Differential Treatment Decisions
Consistent with this treatment philosophy, findings from a large meta-analysis of comparative efficacy and tolerability of 15 antipsychotic drugs in patients with schizophrenia challenged the stringent grouping of antipsychotics into “first-generation” and “second-generation” classes.17
In this analysis, all antipsychotic drugs were significantly more effective in improving symptoms compared with placebo. However, the differences in efficacy between drugs were small (standardized mean differences 0.11–0.55, median 0.24), and smaller overall than those for side effects. All drugs, except zotepine, were significantly better than placebo for all-cause discontinuation (a measure of drug acceptability); the most effective drugs also had the lowest discontinuation rates.
Antipsychotics differed in side-effects in this analysis.17 However, the stringent dichotomy between “first-generation” and “second-generation” antipsychotics based on weight gain or extrapyramidal side effects was an oversimplification. Apart from haloperidol, ziprasidone, and lurasidone, all drugs produced more weight gain than placebo. Haloperidol caused the most extrapyramidal side effects, followed by zotepine and chlorpromazine. However, chlorpromazine did not produce significantly more extrapyramidal side-effects than most “second-generation” antipsychotics. Five “second-generation” drugs were associated with significantly more extrapyramidal side effects than placebo. Differences among antipsychotics in QTc prolongation and prolactin concentration were large, but strictly dichotomous classifications into “first-generation” and “second-generation” antipsychotics were simplistic based on the analysis.
Overall, the authors concluded that antipsychotic drugs differed in many properties, but could not be “categorized into first- and second-generation groupings.” Rather, they argued that hierarchies in different domains (efficacy, discontinuation, and side effect, etc.) should guide clinicians in selection of antipsychotic drugs to meet the needs of individual patients. They further advised that their findings should be considered in the revision of clinical practice guidelines.
In line with the concept differential treatment selection, the current NICE guidelines for schizophrenia, updated in 2014, recommend that choice of antipsychotic medication in first-episode patients should be made by the patient and healthcare professional together, taking the benefits and possible side effects of each drug (ie, metabolic, extrapyramidal, cardiovascular, hormonal, etc.) into account.9 The selection of a drug for subsequent acute episodes and maintenance care should be influenced by the same criteria recommended for starting treatment.
In the United States, the NICE schizophrenia guidelines9 and PORT treatment recommendations10 are among the major guidelines used and/or influencing the treatment of schizophrenia18 along with the APA Practice Guidelines,7 the Expert Consensus Guidelines,19 the International Psychopharmacology Algorithm Project (IPAP),20 and the Texas medication algorithm project (T-MAP) antipsychotic algorithm21 for schizophrenia. The most recently updated guidelines from NICE integrate results from CATIE, CUtLASS, and EUFEST in its analysis. The 2006 T-MAP algorithm and the 2010 PORT recommendations incorporate CATIE and CUtLASS findings into their recommendations, but at the time of T-MAP’s publication, EUFEST results were not available.
In addition to timeliness, each guideline differs slightly in content, scope, focus, and goals. In brief, the PORT and T-MAP guidelines concisely present recommendations, and T-MAP and IPAP both feature easy-to-use algorithms.10, 21, 20 The NICE guidelines provide a relatively thorough examination of interventions.9 The APA Practice Guidelines and Expert Consensus Guidelines are more dated, but a number of their recommendations remain relevant today.7, 19
Unfortunately, clinician adherence to clinical practice guidelines in schizophrenia remains suboptimal,22, 23, 24-27 and uncertainty exists regarding how best to implement guidelines for maximum benefits.28 Nevertheless, clinical care systems should proceed with the elements of guideline implementation that are clinically warranted and reach consensus29, 30 in an effort to both achieve more effective. efficient care and close the gap between clinical practice and evidence-based medicine.
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19. Treatment of schizophrenia 1999. The expert consensus guideline series. J Clin Psychiatry. 1999;60:3-80.
20. International Psychopharmacology Algorithm Project (IPAP) schizophrenia algorithm 2006. Available from http://www.ipap.org/pdf/schiz/IPAP_Schiz_flowchart20060327.pdf. Accessed April 5, 2016.
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