title: Long-acting injectable risperidone and metabolic ratio: a possible index of clinical outcome in treatment-resistant schizophrenic patients.
abstract: BACKGROUND
  It is still common to encounter a partial or no response to antipsychotic treatment in clinical practice, but only individual case reports are currently available concerning the efficacy of long-acting risperidone (RLAI) in treatment-resistant schizophrenia. The relationship between RSP and 9-OH-RSP plasma levels, and clinical response or tolerability has not yet been thoroughly assessed.
  
  
  METHODS
  This open-label, non-randomised study involved 30 outpatients with treatment-resistant schizophrenia, who were prescribed RLAI for 6 months, and clinically evaluated using the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Symptoms Scale (PANSS), the Clinical Global Impression-Improvement Scale (CGI-I), and the Simpson and Angus Scale for Extrapyramidal Side Effects (EPSE). Plasma RSP and 9-OH-RSP levels were determined at steady-state, and the metabolic ratio (MR) was calculated as plasma 9-OH-RSP/RSP levels.
  
  
  RESULTS
  At the end of the study, 60% of the patients responded to RLAI (a >or=20% reduction in the PANSS score). Linear regression analysis showed a significant positive relationship between the RSP dose and active moiety (RSP + 9-OH-RSP) (r = 0.4; p = 0.02). There was a significant positive relationship between active moiety and EPSE scores (r = 0.6; p = 0.00). The BPRS responders had a significantly higher mean MR than the non-responders (3.41 +/- 1.87 SD vs 1.60 +/- 0.98 SD) (p = 0.00).
  
  
  CONCLUSIONS
  Therapeutic drug monitoring seems to be useful in optimising the dose of RLAI, especially in the case of tolerability problems. MR might be a better index of clinical response to RLAI than the value of the active moiety, although this needs to be confirmed by further data.
authors.affiliation: Department of Neuroscience, Clinical Psychiatry, Ospedale Fatebenefratelli and Oftalmico, Milan, Italy. lucia.volonteri@fbf.milano.it
authors.forename: Lucia Sara
authors.initials: LS
authors.lastname: Volonteri
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Cerveri
authors.forename: Ilaria Francesca
authors.initials: IF
authors.lastname: De Gaspari
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Baldi
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Rolandi
authors.forename: Pietro
authors.initials: P
authors.lastname: Papa
authors.forename: Massimo Carlo
authors.initials: MC
authors.lastname: Mauri
authors.forename: Claudio
authors.initials: C
authors.lastname: Mencacci
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000097:blood*; D054316:Biomarkers, Pharmacological / Q000097:blood*; D010054:Brief Psychiatric Rating Scale; D003692:Delayed-Action Preparations / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods*; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D007555:Isoxazoles / Q000097:blood*; D008297:Male; D008875:Middle Aged; D000068882:Paliperidone Palmitate; D011569:Psychiatric Status Rating Scales; D011743:Pyrimidines / Q000097:blood*; D018967:Risperidone / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood*; D012559:Schizophrenia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D012720:Severity of Illness Index
chemical_list: D014150:Antipsychotic Agents; D054316:Biomarkers, Pharmacological; D003692:Delayed-Action Preparations; D007555:Isoxazoles; D011743:Pyrimidines; D018967:Risperidone; D000068882:Paliperidone Palmitate