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A Brief History of Schizophrenia Treatment
One of the most important milestones in the treatment of schizophrenia has been the recognition that mental disorders are indeed treatable illnesses—not the result of upbringing or character flaws in those affected.
Following, a brief overview of prejudice and progress in schizophrenia treatment from the 17th century to today:
1600s
Native American shamans, or medicine men, summoned supernatural powers to treat the mentally ill, incorporating rituals of atonement and purification.
1692
Witchcraft and demonic possession were common explanations for mental illness. The Salem witchcraft trials sentenced 19 people to hanging.
1724
Puritan clergyman Cotton Mather (1663-1728) broke with popular belief by advancing physical explanations for mental illnesses.
1812
Benjamin Rush (1745-1813) became one of the earliest advocates of humane treatment for the mentally ill with the publication of Medical Inquiries and Observations Upon Diseases of the Mind, the first American textbook of psychiatry.
1843
There were approximately 24 hospitals – totaling only 2,561 beds – available for treating mental illness in the United States.
1909
Sigmund Freud visited America and lectured on psychoanalysis at Clark University in Worcester, Massachusetts.
1920s
Harry Stack Sullivan's ward for schizophrenic patients at Sheppard-Pratt Hospital demonstrates the impact of a therapeutic milieu when patients are able to be returned to the community.
1930s
Psychiatrists began to inject insulin to induce shock and temporary coma as a treatment for schizophrenia.
1936
Egas Moniz published an account of the first human frontal lobotomy. Between 1936 and the mid-1950s, an estimated 20,000 of these surgical procedures were performed on American mental patients.
1940s
Electrotherapy (applying electric current to the brain) was first used in American hospitals to treat mental illnesses.
1947
Fountain House in NYC begins psychiatric rehabilitation for mentally ill persons.
1952
The first conventional antipsychotic drug, Thorazine® (chlorpromazine), was introduced to treat patients with schizophrenia and other major mental disorders.
1960s
Conventional antipsychotic drugs, such as haloperidol, were first used to control outward (positive) symptoms of psychosis, bringing a significant measure of calm and order to psychiatric wards.
1962
422,000 individuals were hospitalized for psychiatric care in the United States.
1970
Mass deinstitutionalization (discharge of patients from the hospital to the community) began. Patients and their families were left to their own resources due to the lack of outpatient programs for rehabilitation and reintegration back into society.
1980
Rise of managed care—short-stay hospitalization with community treatment—became the standard of care for mental illness.
1989
The first atypical antipsychotic, Clozaril® (clozapine), was introducted for patients with
treatment-resistant/intolerant schizophrenia.
1990
Researchers begin to use brain imaging to learn more about the development of major mental illnesses.
1994
The 1st first-line of the atypical antipsychotic drugs is introduced. It is the 1st new first-line antipsychotic drug in almost 20 years. RISPERDAL® (risperidone) becomes available in the United States.
2003
RISPERDAL® CONSTA® (risperidone) Long-Acting Injection becomes the only long-acting form of the atypical antipsychotic drugs available in the United States.
2006
A new atypical, INVEGA® (paliperidone), becomes available in the United States.
For additional medical or clinical information, please call 1-800-JANSSEN (1-800-526-7736).
INVEGA® (paliperidone) extended-release tablets are indicated for the acute and maintenance treatment of schizophrenia.
RISPERDAL® (risperidone) is indicated for the treatment of schizophrenia in adults and children aged 13-17 years.
RISPERDAL® CONSTA® (risperidone) long-acting injection is indicated for the treatment of schizophrenia.
IMPORTANT SAFETY INFORMATION FOR INVEGA®, RISPERDAL®, AND RISPERDAL® CONSTA®
Increased Mortality in Elderly Patients with Dementia-Related Psychosis
Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death. Analyses of 17 placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in the drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. INVEGA® (paliperidone), RISPERDAL® (risperidone), and RISPERDAL® CONSTA® (risperidone) are not approved for the treatment of patients with dementia-related psychosis.
Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death. Analyses of 17 placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in the drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. INVEGA® (paliperidone), RISPERDAL® (risperidone), and RISPERDAL® CONSTA® (risperidone) are not approved for the treatment of patients with dementia-related psychosis.
Cerebrovascular Adverse Events (CAEs): CAEs, including fatalities, have been reported in elderly patients with dementia-related psychosis taking atypical antipsychotics in clinical trials. INVEGA®, RISPERDAL®, and RISPERDAL® CONSTA® are not approved for treating these patients.
Neuroleptic Malignant Syndrome (NMS): NMS, a potentially fatal symptom complex, has been reported with the use of antipsychotic medications, including INVEGA®, RISPERDAL®, and RISPERDAL® CONSTA®. Clinical manifestations include muscle rigidity, fever, altered mental status and evidence of autonomic instability (see full Prescribing Information). Management should include immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy, intensive symptomatic treatment and medical monitoring, and treatment of any concomitant serious medical problems.
QT Prolongation: INVEGA® causes a modest increase in the corrected QT (QTc) interval. INVEGA® should be avoided in combination with other drugs that are known to prolong the QTc interval, in patients with congenital long QT syndrome or a history of cardiac arrhythmias. Certain circumstances may increase the risk of torsades de pointes and/or sudden death in association with the use of drugs that prolong the QTc interval.
Tardive Dyskinesia (TD): TD is a syndrome of potentially irreversible, involuntary, dyskinetic movements that may develop in patients treated with antipsychotic medications. The risk of developing TD and the likelihood that dyskinetic movements will become irreversible are believed to increase with duration of treatment and total cumulative dose. Elderly patients appeared to be at increased risk for TD. Prescribing should be consistent with the need to minimize the risk of TD. The syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn.
Hyperglycemia and Diabetes: Hyperglycemia, some cases extreme and associated with ketoacidosis, hyperosmolar coma or death has been reported in patients treated with atypical antipsychotics (APS). Patients starting treatment with APS who have or are at risk for diabetes should undergo fasting blood glucose testing at the beginning of and during treatment. Patients who develop symptoms of hyperglycemia should also undergo fasting blood glucose testing.
Hyperprolactinemia: As with other drugs that antagonize dopamine
Potential for Gastrointestinal Obstruction: INVEGA® should ordinarily not be administered to patients with pre-existing severe gastrointestinal narrowing. Rare instances of obstructive symptoms have been reported in patients with known strictures taking nondeformable formulations. INVEGA® should only be used in patients who are able to swallow the tablet whole.
Orthostatic Hypotension and Syncope: INVEGA®, RISPERDAL®, and RISPERDAL® CONSTA® may induce orthostatic hypotension associated with dizziness, tachycardia, and in some patients, syncope, especially during the initial dose-titration period. Monitoring should be considered in patients for whom this may be of concern. INVEGA®, RISPERDAL®, and RISPERDAL® CONSTA® should be used with caution in patients with known cardiovascular disease, and conditions that would predispose patients to hypotension.
Potential for Cognitive and Motor Impairment: INVEGA®, RISPERDAL®, and RISPERDAL® CONSTA® have the potential to impair judgment, thinking, or motor skills. Patients should be cautioned about operating hazardous machinery, including motor vehicles, until they are reasonably certain that INVEGA®, RISPERDAL®, and RISPERDAL® CONSTA® do not affect them adversely.
Seizures: INVEGA®, RISPERDAL®, and RISPERDAL® CONSTA® should be used cautiously in patients with a history of seizures.
Suicide: The possibility of suicide attempt is inherent in psychotic illnesses and close supervision of high-risk patients should accompany drug therapy.
Maintenance Treatment: Physicians who elect to use INVEGA®, RISPERDAL®, and RISPERDAL® CONSTA® for extended periods should periodically re-evaluate the long-term risks and benefits of the drug for the individual patient.
Drug Interactions: Co-administration of INVEGA® 6 mg once daily with carbamazepine 200 mg twice daily caused a decrease of approximately 37% in the mean steady-state
Extrapyramidal Symptoms (EPS): Total EPS-related adverse events with INVEGA® in the higher 9-mg and 12-mg treatment groups were 25% and 26%, respectively, versus 11% for the placebo group.
Weight Gain: The proportion of subjects having a weight gain of >7% body weight with INVEGA® were comparable to placebo (5%) for 3 mg (7%) and 6 mg (6%). A higher incidence was seen for 9 mg (9%) and 12 mg (9%).
Renal Impairment: Dosing must be individualized according to the patient's renal function status. The maximum recommended dose of INVEGA® is 6 mg for patients with mild renal impairment and 3 mg for patients with moderate to severe renal impairment (see Dosing for Special Populations).
Elderly: No dosage adjustment is recommended based on age alone. However, dose adjustment may be required because of age-related decreases in creatinine clearance (see Dosing for Special Populations).
Commonly observed adverse reactions for INVEGA®: The most commonly observed adverse reactions, occurring at an incidence of >5% and at least 2 times placebo, were akathisia and extrapyramidal disorder.
Commonly observed adverse reactions for RISPERDAL®: The most common adverse reactions from all clinical trials (>10%) were: somnolence, appetite increased, fatigue, rhinitis, upper respiratory tract infection, vomiting, coughing, urinary incontinence, saliva increased, constipation, fever, Parkinsonism, dystonia, abdominal pain, anxiety, nausea, dizziness, dry mouth, tremor, rash, akathisia, and dyspepsia.
Commonly observed adverse events for RISPERDAL® CONSTA®: The most commonly observed adverse events, occurring at an incidence of >5% and at least 2 times placebo were somnolence, akathisia, Parkinsonism, dyspepsia, constipation, dry mouth, fatigue and weight increase.
Use with Risperidone: Concomitant use of paliperidone with risperidone has not been studied. Since paliperidone is the major active metabolite of risperidone, consideration should be given to the additive paliperidone exposure if risperidone is co-administered.
01JN778R1
Please see the full US Prescribing Information for INVEGA, RISPERDAL and RISPERDAL CONSTA.
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This page was last modified on: Jan 10 2008 at 16:40:10 EST