Does the frequency of administration of long acting injectable antipsychotics impact psychiatric outcomes and adverse effects: A systematic review and meta-analysis

Abstract

words)Dosing regimens for depot antipsychotics range from two-to twelve-weekly administration.There are limited meta-analytic data regarding the effect of different injection frequencies of the same depot antipsychotic at the equivalent dose on psychiatric outcomes and adverse effects. This study investigated differences in psychiatric outcomes and adverse effects between different frequencies of depot antipsychotics through a systematic review and metaanalysis. We performed a systematic search of MEDLINE, EMBASE, Cochrane database, PsycINFO and two Chinese databases for RCTs that compared the frequency of depot antipsychotic administration. The primary outcome was psychiatric symptomatology, with secondary outcomes of quality of life, admission rates, adverse drug reactions, costeffectiveness and compliance. Twelve studies were included in the meta-analysis. Most studies compared two-and four-weekly injections (n = 10). Different injection frequencies did not lead to differences in clinical outcomes or adverse events. However, two-weekly injections led to significantly greater improvements on the CGI-S scale than four-weekly administration. A sensitivity analysis by removing low quality studies showed lower incidence of somnolence and injection site pain for 2-weekly compared with 4-weekly injections. There were limited data on admission rates and no RCT data on cost-effectiveness or compliance. While there is limited evidence on secondary measures to support 2-weekly over 4-weekly injections, patient choice and convenience should remain the priority when considering certain antipsychotics. Cost-effectiveness and adherence should also be considered, although further studies are required to further evaluate these parameters.

Long-Acting Injectable Antipsychotics: A Systematic Review of Their Non-Systemic Adverse Effect Profile

“… Investigator-rated injection site reactions for PP3M vs PP1M: Induration (12% vs 10%), redness (10% vs 9%), swelling (7% vs 9%). 12 Ting et al (2019) 27 Olanzapine q2w or q1M Paliperidone q1M or q3M Fluphenazine Aripiprazole q1M Risperidone q2w Q2w injections were less likely to cause injection site pain than q1M injections (finding from sensitivity analysis). Abbreviations: q1M, once-monthly; q3M, every 3-months; q2w, every 2 weeks; FGAPs, first generation antipsychotics.…”

“…Injection site reactions and pain were infrequent, low and mild, and were similar between the PP1M and the PP3M, regardless of the dose and of the volumen or location of the injection. The systematic reviews and meta-analyses conducted by Kisely et al 24 and Ting et al 27 comparing several types of LAI antipsychotics, reported that 2 weekly administration was less likely to lead to injection site pain than 4 weekly administration. The studies by Hay 17 and Jones et al 18 both reported clinically significant reactions such as pain, bleeding, nodules, thickening, hematoma and indurations primarily associated with the administration of haloperidol decanoate, although these were not significantly different from those reported with other depot antipsychotics.…”

“…Therefore, a total of 12 articles were selected for full review and data extraction using a standardized data collection tool. 11,[17][18][19][20][21][22][23][24][25][26][27] Table 1 provides general information about these studies, their design and the outcomes that were reported. Table 2 lists the different LAI antipsychotics investigated in the 12 articles included in this review, and provides a summary of the associated injection-site reactions that were reported.…”

“…Table 2 lists the different LAI antipsychotics investigated in the 12 articles included in this review, and provides a summary of the associated injection-site reactions that were reported. 11,[17][18][19][20][21][22][23][24][25][26][27] Various injection site reactions for different LAI antipsychotics were reported in these studies, including pain, bleeding, and swelling. The most common injection site reaction was pain which was mainly reported in the studies by Hay, 17 Jones et al, 18 Atkins et al, 23 and Kern Sliwa et al 26 (Table 2).…”

“… 13 The study by Hay 17 concluded that the effects of repeated injections of high doses over many years, along with the irritant properties of the drug, contributed to the development of site reactions. The study by Ting et al 27 suggested that the incidence of injection site pain may decrease as the number of injections received increases, possibly because it has been observed that patients become desensitized to the injections when used over a long period of time. 31 In the study by Jones et al 18 a clinically significant increase of site reactions was reported with higher concentrations of LAI antipsychotics among patients who had been receiving more frequent injections, and a significantly higher volume of depot administered in the previous 12 months.…”