Side Effects of Acetaminophen – ADHD?

Stephen V. Faraone, PhD on August 25, 2016

Does Acetaminophen use During Pregnancy Cause ADHD in Offspring?

Many media outlets have reported on a study suggesting that mothers who use acetaminophen during pregnancy may put their unborn child at risk for ADHD.   Given that acetaminophen is used in many over-the-counter pain killers, correctly reporting such information is crucial. 

As usual, rather than relying on one study, looking at the big picture using all available studies is best.  Because it is not possible to examine this issue with a randomized trial, we must rely on naturalistic studies.  

One registry study (http://www.ncbi.nlm.nih.gov/pubmed/24566677) reported that fetal exposure to acetaminophen predicted an increased risk of ADHD with a risk ratio of 1.37.  The risk was dose-dependent in the sense that it increased with increased maternal use of acetaminophen.  Of particular note, the authors made sure that their results were not accounted for by potential confounds (e.g., maternal fever, inflammation and infection). 

Similar results were reported by another group, which also showed that risk for ADHD was not predicted by maternal use of aspirin, antacids, or antibiotics.  But that study only found an increased risk at age 7 (risk ratio = 2.0) not at age 11. (http://www.ncbi.nlm.nih.gov/pubmed/25251831)

In a Spanish study, (http://www.ncbi.nlm.nih.gov/pubmed/27353198), children exposed prenatally to acetaminophen were more likely to show symptoms of hyperactivity and impulsivity later in life.  The risk ratio was small (1.1) but it increased with the frequency of prenatal acetaminophen use by their mothers. 

We can draw a few conclusions from these studies.  There does seem to be a weak, yet real, association between maternal use of acetaminophen while pregnant and subsequent ADHD or ADHD symptoms in the exposed child.  The association is weak in several ways: there are not many studies, they are all naturalistic and the risk ratios are small.  

So mothers that have used acetaminophen during pregnancy and have an ADHD child should not conclude that their acetaminophen use caused their child’s ADHD.  On the other hand, pregnant women who are considering the use of acetaminophen for fever or pain should discuss other options with their physician.  As with many medical decisions, one must balance competing risks to make an informed decision.

Collateral Information in Adult ADHD

Lenard A. Adler, on March 3, 2016

Breda,V;, Rovaris, DL; Schneider Vitola, E.; et al.

Does collateral retrospective information about childhood attention- deficit/hyperactivity disorder symptoms assist in the diagnosis of attention- deficit/hyperactivity disorder in adults? Findings from a large clinical sample.

Australian & New Zealand Journal of Psychiatry, 1–9, DOI: 10.1177/0004867415609421.

Collateral information is commonly used in making the diagnosis of ADHD in a child or adolescent. The role of collateral information in making the diagnosis in adults presenting for evaluation for ADHD has been less well investigated.

This is an investigation of the relative importance of childhood collateral information in making a diagnosis of ADHD in an adult presenting for evaluation. 449 adults with ADHD and 143 controls were evaluated for the diagnosis of ADHD and co-morbidities with a modification of the K-SADS, ADHD symptoms with the SNAP-IV, and current/childhood impairment with the Barkley Current and Childhood Symptom scales. Collateral childhood ADHD symptoms/impairments were also evaluated with the Barkley Childhood Symptom Scale, completed by a first or second degree relative.

A diagnosis of ADHD via patient or collateral report required full childhood symptom onset prior to the age of 12. A subset of adults with ADHD were also treated with methylphenidate immediate release (0.13-1.23 mg/kg/day); treatment response was measured via changes in SNAP-IV from baseline to endpoint.

The data analyses were performed on three cohorts: 1) adults with ADHD where there was agreement as to childhood symptoms from the subject and informant (n=277), 2) adults with ADHD where there was disagreement between subjects and informants (n=172) and 3) controls. ADHD patients (all) vs. controls did not significantly differ in terms of age, gender, years of education or income, but did have significantly more school failure problems with discipline and problems with the law. The levels of impairment for the ADHD cohort were quite similar (collateral agreement + vs. -), except that the group with collateral and patient childhood agreement had higher levels of school suspensions and problems with discipline. It is not that surprising that the collaterals and subjects had better agreement in these areas as school suspensions and discipline problems are more likely to be remembered by both subjects and collaterals.

The ADHD cohorts (collateral agreement + vs. -) had similar levels of co-morbidity and treatment response to methylphenidate. The combined ADHD cohorts had higher rates of tobacco use, bipolar disorder, current ODD, conduct disorder and non-alcohol SUD than controls. A salient finding of this investigation is that 40% of subjects with adult ADHD had collateral informants who were unable to extensively corroborate their symptoms.

Limitations of this study include the self-report nature of the SNAP-IV and the fact that this scale has not been validated for adults. Also, of note, the subjects with adult ADHD had full childhood onset of the disorder retrospectively, which is a more stringent criteria than utilized in DSM-IV. It is not clear how utilizing more strict childhood criteria will influence the generalizability of these findings to clinically evaluated subjects using DSM-IV or DSM-5 guidelines.

Clinicians remain the final and optimal arbiter in establishing a diagnosis of adult ADHD; it remains up to clinicians to integrate information from all sources in establishing this diagnosis, be it from the subject, current significant others, collateral informants about childhood or clinician observations during the interview.