EPS. Risk of EPS-related AEs (such as akathisia and parkinsonian symptoms) with 3-mg and 6-mg paliperidone ER doses (13% and 10%, respectively) was similar to placebo (11%) but increased with the 9-mg, 12-mg, and 15-mg doses (25%, 26%, and 24%, respectively). Should EPS occur, reduce the paliperidone ER dose or consider adding antiparkinsonian medications.
Lab values. No clinically relevant changes were noted in blood glucose, insulin, or lipids.12 Similar to risperidone, paliperidone ER elevated prolactin levels.
Weight gain with paliperidone ER is dose-dependent; in the clinical trials, mean body weight change for all doses was ≤1.9 kg, which is similar to the weight gain seen with risperidone and in the moderate range compared with other SGAs. When using paliperidone ER, follow the American Diabetes Association/American Psychiatric Association guidelines13 for monitoring weight gain and metabolic parameters with antipsychotics. Also monitor patients for clinical symptoms of hyperprolactinemia, and—if intolerable—adjust the dose or switch to another SGA.
Tachycardia. Advise patients that they may experience a rapid heart rate while taking paliperidone ER. In clinical trials, tachycardia occurred in ≤14% of patients—twice the rate with placebo—but did not contribute to more serious cardiac rhythm disturbances or to discontinuation. Incidence of prolonged corrected QT interval (QTc) was 3% to 5% in the paliperidone ER group vs 3% in the placebo group.
Patient education. Because of paliperidone ER’s pharmacokinetic properties, counsel patients to:
- take 1 tablet each day in the morning
- not chew, split, or crush the tablets but swallow whole to preserve the controlled-release delivery.
Table 3
Paliperidone ER’s potential benefits and risks in clinical practice
| Potential benefits | Details |
|---|---|
| Efficacy | Data support acute (6 weeks) and chronic (up to 24 weeks) improvement in schizophrenia symptoms, patient function, and quality of life |
| Pharmacokinetics | Primarily renal excretion decreases risk of hepatic drug-drug or drug-disease interactions |
| Long-acting formulation | Once-daily dosing simplifies treatment and may improve adherence |
| EPS | Risk similar to placebo at 3-mg and 6-mg doses, but increased at higher doses |
| Weight gain | Similar to risperidone |
| Hyperprolactinemia | Similar to risperidone |
| Tachycardia | Occurred in up to 14% of patients in clinical trials (twice the rate of placebo [7%]) |
| QTc prolongation | Increase up to 12 msec on average, with no patients exceeding 500 msec and no clinically adverse events during trials; use paliperidone with caution in patients with arrhythmias or cardiovascular disease or who are taking other medication that can prolong the QT interval |
| EPS: extrapyramidal symptoms | |
| Source: References 1-3 | |
Efficacy trials in schizophrenia
Three 6-week trials1-3 examined paliperidone ER’s efficacy in a total of 1,692 patients with chronic schizophrenia who were hospitalized ≥14 days with acute exacerbations. The trials were double-blind, randomized, fixed-dose, parallel-group, and placebo- and active-controlled (compared with olanzapine, 10 mg/d). Patients showed no significant differences in demographic or baseline characteristics or in the use of rescue medications.
The primary outcome measure was mean change in Positive and Negative Syndrome Scale (PANSS) total score, which quantifies positive, negative, and global psychopathologic symptom severity. Secondary outcome measures included:
- PANSS Marder factor scores14 (derived from PANSS items that reflect positive and negative symptoms, anxiety and depression, hostility, and thought disorganization).
- Clinical Global Impressions-Severity (CGI-S) score, which measures overall illness severity.15
- Personal and Social Performance (PSP) scores, which rate socially useful activities, relationships, self-care, and disturbing and aggressive behaviors; improvement by 1 category (10 points) reflects a clinically meaningful change.16,17
A total of 43% of patients completed the study—34% taking placebo; 46% taking paliperidone ER, 6 mg; 48% taking paliperidone ER, 12 mg; and 45% taking olanzapine. Demographic and baseline characteristics of the 432 patients who received ≥1 dose were similar across all groups. Approximately 75% of patients in each group used rescue medications—primarily lorazepam—for agitation, restlessness, or insomnia for a mean of 8 days.