Acceptability and Disintegration Rates of Orally Disintegrating Risperidone Tablets in Patients with Schizophrenia or Schizoaffective Disorder
Chue, Pierre, Welch, Ron, Binder, Carin, Canadian Journal of Psychiatry
Objective: To investigate the disintegration profile, acceptability, and tolerability of orally disintegrating risperidone tablets in patients with schizophrenia or schizoaffective disorder.
Method: Ten patients stable for at least 10 days on monotherapy with oral risperidone 2 mg to 4 mg taken once daily were switched for 7 days to an equivalent dosage of orally disintegrating risperidone. Visual assessments for time to initial and complete disintegration were collected at each visit. Clinical Global Impression of Severity scores were collected at baseline and at the last visit. Patient acceptance of the new formulation, rated according to a visual analog scale, was obtained at the last visit.
Results: All patients maintained stable clinical status. Mean time to initial disintegration was 5.1 seconds, SD 0.8, and mean time to complete disintegration was 29.4 seconds, SD 18.4. The formulation was rated as very acceptable. Adverse events were reported by 5 patients; all were mild.
Conclusion: The orally disintegrating risperidone tablets were well tolerated and rated as very acceptable by all patients.
(Can J Psychiatry 2004;49:701-703)
Information on funding and support and author affiliations appears at the end of the article.
* Risperidone orally disintegrating tablets may be an alternative to patients who dislike swallowing traditional tablets.
* This formulation demonstrated faster disintegration than other rapidly disintegrating antipsychotic tablets.
* All patients maintained their clinical response as measured by Clinical Global Impression Severity scores.
* The sample size was small and trial duration was short.
* This was a single-centre, open-label trial.
* There was no control group.
Key Words: risperidone, orally disintegrating tablet, schizophrenia
There has been recent interest in the development of different formulations of atypical antipsychotics, including both short-acting and long-acting injections, solutions (that is, liquid concentrates), granules, and orally disintegrating tablets, to address some of the determinants of medication nonadherence in certain clinical situations (1-3). Medication status is an important predictor of outcome in schizophrenia, and nonadherence accounts for more than 50% of relapses (4-6).
Risperidone is an atypical, or novel, antipsychotic that is available in Canada as an oral tablet, a long-acting injection, a solution, and most recently, as an orally disintegrating (orodispersible) tablet (7). This new formulation has been shown to be bioequivalent to the traditional tablet in both healthy volunteers and in patients with schizophrenia (8). It disintegrates rapidly in the mouth, releasing the polacrilex (methacrylic polymer) resin onto which risperidone is bound. The risperidone (still bound to the resin) is swallowed with the saliva and released from the resin in the digestive system. The resin docs not disintegrate or dissolve and is excreted unchanged.
This orally disintegrating formulation can be taken without water. Its main constituents are gelatin A, a coloring agent, and a sweetener (aspartame). It is available in 0.5-mg, 1-mg, and 2-mg mint-flavoured tablets. We report on a pilot trial investigating the disintegration profile, acceptability, and tolcrability of orally disintegrating risperidone tablets in patients with schizophrenia or schizoaffective disorder.
This single-centre, open-label pilot study was approved by the University of Alberta Review Ethics Board and the Canadian regulatory authority. For inclusion, participants had to meet the following criteria: 1) outpatient, aged 18 to 65 years; 2) DSM-IV diagnosis of schizophrenia or schizoaffective disorder; 3) stable for at least 10 days on monotherapy with once-daily risperidone 2 mg to 4 mg; 4) signed informed consent; 5) ability to comply with visit schedule; 6) physically healthy; and 7) if female, not pregnant and using appropriate measures of birth control while in the study (9). Exclusion criteria were as follows: 1 ) serious or unstable medical illness, 2) antipsychotic use other than risperidone, 3) use of carbamazepine, 4) intolerance to aspartame, or 5) a history of ncuroleptic malignant syndrome.
Patients underwent a physical exam including weight, height, blood pressure and heart rate, medical and psychiatric history, and laboratory tests (biochemistry, hematology, and urine pregnancy test for women having child-bearing potential). Eligible patients were switched to the same dosage (in 1-mg and 2-mg tablets) of orally disintegrating risperidone (supplied by Jansscn Ortho Inc) for 7 days. After the screening visit, visits were approximately 2 days apart, for a total of 5 visits. At each visit, 1 minute after the patient swallowed a 30-ml drink of water, the same rater placed a risperidone tablet(s) on the patient's tongue with clean, dry (nongloved) hands. Water is not required for tablet disintegration; however, given that these patients attended a regular psychiatric clinic, it was felt important to control for recent nicotine or coffee use by ensuring the same degree of oral hydration and comparability to other studies with orally disintegrating tablets. Patients opened their mouths every 5 seconds until the start of disintegration and then at 10-second intervals. If the tablet appeared close to disintegration, patients kept their mouths open to time the exact end point of total disintegration. The same rater visually assessed disintegration by using a stopwatch to record disintegration start and end times. Adverse events (AEs) were collected at each visit.
At baseline and last visit, the same investigator also assessed each patient with the Clinical Global Impression of Severity Scale (CGI-S), a 7-point scale on which 7 equals being very severely ill. At the last visit, patients were asked to rate the overall acceptability of the orally disintegrating risperidone tablet(s) on a visual analog scale (specifically, a ??-cm line with anchors of O = "not acceptable" and 10 = "very acceptable").
Ten patients (8 men and 2 women) were enrolled, and all completed the study. Their mean age was 38.8 years, SD 11.1; 9 were white and 1 was black. Of the patients, 8 had a DSM-IV diagnosis of schizophrenia, and 2 had a DSM-IV diagnosis of schizoaffective disorder; the mean duration of illness was 7.3 years. Three patients were receiving risperidone dosages of 2 mg daily, 3 were receiving dosages of 3 mg daily, and 4 were receiving dosages of 4 mg daily. The mean duration of risperidone treatment was 3.7 years, SD 3.5.
The CGI-S was rated as very mild in 3 patients and as mild in 7 patients (mean 2.7, SD 0.5) at baseline and at the last visit (day 7). all patients maintained their response over the study period. Table 1 shows the mean time to start of disintegration and to complete disintegration of the tablet at every visit.
Across all visits, the overall mean time to initial disintegration was 5.1 seconds (SD 0.8, range 5 to 10 seconds), and the mean time to complete disintegration was 29.4 seconds (SD 18.4, range 12 to 118 seconds). The mean time to initial disintegration was the same regardless of the number of orally disintegrating risperidone tablets placed on the patient's tongue; the mean time to complete disintegration was also similar. The total time to complete disintegration was a mean of 36.6 seconds for the 2-mg dose (one 2-mg tablet), 23.8 for the 3-mg dose (one 1-mg tablet and one 2-mg tablet), and 28.3 for the 4-mg dose (two 2-mg tablets).
At the end of the study, mean patient acceptability of the tablets was9.61 (SD 0.61,range 8.2 to 10). Five patients reported AEs, all of which were rated mild. There were no serious AEs reported and no abnormalities in vital signs during the study. The most frequently reported AE, somnolence, likely resulted from a change in dosing time from bedtime to afternoon. None of the AEs required any intervention or withdrawal from the study.
Orally disintegrating tablets may be particularly useful for patients who have difficulty swallowing or who do not like to swallow traditional tablets. They may also be another option in emergency room situations for patients who do not wish to take short-acting injectable forms of medication or for patients who "cheek" medications.
Currier and others found that risperidone liquid concentrate and oral lorazepam compared very favourably with intramuscular (IM) haloperidol and IM lorazepam in the treatment of psychotic agitation (10). Risperidone orally disintegrating tablets may be useful in similar clinical situations. In addition, they may offer advantages over orally disintegrating olanzapine tablets by virtue of their larger size and more rapid disintegration, which make concealment of the tablets in the mouth more difficult (11). In this study, disintegration times for orally disintegrating risperidone tablets (both time to onset and mean time to complete disintegration) were significantly more rapid than those reported for orally disintegrating olanzapine tablets (12).
To summarize, in this study, orally disintegrating risperidone tablets were well tolerated and rated as very acceptable by patients with schizophrenia or schizoaffective disorder. Further, all patients maintained their stable clinical status with no changes in CGI-S from baseline.
Funding and Support
Janssen Ortho Inc sponsored this study.
The authors acknowledge the statistical support of Jenny Wang, PhD.
Résumé : Acceptabilité des taux de désintégration des comprimés de rispéridone désintégrables oralement chez les patients souffrant de schizophrénie ou de trouble schizo-affectif
Objectif : Examiner le profil et l'acceptabilité de la désintégration ainsi que la tolérabilité des comprimés de rispéridone désintégrables oralement chez les patients souffrant de schizophrénie ou de trouble schizo-affectif.
Méthode : Dix patients stables depuis au moins 10 jours suivant une monothérapic de rispéridonc orale à raison de 2 à 4 mg une fois par jour ont reçu pendant 7 jours une dose équivalente de rispéridone désintégrable oralement. Des évaluations visuelles du temps écoulé entre la désintégration initiale et complète ont été effectuées à chaque visite. Les scores à l'Impression clinique globale de gravité ont été recueillis au départ et à la dernière visite. L'acceptation de la nouvelle formule par les patients a été obtenue à la dernière visite, d'après une échelle visuelle analogue.
Résultats : Tous les patients ont maintenu un état clinique stable. Le temps moyen pour la désintégration initiale était de 5,1 secondes (ET 0,8), et celui de la désintégration complète était de 29,4 secondes (ET 18,4). La formule a été cotée très acceptable. Des effets indésirables ont été rapportés par 5 patients; tous étaient bénins.
Conclusion : Les comprimés de rispéridone désintégrables oralement ont été bien tolérés et jugés très acceptables par tous les patients.
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Pierre Chue, FRCPC1, Ron Welch, BSc Pharm2, Carin Binder, MBA3
Manuscript received August 2003, revised, and accepted November 2003.
1 Associate Professor of Psychiatry, University of Alberta Hospital, Edmonton, Alberta.
2 Clinical Pharmacist, Alberta Hospital, Edmonton, Alberta.
3 Director, Clinical Affairs-CNS, Janssen Ortho Inc, Toronto, Ontario.
Address for correspondence: DrP Chue, 9942 108 Street, Edmonton, AB T5K 2J5
Questia, a part of Gale, Cengage Learning. www.questia.com
Publication information: Article title: Acceptability and Disintegration Rates of Orally Disintegrating Risperidone Tablets in Patients with Schizophrenia or Schizoaffective Disorder. Contributors: Chue, Pierre - Author, Welch, Ron - Author, Binder, Carin - Author. Journal title: Canadian Journal of Psychiatry. Volume: 49. Issue: 10 Publication date: October 2004. Page number: 701+. © Canadian Psychiatric Association Feb 2009. Provided by ProQuest LLC. All Rights Reserved.