Children and Adolescents

• Safety and efficacy have not been established under age 12

• Adolescents <51 kg: initial 3 mg/day; recommended 3–6 mg/day; maximum 6 mg/day

• Adolescents >51 kg: initial 3 mg/day; recommended 3–12 mg/day; maximum 12 mg/day

• Children and adolescents using paliperidone may need to be monitored more often than adults

Pregnancy

• Risk Category C [some animal studies show adverse effects; no controlled studies in humans]

• There is a risk of abnormal muscle movements and withdrawal symptoms in newborns whose mothers took an antipsychotic during the third trimester; symptoms may include agitation, abnormally increased or decreased muscle tone, tremor, sleepiness, severe difficulty breathing, and difficulty feeding

• Psychotic symptoms may worsen during pregnancy and some form of treatment may be necessary

• Paliperidone may be preferable to anticonvulsant mood stabilizers if treatment is required during pregnancy

• Effects of hyperprolactinemia on the fetus are unknown

Breast Feeding

• Some drug is found in mother’s breast milk

• Recommended either to discontinue drug or bottle feed

• Infants of women who choose to breast feed while on paliperidone should be monitored for possible adverse effects

PALIPERIDONE: THE ART OF PSYCHOPHARMACOLOGY

Potential Advantages

• Some cases of psychosis and bipolar disorder refractory to treatment with other antipsychotics

• Patients requiring rapid onset of antipsychotic action without dosage titration

Potential Disadvantages

• Patients for whom elevated prolactin may not be desired (e.g., possibly pregnant patients; pubescent girls with amenorrhea; postmenopausal women with low estrogen who do not take estrogen replacement therapy)

Primary Target Symptoms

• Positive symptoms of psychosis

• Negative symptoms of psychosis

• Cognitive symptoms

• Unstable mood (both depression and mania)

• Aggressive symptoms

Pearls

• Some patients respond to paliperidone or tolerate paliperidone better than the parent drug risperidone

• Hyperprolactinemia in women with low estrogen may accelerate osteoporosis

• Less weight gain than some antipsychotics, more than others

• May cause more motor side effects than some other atypical antipsychotics, especially when administered to patients with Parkinson’s disease or Lewy body dementia

• Trilayer tablet consists of 3 compartments (2 containing drug, 1 a “push” compartment) and an orifice at the head of the first drug compartment; water fills the push compartment and gradually pushes drug up and out of the tablet through the orifice

• Long-acting injectable does not require simultaneous oral medication

• Long-acting injectable may work better and better after a few weeks of treatment in some patients

• Long-acting injectable may be very well tolerated

• LAI may be combined with a second antipsychotic administered orally for difficult cases

• Patients with inadequate responses to atypical antipsychotics may benefit from determination of plasma drug levels and, if low, a dosage increase even beyond the usual prescribing limits

• For treatment-resistant patients, especially those with impulsivity, aggression, violence, and self-harm, long-term polypharmacy with 2 atypical antipsychotics or with 1 atypical antipsychotic and 1 conventional antipsychotic may be useful or even necessary while closely monitoring

• In such cases, it may be beneficial to combine 1 depot antipsychotic with 1 oral antipsychotic

• Patients with inadequate responses to atypical antipsychotics may also benefit from a trial of augmentation with a conventional antipsychotic or switching to a conventional antipsychotic

• However, long-term polypharmacy with a combination of a conventional antipsychotic with an atypical antipsychotic may combine their side effects without clearly augmenting the efficacy of either

• Although a frequent practice by some prescribers, adding 2 conventional antipsychotics together has little rationale and may reduce tolerability without clearly enhancing efficacy

THE ART OF SWITCHING