Long-Acting Injectable Antipsychotics and Side Effects Compared to Oral Formulations
Long-acting injectable antipsychotics do not have fewer side effects than oral antipsychotics overall, but some specific side effects may be less frequent with LAIs compared to their oral counterparts. 1, 2
Side Effect Profile Comparison
Overall Side Effect Burden
- LAIs and oral formulations of the same antipsychotic demonstrate comparable side effect profiles, with the LAI side effects corresponding to the patterns already known from the oral formulations 2
- There is no definite evidence that LAIs are superior to oral antipsychotics in terms of overall side effects, though they may differ in specific side-effect profiles 3
Specific Side Effects That May Be Reduced with LAIs
- Some side effects were less pronounced under LAIs than under their oral formulations in indirect comparisons against placebo, though this finding requires confirmation through head-to-head randomized controlled trials 2
- A 2024 network meta-analysis found that some side effects were less frequent under LAIs than under oral counterparts when examining acute schizophrenia treatment 1
- Long-acting risperidone may be associated with equal or fewer side effects than oral risperidone, whereas first-generation LAIs like fluphenazine decanoate may be associated with equal or more side effects than oral fluphenazine 4
Important Caveat: Injection Site Reactions
- If injection site reactions are taken into account, LAI preparations demonstrate comparable safety and tolerability to oral counterparts 5
- This means LAIs introduce a unique side effect (injection site reactions) not present with oral formulations 5
Second-Generation vs First-Generation LAIs
- Second-generation LAIs are preferred over first-generation agents due to better tolerability and fewer neurological side effects 6, 7, 8
- This recommendation applies when comparing LAI classes, not when comparing LAI versus oral formulations of the same agent 6
Clinical Implications
The Real Advantage of LAIs
- The primary benefit of LAIs is improved adherence leading to reduced relapse and hospitalization rates, not a superior side effect profile 3, 6
- LAIs reduce hospitalization rates as a consequence of improved adherence through guaranteed medication delivery 6
- Medication adherence was significantly better in groups receiving injections compared to oral formulations 3
Pharmacokinetic Considerations
- LAIs provide more stable pharmacokinetics compared to oral antipsychotics, which theoretically could reduce side effects related to peak-trough fluctuations, though this has not been definitively proven in clinical trials 4
Evidence Quality and Limitations
- Confidence in the evidence was moderate for most comparisons in the 2024 network meta-analysis examining this question 1
- There are still relatively few well-designed, head-to-head, long-term comparisons of LAIs and oral medications specifically examining side effect profiles 3
- Most evidence comparing side effects between LAIs and oral formulations comes from indirect comparisons through placebo-controlled trials, which must be interpreted cautiously 2