The key feature of psychosis is the misinterpretation of reality as shown by altered perceptions, false beliefs, and disorganized patterns of speech and behavior. In the elderly, psychotic symptoms arise in a number of conditions: schizophrenia, schizoaffective disorder, delusional disorder, mood disorder, delirium secondary to medical conditions, and neurodegenerative conditions including Alzheimer’s disease, vascular dementia, dementia with Lewy bodies and Parkinson’s disease. Social isolation, sensory deficits, and polypharmacy are additional risk factors.1
Approximately 15% of all patients with schizophrenia have an onset of symptoms after the age of 40 years, 7% after the age of 50 and 3% thereafter.2
Hallucinations and persecutory delusions are common and generally follow a chronic course.3
In people with Alzheimer’s disease, the prevalence of psychotic symptoms ranges from 30% to 50%.4
In dementia with Lewy bodies, visual hallucinations occur in 80% of cases while auditory hallucinations and paranoid delusions have a prevalence of 20% and 65%, respectively.5
Between 20% and 60% of people with Parkinson’s disease develop psychotic symptoms.6
Psychotic symptoms can be associated with aggressive or disruptive behavior, are a source of distress to caregivers, and often result in institutionalization.7
Antipsychotic medications form the mainstay of treatment of psychotic symptoms. In recent years, second generation antipsychotics like risperidone, olanzapine, and clozapine have been preferred over older drugs like haloperidol because of their lower incidence of extrapyramidal, anticholinergic and cardiac side effects and a possible greater efficacy in reducing negative and neurocognitive symptoms.8
Treatment nonadherence is one of the greatest challenges facing prescribers with 20% to 50% of all patients failing to comply fully with medical recommendations.9
Rates of nonadherence to antipsychotic prescriptions are even higher. In the large, prospective CATIE Schizophrenia Study on the effectiveness of antipsychotics, for example, 75% of patients discontinued treatment within 18 months.10
Risk factors for nonadherence include ongoing psychosis, limited insight, adverse reactions, stigma, and poor rapport with the treating clinician.11
In addition, older people may have difficulty taking medications correctly because of sensory impairment, cognitive deficits, medical co-morbidity, polypharmacy, and heightened sensitivity to adverse effects.12
For patients with psychosis who will not or cannot take oral medication on a regular basis a long-acting injectable antipsychotic may offer a solution. Until recently choice was limited to first generation preparations such as haloperidol decanoate and flupenthixol decanoate, all of which can provoke parkinsonism, unsteadiness, and falls to which the elderly are vulnerable. Long-acting risperidone injection is the first “atypical” or second generation antipsychotic freely available for the treatment of psychosis.
This paper focuses on this treatment formulation and its use in the older patients with schizophrenia and related psychoses. Suitable papers were identified by means of an electronic search of MEDLINE, EMBASE, Scopus, PsycINFO and CINAHL databases using combinations of the key terms “risperidone”, “antipsychotic agents”, “therapeutic use”, “adverse effects”, and “aged”.
Pharmacology of risperidone long-acting injection
Both risperidone and its active metabolite 9-hydroxy risperidone are thought to have antipsychotic potency.13
Long-acting risperidone injection is an extended release microsphere formulation of risperidone encapsulated in polyglactin for intramuscular injection. Traditional anti-psychotic depot preparations are esterified and delivered in an oil-based suspension. Because of its lack of a hydroxyl group, risperidone cannot be esterified, but its encapsulation in biodegradable polymer microspheres makes possible its delivery in a water-based vehicle. The polymer dissolves into water and carbon end products, providing a steady release of medication.
After a single intramuscular injection, less than 1% of the dose is released followed by a lag of three weeks, which makes it necessary to prescribe an oral antipsychotic during this time. From that point on, release occurs steadily between weeks 4 to 6 and subsides by week 7. Thereafter, twice-weekly injections result in sustained therapeutic plasma concentrations that persist for four to six weeks after the last injection The elimination phase is complete at seven to eight weeks following microsphere breakdown.
The pharmacokinetics of long-acting risperidone is linear in the dose range of 25 to 50 mg. Following extensive first-pass metabolism of risperidone by the liver, 90% is bound in plasma to albumin and alpha-1 acid glycoprotein prior to elimination via the kidneys. Plasma levels are normal in patients with hepatic insufficiency, but may be raised by 60% in patients with renal impairment.14
Since aging is associated with decreased rates of renal blood flow, glomerular filtration and renal clearance as well as reduced levels of synthesis and activity of hepatic microsomal enzymes, caution is required in older patients with renal or hepatic impairment. An age-related fall in total body water results in higher plasma concentrations of this water-based medication, increasing both its activity and the potential for adverse effects. Reduced cerebrovascular perfusion and the increased sensitivity of alpha-1 adrenergic receptors also make the elderly more susceptible to orthostatic hypotension, dizziness and falls. With age, the loss of ascending dopaminergic neurones and postsynaptic dopamine receptors can halve the levels of striatal dopamine by age 65 years, resulting in parkinsonism and tardive dyskinesia given risperidone’s high affinity for dopaminergic D2 receptors.12
Risperidone must be used with caution with other centrally acting medicines. It antagonizes the effects of levodopa and other dopamine agonists and potentiates the orthostatic effects of tricyclic antidepressants and antihypertensives. Caution is advised when combining risperidone with drugs known to prolong the QT interval because of the risk of cardiac arrhythmias. Risperidone levels are increased by cytochrome 450 2D6 inhibitors such as paroxetine and fluoxetine and decreased by cytochrome 450 3A4 inducers like carbamazepine, corticosteroids, and barbiturates.