Review ArticlePharmacotherapy for pregnant women with addictions
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,
References (104)
- et al.
Is benzodiazepine use during pregnancy really teratogenic?
Reprod Toxicol
(1998) - et al.
Effects of exposure to benzodiazepine during fetal life
Lancet
(1992) - et al.
The teratogenic effect of carbamazepine: a meta-analysis of 1255 exposures
Reprod Toxicol
(2002) - et al.
Effect of folic acid supplementation on congenital malformations due to anticonvulsant drugs
Eur J Obstet Gynecol Reprod Biol
(1984) - et al.
Fetal growth, major malformations, and minor anomalies in infants born to women receiving valproic acid
J Pediatr
(1986) - et al.
Failure of periconceptual folic acid to prevent a neural tube defect in the offspring of a mother taking sodium valproate
Seizure
(1999) - et al.
Limb-reduction anomalies in infants born to disulfiram-treated alcoholic mothers
Lancet
(1977) - et al.
Prenatal naltrexone facilitates male sexual behavior in the rat
Pharmacol Biochem Behav
(1996) - et al.
Maternal methadone dose and neonatal withdrawal
Am J Obstet Gynecol
(2003) - et al.
A controlled comparison of buprenorphine and clonidine for acute detoxification from opioids
Drug Alcohol Depend
(1994)
Use of buprenorphine in pregnancy: patient management and effects on the neonate
Drug Alcohol Depend
Opioid detoxification in pregnancy
Obstet Gynecol
Alcohol, smoking and incidence of spontaneous abortion in first and second trimester
Lancet
Fetal hemodynamic response to maternal intravenous nicotine administration
Am J Obstet Gynecol
Transdermal nicotine replacement in pregnancy: maternal pharmacokinetics and fetal effects
Am J Obstet Gynecol
Effects of transdermal nicotine or smoking on nicotine concentrations and maternal-fetal hemodynamics
Obstet Gynecol
Nicotine patch use in pregnancy: nicotine and cotinine levels and fetal effects
Am J Obstet Gynecol
Effectiveness of propranolol for cocaine dependence treatment may depend on cocaine withdrawal symptom severity
Drug Alcohol Depend
Fetal outcome following intrauterine amantadine exposure
Reprod Toxicol
Substance abuse in pregnancy
ACOG Tech Bull
Epidemiology of substance use disorders in women
Obstet Gynecol Clin N Am
The prevalence of substance abuse among pregnant women in Utah
Am J Obstet Gynecol
The prevalence of illicit drug and alcohol use during pregnancy and discrepancies in mandatory reporting in Pinellas County, Florida
N Engl J Med
Current statewide prevalence of illicit drug use by pregnant women: Rhode Island
MMWR Morb Mortal Wkly Rep
Screening for substance use in pregnancy: a practical approach for the primary care physician
Am J Obstet Gynecol
Drug use among women delivering live births: 1992
NIDA survey provides first national data on drug use during pregnancy
NIDA Notes
Co-occurring psychiatric disorders in women with addictions
Obstet Gynecol Clin N Am
Benzodrozepines and other psychotropic drugs abused by patients on a methadone maintenance program: familiarity and preference
J Clin Psychopharmacol
Gender differences in pharmaco/kinetics and pharmacodynamics of psychotropic medication
Am J Psychiatry
Lack of relation of oral clefts to diazepam use during pregnancy
N Engl J Med
The effect of benzodiazepines on the fetus and the newborn
Neuropediatrics
Neurodevelopment in late infancy after prenatal exposure to benzodiazepines: a prospective study
Neuropediatrics
Use of benzodiazepines during pregnancy, labour and lactation, with particular reference to pharmacokinetic considerations
Drugs
Floppy infant syndrome: Is oxazepam the answer?
Lancet
Prenatal exposure to diazepam alters behavioral development in rats
Science
Effect of benzodiazepines in neonates
N Engl J Med
Double-blind controlled trial comparing carbamazepine to oxazepam treatment of alcohol withdrawal
Am J Psychiatry
Carbamazepine versus oxazepam in the treatment of alcohol withdrawal: a double-blind study
Alcohol Alcohol
The effects of carbamazepine and lorazepam on single versus multiple previous alcohol withdrawals in an outpatient randomized trial
J Gen Intern Med
Benzodiazepines and other sedative-hypnotics
Quality Standards Subcommittee of the American Academy of Neurology. Practice parameter: management issues for women with epilepsy
Neurology
Folic acid antagonist during pregnancy and the risk of birth defects
N Engl J Med
Teratogenic effects of carbamazepine
N Engl J Med
Psychomotor development and minor anomalies in children exposed to antiepileptic drugs in utero: a prospective population-based study
Dev Med Child Neurol
Divalproex sodium in alcohol withdrawal: a randomized double-blind placebo-controlled clinical trial
Alcohol Clin Exp Res
The fetal valproate syndrome
Am J Med Genet
Antiepileptic drug treatment in pregnancy: drug side effects in the neonate and neurological outcome
Acta Paediatr
Cited by (70)
Substance Abuse in Pregnancy
2022, Maternal Cardiac Care: A Guide to Managing Pregnant Women with Heart DiseaseAnalysis of natural product regulation of opioid receptors in the treatment of human disease
2018, Pharmacology and TherapeuticsSuccess of smoking cessation interventions during pregnancy
2016, American Journal of Obstetrics and GynecologyThe management of alcohol withdrawal in pregnancy - case report, literature review and preliminary recommendations
2015, General Hospital PsychiatryCitation Excerpt :Owing to the inconclusively proven association of benzodiazepines with teratogenicity, alternate treatments have been suggested. These include hospitalization with gradual reduction in amount of alcohol consumed, hydroxyzine, phenobarbital and acupuncture [12]; and, in late pregnancy, carbamazepine, valproic acid and clonidine [13]. However, these are recommendations extrapolated from data on nonpregnant adults.
Interventions Addressing Cannabis Use During Pregnancy: A Systematic Review
2023, Journal of Addiction MedicineMaintenance agonist treatments for opiate-dependent pregnant women
2020, Cochrane Database of Systematic Reviews
Supported by the Seligman Perinatal Research Fund.