Long acting injectable antipsychotics are prescribed to reduce non adherence and hopefully thus reduce relapse in schizophrenia. First of the second generation agent to be available in Long acting (LA) form was risperidone (2003). Paliperidone palmitate came to market in 2009. It does not require refrigeration like risperidone LA and is given monthly as opposed to biweekly for risperidone made it attractive for many. Benefits of second generation agents in general are often questioned. CATIE trial found that when an older drug (perphenazine) was used at moderate doses, several newer ones were not superior in safety or effectiveness . The SGA’s association with metabolic syndrome is another growing worry. It is on this back ground that this study by Joseph P. McEvoy at al becomes important.
ACLAIMS (A Comparison of Long-acting Medications for Schizophrenia) trial,is the first randomized comparison of first- and second-generation long-acting injectable antipsychotics. It compared the effects of long-acting injectable paliperidone palmitate and haloperidol decanoate.
22 US clinical sites ( NIMH- Schizophrenia Trials Network) recruited adults with diagnosis of schizophrenia or schizoaffective disorder who were thought to benefit from LA due to history of medication noncompliance, significant substance abuse, or both. Those who failed to benefit from oral risperidone or paliperiodone in the past were excluded. 311 patients were randomised. oral medication phase lasted 4-7 days before giving injection. Prescriptions followed these recommendations : paliperidone 234mg ( day 1), 156 mg ( day 8), 117 mg (monthly), haloperidol was 50 mg ( day 1), 50mg ( day 8) and 75 mg ( day 28) and then 50 mg monthly. These schedules were adjusted according to the clinical situation. Primary outcome was efficacy failure, judged by a panel blind to the allocation status. Panel considered following factors: psychiatric hospitalization; a need for crisis stabilization; increase in outpatient visits; a clinician’s decision that oral antipsychotic medication could not be discontinued within 8 weeks after starting the long-acting injectable and a clinician’s decision of inadequate therapeutic benefit. Once established, mean monthly dose of paliperidone pal- mitate ranged from 129 to 169 mg and the mean monthly dose of haloperidol decanoate ranged from 67 to 83 mg . Patients were originally planned for 24 m follow up, but patients recruited in the second year was followed only for 12 months.Analysis was limited to all those who received at least 1 injection and at least 1 postbaseline assessment. (=modified intent-to-treat population).
There is no statistically significant difference in the rate of efficacy failure between paliperidone palmitate group (49 [33.8%]) and in the haloperidol decanoate group (47 [32.4%].PANSS total score decrease was similar among both groups.
Common reasons for efficacy failure: hospitalization (44 [89.8%] of paliperidone palmitate events and 34 [72.3%] of haloperidol decanoate ones) and clinician discontinuation of study medication due to inadequate therapeutic effect (34 [69.4%] paliperidone events and 28 [59.6%] haloperidol ). Participants taking paliperidone gained weight progressively over time, while those taking haloperidol lost weight . There were no differences in blood metabolic parameters. No statistically significant differences between groups in ratings of abnormal involuntary movement or Tardive dyskinesia. Akathisia increased more for haloperidol , and they also required more medications to manage akathisia and parkinsonism. Though Paliperidone caused huge increase in prolactin levels, sexual dysfunction did not differ among groups.
The only adverse event with a difference of 5% or more between the groups was sialorrhea (16.3% of patients taking paliperidone palmitate compared with 10.9% in the haloperidol decanoate group )
Conclusion: No evidence that long- acting injectable paliperidone palmitate is superior to haloperidol decanoate. Roughly one third of patients were deemed failed in both groups.
Comments: Cost difference between these two medications is huge. ( US: $35 ( haloperidol) vs $1000 (paliperidone palmitate). Is the new one worth it? The evidence speaks for itself.
Summary of the article:
McEvoy JP, Byerly M, Hamer RM, Dominik R, Swartz MS, Rosenheck RA, Ray N, Lamberti JS, Buckley PF, Wilkins TM, Stroup TS.
JAMA. 2014 May 21;311(19):1978-87