Research highlights: Continuous antipsychotic treatment helps prevent relapse more than discontinuous treatment and patients remain relapse-free longer; discontinuous treatment studies tend to select patients with relatively mild disease, thereby creating an inflated treatment success rate compared to true regression in daily clinical practice. While continuous antipsychotic treatment is still the preferred treatment for all patients with schizophrenia, the topic of continuous exposure to drug-related adverse effects has also raised concerns. Whether the continuous treatment model is really necessary or even justified for patients who have achieved stabilization with antipsychotic treatment has also raised questions among some physicians. In this context, a number of discontinuous treatment modalities are emerging as hot topics for research, including: ★ Intermittent or “targeted” treatment strategies (also known as guided discontinuation): medication is administered only at the beginning of a relapse or when symptoms worsen; in other words, patients use antipsychotics only when they “need” them Dose stretching: dosing at 1, 2 or even 3 day intervals, based on the correlation between dose and D2 receptor occupancy. In this context, researchers from KU Leuven, Belgium, and other institutions conducted a systematic review and meta-analysis study aimed at exploring the risk of relapse and hospital admission of patients under continuous versus discontinuous antipsychotic treatment. The results showed that patients on continuous treatment had a lower risk of relapse and a longer duration of non-relapse than those on intermittent treatment; the “success rate” of discontinuous treatment was artificially inflated for reasons of bias. In short, the drug still can’t be stopped. The investigators conducted a systematic search of the MEDLINE database, targeting randomized controlled studies published in English between 1950 and November 2014 that compared relapse/readmission risk under continuous versus discontinuous treatment (including intermittent treatment and placebo substitution) in stable schizophrenia patients on first- or second-generation oral/antipsychotic injectable injections. readmission risk, and/or time from baseline to relapse, with a follow-up period of at least 6 months. The investigators also supplemented the studies by searching the citation lists of other systematic reviews and Cochrane reports. The investigators conducted two meta-analysis studies comparing the risk of relapse and readmission with placebo replacement therapy vs. continuous therapy and intermittent therapy vs. continuous therapy, respectively, and assessed the role of study characteristics in this. For the time taken from baseline to relapse, the investigators explored this by descriptive analysis. Relapse rates in patients with stable schizophrenia treated with second-generation antipsychotics (De Hert M et al. 2015) Red: placebo treatment Green: active drug treatment Relapse rates in patients with first-episode psychosis treated with intermittent versus continuous antipsychotics (De Hert M et al. 2015) Red: intermittent treatment Green: continuous treatment The investigators found 48 studies, 21 of which met the inclusion criteria; the investigators added an additional 25 studies from other systematic reviews. The analysis of these 46 studies showed that: ★ For patients with stable schizophrenia exposed to non-continuous treatment for at least 6 months, the risk of relapse was 3.36 (OR 3.36; 95% CI 2.36C5.45; p<0.0001) to 5.64 times higher (OR 5.64; 95% CI 4.47C7.11; p<0.0001) than for patients on continuous treatment 0.0001); ★ Salvage drug use (p = 0.0102) was the only study feature that explained systematic differences in the risk of relapse between placebo and continuous treatment; ★ Studies reporting time from baseline to relapse showed that continuous treatment always significantly delayed relapse compared with discontinuous treatment; ★ Despite high inconsistency in the time between treatment interruption and symptom recurrence, the mean baseline to relapse ★ Although there was a high degree of inconsistency in the time between treatment interruption and symptom recurrence, data on mean baseline to relapse time suggested that clinical instability could occur by 11-14 months with intermittent treatment and by 5 months with placebo treatment; ★ In this systematic review, for patients receiving continuous treatment, their median baseline to relapse time could not be estimated because the proportion of patients who relapsed by the end of the study was <50%. The investigators concluded that patients with stable schizophrenia had a lower risk of relapse and a longer duration of sustained non-relapse under continuous treatment compared to non-continuous treatment. In addition, the success rate of discontinuous treatment was not as high as expected for various reasons. Therefore, continuous treatment remains the gold standard to be followed in the treatment of patients with schizophrenia. Given that only a few rather general factors predict relapse in patients with schizophrenia, and that subsequent relapses may lead to worsening functioning and increasingly intractable disease, continuous treatment is of even greater importance. Literature Index: De Hert M et al. The Use of Continuous Treatment Versus Placebo or Intermittent Treatment Strategies in Stabilized Patients with Schizophrenia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials with First- and Second-Generation Antipsychotics. CNS Drugs. 2015 Aug 21. [Epub ahead of print]