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“Meta-guidelines” for the management of patients with schizophrenia

Published online by Cambridge University Press:  16 April 2013

Stephen M. Stahl ,
Debbi A. Morrissette ,
Leslie Citrome ,
Stephen R. Saklad ,
Michael A. Cummings ,
Jonathan M. Meyer ,
Jennifer A. O'Day ,
Laura J. Dardashti  and
Katherine D. Warburton
Stephen M. Stahl*
Affiliation:
Department of Psychiatry, University of California–San Diego, San Diego, California, USA Department of Psychiatry, University of Cambridge, Cambridge, UK Neuroscience Education Institute, Carlsbad, California, USA California Department of State Hospitals, Sacramento, California, USA
Debbi A. Morrissette
Affiliation:
Neuroscience Education Institute, Carlsbad, California, USA
Leslie Citrome
Affiliation:
New York Medical College, Valhalla, New York, USA
Stephen R. Saklad
Affiliation:
San Antonio State Hospital, Texas Department of State Health Services, San Antonio, Texas, USA College of Pharmacy, Pharmacotherapy Division, The University of Texas at Austin, Austin, Texas, USA School of Medicine, University of Texas Health Science Center, San Antonio, Texas, USA
Michael A. Cummings
Affiliation:
California Department of State Hospitals, Sacramento, California, USA
Jonathan M. Meyer
Affiliation:
Department of Psychiatry, University of California–San Diego, San Diego, California, USA California Department of State Hospitals, Sacramento, California, USA
Jennifer A. O'Day
Affiliation:
California Department of State Hospitals, Sacramento, California, USA
Laura J. Dardashti
Affiliation:
California Department of State Hospitals, Sacramento, California, USA
Katherine D. Warburton
Affiliation:
California Department of State Hospitals, Sacramento, California, USA
*
*Address for correspondence: Stephen M. Stahl, MD, PhD, 1930 Palomar Point Way, Suite 103, Carlsbad, CA 92008, USA. (Email smstahl@neiglobal.com)
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Abstract

Guidelines for treating various conditions can be helpful in setting practice standards, but the presence of several sets of guidelines from different countries, experts, and settings, written at different times, can also create confusion. Here we provide a “guideline of guidelines” for the treatment of schizophrenia, or “meta-guidelines,” which not only reconcile the various existing standards but also update them to include the use of several newer agents, most of which were marketed following the publication of existing standards.

Keywords

Assessmentacutemaintenanceantipsychoticsdepot

Information

Type
Guidelines
Information
CNS Spectrums , Volume 18 , Issue 3 , June 2013 , pp. 150 - 162
Copyright
Copyright © Cambridge University Press 2013 

Introduction

Managing patients with schizophrenia can be challenging, even for the most experienced of clinicians. Over the past decade, numerous experts in various countries have made recommendations in a number of published guidelines.1–Reference Kreyenbuhl, Buchanan and Dickerson8 In addition, many institutions and hospitals have their own unpublished versions of guidelines for how to treat patients with schizophrenia. Often these recommendations contradict one another and are quickly out of date as the ever-increasing influx of new data accumulate and novel therapeutic agents are made available. In the “meta-guidelines” presented here, we have collected recommendations from various sources, both published and unpublished, and have updated and reconciled the differences from the Patient Outcomes Research Team (PORT), the Texas Medication Algorithm Project (TMAP), the American Psychiatric Association (APA), various state and federal hospitals, and current experts with decades of experience in treating this patient population in order to create an up-to-date “guideline of guidelines.” These meta-guidelines have also been extensively reviewed by a number of anonymous peer reviewers. The goal was to create a comprehensive yet concise set of meta-guidelines that reflects all the current data in order to provide clinicians with an aid in the management of patients with schizophrenia at different stages of illness, including acute and maintenance phases. Although clinical judgment must be exercised in the care of individual patients, these meta-guidelines may serve to assist clinicians in choosing the most evidence-based and up-to-date strategies for addressing treatment selection, medication-induced side effects, treatment nonadherence, and other issues commonly encountered in treating patients with schizophrenia. These meta-guidelines are intended for rank-and-file patients with schizophrenia who are not violent, self-harming, or complicated by various comorbidities, as such patients are excluded from most evidence-based randomized controlled efficacy trials that are the basis of both previously published guidelines and also of the meta-guidelines provided here.1–Reference Kreyenbuhl, Buchanan and Dickerson8 We will provide separate meta-guidelines for more complex, yet commonly encountered patients with schizophrenia, for use and guidance for what to do when the meta-guidelines provided here fail to provide adequate outcomes.Reference Stahl9–Reference Ritsner14 The meta-guidelines are presented here as Tables 1–15 and Figure 1.

Table 1

Overview and key points

Table 2

Assessment

Table 3

Suggested physical and laboratory assessments to monitor physical status and detect concomitant physical conditions in patients with schizophrenia

Table 4

Suggested physical and laboratory assessments to monitor possible treatment-induced side effects in patients with schizophrenia

Table 5

Treatment

Table 6

Treatment plan

Table 7

Acute-phase treatment

Table 8

Stabilization phase treatment

Table 9

Stable phase treatment

Table 10

Treatment in special circumstances

Table 11

Commonly used medications: conventional antipsychotics

*Dose range recommendations are adapted from the 2009 Schizophrenia Patient Outcome Research Team recommendations.Reference Dixon, Perkins and Calmes5–Reference Kreyenbuhl, Buchanan and Dickerson8 See full prescribing information for details.

**Chlorpromazine equivalents represent the approximate dose equivalent to 100 mg of chlorpromazine (relative potency).

Table 12

Commonly used medications: atypical antipsychotics

*Dose range recommendations are adapted from the 2009 Schizophrenia Patient Outcome Research Team recommendations.Reference Dixon, Perkins and Calmes5–Reference Kreyenbuhl, Buchanan and Dickerson8 See full prescribing information for details.

Table 13

Commonly used medications: other

*Dose range recommendations are adapted from the 2009 Schizophrenia Patient Outcome Research Team recommendations.Reference Dixon, Perkins and Calmes5–Reference Kreyenbuhl, Buchanan and Dickerson8 See full prescribing information for details.

Table 14

Choice of medication in the acute phase of schizophrenia

Table 15

Receptor-binding profiles of atypical antipsychotics

Abbreviations: BMI, body mass index; BUN, blood urea nitrogen; CBC, complete blood count; CBT, cognitive behavioral therapy; CRT, cognitive remediation therapy; CT, computerized tomography; ECG, electrocardiogram; ECT, electroconvulsive therapy; EEG, electroencephalogram; EPS, extrapyramidal symptoms; MRI, magnetic resonance imaging; NMS, neuroleptic malignant syndrome; SNRI, serotonin norepinephrine re-uptake inhibitor; SSRI, selective serotonin re-uptake inhibitor.

Figure 1

Antipsychotic algorithm for schizophrenia. For many acute inpatient settings with limited lengths of stay, trials of antipsychotics may be only 2–3 weeks prior to trying another. Many clinicians do not proceed to clozapine at all or until multiple failures with other antipsychotics; clozapine can be underutilized when this is the case. Response is generally defined as a clinically significant reduction in symptoms, eg, a modest 20% reduction in Positive and Negative Symptom Scale (PANSS) score observed at 2 weeks can predict a more robust 40% decrease in PANSS at 6 months. Lack of any response at 2 weeks is discouraging and requires reevaluation, including compliance and pharmacokinetics/therapeutic drug levels.

Disclosures

Stephen Stahl has the following disclosures: Avanir, consultant, consulting fees; Biomarin, consultant, consulting fees; Forest, consultant, consulting fees; Genetech, consultant, consulting fees; Genomind, consultant, consulting fees; GSK, consultant, consulting fees; Jazz, consultant, consulting fees; Merck, consultant, consulting fees; Navigant, consultant, consulting fees; Novartis, consultant, consulting fees; Noveida Health, consultant, consulting fees; Otsuka, consultant, consulting fees; PamLambs, consultant, consulting fees; Reviva, consultant, consulting fees; Shire, consultant, consulting fees; Sunovion, consultant, consulting fees; Teva, consultant, consulting fees; Trius, consultant, consulting fees; Arbor Scientia, speakers bureau, speakers fee; Genomind, speakers bureau, speakers fee; Janssen, speakers bureau, speakers fee; Lilly, speakers bureau, speakers fee; Neuroscience Education Institute; PamLabs, speakers bureau, speakers fee; Pfizer, speakers bureau, speakers fee; Avanir, grant recipient, grant; Cenerex, grant recipient, grant; Dey Pharma, grant recipient, grant; Eli Lilly, grant recipient, grant; Forest, grant recipient, grant; Genomind, grant recipient, grant; Mylan, grant recipient, grant; Otsuka, grant recipient, grant; PamLabs, grant recipient, grant; Servier, grant recipient, grant; Shire, grant recipient, grant; Sunovion, grant recipient, grant; Takeda, grant recipient, grant. Dr. Stahl is also a board member of RCT Logic and GenoMind. Leslie Citrome has the following disclosures: Alexza, consultant, consultant fees; Alkermes, consultant, consultant fees; Avanir, consultant, consultant fees; Bristol-Myers Squibb, consultant, speaker, consultant and speaker fees, small amount of common stock; Eli Lilly, speaker, speaker fees, small amount of common stock; Envivo, consultant, consultant fees; Forest, consultant, consultant fees; Genentech, consultant, consultant fees; Janssen, consultant, consultant fees; Lundbeck, consultant, consultant fees; Merck, speaker, speaker fees, small amount of common stock; Mylan, consultant, consultant fees; Novartis, consultant, speaker, consultant and speaker fees; Noven, consultant, consultant fees; Otsuka, consultant, speaker, consultant and speaker fees; Pfizer, speaker, speaker fees, small amount of common stock; Shire, consultant, consultant fees; Sunovion, consultant, speaker, consultant and speaker fees; J&J, small amount of common stock; AstraZeneca, speaker, speaker fees. Stephen Saklad has the following disclosures: Merck, speaker's bureau, honoraria; Novartis, speaker's bureau, honoraria; Sunovion, speaker's bureau, honoraria; Janssen, research (grant recipient), research support (grant). Jonathan Meyer has the following disclosures: Sunovion, speaker's bureau, speaker's fees; BMS, speaker's bureau, speaker's fees; Genetech, advisor, consulting fees; Otsuka, advisor, consulting fees. The remaining authors do not have anything to disclose.

References

1.American Psychiatric Association. Practice Guideline for the Treatment of Patients with Schizophrenia, 2nd ed. Washington, DC: American Psychiatric Association; 2004.Google Scholar
2.American Psychiatric Association. Treating Schizophrenia: A Quick Reference Guide. Washington, DC: American Psychiatric Association; 2004.Google Scholar
3.Kane, JM, Leucht, S, Carpenter, D, etal. The expert consensus guideline series. Optimizing pharmacologic treatment of psychotic disorders. Introduction: methods, commentary, and summary. J Clin Psychiatry. 2003; 64(suppl 12): 5–19.Google ScholarPubMed
4.Moore, TA, Buchanan, RW, Buckley, PF, etal. The Texas Algorithm Project antipsychotic algorithm for schizophrenia: 2006 update. J Clin Psychiatry. 2007; 68(11): 1751–1762.CrossRefGoogle ScholarPubMed
5.Dixon, L, Perkins, D, Calmes, C. Guideline Watch (September 2009): Practice Guideline for the Treatment of Patients with Schizophrenia. Washington, DC: American Psychiatric Association; 2009.CrossRefGoogle Scholar
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7.Dixon, LB, Dickerson, F, Bellack, AS, etal. The 2009 PORT psychosocial treatment recommendations and summary statements. Schizophr Bull. 2010; 36(1): 48–70.CrossRefGoogle ScholarPubMed
8.Kreyenbuhl, J, Buchanan, RW, Dickerson, FB, etal. The Schizophrenia Patient Outcomes Research Team (PORT): updated treatment recommendations 2009. Schizophr Bull. 2010; 36(1): 94–103.CrossRefGoogle ScholarPubMed
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Figure 0

Table 1 Overview and key points

Figure 1

Table 2 Assessment

Figure 2

Table 3 Suggested physical and laboratory assessments to monitor physical status and detect concomitant physical conditions in patients with schizophrenia

Figure 3

Table 4 Suggested physical and laboratory assessments to monitor possible treatment-induced side effects in patients with schizophrenia

Figure 4

Table 5 Treatment

Figure 5

Table 6 Treatment plan

Figure 6

Table 7 Acute-phase treatment

Figure 7

Table 8 Stabilization phase treatment

Figure 8

Table 9 Stable phase treatment

Figure 9

Table 10 Treatment in special circumstances

Figure 10

Table 11 Commonly used medications: conventional antipsychotics

Figure 11

Table 12 Commonly used medications: atypical antipsychotics

Figure 12

Table 13 Commonly used medications: other

Figure 13

Table 14 Choice of medication in the acute phase of schizophrenia

Figure 14

Table 15 Receptor-binding profiles of atypical antipsychotics

Figure 15

Figure 1 Antipsychotic algorithm for schizophrenia. For many acute inpatient settings with limited lengths of stay, trials of antipsychotics may be only 2–3 weeks prior to trying another. Many clinicians do not proceed to clozapine at all or until multiple failures with other antipsychotics; clozapine can be underutilized when this is the case. Response is generally defined as a clinically significant reduction in symptoms, eg, a modest 20% reduction in Positive and Negative Symptom Scale (PANSS) score observed at 2 weeks can predict a more robust 40% decrease in PANSS at 6 months. Lack of any response at 2 weeks is discouraging and requires reevaluation, including compliance and pharmacokinetics/therapeutic drug levels.