# Presentation: 207116

## Drug Treatment Issues in Drug-Dependent, Pregnant Women 

- Hendrée E. Jones, Ph.D. Department of Psychiatry
- and Behavioral SciencesJohns Hopkins University School of Medicine
- Baltimore, Maryland

## Disclosure

- During this presentation at the annual APA meeting, Dr. Jones will be discussing the uses of commercial products not yet approved for this purpose by the FDA.  She has no actual or potential conflict of interest in regards to this program.

## Presentation Goals

**Use of medication to treat opioid dependence during pregnancy**
**Clinical trial of methadone and buprenorphine during pregnancy**
**Behavioral interventions enhance maternal outcomes **

## Studies of Medication During Pregnancy

**Controversial**
**Some say unethical**
**Stigma associated with medication treatment for pregnant women is severe**

## Goals of Opioid Agonist Treatment 	

**Cessation of opioid use**
**Stabilize intrauterine environment**
**Increased prenatal care compliance**
**Enhanced pregnancy outcomes**

## Methadone is effective during pregnancy

**Methadone is *****recommended *****for the treatment of opioid-dependent women**
** ****Over 30 years of experience and research**
**Not appear to have teratogenic potential**

## Neonatal Abstinence Syndrome (NAS)

** **_**Neuralgic excitability**_** (hyperactivity, irritability, sleep disturbance)**
_**Gastrointestinal dysfunction**_** **
**   ****(uncoordinated sucking/swallowing, vomiting)**
_**Autonomic Signs**_** (fever, sweating, nasal stuffiness)**

## The NAS of Opioid-Exposed Neonates

**55-90% exhibit  NAS**
**Methadone dose relationship to NAS     severity is inconsistent**
**Onset within 48 to 72 hours after birth**
**Subacute signs up to 12 months**

## Buprenorphine

**A derivative of thebaine**
**Marketed as Subutex                         or Suboxone**

- Full

- Agonist

- Full

- Antagonist

- Heroin

- Methadone

- Morphine

- Naltrexone

- Naloxone

-  Nalmefene

## Buprenorphine

**Birth outcomes improved with agonist therapy (e.g., methadone)**
**Withdrawal associated with agonist therapy can require hospitalization**
**Buprenorphine reported to produce less physical dependence in adults**

## Case Reports and Open-Label Studies

**Since 1995, 23 reports of prenatal exposure to buprenorphine **
**22 reports from Europe and 1 from U.S.**
**Number of cases ranged from 1 to 153 (median=6) **
**TOTAL 338 babies**

## Outline

**Use of medication to treat opioid dependence during pregnancy**
**Clinical trial of methadone and buprenorphine during pregnancy**
**Behavioral interventions enhance mother and child outcomes **

## Randomized Controlled Study

**Double-blind (staff and patient)**
**Double-dummy (two medications) **
**Two groups: Methadone or Buprenorphine**
**Flexible dosing **
** ****Methadone 40-100 mg **
** ****Buprenorphine 4-24 mg**

## Setting: Center for Addiction & Pregnancy

- Interdisciplinary Approach
- Psychiatry
- Obstetrics
- Pediatrics
- Nursing

## Criteria

**Inclusion:**
-   **18 - 40 years of age**
**  ****Gestational age 16 - 30 weeks**
**  ****Opioid dependent (DSM-IV, SCID I)**
**  ****Recent opioid use**
**  ****Opioid positive urine**

## Criteria

**Exclusion:**
**  ****Methadone positive urine at admission**
**  ****DSM IV axis I current diagnosis other    ****	****than psychoactive substance use**
**  ****Serious medical or psychiatric illness**
**  ****Diagnosis of preterm labor**
**  ****Congenital fetal malformation**
**  ****Current alcohol abuse/dependence**
**  ****Benzodiazepine use **
**(8 or more times/month and/or 2 or more times/week)**

## Primary Outcome Measures                     Infant

**Neonatal Abstinence Syndrome **
**   ****(NAS)**
**Length of Hospital Stay**
**   ****(LOS)**

## Selected Secondary Outcome Measures

**Maternal **
**Days of treatment**
**Prenatal care visits**
**Illicit drug use**
**Infant**
**Physical birth parameters**

## Patient Flow

**Number screened**
**1490**

**Not Qualify Initially**
**1433**

**Qualify and sign consent**
**57**

**Randomized **
**30**

**Buprenorphine**
**15**

**Methadone**
**15**

**Buprenorphine**
**9**

**Methadone**
**11**

## Induction

- Patients stabilized on immediate release morphine (IRM) prior to randomization
- Is transition from IRM to methadone or buprenorphine similar?
- Withdrawal scores over first 3 days appeared mild for both medications

## Maternal OutcomeDrug Use During Pregnancy

**% opioid +****	****	****	****15.6****	****	****16.7**
**% cocaine +****	****	****11.2****	****	****15.2**
**% amphetamine +****	****  0.0****	****	****  0.0**
**% barbiturates +****	****  0.0****	****	****  0.0**
**% benzo +****	****	**** ****	****  0.4****	****	****  2.5**
**% THC+****	****	****  ****	****  7.5****	****	****  0.0**

- Methadone
-        N=11

- Buprenorphine
-      N=9

## Maternal Characteristics

**    ****EGA (weeks)****	****	****23.6****	****	****22.8**
**    ****Education (yrs)****	****10.0****	****	****10.3**
**% Employed****	**** ****	**** 0.0****	****	****  0.0**
**    ****Age (yrs)****	****	****30.3****	****	****30.0**

- Methadone
-        N=11

- Buprenorphine
-      N=9

## Maternal Outcomes

**Days in Treatment****	****	****         99.9****	****	****115.6**
**Prenatal care visits****	****	****3.4****	****	****    3.6**
**LOS mom****	****	****	****	****2.2****	****	****    2.2**
**C section %****	****	****	****	****9.1****	****	****  11.1**
**Tox. + delivery (mom)%****	****	****9.1****	****	****    0.0**
**normal presentation %****	****	****100****	****	****   100**
**Preterm birth %****	****	****	****9.1****	****	****    0.0**
**Gestational age delivery****	****	****38.8****	****	****  38.8**
**Ave. dose at delivery (mg) ****	****79.1****	****	****  18.7**
**	****	**

- Methadone
- N=11

- Buprenorphine
- N=9

## Birth Outcomes

**Birth Weight (gm)*        3001.8****	****       3530.4**
**LOS baby****	****	****	****  8.1****	****	****  6.8**** ****	**
**% NICU treatment****	****	****18.0****	****	****10.0**
**APGAR 1****	****	****	****  8.3****	****	****  8.1**
**APGAR 5****	****	****	****  8.9****	****	****  8.7**
**Length (cm)*****	****	****49.6****	****	****52.8**
**Head Cir. (cm)*****	****	****33.2****	****	****34.9**
**%Tox + (Baby)*****	****	****  0.0****	****	****20.0**

- Methadone
-        N=11

- Buprenorphine
- N=9 deliveries (10 babies)

- * data safety monitoring board recommended removing twin data from these variables

## Limitations of Study

**Small sample size**
**I/E criteria limits generalizability**
**Nicotine exposure and effect on NAS  needs more study**
**Long-term outcomes beyond scope of study **

## Conclusions

**Both methadone and buprenorphine provide positive benefits to mothers**
**100% of infants had NAS signs/symptoms**
**Tendency for fewer buprenorphine-exposed babies to be treated for NAS**
**Significantly fewer days of hospitalization with buprenorphine exposure**

## Bottom Line

**Both medications have strong support to document safety and efficacy for mother and infant**
**NAS is only part of the complete risk:benefit ratio **
** ****More medication options will improve the treatment of pregnant women**

## Issues Pregnant, Drug-Dependent Women Face

**Multigenerational**
**	****drug use**
**Lack of education**
**Maladaptive behaviors**
**poor self-control**
**trust issues**
**Legal **
**Parenting**

**Unstable housing**
**Victimization and  violence**
** ****physical **
** ****sexual **
** ****emotional**
**Severe stigma**
**Other psychiatric issues**

## Presentation Goals

**Use of medication to treat opioid dependence during pregnancy**
**Clinical trial of methadone and buprenorphine during pregnancy**
**Behavioral Interventions enhance maternal outcomes**

## Types of Behavioral Interventions Examined at CAP 

**Contingency Management**
**Rewards for drug-abstinence include housing, gift certificates, goods and services**
**Community Reinforcement Approach**
**Motivational Interviewing**

## Relationships as Barriers to Treatment

**Female drug use starts and continues in context of male romantic relationships**
**Level of partner support impacts outcomes among pregnant methadone-maintained women (Jeremy, 1984; Marcus, 1984)**

## Women’s Treatment Retention

- *

**Mean relationship of 4 yrs +**
** ****Drug using partners**
**      ****-less employed**
**      ****- less supportive **
**        ****of woman’s treatment**
**      ****-more legal involvement**
**      ****-more dental and**
**       ****medical needs**

***** P<0.05; Data adapted from Drug and Alcohol Dependence (2003)

## Partner Treatment

- 2 group randomized design
- Control-- receive weekly support group
- Intervention --
- Methadone or detox + aftercare
- MI type counseling
- abstinent contingent vouchers
-  1, 3, and 6 month follow-up interviews

## Partner Results

- 35 years old
- 73% unemployed
- 59% African-American
- 72% used cocaine
- 94% believed they were the father of the baby

## Intervention Increases Drug Abstinence in Male Partners

- *

***p**_**<**_**.05**

## Intervention Increases Drug Abstinence in Women

- *

***p**_**<**_**.05**

## Intervention Increases Partner Support of the Woman

***p**_**<**_**.05**

- *

## Conclusions

**Interventions are available to engage and retain male partners**
**Treating the male partner is associated with enhanced treatment outcomes for pregnant opioid-dependent women**

## Take Home Message

**Pregnancy is area where most certainty is desired, but there is often the least data  **
** ****More medication options will improve the treatment of pregnant women  **
** ****Engaging and treating the male drug using partners can improve the outcomes of women in drug treatment**

## Acknowledgements

**Rolley “Ed” Johnson **
**Patients and infants**
**NIDA R01 DA12220 and DA13496**
**Co-Investigators**
**Staff at Center for Addiction and Pregnancy**
**Staff at BPRU**