Schizophrenia is a chronic disease, which may induce a progressive functional, cognitive and social impairment if it is not adequately treated: therefore it requires long-term treatment with efficacious, tolerable and safe drugs. Lack of adherence to treatment is the cause of at least half of relapses, and this should be taken into account in their prevention. Paliperidone ER is the main active metabolite of risperidone, an atypical antipsychotic drug. Paliperidone is similar to risperidone in binding to specific receptors and antagonism to serotonin and dopamine. Paliperidone ER is available as controlled-release tablets based on an osmotic system, allowing controlled release of the drug within 24 hours and it does not require an initial dose titration. After oral administration, drug bioavailability is 28%; maximal plasma concentrations are attained after about 24 hours and steady state after 4-5 days. Renal excretion is the major route of elimination, with 59% of the dose excreted unchanged in urine. CYP2D6 and CYP3A4 isoenzymes have a limited role in paliperidone metabolism. Its terminal half-life is about 23 hours.
The aim of this work was to carry out a review of international literature on paliperidone, in order to evaluate its clinical efficacy and effects on psychosocial parameters, as well as tolerability and safety.
The efficacy of paliperidone in acute patients has been evaluated in 3 double-blind randomized studies, lasting 6 weeks (Table I). All studies demonstrated a significant improvement of mean PANSS scores and of PANSS Marder factor scores versus placebo. All doses (3, 6, 9, 12 and 15 mg) used in these studies were effective, even though 3 mg dose was the least effective; the results suggest that the best starting dose of paliperidone ER in the treatment of schizophrenia is 6 mg/day.
The efficacy of paliperidone ER in the prevention of relapses has been evaluated in 3 long-term studies (Table II), lasting 52 weeks: in all studies paliperidone ER was superior to placebo in preventing relapse after stabilization of the disease. In patients with recent exacerbation of schizophrenia requiring hospital admission, paliperidone ER caused a more rapid and greater improvement of symptoms with respect to quetiapine IR. The effects of paliperidone ER on psychosocial parameters, such as quality of life and social functioning, were also studied extensively: the analysis of the data of three randomized controlled studies lasting 6 weeks, carried out on 1306 patients with acute schizophrenia (Table V), demonstrated that all subjects treated with paliperidone, at any dosage (ranging from 3 to 15 mg/day), obtained a significant improvement of PSP (Personal and Social Performance Scale) score with respect to placebo (p < 0.001). Paliperidone decreased consistently the risk of worsening of social functioning with respect to placebo also in studies evaluating its long-term effects (until 52 weeks). Several works showed the positive effect of paliperidone ER on social functioning in populations with specific features, such as patients with prevalent mood disorders, with recent onset of the disease, or previously treated with other antipsychotics, such as risperidone, quetiapine, olanzapine and aripiprazole: the switch to paliperidone ER induced a significant increase in PSP score.
Extrapiramidal symptoms (EPS) induced by paliperidone are similar to those caused by risperidone, with a low frequency of EPS at doses lower that 3-6 mg/day and a progressive increase of the EPS risk at greater dosage.
However, data deriving from switch studies suggest that paliperidone causes an improvement of EPS induced by previous treatments with second-generation antipsychotics. The more frequent metabolic effect of paliperidone is weight gain, which seems to be dose-correlated and quite mild in the therapeutic range of dosage (3-12 mg/day), consistently lower than that induced by quetiapine and olanzapine. There are no significant changes in glucose and lipid profile during treatment with paliperidone. Among endocrine effects, paliperidone is similar to risperidone in inducing hyperprolactinemia. However, the rate of adverse effects on sexual function is relatively low and, most of all, these events do not seem to induce the patients to stop treatment.
In conclusion, clinical studies demonstrated that paliperidone ER is effective in inducing clinical remission and preventing relapses in patients with schizophrenia, as well as in improving social functioning both at short- and long-term. Moreover, the favorable safety/tolerability profile of the drug may improve the adherence to therapy, which currently represents one of the main issues in long-term treatment of schizophrenia.