Atypical Antipsychotics for the Treatment of Schizophrenia-Spectrum Disorders

Antipsychotics: Cornerstone of Treatment

AntipsychoticsAntipsychotic treatment in teenagers has increased significantly within office-based medical practice.[1] The onset of schizophrenia by age 19 occurs in 40 percent of male patients and 23 percent of female patients, [2] with its incidence rising sharply after puberty.[3] As a longer duration of untreated psychosis predicts poor outcomes after the individual experiences their first episode, early treatment is crucial.[4] The goals of antipsychotic treatment for psychosis are improvement of symptoms, maintenance of treatment effects, and functionality recovery in the areas of academics, peer relations, and family life.[5] However, while antipsychotic medicines may be the cornerstone of treatment, it is also crucial for adolescents to undergo multiple treatments at once, including individual supportive therapy, family psychoeducation, and special classroom placement.5 These additional treatments will help prevent relapse of symptoms, enhance treatment adherence, and aid in improving social skill deficits.5 As the atypical antipsychotics have now become standard treatment for youths with early-onset schizophrenia spectrum disorders,[6] Instructor of the Division of Child and Adolescent Psychiatry and Postdoctoral Research Fellow at the Center for Neurobehavioral Development Kathryn Cullen and colleagues review several atypical antipsychotics in their article “Atypical Antipsychotics for Treatment of Schizophrenia Spectrum Disorders.”5

FDA-Approved Antipsychotics

The first FDA-approved atypical antipsychotic, clozapine is known for its efficacy, as well as its adverse effects.5 Although it is not approved for use in children and adolescents, studies have shown that it is effective in treating youth.[7] However, because of its associated risk of neutropenia and agranulocytosis, it is usually only prescribed to youth with treatment-resistant schizophrenia.[8] Two trials of clozapine treatment in youths demonstrated efficacy at dosages of 370 mg/d[9] and 227 mg/d.[10] Another trial compared the use of clozapine with the use of haloperidol in adolescent patients with treatment-resistant schizophrenia.[11] Results stated that although clozapine was more effective than haloperidol, it was associated with more adverse effects, including hypotension, dizziness, sialorrhea, seizures, and myocarditis.11

The first atypical antipsychotic to be released as a first-line agent in the United States, risperidone is the most frequently prescribed atypical antipsychotic for children and adolescents.5 Cullen and colleagues state that it is FDA-approved for the treatment of schizophrenia in adolescents and autistic spectrum disorders in children.5 Risperidone is known to reduce psychotic symptoms in adolescents5; however, it is associated with adverse effects, including weight gain, mild sedation, and dose-related EPS.[12] Haas and colleagues established the efficacy of risperidone with their study of 160 adolescents, aged 13 to 17, who were diagnosed with schizophrenia.[13] The participants were split into three groups: one received 1 to 3 mg/d of risperidone, another received 4 to 6 mg/d of risperidone, and a third received placebo.13 Results showed improvements in treatment outcomes for both risperidone groups compared with placebo.13 However, risks associated are movement disorders,[14] prolactin elevation,[15] and significant weight gain.13

The next atypical antipsychotic introduced in the United States was olanzapine.5 According to Cullen and colleagues, while initial studies of the medicine’s use in youths focused on treatment-resistant schizophrenia, recent research has assessed the use of the medicine as a first-line treatment option for youth with early-onset schizophrenia spectrum disorders.5 Many findings state that olanzapine is effective in reducing psychotic symptoms and is associated with a low incidence of adverse effects.5 A recently completed study conducted by Kryzhanovskaya and colleagues found olanzapine to be more effective than placebo in reducing psychotic symptoms in adolescents.[16] However, patients gained an average of 9.5 pounds in a four- to six-week period, which continued to rise after six months.16 Among all of the atypical antipsychotics, olanzapine is the medicine most associated with weight gain, and therefore is not used as much.5

The most recent atypical antipsychotic to be introduced to the United States is aripiprazole.5 As it is a newer medicine, there are less studies completed assessing its use in children and adolescents, state Cullen and colleagues. However, one study that has recently been completed has led to the approval of aripiprazole treatment of early-onset schizophrenia spectrum disorders in adolescents.5 Robb and colleagues conducted a study of 300 adolescents, aged 13 to 17, who were diagnosed with schizophrenia.[17] The participants were split into three groups: group one received 10 mg/d of aripiprazole, group two received 30 mg/d of aripiprazole, and group three received placebo.17 Results stated that both 10 and 30 mg/d of aripiprazole showed significant efficacy compared with placebo.17 Adverse effects included EPS, minimal weight change, and a decrease in prolactin levels.[18]

Antipsychotics and Early-Onset Schizophrenia

Now, clinicians are able to use the recent emerging data to help them choose between the atypical antipsychotics for treatment of adolescents with early-onset schizophrenia spectrum disorders.5 Although the atypical antipsychotic medicines are associated with fewer adverse motor effects than typical antipsychotics, atypicals are associated with other adverse effects, including sedation and metabolic abnormalities.5 However, weight gain is especially important to teenagers, as it causes distress and nonadherence to medicines; therefore, this should be taken into consideration when choosing a medicine.5 Also, while there are few studies available regarding the differences between atypical antipsychotics, additional comparative studies should be completed on the tolerability and efficacy between them in order to further aid a clinician in choosing a first-line treatment.5

[1] Olfson M, Blanco C, Liu L, et al. National trends in the outpatient treatment of children and adolescents with antipsychotic drugs. http://euromessengers.org/?biodetd=unterschied-zwischen-forex-und-bin%C3%A4re-optionen&723=d5 Arch Gen Psychiatry. 2006; 63:679-685.

[2] Loranger AW. Sex differences in age at onset of schizophrenia. تدريب الخيارات الثنائية Arch Gen Psychiatry. 1984;41:157-161.

[3] Hafner H, an der Heiden W. Epidemiology of schizophrenia. watch Can J Psychiatry. 1997;42:139-151.

[4] Perkins DO, Gu H, Boteva K, Lieberman JA. Relationship between duration of untreated psychosis and outcome in first-episode schizophrenia: a critical review and meta-analysis. http://clgsecurities.com/?hixorisima=verlegenheit-beim-flirten&775=0c Am J Psychiatry. 2005; 162:1785-1804.

[5] Cullen, K.R.; Kumra, S.; Regan, J.; Westerman, M.; and Schulz, C. (2008, March 1). Atypical Antipsychotics for Treatment of Schizophrenia Spectrum Disorders. Psychiatric Times. Retrieved from http://www.psychiatrictimes.com/schizophrenia/content/article/10168/1147536

[6] American Academy of Child and Adolescent Psychiatry. Practice parameter for assessment and treatment of children and adolescents with schizophrenia. http://svahn.it/?add-to-cart=122 J Am Acad Child Adolesc Psychiatry. 2001;40:S4-S23.

[7] Birmaher B, Baker R, Kapur S, et al. Clozapine for the treatment of adolescents with schizophrenia. http://podzamcze-dobczyce.pl/index.php/restauracja/assets/assets/js/jquery.flexslider.js J Am Acad Child Adolesc Psychiatry. 1992;31:160-164.

[8] Findling RL, Frazier JA, Gerbino-Rosen G, et al. Is there a role for clozapine in the treatment of children and adolescents? J Am Acad Child Adolesc Psychiatry. 2007;46:423-428.

[9] Frazier JA, Gordon CT, McKenna K, et al. An open trial of clozapine in 11 adolescents with childhood- onset schizophrenia. http://www.batsoft.lv/espamie/bambyk/8176 J Am Acad Child Adolesc Psychiatry. 1994;33:658-663.

[10] Jacobsen LK, Hommer DW, Hong WL, et al. Blink rate in childhood-onset schizophrenia: comparison with normal and attention-deficit hyperactivity disorder controls. mujer busca hombre manzanillo Biol Psychiatry. 1996;40:1222-1229.

[11] Kumra S, Frazier JA, Jacobsen LK, et al. Childhood-onset schizophrenia: a double-blind clozapine-haloperidol comparison. http://www.backclinicinc.com/?jixer=trading-oline-con-le-binarie&bcd=84 Arch Gen Psychiatry. 1996; 53:1090-1097.

[12] Armenteros J, Whitaker A, Welikson M, et al. Risperidone in adolescents with schizophrenia: an open pilot study. http://www.prestatraining.com/anys/brokoli/2894 - Saxo trader demo. Shyam Networks participated in the recently held 3rd Security India 2011 organised by Comnet Conferences, a division of Exhibitions India Group. The conference themed as “Changing Landscape of Security & Surveillance”, took place at Hotel Shangri-La Eros on 7th July 2011 at New Delhi. J Am Acad Child Adolesc Psychiatry. 1997;36:694-700.

[13]Haas M, Unis A, Copenhaver M, et al. Efficacy and safety of risperidone in adolescents with schizophrenia. Presented at: the 160th Annual Meeting of the American Psychiatric Association; May 19-24, 2007; San Diego.

[14] Mandoki MW. Risperidone treatment of children and adolescents: increased risk of extrapyramidal side-effects? J Child Adolesc Psychopharmacol. 1995;5:49-67.

[15] Saito E, Correll CU, Gallelli K, et al. A prospective study of hyperprolactinemia in children and adolescents treated with atypical antipsychotic agents. J Child Adolesc Psychopharmacol. 2004;14:350-358.

[16] Kryzhanovskaya LA, Schulz S, McDougle C, et al. Double-blind placebo-controlled trial of olanzapine in adolescents with schizophrenia. Presented at: the 159th Annual Meeting of the American Psychiatric Association; May 20-25, 2006; Toronto.

[17] Robb A, Findling R, Nyilas M, et al. Efficacy of aripiprazole in the treatment of adolescents with schizophrenia. Poster presented at: the 160th Annual Meeting of the American Psychiatric Association; May 19-24, 2007; San Diego.

[18] Findling RL, Frazier JA, Gerbino-Rosen G, et al. Is there a role for clozapine in the treatment of children and adolescents? J Am Acad Child Adolesc Psychiatry. 2007;46:423-428.

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