Best Strategy to Prevent Schizophrenia Relapse Yields Unexpected Results

Megan Brooks

June 29, 2022

A large meta-analysis sheds light on the best antipsychotic maintenance strategy to prevent relapse in clinically-stable schizophrenia — with some unexpected results that have potential implications for changes to current guidelines.

Consistent with the researchers' hypothesis, continuing antipsychotic treatment at the standard dose, switching to another antipsychotic, and reducing the dose were all significantly more effective than stopping antipsychotic treatment to prevent relapse.

However, contrary to the researchers' hypothesis, which was based on current literature, switching to another antipsychotic was just as effective as continuing an antipsychotic at the standard dose.

Switching to another antipsychotic "does not increase the risk of relapse. This result was not expected, as previous literature suggested otherwise," Giovanni Ostuzzi, MD, PhD, with University of Verona, Italy, told Medscape Medical News.

"On the other hand, reducing the dose below the standard range used in the acute phase carries a tangible risk of relapse, and should be limited to selected cases, for example those where the risk of withdrawing the treatment altogether is particularly high," Ostuzzi said.

"These results should inform evidence-based guidelines, considering that clinical practices for relapse prevention are still heterogeneous and too often guided by clinical common sense only," he added.

The study was published online June 23 in Lancet Psychiatry.

Guideline Update Warranted

The researchers evaluated the effect of different antipsychotic treatment strategies on risk for relapse in a network meta-analysis of 98 randomized controlled trials (RCTs) involving nearly 14,000 patients.

Compared to stopping the antipsychotic, all continuation strategies were effective in preventing relapse.

The risk for relapse was largely (and similarly) reduced when continuing the antipsychotic at the standard dose or switching to a different antipsychotic (relative risk [RR] 0.37 and 0.44, respectively), the researchers found.

Both strategies outperformed the strategy of reducing the antipsychotic dose below the standard (RR, 0.68), which was inferior to the other two strategies.

For every three patients continuing an antipsychotic at standard doses, one additional patient will avoid relapse compared to stopping an antipsychotic, "which can be regarded as a large effect magnitude according to commonly used thresholds and results from RCTs in acute schizophrenia," the researchers write.

The number needed to treat (NNT) slightly increased to about 3.5 for patients who switched antipsychotic treatment — "still regarded as a large effect magnitude," they note.

"Currently, most psychiatrists are aware of the benefits of continuing antipsychotics in clinically stable individuals. However, they might face the necessity of changing the ongoing treatment strategy, generally because of burdening side effects, poor adherence, or both," said Ostuzzi.

"Our findings support updating clinical guidelines to recognize that switching to another antipsychotic during maintenance treatment can be as effective as continuing antipsychotics at standard dose, whereas dose reduction below standard doses should be limited to selected cases," the investigators write.

More to the Story

In an accompanying editorial, Marieke J.H. Begemann, PhD, University Medical Center Groningen, Gronigen, the Netherlands, and colleagues note the large number of patients included in the analysis provide "great credibility" to the findings, which are "trustworthy and important, yet only tell part of the story."

They note that while tapering information was often missing, antipsychotic discontinuation was probably abrupt for about two thirds of the included studies. 

"The issue of slow versus swift tapering is not yet settled, as there is a scarcity of RCTs that provide very gradual tapering over several months," the editorialists write.

To fill this gap, several randomized trials are now in progress to specifically address the effects of gradual tapering or discontinuation vs antipsychotic maintenance treatment in clinically stable schizophrenia.

"Time is pressing, as patients, their families, and clinicians need evidence-based data to weigh up the risks and benefits of maintaining, switching, or reducing medication with respect to a range of outcomes that are important to them, including social functioning, cognition, physical health, sexual health, and quality of life, thus going well beyond relapse prevention," the editorialists note.

"Schizophrenia-spectrum disorders are heterogeneous with a largely unpredictable course, and we have known for a long time that a substantial proportion of patients who experienced a first psychosis can manage without antipsychotic medication. The challenge for future research is therefore to identify this subgroup on the basis of individual characteristics and guide them in tapering medication safely," they add.

The study had no funding source . Ostuzzi reports no relevant financial relationships. A complete list of author disclosures is available with the original article. The editorialists have reported no relevant financial relationships.

Lancet Psychiatry. Published online June 23, 2022. Abstract, Editorial  

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