THE USE OF ANTIPSYCHOTIC MEDICATIONS IN CHILDREN

Increasing Use of Antipsychotic Medications. Mark Olfson and colleagues have been monitoring the use of antipsychotic medications for the treatment of children over many years. Since the mid-1990s antipsychotic medications have been increasingly prescribed for children, adolescents, and adults (Correll & Blader, 2015; Littrell, 2015). In the most recent report, Olfson, King, and Schoenbaum (2015) find a small reduction in the use of antipsychotics for younger children from 2006 to 2010, but an increase in use for older children from 2006 to 2010. According to the report, “The percentages of young people using antipsychotics in 2006 and 2010, respectively, were 0.14% and 0.11% for younger children, 0.85% and 0.80% for older children, 1.10% and 1.19% for adolescents, and 0.69% and 0.84% for young adults”, p.867.

Antipsychotics Are Primarily Used for Behavioral Control in Young Children. In an editorial discussing the Olfson et al. publication, Correll and Blader (2015) indicated that antipsychotic drugs have only received FDA approval for schizophrenia, bipolar mania, irritability associated with autism, and Tourette syndrome in children. Correll and Blader noted that most of the prescriptions of antipsychotics for children reported by Olfson et al. were for conditions which had not been approved by the FDA (called off-label use). Olfson et al. reported that for younger children those receiving antipsychotic medications most often carried a diagnosis of ADHD with aggression and/or disruptive behavior disorders. For adolescents, most carried a diagnosis of depression. Less than 25% of the children being treated with antipsychotics were receiving any type of talk therapy or family instructions on behavioral control.

Horrendous Side Effects of Antipsychotic Medications.   Antipsychotic drugs all share the property of blocking dopamine receptors. They have very significant side effects. Their use has been questioned for even the conditions for which they were initially designed to treat (see below).

  • Antipsychotic drugs, particularly the second generation antipsychotics such as risperidone, olanzapine, Seroquel cause weight gain that does not plateau. They induce diabetes and increase fats in the blood such that risk of heart disease is greatly increased. Children are much more sensitive to these effects (Correll & Blader, 2015)
  • Antipsychotics induce breast development in boys (references in Chapter 6 of Littrell)
  • Antipsychotics induce hormonal changes associated with osteoporosis (decreased bone strength) (references in Chapter 6 of Littrell)
  • Some second generation antipsychotics induce cardiac arrhythmias that are associated with risk of sudden death (references in Chapter 6 of Littrell)
  • Antipsychotics induce the expression of more dopamine receptors to which dopamine will bind more avidly such that after removal rebound psychosis might ensue (Grace, 2012; Seeman et al., 2005)
  • Antipsychotics induce dystonia or involuntary movement disorders which can make walking and locomotion almost impossible; dystonia occurs immediately upon antipsychotic initiation in about 15.7% of persons (Ballerini, Bellin, Niccolai, Pieroni, Ferrara, 2002); antipsychotics also can induce a second type of motor problem which is similar to the motor problems seen in those with Parkinson’s disease, although second generation antipsychotics are less likely to induce these effects (See Chapter 6 in Littrell, 2015)
  • Antipsychotics have been shown in primates to reduce the volume of the brain by significant amounts (Dorph-Petersen et al., 2005; Konopaske et al., 2007). Brain volume reduction has also been shown in people as well (Fusar-Poli et al., 2013; Ho, Andreasen, Ziebell, Pierson, & Magnotta, 2011). In terms of mechanism through which antipsychotics might reduce brain volume, recent research suggests that these drugs induce activation of white blood cells in the cortex (Cotel et al., 2015).

Concurrent Use of Antipsychotics with Other Medications. According to the Olfson et al. (2015) report, many children prescribed antipsychotic medications were concurrently prescribed other classes of medication in addition to their antipsychotics. For small children, 58.7% were also receiving stimulants; for older children 68.7% were receiving concurrent stimulants; for older adolescents, 59.1% were receiving concurrent antidepressants. Poly-pharmacy is alarming because drugs are evaluated for safety individually. Little information is available regarding the safety of various drug combinations.

Not only is poly-pharmacy an adventure into the land of the unknown with regard to safety, but knowledge regarding the mechanism of action of various drugs introduces wonderment over the rationale for the combinations being used in the treatment of children. Stimulants increase the release of dopamine, while antipsychotics block dopamine receptors that will receive the dopamine or serotonin message. The purported mechanism of action of antidepressants is increasing the availability of serotonin, which will be countered by the action of the atypical antipsychotic, which block serotonin receptor (Loy et al., 2012). It makes no sense to increase a neurotransmitter and then block its action.

Rather than having a theoretical basis for the use of antipsychotics, the current use of antipsychotics is based on the limited findings from 8 studies that they decrease aggressive behavior. The Cochrane Review (Loy et al., 2012) concluded that “there was some evidence of limited efficacy of risperidone in reducing aggression and conduct problems in children and youths (aged 5 to 18 years) with disruptive behavior disorders in the short term (four to 10 weeks) from a small number of studies in which there was some risk of bias of overestimating the true intervention effect” p. 19.

Irony that Antipsychotics Are Being Questioned for Use in Those Who Have Psychosis.  Antipsychotics are able to significantly reduce auditory hallucinations in those with psychosis. However, even for those with psychosis, antipsychotic use is being questioned. Long term studies find that those who are not medicated have better long term functional recovery (employment and social relationships) than those who are medicated (Harrow, Jobe, & Faull, 2012; Wunderink et al., 2013, see discussion in Chapter 6 of Littrell, 2015). It’s ironic that while antipsychotics are being questioned for the population for which they were initially named, they are being extended for use in new populations.

Alternatives to Antipsychotics for the Treatment of Aggression/Disruptive Behavior in Children. Physicians may feel compelled to prescribe antipsychotics for children because they are motivated to decrease the distress in families who are raising difficult children. However, alternatives to antipsychotics, without the horrendous side-effects, are available. Omega-3s have been shown to improve aggressive behavior in children (Raine, Portnoy, Liu, Mahoomed, & Hibbein, 2015). With regard to the older children treated for depression with antipsychotics, omega-3s, exercise, meditation all ameliorate depression (see Chapter 4 in Littrell, 2015). Perhaps, today’s physicians need to remember the admonition to “first, do no harm”?

Ballerini, M., Bellin, S., Niccolai, C., Pieroni, V., & Ferrara, M. (2002). Neuroleptic-induced dystonia: incidence and risk factors. European Psychiatry, 17 (6), 366-368.

Correll, C. U., & Blader, J. C. (2015). Antipsychotic use in youth without psychosis: a double-edged sword. JAMA Psychiatry, 72(9), 859-860.

Cotel, M-C., Lenartowicz, E. M., Natesan, S., Modo, M. M., Cooper, J. D., Williams, S. C. R., Kapur, S., & Vernon, A. C. (2015). Microglial activation in the rat brain following chronic antipsychotic treatment at clinically relevant doses. European Neuropsychopharmacology, http://dx.doi.org/10.1016/j.euroneuro.2015.08.004.

Dorph-Petersen, K. A., Pierri, J. N., Perel, J. M., Sun, Z., Sampson, A. R., & Lewis, D. A. (2005). The influence of chronic exposure to antipsychotic medications on brain size before and after tissue fixation: A comparison of haloperidol and olanzapine in macaque monkeys. Neuropsychophramacology, 30(9), 1649=1661.

Fusar-Poli, P., Smieskova, R., Kempton, M. J., Ho, B. C., Andeasen, N. C. & Borgwardt, S. (2013). Progressive brain changes in schizophrenia related to antipsychotic treatment: A meta-analysis of longitudinal MRI studies. Neuroscience and Biobehavioral Reviews, 37(8), 1680-1691.

Grace, A. A. (2012). Dopamine dysregulation by the hippocampus: implications for the pathophysiology and treatment of schizophrenia. American Journal of Psychiatry, 161(9), 1750-1780.

Harrow, M., Jobe, T. H., Faull, R. N. (2012). Do all schizophrenia patients need antipsychotic treatment continuously throughout their lifetime? A 20-year longitudinal study. Psychological Medicine, 42(10), 2145-2155.

Ho, B. C., Andreasen, N. C., Ziebell, S., Pierson, R., & Magnotta, V. (2011). Long-term antipsychotic treatment and brain volume: a longitudinal study of first-episode schizophrenia. Archives of General Psychiatry, 68 (2), 128-137.

Konopaske, G. T., Dorph-Petersen, K. A., Pierri, J. N., Wu, Q., Sampson, A. R., & Lewis, D. A. (2007). Effect of chronic exposure to antipsychotic medication on cell numbers in the parietal cortex of macaque monkeys. Neuropsychopharmacology, 32 (6), 1216-1223.

Littrell, J. (2015).  Neuroscience for psychologists and other mental health professionals: promoting well-being and treating mental illness.  New York:  Springer.

Loy, J. H., Merry, S. N., Hetrick, S. E., & Stasiak, K. (2012). Atypical antipsychotics for disruptive behavior disorders in children and youths. Cochrane Database System Review, doi: 10.1002/14651858.CD008559.pub.2.

Olfson, M., King, M., & Schoenbaum, M. (2015). Treatment of young people with antipsychotic medications in the United States. JAMA Psychiatry, 72 (9), 867-874.

Raine, A., Portnoy, J., Liu, J., Mahoomed, T., & Hibbeln, J. R. (2015). Reduction in behavior problems with omega-3 supplementation in children aged 8-16 years: a randomized, double-blind, placebo-controlled, stratified, parallel-group trial. Journal of Child Psychology and Psychiatry, 56 (5), 509-520.

Seeman, P., Weinshenker, D., Quirion, R., Srivastava, L. K., Bhardwaj, S. K., Grandy, D. K., . .. Tallercio, T. (2005). Dopamine supersensitivity correlates with D2high states, implying many paths to psychosis. Proceedings of the National Academy of Sciences, 102(9), 3513-3518.

Wunderink, L., N., Nieboer, R. M., Wiersma, D., Sytema, S. & Nienhuis, F. J. (2013). Recovery in remitted first-episode psychosis at 7 years of follow-up of an early dose reduction/discontinuation or maintenance treatment strategy: long-term follow-up of a 2-year randomized clinical trial. JAMA Psychiatry, 70 (9), 913-920.

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