Introduction

William Klykylo

Child psychopharmacology is a relatively new field. The 1937 publication by Charles Bradley reporting the effects of administering racemic amphetamine sulfate (Benzedrine) to 30 children 5 to 14 years of age with various behavioral disturbances is usually considered to mark the beginning of the modern era of child psychopharmacology.

More than 20 years later, the first book concerned exclusively with psychopharmacologic research in child psychiatry, Child Research in Psychopharmacology, evolved out of the 1958 Conference on Child Research in Psychopharmacology sponsored by the National Institute of Mental Health (Fisher, 1959). The book contains an annotated list of 159 references of studies of the effects of psychopharmacologic agents administered to children with psychiatric problems, beginning with Bradley’s 1937 publication. Interestingly, M. Molitch and coworkers also published, in 1937, three papers concerning the use of amphetamine sulfate in children, including two placebo-controlled studies (Molitch and Eccles, 1937; Molitch and Poliakoff, 1937; Molitch and Sullivan, 1937). Two of the studies found that amphetamine sulfate improved scores of children on intelligence tests, and one reported that 86% of 14 enuretic boys who had not responded to placebo were dry when given increasing doses of amphetamine sulfate and reverted to bedwetting within 2 weeks after the drug was discontinued.

In the 1950s, the classes of drugs currently most important in general psychiatry were introduced: the antipsychotics (chlorpromazine and other compounds), the antidepressants, and lithium carbonate. The benzodiazepines, in particular diazepam and chlordiazepoxide, were introduced into clinical psychiatric practice in the early 1960s. Then in the late 1980s and throughout the 1990s, the selective serotonin reuptake inhibitor (SSRI) antidepressants and the atypical antipsychotics, now referred to as second-generation antipsychotics, began to be introduced. Because of increased difficulties in conducting psychopharmacologic research and in obtaining FDA approval of the safety and efficacy of psychoactive drugs in children and younger adolescents, the investigation and introduction into clinical practice of psychoactive drugs in children have always lagged somewhat behind that for adults. Weiner and Jaffe (1985) have written a brief but interesting overview of the earlier history of child and adolescent psychopharmacology.

Texts focusing entirely or significantly on child and adolescent psychopharmacology include those by Aman and Singh (1988), Bezchlibnyk-Butler and Virani (2004), Campbell et al. (1985), Gadow (1986a, 1986b), Klein et al. (1980), Kutcher (1997, 2002), Martin et al. (2003), Riddle (1995a, 1995b), Rosenberg et al. (1994, 2002), Walsh (1998), Weiner (1985), Werry (1978), Werry and Aman (1999), Trivedi and Chang (2012), and McVoy (2012). The reader who wishes an in-depth review of major issues of the recent past is referred to Neuropsychopharmacology: The Fifth Generation of Progress (Davis et al., 2002) and the fascinating An Oral History of Neuropsychopharmacology: The First Fifty Years, Peer Interviews (Volumes 1-10) (Ban, 2011). A review of these texts, and indeed their very proliferation, documents the massive growth of psychopharmacology as a component of the medical care of children and adolescents.

In most instances, reviews of the literature establishing the clinical efficacy and safety of earlier FDA-approved treatments for the psychiatric disorders of children and adolescents are not included in this book. Readers who wish to review the research data establishing these standard treatments will find such information to be accessible in the texts cited above.

Section II of this book not only summarizes the standard treatments but also focuses in greater detail on research into new and not yet approved uses of drugs in child and adolescent psychiatry and reviews these studies. Some knowledge of psychopharmacologic research principles and techniques is essential to critically evaluate the data that appear in the psychiatric literature and to make informed clinical decisions about whether a trial of a particular drug is warranted for a particular patient.

Most important psychopharmacologic research designs include comparison of the drug being investigated with either placebo or a drug approved as a standard treatment for the psychiatric disorder in question. Hence it is important to have a basic understanding of placebos.

PLACEBOS

According to the Oxford English Dictionary (OED) (1989), the English word placebo was directly adopted from the Latin word meaning “I shall be pleasing or acceptable.” By 1811, it was defined in Hooper’s Medical Dictionary (OED, 1989) as “an epithet given to any medicine adapted more to please than benefit the patient.” In 1982, the OED added the following definition of placebo, which fairly accurately described its current use in psychopharmacologic research: “A substance or procedure which a patient accepts as a medicine or therapy but which actually has no specific therapeutic activity for his condition or is prescribed in the belief that it has no such activity.” Although placebos are often composed of substances thought to be inert, in psychopharmacologic research, placebos may also contain active ingredients chosen to simulate adverse effects of the drug to which the placebo is being compared. The purpose of this is to keep all participants “blind” by making it more difficult for patients and observers to distinguish between drug and placebo based solely on the drug’s adverse effects.

Placebos play a crucial role in clinical psychopharmacologic research by providing nonspecific treatment effects for comparison with the drug under investigation. These nonspecific psychological and physiologic changes are not drug specific and may be measured by rating scales (Prien, 1988). These changes include both beneficial and adverse effects produced by the expectations the patient or observers have about the drug, natural fluctuations in the clinical course of the disease, and spontaneous alterations in the patient’s condition that may have nothing to do with the illness under consideration; effects of the relationship among the patient, therapist, and other medical staff; and other unknown effects.

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