Treatment Strategies for Dosing the Second Generation Antipsychotics

Overview

Journal CNS Neurosci Ther

Specialties Neurology
Pharmacology

Date 2011 Mar 16

PMID 21401911

Citations 12

Authors

Thomas L Schwartz

Stephen M Stahl

Affiliations

Soon will be listed here.

Abstract

Background: The second generation antipsychotics now have clinical approvals for the treatment of schizophrenia, bipolar depression, bipolar mania, autism, major depressive disorder and are used furthermore off-label to treat other mental disorders. Each agent is unique in its pharmacodynamic profile and allows for unique dosing strategies to be employed when treating these different disorders.

Aims: To review relevant data regarding the second generation antipsychotics and their empirical dosing strategies. To further review and comment theoretically in these areas where substantial, definitive data are lacking.

Materials And Methods: A MEDLINE and recent textbook review was conducted regarding each second generation antipsychotic and cross-referenced with searches for major mental disorders. The findings are compiled in the review below.

Discussion: The second generation antipsychotics are clearly delineated in the treatment of psychosis and mania and share similar mechanisms of action to achieve these results: dopamine-2 receptor antagonism for efficacy and serotonin-2a receptor antagonism for EPS tolerability. From here, each agent has a unique pharmacodynamic and pharmacokinetic profile where some agents carry more, or less antidepressant, anxiolyic, or hypnotic profiles. Choosing an agent, and dosing it in low, middle, or high ranges may result in differential effectiveness and tolerability.

Conclusion: The second generation antipsychotics have many clinical applications in psychiatric practice. This article serves to review this and also suggests ways clinicians may optimize treatment based upon patient diagnosis and utilizing appropriate dosing of each individual second generation antipsychotic.

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References

Nguyen D, Brakoulias V, Boyce P . An evaluation of monitoring practices in patients on second generation antipsychotics. Australas Psychiatry. 2009; 17(4):295-9. DOI: 10.1080/10398560902842519. View

Holt R, Peveler R . Obesity, serious mental illness and antipsychotic drugs. Diabetes Obes Metab. 2009; 11(7):665-79. DOI: 10.1111/j.1463-1326.2009.01038.x. View

Seeger T, Seymour P, Schmidt A, Zorn S, Schulz D, Lebel L . Ziprasidone (CP-88,059): a new antipsychotic with combined dopamine and serotonin receptor antagonist activity. J Pharmacol Exp Ther. 1995; 275(1):101-13. View

Mathews J, Garcia K, Mintun M, Sheline Y . Antidepressant efficacy of olanzapine as monotherapy in major depressive disorder, without psychosis: a pilot study. Psychiatry Res. 2006; 146(2):149-55. DOI: 10.1016/j.pscychresns.2005.08.003. View

Patel J, Buckley P, Woolson S, Hamer R, McEvoy J, Perkins D . Metabolic profiles of second-generation antipsychotics in early psychosis: findings from the CAFE study. Schizophr Res. 2009; 111(1-3):9-16. DOI: 10.1016/j.schres.2009.03.025. View

Shayegan D, Stahl S . Atypical antipsychotics: matching receptor profile to individual patient's clinical profile. CNS Spectr. 2004; 9(10 Suppl 11):6-14. DOI: 10.1017/s1092852900025086. View

Shajahan P, Taylor M . The uses and outcomes of quetiapine in depressive and bipolar mood disorders in clinical practice. J Psychopharmacol. 2009; 24(4):565-72. DOI: 10.1177/0269881108100774. View

Edlinger M, Baumgartner S, Eltanaihi-Furtmuller N, Hummer M, Fleischhacker W . Switching between second-generation antipsychotics: why and how?. CNS Drugs. 2005; 19(1):27-42. DOI: 10.2165/00023210-200519010-00003. View

Khanna S, Vieta E, Lyons B, Grossman F, Eerdekens M, Kramer M . Risperidone in the treatment of acute mania: double-blind, placebo-controlled study. Br J Psychiatry. 2005; 187:229-34. DOI: 10.1192/bjp.187.3.229. View

10.

Citrome L, Jaffe A, Levine J . Datapoints: The ups and downs of dosing second-generation antipsychotics. Psychiatr Serv. 2007; 58(1):11. DOI: 10.1176/ps.2007.58.1.12. View

11.

Cutler A, Ball S, Stahl S . Dosing atypical antipsychotics. CNS Spectr. 2008; 13(5 Suppl 9):1-16. View

12.

Gao K, Sheehan D, Calabrese J . Atypical antipsychotics in primary generalized anxiety disorder or comorbid with mood disorders. Expert Rev Neurother. 2009; 9(8):1147-58. PMC: 3432909. DOI: 10.1586/ern.09.37. View

13.

Citrome L, Stauffer V, Chen L, Kinon B, Kurtz D, Jacobson J . Olanzapine plasma concentrations after treatment with 10, 20, and 40 mg/d in patients with schizophrenia: an analysis of correlations with efficacy, weight gain, and prolactin concentration. J Clin Psychopharmacol. 2009; 29(3):278-83. DOI: 10.1097/JCP.0b013e3181a289cb. View

14.

Keitner G, Garlow S, Ryan C, Ninan P, Solomon D, Nemeroff C . A randomized, placebo-controlled trial of risperidone augmentation for patients with difficult-to-treat unipolar, non-psychotic major depression. J Psychiatr Res. 2008; 43(3):205-14. PMC: 3685867. DOI: 10.1016/j.jpsychires.2008.05.003. View

15.

Franberg O, Marcus M, Ivanov V, Schilstrom B, Shahid M, Svensson T . Asenapine elevates cortical dopamine, noradrenaline and serotonin release. Evidence for activation of cortical and subcortical dopamine systems by different mechanisms. Psychopharmacology (Berl). 2009; 204(2):251-64. DOI: 10.1007/s00213-008-1456-5. View

16.

Haas M, Unis A, Armenteros J, Copenhaver M, Quiroz J, Kushner S . A 6-week, randomized, double-blind, placebo-controlled study of the efficacy and safety of risperidone in adolescents with schizophrenia. J Child Adolesc Psychopharmacol. 2009; 19(6):611-21. DOI: 10.1089/cap.2008.0144. View

17.

Nelson J, Mankoski R, Baker R, Carlson B, Eudicone J, Pikalov A . Effects of aripiprazole adjunctive to standard antidepressant treatment on the core symptoms of depression: a post-hoc, pooled analysis of two large, placebo-controlled studies. J Affect Disord. 2009; 120(1-3):133-40. DOI: 10.1016/j.jad.2009.06.026. View

18.

Keck Jr P, McElroy S, Arnold L . Ziprasidone: a new atypical antipsychotic. Expert Opin Pharmacother. 2001; 2(6):1033-42. DOI: 10.1517/14656566.2.6.1033. View

19.

McIntyre A, Gendron A, McIntyre A . Quetiapine adjunct to selective serotonin reuptake inhibitors or venlafaxine in patients with major depression, comorbid anxiety, and residual depressive symptoms: a randomized, placebo-controlled pilot study. Depress Anxiety. 2006; 24(7):487-94. DOI: 10.1002/da.20275. View

20.

Suppes T, Datto C, Minkwitz M, Nordenhem A, Walker C, Darko D . Effectiveness of the extended release formulation of quetiapine as monotherapy for the treatment of acute bipolar depression. J Affect Disord. 2009; 121(1-2):106-15. DOI: 10.1016/j.jad.2009.10.007. View