Charles W. Popper

Sudden death and tricyclic antidepressants: clinical considerations for children.

ABSTRACT The sudden collapse and death in three prepubertal children during routine treatment with desipramine was recently reported in brief statements. Insufficient clinical information is available to infer a cause-and-effect relationship between the therapeutic use of desipramine and sudden death in these children. Speculatively, a variety of possible mechanisms could account for sudden death in children receiving treatment with tricyclic antidepressants: a cardiac event, an increase or decrease in blood pressure, an increase in pulse, a seizure (with complications), or heat stroke. The extent of medical monitoring in the three cases is not clear, leaving unresolved whether a change in standard monitoring procedures is indicated. The total number of children who have received desipramine treatment is not known, so it is not possible to specify the incidence of this putative adverse effect. It is clear that the incidence of death from accidental overdose is substantially higher. Given the current available level of knowledge about these cases, no clinical recommendations are offered concerning when to avoid or to use desipramine; however, certain clinical considerations regarding the use of antidepressants in children are raised and discussed.

Single-micronutrient and broad-spectrum micronutrient approaches for treating mood disorders in youth and adults.

Several different vitamins and minerals appear to be effective augmenting agents for mood-modifying drugs, but are not potent monotherapies in themselves for treating psychiatric disorders. In contrast, broad-spectrum micronutrient interventions appear in early trials to be as effective as psychiatric medications with fewer adverse effects for treating mood disorders, ADHD, aggressivity, and misconduct in youth and adults. Broad-spectrum treatments also may improve stress responses, cognition, and sense of well-being in healthy adults, but have been less well studied in youth. Current clinical data justify an extensive expansion of research on micronutrient mechanisms and treatments in psychiatry.

The MAVRIC–C and MAVRIC–P: A Preliminary Reliability and Validity Study

We administered the Measure of Aggression, Violence, and Rage in Children (MAVRIC; Bass, Geenens, & Popper, 1993a, 1993b), a questionnaire assessing the severity of reactive, impulsive aggression, to 28 prepubertal psychiatrically hospitalized children and 54 prepubertal lowrisk nonpatients and their mothers. Cross-informant reliability was supported between the MAVRIC–Child Version (MAVRIC–C; Bass et al., 1993a) and MAVRIC–Parent Version (MAVRIC–P; Bass et al., 1993b), r = .62, p < .001. Convergent validity was supported with the Aggressive Behavior factor of the Child Behavior Checklist (Achenbach, 1991a) for the MAVRIC–C, r = .62, p < .001, and MAVRIC–P, r = .74, p < .001. Both versions were also associated with disruptive behavior disorders, inpatient status, and assaultive behavior. We discuss the differences in the perception of aggression as a function of informant.

Mood Disorders in Youth: Exercise, Light Therapy, and Pharmacologic Complementary and Integrative Approaches

The therapeutic value of physical exercise, bright light therapy and dawn simulation, and several pharmacologic treatments, including hypericum (St. Johns wort), S-adenosylmethionine, and 5-hydroxytryptophan, are reviewed, with a focus on their use for treating major depressive disorder in children and adolescents and also for alleviating depressed mood in the general (nonclinical) population of youth. For each treatment discussed, all published randomized, double-blind, placebo-controlled trials are summarized, along with some additional selected studies. Nutritional psychopharmacology and several other approaches to treating depression will be presented in an upcoming volume in the Child and Adolescent Psychiatric Clinics of North America.

Postmortem Pharmacokinetics of Tricyclic Antidepressants: Are Some Deaths During Treatment Misattributed to Overdose?

Postmortem TCA blood levels have long been used to make decisions about the cause of death in lethalities arising from overdoses of tricyclic antidepressants (TCAs). However, high TCA levels in postmortem blood are not easy to interpret, and raise some unexpected questions for all clinicians who prescribe TCAs for children. When a child dies with a postmortem TCA level over 1,000 ng/ml, the question of medication overdose is immediately raised. For example, the customary blood levels in children and adults during treatment with desipramine are generally below 300 ng/ml, and levels above 500 ng/ml are usually interpreted as toxic. A frequent concern is that a child with a very high postmortem TCA level may have taken an acute

Overview of integrative medicine in child and adolescent psychiatry.

Complementary and alternative medicine (CAM) defies simple definition, because the distinction between CAM and conventional medicine is largely arbitrary and fluid. Despite inconclusive data on the efficacy and safety of many CAM treatments in child and adolescent psychiatry, there are enough data on certain treatments to provide guidance to clinicians and researchers. CAM treatments, as adjunctive therapy or monotherapy, can be clinically beneficial and sensible. The low stigma and cost-competitiveness of many CAM psychiatric treatments are highly attractive to children and parents. Physicians need to be knowledgeable about CAM treatments to provide clinically valid informed consent for some conventional treatments.

Psychosis Resulting From Herbs Rather Than Nutrients

To the Editor: The very useful case report by Wong et al1 illustrates the potential harm of psychosis resulting from concurrent administration of over 50 ingredients, including 18 unregulated herbal agents, 19 digestive enzymes, 6 probiotic strains, and other over-the-counter substances. This is a valuable cautionary message, but the title and abstract lead readers astray. Instead of using specific language to identify the offending agents as herbs, the authors use the general term dietary supplements, an erroneous rubric often used in marketing herbs. By publishing evidence for an adverse herbal interaction with the term dietary supplements, this article inadvertently leads readers (many of whom read only the title and abstract) to believe that this case demonstrates harm from consumption of nutrients fundamental for human health. Without careful reading of the full text and Table 1, readers will not recognize that only 4 of the > 50 ingredients this patient consumed were minerals or vitamins (chromium, vitamin B6, folate, vitamin B12). And, given that the patient’s B12 levels, when tested, were in the low normal range, resulting in treatment with cyanocobalamin 1,000 μg, there is good reason to suspect that even these few nutrients were not very bioavailable or had trivial physiologic impact. It is unlikely that the patient’s psychosis resulted from the direct or combined effects of minerals, vitamins, enzymes, or probiotics. Rather, it is most likely that the patient’s physical and mental impairments resulted from the concurrent use of 18 botanicals, each with its own complex, nonspecific, and largely unmapped pharmacologic actions. Humans have evolved to need dietary nutrients such as minerals and vitamins for the function of every mitochondrion (and hence every cell) of our brains and bodies. In contrast, there is no evidence of evolutionary need of herbs. In fact, physiologically active herbs could be more accurately described as crude drugs that have been misclassified as dietary supplements (eg, St John’s wort, tobacco, marijuana, coca leaf, and poppies are plant parts with psychoactive chemicals). The signatories to this letter have contributed to the rapidly growing empirical literature demonstrating mental health benefits from nutrients (not herbs)2–8 as well as establishing safety of these nutrients,9 even when multiple nutrients are used in combination. It concerns us that the nonspecific use of the term dietary supplements could prejudice interpretation of the scientifically valid studies on nutritional approaches to treating psychiatric conditions. In addition to our own work, there is a large literature supporting the association between dietary patterns and mental health in population studies,10 and a new international society of scientists has formed to study this area (International Society for Nutritional Psychiatry Research; ISNPR.org).11 If the title and abstract of the report had accurately specified that it was primarily about the risk of the concurrent use of multiple unregulated botanical substances, there would be no confusion. Given the present situation, we respectfully ask that a correction be issued.

CAM encompasses a vast range of types of treatments, systems of health care, and lifestyle philosophies. Preface.

In deciding what topics to cover in this introduction to complementary and alternative medicine (CAM) treatments in child and adolescent psychiatry, we were primarily interested in focusing on treatments backed by useful research—data that allow us to evaluate the clinical value of these treatments for youth with psychiatric disorders. The CAM treatments covered here have been chosen because the available data in youth allow some inferences about their effects (positive or otherwise), because the limited data justify more research, or because of widespread public interest or common use of these treatments. A huge variety of interventions were considered, but the scientific literature is too scant to support the meaningful discussion of most CAM treatments, especially in youth. We have found increasing activity and improving quality in CAM research in child and adolescent psychiatry, so the Child and Adolescent Psychiatric Clinics of North America have expanded their original plans and have allowed child and adolescent CAM psychiatry to be covered in 2 volumes. In these volumes, it will be clear that the data on many CAM treatments are often too limited to draw firm conclusions about their efficacy in youth, but are promising enough to offer helpful guidance to clinicians and researchers in child and adolescent psychiatry. These 2 volumes are, by necessity, highly selective. CAM encompasses a vast range of types of treatments, systems of health care, and lifestyle philosophies. The selection of treatments discussed in these volumes tends toward the more conventional “near” side of CAM. We have not included alternative or non-Western systems of medicine. Acupuncture has gained a strong foothold in American medicine, even though its mechanism remains difficult to explain based on the Western traditions of anatomy and physiology. We have not included acupuncture in these volumes because we could not find any data regarding its use for psychiatric indications in youth (at least in the literature published in English). Chiropractic manipulation for physical conditions, although covered by health insurance companies, is supported by data, but the magnitude of its effects remains uncertain, and there are little data

Using drug information sheets for parents.

IN every clinical encounter with every patient, clinicians make judgments about how to communicate information. Parents need facts about medications for their children. They cannot comfortably administer pills and support a child through medication treatment without sufficient information to be cognitively clear and affectively steady about their appropriate usage. Although adolescents and children receive information about medications directly from doctors and nurses, parents often are their most important and enduring informants about proper medication utilization. Every clinician who has helped parents leam about child psychopharmacological treatment is aware that no single standard set of sentences will work for all parents. Each discussion is tailored and individualized to the characteristics of the parents and to their reactions to the information as it is being provided. These discussions, developed largely out of the give-and-take between physician and parent, result in an educational process that respects the individuality of the parents and their circumstance. As the discussion goes along, the physician makes numerous decisions about just what to say. It is easy for a clinician to speak on too high a level, or to talk at too low a level. Too much information might be provided, or too little information may be offered. Deviations in either direction can increase parental anxiety. Effective education of parents can directly promote consent to proceed with treatment, influence attitudes and behaviors toward medication, help control uncertainty or anxiety, and improve prospects for compliance with prescribed treatment by parents and children. There is no reasonable way to provide parents with all information. Nor is it desirable to do so. Parents forget and become anxious when overloaded. Some may feel toó preoccupied to listen. Some will not want to know everything that is being said. The goal behind parent education is not to achieve completeness, but to increase understanding and provide adequate knowledge. What about the details ofwording? Exactly what should be said to aid identification of side effects? How do you explain when a parent should telephone the physician between appointments? Should scientific names or brand names be used in these common communications? The problems of communication take on additional complexity when converting information into written form. All of the individualized subtleties must be sacrificed. Further, however fluent and even articulate a parent may be in spoken language, there is a wide range of literacy and reading ability in the population. Parents who themselves have certain language disorders may find written fact sheets particularly troublesome. Alternatively, parents with language processing problems might find it easier to read information than to hear it. For patients who do not readily understand spoken English, for parents who are too preoccupied in the doctors office to listen carefully, for those who learn best through repetition, written information may be the most and perhaps only effective route of providing information. In this issue of JCAP, Dr. Mina Dulcan provides us with a set of drug information sheets that can be used in clinical situations to aid in the education of parents about psychopharmacological treatments of adolescents and children. As she emphasizes, such standardized written material can never substitute for individually directed and conversationally refined discussions in the doctors office. However, these information sheets