone 50 mg and Relapse Prevention therapy was effective in reducing cocaine use.
- Treatment integrity measures showed evidence of therapy adherence and discriminability.
-  For CBT, a positive relationship between homework compliance and cocaine outcome was found.  Motivation to change affected the direction of this relationship.
- Need to replicate and extend to determine the robustness of this treatment.

## Naltrexone Studies

- Naltrexone and relapse prevention treatment for cocaine-dependent patients
**Naltrexone and relapse prevention treatment for cocaine-****alcohol**** dependent patients**

## Study Design

**Pharmacotherapy**
**(Naltrexone)**

- 0 mg

- 50 mg

**Psycho-**
**Therapy**

**Drug Counseling**
**        ****(DC)**

**Relapse Prevention**
**        ****(RP)**

**Notes:**
It was set up according to a full 2 x 2 factorial design.

One main IV was NALTREXONE, placebo or 50 mg/d

The second IV was psychotherapy.  Here we compared Drug Counseling and Relapse Prevention therapy.  

We expected to find a MAIN EFFECT for medication, favoring the active condition, as well as a MAIN EFFECT for psychotherapy, favoring the RP condition.

But most importantly, we hypothesized an INTERACTION effect, with the best outcomes expected in the group of patients receiving 50 mg NTX and RP.

## TABLE 1

- Characteristics of Participants in Each Treatment Group

- a Attended at least six weeks of treatment.

## Retention

- Log Rank (df = 3) = 3.62, ns.

## Cocaine Use

- Time x Therapy* F* (11, 332) = 2.09, *p* < 0.02.

## Conclusions

- Naltrexone did not reduce cocaine or alcohol use in this sample of dually-dependent patients.
- Patients receiving Drug Counseling used less cocaine over time than those receiving Relapse Prevention.
- Naltrexone’s lack of efficacy in treating this type of comorbidity,  also reported by Hersh et al., 1998, may be due to greater impairment in this population.

## Pharmacotherapy

-  R01 DA15801

**Pharmacotherapy**
**(Naltrexone)**

- 0 mg

- 100 mg

**Behavior**
**Therapy**

**Relapse Prevention**
**        ****(RP)**

**            ****RP +**
**Conting. Manag. Proc**

## Men

**Results: % cocaine abstinent Ss                 *****Pettinati et al, 2004***

**Men**

## Conclusions

- Among cocaine dependent patients:
- 	Naltrexone 50mg
- reduced cocaine use
- was well tolerated
- worked best with CBT
- Among cocaine-alcohol dependent patients:
-   Naltrexone 50 mg
- ineffective with/without CBT

## Future Considerations

- Optimal dosing
- Combination pharmacotherapy
- Relapse prevention vs abstinence initiation
- Enhancing compliance, increasing motivation
- Patients’ conceptualization of behavior therapy + medication

## Treatment expectancies