1. Nelson, Roxanne


Nurses and patients need better information about side effects and risks.


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The off-label use of high-dose antipsychotics for conditions such as attention deficit-hyperactivity disorder (ADHD) appears to significantly increase the risk of unexpected death in children and young adults, according to a recent retrospective study.

Figure. An antipsych... - Click to enlarge in new window An antipsychotic drug prescribed to teenager Thomas Oliver McGowan caused him to suffer from a rare condition the coroner called a "significant contributory factor" to his death. Photo (C) PA Images / Alamy Stock Photo.

Ray and colleagues compared the risk of unexpected death in a population of Medicaid recipients ages five to 24 years who were prescribed antipsychotic medications (most commonly quetiapine) at higher than 50-mg doses (30,120 participants) with those who received antipsychotic medications (most commonly risperidone) at 50-mg or lower doses (28,377 participants) and a control group receiving standard medications (such as psychostimulants) for ADHD or other nonpsychotic diagnoses (189,361 participants).


The researchers found a 3.5-fold greater risk of unexpected death in the higher-dose group compared with the lower-dose or control group. The risk of death due to cardiovascular and metabolic causes in the higher-dose group was increased 4.3-fold. No significant increased risk was found in the lower-dose group.


These findings reinforce the importance of adhering to medication guidelines, including first trying alternative treatments, including psychosocial interventions; cardiometabolic assessment before treatment; and close monitoring of patients for the duration of treatment, according to the study. "The literature suggests the majority of antipsychotics are prescribed by nonpsychiatrists," said lead study author Wayne A. Ray, professor of health policy, Vanderbilt University School of Medicine, in Nashville, Tennessee. "Patients benefit if all members of the therapeutic team have better knowledge of medication effects and alternatives."


When used on label to treat schizophrenia spectrum, tic, Tourette, autism spectrum, and bipolar disorders in children and adolescents, 50 mg of a second-generation antipsychotic is a relatively low dose, explained Aaron Miller, assistant clinical professor and psychiatric NP at the University of California San Francisco School of Nursing. "From an advanced practice nursing perspective, this study highlights the need to carefully consider other evidence-based treatment options, both nonpharmacological and pharmacological, before using a second-generation antipsychotic as an off-label treatment," he said. For nurses in general, Miller noted, the findings underscore the importance of also educating patients and their families on these medications so they can participate knowledgably in evaluating risks and treatment options with their psychiatric providers and monitor for side effects if antipsychotic treatment is initiated.


"Much like how it is commonplace to provide parents with informed consent about the associated risks of suicidal ideations and behavior during the early stages of antidepressant therapy, we have to expand the list to sensitize parents about what the evidence says regarding[horizontal ellipsis] off-label antipsychotic usage with this population," said Sean Convoy, assistant professor and lead faculty, Psychiatric Mental Health Nurse Practitioner Program, Duke University School of Nursing, in Durham, North Carolina.


Convoy added that such comprehensive discussion is also needed at policymaking levels, including in government agencies and national health care organizations. "While nurses can't control provider practice behavior, they often function as the system's observing ego," said Convoy. "Nurses can assess their patients for sufficient informed consent and adverse events as they relate to the identified risk and then report patterns and trends to stakeholders within their work settings to generate grassroots change."-Roxanne Nelson




Ray WA, et al. JAMA Psychiatry 2018 Dec 12 [Epub ahead of print].