A 2018 meta-analysis investigated the risk of drug-induced tardive dyskinesia (TD) with first- and second-generation antipsychotics (FGA and SGA). From 57 head-to-head randomized controlled trials (32 FGA-SGA pairs and 35 SGA-SGA pairs), the annual incidence of TD in the FGA groups was found to be 6.5% (95% confidence interval [CI] 5.3 to 7.8%) versus 2.6% (95% CI 2.0 to 3.1) among SGA groups. Chlorpromazine and fluphenazine were the highest among the FGAs and SGAs with > 10% mean annualized TD incidence; however, there was only one study each to provide data for chlorpromazine and fluphenazine. Haloperidol, represented by 22 studies, reported the third-highest mean annualized incidence rate at 7.5% (95% CI 5.9 to 9.2%). The estimated TD risk ratio (RR) and annualized rate ratio (RaR) were found to be significantly lower for SGAs compared to the FGAs (RR 0.47, 95% CI 0.39 to 0.57, p<0.0001; RaR 0.35, 95% CI 0.28 to 0.45, p<0.0001). [1]
Exploratory analysis revealed that olanzapine had a significantly lower RaR compared to other non-clozapine SGAs (RaR 0.66; 95% CI 0.49 to 0.88; p= 0.006). Based on these results, the SGAs appear to have a lower risk for TD compared to the FGAs, but more data is needed to confirm the risk between individual agents within drug classes. The individual incidences of TD with the antipsychotics included in this meta-analysis can be found in Table 1. [1]
A 2015 meta-analysis focusing on older adults compared the risk of TD from FGA and SGA use. What defines an older adult is not specified within the meta-analysis, but the youngest age from included studies was 50 years. From 23 studies, the incidence estimate for probable TD at 1 year was 23% (95% CI 15.3 to 30.6) for FGAs and 7% (95% CI 4.4 to 10.2) for SGAs. Furthermore, the incidence estimate for persistent TD for SGAs was 3% (95% CI 1.5 to 4.2). While these findings indicate a lower risk with SGAs, data for long-term use is limited compared to FGAs. The prevalence estimates for FGAs were 53% (95% CI 39.0 to 68.4%) for mild TD and 38% (95% CI 25.9 to 50.3%) for probable TD. [2]
A 2021 meta-analysis aimed to determine the magnitude of antipsychotic-induced extrapyramidal side effects (EPSEs) including parkinsonism, akathisia, and TD. A total of 15 studies conducted between 2000 and 2019 were included for analysis. The pooled estimate of antipsychotic-induced EPSEs was found to be 37% (95% CI 18 to 55%). Patients treated in a hospital setting had higher rates of antipsychotic-induced EPSEs (33%; 95% CI 17 to 49%) than those treated at a rehabilitation center (13%; 95% CI 9.0 to 17%). Overall, the pooled prevalence of tardive dyskinesia was approximately 7% (95% CI 4 to 9%). Despite this finding, significant publication bias was evident in studies reporting TD (p= 0.021). [3]
A 2017 article discusses known data for antipsychotics and developing TD. While it is presumed that SGAs were associated with less risk of developing TD, the risk seems to increase the longer they are used at higher doses. Therefore, long-term use of FGAs or SGAs should be considered only when discontinuing leads to worsening illness. Off-label use of antipsychotic agents is also not recommended, and alternative regimens should be considered when feasible. [4]