The crossover approach to switching antipsychotics: What is the evidence?

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Abstract

Clinicians frequently use a crossover approach in switching antipsychotics, although historically there has been a lack of data addressing the question of switch strategies. To establish if there is now empiric evidence that may guide clinicians in this regard, a MEDLINE search to April 2004 was carried out to identify published, randomized and controlled trials that have addressed this topic. A total of 404 articles were identified in the search, which resulted in the identification of four reports meeting the criteria. The four studies evaluated switching strategies to one of three atypical antipsychotics: aripiprazole, olanzapine (two reports), and ziprasidone. The switching process itself could be subdivided as follows: discontinuation (abrupt vs. gradual); and, replacement (abrupt vs. gradual). Meta-analyses confirmed a lack of difference in outcome, regardless of approach. While a crossover approach does not appear to increase adverse events, the available empiric evidence does not support its clinical superiority on various outcome measures. The existing data therefore argue against the position that a crossover approach in switching antipsychotics represents a ‘safer’ means of preventing clinical deterioration during the switch.

Introduction

Switching antipsychotics is a routine part of daily practice for clinicians treating illnesses such as schizophrenia. Limitations with the conventional antipsychotics related to both efficacy and tolerability (Brenner et al., 1990), in conjunction with an array of such compounds, encouraged switching as a means of achieving the best clinical response. The subsequent introduction of the ‘atypical’ antipsychotics provided yet another rationale for switching based on evidence that these drugs were not only superior clinically, but also better tolerated (Fleischhacker and Hummer, 1997, Remington and Kapur, 2000, Stip, 2000). With a number of atypical agents now available, switching continues to occur frequently (Leslie and Rosenheck, 2002) as clinicians seek the optimal balance between response and side effects for their individual patients.

Given how often switching antipsychotics takes place, it is remarkable how little research has been done addressing this topic. Switching antipsychotics can be associated with an increased risk of relapse, which has been demonstrated (Gardos, 1974), and it is perhaps this line of thinking that has led to the notion that a ‘crossover’ (or crosstaper) approach is the safest means of effecting a switch (Masand and Berry, 2000, Weiden et al., 1997). With this model, clinicians gradually decrease and taper the existing antipsychotic, while at the same time initiating and gradually increasing the next.

Empiric evidence to support this approach, or in fact any other alternative, has been lacking until recently. However, we now have a small but growing number of studies that address this issue, driven in large part it seems by the development of the atypicals and accompanying efforts to provide evidence on how to carry out successful switches. The present paper has reviewed these data with the purpose of providing clinicians with a summary of available evidence.

Section snippets

Search

A MEDLINE search (April 2004) of the English language literature was carried out to identify all published, randomized and controlled trials that compared different strategies for switching antipsychotics (excluding depots). The following phrases formed the basis of the search: antipsychotic switching (165 references), switching antipsychotics (213 references), and antipsychotic switching strategies (26 references). A manual search (January 1980–April 2004) of the following journals was also

Results

As shown in Table 2, separate meta-analyses were conducted for the effects of 1) abrupt vs. gradual discontinuation off the old antipsychotic medication and 2) for immediate versus titrated replacement. For the discontinuation analyses, results from groups 1 and 2 of Kinon et al. (2000) were first combined and compared to groups 3 and 4 (see Table 1). Similarly, the group 1s Casey et al. (2003) and Weiden et al. (2003) were contrasted with the amalgamation of the respective study's groups 2 and

Discussion

Based on the current empiric evidence, albeit limited, a crossover approach in switching antipsychotics is not ‘safer’ in preventing clinical deterioration when compared to a strategy that involves abrupt discontinuation of the exisitng antipsychotic. It is worth pointing out as well though that using a crossover approach during switching, even when starting the next antipsychotic at higher doses, does not appear to be associated with a significant increase in risk of adverse events. This does

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