Does L-Methylfolate Supplement Methylphenidate Pharmacotherapy in Attention-Deficit/Hyperactivity Disorder?: Evidence of Lack of Benefit From a Double-Blind, Placebo-Controlled, Randomized Clinical Trial.

PURPOSE/BACKGROUND: Interventions for attention-deficit/hyperactivity disorder (ADHD) may be inadequate for some patients. There is evidence that supplementation with L-methylfolate augments antidepressant agent effects and thus might also augment ADHD treatment effects by a common catecholaminergic mechanism. METHODS: Forty-four adults with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of ADHD participated in a randomized, double-blind, placebo-controlled, 12-week trial of 15 mg of L-methylfolate in combination with osmotic-release oral system methylphenidate. Osmotic-release oral system methylphenidate was dose optimized over the first 6 weeks. We evaluated the effects on ADHD symptoms, self-report on the Behavior Rating Inventory of Executive Function of executive function, methylphenidate dosing, neuropsychological test measures, the Adult ADHD Self-report scale, emotional dysregulation, social adjustment, and work productivity, as well as moderating effects of body mass index, autoantibodies to folate receptors, and select genetic polymorphisms. RESULTS: L-Methylfolate was well tolerated, with no significant effect over placebo except improvement from abnormal measures on the mean adaptive dimension of the ASR scale (χ = 4.36, P = 0.04). Methylphenidate dosing was significantly higher in individuals on L-methylfolate over time (χ = 7.35, P = 0.007). Exploratory analyses suggested that variation in a guanosine triphosphate cyclohydrolase gene predicted association with higher doses of methylphenidate (P < 0.001). CONCLUSIONS: L-Methylfolate was associated with no change in efficacy on measures relevant to neuropsychiatric function in adults with ADHD, other than suggestion of reduced efficacy of methylphenidate. Further investigation would be required to confirm this effect and its mechanism and the genotype prediction of effects on dosing.

Adolescent substance use and unplanned pregnancy: strategies for risk reduction.

Substance use among adolescents increases the risk of unplanned pregnancies, which then increases the risk of fetal exposure to addictive, teratogenic substances. Specific interventions are necessary to target pregnancy planning and contraception among reproductive-age substance users. Screening for substance use using the CRAFFT is recommended in all health care settings treating adolescent patients. Screening for tobacco and nicotine use is also recommended along with the provision of smoking cessation interventions. Using motivational interviewing style and strategies is recommended to engage adolescents in discussions related to reducing substance use, risky sexual behavior, and probability of unplanned pregnancy or late-detection pregnancy.

Medical students' comfort with pregnant women with substance-use disorders: a randomized educational study.

OBJECTIVE: The study objective was to determine whether medical students' attendance at a rehabilitation residence for pregnant women with substance-use disorders yielded changes in their attitudes and comfort levels in providing care to this population. METHODS: This randomized educational trial involved 96 consecutive medical students during their obstetrics and gynecology clerkship. In addition to attending a half-day prenatal clinic designed for women with substance-use disorders, every student was randomly assigned either to attend (Study group) or not to attend (Control group) a rehabilitation residence for pregnant women with substance-use disorders. The primary objective was to measure differences in responses to a confidential 12-question survey addressing comfort levels and attitudes, at the beginning and end of the clerkship. RESULTS: Survey responses revealed improvements in students' comfort levels and attitudes toward pregnant women with substance-use disorders by attending the clinic alone or the clinic and residence. Those who attended the residence reported becoming more comfortable in talking with patients about adverse effects from substance abuse, more understanding of "street" terms, and stronger belief that patients will disclose their substance use to providers. Residents expressed more openly their hardships and barriers while trying to set therapeutic goals. CONCLUSIONS: Medical students became more comfortable and insightful about pregnant women with substance-use disorders after attending a rehabilitation residence in addition to a prenatal clinic dedicated to this population.

Changes in methadone maintenance therapy during and after pregnancy.

OBJECTIVE: The aim of this study is to better understand anticipated changes in daily methadone doses as a guide for prescription during pregnancy. METHODS: This retrospective case series involved a single cohort longitudinal design of 139 consecutively chosen women who began methadone therapy before 26 completed gestational weeks. Changes in the single daily dose were based on a standard opiate withdrawal scale and determined from early pregnancy until 6 weeks postpartum. RESULTS: As gestation advanced, the methadone dose increased (86%) rather than remained the same (8%) or decreased (7%). This gradual increase in daily dose during pregnancy (mean increase = 24 mg, 95% confidence level = 20-28 mg) was statistically significant (p < .001) regardless of the initial maintenance dose. By the sixth postpartum week, most subjects (85%) took within 10 mg of their dose at delivery (mean change in dose = -4 mg, 95% confidence interval = -6 to -2 mg). CONCLUSIONS: Daily doses of methadone increased until the third trimester, then remained essentially unchanged through the sixth postpartum week.

Association between intrapartum fetal heart rate patterns and neonatal abstinence syndrome in methadone exposed neonates.

OBJECTIVE: Determine whether infants exposed to chronic maternal methadone with abnormal intrapartum fetal heart rate (FHR) patterns are more likely to require treatment for neonatal abstinence syndrome (NAS). STUDY DESIGN: Intrapartum FHR tracings analyzed in 104 pregnancies at ≥ 34 weeks gestation for FHR variability, accelerations, and decelerations. FHR patterns compared between neonates based on treatment with methadone for NAS. Secondary analysis included relation between maternal methadone dose and intrapartum FHR patterns, initiation of methadone, age at methadone initiation, and total neonatal methadone dose. Study powered to detect 30% increase in NAS incidence in neonates with abnormal FHR tracings. RESULTS: Seventy-six (73%) of 104 neonates required methadone treatment for NAS. Neonates who required methadone had higher average baseline FHR (131 vs. 126 bpm; p < 0.04) in active labor and less likely to have FHR tracings without accelerations (1.7% vs. 20.3%; p = 0.007) in latent labor. No significant associations between neonate's need for methadone and intrapartum FHR variability or FHR decelerations. No association between maternal methadone dose (range 30-280 mg) and treatment for NAS. CONCLUSION: The need for an infant to require methadone treatment for NAS was not reliably predicted by the intrapartum FHR patterns or the maternal methadone dose.

Substance abuse among reproductive age women.

Substance abuse poses significant health risks to reproductive age women in the United States and, for those who become pregnant, to their children. Substance abuse or dependence is defined as a maladaptive pattern of substance use marked by recurrent and significant negative consequences related to the repeated use of substances. Alcohol is the most prevalent substance consumed by childbearing-aged women, followed by tobacco and various illicit drugs. Substance use in the preconception period predicts continued but often limited substance use during the prenatal period. Providers must be aware of reproductive age women's unique physiologic, psychological, and social needs and the related legal and ethical ramifications surrounding substance abuse before referral to a community-based multidisciplinary team for often long-term treatment.

Medical students' awareness of traditional Southwest Native American values during pregnancy: a randomized, controlled trial.

OBJECTIVE: To determine if medical students' attendance at specialized prenatal clinics for Southwest Native American women would impact their awareness of and comfort in discussing traditional and unique values during pregnancy. STUDY DESIGN: In this unblinded, randomized trial, all 154 third-year students rotating consecutively on our obstetrics-gynecology clerkship consented to enrolling in this study. Participants were randomly assigned either to attend a high-risk prenatal clinic (rural or urban locations) for Native American women or to not attend (control group). Each anonymously answered a 20-question survey at the beginning and end of the clerkship about their comfort level and their awareness of patients' beliefs. A mixed model ANOVA was used to compare differences in scores between the groups while accounting for cluster effects in the study design. RESULTS: Regardless of whether the clinic was rural or urban, students became much more comfortable than controls in talking with Native American women about their pregnancy (p < 0.005). This applied especially to discussions about patients' spiritual beliefs, taboos that may affect pregnancy, participation in tribal ceremonies and belief in traditional medicine. As compared with the control group, students assigned to either clinic became more aware of how spirituality played an integral role in pregnancy (p < 0.05). CONCLUSION: Attendance at these specialized prenatal clinics enhanced medical students' comfort in talking with pregnant Native American women about the integrative roles of spiritual beliefs, tribal ceremonies and complementary medicine in their pregnancy outcome.