Pharmacotherapy in Children and Adolescents at Clinical-High Risk for Psychosis and Bipolar Disorder

Abstract

This review aims to describe the importance of i) detecting individuals at clinical high-risk for psychosis (schizophrenia) or bipolar disorder, especially in children and adolescents, in order to enable early intervention, and ii) evaluating different intervention strategies, especially pharmacotherapy, during the subsyndromal or "prodromal" stages of these severe and often debilitating disorders. The different approaches regarding the psychotic and bipolar clinical high-risk state are discussed, including reasons and evidence for early (pharmacological) intervention and risks of treatment vs. non-treatment. Only 10 prospective studies of antipsychotics (randomized=4) and 6 prospective studies of non-antipsychotic pharmacologic agents (randomized=3, i. e., omega-3 fatty acids=2, glycine=1) for the psychotic clinical high-risk state and only 4 prospective studies of mood stabilizing medications for the bipolar clinical high-risk state (randomized=2, i. e., lithium=1, valproate=1) were detected. Based on the minimal efficacy data, adverse effect risks, especially in pediatric populations, nonspecific psychopathology, and unknown true risk for the development of either psychosis or bipolar disorder or of chronically disabling symptoms and disability, medication treatment currently remains second choice after psychosocial intervention. Additional research in this area is clearly needed in order to shed more light on the relevance and predictive value of potentially prodromal symptoms, their identification and most appropriate management options.

Safety and Tolerability of Antipsychotic Drugs in Pediatric Patients: Data From a 1-Year Naturalistic Study

“…Moreover, the efficacy and safety of APs when used in this particular population are still supported by few studies often plagued by several methodological limitations such as a short observational period, a relatively low number of involved subjects, and the exclusion of patients (such as those presenting comorbidities or being treated with more than one drug) that will eventually be treated with APs. Young patients affected by bipolar disorder, psychosis, or schizophrenia have been shown to be particularly prone to experiencing ADRs due to APs (11). Also, children and adolescents seem to present a higher sensitivity to several ADRs such as neurologic disturbances, hyperprolactinemia, cardiovascular-related adverse events, weight gain, and related metabolic features in comparison to adult patients (12)(13)(14).…”

Is “early intervention” in bipolar disorder what it claims to be?

“…While these medications have been shown to be effective in managing BD in adults, the lack of empirical evidence to support the efficacy of these medications in treating early‐stage BD among children and adolescent populations is concerning. In fact, only four prospective studies have examined the efficacy of prescribing psychotropic medications for subsyndromal populations, with differing findings . For example, one study found no difference between valproate monotherapy and placebo for adolescents with prodromal BD.…”

“…Future early intervention research involving pharmacotherapies should be refined to focus on perhaps more novel agents that target the potentially unfolding pathophysiology, rather than encouraging the earlier commencement and administration of potent medications designed to treat more chronic and severe phases of illness. In this vein, psychosocial interventions as first choice and pharmacological therapy as second line have been recommended in more recent early intervention models . However, even here, primacy should be given to safer agents with lower likelihood of side effects.…”

“…Despite the many serious and, as yet, unknown side effects of psychotropic medications, research examining the trends of diagnosis and treatment of BD in younger populations has revealed that, over time, there has been a substantial increase in the number of children and young people prescribed psychotropic medication . Although this increase in administering psychotropic medications could be due to more effective detection of the early signs and symptoms, it could also reflect a dangerous shift in clinical practice, whereby clinicians are engaging in “off‐label” prescribing of psychotropic medications to patients who have yet to be formally diagnosed with BD . This trend has been observed in the treatment of major depression, where a cohort study of young patients in Wales indicated that, from 2003 to 2013, the prescription of antidepressants increased, although the number of young people recorded with a diagnosis of depression declined .…”

The Challenge of Defining Prodromal Symptoms of Schizophrenia and Bipolar Disorders

“…In this journal, Lambert and colleagues [1] present an excellent critical review of the existing literature regarding the prodromal symptoms of psychotic related disorder (e. g., schizophrenia) and bipolar disorders, illnesses that usually begin during youth and young adulthood and are associated with significant psychosocial impairment. The authors highlighted the importance of identifying the prodromal symptomatology and factors associated with increased risk to develop these disorders and summarized the deficiencies of the current literature.…”