Daniel J. Safer

Nonpromotion Correlates and Outcomes at Different Grade Levels.

A comprehensive survey of 200 student folders revealed that elementary school (ES) nonpromotion is primarily associated with low academic achievement and low IQ, whereas a junior high school (JHS) nonpromotion is mainly correlated to behavioral suspensions and excessive absenteeism. Having an ES nonpromotion increases the risk of a later grade retention five fold. During the year following an ES nonpromotion, the behavioral and academic outcome is significantly improved and is generally satisfactory. This is clearly not the case after a JHS grade retention.A comprehensive survey of 200 student folders revealed that elementary school (ES) nonpromotion is primarily associated with low academic achievement and low IQ, whereas a junior high school (JHS) nonpromotion is mainly correlated to behavioral suspensions and excessive absenteeism. Having an ES nonpromotion increases the risk of a later grade retention five fold. During the year following an ES nonpromotion, the behavioral and academic outcome is significantly improved and is generally satisfactory. This is clearly not the case after a JHS grade retention.

Growth rebound after termination of stimulant drugs

To explore further the report of an accelerated weight gain following termination of treatment with a stimulant drug, 66 biannual growth measurements were obtained from 1970 to 1973 on hyperactive schoolchildren who were receiving medication. All received either dextroamphetamine or methylphenidate during the school year; some also received it during the summer. The data revealed that those whose stimulant medication was terminated at the start of summer subsequently grew in weight and height at a significantly greater rate than those who continued to receive medication from June to September. In fact, discontinuance of the medication resulted in a growth rebound for this period which was 15-68% above the age-expected increment.

Self-reported suicide attempts by adolescents

A thorough medical literature review of adolescent self-reported suicide attempts focused on comparing the following: (1) the prevalence of attempts in anonymous vs. face-to-face surveys; (2) the prevalence rates in the United States and Canada vs. those reported elsewhere; and (3) the prevalence of attempt findings vs. self-harm behavior in anonymous surveys. The major findings were: (1) 29 anonymous self-report questionnaire studies from nine countries revealed that a median of 7–10% of adolescent students acknowledged having made one or more suicide attempts; (2) seven structured interview studies revealed a 3–4% lifetime prevalence of attempted suicide by adolescents; (3) self-report questionnaire responses failed to reveal any overlap between deliberate self-harm behavior and suicide attempts; (4) nonanonymous studies had an unusually high rate of refusal. Thus, self-reported suicide attempts are surprisingly frequent in adolescence and are reported two to three times more often under conditions of anonymity. Furthermore, youths report self-harm behavior as distinct from suicide attempts.

A familial factor in minimal brain dysfunction

The medical and social service charts of siblings and half siblings of 17 children with minimal brain dysfunction, (MBD)-all of whom began foster care at a young age — were reviewed for signs and findings of MBD. Compared to the half siblings, the full siblings of index MBD children had a significantly greater occurrence of short attention span, repeated childhood antisocial behavior, and diagnostic evidence for MBD. Appraised also for the sib and half sib groups were the following factors reportedly associated with MBD: presence of a seizure or a congenital disorder, low IQ, low birth weight, being male, and being first in the birth order. From these data, the most impressive findings were the high rate (30%) of seizure histories in designated MBD children and the evidence that there was a far greater occurrence of possible and likely MBD when both genetic and high rate factors coexisted.

Pemoline Hepatotoxicity and Postmarketing Surveillance

OBJECTIVE To review the numerous reports of hepatotoxic adverse drug reactions (ADRs) ascribed to pemoline that were sent to the U.S. Food and Drug Administration (FDA) between 1975 and 1996 and to describe the medical communitys lack of awareness of these reports. METHOD All ADR reports from 1975 through 1996 wherein pemoline was the suspect agent were obtained from the FDA MedWatch Internet site, and some details of nine pemoline-related deaths in youths were obtained directly from the FDA. The published literature on this subject was fully reviewed. RESULTS (1) In premarketing clinical trials with pemoline in the early 1970s, hepatic abnormalities were noted in enzyme levels (1%-3% of youths receiving maintenance treatment), during rechallenges (6 of 6), and in biopsies (2 of 2). (2) Between 1975 and 1989, 12 cases of jaundice and 6 deaths in youths ascribed to pemoline hepatotoxicity were reported to the FDA. (3) The first medical literature report of a serious ADR ascribed to pemoline was in a 1989 letter to the editor. (4) Physicians generally only became aware of serious pemoline hepatotoxicity in December 1996. (5) Pemoline use increased until 1997. CONCLUSION Limitations in postmarketing surveillance and public reporting in the United States, particularly in the 1980s, largely accounted for delays in an appropriate response to pemoline hepatotoxicity.

Absence of tolerance to the behavioral effects of methylphenidate in hyperactive and inattentive children

To determine whether the behavioral benefits of methylphenidate in hyperactive and inattentive children decline during long-term treatment, we analyzed data from 108 hyperactive students who responded well to methylphenidate therapy for 3 to 10 years. Responders were identified by their consistent improvement from baseline on standard teacher rating scales. The therapeutically effective drug doses were corrected for body size and evaluated in relation to increasing age and treatment duration. Body size corrections included milligrams per kilogram, milligrams per kilogram to the 0.7th power, and milligrams per square meter of estimated body surface area. The major findings were that (1) the dose of methylphenidate, when adjusted for growth, did not change significantly during the 3 to 10 years of treatment; (2) the loss of a previously satisfactory response to methylphenidate treatment was uncommon (6%) and when present was related to middle school enrollment, male gender, noncompliance with medication, and lower than customary dosage; (3) the dose calculations that minimized the effects of growth with age were milligrams per kilogram to the 0.7th power and milligrams per square meter of estimated body surface area; and (4) the commonly used milligrams per kilogram dose consistently overcorrected for growth with advancing age.

Are stimulants overprescribed for youths with ADHD

Critics of stimulant treatment for youths with attention deficit hyperactivity disorder (ADHD) have increased their rhetoric of late, contending that the leading medication for it, Ritalin®, is vastly overprescribed. Additionally, they claim that Ritalin (methylphenidate) is inherently dangerous and that the entire system of the diagnosis and treatment of ADHD is seriously flawed. The critics view the underlying reason for the “epidemic” as societal, due to our modern pace of living, our competitive society, and our consumer emphasis. Rejoinders to and clarifications of the more tangible points of the critics are presented, followed by a discussion of some more practical and legitimate concerns for researchers in this area. These concerns include changes within the ADHD category, the clinical need for multiple sources of diagnostic data, infrequent teacher–physician communication, problematic ADHD/conduct disorder comorbidity in adolescence, and the limited amount of community-based research.

Services and prevention: Pharmacoepidemiology of antidepressant use

Between 1988 and 1994, data from 3 large sites revealed a 3-5 fold increase in the prevalence of antidepressant (ATD) treatment for U.S. youths aged 2-19 years. In 1994, the ATD prevalence for youths of this age ranged from 13 per 1000 (in the HMO) to 18 per 1000 (in 2 state Medicaid systems). Males predominated in the 10-14-year-olds treated with ATDs, whereas females predominated among 15-19-year-olds. Caucasians were more than twice as likely to receive ATD therapy than their African-American counterparts. Primary care providers were the major source of ATD prescriptions for youths. The leading diagnoses in primary care were ADHD followed by depression, whereas the diagnostic order was reversed for youths who received psychiatric services. This review provides details concerning these patterns and trends in ATD treatment of youths from community-based clinical data sources. In addition, the role of these data in an expanded, comprehensive psychotropic knowledge base is discussed. Finally, the implications of an expanded knowledge base for ATD treatments are discussed in regard to generating research questions on effectiveness and safety and to improve treatment consensus within a public-health perspective.

Trends in Medication Treatment of Hyperactive School Children Results of Six Biannual Surveys

In biannual school surveys from 1971 through 1981, it was found that the rate of medication treatment of hyperactive students increased two- to threefold over the decade. This increase applied similarly to parochial, public elementary, and public middle/junior high school stu dents. Other findings over the decade include the following: methylphenidate use increased from 40 per cent to 91 percent of all the medication prescribed for hyperactivity, administration of medication for hyperactivity in the school increased from 61 per cent to 87 per cent of the total, and the number treated with medication prescribed by the family doctor decreased from 98 per cent to 59 per cent. Noteworthy fandings in 1981 were as follows: 19 per cent of public elementary school students in special education classes were treated with medication for hy peractivity ; hyperactive students in middle/junior high school had received medication treat ment for an average of five to six years; the most common school period of medication use was grades one through four; entrance into first grade and secondary school corresponded to an increased use of medication for hyperactivity; and female, relative to male, students were treated with medication for hyperactivity less often than would be expected in teacher surveys of class room hyperactivity, a finding particularly striking in middle/junior high school.

Adolescent/Adult Differences in Suicidal Behavior and Outcome

A comprehensive literature review compared the patterns of suicide and suicidal behavior for adolescents and adults to identify age-related similarities and differences. Particular attention was given to follow-up rates of suicide by psychiatrically treated persons in these age groups. The major findings were that (1) adults and adolescent suicide completers were similar with respect to their gender ratio, use of guns in the attempt, completion of the initial attempt, and serious psychopathology; (2) adolescents differed from adults in suicidal behavior in their greater attempt rate, higher attempt/completion ratio, and lower rates of short and intermediate completion following psychiatric treatment; (3) the suicide outcome following psychiatric hospitalization is eightfold greater in adults than in youths during the first 3.5 years postdischarge; and (4) the 5:1 male/female ratio is the same for both adolescent attempters who later suicide and for all U.S. 15-19-year-old suicide completers. The frequent practice of combining adult and adolescent suicide and suicide behavior findings can result in misleading conclusions.