Paliperidone
Encyclopedia
Paliperidone also known as 9-hydroxyrisperidone, is an atypical antipsychotic
developed by Janssen Pharmaceutica
. Invega is an extended release formulation of paliperidone that uses the OROS
extended release system to allow for once-daily dosing. Paliperidone palmitate (trade name Invega Sustenna) is a long-acting injectable formulation of paliperidone palmitoyl
ester
indicated for once-monthly injection after an initial titration period. Chemically, paliperidone is one of many active metabolite
s of the older atypical antipsychotic risperidone
(paliperidone is 9-hydroxyrisperidone, i.e. risperidone
with an extra hydroxyl
group). It is indicated for the acute and maintenance treatment of schizophrenia
.
antagonism. Paliperidone also has antagonist effect at α1 and α2 adrenergic receptor
s and at H1 histamine receptors. It does not bind to muscarinic acetylcholine receptor
s.
Paliperidone (as Invega) was approved by the FDA for the treatment of schizophrenia
in 2006. It is marketed for the treatment of schizophrenia and for bipolar mania. Clinical trials of paliperidone for the treatment of schizoaffective disorder
are also planned. It may also be used off-label for other conditions. Like risperidone, its possible use in people with autism
and Asperger syndrome
may be studied. Recently, the long-acting injectable form of paliperidone, marketed as INVEGA Sustenna, was approved by the FDA on July 31, 2009.
and extrapyramidal disorder, including involuntary movements, tremors and muscle stiffness. Some users reported experiencing sexual dysfunction
while administering this drug in combination with SSRIs such as Zoloft. Invega website's Important Safety Information page includes this warning: Elderly Patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared to placebo. Invega (paliperidone) is not approved for the treatment of patients with dementia-related psychosis.
Neuroleptic malignant syndrome
is a rare, but potentially lethal reaction to the medication. Heart rhythm changes—potentially serious—may make paliperidone risky for people with some heart conditions.
Other risks include:
Atypical antipsychotic
The atypical antipsychotics are a group of antipsychotic tranquilizing drugs used to treat psychiatric conditions. Some atypical antipsychotics are FDA approved for use in the treatment of schizophrenia...
developed by Janssen Pharmaceutica
Janssen Pharmaceutica
Janssen Pharmaceutica is pharmaceutical company, established in Belgium in 1953 by Paul Janssen. Its headquarters are located in Beerse, in the Campine region of the province of Antwerp, Belgium. It was created not as a subsidiary of a chemical factory but solely with the aim of conducting...
. Invega is an extended release formulation of paliperidone that uses the OROS
OROS
OROS, , is a controlled release oral drug delivery system in the form of a tablet. The tablet has a rigid water-permeable jacket with one or more laser drilled small holes...
extended release system to allow for once-daily dosing. Paliperidone palmitate (trade name Invega Sustenna) is a long-acting injectable formulation of paliperidone palmitoyl
Palmitic acid
Palmitic acid, or hexadecanoic acid in IUPAC nomenclature, is one of the most common saturated fatty acids found in animals and plants. Its molecular formula is CH314CO2H. As its name indicates, it is a major component of the oil from palm trees . Palmitate is a term for the salts and esters of...
ester
Ester
Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...
indicated for once-monthly injection after an initial titration period. Chemically, paliperidone is one of many active metabolite
Metabolite
Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...
s of the older atypical antipsychotic risperidone
Risperidone
Risperidone is a second generation or atypical antipsychotic, sold under the trade name . It is used to treat schizophrenia , schizoaffective disorder, the mixed and manic states associated with bipolar disorder, and irritability in people with autism...
(paliperidone is 9-hydroxyrisperidone, i.e. risperidone
Risperidone
Risperidone is a second generation or atypical antipsychotic, sold under the trade name . It is used to treat schizophrenia , schizoaffective disorder, the mixed and manic states associated with bipolar disorder, and irritability in people with autism...
with an extra hydroxyl
Hydroxyl
A hydroxyl is a chemical group containing an oxygen atom covalently bonded with a hydrogen atom. In inorganic chemistry, the hydroxyl group is known as the hydroxide ion, and scientists and reference works generally use these different terms though they refer to the same chemical structure in...
group). It is indicated for the acute and maintenance treatment of schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
.
Pharmacology
Paliperidone is the primary active metabolite of the older antipsychotic risperidone . While its specific mechanism of action is unknown, it is believed paliperidone and risperidone act via similar, if not identical, pathways; therapeutic effect may be due to a combination of D2 and 5-HT2A receptor5-HT2A receptor
The mammalian 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor . This is the main excitatory receptor subtype among the GPCRs for serotonin , although 5-HT2A may also have an inhibitory effect on certain areas such...
antagonism. Paliperidone also has antagonist effect at α1 and α2 adrenergic receptor
Adrenergic receptor
The adrenergic receptors are a class of metabotropic G protein-coupled receptors that are targets of the catecholamines, especially noradrenaline and adrenaline ....
s and at H1 histamine receptors. It does not bind to muscarinic acetylcholine receptor
Muscarinic acetylcholine receptor
Muscarinic receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled in the plasma membranes of certain neurons and other cells...
s.
Paliperidone (as Invega) was approved by the FDA for the treatment of schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
in 2006. It is marketed for the treatment of schizophrenia and for bipolar mania. Clinical trials of paliperidone for the treatment of schizoaffective disorder
Schizoaffective disorder
Schizoaffective disorder is a psychiatric diagnosis that describes a mental disorder characterized by recurring episodes of elevated or depressed mood, or of simultaneously elevated and depressed mood, that alternate with, or occur together with, distortions in perception.Schizoaffective disorder...
are also planned. It may also be used off-label for other conditions. Like risperidone, its possible use in people with autism
Autism
Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...
and Asperger syndrome
Asperger syndrome
Asperger's syndrome that is characterized by significant difficulties in social interaction, alongside restricted and repetitive patterns of behavior and interests. It differs from other autism spectrum disorders by its relative preservation of linguistic and cognitive development...
may be studied. Recently, the long-acting injectable form of paliperidone, marketed as INVEGA Sustenna, was approved by the FDA on July 31, 2009.
Side effects and adverse reactions
The most common side effects of paliperidone are restlessnessPsychomotor agitation
Psychomotor agitation is a series of unintentional and purposeless motions that stem from mental tension and anxiety of an individual. This includes pacing around a room, wringing one's hands, pulling off clothing and putting it back on and other similar actions...
and extrapyramidal disorder, including involuntary movements, tremors and muscle stiffness. Some users reported experiencing sexual dysfunction
Sexual dysfunction
Sexual dysfunction or sexual malfunction refers to a difficulty experienced by an individual or a couple during any stage of a normal sexual activity, including desire, arousal or orgasm....
while administering this drug in combination with SSRIs such as Zoloft. Invega website's Important Safety Information page includes this warning: Elderly Patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared to placebo. Invega (paliperidone) is not approved for the treatment of patients with dementia-related psychosis.
Neuroleptic malignant syndrome
Neuroleptic malignant syndrome
Neuroleptic malignant syndrome is a life- threatening neurological disorder most often caused by an adverse reaction to neuroleptic or antipsychotic drugs...
is a rare, but potentially lethal reaction to the medication. Heart rhythm changes—potentially serious—may make paliperidone risky for people with some heart conditions.
Other risks include:
- Tardive dyskinesiaTardive dyskinesiaTardive dyskinesia is a difficult-to-treat form of dyskinesia that can be tardive...
, a serious, sometimes permanent side effect reported with INVEGA and other neuroleptics. The risk of tardive dyskinesia increases with total dose and thus becomes more likely the longer a person takes Invega. - High blood sugar and diabetes
- Hyperprolactinemia, or elevated levels of the hormone prolactin, potentially leading to the absence of a menstrual period; breasts producing milk; the development of breasts by males; and erectile dysfunction.
- Complications associated with pre-existing narrowing or blockage of the gastrointestinal tract (esophagus, stomach or small or large intestine)
- Fainting or lightheadedness when standing up or sitting up too quickly.
- Impairment of alertness and driving ability
- Risk in people with a seizure disorder or a history or health conditions that make seizures more likely
- Extrapyramidal effects -- persistent movement disorders or muscle disturbances, such as restlessness, tremors, and muscle stiffness.
- Caution should be exercised before prescribing Invega to pregnant or nursing women.
- Increased sensitivity to heat, difficulty cooling off, and increased likelihood of dehydration.