Psychopharmacologic Interventions in Childhood Cancer Survivors
Adolescent and young adult survivors of childhood cancers have been shown to have elevated risks of adverse behavioral and social outcomes including depression, anxiety, attention deficits, antisocial behaviors [1, 2] post-traumatic stress and suicidal ideation [4, 5]. These symptoms may lead health care providers to consider psychopharmacologic agents to treat these symptoms and improve function and quality of life in this population. Survivors may also have medical late effects such as endocrine dysfunction [6, 7], insomnia and fatigue [8–10], as well as increased rates of obesity  that may interact with or mediate psychiatric syndromes. Prevalent neurocognitive late effects in survivors [12–14] also affect educational, health and behavioral outcomes, and may be a common focus of psychopharmacologic intervention. The data on the use of psychotropic use in survivors of childhood cancer is limited to stimulant treatment of attentional and cognitive dysfunction . However, survivors with other significantly impairing symptoms of depression, anxiety, or behavioral dysregulation may nonetheless benefit from psychopharmacologic intervention. Clinicians seeking to treat survivors with psychotropic medications need to consider both their psychological vulnerabilities, and how their medical late effects may impact their treatment responses and their susceptibility to side effects of psychiatric medications.
KeywordsPharmacological intervention Depression Anxiety Attention Deficit Behavioral dysregulation
- 1.Schultz, K. A., Ness, K. K., Whitton, J., Recklitis, C., Zebrack, B., Robison, L. L., et al. (2007). Behavioral and social outcomes in adolescent survivors of childhood cancer: A report from the childhood cancer survivor study. Journal of Clinical Oncology, 25, 3649–3656.Google Scholar
- 2.Zebrack, B. J., Zeltzer, L. K., Whitton, J., Mertens, A. C., Odom, L., Berkow, R., & Robinson, L. L. (2002). Psychological outcomes in long-term survivors of childhood leukemia, Hodgkin’s disease, and non-Hodgkin’s lymphoma: A report from the Childhood Cancer Survivor Study. Pediatrics, 110, 42–52.Google Scholar
- 3.Schwartz, L., & Drotar, D. (2006). Posttraumatic stress and related impairment in survivors of childhood cancer in early adulthood compared to healthy peers. Journal of Pediatric Psychology, 31, 356–366.Google Scholar
- 4.Recklitis, C. J., Lockwood, R. A., Rothwell, M. A., & Diller, L. R. (2006). Suicidal ideation and attempts in adult survivors of childhood cancer. Journal of Clinical Oncology, 24, 3852–3857.Google Scholar
- 5.Recklitis, C. J., Diller, L. R., Li, X., Najita, J., Robison, L. L., & Zeltzer, L. (2010). Suicide ideation in adult survivors of childhood cancer: A report from the Childhood Cancer Survivor Study. Journal of Clinical Oncology, 28, 655–661.Google Scholar
- 6.Brabant, G., Toogood, A. A., Shalet, S. M., Frobisher, C., Lancashire, E. R., Reulen, R. C., et al. (2012). Hypothyroidism following childhood cancer therapy-an under diagnosed complication. International Journal of Cancer, 130(5), 1145–1150. doi: 10.1002/ijc.26086.
- 7.Shalitin, S., Gal, M., Goshen, Y., Cohen, I., Yaniv, I., & Phillip, M. (2011). Endocrine outcome in long-term survivors of childhood brain tumors. Hormone Research in Pædiatrics, 76, 113–122.Google Scholar
- 8.Clanton, N. R., Klosky, J. L., Li, C., Jain, N., Srivastava, D. K., Mulrooney, D., et al. (2011). Fatigue, vitality, sleep, and neurocognitive functioning in adult survivors of childhood Cancer: a report from the Childhood Cancer Survivor Study. Cancer. doi: 10.1002/cncr.25797.
- 9.Johannsdottir, I. M., Hjermstad, M. J., Moum, T., Wesenberg, F., Hjorth, L., Schroder, H., et al. (2012). Increased prevalence of chronic fatigue among survivors of childhood cancers: a population-based study. Pediatric Blood & Cancer, 58(3), 415–420. doi: 10.1002/pbc.23111.
- 10.Green, D. M., Cox, C. L., Zhu, L., Krull, K. R., Srivastava, D. K., Stovall, M., et al. (2012). Risk factors for obesity in adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Journal of Clinical Oncology, 30(3), 246–255. doi: 10.1200/JCO.2010.34.4267.
- 11.Edelstein, K., D’Agostino, N., Bernstein, L. J., Nathan, P. C., Greenberg, M. L., Hodgson, D. C., et al. (2011). Long-term neurocognitive outcomes in young adult survivors of childhood acute lymphoblastic leukemia. Journal of Pediatric Hematology/Oncology, 33(6), 450–458. doi: 10.1097/MPH.0b013e31820d86f2.
- 12.Mulhern, R. K., Merchant, T. E., Gajjar, A., Reddick, W. E., & Kun, L. E. (2004). Late neurocognitive sequelae in survivors of brain tumours in childhood. The Lancet Oncology, 5, 399–408.Google Scholar
- 13.Krull, K. R., Annett, R. D., Pan, Z., Ness, K. K., Nathan, P. C., Srivastava, D. K., et al. (2011). Neurocognitive functioning and health-related behaviours in adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. European Journal of Cancer, 47(9), 1380–1388. doi: 10.1016/j.ejca.2011.03.001.
- 14.Conklin, H. M., Reddick, W. E., Ashford, J., Ogg, S., Howard, S. C., Morris, E. B., et al. (2010b). Long-term efficacy of methylphenidate in enhancing attention regulation, social skills, and academic abilities of childhood cancer survivors. Journal of Clinical Oncology, 28(29), 4465–4472. doi: 10.1200/JCO.2010.28.4026.
- 15.Fulbright, J. M. (2011). Review of cardiotoxicity in pediatric cancer patients: During and after therapy. Cardiology Research and Practice, 2011, 942090.Google Scholar
- 16.Lipshultz, S. E., Landy, D. C., Lopez-Mitnik, G., Lipsitz, S. R., Hinkle, A. S., Constine, L. S., et al. (2012). Cardiovascular status of childhood cancer survivors exposed and unexposed to cardiotoxic therapy. Journal of Clinical Oncology. doi: 10.1200/JCO.2010.33.7907.
- 17.Steinberger, J., Sinaiko, A. R., Kelly, A. S., et al. (2012). Cardiovascular risk and insulin resistance in childhood cancer survivors. The Journal of Pediatrics, 160, 494–499.Google Scholar
- 18.Lown, E. A., Goldsby, R., Mertens, A. C., Greenfield, T., Bond, J., Whitton, J., et al. (2008). Alcohol consumption patterns and risk factors among childhood cancer survivors compared to siblings and general population peers. Addiction, 103(7), 1139–1148. doi: 10.1111/j.1360-0443.2008.02242.x.
- 19.Lu, Q., Krull, K. R., Leisenring, W., Owen, J. E., Kawashima, T., Tsao, J. C., et al. (2011). Pain in long-term adult survivors of childhood cancers and their siblings: a report from the Childhood Cancer Survivor Study. Pain, 152(11), 2616–2624. doi: 10.1016/j.pain.2011.08.006.
- 20.Mulder, R. L., van Dalen, E. C., Van den Hof, M., Bresters, D., Koot, B. G., Castellino, S. M., et al. (2011). Hepatic late adverse effects after antineoplastic treatment for childhood cancer. Cochrane Database of Systematic Reviews, 7, CD008205. doi: 10.1002/14651858.CD008205.pub2.
- 21.Moore, B. D., 3rd. (2005). Neurocognitive outcomes in survivors of childhood cancer. Journal of Pediatric Psychology, 30, 51–63.Google Scholar
- 22.Kirchhoff, A. C., Krull, K. R., Ness, K. K., Armstrong, G. T., Park, E. R., Stovall, M., et al. (2011). Physical, mental, and neurocognitive status and employment outcomes in the Childhood Cancer Survivor Study Cohort. Cancer Epidemiology, Biomarkers and Prevention, 20(9), 1838–1849. doi: 10.1158/1055-9965.EPI-11-0239.
- 23.Kunin-Batson, A., Kadan-Lottick, N., Zhu, L., Cox, C., Bordes-Edgar, V., Srivastava, D. K., et al. (2011). Predictors of independent living status in adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Pediatric Blood & Cancer, 57(7), 1197–1203. doi: 10.1002/pbc.22982.
- 24.Spiegler, B. J., Kennedy, K., Maze, R., Greenberg, M. L., Weitzman, S., Hitzler, J. K., et al. (2006). Comparison of long-term neurocognitive outcomes in young children with acute lymphoblastic leukemia treated with cranial radiation or high-dose or very high-dose intravenous methotrexate. Journal of Clinical Oncology, 24, 3858–3864.Google Scholar
- 25.Copeland, D. R., Moore, B. D., 3rd, Francis, D. J., Jaffe, N., & Culbert, S. J. (1996). Neuropsychologic effects of chemotherapy on children with cancer: A longitudinal study. Journal of Clinical Oncology, 14, 2826–2835.Google Scholar
- 26.Waber, D. P., Carpentieri, S. C., Klar, N., Silverman, L. B., Schwenn, M., Hurwitz, C. A., et al. (2000). Cognitive sequelae in children treated for acute lymphoblastic leukemia with dexamethasone or prednisone. Journal of Pediatric Hematology/Oncology, 22, 206–213.Google Scholar
- 27.Brouwers, P., Riccardi, R., Fedio, P., & Poplack, D. G. (1985). Long-term neuropsychologic sequelae of childhood leukemia: Correlation with CT brain scan abnormalities. The Journal of Pediatrics, 106, 723–728.Google Scholar
- 28.Thompson, S. J., Leigh, L., Christensen, R., et al. (2001). Immediate neurocognitive effects of methylphenidate on learning-impaired survivors of childhood cancer. Journal of Clinical Oncology, 19, 1802–1808.Google Scholar
- 29.Conklin, H. M., Helton, S., Ashford, J., Mulhern, R. K., Reddick, W. E., Brown, R., et al. (2010a). Predicting methylphenidate response in long-term survivors of childhood cancer: a randomized, double-blind, placebo-controlled, crossover trial. Journal of Pediatric Psychology, 35(2), 144–155. doi: 10.1093/jpepsy/jsp044.
- 30.Olfson, M., Huang, C., Gerhard, T., Winterstein, A. G., Crystal, S., Allison, P. D., et al. (2012). Stimulants and cardiovascular events in youth with attention-deficit/hyperactivity disorder. Journal of the American Academy of Child and Adolescent Psychiatry, 51(2), 147–156. doi: 10.1016/j.jaac.2011.11.008.
- 31.Barkley, R. A., McMurray, M. B., Edelbrock, C. S., & Robbins, K. (1990). Side effects of methylphenidate in children with attention deficit hyperactivity disorder: A systemic, placebo-controlled evaluation. Pediatrics, 86, 184–192.Google Scholar
- 32.DeLong, R., Friedman, H., Friedman, N., Gustafson, K., & Oakes, J. (1992). Methylphenidate in neuropsychological sequelae of radiotherapy and chemotherapy of childhood brain tumors and leukemia. Journal of Child Neurology, 7, 462–463.Google Scholar
- 33.Kessler, R. C., Berglund, P., Demler, O., Jin, R., Koretz, D., Merikangas, K. R., et al. (2003). The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA, 289(23), 3095–3105. doi: 10.1001/jama.289.23.3095.
- 34.American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (DSM-5®). American Psychiatric Pub.Google Scholar
- 35.Papakostas, G. I., Petersen, T. J., Iosifescu, D. V., Summergrad, P., Sklarsky, K. G., Alpert, J. E., et al. (2004). Somatic symptoms as predictors of time to onset of response to fluoxetine in major depressive disorder. The Journal of Clinical Psychiatry, 45(4), 543–546.Google Scholar
- 36.Masand, P. S., & Gupta, S. (1999). Selective serotonin-reuptake inhibitors: An update. Harvard Review of Psychiatry, 7, 69–84.Google Scholar
- 37.Fava, M., & Rankin, M. (2002). Sexual functioning and SSRIs. The Journal of Clinical Psychiatry, 63(Suppl 5), 13–16. discussion 23–5.Google Scholar
- 38.Brown, C. H. (2008). Overview of drug–drug interactions with SSRIs. In: USPharmacistcom; HS-3-HS-19.Google Scholar
- 39.Vieweg, W. V., Hasnain, M., Howland, R. H., et al. (2012). Citalopram, QTc interval prolongation, and torsade de pointes. how should we apply the recent FDA ruling? American Journal of Medicine, 125, 859–868.Google Scholar
- 40.Valuck, R. J., Libby, A. M., Sills, M. R., Giese, A. A., & Allen, R. R. (2004). Antidepressant treatment and risk of suicide attempt by adolescents with major depressive disorder: A propensity-adjusted retrospective cohort study. CNS Drugs, 18, 1119–1132.Google Scholar
- 41.Jick, H., Kaye, J. A., & Jick, S. S. (2004). Antidepressants and the risk of suicidal behaviors. JAMA, 292, 338–343.Google Scholar