Risperidone is a benzisoxazole derivative with the antipsychotic property. Risperidone selectively antagonizes serotonin (5-HT) effects via the cortical 5-HT2 receptor, and, to a lesser extent, competes with dopamine at the limbic dopamine D2 receptor. The antagonism leads to decreased psychotic effects, such as hallucinations and delusions. In addition, risperidone has low to moderate affinity for histamine H1, 5-HT1A, 5-HT1C, and 5-HT1D receptors, while it has weak affinity for dopamine D1 and haloperidol-sensitive sigma site receptors.
Risperidone is an antipsychotic medication & it is mainly used to treat schizophrenia, bipolar disorder, and irritability in people with autism. Schizophrenia and various mood disorders are thought to be caused by an excess of dopaminergic D2 and serotonergic 5-HT2A activity, resulting in overactivity of central mesolimbic pathways and mesocortical pathways, respectively. Risperidone inhibits dopaminergic D2 receptors and serotonergic 5-HT2A receptors in the brain. It is also said to block histamine receptors and other neural receptors which are currently being studied.
Mechanism of Action of Risperidone
Though its mechanism of action is not fully understood at this time, the current focus is on the ability of risperidone to inhibit the D2 dopaminergic receptors and 5-HT2A serotonergic receptors in the brain. Schizophrenia is thought to be caused by an excess of dopaminergic D2 and serotonergic 5-HT2A activity, resulting in overactivity of central mesolimbic pathways and mesocortical pathways, respectively.
D2 dopaminergic receptors are transiently inhibited by risperidone, reducing dopaminergic neurotransmission, therefore decreasing positive symptoms of schizophrenia, such as delusions and hallucinations. Risperidone binds transiently and with loose affinity to the dopaminergic D2 receptor, with an ideal receptor occupancy of 60-70% for optimal effect. Rapid dissociation of risperidone from the D2 receptors contributes to the decreased risk of extrapyramidal symptoms (EPS), which occur with permanent and high occupancy blockade of D2 dopaminergic receptors. Low-affinity binding and rapid dissociation from the D2 receptor distinguish risperidone from the traditional antipsychotic drugs. A higher occupancy rate of D2 receptors is said to increase the risk of extrapyramidal symptoms and is, therefore, to be avoided.
Risperidone is an atypical antipsychotic drug that is widely prescribed for young patients with different psychotic disorders. The long-term effects of this antipsychotic agent on neuronal receptors in developing brain remain unclear and require further investigation. In this study, we examined the effects of long-term treatment of risperidone on two serotonin receptor subtypes in brain regions of juvenile rat. Levels of 5-HT(1A) and 5-HT(2A) receptors in forebrain regions of juvenile rats were quantified after 3 weeks of treatment with three different doses of risperidone (0.3, 1.0 and 3.0mg/kg). Findings were compared to previously reported changes in 5-receptors after risperidone treatment (3.0mg/kg) in the adult rat brain. The three doses of risperidone selectively and dose-dependently increased levels of 5-HT(1A) receptors in medial-prefrontal and dorsolateral-frontal cortices of juvenile animals. The higher doses (1.0 and 3.0mg/kg) of risperidone also increased 5-HT(1A) receptor binding in hippocampal CA(1) region of juvenile but not adult rats. In contrast, the three doses of risperidone significantly reduced 5-HT(2A) labeling in medial-prefrontal and dorsolateral-frontal cortices in juvenile as well as in adult animals in an equipotent fashion. 5-HT(1A) and 5-HT(2A) receptors in other forebrain regions were not altered by repeated risperidone treatment. These findings indicate that there are differential effects of risperidone on 5-HT(1A) and 5-HT(2A) receptors in juvenile animals and that the 5-HT system in developing animals is more sensitive than adults to the long-term effects of risperidone
Indications of Risperidone
- Schizophrenia
- Bipolar Disorder
- Autism
- Anxiety
- Body Dysmorphic Disorder
- Borderline Personality Disorder
- Depression
- Head Injury
- Nightmares
- Paranoid Disorder
- Post Traumatic Stress Disorder
- Schizoaffective Disorder
- Severe Mood Dysregulation
- Social Anxiety Disorder
- Acute Agitation
- Acute Mania
- Delusional Parasitosis
- Gilles de la Tourette’s Syndrome
- Irritability
- Mixed manic depressive episode
- Treatment-Resistant Major Depressive Disorder
- Severe Dementia Alzheimer’s type
Contra-Indications of Risperidone
- Diabetes
- Excessive fat in the blood
- Low amount of magnesium in the blood
- Extreme Loss of Body Water
- Low amount of potassium in the blood
- Overweight
- Decreased Function of Bone Marrow
- Deficiency of Granulocytes a type of white blood Cell
- Increased eosinophils in the Blood
- Abnormal movements of facial muscles and tongue
- Neuroleptic malignant syndrome
- Lower seizure threshold
- Closed-angle glaucoma
- Very Rapid Heartbeat – Torsades de Pointes
- Slow Heartbeat
- Stroke
- Disorder of the Blood Vessels of the Brain
- the blood clot in a deep vein of the extremities
- Blood Pressure Drop Upon Standing
- Abnormally low blood pressure
- Paralysis of the Intestines
- Constipation
- Liver problems
- Acute Inflammation of the Pancreas
- Enlarged Prostate
- Seizures
- Cannot Empty Bladder
- High Blood Sugar
- abnormal liver function tests
- Susceptible to Breathing Fluid Into Lungs
- a mother who is producing milk and breastfeeding
- Metabolic Syndrome X
- Dementia in an Elderly Person
- Decreased Motility Function of Stomach or Intestines
Dosage of Risperidone
Strengths: 0.25 mg; 0.5 mg; 1 mg; 2 mg; 3 mg; 4 mg; 25 mg/2 weeks; 37.5 mg/2,
Schizophrenia
Oral Formulations
- Initial dose: 2 mg orally per day
- Titration dose: May increase in increments of 1 to 2 mg per day at the interval of 24 hours or more, as tolerated.
- Maintenance dose: 2 to 8 mg orally per day
- Maximum dose: 16 mg orally per day
Long-acting IM Injection
- Initial dose: 25 mg IM every 2 weeks
- Titration dose: May increase to 37.5 mg or 50 mg if needed; dose titration should occur no more frequently than every 4 weeks as expected drug release starts 3 weeks after injection.
- Maximum dose: 50 mg IM every 2 weeks
Bipolar Disorder
Oral Formulations
- Initial dose: 2 to 3 mg orally per day
- Titration dose: May increase in increments of 1 mg per day at the interval of 24 hours or more, as tolerated.
- Maximum dose: 6 mg orally per day
Long-acting IM Injection
- Initial dose: 25 mg IM every 2 week
- Titration dose: May increase to 37.5 mg or 50 mg if needed; dose titration should occur no more frequently than every 4 weeks as expected drug release starts 3 weeks after injection.
- Maximum dose: 50 mg IM every 2 weeks
Pediatric Schizophrenia
13 years or older
- Initial dose: 0.5 mg orally once a day
- Titration dose: May increase in increments of 0.5 mg to 1 mg per day at the interval of 24 hours or more, as tolerated.
- Maintenance dose: 3 mg orally per day
- Maximum dose: 6 mg orally per day
Pediatric Bipolar Disorder
10 years or older
- Initial dose: 0.5 mg orally once a day
- Titration dose: May increase in increments of 0.5 mg to 1 mg per day at the interval of 24 hours or more, as tolerated.
- Maximum dose: 6 mg orally per day
Pediatric Autism
5 to 17 years Greater than 15 kg and less than 20 kg
- Initial dose: 0.25 mg orally once a day
- Titration: after a minimum of 4 days, may increase to 0.5 mg per day; maintain this dose for a minimum of 14 days; subsequent dose increases may be made in increments of 0.25 mg at intervals of 2 weeks or more, as tolerated.
- Maintenance dose: Once sufficient clinical response has been achieved and maintained, healthcare providers should consider gradually reducing the dose to achieve the optimal balance of safety and efficacy.
20 kg or greater
- Initial dose: 0.5 mg orally once a day
- Titration: After a minimum of 4 days, may increase to 1 mg per day; maintain this dose for a minimum of 14 days; subsequent dose increases in increments of 0.5 mg at intervals of 2 weeks or more, as tolerated.
- Maintenance dose: Once sufficient clinical response has been achieved and maintained, healthcare providers should consider gradually reducing the dose to achieve the optimal balance of safety and efficacy.
Side Effects of Risperidone
The most common
- Blurred vision
- Aggressive behavior
- agitation
- anxiety
- changes in vision, including blurred vision
- difficulty concentrating
- difficulty speaking or swallowing
- dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
- Chest pain or tightness
- dry mouth
- trembling or shaking of the hands or feet
- stomach pain or cramping
- diarrhea
- a headache
- stomach pain;
- back pain, joint or muscle pain.
- problems with your vision (including color vision);
- sudden chest pain or trouble breathing;
- pain or swelling in one or both legs;
- a migraine headache;
- pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating; or
- feeling like you might pass out.
More common
- Abdominal or stomach pain, discomfort, or tenderness
- chills or fever
- difficulty with moving
- a headache, severe and throbbing
- joint or back pain
- muscle aching or cramping
- muscle pains or stiffness
- chest pressure or squeezing pain in the chest
- discomfort in arms, shoulders, neck or upper back
- excessive sweating
- feeling of heaviness, pain, warmth and/or swelling in a leg or in the pelvis
- sudden tingling or coldness in an arm or leg
- sudden slow or difficult speech
- sudden drowsiness or need to sleep
- fast breathing
- sharp pain when taking a deep breath
- fast or slow heartbeat
- coughing up blood
- rust colored urine
- decreased amount of urine
Rare
- Anxiety
- change in vision
- chest pain or tightness
- confusion
- a cough
- Agitation
- arm, back, or jaw pain
- blurred vision
- chest pain or discomfort
- convulsions
- extra heartbeats
- fainting
- hallucinations
- a headache
- irritability
- lightheadedness
- mood or mental changes
- muscle pain or cramps
- muscle spasm or jerking of all extremities
- nervousness
Drug Interactions
Risperidone may interact with the following drug, supplements, & may change the efficacy of the drug
- antihistamines (e.g, cetirizine, doxylamine, diphenhydramine, hydroxyzine, loratadine)
- anti-Parkinsons medications (e.g., amantadine, apomorphine, bromocriptine, levodopa, pramipexole, ropinirole)
- antipsychotics (e.g., chlorpromazine, haloperidol, quetiapine, risperidone)
- antiseizure medications (e.g., clobazam, ethosuximide, felbamate, levetiracetam, phenobarbital, phenytoin, topiramate, valproic acid, zonisamide)
- aripiprazole
- “azole” antifungals (e.g., itraconazole, ketoconazole, voriconazole)
- baclofen
- barbiturates (e.g., butalbital, pentobarbital, phenobarbital)
- benzodiazepines (e.g., alprazolam, diazepam, lorazepam)
- beta-adrenergic blockers (e.g., atenolol, propranolol, sotalol)
- bupropion
- calcitriol
- calcium channel blockers (e.g., amlodipine, diltiazem, nifedipine, verapamil)
- captopril
- celecoxib
- chloroquine
- cholecalciferol
- cyclosporine
- dantrolene
- domperidone
- “gliptin” diabetes medications (e.g., linagliptin, saxagliptin, sitagliptin)
- gabapentin
- H2 antagonists (e.g., famotidine, ranitidine)
- ipratropium
- macrolide antibiotics (e.g., clarithromycin, erythromycin)
- mirabegron
- mirtazapine
- monoamine oxidase inhibitors (MAOIs; moclobemide, phenelzine, rasagiline, selegiline, tranylcypromine)
- non-steroidal anti-inflammatory medications (NSAIDs; e.g., diclofenac, ibuprofen, naproxen)
- phosphodiesterase 5 inhibitors (e.g., sildenafil, vardenafil)tadalafil,
- proton pump inhibitors (e.g., lansoprazole, omeprazole)
- quinolone antibiotics (e.g., levofloxacin, norfloxacin, moxifloxacin)
- selective serotonin reuptake inhibitors (SSRIs; e.g., paroxetine, fluoxetine, citalopram)
- serotonin antagonists (anti-emetic medications; e.g., granisetron, ondansetron)
- tapentadol
- theophylline
- thiazide diuretics (water pills; e.g., hydrochlorothiazide, indapamide, metolazone)
- tramadol
- tricyclic antidepressants (e.g., amitriptyline, clomipramine, desipramine, trimipramine)
- trimethoprim
Pregnancy Catagory of Risperidone
FDA Pregnancy Category C
Pregnancy
The safety of risperidone for use during pregnancy has not been established. Risperidone should not be used during pregnancy unless the expected benefits outweigh the potential risks. If you become pregnant while taking risperidone, contact your doctor immediately.
Lactation
Risperidone passes into breast milk. Women should not breast-feed while taking risperidone. The safety and effectiveness of risperidone have not been established for use by children and adolescents under 18 years of age.
References
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