Efficacy, acceptability and side-effects of oral versus long-acting- injectables antipsychotics: Systematic review and network meta-analysis

• Published in: European neuropsychopharmacology 2024-06, Vol.83, p.11-18
• Main Authors: Wang, Dongfang, Schneider-Thoma, Johannes, Siafis, Spyridon, Qin, Mengchang, Wu, Hui, Zhu, Yikang, Davis, John M, Priller, Josef, Leucht, Stefan
• Format: Article
• Language: English
• Subjects: Acute schizophrenia; Administration, Oral; Antipsychotic Agents - administration & dosage; Antipsychotic Agents - adverse effects; Antipsychotic Agents - therapeutic use; Delayed-Action Preparations - administration & dosage; Humans; Injections; Long-acting injectable antipsychotics; Network Meta-Analysis; Oral antipsychotics; Randomized Controlled Trials as Topic - methods; Schizophrenia - drug therapy; Treatment Outcome
• ISSN: 0924-977X; 1873-7862; 1873-7862
• DOI: 10.1016/j.euroneuro.2024.03.003

•We provide the first network meta-analysis comparing long-acting injectable antipsychotics and their oral counterparts for the acute treatment of schizophrenia.•The efficacy of long-acting injectable and oral antipsychotics for acute schizophrenia is similar.•Some side-effects may be less frequent under LAIs, although this pattern is not consistent across outcomes and drugs. Long-acting injectable antipsychotics (LAIs) are primarily used for relapse prevention, but in some settings and situations, they may also be useful for acute treatment of schizophrenia. We conducted a systematic review and frequentist network meta-analysis of randomized-controlled trials (RCTs), focusing on adult patients in the acute phase of schizophrenia. Interventions were risperidone, paliperidone, aripiprazole, olanzapine, and placebo, administered either orally or as LAI. We synthesized data on overall symptoms, complemented by 17 other efficacy and tolerability outcomes. Confidence in the evidence was assessed with the Confidence-in-Network-Meta-Analysis-framework (CINeMA). We included 115 RCTs with 25,550 participants. All drugs were significantly more efficacious than placebo with the following standardized mean differences and their 95 % confidence intervals: olanzapine LAI -0.66 [-1.00; -0.33], risperidone LAI -0.59[-0.73;-0.46], olanzapine oral -0.55[-0.62;-0.48], aripiprazole LAI -0.54[-0.71; -0.37], risperidone oral -0.48[-0.55;-0.41], paliperidone oral -0.47[-0.58;-0.37], paliperidone LAI -0.45[-0.57;-0.33], aripiprazole oral -0.40[-0.50; -0.31]. There were no significant efficacy differences between LAIs and oral formulations. Sensitivity analyses of the primary outcome overall symptoms largely confirmed these findings. Moreover, some side effects were less frequent under LAIs than under their oral counterparts. Confidence in the evidence was moderate for most comparisons. LAIs are efficacious for acute schizophrenia and may have some benefits compared to oral formulations in terms of side effects. These findings assist clinicians with insights to weigh the risks and benefits between oral and injectable agents when treating patients in the acute phase.