Can We Predict Short-Term Side Effects of Methylphenidate Immediate-Release

Abstract

Objective. In children and adolescents who were prescribed immediate-release methylphenidate (MPH-IR) for the first time, we aimed to investigate the effect of gender, psychiatric co-morbidity and the baseline severity of clinical symptoms on the short-term side-effects of the medication. Method. In a clinical sample, over a period of 6 months, all MPH-naive patients with attention deficit hyperactivity disorder (ADHD) (N=90; male, n=73; female, n=17) age: 9.0±2.2 years (5-16 years)) were included. Patients were prescribed MPH-IR 10-30 mg/day (17.6±4.95). The assessment included structured measurements, including the Turgay Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV)-Based Child and Adolescent Behavior Disorders Screening and Rating Scale (T-DSM-IV-S) (parents and teachers), Conners' Teacher Rating Scale for ADHD-Short version (teachers). Parents also completed the "Barkley Stimulants' Side Effects Rating Scale" (BSSERS) at baseline and on the third, seventh and 15th days of medication. Results. Repeated measures multiple ANOVA revealed an overall significant difference in BSSERS between the baseline measures and the 15th day (P<0.01). On the 15th day, only the "loss of appetite" item severity scores increased (P=0.001), whereas the scores of "irritability", "proneness to cry", "anxiety", "nail biting" and "euphoria" items decreased significantly. In post hoc analyses, when subjects whose side effects increased and did not increase were compared, chi-square tests revealed a significant difference (P=0.029) only for the presence of co-morbidity, and no difference for the gender, age, dosage of MPH, and the baseline severity of inattentiveness and/or hyperactivity. Discussion. The only significant increase during MPH treatment was for the "loss of appetite" item on BSSERS. Our results suggest that some of the BSSERS items may represent both the ADHD symptoms and the side effects. When overall BSSERS item severity is considered, having a co-morbid diagnosis may be predictive of more severe adverse effects. © 2008 Taylor & Francis.; Indications:90 patients with attention deficit hyperactivity disorder. Coexisting diseases: 24 learning disorders, 15 conduct disorder, 15 obsessive-compulsive disorder, 9 Tourette syndrome and 8 depression.Patients:90 de novo patients, 73 males and 17 females, mean age 9.0 years, age range 5-16 years; 13 dropouts, 18 were due to side effects; 28 were considered as "affected" and 46 as "not affected".TypeofStudy:An open study investigating the effect of gender, psychiatric co-morbidity and the baseline severity of clinical symptoms on the short-term side-effects of Ritalin immediate-release (IR) in children and adolescents with attention deficit hyperactivity disorder (ADHD) who were prescribed with this medication for the first time.DosageDuration:10-30 mg daily (average of 17.6 mg daily) bid or tid (given as an immediate-release formulation). Duration was 6 months.FreeText:Mean Clinical Global Impression (CGI) for ADHD was 4.3 (2-7). Of the patients with ADHD, 70.5% (63/90) had at least 1 co-morbid diagnosis, including learning disorders (26.7%; 24/90), conduct disorder (16.7%; 15/90), obsessive-compulsive disorder (16.3%; 15/90), Tourette syndrome (TS) (10.1%; 9/90), and depression (9.2%; 8/90). The Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version-Turkish Version (K-SADS-PL-T) was used. The assessment included structured measurements, including the Turgay Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV)-Based Child and Adolescent Behavior Disorders Screening and Rating Scale (T-DSM-IV-S) (parents and teachers) (0=absent, severity rated from 1 to 3), and the Conners Teacher Rating Scale for ADHD-Short version (teachers). Parents completed the "Barkley Stimulants Side Effects Rating Scale" (BSSERS; [17 symptoms; 0=absent, severity rated from 1 to 9]) at baseline and on the third, seventh and 15th days of the medication. Baseline measures also included CGI for ADHD, structured diagnostic interview based on DSM-IV (K-SADS-PL-T), socio-economic status index, and family history for psychiatric disorders. The total sum of all items in BSSERS was calculated. The subjects with an increase in the sum, as well as subjects who discontinued medication because of side effect, were accepted as "affected" and the ones who showed decrease or no difference were accepted as "not-affected".Results:Seventy-seven patients out of 90 (85.6%) maintained treatment beyond the 15th day. 5 patients discontinued Ritalin-IR due to "noncompliance", and/or "lack of efficacy". 8 (8.9%) patients discontinued due to the side effects of Ritalin, which included "loss of appetite" in 3 patients, "exacerbation in tic severity" in 2 patients, "irritability" in 2 patients, and "proneness to cry" in 1 patient. 1 of the patients who discontinued Ritalin because of "loss of appetite", additionally had "withdrawal", the second had "delay of sleep onset", and the third had "stomach aches" as side effects. 7 out of these 8 cases had one or two comorbid diagnosis (2 TS, 2 learning disorder, 2 depression, 1 obsessive-compulsive disorder and 1 conduct disorder). Repeated measures multiple analyses of variance revealed an overall significant difference on Barkleys Side Effects Severity Scale points. Significant changes were found on the items of "loss of appetite", "irritability", "proneness to cry", "anxiety", "nail biting", and "euphoria". Only the severity of the "loss of appetite" item increased, while the remaining 5 symptoms decreased significantly. When the "affected" and "not-affected" groups were compared, a significant difference, in terms of side effect severity of Ritalin-IR, only for the for the presence of a co-morbidity, but not for gender, age, dosage of Ritalin, CGI for ADHD, severity of "inattention" and "impulsivity-hyperactivity".AdverseEffects:An unspecified number of patients had delay of sleep onset, loss of appetite leading to withdrawal in 3, irritability leading to withdrawal in 2, proneness to cry leading to withdrawal in 1, anxiety, sadness, headache, stomachache, nightmares, day dreaming, talking less to others, withdrawal, drowsiness, nail biting, euphoria, dizziness, tics leading to withdrawal in 2.AuthorsConclusions:The results indicate that some items of the BSSERS could themselves be symptoms, but not side effects, and decrease in severity by the MPH-IR [methylphenidate immediate-release] medication. Therefore, baseline measurement of the severity of possible side effects and/or symptoms should be obtained before medication. In the short-term, MPH-IR can be considered as a safe medication for ADHD. When the overall BSSERS item severity is considered, our findings suggest having a comorbid diagnosis predicts more untoward effects. Co-morbid cases should be more closely monitored for side effects and these untoward effects mey [sic] benefit from concurrent medication for the comorbid psychiatric condition.