by Kristen Fescoe • April 17, 2006
Running Head: Risperidone
Risperidone (United States brand name: Risperdal) is a commonly used medication for schizophrenia and other psychotic disorders. Recently Risperidone has been used to treat a myriad of psychological disorders, including depression, anxiety, mania, Tourette’s Syndrome, and many other disorders. Despite its’ usefulness in treating psychotic disorders, there are a variety of side effects that are related to the use of Risperidone which require evaluation before prescribing this medication.
Risperidone is a novel and atypical medications that has proved effect in the treatment of schizophrenia and other psychotic disorders. In addition to the treatment of psychotic disorders, Risperidone is currently being used for a myriad of other psychological disorders. A variety of studies have shown Risperidone to have reasonable effectiveness in the treatment of disorders such as Tourette’s Syndrome, Autism, Depression, Anxiety and a variety of others. Risperidone carries the United States brand name of Risperdal and there is no generic forms of this drug. The pharmacological categories are antipsychotic agent and Benzisoxazole.
This medication has a Pregnancy Risk Factor of category C. This means that either studies of animals have revealed adverse effects on the fetus and there are no controlled studies in women, or that studies in women and animals are not available. Therefore, drugs should be given only if the potential benefits justify the potential risk to the fetus (Fuller & Sajatovic, 2001).
Mechanism of Action:
Risperdal is a benzisoxazole derivative, mixed seratonin –dopamine antagonist. It binds to 5-HT2 receptors in the CNS and in the periphery with a very high affinity, while binding to dopamine – D2 receptors with less affinity. The binding affinity to the dopamine-D2 receptor is 20 times lower that the 5-HT2 affinity. The addition of seratonin antagonism to dopamine antagonism (classic neuroleptic mechanism) is thought to improve negative symptoms of psychoses and reduce the incidence of extrapyramidal side effects. Alpha1, alpha2, adrenergic, and histaminergic receptors are also antagonized with high affinity. Risperidone has low to moderate affinity for 5HTIC, 5HTID, and 5HTIA receptors (Fuller & Sajatovic, 2001).
The recommended starting dosage is 0.5 to 1 mg twice daily and this is slowly increased to the optimum range of 3-6 mg/day. Research has shown that daily dosage amounts which exceed 10mg do not appear to confer any additional benefit, and the incidence of extrapyramidal reactions is higher than with lower doses (Fuller & Sajatovic, 2001). In a study of dosage amounts of atypical neuroleptics for schizophrenic patients, Kasper found that 6 mg a day or less of Risperidone is the optimal dosage amount (1998). A more recent study conducted by Williams (2001), suggested that the optimal dose of risperidone for schizophrenic patients is 4 mg per day.
The following three dosage form exist for use in the United States: an oral solution of 1mg/mL; tablet form in the amounts of 0.25 mg, 0.5 mg and 1 mg; and a scored tablet form in the amounts of 2mg, 3 mg, and 4mg.
In the study conducted by Moritz, et al. Risperidone was evalu;ated in terms of the effect of neuroleptic medication on subjective cognition in patients treated with either conventional or atypical agents (Clozapine, Risperidone and olanzapine) (2002). Subjective measures administered to patients showed that subjective cognitive impairment was positively correlated with greater conventional neuroleptic dosage. This study found that when a high dosage is indicated, atypical neuroleptics (including Risperidone) should be prescribed because medication-induced deficits are more likely to occur when conventional neuroleptics are prescribed.
Some signs of Risperidone overdose include drowsiness, sedation, tachycardia, hypotension, and extrapyramidal symptoms. The treatment of Risperidone overdose include first establishing and maintaining an airway to ensure adequate oxygenation and vantilation. Treating physicians may consider gastric lavage and activated charcoal together with a laxative. They must also regularly monitor cardiovascular status. The use of epinephrine or norepinephrine for hypotension is not indicated, as the beta stimulation may worsen this symptom. Finally, anticholinergics may be required for severe extrapyramidal side effects (Fuller & Sajatovic, 2001).
Research has been conducted in order to determine what possible drug interactions may exist between Risperidone and other medications. A study conducted by DeVane & Nemeroff (2001) evaluated potential durg-drug interactions which may affect patient outcome. By using controlled studies and case reports the researchers found that Risperidone has a low potential for metabolic drug interactions. Drugs which contain cytochrome P450 (CYP)2D6 or induce or inhibit CYP3A4 may alter Risperidone plasma concentration. This research showed that by using a few guidelines when prescribing Risperidone, drug-drug interactions should be minimal.
Risperidone has been used most often in the treatment of the psychotic symptoms related to Schizophrenia, Schizophreniform disorder, and Schizo-affective disorder. In a study conducted by Glick, et al. (2001), neuroleptic medications were evaluated for their effectiveness in treating the symptoms of schizophrenia. Three different groups were included in this study, and all participants were chronic schizophrenic patients. The groups included a Risperidone group, a Haloperidol group and a group including other antipsychotics. This study found that Risperidone had a greater decrease in psychopathology that the other two groups. In other words, this study shows Risperidone as more efficacious than haloperidol and other antipsychotics in treating psychotic symptoms.
A 2001 study conducted by Schweitzer, evaluated evidence that Risperidone may be safe and effective for treating psychotic, affective and behavioral symptoms associated with many disorders other than Schizophrenia, Schizophreniform disorder, and Schizo-affective disorder. These conditions include BiPolar Disorder, Obsessive-Compulsive Disorder, Tourette’s Syndrome, dementia, Lewy Body disease, mental retardation, Parkinson’s Disease, Idiopathic Segmental Dystonia and Organic Catatonia.
A variety of side effects have been associated with the use of Risperidone. This medication is associated with side effects that fall into a variety of categories. The first of which is anticholinergic effects, including: confusion, agitation, constipation, dry mouth, blurred vision and urinary retention. Second are the extrapyramidal reactions, including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia (Fuller & Sajatovic, 2001). In greater than 10% of cases insomnia, agitation, anxiety, and headache were reported by patients using Risperidone. In 1 to 10% of cases, side effects were reported in Cardiovascular, Central Nervous System, Dermatological, Endocrine & Metabolic, Gastrointestinal, Ocular, and Respiratory systems (Fuller & Sajatovic, 2001). Risperidone has also been associated with a variety of Central Nervous System effects, including sedation. Gaffney’s research showed a mild to moderate sedating effect in adolescents being treated for Tourette’s Syndrome with Risperidone (2002).
Weight gain has been attributed with Risperidone use by a variety of studies. Ratzoni, et al. (2002) found that Risperidone is associated with extreme weight gain in adolescents. Risperidone users showed an average weight gain varying from 6.6% to 8.6%. A study evaluating the use of Risperidone in the treatment of autism, found a significant increase in appetite and weight gain in patients who were prescribed this medication (Malone, et al., 2002).
A number of more serious side effects have been associated with the use Risperidone. Research conducted by Malone, et al. found that 15.4% of subjects developed mild, reversible dyskinesia when Risperidone was discontinued (2002). Additionally, Alevizos, et al. evaluated a series of six cases where Risperidone users developed obsessive-compulsive symptoms (four cases) or exacerbated previous obsessive-compulsive symptoms (two cases)(2002). In all but one case, the symptoms emerged shortly after the initiation of a Risperidone dosage of 3 mg or more a day.
More rare side effects were found by Cordeiro & Elkis (2001) in a patients taking Risperidone to treat paranoid schizophrenia. After one week of beginning the drug therapy the patient developed abdominal pain, nausea, vomiting, jaundice and other physical symptoms. Several tests were conducted to evaluate the cause of the symptoms and the researchers found that the patient developed cholestatic hepatitis and pancreatitis, induced by the Risperidone. (The medication was discontinued and the patient’s condition improved).
Risperidone has been used, in recent years, to treat several child and adolescent disorders. In 2002, a research team used Risperidone in an attempt to reduce the disruptive behaviors (such as aggression, impulsivity, defiance of authority figures, and property destruction) associated with conduct disorder, oppositional defiant disorder and disruptive behavioral disorder not otherwise specified. Researchers found a decrease in mean scores in the Conduct Problem subscale of the Nisonger Child Behavior Rating Form (NCBRF).
In another study involving children, Malone and colleagues (2002) evaluated the use of Risperidone in treating children with Autism. By using the Clinical Global Impressions (CGI) and Children’s Psychiatric Rating Scale (CPRS) the researchers were able to assess the effects of the Risperidone on the autistic participants. The children showed significant clinical improvement as measured by the CGI and CPRS. Despite the overall effectiveness of the medication, side effects were reported, including sedation, increased appetite, weight gain, and in 15.4% of participants, dyskinesias was reported when the Risperidone was discontinued.
Another study, conducted by Gaffney and colleagues (2002) compared Risperidone versus Clonidine in the treatment of children and adolescents with Tourette’s Syndrome. The researchers used the Yale Global Tic Severity Scale (YGTSS) to evaluate the effectiveness of the two medications. The two medications appeared equally effective in treating tics. Some participants did report experiencing mild to moderate sedation while on Risperidone.
Another population that may be benefited by the use of Risperidone is the geriatric population. A study of Risperidone use in treating geriatric psychosis was conducted by Hwang and colleagues in 2001. They found that 87.5% of participants showed a mild to substantial improvement in their psychotic symptoms by use of the Clinical Global Impression scale. Adversely, several side effects were experienced by this sample; 39% experienced weakness of legs or walking problems, 29% reported dizziness, and 16% reported peripheral edema. These side effects had not been seen to this degree in younger samples.
Cocaine Use in Schizophrenia
A large number of schizophrenic patients have comorbid substance abuse issues. As much as 50% of all patients diagnosed with schizophrenic disorders also meet lifetime diagnostic criteria for substance use problems(Reiger, et al., 1990). Drug use by schizophrenic patients has been associated with exacerbation of psychotic symptoms, increased aggression, deterioration of function and poorer prognosis (Drake, et al., 1991)). Some researchers propose that cocaine produces please by increasing dopamine concentration through inhibiting reuptake of the neurotransmitters dopamine and serotonin (Gawin, 1991). Therefore, some authors have suggested that Risperidone may be able to decrease cocaine craving through it’s serotonergic (5-HT2a) and dopamine (D2) action (Grabowski, Rhoades & Silverman, 2000).
Research has shown that Risperidone may prove effective in the treatment of addictive disorders within this population. A Case study conducted by Tsuang and colleagues showed a reduction in cocaine use following treatment with Risperidone at a 2 to 4 mg daily dose (2002).
It is apparent that Risperidone is an atypical neuroleptic agent with a variety of effects on different disorders. It is being used not only as an anti-psychotic medication, but also to treat affective, behavioral, mood and other disorders. Although it has shown initial efficacy to treat this plethora of disorders, future research is necessary to determine the specific efficacy of this medication on individual disorders.
Because of the large number of possible side effects, Risperidone must be prescribed with caution. Researchers have begun evaluating Risperidone’s effectiveness on many psychological disorder. It is imperative that physicians use prudence when deciding to prescribe this versus other medications.
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