Effectiveness of paliperidone palmitate vs haloperidol decanoate for maintenance treatment of schizophrenia: a randomized clinical trial.
OBJECTIVE
Long-acting injectable antipsychotics are used to reduce medication nonadherence and relapse in schizophrenia-spectrum disorders. The relative effectiveness of long-acting injectable versions of second-generation and older antipsychotics has not been assessed.


OBJECTIVE
To compare the effectiveness of the second-generation long-acting injectable antipsychotic paliperidone palmitate with the older long-acting injectable antipsychotic haloperidol decanoate.


METHODS
Multisite, double-blind, randomized clinical trial conducted from March 2011 to July 2013 at 22 US clinical research sites. Randomized patients (n = 311) were adults diagnosed with schizophrenia or schizoaffective disorder who were clinically assessed to be at risk of relapse and likely to benefit from a long-acting injectable antipsychotic.


METHODS
Intramuscular injections of haloperidol decanoate 25 to 200 mg or paliperidone palmitate 39 to 234 mg every month for as long as 24 months.


METHODS
Efficacy failure, defined as a psychiatric hospitalization, a need for crisis stabilization, a substantial increase in frequency of outpatient visits, a clinician's decision that oral antipsychotic could not be discontinued within 8 weeks after starting the long-acting injectable antipsychotics, or a clinician's decision to discontinue the assigned long-acting injectable due to inadequate therapeutic benefit. Key secondary outcomes were common adverse effects of antipsychotic medications.


RESULTS
There was no statistically significant difference in the rate of efficacy failure for paliperidone palmitate compared with haloperidol decanoate (adjusted hazard ratio, 0.98; 95% CI, 0.65-1.47). The number of participants who experienced efficacy failure was 49 (33.8%) in the paliperidone palmitate group and 47 (32.4%) in the haloperidol decanoate group. On average, participants in the paliperidone palmitate group gained weight and those in the haloperidol decanoate group lost weight; after 6 months, the least-squares mean weight change for those taking paliperidone palmitate was increased by 2.17 kg (95% CI, 1.25-3.09) and was decreased for those taking haloperidol decanoate (-0.96 kg; 95% CI, -1.88 to -0.04). Patients taking paliperidone palmitate had significantly higher maximum mean levels of serum prolactin (men, 34.56 µg/L [95% CI, 29.75-39.37] vs 15.41 µg/L [95% CI, 10.73-20.08]; P <.001, and for women, 75.19 [95% CI, 63.03-87.36] vs 26.84 [95% CI, 13.29-40.40]; P<.001). Patients taking haloperidol decanoate had significantly larger increases in global ratings of akathisia (0.73 [95% CI, 0.59-0.87] vs 0.45 [95% CI, 0.31-0.59]; P=.006).


CONCLUSIONS
In adults with schizophrenia or schizoaffective disorder, use of paliperidone palmitate vs haloperidol decanoate did not result in a statistically significant difference in efficacy failure, but was associated with more weight gain and greater increases in serum prolactin, whereas haloperidol decanoate was associated with more akathisia. However, the CIs do not rule out the possibility of a clinically meaningful advantage with paliperidone palmitate.


BACKGROUND
clinicaltrials.gov Identifier: NCT01136772.
Department of Psychiatry and Health Behavior, Georgia Regents University, Augusta.
Joseph P
JP
McEvoy
Department of Psychiatry, UT Southwestern Medical Center, Dallas.
Matthew
M
Byerly
Department of Biostatistics, Gillings School of Public Health, University of North Carolina, Chapel Hill.
Robert M
RM
Hamer
Department of Biostatistics, Gillings School of Public Health, University of North Carolina, Chapel Hill.
Rosalie
R
Dominik
Department of Psychiatry, Division of Social and Community Psychiatry, Duke University, Durham, North Carolina.
Marvin S
MS
Swartz
Yale School of Medicine, Yale University, and Northeast Program Evaluation Center, West Haven, Connecticut.
Robert A
RA
Rosenheck
Department of Biostatistics, Gillings School of Public Health, University of North Carolina, Chapel Hill.
Neepa
N
Ray
Department of Psychiatry, School of Medicine and Dentistry, University of Rochester, Rochester, New York.
J Steven
JS
Lamberti
Department of Psychiatry and Health Behavior, Georgia Regents University, Augusta.
Peter F
PF
Buckley
Department of Biostatistics, Gillings School of Public Health, University of North Carolina, Chapel Hill.
Tania M
TM
Wilkins
Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, New York8New York State Psychiatric Institute, New York, New York.
T Scott
TS
Stroup
D000328:Adult; D017109:Akathisia, Drug-Induced; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006220:Haloperidol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006760:Hospitalization; D006801:Humans; D007273:Injections, Intramuscular; D007555:Isoxazoles / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000068882:Paliperidone Palmitate; D010168:Palmitates / Q000009:adverse effects / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy; D017211:Treatment Failure; D016896:Treatment Outcome; D015430:Weight Gain
D014150:Antipsychotic Agents; D007555:Isoxazoles; D010168:Palmitates; C033563:haloperidol decanoate; D006220:Haloperidol; D000068882:Paliperidone Palmitate