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Overview of Schizophrenia and Its Impact on Patients and Families
Author(s):
DR. ALVA: Hello, and welcome to this Psychiatric Times Expert Perspectives video series. I’m Dr. Gus Alva, Medical Director of ATP Clinical Research in Costa Mesa, California, and I am joined by Desiree Matthews, PMHNP, owner and Clinical Director at Different MHP.
Today we will be discussing schizophrenia and the inherent challenges with managing this complex and chronic brain disorder, including treatment nonadherence and delaying relapse. In my opinion, there are so many appropriate adult patients that may benefit from these treatments but may not even be aware that there is an option without your help to educate them. The conversation will then pivot to long-acting injectables, or LAIs–such as once-monthly INVEGA SUSTENNA® (or paliperidone palmitate), which is part of the Johnson & Johnson LAI portfolio that includes pathway options to 3 and 6 months.
We will then review comparative safety and efficacy data on INVEGA SUSTENNA® compared to orals and discuss ways by which J&J LAIs may help address challenges of managing schizophrenia.
MATTHEWS: Thank you for that introduction, Dr. Alva, and hello, everyone. Happy to be speaking with you today. Before we get started, I’d like to note that this program is sponsored by Johnson & Johnson. Now, let’s get started.
DR. ALVA: We’ll begin with a general overview of schizophrenia. Desiree, can you describe the overall nature of the condition and how it affects adult patients?
MATTHEWS: Absolutely. I’ll start by saying that schizophrenia affects millions of adults in the U.S., and it is associated with a substantial burden to the healthcare system. It is one of the top 20 reasons for disability in the world. In the U.S., the estimated annual economic burden can range from $94 million to $102 billion U.S. dollars per year.
The condition can be debilitating to those living with it without proper management and treatment. But living a more stable, productive life may be possible for these adult patients. Symptoms can include delusions, hallucinations, and disorganized speech, as well as behaviors such as a lack of motivation or a lack of interest in daily life experiences.
These symptoms can considerably impair daily activities, including work and relationships with family and loved ones, making it difficult for adult patients to prioritize self-care and, when unmanaged, can create a cycle of crisis. That being said, it’s important to clarify that a schizophrenia diagnosis doesn’t mean that a person can’t go on to live a fulfilling life.
DR. ALVA: Desiree, you know, you’re so right. I think that stigma and a sense of, you know, futility almost pervades in the minds of many individuals, including clinicians, and you know, it’s not a bad idea for us to get everybody up to speed with the latest developments of where we’re at right now, how we might be able to tackle this condition, how we might be able to better serve the people that need our help.
MATTHEWS: Absolutely. I think giving hope back to the family, back to the patient and clearly laying out all of their options to manage this condition, both medication as well as therapy options.
DR. ALVA: Absolutely.
MATTHEWS: It’s also a condition that is unfortunately still misunderstood and stigmatized today – even by adult patients, their loved ones, and providers. So, we must do everything we can to support our adult patients living with schizophrenia and ensure they know about all of their treatment options, including long-acting injectables, and that living a more routinely normal life with schizophrenia is possible.
DR. ALVA: To reiterate what you said, this condition can profoundly affect every aspect of life for an adult living with schizophrenia. For most, schizophrenia is a chronic, lifelong disease that requires ongoing management and consistent treatment regardless of whether symptoms are present. Relapse, which may include symptoms that lead to episodes of psychosis, hallucinations, or other disruptive behaviors, is of particular concern for both healthcare providers and adult patients, so it’s very important to delay whenever possible.
With each relapse in schizophrenia, adult patients run the risk of further deterioration in function, such as an increase of symptoms or the need for an adjustment in dosing, reduced treatment response, and poorer outcomes in general.
In addition, a relapse can greatly disrupt an adult patient’s life, with events such as hospitalization, loss of employment, or dropping out of school. After a relapse, some adult patients do not ever regain their original level of functioning, making it even harder to get back to that sense of normality they may have had pre-diagnosis.
Therefore, it’s critical for providers like us to initiate treatment earlier in the disease course to delay the risk of relapse and set our adult patients up for success. Early treatment initiation is also important with consideration to what we call the “critical period” during the first few years after diagnosis. Desiree, can you provide details on that?
MATTHEWS: Certainly. The “critical period” is considered to be within the first 5 years following diagnosis, during which time the disease can progress rapidly. After this time, progression tends to plateau. While HCPs can work to treat the condition at various stages, initiating treatment early, during this critical period, may positively influence short- and long-term clinical outcomes.
DR. ALVA: You know, you’re so right Desiree. With my adult patients, I approach treating them during this critical period by enhancing their educational base. By letting them know that, left to its own devices, psychosis is truly neurotoxic. It creates more problems for people. It fries out different connections in the brain and then subsequently leads towards greater periods for which they might not necessarily respond to the same dose that would have actually provided some support for them. What are your thoughts with that?
MATTHEWS: I completely agree. And early on in the disease course, it’s important to not only educate the patients, but also their families, and giving them that hope that when it’s well managed, individuals can go on to resume their daily activities, whether that’s enrolling back into school, going back to work, and having really those meaningful connections with both friends and family.
DR. ALVA: So being more aspirational in nature, I love that.
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INDICATION
INVEGA HAFYERA®, an every-six-month injection, is an atypical antipsychotic indicated for the treatment of schizophrenia in adults after they have been adequately treated with:
- A once-a-month paliperidone palmitate extended release injectable suspension (e.g., INVEGA SUSTENNA®) for at least four months or
- An every-three-month paliperidone palmitate extended release injectable suspension (e.g., INVEGA TRINZA®) for at least one three-month cycle.
INVEGA TRINZA® is an atypical antipsychotic indicated for the treatment of schizophrenia in patients after they have been adequately treated with INVEGA SUSTENNA® for at least four months.
INVEGA SUSTENNA® is an atypical antipsychotic indicated for the treatment of schizophrenia in adults.
IMPORTANT SAFETY INFORMATION
Contraindications: INVEGA HAFYERA®, INVEGA TRINZA® and INVEGA SUSTENNA® are contraindicated in patients with a known hypersensitivity to either paliperidone, risperidone, or to any excipients of their formulation.
Cerebrovascular Adverse Reactions: Cerebrovascular adverse reactions (e.g., stroke, transient ischemic attacks), including fatalities, were reported at a higher incidence in elderly patients with dementia-related psychosis taking risperidone, aripiprazole, and olanzapine compared to placebo. No studies have been conducted with oral paliperidone, INVEGA HAFYERA®, INVEGA TRINZA® or INVEGA SUSTENNA® in elderly patients with dementia. These medications are not approved for the treatment of patients with dementia-related psychosis.
Neuroleptic Malignant Syndrome (NMS): NMS, a potentially fatal symptom complex, has been reported in association with antipsychotic drugs, including paliperidone.
Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status including delirium, and autonomic instability (irregular pulse of blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure.
If NMS is suspected, immediately discontinue INVEGA HAFYERA®, INVEGA TRINZA® or INVEGA SUSTENNA® and provide symptomatic treatment and monitoring.
QT Prolongation: Paliperidone causes a modest increase in the corrected QT (QTc) interval. Avoid the use of drugs that also increase QTc interval and in patients with risk factors for prolonged QTc interval. Paliperidone should also be avoided in patients with congenital long QT syndrome and in patients with a history of cardiac arrhythmias. Certain circumstances may increase the risk of the occurrence of torsades de pointes and/or sudden death in association with the use of drugs that prolong the QTc interval.
Tardive Dyskinesia (TD): TD, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements, may develop in patients treated with antipsychotic drugs. Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to predict which patients will develop the syndrome. Whether antipsychotic drug products differ in their potential to cause tardive dyskinesia is unknown.
The risk of developing TD and the likelihood that it will become irreversible appear to increase with the duration of treatment and the cumulative dose. The syndrome can develop after relatively brief treatment periods, even at low doses. It may also occur after discontinuation. TD may remit, partially or completely, if antipsychotic treatment is discontinued. Antipsychotic treatment itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome, possibly masking the underlying process. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown.
If signs and symptoms of TD appear in a patient on INVEGA HAFYERA®, INVEGA TRINZA® or INVEGA SUSTENNA®, drug discontinuation should be considered. However, some patients may require treatment with INVEGA HAFYERA®, INVEGA TRINZA® or INVEGA SUSTENNA® despite the presence of the syndrome. In patients who do require chronic treatment, use the lowest dose and the shortest duration of treatment producing a satisfactory clinical response. Periodically reassess the need for continued treatment.
Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular/cerebrovascular risk. These metabolic changes include hyperglycemia, dyslipidemia, and body weight gain. While all of the drugs in the class have been shown to produce some metabolic changes, each drug has its own specific risk profile.
Hyperglycemia and Diabetes Mellitus: Hyperglycemia and diabetes mellitus, in some cases extreme and associated with ketoacidosis, hyperosmolar coma or death, have been reported in patients treated with all a typical antipsychotics (APS). Patients starting treatment with APS who have or are at risk for diabetes mellitus should undergo fasting blood glucose testing at the beginning of and during treatment. Patients who develop symptoms of hyperglycemia during treatment should also undergo fasting blood glucose testing. All patients treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia. Some patients require continuation of antidiabetic treatment despite discontinuation of the suspect drug.
Dyslipidemia: Undesirable alterations have been observed in patients treated with atypical antipsychotics.
Weight Gain: Weight gain has been observed with atypical antipsychotic use. Clinical monitoring of weight is recommended.
Orthostatic Hypotension and Syncope: INVEGA HAFYERA®, INVEGA TRINZA® and INVEGA SUSTENNA® may induce orthostatic hypotension in some patients due to its alpha-adrenergic blocking activity. INVEGA HAFYERA®, INVEGA TRINZA® and INVEGA SUSTENNA® should be used with caution in patients with known cardiovascular disease, cerebrovascular disease or conditions that would predispose patients to hypotension (e.g., dehydration, hypovolemia, treatment with antihypertensive medications). Monitoring should be considered in patients for whom this may be of concern.
Falls: Somnolence, postural hypotension, motor and sensory instability have been reported with the use of antipsychotics, including INVEGA HAFYERA®, INVEGA TRINZA® and INVEGA SUSTENNA®, which may lead to falls and, consequently, fractures or other fall-related injuries. For patients, particularly the elderly, with diseases, conditions, or medications that could exacerbate these effects, assess the risk of falls when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy.
Leukopenia, Neutropenia and Agranulocytosis have been reported with antipsychotics, including INVEGA HAFYERA®, INVEGA TRINZA® and INVEGA SUSTENNA®. In patients with a history of clinically significant low white blood cell count (WBC)/absolute neutrophil count (ANC) or drug-induced leukopenia/neutropenia, perform a complete blood count frequently during the first few months of therapy. Consider discontinuing INVEGA HAFYERA®, INVEGA TRINZA® and INVEGA SUSTENNA® at the first sign of a clinically significant decline in WBC in the absence of other causative factors. Monitor patients with clinically significant neutropenia for fever or other symptoms or signs of infection and treat promptly if such symptoms or signs occur. Discontinue INVEGA HAFYERA®, INVEGA TRINZA® and INVEGA SUSTENNA® in patients with severe neutropenia (absolute neutrophil count <1000/mm3) and follow their WBC until recovery.
Hyperprolactinemia: As with other drugs that antagonize dopamine D2 receptors, INVEGA HAFYERA®, INVEGA TRINZA® and INVEGA SUSTENNA® elevate prolactin levels, and the elevation persists during chronic administration. Paliperidone has a prolactin-elevating effect similar to risperidone, which is associated with higher levels of prolactin elevation than other antipsychotic agents.
Potential for Cognitive and Motor Impairment: Somnolence, sedation, and dizziness were reported as adverse reactions in subjects treated with INVEGA HAFYERA®, INVEGA TRINZA® and INVEGA SUSTENNA®. INVEGA HAFYERA®, INVEGA TRINZA® and INVEGA SUSTENNA® have the potential to impair judgment, thinking, or motor skills. Patients should be cautioned about performing activities that require mental alertness such as operating hazardous machinery, including motor vehicles, until they are reasonably certain that INVEGA HAFYERA®, INVEGA TRINZA® and INVEGA SUSTENNA® do not adversely affect them.
Seizures: INVEGA HAFYERA®, INVEGA TRINZA® and INVEGA SUSTENNA® should be used cautiously in patients with a history of seizures or with conditions that potentially lower seizure threshold. Conditions that lower seizure threshold may be more prevalent in patients 65 years or older.
Administration: For intramuscular injection only by a healthcare professional using only the needles provided in the INVEGA HAFYERA®, INVEGA TRINZA® or INVEGA SUSTENNA® kits. Care should be taken to avoid inadvertent injection into a blood vessel.
Drug Interactions: Strong CYP3A4/P-glycoprotein (P-gp) inducers: Avoid using a strong inducer of CYP3A4 and/or P-gp (e.g., carbamazepine, rifampin, St John’s Wort) during a dosing interval for INVEGA HAFYERA®, INVEGA TRINZA® or INVEGA SUSTENNA®. If administering a strong inducer is necessary, consider managing the patient using paliperidone extended-release tablets.
Pregnancy/Nursing: INVEGA HAFYERA®, INVEGA TRINZA® and INVEGA SUSTENNA® may cause extrapyramidal and/or withdrawal symptoms in neonates with third trimester exposure. Advise patients to notify their healthcare professional if they become pregnant or intend to become pregnant during treatment with INVEGA HAFYERA®, INVEGA TRINZA® or INVEGA SUSTENNA®. Patients should be advised that there is a pregnancy registry that monitors outcomes in women exposed to INVEGA HAFYERA®, INVEGA TRINZA® or INVEGA SUSTENNA® during pregnancy.
INVEGA HAFYERA®, INVEGA TRINZA® and INVEGA SUSTENNA® can pass into human breast milk. The benefits of breastfeeding should be considered along with the mother’s clinical need for INVEGA HAFYERA®, INVEGA TRINZA® or INVEGA SUSTENNA® and any potential adverse effect on the breastfed infant from INVEGA HAFYERA®, INVEGA TRINZA® or INVEGA SUSTENNA® or the mother’s underlying condition.
Commonly Observed Adverse Reactions for INVEGA HAFYERA®: The most common adverse reactions (incidence at least 5% in the double-blind phase) in the INVEGA HAFYERA® clinical trial were upper respiratory tract infection, injection site reaction, weight increased, headache and parkinsonism.
Commonly Observed Adverse Reactions for INVEGA TRINZA®: The most common adverse reactions (incidence ≥ 5% and occurring at least twice as often as placebo) were injection site reaction, weight increased, headache, upper respiratory tract infection, akathisia and parkinsonism.
Commonly Observed Adverse Reactions for INVEGA SUSTENNA®: The most common adverse reactions in clinical trials in patients with schizophrenia (incidence ≥ 5% and occurring at least twice as often as placebo) were injection site reactions, somnolence/sedation, dizziness, akathisia and extrapyramidal disorder.
Please click here to read the full Prescribing Information, including Boxed WARNING, for INVEGA HAFYERA®, click here to read the full Prescribing Information, including Boxed WARNING, for INVEGA TRINZA® and click here to read the full Prescribing Information, including Boxed WARNING, for INVEGA SUSTENNA®.
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