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Paliperidone

Brands and Forms

  • Invega
    • Extended-release tablet: 3mg, 6mg, 9mg.

Uses of Paliperidone

Paliperidone is used in the treatment of Psychotic Disorders, Bipolar Disorder, Depressive Disorders, PTSD, OCD, and Tic Disorder.

Paliperidone can also be used in the management of behavioral disturbances, such as agitation and impulsivity, that can occur in various conditions like Impulse-Control Disorders, Disruptive Behavior Disorders, and Borderline Personality Disorder.

Paliperidone is the active metabolite of Risperidone, and would be expected to work for all the same conditions. There is no evidence that Paliperidone causes fewer side-effects than Risperidone, but it does have fewer drug-drug interactions.

How Paliperidone Works

Paliperidone is an Atypical Antipsychotic. It is an antagonist at the dopamine D2 receptor, the serotonin 2a receptors, and the adrenergic alpha-2 receptor, but also has interactions with a myriad of other receptors.

Cautions when Using Paliperidone

In elderly individuals with Dementia, use of Antipsychotics has been associated with increased rates of sudden death. It is unclear whether the antipsychotic use is a cause, or simply a marker, of deteriorating health in these individuals.

Weight gain and metabolic side-effects (elevated glucose, lipids and cholesterol) can be pronounced in some individuals.

Individuals with Parkinson disease or Lewy-Body Dementia may have increased sensitivity to Paliperidone, which may manifest as confusion, obtundation, severe extrapyramidal symptoms, and neuroleptic malignant syndrome.

Use with caution in people at risk for seizures or aspiration pneumonia.

People using Paliperidone should become familiar with its effects before driving or operating heavy machinery.

Dosing of Paliperidone

The starting dose of Paliperidone is 6 mg once daily in the morning, which is also considered a therapeutic dose. Some individuals may benefit from as little as 3mg/day to up to 12 mg/day. The dose can be increased in increments of 3mg every 5 days, though it is recommended to wait for about two weeks at a dose of 6mg/day for therapeutic effects to occur before increasing further.

When wanting to stop Paliperidone, the dose should be decreased gradually over a period of 6-8 weeks.

Onset of action

Symptoms of Mania and Psychosis can improve within 1 week of use, but full therapeutic effect may take several weeks. If there is no significant effect after 4-6 weeks, including a couple of weeks at doses above 6mg/day, then it may not work at all.

Acute agitation can improve after a single dose.

For other conditions, 4-6 weeks may be needed to see a therapeutic effect.

Kidney impairment

For mild impairment (CrCl 50-80mL/min), do not exceed 6mg/day once daily. For moderate or severe impairment (CrCl 10- 50mL/min), do not exceed 3mg/day.

Liver impairment

No dose adjustment necessary for mild or moderate impairment. Use caution in severe liver impairment.

Side-effects of Paliperidone

Below is a list of most of the reported side-effects of Paliperidone. Most of these side-effects occur in only a minority of individuals, and many also resolve with time while the medication is continued.

Cardiovascular: tachycardia; orthostatic hypotension; cardiac arrhythmias including bundle branch block, first-degree AV block, sinus arrhythmia, and QTc prolongation.

Central Nervous System: extrapyramidal symptoms; headache; somnolence; dizziness; tremor; weakness; fatigue; loss of libido; seizures (rare); stroke (rare).

Endocrine/Metabolic: Weight gain; metabolic syndrome (insulin resistance, elevated blood sugars, hyperlipidemia and hypercholesterolemia); elevated prolactin; breast pain, enlargement, or milk production in men and women; trouble conceiving; hyperthermia.

Gastrointestinal: excessive saliva; dry mouth; abdominal pain; dysphagia.

Genitourinary: priapism; erectile dysfunction.

Musculoskeletal: muscle stiffness; muscle pains; muscle spasms; neuroleptic malignant syndrome (rare).

Psychiatric: emotional lability; obsessive-compulsive symptoms; psychosis (rare); mania (rare).

Respiratory: aspiration pneumonia (due to esophageal dysmotility; rare).

Common side-effects of Paliperidone

Extrapyramidal symptoms, rapid heart rate, somnolence, headache, weight gain, metabolic syndrome (elevated blood sugars, lipids and cholesterol).

Rare but serious side-effects of note of Paliperidone

  • severe hypoglycemia with associated ketoacidosis
  • increased risk of sudden death in elderly individuals with Dementia.
  • neuroleptic malignant syndrome
  • cardiac arrhythmias including QTc prolongation
  • seizures
  • priapism (sustained erection)

Paliperidone overdose

Drowsiness, extrapyramidal symptoms, hypotension, QTc prolongation, sedation, tachycardia, unsteady gait, neuroleptic malignant syndrome.

Paliperidone and pregnancy

Category C: some animal studies show adverse effects at very high doses, but no controlled human studies have been done; should only be used in pregnancy if clearly needed and if benefits outweigh potential risks.

Paliperidone, weight gain and metabolic syndrome

Metabolic side-effects, including weight gain, elevated glucose and lipids can occur with Paliperidone. See here for further information on these side-effects, and how they can be managed.

Medical Monitoring for Paliperidone

Monitoring for weight gain and a metabolic syndrome requires the following measures to be taken prior to starting the medication, then monthly for the first 3 months of use, and then every 3 months:

  • Body Mass Index (BMI)
  • waistline circumference at umbilicus
  • blood pressure
  • fasting blood glucose
  • fasting blood lipids and cholesterol

To monitor for elevated prolactin, prolactin levels should be measured prior to starting the medication, and then one month after starting and after every dose increase.

An electrocardiogram should be obtained prior to starting the medication, then a few weeks after starting it and after every dose change, in order to monitor for cardiac arrhythmias including QTc prolongation.

Drug Interactions with Paliperidone

  • Avoid combining with medications that can prolong the QTc interval, including Gatifloxacin, Moxifloxacin, Chlorpromazine, Thioridazine, Ziprasidone, class IA antiarrhythmic agents (eg. Procainamide, Quinidine), class III antiarrhythmic agents (eg. Amiodarone, Sotalol).
  • Use caution when combining with other medications that can lower blood pressure.