Review Article
Pharmacotherapy for pregnant women with addictions

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Objective

Dependence on alcohol, nicotine, or illicit drugs during pregnancy continues to be a problem of major medical, social, and fetal consequences. The purpose of this systematic review was to summarize current experience that pertains to pharmacotherapy for pregnant women with specific chemical addictions.

Study design

Studies were identified through Medline and HealthSTAR (1979-2003) that linked specific pharmacotherapy with pregnancy. This article reviews the English language literature for clinical studies that link the 2 conditions. In addition, reference lists of all articles that were obtained were evaluated for other potential citations.

Results

Pregnant women are excluded systematically from almost all drug trials. Most knowledge about the fetal effects from maternal substance and medication use comes from animal data and from case reports and small clinical series. With the exception of methadone and nicotine replacement, clinical experience with antiaddictive medications in pregnant women is either very limited (alcohol, stimulants) or nonexistent (cannabis, hallucinogens).

Conclusion

Antiaddiction medications are important in the treatment of pregnant women with opioid and nicotine dependence and are of growing importance in the treatment of alcohol and stimulant dependence. Future directions will be toward increasing knowledge about current drug therapy and in developing new antiaddiction medications.

Section snippets

Substance use during pregnancy

Substance use is most prevalent in reproductive-aged people. In a survey among women aged 15 to 44 years, almost 90% of the women drank alcohol; approximately 44% of the women smoked marijuana, and at least 14% of the women used cocaine.1 Women have an estimated lifetime prevalence of 17.9% and a 12-month prevalence of 6.6% for any substance use disorder (excluding nicotine dependence). Although substance use disorders are still more prevalent in men than in women, comparable rates of alcohol,

Fetal effects from substance abuse

Unbound drugs and metabolites generally cross the placenta easily and enter into the fetal central nervous system. Our search revealed that most knowledge about the effects of these substances on embryonic/fetal development comes either from animal data or from case reports, adverse event reports, or small clinical series in humans. For most substances of abuse, data are either insufficient or inconsistent, which prevents the identification of a causal relation between a specific substance and

Principles of treatment during pregnancy

In treating pregnant women with a substance dependence, psychologic and pharmacologic treatments are often intertwined. Effective psychosocial treatments for women with addictions are many: contingency treatment, community reinforcement, behavioral marital therapy, cognitive behavioral skills training, motivational enhancement therapy, 12-step approaches, and “seeking safety” (a therapy designed for addicted women with co-occurring post–traumatic stress disorder).

As with all medications taken

Alcohol dependence

Alcohol affects several neurotransmitter systems, including gamma-aminobutyric acid, glutamate, serotonin, dopamine, norepinephrine, and endogenous opioid systems. All receptors are believed to be present in the fetus from early in gestation. A stepwise treatment plan for detoxification followed by minimizing relapse is proposed.

Detoxification

Benzodiazepines remain a first-line therapy for alcohol withdrawal. All members of the benzodiazepine class act at their own receptors, which are coupled with the gamma-aminobutyric acid–A receptor. This receptor complex mediates an increase in inhibitory neurotransmission that counteracts the excitatory state of the brain in alcohol withdrawal. Longer-acting agents, such as chlordiazepoxide, provide a smoother withdrawal during pregnancy, with fewer breakthroughs or rebound symptoms, than

Preventing or minimizing relapse

Disulfiram, approved by the FDA in 1952 for the abstinence phase of alcohol dependence, inhibits aldehyde dehydrogenase that leads to an accumulation of acetaldehyde when alcohol is ingested; symptoms of the disulfiram-alcohol reaction include facial flushing, tachycardia, hypotension, nausea, vomiting, and general malaise. Disulfiram treatment has met with mixed results in controlled studies of nonpregnant adults.42 Certain persons may not feel capable of abstinence without it and may wish to

Opioid dependence

Signs and symptoms of opioid withdrawal can be understood as a physiologic rebound from their chronic effects on brain function. Opioids or opiates act by binding to specific types of opioid receptors (μ, δ, and κ) that are distributed throughout the central nervous system. The phenomenon of cross-tolerance explains the efficacy of substituting 1 opioid for another. Like alcohol pharmacotherapy, drug treatment for opioid dependence involves detoxification and maintenance/relapse prevention

Nicotine dependence

FDA-approved medications for smoking cessation include several nicotine replacement therapies (gum, transdermal patch, lozenge, inhaler, and nasal spray) and an antidepressant (bupropion). There is no quantity criterion (eg, number of cigarettes smoked daily) for prescribing an antiaddictive medication, although one-half pack per day is considered to be excessive. An extensive body of research on pharmacotherapy of nicotine dependence includes >6000 studies and 50 meta-analyses.79 The use of

Stimulant dependence

Currently, there is no FDA-approved or clearly effective medication for the treatment of cocaine, amphetamine, or other stimulant dependence. Most pharmacotherapies for addiction to stimulants reduce the symptoms of a protracted withdrawal and craving, although there are investigational agents that also aim to reduce the rewarding effects of stimulants. Protracted withdrawal can last weeks to months and may lead to a relapse. A physiologic rebound of intoxicating effects explains many of the

Cannabis dependence

Marijuana from cannabis plants is the most common illicit drug used during pregnancy. It is taken commonly in combination with alcohol, tobacco, and other illicit substances. Several active compounds with various effects are found in cannabis plants, but the primary active agent is delta-9-tetrahydrocannabinol. Placental transfer of delta-9-tetrahydrocannabinol has been well documented in animals and humans.100., 101.

There is no indication that a pattern of minor malformations results from

Clinical applications for the obstetrician

Obstetricians have an ethical obligation to ask universal screening questions about substance use and to determine when to implement a brief intervention and selectively refer affected patients to receive counseling and medical care that is state-of-the-art, comprehensive, and effective. Progress in addiction pharmacotherapy will depend on success in 2 areas: (1) increasing the availability and usefulness of the agents that are currently prescribed and (2) focusing on new classes of drugs,

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