S229. CAN LONG-ACTING INJECTABLE PALIPERIDONE DOSING BE OPTIMIZED WITH PLASMA LEVEL MEASUREMENTS?
Notice bibliographique
Résumé
Most people with schizophrenia respond robustly to antipsychotic medication but are at very high risk of relapse if these medications are stopped. Long-term maintenance treatment with antipsychotic medication can dramatically reduce the risk of relapse. With long-acting injectable antipsychotic medication (LAI), adherence is documented which may account for superior efficacy in relapse prevention reported in some studies. It is known that plasma antipsychotic levels vary greatly across individuals with standard doses of LAIs. Establishing the lowest effective plasma levels for relapse prevention may also help in minimizing side effects that may contribute to problems with adherence. This study was carried out to describe the plasma paliperidone levels associated with clinical stability in patients receiving the LAI, paliperidone palmitate. We predicted that higher paliperidone plasma levels would be associated with lower subjective well-being and greater levels of sexual dysfunction. Patients with clinical diagnoses of schizophrenia and schizoaffective disorder attending specialized schizophrenia outpatient clinics at St. Joseph’s Healthcare Hamilton were invited to participate if they were receiving maintenance treatment with paliperidone palmitate. The study involved two visits, 3 to 4 weeks apart, on days that subjects were scheduled to receive consecutive injections of paliperidone palmitate. Plasma paliperidone levels and prolactin levels were drawn prior to the injection at Visit 1 and a second paliperidone levels was drawn at Visit 2. At Visit 1, a series of rating scales were also completed including the Subjective Well-being under Neuroleptic scale – Short version (SWN), the Changes in Sexual Functioning Questionnaire (CSFQ) and the Drug Attitude Inventory (DAI). Twenty-one subjects (11F/10M) provided informed consent for this study and had plasma paliperidone levels measured. Patients had been receiving LAI paliperidone for a mean of 18 months (SD = 11.4). Mean paliperidone levels at Visit 1 (n=21) and Visit 2 (n=18) were 34.9 ng/ml (SD = 20.0 ng/ml; range = 5.1–73.9 ng/ml) and 35.1 ng/ml (SD = 17.2 ng/ml; range = 9.0–67.5 ng/ml), respectively. Plasma paliperidone levels measured at Visit 2 were highly correlated with levels from Visit 1 (n=18; r = .89, p <.001). Plasma prolactin levels were correlated with levels of plasma paliperidone (n=21, r=0.56, p < .01). Lower scores on the CSFQ – Sexual Desire factor were associated with higher levels of paliperidone (n=19, r =-.61, p<.01) and prolactin (n=19, r=-.56, p <.01). Higher paliperidone levels were associated with more negative scores on the Drug Attitude Inventory (n=19, r=-0.49, p < .05). Plasma paliperidone levels were not associated with scores on the SWN (n=21, r=-.-02). In patients receiving maintenance treatment with paliperidone palmitate, plasma paliperidone levels varied approximately 15-fold. Higher paliperidone levels were associated with more negative attitudes towards medication and more severe deficits in sexual desire but not with subjective well-being. Many stable patients had plasma level close to the 20ng/ml level which in PET studies leads to 65% dopamine D2 receptor occupancy, a level reported to be associated with antipsychotic response. Our findings raise the possibility that maintaining patients at levels just above the 20ng/ml level may be sufficient for relapse prevention but may spare the adverse effects such as sexual dysfunction associated with higher plasma levels. These results suggest that measuring plasma levels in patients receiving paliperidone as a LAI may be of value in identifying the minimum effective dose for prevention of relapse and side effects.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,001 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».