3mg, 6mg, 9mg sustained-release tablets.
Sustained-release tablets allow once daily dosing.
Treatment of schizophrenia.
Click here to view the full drug entry on MIMS online.
Paliperidone selectively blocks monoamine effects by binding strongly to serotonergic 5HT2- and dopaminergic D2- receptors.
The efficacy of paliperidone has been evaluated in three double-blind, randomised six-week studies in patients experiencing an acute episode of schizophrenia, as represented by a Positive and Negative Syndrome Scale (PANSS) total score between 70 and 120.
A study1 conducted in 630 patients assessed the efficacy of once daily paliperidone versus placebo. Patients received fixed oral doses of paliperidone 6mg (n=123), 9mg (n=122), 12mg (n=129), placebo (n=126) or olanzapine 10mg (n=128) once daily in the morning for six weeks. PANSS and Clinical and Global Impressions-Severity (CGI-S) scale scores were assessed at baseline, days four, eight and 15, and then every seven days up to and including day 43 (end point).
The mean change from baseline to end point in PANSS total score was significantly greater in all paliperidone treatment groups compared with the placebo group (a negative change in score indicates improvement). The mean decrease in PANSS score was -17.9±22.2, -17.2±20.2 and -23.3±20.1 in the paliperidone 6mg, 9mg and 12mg groups, respectively, compared with -4.1±23.2 in the placebo patients. The mean change in the olanzapine group was -19.9±19.0.
Significant improvements from baseline to end point were also observed on the CGI-S scale compared with placebo. At end point, substantially fewer patients in the paliperidone groups were classified as ‘marked’ or ‘severely ill’ on the CGI-S scale (paliperidone 6mg, 62.6 per cent at baseline versus 21.3 per cent at end point; 9mg, 57.3 per cent at baseline versus 23.0 per cent at end point; 12mg, 64.4 per cent at baseline versus 16.3 per cent at end point; placebo 59.5 per cent at baseline versus 50.8 per cent at end point). In the olanzapine group, 64.1 per cent of patients were ‘marked’ or ‘severely ill’ at baseline, compared with 23.5 per cent at end point.
Another study2 conducted in 618 patients also assessed the efficacy of paliperidone versus placebo. Patients were assigned to receive fixed oral doses of paliperidone 3mg (n=123), 9mg (n=123), 15mg (n=113), placebo (n=120) or olanzapine 10mg (n=126) once daily in the morning for six weeks.
The mean change from baseline to end point in PANSS total scores was significantly greater in all paliperidone treatment groups than in the placebo group. The mean decreases in PANSS total score in the placebo and paliperidone 3mg, 9mg and 15mg groups were -2.8±20.9, -15.0±19.6, -16.3±21.8 and -19.9±18.4, respectively.
A third study3 conducted in 444 patients evaluated the efficacy of two fixed doses of paliperidone compared with placebo. Patients were assigned to receive fixed oral doses of paliperidone 6mg or 12mg, placebo, or olanzapine 10mg once daily in the morning for six weeks.
Mean change from baseline to endpoint in PANSS total score was significantly greater for paliperidone 6mg and 12mg versus placebo. Patients in the olanzapine group improved to a similar extent as the paliperidone groups.
The six-week analysis period in all these studies is limited. However, a recent trial4 assessing recurrence prevention showed encouraging longer-term effects of paliperidone and long-term studies (up to one year) are ongoing.
1. Kane J, Canas F, Kramer M et al. Treatment of schizophrenia with paliperidone extended-release tablets: A 6-week placebo-controlled trial. Schizophrenia research 2007: 90; 147—161.
2. Davidson M, Emsley R, Kramer M et al. Efficacy, safety and early response of paliperidone extended-release tablets (paliperidone ER): results of a 6-week, randomised, placebo-controlled study. Schizophrenia Research 2007: 93; 117—130.
3. Marder S, Kramer M, Ford L et al. Efficacy and safety of paliperidone extended release tablets: results of a 6-week, randomised, placebo-controlled study. Biol Psychiatry 2007.
4. Kramer M, Simpson G, Maciulis V et al. Paliperidone extended-release tablets for prevention of symptom recurrence in patients with schizophrenia. J Clin Psychopharmacol 2007:27;6—14.
Further information: Janssen-Cilag 01494 567444