Second-generation antipsychotic medications: Pharmacology, administration, and comparative side effects
- Michael D Jibson, MD, PhD
Michael D Jibson, MD, PhD
- Professor of Psychiatry
- University of Michigan
Antipsychotic medications have efficacy in the treatment of acute psychosis (irrespective of cause), chronic psychotic disorders, and other psychiatric conditions.
First-generation antipsychotics (FGAs), also known as neuroleptics or conventional antipsychotics, cause extrapyramidal side effects, including rigidity, bradykinesia, tremor, and akathisia (restlessness). They also frequently lead to tardive dyskinesia—hyperkinetic, involuntary movements most readily observed in the face and extremities.
Second-generation antipsychotics (SGAs), also known as atypical antipsychotics, generally have lower risks of extrapyramidal side effects and tardive dyskinesia compared to FGAs. However, these medications generally cause higher rates of weight gain and metabolic side effects, although the side effect profiles of individual drugs vary. One SGA, clozapine, has sufficiently unique properties to justify separate consideration.
The pharmacology, administration, and comparative side effects of second-generation antipsychotics available in the US are discussed here. First-generation antipsychotics and antipsychotics in the treatment of schizophrenia and bipolar disorder are discussed separately, as are antipsychotic poisoning, tardive dyskinesia, and neuroleptic malignant syndrome (See "Pharmacotherapy for schizophrenia: Acute and maintenance phase treatment" and "Pharmacotherapy for schizophrenia: Side effect management" and "First generation (Typical) antipsychotic medication poisoning" and "Second generation (atypical) antipsychotic medication poisoning" and "Neuroleptic malignant syndrome" and "Tardive dyskinesia: Etiology and epidemiology" and "Bipolar disorder in adults: Pharmacotherapy for acute mania and hypomania" and "Guidelines for prescribing clozapine in schizophrenia".)
Second-generation antipsychotic medications are also referred to as “atypical antipsychotics”. First-generation antipsychotics may be referred to as “conventional antipsychotics” or “neuroleptics”. The older term "major tranquilizer" does not accurately describe the action of these medications, and is no longer encouraged.
- Iloperidone [package insert]. Vanda Pharmaceutical, Inc.; 2009. Available online at www.fanapt.com/fanapt-pi-may09.pdf.
- Potkin SG, Cohen M, Panagides J. Efficacy and tolerability of asenapine in acute schizophrenia: a placebo- and risperidone-controlled trial. J Clin Psychiatry 2007; 68:1492.
- Buchanan RW, Kreyenbuhl J, Kelly DL, et al. The 2009 schizophrenia PORT psychopharmacological treatment recommendations and summary statements. Schizophr Bull 2010; 36:71.
- Risperdal [package insert]. Ortho-McNeil-Janssen Pharmaceuticals; 2010. Available online at http://www.risperdal.com/sites/default/files/shared/pi/risperdal.pdf.
- Currier GW, Simpson GM. Risperidone liquid concentrate and oral lorazepam versus intramuscular haloperidol and intramuscular lorazepam for treatment of psychotic agitation. J Clin Psychiatry 2001; 62:153.
- Marder SR, Meibach RC. Risperidone in the treatment of schizophrenia. Am J Psychiatry 1994; 151:825.
- Peuskens J. Risperidone in the treatment of patients with chronic schizophrenia: a multi-national, multi-centre, double-blind, parallel-group study versus haloperidol. Risperidone Study Group. Br J Psychiatry 1995; 166:712.
- Szarfman A, Tonning JM, Levine JG, Doraiswamy PM. Atypical antipsychotics and pituitary tumors: a pharmacovigilance study. Pharmacotherapy 2006; 26:748.
- http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm277022.htm (Accessed on July 11, 2012).
- Olesen OV, Linnet K. Determination of olanzapine in serum by high-performance liquid chromatography using ultraviolet detection considering the easy oxidability of the compound and the presence of other psychotropic drugs. J Chromatogr B Biomed Sci Appl 1998; 714:309.
- Kinon BJ, Volavka J, Stauffer V, et al. Standard and higher dose of olanzapine in patients with schizophrenia or schizoaffective disorder: a randomized, double-blind, fixed-dose study. J Clin Psychopharmacol 2008; 28:392.
- Lieberman JA, Stroup TS, McEvoy JP, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005; 353:1209.
- Fontaine CS, Hynan LS, Koch K, et al. A double-blind comparison of olanzapine versus risperidone in the acute treatment of dementia-related behavioral disturbances in extended care facilities. J Clin Psychiatry 2003; 64:726.
- Meehan KM, Wang H, David SR, et al. Comparison of rapidly acting intramuscular olanzapine, lorazepam, and placebo: a double-blind, randomized study in acutely agitated patients with dementia. Neuropsychopharmacology 2002; 26:494.
- Allen MH, Currier GW, Carpenter D, et al. The expert consensus guideline series. Treatment of behavioral emergencies 2005. J Psychiatr Pract 2005; 11 Suppl 1:5.
- Beasley CM Jr, Hamilton SH, Crawford AM, et al. Olanzapine versus haloperidol: acute phase results of the international double-blind olanzapine trial. Eur Neuropsychopharmacol 1997; 7:125.
- Tran PV, Dellva MA, Tollefson GD, et al. Extrapyramidal symptoms and tolerability of olanzapine versus haloperidol in the acute treatment of schizophrenia. J Clin Psychiatry 1997; 58:205.
- Bobes J, Rejas J, Garcia-Garcia M, et al. Weight gain in patients with schizophrenia treated with risperidone, olanzapine, quetiapine or haloperidol: results of the EIRE study. Schizophr Res 2003; 62:77.
- Leslie DL, Rosenheck RA. Incidence of newly diagnosed diabetes attributable to atypical antipsychotic medications. Am J Psychiatry 2004; 161:1709.
- Brooks JO 3rd, Chang HS, Krasnykh O. Metabolic risks in older adults receiving second-generation antipsychotic medication. Curr Psychiatry Rep 2009; 11:33.
- Correll CU, Manu P, Olshanskiy V, et al. Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents. JAMA 2009; 302:1765.
- FDA MedWatch safety alert. Zyprexa (olanzapine): Use in adolescents. January 29, 2010.
- Zyprexa [package insert]. Eli Lilly and Company; 2010. Available online at http://pi.lilly.com/us/zyprexa-pi.pdf.
- McManus DQ, Arvanitis LA, Kowalcyk BB. Quetiapine, a novel antipsychotic: experience in elderly patients with psychotic disorders. Seroquel Trial 48 Study Group. J Clin Psychiatry 1999; 60:292.
- Seroquel [package insert]. AstraZeneca Pharmaceuticals LP; 2011. Available online at http://www1.astrazeneca-us.com/pi/Seroquel.pdf.
- Borison RL, Arvanitis LA, Miller BG. ICI 204,636, an atypical antipsychotic: efficacy and safety in a multicenter, placebo-controlled trial in patients with schizophrenia. U.S. SEROQUEL Study Group. J Clin Psychopharmacol 1996; 16:158.
- Small JG, Hirsch SR, Arvanitis LA, et al. Quetiapine in patients with schizophrenia. A high- and low-dose double-blind comparison with placebo. Seroquel Study Group. Arch Gen Psychiatry 1997; 54:549.
- Mullen J, Jibson MD, Sweitzer D. A comparison of the relative safety, efficacy, and tolerability of quetiapine and risperidone in outpatients with schizophrenia and other psychotic disorders: the quetiapine experience with safety and tolerability (QUEST) study. Clin Ther 2001; 23:1839.
- http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020639s049s054lbl.pdf (Accessed on July 11, 2012).
- Komossa K, Rummel-Kluge C, Schmid F, et al. Quetiapine versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev 2010; :CD006625.
- Citrome L. Using oral ziprasidone effectively: the food effect and dose-response. Adv Ther 2009; 26:739.
- Ziprasidone [package insert]. Pfizer, Inc.; 2009. Available online at http://media.pfizer.com/files/products/uspi_geodon.pdf
- Tandon, R, Harrigan E, Zorn, S. Ziprasidone: a novel antipsychotic with unique pharmacology and therapeutic potential. J Serotonin Res 1997; 4:159.
- Komossa K, Rummel-Kluge C, Hunger H, et al. Ziprasidone versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev 2009; :CD006627.
- Newcomer JW, Haupt DW. The metabolic effects of antipsychotic medications. Can J Psychiatry 2006; 51:480.
- Weiden PJ, Iqbal N, Mendelowitz AJ, et al. Best clinical practice with ziprasidone: update after one year of experience. J Psychiatr Pract 2002; 8:81.
- Kane JM, Carson WH, Saha AR, et al. Efficacy and safety of aripiprazole and haloperidol versus placebo in patients with schizophrenia and schizoaffective disorder. J Clin Psychiatry 2002; 63:763.
- Tran-Johnson TK, Sack DA, Marcus RN, et al. Efficacy and safety of intramuscular aripiprazole in patients with acute agitation: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry 2007; 68:111.
- Citrome L, Macher JP, Salazar DE, et al. Pharmacokinetics of aripiprazole and concomitant carbamazepine. J Clin Psychopharmacol 2007; 27:279.
- Alexopoulos GS, Streim J, Carpenter D, et al. Using antipsychotic agents in older patients. J Clin Psychiatry 2004; 65 Suppl 2:5.
- Abilify [package insert]. Otsuka Pharmaceutical Company; 2011. Available online at http://www.abilify.com/pdf/pi.aspx.
- Komossa K, Rummel-Kluge C, Schmid F, et al. Aripiprazole versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev 2009; :CD006569.
- Nelson S, Leung JG. Torsades de pointes after administration of low-dose aripiprazole. Ann Pharmacother 2013; 47:e11.
- Woosley RL, Anthony M, Armstrong EP, Assenzo JR. for Arizona CERT - QT Drug Lists by Risk Groups. http://www.azcert.org/medical-pros/drug-lists/drug-lists.cfm.
- Boom S, Thyssen A, Crauwels H, et al. The influence of hepatic impairment on the pharmacokinetics of paliperidone. Int J Clin Pharmacol Ther 2009; 47:606.
- Nussbaum A, Stroup TS. Paliperidone for schizophrenia. Cochrane Database Syst Rev 2008; :CD006369.
- Potkin SG, Litman RE, Torres R, Wolfgang CD. Efficacy of iloperidone in the treatment of schizophrenia: initial phase 3 studies. J Clin Psychopharmacol 2008; 28:S4.
- Weiden PJ, Cutler AJ, Polymeropoulos MH, Wolfgang CD. Safety profile of iloperidone: a pooled analysis of 6-week acute-phase pivotal trials. J Clin Psychopharmacol 2008; 28:S12.
- Shahid M, Walker GB, Zorn SH, Wong EH. Asenapine: a novel psychopharmacologic agent with a unique human receptor signature. J Psychopharmacol 2009; 23:65.
- Saphris [package insert]. Schering Corporation; 2009. Available online at http://www.spfiles.com/pisaphrisv1.pdf.
- Chapel S, Hutmacher MM, Haig G, et al. Exposure-response analysis in patients with schizophrenia to assess the effect of asenapine on QTc prolongation. J Clin Pharmacol 2009; 49:1297.
- US Food & Drug Administration Safety Communication: Serioius allergic reactions reported with the use of Saphris (asenapine maleate) http://www.fda.gov/Drugs/DrugSafety/ucm270243.htm (Accessed on March 30, 2012).
- Risbood V, Lee JR, Roche-Desilets J, Fuller MA. Lurasidone: an atypical antipsychotic for schizophrenia. Ann Pharmacother 2012; 46:1033.
- Ishibashi T, Horisawa T, Tokuda K, et al. Pharmacological profile of lurasidone, a novel antipsychotic agent with potent 5-hydroxytryptamine 7 (5-HT7) and 5-HT1A receptor activity. J Pharmacol Exp Ther 2010; 334:171.
- Latuda (lurasidone hydrochloride) US prescribing information. http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=afad3051-9df2-4c54-9684-e8262a133af8 (Accessed on December 12, 2012).
- Meyer JM, Loebel AD, Schweizer E. Lurasidone: a new drug in development for schizophrenia. Expert Opin Investig Drugs 2009; 18:1715.
- Loebel A, Cucchiaro J, Pikalov A, et al. Lurasidone in the Treatment of Acute Schizophrenia: Results of the Double-Blind, Placebo-Controlled, 6-Week, PEARL 3 Trial. Neuropsychopharmacology 2010; 35:S313.
- Citrome L. Lurasidone in schizophrenia: new information about dosage and place in therapy. Adv Ther 2012; 29:815.
- Nakamura M, Ogasa M, Guarino J, et al. Lurasidone in the treatment of acute schizophrenia: a double-blind, placebo-controlled trial. J Clin Psychiatry 2009; 70:829.
- Rado J, Janicak PG. Pharmacological and clinical profile of recently approved second-generation antipsychotics: implications for treatment of schizophrenia in older patients. Drugs Aging 2012; 29:783.
- Kane J, Honigfeld G, Singer J, Meltzer H. Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine. Arch Gen Psychiatry 1988; 45:789.
- Kreyenbuhl J, Buchanan RW, Dickerson FB, et al. The Schizophrenia Patient Outcomes Research Team (PORT): updated treatment recommendations 2009. Schizophr Bull 2010; 36:94.
- Barak Y, Wittenberg N, Naor S, et al. Clozapine in elderly psychiatric patients: tolerability, safety, and efficacy. Compr Psychiatry 1999; 40:320.