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Adderall and ritalin: potential influence on perinatal health.

Potential Problems of Common Drugs Used to Treat Attention Deficit Disorders

Prescription amphetamines and amphetamine-like drugs have potential for abuse. There should be increasing concern about prenatal exposure to these substances. This article focuses primarily on the abuse of two drugs: Adderall (amphetamine salts) and Ritalin (methylphenidate). These drugs are widely used for treatment of attention-deficit disorder (ADD) and attention-deficit/hyperactivity disorder (ADHD). ADD and ADHD are used interchangeably in this article, even though the author is aware that they are different. The article merely touches upon these disorders; thorough and comprehensive description of these disorders is not the intent of the article. The objective of the article is to relay how two of the drugs used to treat these disorders can be misused and why, along with potential dangers of the drugs, particularly in women of childbearing age.

Brief Overview of ADHD

In the United States alone the number of children and teens diagnosed with ADHD increased by 66% between 2000 and 2010, bringing the number to 10.4 million (Edmunds & Mayhew, 2014). In 2003, ADHD was estimated to affect 2-6% of adults. It is probably underestimated how many adults have ADHD because large scale mental disorder screening does not usually include adult ADHD (Weiss & Murray, 2003). According to several sources, Adderall and Ritalin appear to be very popular substances abused by traditional college-age students (DeSantis, Webb, & Noar, 2008; Herman et al., 2011; Teter, McCabe, LaGrange, Cranford, & Boyd, 2006). College students are prime child-bearing age. Considering potential adverse effects of a mother's perinatal use of Adderall and Ritalin, it is important for childbirth educators to screen current and future clients for abuse of these drugs, educating about possible dangers.

Definition of Terms

Central nervous system stimulants increase wakefulness and focus of attention and diminish appetite and fatigue. Examples include cocaine, amphetamines, dextroamphetamines, amphetamine-derivatives such as methylphenidate, methamphetamines, and caffeine. Three types of synthetic psychostimulants are amphetamine compounds, methylphenidate, and dextroamphetamine (Mayhew, 2007). "These drugs are generally recognized as addictive, meaning that tolerance and a withdrawal syndrome can occur" (Hamilton, 2009, p. 893). Adderall is an intermediate-acting amphetamine/dextroamphetamine compound (with Adderall XR being long-acting). Ritalin is a short-acting methylphenidate (with Ritalin SR being intermediate-acting and Ritalin LA being long-acting) (Edmunds & Mayhew, 2014).

Youth and young adults sometimes intentionally abuse prescription medications. These are not limited to but do include stimulants. Intentional abuse is defined as use "for reasons other than those for which the drug is legitimately prescribed" (Hamilton, 2009, p. 892). This is also known as illicit use. Nonmedical use of prescription drugs (NMUPD) is a major public health issue and is defined as "the intentional use of an approved medication without a prescription, in a manner other than how it was prescribed, for purposes other than prescribed, or for the experience or feeling the medication can produce" (Bettinardi-Angres, Bickelhaupt, & Bologeorges, 2012, p. 39). Non-prescribed means that the user of the drug "did not obtain the drug through a physician's prescription written specifically for the user" (Hernandez & Nelson, 2010, p. 308). Many of these terms are often used interchangeably.

Nonmedical use of prescription drugs (NMUPD) is a major public health issue

The term neuroenhancement means drug use in healthy people who do not need stimulants who attempt to improve their cognitive, emotional, and motivational functions by using the drug (Repantis, Schlattmann, Laisney, & Heuser, 2010).

Pharmacological Treatment of ADHD

First-line drugs for treatment of ADHD are Adderall (amphetamine salts), Ritalin (methylphenidate), and Dexedrine (dextroamphetamine). The mechanisms of these drugs serve to regulate neurobiologic processes to allow individuals who have ADD or ADHD to better concentrate, be less forgetful, be more organized, and make better decisions than they can without the drug (Edmunds & Mayhew, 2014). Adverse effects of stimulants in general include cardiovascular symptoms such as hypertension, tachycardia, vasospasm, and dysrhythmia in addition to neurological and psychiatric symptoms (Hernandez & Nelson, 2010). Detailed explanation of the pathophysiology of ADHD is beyond the scope of this article; however, the two most commonly prescribed drugs for ADHD are Adderall and Ritalin, which are briefly discussed here. In-depth pharmacology can be found in any pharmacological text or drug resource handbook.

Adderall. Adderall, an amphetamine, is the most widely prescribed drug for ADHD and is classified as a Schedule II substance by the United States Drug Enforcement Administration because of its potential for psychological and physical dependency and abuse (DeSantis, Webb, & Noar, 2008). It is considered a stimulant. Similar to how cocaine works, amphetamine binds to dopamine, serotonin, and norepinephrine, and catecholamines are released (Edmunds & Mayhew, 2014). This alteration of neurotransmitters in the brain modifies "behaviors to improve and maintain function in patients with attention-deficit disorder with or without hyperactivity and narcolepsy" (Edmunds & Mayhew, 2014). Use by someone who has not been determined to need this drug due to a true neurobiologic disorder can be considered NMUPD. The most common side effects of Adderall are anorexia, weight loss, nausea, abdominal pain, diarrhea or constipation, and xerostomia. Side effects are typically worse during initial days of treatment. Required "Black Box" warnings for Adderall include high abuse potential, drug dependence, and increased risk of serious cardiovascular adverse events and sudden death (Barr Laboratories, 2007).

Ritalin. Ritalin is considered an amphetamine-like drug and is called methylphenidate. It, too, is a stimulant. Ritalin acts mainly on dopamine and to a lesser extent norepinephrine. Although Ritalin is also a Schedule II drug, it is felt to have less potential for abuse (Edmunds & Mayhew, 2014, p. 41). Amphetamines, however, may be required for patients who do not respond to Ritalin (Edmunds & Mayhew, 2014). The medical indications for both Adderall and Ritalin, in addition to ADD and ADHD, include narcolepsy and shortterm weight loss. Management of these conditions with pharmacological treatment should be under the supervision of a healthcare provider.

The most common side effects of Ritalin are nervousness and insomnia, but other common side effects are decreased appetite, weight loss, headache, abdominal pain, depression, irritability, and what are called "rebound symptoms" (Edmunds & Mayhew, 2014). Less common side effects are dizziness, tachycardia, psychotic symptoms, and tics, and occasional visual disturbances have been reported (Edmunds & Mayhew, 2014). Side effects of Ritalin may subside after the first few weeks of treatment.

"Black Box" warnings for Ritalin include lower threshold for seizures for some patients; sudden death in children with underlying structural heart and cardiac rhythm disorders; increases in blood pressure; and mania and other psychotic symptoms (Edmunds & Mayhew, 2014).

Stimulant Abuse among College Students

NMUPD has become a "modern-day epidemic in the United States and is now second only to marijuana use" (Hernandez & Nelson, 2010, p. 307). NMUPD may be considered by users as more socially acceptable than an illegal drug such as heroin or cocaine. On university campuses in the United States among students aged 18-24 years, NMUPD of stimulants is a fairly common practice. In Hernandez and Nelson's (2010) survey of students taking methylphenidate for ADHD, 16% of the students reported being asked by other students to give, sell, or trade their prescription stimulants. Among the student population admitting to using methylphenidate within the last year, the major motive identified was to increase focus and study concentration to increase their academic performance (Hernandez & Nelson, 2010).

There are many ways to track the prevalence of NMUPD. National surveys are conducted; local surveys on college campuses are done, and reasons for emergency department visits are followed. Often drug abuse is accompanied by alcohol abuse. Prevalence statistics and numerous reports and studies can be located in the literature. Some but not all of the sponsors of this type of information are: National Institute on Drug Abuse (NIDA), Drug Abuse Warning Network (DAWN), Drug Evaluation Network System (DENS), The National Epidemiological Survey on Alcohol and Related Conditions (NESARC), and The National Survey on Drug Use and Health (NSDUH) (Hernandez & Nelson, 2010).

Reasons and route. As important as being aware of illicit use of prescription stimulants is the understanding of routes of administration and the reasons for use. A survey done by Herman et al. (2011) of graduate and undergraduate health care students at a northeastern university in the United States explored the nonmedical use of prescription stimulants, frequency of use, and route of administration. The most commonly used stimulants were Adderall and Adderall XR, followed by Ritalin (Herman et al., 2011). The most common route of administration was oral (81%), followed by intranasal (14%) (Herman et al., 2011). The top reasons for using these drugs were to focus and concentrate during studying, to increase alertness during studying, and to study for longer periods of time (Herman et al., 2011).

Teter et al. (2006) found that more illicit users began using in college (65.2%) compared with high school (34.8%). In Teter et al.'s study of 4,580 college students, the most commonly reported motives were to help with concentration, to help study, to increase alertness, to get high, and to experiment. More men than women cited experimentation as the reason to use simulants, whereas more women than men cited the desire to lose weight as a reason (Teter et al., 2006). There were no gender differences in the primary reason, which was to assist with concentration (Teter et al., 2006).

Access. How do so many students obtain such highly controlled drugs? Adderall and Ritalin are available only by prescription with a limit of 30 days' worth of doses and no refills. This appears to be no barrier to college students, according to comments such as "The stuff is everywhere. Just ask anybody, and they will either have it or know somebody that has it" (DeSantis et al., 2008, p. 320). In DeSantis et al.'s (2008) sample of 1,811 college students, 85% of the students identified illicit stimulants as somewhat easy or very easy to obtain. Underage (under 21 years) students noted that it was easier to get than beer (DeSantis et al., 2008). For members of sororities and fraternities. access is even easier (DeSantis et al., 2008). Someone always has these stimulants, and they are especially in demand during finals. "Sisters and brothers" take care of each other. "For those without such bonds, there is always the university's library, the seeming epicenter for stimulant drug distribution" (DeSantis et al., 2008, p. 321).

A fascinating study of wastewater on a university campus showed concrete evidence of abuse of Adderall and Ritalin. Wastewater analysis downstream from campus dorms showed increased metabolites of Adderall and Ritalin during periods of high academic stress, such as midterms, the last week of classes and finals week (Burgard, Fuller, Becker, Ferrell, & Dinglasan-Panlilio, 2013). One can see why this phenomenon is nicknamed "academic doping" and the drugs referred to as "Viagra for the brain" and "Smart Drugs" (Burgard et al., 2013; Lucke, Bell, Partridge, & Hall, 2011).

Relationship to Women's Health

Concern about medication use among pregnant women must focus on not only the pregnant woman, but also the fetus (Mitchell et al., 2011). Since college-age women are of prime childbearing age and there is a time lapse before a woman knows she is pregnant, obstetrical healthcare providers and educators must have honest dialogue with clients. Health care professionals must be aware of current knowledge regarding potential adverse effects of Adderall and Ritalin to an unborn child.

Sometimes communication is not open enough between provider and patient regarding drug use, and screening may not occur because providers may "assume that substance abuse is not prevalent among their patients" (Chasnoff, Neuman, Thornton, & Callaghan, 2001, p. 752). Typically when one thinks of substance abuse, drugs such as cocaine, marijuana, heroin, and other illicit drugs come to mind. Neurostimulants such as those being discussed in this article are, however, some of the most widely abused drugs in the world (Oei et al., 2012). Unfortunately there are few data about the long-term effects on fetal development. What does exist is difficult to extract and separate from various lifestyle factors such as alcohol, nicotine, nutrition, and other factors. Because this is an under-researched area, perinatal experts suggest that exposed children may be at risk of long term sequelae. Oei et al. recommend efforts be in early detection of perinatal exposure and early-intervention programs for those at risk. According to Oei et al. (2012), "there are no definitive numbers of amphetamine-exposed pregnant and lactating women" (p. 739). Oei et al. (2012) also state that there are two types of amphetamine users--those who are legally prescribed these drugs for a medical reason such as ADHD and those who are using the drugs for nonmedical reasons such as those described above (academic performance, weight loss, staying awake, etc.). Since it is documented that up to 5% of adults may have an attention deficit disorder, some of these are likely women of childbearing age (Oei et al., 2012). Combine legal prescription users with illicit users of the same drug and there is reasonable need for screening.

Potential Harm of Amphetamines to Mother

There is an association between amphetamine use and psychosis. For children with ADHD taking a legitimate amphetamine prescription, psychosis is a rare but devastating adverse event. For illicit users, it is poorly understood whether psychosis is due to amphetamine use itself or because of the sleep deprivation that can occur as a result of it. Furthermore, users often end their binge with it by using sedating-type drugs like alcohol, benzodiazepines, opiates, or cannabis; therefore, users often develop problems with several drugs (Bramness et al., 2012). The psychosis associated with amphetamine-type drugs is difficult to treat and may occur intermittently for months to years after discontinuing the drug (Oei et al., 2012). The presence of a psychotic disorder can make parenting, which is complex enough, even more difficult.

Increased libido is another drug effect, which can lead to risky sexual behavior, sexually transmitted diseases, and possibly unplanned pregnancy (Oei et al., 2012). Tachycardia, tachypnea, fever, diaphoresis and seizures can occur. The seizures can be exacerbated by sleep deprivation. Ischemic heart disease is rare but has been seen and is caused by coronary vasospasm. Acute myocardial infarction has been noted. Chronic users may be at greater risk for Parkinson's disease. Neurological deficits such as short-term memory loss, impaired executive function, and impaired manual dexterity may continue even after discontinuation of drug. Dry mouth and dental caries, leading to poor oral hygiene, can occur. Poor oral hygiene in pregnant women is believed in some cases to be related to premature labor and preeclampsia (Oei et al., 2012). Amphetamines are highly addictive and can lead to abuse of other substances, which would affect a mother's ability to care for a child.

Animal studies have shown that chronic exposure to amphetamines can cause either a tolerance (called attenuated response) or a sensitization (called an augmented response) (Berman, Kuczenski, McCracken, & London, 2009). Both of these represent what is called "neurobiological adaptation" and indicate that prolonged exposure to amphetamines can damage the central nervous system (Berman et al., 2009, p. 127). There is no research available describing the precise effects on the central nervous system of a developing fetus exposed to prenatal stimulants such as amphetamines.

Placental and Fetal Transfer of Amphetamines

Amphetamine metabolites have been detected in the umbilical cord, placenta, and amniotic fluid. Amphetamines may increase the risk of placental hemorrhage because they affect platelet activation (Oei et al., 2012).

Fetal Effects

Amphetamines are believed to have an affinity for developing cardiac and neural cells, but the research in this area has been only with animals. A definitive link to structural abnormalities in human infants has not been established, in part because of so many confounding factors.

Healthy full-term infants have been born to mothers on long-time dextroamphetamine for narcolepsy. No definitive evidence of increased fetal demise linked to amphetamine exposure exists, again because of other confounding factors such as polydrug use, lack of disclosure from the patient, maternal domestic stress, malnutrition, among others. When compared to the general population of pregnant women, amphetamine users are more likely to have complications such as hypertension and placental abruption; however, these complications are hard to separate from psychosocial circumstances, so again there is not a clear and direct link to amphetamines (Oei et al., 2012). In summary, direct causes and effects are nearly impossible to tease out.

Neonatal Effects

Low birth weight is a consistent finding in amphetamine-exposed infants, although the definite etiology is unknown. Perhaps more important is the fact that commonly used neonatal scoring systems for assessing drug withdrawal may not be identifying amphetamine exposure. The commonly used assessment scales are "opiate-centric" and are not validated for use in amphetamine assessment. This is essential for childbirth educators to understand. The most common presentation of amphetamine-exposed neonates is lethargy, somnolence, and poor feeding. The mother may be difficult to arouse as well. There is a need for a more sensitive instrument to measure amphetamine withdrawal. Until one is developed, keen physical assessment skills are irreplaceable. Fortunately, most neonates that do have either amphetamine withdrawal or amphetamine saturation require only minimal supportive treatment (Oei et al., 2012).

Use of Ritalin During Pregnancy

The safety of methylphenidate during pregnancy has not been established. There is relatively little research as of yet. There is good news in that animal studies with mice and rats show that there are no teratogenic effects except at very high doses (Dideriksen, Pottegard, Hallas, Aagaard, & Damkier, 2013). Dideriksen et al.'s (2013) systematic mini-review of first trimester in utero exposure concluded that there was no significant (i.e. more than twofold) increased risk of congenital malformations but also stated that "the quality and quantity of the available exposure data does not allow for a specific risk assessment" (p. 75). Dideriksen et al. (2013) identified four malformations among 180 subjects in the small studies that they could find in the literature. "The more widespread use of methylphenidate in the adult population over the last decade should allow for more comprehensive, valid and generalizable pharmacoepidemiological data to be generated in the future" (Dideriksen et al., 2013, p. 75).

Implications

There is not much empirical evidence in the literature of exactly what ramifications may come to an unborn child due to amphetamine exposure in utero (and even less for Ritalin), for a number of reasons: i) self-report may not be honest, especially from women who have used the "Smart Drug" without a prescription to get ahead in school or stay awake for whatever reason; 2) what research data there are originate more from heavier amphetamine compounds such as methamphetamine (MA or "meth) rather than Adderall and/ or Ritalin; 3) experimental research with amphetamines and pregnancy has been done only in animals; and 4) social and behavioral research is in context and has many confounding variables which cannot be changed. Most of the published research does not statistically adjust for these confounders, making it hard to draw any strong conclusions. Data analysis that has controlled for confounding variables, however, does show a relationship between maternal amphetamine use and pre-term birth (PTB), small for gestational age (SGA), and low birth weight (LBW) babies (Ladhani, Shah, Murphy, & the Knowledge Synthesis Group on Determinants of Preterm/LBW births, 2011).

We Still Should Be Concerned

The fact that there is little empirical evidence tying Adderall and Ritalin to harmful effects on an unborn child is not reason to be unconcerned. Exposure to methamphetamines has been linked with birth defects such as cleft lip, heart malformations, biliary defects, low birth weight, small head circumference, stillbirth, cerebral hemorrhage, undescended testicles, developmental delays, and impaired memory in the cerebral cortex (Slamberova, 2012). Adderall has chemical similarities and bears caution if used in pregnancy. Further research is needed.

Recommendations for Childbirth Educators

Screening and compassion. An area where childbirth educators can make a significant difference is in the quality of life of a mother and her child. The psycho-social-emotional dynamics in the life of an expectant or new mother, who uses or has used psycho-stimulants for whatever reason, may be complicated. This individual could benefit from the support of a knowledgeable, informed, and understanding professional who is non-judgmental.

To be able to offer help, people who need it must be identified, and this begins with screening. "Given the risks associated with untreated substance abuse and dependence in women, the integration of drug and alcohol screening into daily clinical practice is imperative" (Goodman & Wolff, 2013, p. 278). Screening for drug and alcohol use is associated with reduction in abuse, savings in health care costs, and decreases in emergency room visits and motor vehicle accidents (Goodman & Wolff, 2013). Goodman and Wolff (2013) also state that "midwives should oppose legislation that criminalizes women using drugs and alcohol or drugs during pregnancy and promote policies that increase access to treatment" (p. 279). Goodman and Wolff go on to admit that integrating a screening program into clinical practice can present challenges, cautioning the clinician to screen for substance abuse with a woman alone, both to protect her privacy and prevent potential backlash from her partner or family members. "Ultimately, the goal of screening ... is not to ... punish women but to start the conversation about healing the problems caused by substance abuse and dependence ...." (Goodman & Wolff, 2013, p. 285).

Assistance with alternatives. Perhaps the problem is not really substance abuse because the woman truly has ADHD and needs her prescribed Adderall or Ritalin to function. Given the side effects and risk for other problems, however, other options for treating ADHD such as nonaddicting medications (for e.g. atomoxetine) or proposing non-chemical solutions to problems (i.e. time management and organizational skills, tutoring, supportive therapy) could be suggested (Bettinardi-Angres et al., 2012). Perhaps a single mother is engaging in NMUPD using Adderall or Ritalin inappropriately to stay awake and study all night as she works on a high school diploma or college degree. Healthier strategies could be suggested such as a babysitter to allow for mom's study time, or simply educating the client on the risks of misusing a potent drug, no matter how well-intended the reason. Educators can also recommend community resources for struggling mothers.

Conclusion

Even though there is little tangible evidence at this time of definite harm to an unborn child, it is reasonable to be concerned about the potential deleterious effects of Adderall and Ritalin on the health of children whose mothers use these drugs and to prenatal effects on infants. Child birth educators who quickly develop a trusting rapport with their clients are more likely to ascertain untoward use of prescription drugs and support clients' healthy choices and lifestyle modifications. The appropriate use of such drugs for legitimate treatment of challenging disorders is currently acceptable according to a review of the literature, but as with any drug taken during pregnancy administration of it should be carefully evaluated for potential risk versus benefit. Non-monitored use of a drug as in the case of NMUPD is always contraindicated, especially in the circumstance of pregnancy. Educators should be alert to the increasing prevalence of stimulant abuse in childbearing age women and be skilled in screening for it and giving counsel for healthy alternatives.

References

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Teter, C. J., McCabe, S. E., LaGrange, K., Cranford, J. A., & Boyd, C. J. (2006). Illicit use of specific prescription stimulants among college students: Prevalence, motives, and routes of administration. Pharmacotherapy, 26(10), 1501-1510.

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Shelley Moore is an Assistant Professor of Nursing at Middle Tennessee State University School, teaching online courses in the graduate program, the RN to BSN program, and ground courses in the traditional undergraduate program. Dr. Moore has a 35 year history of working in both community hospitals and academic medical centers, having served in both clinical and leadership positions. Her research interests include the study of structural empowerment in the work environment, structural empowerment within the student learning environment, clinical reasoning, decisional involvement of staff nurses, and the effects of simulation on teamwork.
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Publication:International Journal of Childbirth Education
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Date:Oct 1, 2014
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