Talking psychiatry...Psychosis in the elderly


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Talking psychiatry...Psychosis in the elderly

  1. 1. INDEX  INTRODUCTION INTRODUCTION As the population ages, the number of older patients with psychosis will greatly rise. This review focuses on the etiology, biologic and clinical findings, and treatments of common causes of psychosis in the elderly. Psychosis is a common psychiatric symptom characterized by hallucinations and delusions. In the elderly, causes may include schizophrenia and schizoaffective disorder, affective illnesses, dementia, delirium, delusional disorders, substance-induced disorders, and Parkinson's disease. Prevalence estimates of psychotic disorders in the elderly range widely from 0.2% to 4.75% in community-based samples, and are as high as 10-63% in nursing home populations.[1,2] The elderly currently account for about 12% of the US population, but that figure is expected to rise to 20% by the year 2030.[3] As the population ages, the number of elderly patients with psychosis will also increase significantly. Thus, it is an area of increasing interest and research. Biological
  2. 2. substrates underlie many psychotic symptoms[4] and may be helpful in directing future research into accurate diagnosis and treatment. The author will review some of the common faces of psychosis in the elderly with respect to etiology and biologic findings, clinical correlates, and treatments. Recent studies on psychosis related to Alzheimer's disease indicate that antipsychotic drugs have equivocal efficacy in improving psychotic symptoms and may have side effects or risks that outweigh their benefits. Behavioral interventions for agitation in dementia are showing some promise. In older adults with schizophrenia, intramuscular ziprasidone was found to be effective, and evidence is emerging for the use of hormone replacement therapy. For depression with psychosis, a recent study found that the combination of an antidepressant with an antipsychotic is no more effective than an antidepressant alone. There is support for the use of antipsychotic drugs for all types of psychosis in the elderly. While the atypical antipsychotics have a 'black box warning' on risk of death in elderly patients with dementia, the typical antipsychotics carry an even higher risk of death and adverse effects. Weighing the potential risks and benefits of treatment options is essential. Please refer to your country's regulations regarding the use of antipsychotic drugs.  Psychosocial Correlates of Psychosis in the Elderly Few studies have explored the prevalence of delusions in the nonclinical, elderly population or the association between personality structure and delusions. Laroi and colleagues[5] examined the relationship between age and the prevalence of delusions and the association between personality and delusion proneness. Nonclinical participants completed measures on delusions, hallucinations, and personality traits. Elderly participants scored significantly higher than young participants on the religious ideation factor, and correlational analyses revealed a significant relationship between delusions and the openness facet of the personality measure. Overall, the study revealed that delusional ideation is a relatively common experience for both young and elderly nonclinical participants. In addition, findings were consistent with previous studies suggesting that neuroticism and aspects related to neuroticism increase the risk for the development of psychotic symptoms such as delusions.[5] Biopsychosocial risk factors associated with clinical late-onset psychosis include female sex, low socio-economic status, the experience of immigration, and the presence of sensory or perceptual deficits.[6] Recent research by Giblin and colleagues[6] compared the nature and extent of adverse early life experiences, presence of maladaptive cognitive schemas, and morale in relation to aging between older people with a diagnosis of late-onset psychosis, late-onset depression, or healthy older volunteers (control group). They found that both the late-onset psychosis and late- onset depression groups reported significantly higher levels of adverse life events than the control group. The late-onset psychosis group also scored significantly higher on four out of five schema domains (including rejection and disconnection, impaired autonomy and performance, other- directedness, and over-vigilance and inhibition). Finally, the late-onset psychosis group had significantly lower overall morale with regards to aging than the control group, likely reflecting higher levels of loneliness and dissatisfaction.[6]  Types of psychosis in the elderly  Alzheimer's Dementia In a study of 140 geriatric outpatients that prospectively investigated psychosis in the elderly and the associated clinical diagnoses, 36.7% of patients were diagnosed with dementia.[7] In addition, dementia accounted for the highest number of psychotic diagnoses in this study. Therefore, a
  3. 3. clinician should be highly suspicious of dementia in an elderly patient presenting with psychosis. Alzheimer's disease currently affects about 7% of the population aged 65 and over.[8] As the population ages, the prevalence of Alzheimer's disease is expected to more than triple by the year 2050 from 4 million to approximately 14 million.[9] Psychosis is one of the most prominent noncognitive symptoms of Alzheimer's disease with prevalence estimates ranging from 30% to 50%[9] and is associated with greater cognitive impairment, especially frontal/temporal dysfunction, and possibly a more rapid course.[10] There is considerable neurobiologic and genetic evidence supporting a subtype of Alzheimer's disease based on the presence of psychotic symptoms[11] and possibly even of subtypes within psychotic Alzheimer's disease.[12] Sweet and colleagues[13] have shown a possible association between psychosis in dementia and homozygosity for the DRD1, DRD2, and DRD3 dopamine receptor gene alleles. Histopathological studies have revealed differences in neuronal pathology in psychosis associated with dementia.[14,15] Zubenko and colleagues[16] found significantly increased densities of senile plaques and neurofibrillary tangles in the prosubiculum and middle frontal cortex, respectively, in patients with Alzheimer's disease and psychosis. Studies have also revealed differential neurotransmitter concentrations in Alzheimer's patients with psychosis.[16,17] Finally, radiological studies have shown right and left hemisphere differences in size,[18,19] and regional differences in blood flow and glucose metabolism between psychotic and nonpsychotic patients with Alzheimer's disease.[20-22] Clinical correlates associated with delusions in Alzheimer's disease include anosognosia (limited insight into one's deficits), depression, global cognitive deficits, and elevated mood.[23] Most patients with hallucinations also had delusions, and paranoid delusions reportedly increased across the stages of the illness.[23] Jeste and Finkel[9] have suggested the following operational criteria to aid clinicians in diagnosing psychosis due to Alzheimer's disease and to exclude psychotic symptoms due to schizophrenia, delirium, or other conditions. First, patients must meet all criteria for the diagnosis of Alzheimer's type dementia. They must have the presence of visual or auditory hallucinations or delusions at least intermittently for 1 month or longer, and the psychosis must not have been present continuously prior to the onset of the symptoms of dementia. The psychotic symptoms must be severe enough to cause some disruption in patients' or others' functioning and cannot be better accounted for by another general medical condition, substance-induced psychosis, or occur exclusively in the course of delirium. Finally, criteria for schizophrenia, schizoaffective disorder, delusional disorder, or mood disorder with psychotic features must never have been met. Treatment of psychosis and behavioral disturbances in Alzheimer's disease has largely focused on the use of antipsychotics. Although atypical antipsychotics are more commonly used in the current setting, typical antipsychotics are still used. Devanand and colleagues[24] compared the efficacy and side effects of two doses of haloperidol and placebo in the treatment of psychosis and disruptive behaviors in patients with Alzheimer's disease. They demonstrated that standard-dose (2-3 mg daily) haloperidol was effective and superior to low-dose (0.5-0.75 mg daily) haloperidol for treating psychosis and disruptive behaviors in patients with Alzheimer's disease. Extrapyramidal side effects were greater with the standard dose, but low-dose haloperidol did not differ from placebo with regard to efficacy.[24] More recently, studies have focused on the use of atypical antipsychotics for treating psychosis and agitation in Alzheimer's disease. In 2003, Schneider et al.[25] evaluated the efficacy of risperidone in reducing psychotic and aggressive symptoms in a subgroup of patients who fulfilled operationalized criteria for psychosis in dementia. They found that the severity of both psychosis and aggressiveness was reduced with risperidone compared with placebo in a robust and dose- dependent way. In 2006, Tariot and colleagues[26] evaluated the efficacy, safety, and tolerability of quetiapine for treating psychosis. Two hundred and eighty-four participants were randomized to receive quetiapine, haloperidol, or placebo. They found no differential benefit on any psychosis measure between the groups, but did find that Brief Psychiatric Rating Scale (BPRS) scores
  4. 4. improved with quetiapine versus placebo and not quetiapine versus haloperidol. brief psychiatric rating scale anergia scores, however, worsened with haloperidol versus quetiapine but not for quetiapine versus placebo. Their overall conclusions were that participants treated with quetiapine or haloperidol showed inconsistent evidence of improvement in agitation, and tolerability was better with quetiapine versus haloperidol. Another group led by Ballard[27] evaluated the efficacy of quetiapine and rivastigmine compared with placebo for agitation in 31 people with dementia in institutional care, and they evaluated these treatments with respect to change in cognitive performance. Compared with placebo, neither group showed significant differences in improvement on the agitation inventory at 6 weeks or 26 weeks, and quetiapine was associated with significantly greater cognitive decline. These results are echoed by the recent Clinical Antipsychotic Trials of Intervention Effectiveness - Alzheimer's Disease (CATIE-AD) which showed that there were no significant differences among treatments (olanzapine, risperidone, quetiapine, or placebo) with regard to the time to discontinuation of treatment for any reason.[28] They found that the median time to discontinuation due to lack of efficacy favored olanzapine and risperidone compared with quetiapine and placebo, but that the time to discontinuation due to adverse events or intolerability favored placebo. The authors concluded that the adverse effects offset advantages in the efficacy of atypical antipsychotic drugs for the treatment of psychosis, aggression, or agitation in patients with Alzheimer's disease.[28] Despite the equivocal efficacy and safety issues, which will be discussed later, the behavioral and psychological symptoms of Alzheimer's disease (including psychosis) are most often managed with antipsychotic drugs. A recent cross-sectional study in various geriatric care units (including residential care facilities, nursing homes, group dwellings, rehabilitation units, etc.) was conducted in Sweden to discover factors associated with the use of antipsychotic drugs. The investigators found 11 independent factors that were significantly associated with the use of antipsychotics including aggressive, verbally disruptive and wandering behaviors; hallucinatory and depressive symptoms; male sex; living in a group dwelling for people with dementia; imposed mental workload; the ability to rise from a chair; activities of daily living dependency; and lower age.[29] Alternative treatments for agitation and behavioral symptoms associated with dementia are increasingly being considered. There is mounting evidence for the use of carbamazepine and antidepressants such as trazodone and the selective serotonin reuptake inhibitors.[30-32] Recently, Spira and Edelstein[33] reviewed behavioral interventions for agitation in older adults with dementia and found 23 articles describing interventions that targeted wandering, disruptive vocalization, physical aggression, other agitated behaviors, and a combination of these behaviors. They found that behavioral interventions showed considerable promise and concluded that studies provided a good basis for future, more rigorously designed, intervention studies. Specific interventions that seemed to be beneficial included stimulus control interventions for wandering, differential reinforcement of other behaviors (DRO) for disruptive vocalization, and combinations of antecedent control and DRO for reducing physical and verbal aggression and shower refusal, stereotypy, and other behaviors.  Affective Disorders The second most common cause of psychosis in the elderly, accounting for 20.4% of diagnoses in psychotic geriatric patients, is depression.[7] Although psychosis commonly accompanies bipolar illness, these patients are much less frequently encountered in a geriatric psychiatry clinic.[7] Therefore, clinicians should seriously consider depression when evaluating elderly patients with psychosis. There is clinical evidence of late-onset depression (age > 65 years) being a distinct subtype of depression. Specific findings indicate that patients with a late-onset first depressive episode are more often women and are clinically characterized by more severe depressions and a higher prevalence of psychosis than patients with early-onset depression.[34] In fact, delusions are
  5. 5. present in up to 40% of older patients hospitalized for depression.[35] Several studies have revealed mixed findings on differences in biologic markers between delusional and nondelusional depressed patients.[36-38] Simpson et al.,[39] however, found evidence of structural brain changes in psychotic depression with more brainstem and frontal temporal atrophy and marked enlargement of the third ventricles when compared with nonpsychotic depressed patients. Treatment of psychotic depression generally may include pharmacotherapy or electroconvulsive therapy. In a systematic review of pharmacologic treatment for unipolar psychotic depression, Wijkstra and colleagues[40] found no evidence that the combination of an antidepressant with an antipsychotic is more effective than an antidepressant alone. The combination, however, was statistically more effective than an antipsychotic alone. Thus, treatment of psychotic depression should include an antidepressant and possibly the addition of an antipsychotic if the patient does not respond. Some have argued that combined treatment of pharmacotherapy and psychotherapy would be more effective, but research did not support this.[41] In general, psychotic depression does not respond well to pharmacotherapy, and this may be particularly true in older patients.[42] By contrast, electroconvulsive therapy outcomes are as favorable[43] or perhaps even more favorable in the presence of delusions.[44]  Delirium The third most common cause of psychosis in the elderly, accounting for 12.2% of diagnoses in psychotic geriatric patients, is delirium.[7] The syndrome is characterized by a fluctuating disturbance of consciousness, attention, and cognition. It may also be accompanied by abnormalities in mood, perception, and behavior as well as sleep-wake cycle disturbances. The pathophysiology of delirium is not well understood. Certain neuroanatomical and neurotransmitter systems have been implicated, as well as particular brain regions.[45] One study using single photon emission computed tomography (SPECT) scans suggests that frontal or parietal cerebral perfusion abnormalities occur in delirium.[46] Haloperidol remains the standard of treatment for delirium, but there is increasing evidence for the use of atypical antipsychotics.[45,47] In an open label study, 24 delirious patients with a mean age of 76.5 years were successfully treated with quetiapine doses ranging from 25 to 125 mg/day (mean dose of 54.7 mg/day) and showed significant reductions in their delirium rating scale scores. [48]  Schizophrenia Schizophrenia in the elderly has been largely disregarded by researchers. Over 90% of published papers on schizophrenia have excluded elderly persons with the disorder.[49] Despite this, approximately 23.5% of patients with schizophrenia developed the illness after the age of 40.[50] These persons are considered to have late-onset schizophrenia. Roughly 4% of persons with schizophrenia have onset after the age of 60[51] and are considered to have very-late-onset schizophrenia. Persons who develop schizophrenia before age 45, and who age with it, represent about 85% of all persons with schizophrenia.[50] Overall community prevalence estimates for schizophrenia (both early and late onset) in individuals over the age of 65, however, ranges from only 0.1% to 0.5%.[51] Therefore, while schizophrenia represents a significant cause of psychosis in the elderly, it is not as common a cause of psychosis in the elderly as dementia, depression, and delirium. Later onset of schizophrenia seems to be more common in women.[52,53] In a survey of male and female patients with schizophrenia, onset after age 35 was reported in 17% of women and 2% of men.[54] This is supported in part by the biologic findings in late-onset schizophrenia. There is evidence of sex differences in brain volume loss and dopamine receptor numbers, possibly linked
  6. 6. to estrogen loss in women.[55,56] Other biologic findings associated with late-onset schizophrenia include significant third ventricle enlargement.[57] Elderly people with schizophrenia may also have more dopamine receptors than age-matched normal controls but fewer than younger patients.[58] While some believe that the emergence of schizophrenia spectrum disorders in mid to late life reflects a progressive neurodegenerative process, many studies support the view that late- onset and very-late-onset schizophrenia are static encephalopathies.[59] The clinical presentations of late-onset schizophrenia and early-onset schizophrenia patients are largely similar with some notable differences. Late-onset patients are more likely than their earlier-onset counterparts to have visual, tactile, and olfactory hallucinations; abusive or accusatory auditory hallucinations; a third-person running commentary; and persecutory delusions.[51] They are less likely to display a formal thought disorder or affective blunting.[60] For those patients with early-onset schizophrenia, there is a trend toward a reduction in positive symptoms and debated changes in negative symptom.[61] As previously mentioned, schizophrenia is uncommonly found even in geriatric psychiatry clinics. Only six out of 38 psychotic patients in one study[7] had diagnoses such as mania, schizoaffective disorder, schizophrenia, or delusional disorder. Therefore, clinicians should think of dementia, depression, and delirium as causes of psychosis in their elderly patients ahead of schizophrenia. Some clinical characteristics that distinguish schizophrenia from other forms of psychosis in the elderly include having typically complex, bizarre delusions and auditory hallucinations.[9] Additionally, suicidal ideations are common in patients with schizophrenia and rare in other disorders.[3] Although the majority of research on treatment with antipsychotics has focused on younger adults, there are a number of studies in older adults. Barak and colleagues[62] recently conducted a study in 21 elderly patients admitted to a psychogeriatric ward with acute psychosis related to schizophrenia or schizoaffective disorder. Patients were treated for 3 days with flexible-dose intramuscular ziprasidone injections for acute psychotic agitation. They found significant reduction in the brief psychiatric rating scale after 3 days of treatment (P = 0.001) as well as a significant decrease in the Behavioral Activity Rating Scale after each injection (P = 0.001). Overall they had only one serious adverse event in a patient with benign prostatic hypertrophy who developed urinary retention, and two side effects of mild severity that spontaneously resolved (blurred vision and sedation). They concluded that intramuscular ziprasidone had acceptable safety and efficacy in the management of acute psychotic agitation among elderly patients with schizophrenia.[62] Ritchie et al.[63] compared the efficacy and safety of olanzapine and risperidone in the treatment of elderly patients with schizophrenia. As part of a three and a half year study, they initially switched the treatment of 66 elderly patients with schizophrenia from typical antipsychotic medications to either olanzapine or risperidone.[64] Sixty-one patients from this study were followed further for 6 months to see whether either treatment was superior in terms of efficacy or safety. They found that both drugs were well tolerated and their use was associated with fewer symptoms of schizophrenia and fewer adverse events than were seen when the patients were taking a typical antipsychotic at baseline. Olanzapine seemed to be superior with regards to quality of life.[63] In a similar study, Barak and colleagues[65] examined whether elderly chronic schizophrenic patients would clinically improve if switched to olanzapine from previous typical neuroleptic treatment. The mean duration of treatment was 289 days and the mean dose of olanzapine was 12.9 mg. They found no significant change in body weight and patients had clinically meaningful change in positive and negative psychotic symptomatology. One monumental study, the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE), examined the relative effectiveness of antipsychotic drugs in patients with chronic schizophrenia. The researchers found that olanzapine was the most effective in terms of the rates of
  7. 7. discontinuation, and the efficacy of the conventional antipsychotic agent perphenazine appeared similar to that of quetiapine, risperidone, and ziprasidone.[66] Unfortunately, this study did not include individuals over the age of 65. An interesting new possibility for treatment of schizophrenia in older women was raised by a recent study examining the effect of HRT on cognitive function in women with chronic schizophrenia.[67] Ko and colleagues assessed the cognitive effects of adjuvant HRT when used to treat premenopausal women with chronic schizophrenia using an 8-week, double-blind, placebo- controlled randomized trial. They found significant improvements in the Scale for the Assessment of Negative Symptoms and in cognitive functioning in the HRT group compared with the placebo group. Although this research was done in premenopausal women, it raises the possibility of using HRT for older, postmenopausal women, especially in light of the biologic findings related to loss of estrogen in late-onset schizophrenia as previously discussed.  Special Treatment Considerations Treatment of psychosis in the elderly requires special attention to age-related issues including pharmacokinetic changes, comorbid illnesses and polypharmacy, and possible adverse effects of antipsychotic drugs. One commonly known adverse effect of the typical antipsychotics is extrapyramidal symptoms (or EPSs) which include Parkinsonism (bradykinesia, tremor, cogwheeling rigidity, masked facies), dystonia (muscle spasms that may be painful), and akathisia (feelings of inner tension and anxiety and a compulsive drive to move the body evidenced by pacing and restlessness). The elderly may be especially sensitive to this and all side effects. Although extrapyramidal symptoms are usually treated in adults with anticholinergic drugs such as diphenhydramine or benztropine, these drugs may cause cognitive impairment, worsening of constipation, and other problems in the elderly, so they must be used with caution. Of the atypical neuroleptics, risperidone is associated with the most extrapyramidal symptoms and clozapine is associated with the least.[68] Clinical impression among many providers is that quetiapine and olanzapine also have fairly low incidence of extrapyramidal symptoms. Another serious adverse effect of antipsychotic drugs is tardive dyskinesia. Tardive dyskinesia is a delayed onset movement disorder that continues even after the drug has been discontinued and is characterized by repetitive, purposeless, involuntary movements. The overall mean prevalence of tardive dyskinesia among chronically neuroleptic-treated patients is approximately 24%.[69] The annual incidence in younger adults is 4-5%. Aging, however, is a major risk factor for tardive dyskinesia. Research by Jeste and Caligiuri[69] suggests that the annual incidence in patients older than 45 years is over 30%. Others have found that elderly persons treated with conventional antipsychotics had four to five times the risk of developing tardive dyskinesia than the younger patients.[70] Other risk factors for the development of tardive dyskinesia include the use of anticholinergic medications for those over 40 years of age, long duration of neuroleptic exposure for those over 18 years of age, female sex, mood disorders, 'organic' brain dysfunction or damage, diabetes mellitus, and early extrapyramidal side effects.[69,71] Several studies have found a lower incidence of tardive dyskinesia associated with atypical versus typical antipsychotics.[72,73] A third major adverse effect of antipsychotic drugs is weight gain. In 2003, the US Food and Drug Administration (FDA) required all manufacturers of atypical antipsychotics to change their labeling to include a warning about the risks of hyperglycemia and diabetes with atypical antipsychotics. These findings are somewhat clouded by the fact that drug-naïve schizophrenics also appear to have an increased incidence of impaired glucose metabolism.[74] In 2006, Klein and colleagues[75] conducted a 16-week double-blind, placebo-controlled trial to evaluate the effectiveness of metformin in managing weight gain in 39 patients (ages 10-17) whose weight had increased by more than 10% in less than 1 year on an atypical antipsychotic. They demonstrated that weight in patients receiving metformin stabilized with no serious adverse events, while those receiving placebo continued to gain weight.
  8. 8. Finally, the most serious adverse event associated with the use of antipsychotic drugs is an increased risk of death. In April 2005, the US Food and Drug Administration requested that all manufacturers of atypical antipsychotic medications add a 'black box warning' to their prescribing information regarding the use of these medications in elderly patients with dementia- related psychosis because of an increased risk of death compared with placebo. According to the US Food and Drug Administration, an analysis of 17 placebo-controlled trials (modal duration of 10 weeks) in these patients revealed a risk of death in the drug-treated patients of between 1.6 and 1.7 times that seen in placebo-treated patients. The US Food and Drug Administration further stated that, over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared with 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. In 2005, Schneider and colleagues [76] performed a metaanalysis of 15 randomized, double-blind, placebo-controlled, parallel group trials of atypical antipsychotic use in elderly patients with dementia and found that death occurred more often in patients receiving atypical antipsychotic therapy than in those receiving placebo [118 (3.5%) versus 40 (2.3%), respectively]. This increased risk, however, was identified only when all drugs were pooled for analysis; metaanalyses of individual drugs did not show a statistically significant increased risk. Unfortunately, the US Food and Drug Administration warning described above did not address the increased risk of death associated with typical antipsychotic drug use in the elderly. Several studies have found that there is a significantly higher risk of death associated with the use of typical antipsychotic drugs than with atypical antipsychotic drugs in older patients.[77,78] SUMMARY Psychosis in the elderly occurs most commonly in relation to dementia, depression, or delirium, though schizophrenia and bipolar illness are also common causes. Conditions not discussed, but which may lead to psychosis, include various medical conditions such as Parkinson's disease. The clinical presentation of psychosis is often different in these conditions and appropriate diagnosis should direct treatment. Generally speaking, there is ample evidence of using antipsychotic drugs for all types of psychosis in the elderly. While the atypical antipsychotics now carry a 'black box warning' on risk of death in elderly patients with dementia, the typical antipsychotics are associated with an even higher risk of death, as well as other adverse effects. Weighing the potential risks and benefits of treatment options is essential. Although antipsychotic drugs are commonly used for different types of psychoses in the elderly, it should be noted that none of these drugs (nor any other psychotropic drugs) has been approved by the US Food and Drug Administration for use in any psychosis other than schizophrenia. Please refer to your country's regulatory approvals regarding the use of these antipsychotic drugs. References 1. Desai A, Grossberg G, Cohen CI, editors. Schizophrenia into later life: treatment, research, and policy. Washington, DC: American Psychiatric Publishing, Inc.; 2003. 2. Zayas E, Grossberg T. The treatment of psychosis in late life. J Clin Psychiatry 1998; 59 (Suppl 1):5-12. 3. Mintzer J, Targum S. Psychosis in elderly patients: classification and pharmacotherapy. J Geriatr Psychiatry Neurol 2003; 16:199-206. 4. Karim S, Burns A. The biology of psychosis in older people. J Geriatr Psychiatry Neurol
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  10. 10. 21. Sultzer D, Brown C, Manderlkern M, et al. Delusional thoughts and regional frontal/temporal cortex metabolism in Alzheimer's disease. Am J Psychiatry 2003; 160:341- 349. 22. Mega M, Lee L, Dinov I, et al. Cerebral correlates of psychotic symptoms in Alzheimer's disease. J Neurol Neurosurg Psychiatry 2000; 69:161-171. 23.  Mizrahi R, Starkstein S, Jorge R, et al. Phenomenology and clinical correlates of delusions  in Alzheimer's disease. Am J Geriatr Psychiatry 2006; 14:573-581. 24. Devanand D, Marder K, Michaels K, et al. A randomized, placebo-controlled dose- comparison trial of haloperidol for psychosis and disruptive behaviors in Alzheimer's disease. Am J Psychiatry 1998; 155:1512-1520. 25. Schneider L, Katz I, Park S, et al. Psychosis of Alzheimer's disease: validity of the construct and response to risperidone. Am J Geriatr Psychiatry 2003; 11:414-425. 26.  Tariot  P,  Schneider  L,  Katz  I,  et  al.  Quetiapine  treatment  of  psychosis  associated  with  dementia: a double-blind, randomized, placebo-controlled clinical trial. Am J Geriatr Psychiatry 2006; 14:767-776. 27. Ballard C, Margallo-Lana M, Juszczak E, et al. Quetiapine and rivastigmine and cognitive decline in Alzheimer's disease: randomized double blind plaebo controlled trial. BMJ 2005; 330:1-5. 28.  Schneider L, Tariot P, Dagerman M, et al. Effectiveness of atypical antipsychotic drugs in  patients with Alzheimer's disease. N Engl J Med 2006; 355:1525-1538. 29. Lövheim H, Sandman P, Kallin K, et al. Relationship between antipsychotic drug use and behavioral and psychological symptoms of dementia in old people with cognitive impairment living in geriatric care. Int Psychogeriatr 2006; 18:713-726. 30. Herrmann H, Lanctôt K. From transmitters to treatment: the pharmacotherapy of behavioral disturbances in dementia. Can J Psychiatry 1997; 42:51S-64S. 31. Pollock B, Mulsant B, Rosen J, et al. Comparison of citalopram, perphenazine, and placebo for the acute treatment of psychosis and behavioral disturbances in hospitalized, demented patients. Am J Psychiatry 2002; 159:460-465. 32. Lyketos C, DelCampo L, Steinberg M, et al. Treating depression in Alzheimer's disease: efficacy and safety of sertraline therapy, and the benefits of depression reduction: the DIADS. Arch Gen Psychiatry 2003; 60:737-746. 33.  Spira A, Edelstein B. Behavioral interventions for agitation in older adults with dementia:  an evaluative review. Int Psychogeriatr 2006; 18:195-225. This article is a wonderful review of the empiric literature on behavioral interventions to reduce agitation in older adults with dementia. 34. Kessing L. Differences in diagnostic subtypes among patients with late and early onset of a single depressive episode. Int J Geriatr Psychiatry 2006; 21:1127-1131. 35. Martinez R, Mulsant B, Meyers B, et al. Delusional depression in late life: a research agenda. Am J Geriatr Psychiatry 1996; 4:77-84.
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  12. 12. 53. Castle D, Murray R. The epidemiology of late-onset schizophrenia. Schizophr Bull 1993; 19:691-700. 54. Loranger A. Sex difference in age at onset of schizophrenia. Arch Gen Psychiatry 1984; 41:157-161. 55. Murphy D, DeCarli C, McIntosh A, et al. Sex differences in human brain morphometry and metabolism: an in-vivo quantitative magnetic resonance imaging and positron emission tomography study on the effect of aging. Arch Gen Psychiatry 1996; 53:585-594. 56. Pohjalainen T, Rinne J, Nagren K, et al. Sex differences in the striatal dopamine D2 receptor binding characteristics in vivo. Am J Psychiatry 1998; 155:768-773. 57. Pearlson G, Tune L, Wong D, et al. Quantitative D2 dopamine receptor PET and structural MRI changes in late onset schizophrenia. Schizophr Bull 1993; 19:783-795. 58. Wong D, Pearlson G, Tune L, et al. Quantification of neuroreceptors in the living human brain. IV: Effect of aging and elevations of D2 like receptors in schizophrenia and bipolar illnesses. Cereb Blood Flow Metab 1997; 17:331-342. 59. Palmer B, Bondi M, Twamley E, et al. Are late-onset schizophrenia spectrum disorders neurodegenerative conditions? Annual rates of change on two dementia measures. J Neuropsychiatry Clin Neurosci 2003; 15:45-52. 60. Pearlson G, Kreger L, Rabins P, et al. A chart review study of late-onset and early-onset schizophrenia. Am J Psychiatry 1989; 146:1568-1574. 61. Cohen C, Cohen G, Blank K, et al. Schizophrenia and older adults: an overview: directions for research and policy. Am J Geriatr Psychiatry 2000; 8:19-28. 62.  Barak Y, Mazeh D, Plopski I, et al. Intramuscular ziprasidone treatment of acute psychotic  agitation in elderly patients with schizophrenia. Am J Geriatr Psychiatry 2006; 14:629-633. 63. Ritchie C, Chiu E, Harrigan S, et al. A comparison of the efficacy and safety of olanzapine and risperidone in the treatment of elderly patients with schizophrenia: an open study of six months duration. Int J Geriatr Psychiatry 2006; 21:171-179. 64. Ritchie C, Chiu E, Harrigan S, et al. The impact upon extrapyramidal side effects, clinical symptoms and quality of life of a switch from conventional to atypical antipsychotics (risperidone or olanzapine) in elderly patients with schizophrenia. Int J Geriatr Psychiatry 2003; 18:432-440. 65. Barak Y, Shamir E, Mirecki I, et al. Switching elderly chronic patients to olanzapine. Int J Neuropsychopharmacol 2004; 7:165-169. 66. Lieberman J, Stroup T, McEvoy J, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005; 353:1209-1223. 67.  Ko Y, Joe S, Cho W, et al. Effect of hormone replacement therapy on cognitive function in  women with chronic schizophrenia. Int J Psychiatry Clin Pract 2006; 10:97-104. This intriguing paper evaluates a novel treatment for cognitive function in younger women. Given that late-onset schizophrenia occurs more often in women and is thought to be related to estrogen loss, this research will hopefully pave the way for a similar study in older
  13. 13. women. 68.  Weiden PJ. EPS profiles: the atypical antipsychotics are not all the same. J Psychiatr Pract  2007; 13:13-24. A nice review of the atypical antipsychotics and side effects. 69. Jeste D, Caligiuri M. Tardive dyskinesia. Schizophr Bull 1993; 19:303-315. 70. Kane J. Tardive dyskinesia in the elderly: data from a prospective study. Psychiatr Ann 2002; 32:233-236. 71. Wszola B, Newell K, Sprague R. Risk factors for tardive dyskinesia in a large population of youths and adults. Exp Clin Psychopharmacol 2001; 9:285-296. 72. Nasrallah H. Focus on lower risk of tardive dyskinesia with atypical antipsychotics. Ann Clin Psychiatry 2006; 18:57-62. 73. Correll C, Leucht S, Kane J. Lower risk for tardive dyskinesia associated with second- generation antipsychotics: a systemic review of 1-year studies. Am J Psychiatry 2004; 161:414-425. 74. Mackin P, Watkinson H, Young A. Prevalence of obesity, glucose homeostasis disorders and metabolic syndrome in psychiatric patients taking typical or atypical antipsychotic drugs: a cross-sectional study. Diabetologia 2005; 48:215-221. 75.  Klein  D,  Cottingham  E,  Sorter  M,  et  al.  A  randomized,  double-blind, placebo-controlled trial of metformin treatment of weight gain associated with initiation of atypical antipsychotic therapy in children and adolescents. Am J Psychiatry 2006; 163:2072-2079. 76. Schneider L, Dagerman K, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA 2005; 294:1934- 1943. 77. Wang P, Schneeweiss S, Avorn J, et al. Risk of death in elderly users of conventional vs. atypical antipsychotic medications. N Engl J Med 2005; 353:2335-2341. 78. Nasrallah H, White T, Nasrallah A. Lower mortality in geriatric patients receiving risperidone and olanzapine versus haloperidol: preliminary analysis of retrospective data. Am J Geriatr Psychiatry 2004; 12:437-439. The author: Professor Yasser Metwally Professor of neurology, Ain Shams university school of medicine,Cairo, Egypt To access all issues in quot;talking psychiatryquot; section of quot;http://yassermetwally.netquot; follow the link : or click on if it appears as a link in your PDF reader