TY - JOUR
T1 - Safety and tolerability of long-acting injectable versus oral antipsychotics
T2 - A meta-analysis of randomized controlled studies comparing the same antipsychotics
AU - Misawa, Fuminari
AU - Kishimoto, Taishiro
AU - Hagi, Katsuhiko
AU - Kane, John M.
AU - Correll, Christoph U.
PY - 2016/10/1
Y1 - 2016/10/1
N2 - Objective We aimed to assess whether long-acting injectable antipsychotics (LAIs), which are initiated in a loading strategy or overlapping with oral antipsychotics (OAPs) and which cannot be stopped immediately, are associated with greater safety/tolerability issues than OAPs. Method Systematic review and meta-analysis of randomized controlled trials (RCTs) comparing LAIs and OAPs, including only LAI-OAP pairs of the same OAP (allowing oral risperidone and paliperidone as comparators for either risperidone or paliperidone LAI). Primary outcome was treatment discontinuation due to adverse events. Secondary outcomes included serious adverse events, death, ≥ 1 adverse event and individual adverse event rates. Results Across 16 RCTs (n = 4902, mean age = 36.4 years, males = 65.8%, schizophrenia = 99.1%) reporting on 119 adverse event outcomes, 55 (46.2%) adverse events were reported by ≥ 2 studies allowing a formal meta-analysis. Out of all 119 reported adverse events, LAIs and OAPs did not differ significantly regarding 115 (96.6%). LAIs were similar to OAPs regarding the frequency of treatment discontinuation due to adverse events, serious adverse events, all-cause death and death for reasons excluding accident or suicide. Compared to OAPs, LAIs were associated with significantly more akinesia, low-density lipoprotein cholesterol change and anxiety. Conversely, LAIs were associated with significantly lower prolactin change. Conclusion LAIs and OAPs did not differ on all serious and > 90% of individual adverse events. However, more studies focusing on adverse event frequencies, severity and time course associated with LAI vs OAP formulations of the same antipsychotic are needed. Additionally, adverse events data for LAIs after stopping overlapping oral antipsychotic treatment are needed.
AB - Objective We aimed to assess whether long-acting injectable antipsychotics (LAIs), which are initiated in a loading strategy or overlapping with oral antipsychotics (OAPs) and which cannot be stopped immediately, are associated with greater safety/tolerability issues than OAPs. Method Systematic review and meta-analysis of randomized controlled trials (RCTs) comparing LAIs and OAPs, including only LAI-OAP pairs of the same OAP (allowing oral risperidone and paliperidone as comparators for either risperidone or paliperidone LAI). Primary outcome was treatment discontinuation due to adverse events. Secondary outcomes included serious adverse events, death, ≥ 1 adverse event and individual adverse event rates. Results Across 16 RCTs (n = 4902, mean age = 36.4 years, males = 65.8%, schizophrenia = 99.1%) reporting on 119 adverse event outcomes, 55 (46.2%) adverse events were reported by ≥ 2 studies allowing a formal meta-analysis. Out of all 119 reported adverse events, LAIs and OAPs did not differ significantly regarding 115 (96.6%). LAIs were similar to OAPs regarding the frequency of treatment discontinuation due to adverse events, serious adverse events, all-cause death and death for reasons excluding accident or suicide. Compared to OAPs, LAIs were associated with significantly more akinesia, low-density lipoprotein cholesterol change and anxiety. Conversely, LAIs were associated with significantly lower prolactin change. Conclusion LAIs and OAPs did not differ on all serious and > 90% of individual adverse events. However, more studies focusing on adverse event frequencies, severity and time course associated with LAI vs OAP formulations of the same antipsychotic are needed. Additionally, adverse events data for LAIs after stopping overlapping oral antipsychotic treatment are needed.
KW - Adverse events
KW - Long-acting injectable antipsychotics
KW - Meta-analysis
KW - Oral antipsychotics
KW - Randomized controlled trial
KW - Schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=84995630387&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84995630387&partnerID=8YFLogxK
U2 - 10.1016/j.schres.2016.07.018
DO - 10.1016/j.schres.2016.07.018
M3 - Article
C2 - 27499361
AN - SCOPUS:84995630387
VL - 176
SP - 220
EP - 230
JO - Schizophrenia Research
JF - Schizophrenia Research
SN - 0920-9964
IS - 2-3
ER -