Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
3 mg, 6 mg and 9 mg modified-release tablets
Approved indication: schizophrenia
Australian Medicines Handbook section 18.2.2
Risperidone is an antipsychotic drug which is at the end of its patent. Its manufacturer is now marketing one of its metabolites, paliperidone.
When risperidone is metabolised by cytochrome P450 2D6 it produces 9-hydroxy-risperidone (paliperidone) which exists as two enantiomers. The activity of paliperidone is similar to that of risperidone because it binds to dopamine (D2) and serotonin (5HT2A) receptors.
The tablets of paliperidone are designed to slowly release the drug into the gut. They should not be crushed or broken to assist swallowing. Although food increases bioavailability, the once-daily dose does not have to be taken with meals. However, patients are advised not to alternate taking the drug with or without food. It takes 24 hours to reach the peak plasma concentration and the elimination half-life is of a similar duration. Most of the drug is excreted unchanged in the urine. Lower doses are needed if renal function is reduced.
In a six-week trial, 628 patients with acute schizophrenia were randomised to take a placebo, 10 mg olanzapine or one of three doses of paliperidone (6 mg, 9 mg, 12 mg). The atypical antipsychotics had a significantly larger effect than placebo on the patients' scores on the Positive and Negative Syndrome Scale (PANSS).The mean baseline score of 94 was reduced by 4.1 with placebo, 19.9 with olanzapine, and by 17.9, 17.2 and 23.3 with 6 mg, 9 mg and 12 mg paliperidone respectively.1 Two other six-week studies produced similar results. As it is unclear that higher doses are significantly more effective, the recommended dose of paliperidone is 6 mg taken each morning.
A double-blind, randomised trial looked at paliperidone in the prevention of symptom recurrence. After 207 patients with schizophrenia were stabilised on paliperidone they either continued treatment or were switched to a placebo. The trial was stopped prematurely because a significant difference in efficacy emerged. At the time of the halt the median duration of treatment was 29 days with placebo and 45 days with paliperidone. Schizophrenia symptoms had recurred in 53% of the placebo group and 25% of the paliperidone group.2
The adverse effects of paliperidone are similar to those of risperidone. Extra pyramidal symptoms common to both drugs include tremor, akathisia and dystonia. Other frequent adverse events include headache, somnolence, tachycardia and orthostatic hypotension. The six-week study was too short to show significant changes in metabolism, but a weight increase of 7% or more was seen in 5% of the patients taking paliperidone 6 mg compared with 2% of the placebo group.3 In the recurrence study 20% of the paliperidone group and 12% of the placebo group added at least 7% of their body weight.2 This will add to the risk of developing diabetes.3 An increase in serum prolactin with paliperidone may have the same effect as risperidone, which is associated with an increased risk of tumours in animal studies. As paliperidone can cause a small increase in the QT interval it is not recommended for use with drugs which have a similar effect on the ECG.
While paliperidone is better than placebo in short-term studies, schizophrenia is a long-term illness. Much more is known about risperidone. As paliperidone is a product of the cytochrome P450 system it is not expected to cause interactions with other drugs metabolised by this system. While dose titration is not required at the start of therapy, any advantage of paliperidone over risperidone would be unlikely to justify a higher price. Paliperidone is not approved for patients with dementia-related psychosis.
The Transparency Score ( ) is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.
- Kane J, Canas F, Kramer M, Ford L, Gassmann-Mayer C, Lim P, et al. Treatment of schizophrenia with paliperidone extended-release tablets: a 6-week placebo-controlled trial. Schizophr Res 2007;90:147-61.
- Kramer M, Simpson G, Maciulis V, Kushner S, Vijapurkar U, Lim P, et al. Paliperidone extended-release tablets for prevention of symptom recurrence in patients with schizophrenia. A randomized, double-blind, placebo-controlled study. J Clin Psychopharmacol 2007;27:6-14.
- Proietto J. Diabetes and antipsychotic drugs. Aust Prescr 2004;27:118-9.