title: A six month randomized controlled trial of long acting injectable risperidone 50 and 100mg in treatment resistant schizophrenia.
abstract: It has been suggested that atypical antipsychotic drugs (A-APDs) other than clozapine may be effective to improve positive symptoms in some patients with treatment resistant schizophrenia (TRS), if both the dose is higher, and the duration of the trial longer, than those which have been ineffective in non-TRS (NTRS) patients. This hypothesis was tested with long acting injectable risperidone (Risperdal Consta®, RLAI). One hundred sixty TRS patients selected for persistent moderate-severe delusions or hallucinations, or both, were randomized to RLAI, 50 or 100mg biweekly, in a six month, outpatient, double-blind, multicenter trial. We hypothesized that RLAI, 100mg, would be more effective than RLAI, 50mg. However, both doses produced clinically significant and equivalent improvement in PANSS Total, Positive, and Negative subscale scores, as well as key cognitive, global and functional measures, with increasing response during the course of the study, confirming the value of longer clinical trial duration for patients with TRS, but not superiority of the higher dose. The overall response rate was comparable to that previously reported for clozapine and high dose olanzapine, another A-APD, in TRS. Both doses of RLAI were equally well tolerated, producing minimal extrapyramidal side effects and few drop outs. Plasma levels of the active moiety, risperidone+9-hydroxyrisperidone, during treatment with RLAI 100mg, were comparable to those for 6-8 mg/day oral risperidone, which have not been effective in TRS. Further study of RLAI, ≥ 50-100mg biweekly, should compare it with clozapine and oral risperidone in TRS, with duration of treatment ≥ six months.
authors.affiliation: Northwestern Feinberg School of Medicine, Chicago, IL, United States. Electronic address: h-meltzer@northwestern.edu.
authors.forename: H Y
authors.initials: HY
authors.lastname: Meltzer
authors.affiliation: New York University School of Medicine, New York, NY, United States.
authors.forename: J-P
authors.initials: JP
authors.lastname: Lindenmayer
authors.affiliation: Precise Research Center, Jackson, MS, United States.
authors.forename: J
authors.initials: J
authors.lastname: Kwentus
authors.affiliation: Northwestern Feinberg School of Medicine, Chicago, IL, United States.
authors.forename: D B
authors.initials: DB
authors.lastname: Share
authors.affiliation: Northwestern Feinberg School of Medicine, Chicago, IL, United States.
authors.forename: R
authors.initials: R
authors.lastname: Johnson
authors.affiliation: Northwestern Feinberg School of Medicine, Chicago, IL, United States.
authors.forename: K
authors.initials: K
authors.lastname: Jayathilake
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D003692:Delayed-Action Preparations / Q000009:adverse effects / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000097:blood; D008297:Male; D008875:Middle Aged; D000068882:Paliperidone Palmitate; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000188:drug therapy; D011743:Pyrimidines / Q000097:blood; D018967:Risperidone / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D007555:Isoxazoles; D011743:Pyrimidines; D018967:Risperidone; D000068882:Paliperidone Palmitate
keywords: Extrapyramidal; Long acting injectable; Prolactin; Risperidone; Schizophrenia; Treatment resistant