STIMULANT MEDICATION USE DURING PREGNANCY

IN REVIEWING INFORMATION ON THE USE OF STIMULANT MEDICATION [ADDERALL, DEXEDRINE AND METHYLPHENIDATE] DURING PREGNANCY, THERE ARE A NUMBER OF REFERENCES TO STUDIES ON MICE LEADING TO MISCARRIAGES AND BIRTH DEFECTS. THESE WERE ASSOCIATED WITH A SIGNIFICANT OVERDOSE OF THE MICE COMPARED TO DOSES TAKEN BY HUMANS. IN ADDITION, THERE HAVE ALSO BEEN MENTION OF HEART DEFECTS RELATED TO AMPHETAMINE USE DURING PREGNANCY AND YET A STUDY OUT FROM HARVARD BY LEAD AUTHOR KRISTA HUYBRECHTS INVOLVING A VERY LARGE NUMBER OF PREGNANT WOMEN [IN JAMA PSYCHIATRY 2018 FEB; 75(2): 167-175] FOCUSED ON THE SAFETY OF METHYLPHENIDATE AND AMPHETAMINES [ADDERALL AND DEXEDRINE] FOR PREGNANT WOMEN DURING THE FIRST TRIMESTER OF THEIR PREGNANCY.  THERE WERE NO CARDIAC MALFORMATIONS OR OTHER MALFORMATIONS RELATED TO THE AMPHETAMINES, HOWEVER, THERE WAS A 28% INCREASE IN CARDIAC MALFORMATIONS AND AN 11% INCREASE IN BIRTH DEFECTS FOR PREGNANT WOMEN TAKING METHYLPHENIDATE WITH THE CONCLUSION THAT THERE IS A SMALL INCREASE IN THE RISK OF CARDIAC MALFORMATIONS AND EVEN SMALLER RISK FOR BIRTH DEFECTS FOR PREGNANT WOMEN TAKING METHYLPHENIDATE.

A 2007 ARTICLE ENTITLED "EXPOSURE TO ATTENTION DEFICIT HYPERACTIVITY DISORDER [ADHD] MEDICATIONS DURING PREGNANCY", IN THE CANADIAN FAMILY PHYSICIAN JUL; 53(7):1153-1155, SUMMARIZES RESEARCH RELATED TO TAKING AMPHETAMINE TYPE MEDICATIONS FOR ADHD DURING PREGNANCY. IN THEIR REVIEW THEY REPORT THAT THERE IS NO EVIDENCE FOR AN INCREASE IN MALFORMATIONS USING THERAPEUTIC DOSES. THEY ALSO REPORT THAT ABUSE OF AMPHETAMINES DURING PREGNANCY HAS BEEN ASSOCIATED WITH LOW BIRTH WEIGHT, PREMATURITY, AND INCREASED MATERNAL AND FETAL MORBIDITY.  THIS WAS CONNECTED WITH USE OF COCAINE AND MAY REFLECT PLACENTAL VASOCONSTRICTION.  HOWEVER, THERE WERE OTHER CONFOUNDING FACTORS SUCH AS POLY DRUG ABUSE, POSSIBLE ALCOHOL ABUSE, AND OTHER MEDICAL PROBLEMS ASSOCIATED WITH LIFESTYLE CHOICES. ANY OF THESE COULD HAVE CAUSED THE PROBLEMS NOTED.  ADDITIONALLY, THERE IS A REPORT OF A MILD [100-400 GRAMS] WEIGHT LOSS FOR INFANTS BORN TO WOMEN WHO WERE PRESCRIBED DEXTROAMPHETAMINE FOR WEIGHT CONTROL. THE SIGNIFICANCE OF THIS IS NOT CLEAR AS THERE WERE A NUMBER OF CONFOUNDING VARIABLES IN THIS STUDY AS WELL.  INTERESTINGLY, A PROSPECTIVE STUDY EVALUATED THE RISK OF CONGENITAL ANOMALIES OF INFANTS BORN TO 1694 WOMEN WHO WERE USING AMPHETAMINES AS ANORECTICS [FOR WEIGHT LOSS] WITH NO INCREASE IN MALFORMATIONS. SO, IT APPEARS THAT EVEN WHEN AMPHETAMINES ARE USED [ABUSED?] TO LOSE WEIGHT, THERE ARE NO MALFORMATIONS IN THEIR INFANTS. 

MORE RECENT REVIEWS GO OVER THE STUDIES MENTIONED ABOVE.  THEY CONCLUDE THAT THERE IS NO EVIDENCE OF MALFORMATIONS WITH THE USE OF AMPHETAMINES [INCLUDING ADDERALL] DURING PREGNANCY BY WOMEN WHO HAVE ADHD AND YET WILL OFTEN STILL RECOMMEND STOPPING THE AMPHETAMINE. THIS IS POSSIBLY BECAUSE OF OLDER STUDIES WHERE PREGNANT MICE WERE SIGNIFICANTLY OVERDOSED ON AMPHETAMINES AND HAD SOME MALFORMATIONS IN THEIR INFANTS.

WHEN EVALUATING ANY STUDIES RELATED TO AMPHETAMINES AND PREGNANCY, IT IS IMPORTANT TO BE SURE THAT THE DATA IS FROM WOMEN WITH ADHD WHO ARE PREGNANT. IT IS CLEAR TO ME AFTER TREATING THOUSANDS OF PEOPLE WITH ADHD THAT PEOPLE WITH ADHD DO NOT RESPOND TO AMPHETAMINES LIKE PEOPLE WHO DO NOT HAVE ADHD. TAKING THE AMPHETAMINE TYPE MEDICATION, PEOPLE WITH ADHD ARE CALMER, MORE ALERT, MORE FOCUSED, NOT IRRITABLE AND DO NOT EXPERIENCE SUSTAINED SLEEP OR APPETITE DISTURBANCE.  IF THEY ARE MORE IRRITABLE, MORE HYPERACTIVE AND HAVE REDUCED APPETITE AND SLEEP, THESE ARE SIDE-EFFECTS AND OFTEN MEAN THAT THEY WILL NEED TO CHANGE TO ANOTHER AMPHETAMINE TYPE MEDICATION. 

FINALLY, A STUDY BY JM COHEN, ET AL. OBSTET GYNECOL. 2017 DEC; 130(6): 1192-1201 WITH DR. HUYBRECHTS AN AUTHOR ON THE STUDY, LOOKING FOR RISK FOR PLACENTAL-ASSOCIATED ADVERSE OUTCOMES IN PREGNANT WOMEN TAKING PSYCHOSTIMULANT [INCLUDING ADDERALL] MEDICATIONS, FOUND THAT IN A COHORT OF 1.5 MILLION PREGNANCIES THERE WERE 5000 PREGNANCIES EXPOSED TO STIMULANT MEDICATION AND THERE WAS A SMALL INCREASED RELATIVE RISK OF PREECLAMPSIA AND PRETERM BIRTH. THE RISK WAS SMALL ENOUGH THAT THE AUTHORS DID NOT RECOMMEND STOPPING THE STIMULANT MEDICATION IF IT WOULD HAVE AN IMPACT ON THE MOTHER’S FUNCTIONING. ALSO, THERE WERE SOME CONFOUNDING VARIABLES THAT COULD HAVE INFLUENCED THE FINDINGS OF THIS SMALL RISK.  THESE WERE THAT THERE WERE MOTHERS WHO DID NOT HAVE ADHD WHO TOOK THE STIMULANT MEDICATION AND THERE WERE MOTHERS IN THE CONTROL GROUP WHO HAD ADHD WITHOUT MEDICATION AND THESE MOTHERS WERE FOUND TO HAVE A TWO FOLD INCREASED RISK OF PRETERM BIRTH IN A STUDY BY SP BRO, ET AL. IN CLIN EPIDEMIOL. 2015;7:139-47. 

IN SUMMARY, A NUMBER OF STUDIES OF PREGNANT WOMEN WITH ADHD TAKING ADDERALL HAVE FOUND NO EVIDENCE OF MALFORMATIONS [INCLUDING HEART MALFORMATIONS] IN THEIR INFANTS OR ANY OTHER BIRTH COMPLICATIONS. HOWEVER, A STUDY OF PREGNANT WOMEN TAKING METHYLPHENIDATE HAS FOUND HEART MALFORMATIONS AND OTHER BIRTH COMPLICATIONS. I DO NOT BELIEVE THAT THIS STUDY HAS BEEN REPLICATED YET.  ALSO,THERE WAS ANOTHER STUDY THAT FOUND A SMALL RELATIVE RISK FOR  PREECLAMPSIA AND PRETERM BIRTH BUT NOT ENOUGH TO REQUIRE STOPPING THE MEDICATION IF THE MEDICATION HAD AN IMPACT ON THE MOTHER’S FUNCTIONING.