Letters to the Editor Consider ECT for Treatment-Resistant Childhood Schizophrenia To the Editor: We read with interest the clinical case conference titled “Management of Clozapine-Induced Fever in a Child,” by David I. Driver, M.D., et al., in the April 2014 issue of the Journal (1). The case highlighted an 11-year-old girl, diagnosed with schizophrenia, whose symptoms did not respond to various antipsychotics, antidepressants, clonazepam, melatonin, and a botanical preparation. As a “last resort,” she was treated with clozapine and developed a fever while receiving this medication. We are concerned that the report neglected to mention any consideration of ECT, for which there is a considerable evidence base in children. There are seven published studies from 1997 to 2012, including chart reviews, a controlled prospective case study, and a longitudinal follow-up of 272 children and adolescents with schizophrenia spectrum disorders treated with ECT (2). These studies show a beneficial response in 28%–58% of adolescents treated with ECT, often as an adjunct to antipsychotic medication. As with adults, the greatest efficacy was observed with positive, catatonic, and affective symptoms. ECT is shown to accelerate treatment response and reduce hospital length of stay among children with schizophrenia. The patient described in the report demonstrated delusions, aggression, labile affect, and disorganized thought, all of which would be expected to be ECT responsive. References 1. Driver DI, Anvari AA, Peroutka CM, Kataria R, Overman J, Lang D, Tietcheu M, Parker R, Baptiste K, Rapoport JL, Gogtay N: Management of clozapine-induced fever in a child. Am J Psychiatry 2014; 171:398–402 2. Bloch Y, Stein D, Walter G: ECT for schizophrenia spectrum disorders, in Electroconvulsive Therapy in Children and Adolescents. Edited by Ghaziuddin N, Walter G. Oxford, United Kingdom, Oxford University Press, 2013, pp 191–216
MATTHEW MAJESKE, M.D. CHARLES H. KELLNER, M.D.
From the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York. Dr. Kellner has received grant support from NIMH, honoraria from the North Shore-LIJ Health System, Psychiatric Times, and UpToDate, and royalties from Cambridge University Press. Dr. Majeske reports no financial relationships with commercial interests. This letter (doi: 10.1176/appi.ajp.2014.14050628) was accepted for publication in June 2014.
Response to Majeske and Kellner To the Editor: We thank Drs. Majeske and Kellner for their interest in our work and wish to provide clarification on the points raised. Although it was not listed as a concern, we would like to emphasize that our statement that clozapine was used as a “last resort” was in the context of the psychopharmacological principle of monotherapy. We also intended to draw attention to the fact that although clozapine is considered a third-line
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medication, clinicians generally shy away from its use, especially in pediatric populations, until it is considered a “last resort” (1–4). Regarding the concern that we neglected to consider the use of ECT in this case, Drs. Majeske and Kellner are correct, we did not consider it. The evidence for the use of ECT in children and adolescents with schizophrenia is limited to reports of its use as an adjunct to antipsychotic medication (5), and it is generally recommended that a patient has at least 2–3 adequate trials (adequate dosing and duration) of antipsychotic medication, including a trial of clozapine, before using ECT as an adjunct (5, 6). Given that our patient had not yet had an adequate monotherapy with clozapine, it would have been premature to engage her with adjunctive treatment with ECT. We agree that it is important to consider all treatment options when managing childhood-onset schizophrenia. Our report is in no way intended to be exhaustive of the available treatments or treatment approaches (monotherapy, switching, combination, augmentation, etc.), but rather to provide a reference for providers using clozapine in children who encounter a fever. References 1. Gogtay N, Rapoport J: Clozapine use in children and adolescents. Expert Opin Pharmacother 2008; 9:459–465 2. Vera I, Rezende L, Molina V, Sanz-Fuentenebro J: Clozapine as treatment of first choice in first psychotic episodes: What do we know? Actas Esp Psiquiatr 2012; 40:281–289 3. Driver DI, Gogtay N, Rapoport JL: Childhood onset schizophrenia and early onset schizophrenia spectrum disorders. Child Adolesc Psychiatr Clin N Am 2013; 22:539–555 4. Driver DI, Anvari AA, Peroutka CM, Kataria R, Overman J, Lang D, Tietcheu M, Parker R, Baptiste K, Rapoport JL, Gogtay N: Management of clozapine-induced fever in a child. Am J Psychiatry 2014; 171:398–402 5. Bloch Y, Walter G: ECT for schizophrenia spectrum disorders, in Electroconvulsive Therapy in Children and Adolescents. Edited by Neera G, Walter G. Oxford, United Kingdom, Oxford Press, 2013, pp 191–216 6. Kranzler HN, Kester HM, Gerbino-Rosen G, Henderson IN, Youngerman J, Beauzile G, Ditkowsky K, Kumra S: Treatmentrefractory schizophrenia in children and adolescents: an update on clozapine and other pharmacologic interventions. Child Adolesc Psychiatr Clin N Am 2006; 15:135–159
DAVID I. DRIVER, M.D. JUDITH L. RAPOPORT, M.D. NITIN GOGTAY, M.D.
From the Child Psychiatry Branch, NIMH, Bethesda, Md. The authors’ disclosures accompany the original article. This reply (doi: 10.1176/appi.ajp.2014.14050628r) was accepted for publication in June 2014.
Right Versus Left Hippocampal Activity as a Biomarker in Schizophrenia To the Editor: In their article published in the May 2014 issue of the Journal, Jason R. Tregellas, Ph.D., et al. (1), state that their hypothesis “that patients would show greater intrinsic hippocampal activity than healthy subjects” was supported.
Am J Psychiatry 171:9, September 2014
MATTHEW MAJESKE, M.D. CHARLES H. KELLNER, M.D.
From the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York. Dr. Kellner has received grant support from NIMH, honoraria from the North Shore-LIJ Health System, Psychiatric Times, and UpToDate, and royalties from Cambridge University Press. Dr. Majeske reports no financial relationships with commercial interests. This letter (doi: 10.1176/appi.ajp.2014.14050628) was accepted for publication in June 2014.
Response to Majeske and Kellner To the Editor: We thank Drs. Majeske and Kellner for their interest in our work and wish to provide clarification on the points raised. Although it was not listed as a concern, we would like to emphasize that our statement that clozapine was used as a “last resort” was in the context of the psychopharmacological principle of monotherapy. We also intended to draw attention to the fact that although clozapine is considered a third-line
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medication, clinicians generally shy away from its use, especially in pediatric populations, until it is considered a “last resort” (1–4). Regarding the concern that we neglected to consider the use of ECT in this case, Drs. Majeske and Kellner are correct, we did not consider it. The evidence for the use of ECT in children and adolescents with schizophrenia is limited to reports of its use as an adjunct to antipsychotic medication (5), and it is generally recommended that a patient has at least 2–3 adequate trials (adequate dosing and duration) of antipsychotic medication, including a trial of clozapine, before using ECT as an adjunct (5, 6). Given that our patient had not yet had an adequate monotherapy with clozapine, it would have been premature to engage her with adjunctive treatment with ECT. We agree that it is important to consider all treatment options when managing childhood-onset schizophrenia. Our report is in no way intended to be exhaustive of the available treatments or treatment approaches (monotherapy, switching, combination, augmentation, etc.), but rather to provide a reference for providers using clozapine in children who encounter a fever. References 1. Gogtay N, Rapoport J: Clozapine use in children and adolescents. Expert Opin Pharmacother 2008; 9:459–465 2. Vera I, Rezende L, Molina V, Sanz-Fuentenebro J: Clozapine as treatment of first choice in first psychotic episodes: What do we know? Actas Esp Psiquiatr 2012; 40:281–289 3. Driver DI, Gogtay N, Rapoport JL: Childhood onset schizophrenia and early onset schizophrenia spectrum disorders. Child Adolesc Psychiatr Clin N Am 2013; 22:539–555 4. Driver DI, Anvari AA, Peroutka CM, Kataria R, Overman J, Lang D, Tietcheu M, Parker R, Baptiste K, Rapoport JL, Gogtay N: Management of clozapine-induced fever in a child. Am J Psychiatry 2014; 171:398–402 5. Bloch Y, Walter G: ECT for schizophrenia spectrum disorders, in Electroconvulsive Therapy in Children and Adolescents. Edited by Neera G, Walter G. Oxford, United Kingdom, Oxford Press, 2013, pp 191–216 6. Kranzler HN, Kester HM, Gerbino-Rosen G, Henderson IN, Youngerman J, Beauzile G, Ditkowsky K, Kumra S: Treatmentrefractory schizophrenia in children and adolescents: an update on clozapine and other pharmacologic interventions. Child Adolesc Psychiatr Clin N Am 2006; 15:135–159
DAVID I. DRIVER, M.D. JUDITH L. RAPOPORT, M.D. NITIN GOGTAY, M.D.
From the Child Psychiatry Branch, NIMH, Bethesda, Md. The authors’ disclosures accompany the original article. This reply (doi: 10.1176/appi.ajp.2014.14050628r) was accepted for publication in June 2014.
Right Versus Left Hippocampal Activity as a Biomarker in Schizophrenia To the Editor: In their article published in the May 2014 issue of the Journal, Jason R. Tregellas, Ph.D., et al. (1), state that their hypothesis “that patients would show greater intrinsic hippocampal activity than healthy subjects” was supported.
Am J Psychiatry 171:9, September 2014
