Conventional or typical neuroleptics
Clinical experience and anecdotal reports suggest that neuroleptic therapy produces a positive outcome (remission or reduction in symptoms, and earlier discharge from hospital) in a majority of older patients with schizophrenia (). Nevertheless, few studies have documented the efficacy of conventional antipsychotics with well designed, placebo-controlled clinical trials in patients with late-onset schizophrenia.
Neuroleptic medications do have a number of side-effects that occur more frequently in older subjects, including sedation, orthostatic hypotension, anticholinergic reactions, extrapyramidal symptoms and tardive dyskinesia.
Low-potency neuroleptics with sedative side-effects are excellent sleep inducers and may be helpful for the elderly patient with insomnia or severe daytime sedation. Sedation, however, persists for many hours after the drug has been given, and may interfere with the older patient’s level of arousal during the day.
This may lead to falls and could result in fractures or other injuries.
Dryness of mouth, urinary retention, constipation, worsening of glaucoma and mental confusion may result from anticholinergic toxicity.
Neuroleptic-induced acute and subacute extrapyramidal symptoms
Of all the acute extrapyramidal side-effects, acute dystonic reactions are the only ones that are less common in older, compared with younger, patients. Parkinsonism and akathisia may last for weeks, months, or even longer, if neuroleptic treatment continues. Extrapyramidal symptoms are usually managed by a reduction of the conventional neuroleptic, or use of an anticholinergic (e.g. benztropine), a beta-blocker (e.g. propranolol) or a dopaminergic (e.g. amantadine) drug, or switching to an atypical antipsychotic.
Tardive dyskinesia is characterised by abnormal involuntary movements, typically involving the orofacial region, limbs and trunk (). Movements maybe choreiform (i.e. rapid, jerky, non-repetitive), athetoid (i.e. slow, sinuous, continual), or rhythmic (i.e., stereotypies) and must be present for at least four weeks. According to DSM-IV, at least one month of exposure to neuroleptic medication is required for a diagnosis of tardive dyskinesia in the elderly (as opposed to a minimum of three months’ exposure in younger individuals). Prevalence estimates of tardive dyskinesia in patients over the age of 60 being treated with ‘typical’ neuroleptic drugs are 50% or even higher (). Not only is the incidence higher but so also is the risk of severe and persistent tardive dyskinesia greater in the elderly than in younger patients, especially if neuroleptics are continued.
While tardive dyskinesia is usually mild, severe dyskinesia can produce physical and psychosocial complications such as dental and denture problems and gait disturbances. Psychosocially, ambulatory patients with obvious tardive dyskinesia may experience shame, guilt, anxiety and depression.
There is no proven way to prevent tardive dyskinesia in patients receiving long-term treatment with typical antipsychotic medications. The best strategy involves restricting these drugs to well defined indications, using them in the lowest effective doses and assessing the patient at frequent intervals for early signs of abnormal movements. Discontinuation of antipsychotic therapy, although the most desirable treatment method, may be impractical for some patients with severe, chronic or relapsing psychosis. Typical antipsychotic medications can temporarily suppress symptoms of tardive dyskinesia, but since symptoms quickly return when treatment is withdrawn, use of these drugs specifically for treating tardive dyskinesia is not recommended except in severe cases.
The patient and family should be educated regarding the risks and benefits associated with treatment with antipsychotic medications. If withdrawal and discontinuation of the antipsychotic medication is not clinically feasible when abnormal movements are observed, switching to clozapine or other atypical antipsychotic medications may be considered. If treatment of the tardive dyskinesia is indicated or attempted, benign modalities should be employed initially (e.g. vitamin E).
Atypical antipsychotic medications represent an advance in our pharmacotherapeutic armamentarium for schizophrenia. Very few studies, however, have documented the efficacy of antipsychotic drugs in clinical trials with patients with late-onset schizophrenia.
The primary indication for the use of clozapine is generally considered to be antipsychotic-resistant schizophrenia. Clozapine has been found significantly to improve disorganisation, positive symptoms and negative symptoms in this group, and the incidence of tardive dyskinesia appears to be very low (). Unfortunately, the side-effects of clozapine make its use in older populations problematic (). The mandatory weekly blood samples can be a problem for the older patient, because of decreased mobility and increased bruising. Other side-effects include lethargy, sedation, postural hypotension, confusion and anticholinergic toxicity.
In small, open studies, risperidone has been reported to produce clinical improvement, in terms of a reduction in psychosis, aggression, agitation and other severe behavioural disturbances in elderly patients diagnosed with a variety of conditions, including schizophrenia (). The most commonly reported side-effects associated with risperidone include somnolence and postural hypotension. The threshold at which the elderly experience extrapyramidal symptoms is lower than that in younger adults. In the absence of long-term studies of risperidone the incidence of tardive dyskinesia with this drug is currently unknown. Preliminary data suggest that low-dose risperidone may improve the cognitive performance of some elderly psychotic patients.
While there is a wide variability in the dosage requirements of the elderly, starting dosages of neuroleptics for older patients are often approximately one-quarter of those prescribed for younger adults. Dosage should be increased gradually or decreased according to clinical response or development of side-effects. The neuroleptic dose in older patients with schizophrenia tends to correlate inversely with current age and age at onset of illness. Thus, elderly patients with late-onset schizophrenia require lower doses than younger or early-onset older patients (). As patients with chronic schizophrenia who have been taking neuroleptics for many years continue to age, their dosage requirements often decrease. Doses must therefore be monitored and calibrated according to the clinical needs of the individual patient at different times.
Supportive psychosocial therapy should be an integral part of the overall management of patients with late-onset schizophrenia.
Selections from the book: “Late-Onset Mental Disorders. The Potsdam Conference”, 1999.