Bipolar Mania – Adjunctive Therapy With Lithium Or Valproate
The efficacy of RISPERDAL® with concomitant lithium or valproate in the treatment of acute manic or mixed episodes was established in one controlled trial in adult patients who met the DSM-IV criteria for Bipolar I Disorder. This trial included patients with or without psychotic features and with or without a rapid-cycling course.
- In this 3-week placebo-controlled combination trial, 148 in- or outpatients on lithium or valproate therapy with inadequately controlled manic or mixed symptoms were randomized to receive RISPERDAL®, placebo, or an active comparator, in combination with their original therapy. RISPERDAL®, in a dose range of 1-6 mg/day, once daily, starting at 2 mg/day (mean modal dose of 3.8 mg/day), combined with lithium or valproate (in a therapeutic range of 0.6 mEq/L to 1.4 mEq/L or 50 mcg/mL to 120 mcg/mL, respectively) was superior to lithium or valproate alone in the reduction of YMRS total score.
- In a second 3-week placebo-controlled combination trial, 142 in- or outpatients on lithium, valproate, or carbamazepine therapy with inadequately controlled manic or mixed symptoms were randomized to receive RISPERDAL® or placebo, in combination with their original therapy. RISPERDAL®, in a dose range of 1-6 mg/day, once daily, starting at 2 mg/day (mean modal dose of 3.7 mg/day), combined with lithium, valproate, or carbamazepine (in therapeutic ranges of 0.6 mEq/L to 1.4 mEq/L for lithium, 50 mcg/mL to 125 mcg/mL for valproate, or 4-12 mcg/mL for carbamazepine, respectively) was not superior to lithium, valproate, or carbamazepine alone in the reduction of YMRS total score. A possible explanation for the failure of this trial was induction of Rispex and 9-hydroxyRispex clearance by carbamazepine, leading to subtherapeutic levels of Rispex and 9-hydroxyRispex.
What brand names are available for Rispex?
Risperdal, Risperdal Consta, Risperdal M-TAB
In clinical trial and/or postmarketing experience, events of leukopenia/neutropenia have been reported temporally related to antipsychotic agents, including RISPERDAL® . Agranulocytosis has also been reported.
Possible risk factors for leukopenia/neutropenia include pre-existing low white blood cell count (WBC) and history of drug-induced leukopenia/neutropenia. Patients with a history of a clinically significant low WBC or a drug-induced leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy and discontinuation of RISPERDAL® should be considered at the first sign of a clinically significant decline in WBC in the absence of other causative factors.
Patients with clinically significant neutropenia should be carefully monitored for fever or other symptoms or signs of infection and treated promptly if such symptoms or signs occur. Patients with severe neutropenia (absolute neutrophil count
Antipsychotic drugs have been shown to chronically elevate prolactin levels in rodents. Serum prolactin levels were not measured during the Rispex carcinogenicity studies; however, measurements during subchronic toxicity studies showed that Rispex elevated serum prolactin levels 5-6 fold in mice and rats at the same doses used in the carcinogenicity studies. An increase in mammary, pituitary, and endocrine pancreas neoplasms has been found in rodents after chronic administration of other antipsychotic drugs and is considered to be prolactin-mediated. The relevance for human risk of the findings of prolactin-mediated endocrine tumors in rodents is unknown .
Chronic administration of clozapine with RISPERDAL® may decrease the clearance of Rispex.
Cerebrovascular Adverse Reactions, Including Stroke, In Elderly Patients With Dementia-Related Psychosis
Cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack), including fatalities, were reported in patients (mean age 85 years; range 73-97) in trials of Rispex in elderly patients with dementia-related psychosis. In placebo-controlled trials, there was a significantly higher incidence of cerebrovascular adverse events in patients treated with Rispex compared to patients treated with placebo. RISPERDAL® is not approved for the treatment of patients with dementia-related psychosis.
Should I Avoid Any Food, Drink, or Activity While Taking Rispex?
Rispex can make you feel sleepy. Don't drive or operate machinery until you know how the drug will affect you. Drinking alcohol can make you feel even more tired, so it's important to avoid alcohol while taking this medication.
Rispex is a benzisoxazole derivative approved by the FDA for treatment of schizophrenia in 1994, for short-term treatment of the mixed and manic states of bipolar disorder in 2003, and for treatment of irritability in children with autism in 2006.
SGAs Included in RCTs
Rispex is the most studied SGA in children for treatment of ASDs and DBDs, with 12 of 17 RCTs identified during this review pertaining to Rispex. In other therapeutic domains such as schizophrenia and bipolar disorder, Rispex is also commonly used. A large part of the reason for the disproportional number of studies involving Rispex is that it was the first SGA to market, other than clozapine. Due to the risk for agranulocytosis (a severe deficiency of infection-fighting granulocytes, or neutrophils, in the blood) clozapine use has been restricted and extra monitoring is required. In North America, this rare but potentially fatal adverse effect sharply limits clozapine prescribing to only approved indications of schizophrenia and schizoaffective disorder, and only after two other antipsychotic trials are undertaken. These risks and precautions along with its high adverse effect burden make clozapine an unsuitable candidate for treatment of ASDs and DBDs. Rispex was still under U.S. patent protection when the BPCA, with its incentivization of pediatric medication trials, was signed into law in 2002. Rispex was the first SGA to obtain FDA approval for treatment of irritability of autism in 2006, followed by aripiprazole in 2009.
No RCTs for ASDs or DBDs were identified involving asenapine, clozapine, lurasidone, paliperidone, or ziprasidone. Other than clozapine (see reasons limiting its use detailed above), the other four drugs are relative newcomers to the SGA market, with market release dates subsequent to publication of the bulk of the RCT data detailed in this chapter. Despite the lack of regulatory approval in Canada, Rispex and aripiprazole are in some ways now considered established treatments for ASDs and DBDs, and there may be less clinical interest in studying the newer SGAs for these indications. Rispex is now available in generic formulations in both Canada and the United States, and the drug cost is a fraction of that of branded treatments still under patent protection such as aripiprazole and other newer SGAs.
What Is Risper >
Rispex, the generic form of the brand name drug Risperdal, is in a class of medications called atypical antipsychotics. It works by changing the activity of dopamine and other naturally occurring chemicals in the brain.
Janssen Pharmaceuticals makes Rispex, and the Food and Drug Administration (FDA) first approved Risperdal in 2002 to treat schizophrenia in adults and youths at least 13 years old. Schizophrenia is a mental illness that can cause people to lose interest in life and develop abnormal thoughts and emotions.
In 2003, the FDA also approved Risperdal for the short-term treatment of adults and children 10 and older with bipolar disorder who experience mania, or episodes of unusually excited moods. Doctors can also prescribe the drug to treat mixed episodes that cause people to experience symptoms of both mania and depression. The FDA approved the first generic forms of Risperdal, Rispex tablets, in 2008.
Doctors can also prescribe Rispex for children 5 to 16 years old with autism, a condition that causes repetitive behavior and difficulty communicating and interacting with others. The drug can alleviate symptoms that include aggression, self-injury, and sudden mood changes.
Medical evidence does not indicate whether the drug is safe and effective in younger children.
Janssen, however, also marketed Risperdal as a treatment for older people with agitation from dementia, which is not an FDA-approved use of the medication. In fact, it can be dangerous for older adults with dementia to take antipsychotics, including Risperdal, and Janssen had to pay a fine for misbranding the drug. The combined criminal plea agreement with the Justice Department and a civil settlement totaled more than $1.67 billion.
In This Section:
Can Rispex cause problems?
Along with their useful effects, most medicines can cause unwanted side-effects although not everyone experiences them. The table below contains some of the most common ones associated with Rispex. You will find a full list in the manufacturer's information leaflet supplied with your medicine. The unwanted effects often improve as your body adjusts to the new medicine, but speak with your doctor or pharmacist if any of the following continue or become troublesome.
Rispex, sold under the trade name Risperdal among others, is an antipsychotic medication.