Long-acting injectable risperidone and metabolic ratio: a possible index of clinical outcome in treatment-resistant schizophrenic patients.
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.
Volonteri
Lucia Sara
LS
Department of Neuroscience, Clinical Psychiatry, Ospedale Fatebenefratelli and Oftalmico, Milan, Italy. lucia.volonteri@fbf.milano.it
Cerveri
Giancarlo
G
De Gaspari
Ilaria Francesca
IF
Baldi
Maria Luisa
ML
Rolandi
Maria Laura
ML
Papa
Pietro
P
Mauri
Massimo Carlo
MC
Mencacci
Claudio
C
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
D014150:Antipsychotic Agents; D054316:Biomarkers, Pharmacological; D003692:Delayed-Action Preparations; D007555:Isoxazoles; D011743:Pyrimidines; D018967:Risperidone; D000068882:Paliperidone Palmitate