Effect of Ferritin on Short-Term Treatment Response in Attention Deficit Hyperactivity Disorder

Abstract

Objectives Several studies have shown that iron deficiency and ferritin levels are associated with parent and teacher Attention Deficit Hyperactivity Disorder (ADHD) ratings. Although there are conflicting results, it has also been reported that iron supplementation may help to decrease ADHD symptoms. When all these previous studies are taken into account, it is clear that a large study investigating the effects of iron deficiency and ferritin levels on routine pharmacological treatment of ADHD with stimulants would be helpful to elucidate this treatment from a clinical point of view. Methods A total of 345 subjects with combined or predominantly hyperactive-impulsive (PHI) subtypes of ADHD were included. All diagnoses were based on the DSM-IV criteria and ascertained by direct interviews conducted by the authors, who are experienced child psychiatrists certified in the use of the Schedule for Affective Disorders and Schizophrenia for School-Age Children — Present and Lifetime Version (K-SADS-PL) semi-structured interview. The two treatment response criteria were: 1) 25% or more decrease in pre-treatment Conners Parent Rating Scale (CPRS) and Conners Teacher Rating Scale (CTRS) Hyperactivity (HA) and Total Problems scores; 2) CPRS and CTRS HA scores lower than the cut-off point (“very improved”). Results A total of 255 (73.9%) patients were on OROS-methylphenidate (OROS-MPH) and 90 (26.1%) were on immediate release methylphenidate (IR-MPH). The mean±sd of OROS-MPH and IR-MPH doses were 28.8±8.1 and 20.9±7.1 mg, respectively. More than half (52.5%) of the subjects were previously drug-naive at treatment inception. Two hundred and seventy eight (80.6%) subjects had combined subtype ADHD and the remainder had predominantly hyperactive-impulsive subtype. Only 60 (17.4%) of the subjects had no comorbid disorders, while 38.3% had one comorbid disorder, 32.8% had two comorbid disorders, and 11.6% had three or more comorbid disorders. The most frequent comorbidity was Oppositional Defiant Disorder/Conduct Disorder (ODD/CD, 51.6%), followed by Learning Disabilities (LD, 35.4%) and Anxiety Disorders (AD, 15.9%). Logistic regression analysis showed that subjects with comorbid ODD/CD and LD were less likely to respond to treatment. Ferritin levels and iron deficiency were not associated significantly with outcomes. Conclusions In a large sample of subjects with combined or predominantly hyperactive-impulsive subtypes of ADHD, after controlling for several factors, we found that neither iron deficiency (ferritin <12 ng/ml) nor ferritin levels were associated with less favorable short-term treatment outcomes with stimulants. Subjects with comorbid ODD/CD and LD were less likely to have a 25% or more decrease in CTRS Total score. The presence of ODD/CD was also a negative predictor of treatment response in terms of CPRS Total and HA scores. The lack of a negative treatment response in ADHD subjects with iron deficiency and lack of a negative association with ferritin levels suggest that the relationship between iron met...

Iron deficiency and common neurodevelopmental disorders—A scoping review

“…Overall, the most common indicators of statistically significant positive associations in studies were SF (n = 21) [ 12 – 14 , 17 , 25 , 27 – 34 , 36 , 37 , 39 – 42 , 48 , 59 ], followed by Hb (n = 8) [ 12 , 13 , 17 , 30 , 33 , 40 , 51 , 59 ], SI (n = 6) [ 12 , 25 , 37 , 40 , 51 , 59 ], MCV (n = 5) [ 27 , 33 , 40 , 51 , 59 ], Hct (n = 2) [ 51 , 59 ], and total iron binding capacity (TIBC) (n = 2) [ 25 , 40 ]. Brain iron (BI) [ 39 ], mean corpuscular hemoglobina concentration (MCHC) [ 40 ], red cell distribution width (RDW) [ 34 ], sTfR/log ferritin index (SFI) [ 38 ], soluble transferrin receptor (sTfR) [ 38 ], and transferrin saturation (TSAT) [ 38 ], were indicators of a statistically significant positive association in 1 study each.…”

“…Only 11 association studies identified that fasting blood samples were taken for measuring iron parameters [ 16 , 28 , 29 , 31 , 33 , 35 , 36 , 40 , 42 , 45 , 51 ]. In the remainder, no information on timing of blood sampling was given.…”

“…16/22 studies investigated the degree of ID and the severity of ADHD symptoms, with greater severity being associated with lower iron levels [ 11 , 14 , 25 – 38 ], and 10/22 studies concluded that SF levels were lower in the ADHD population [ 12 , 13 , 25 , 30 – 32 , 36 , 39 – 41 ]. 10/22 studies showed an association with the hyperactivity symptoms of ADHD [ 25 , 27 – 29 , 32 , 33 , 35 , 37 , 38 , 42 ]. Oppositional defiant/conduct disorder (10/22 studies) was the most common comorbidity in the ADHD populations investigated [ 14 , 26 – 29 , 31 , 33 , 34 , 39 , 42 ].…”

“…10/22 studies showed an association with the hyperactivity symptoms of ADHD [ 25 , 27 – 29 , 32 , 33 , 35 , 37 , 38 , 42 ]. Oppositional defiant/conduct disorder (10/22 studies) was the most common comorbidity in the ADHD populations investigated [ 14 , 26 – 29 , 31 , 33 , 34 , 39 , 42 ].…”

Magnesium, Iron, Zinc, Copper and Selenium Status in Attention-Deficit/Hyperactivity Disorder (ADHD)

“…Alternatively, serum iron levels or transferrin [ 72 , 73 ] have been mentioned, although results are controversial. Nevertheless, most of the studies indicate lower serum ferritin levels in ADHD patients [ 32 , 33 , 69 , 70 , 71 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 ]. Other reports found no significant relationship [ 89 , 95 , 96 , 97 , 98 , 99 , 100 ].…”