Prevalence and clinical correlates of psychotic symptoms in Alzheimer's disease

Psychotic symptoms occur commonly in Alzheimer's disease (AD), predict a more rapid rate of cognitive decline and increase the risk of aggressive behaviour. Seventy patients with probable AD, recruited from an old age psychiatry service, were assessed to determine the prevalence and clinical correlates of delusions and hallucinations. Psychiatric symptoms were measured using the Behavioural Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD), Hamilton Rating Scale for Depression (HRSD) and the Depressive Signs Scale (DSS). Thirty-four per cent of the sample experienced delusions and 11% hallucinations in the previous month. Men were more likely than women to have experienced psychotic symptoms. Psychotic and non-psychotic groups did not differ in age, age at illness onset, dementia severity, HRSD or DSS scores. This study confirms the high prevalence of psychotic symptoms in AD patients encountered in clinical practice, and suggests that psychosis and depression represent independent behavioural disturbances in AD. © 1998 John Wiley & Sons, Ltd.     

Arrest among psychotic inpatients: assessing the relationship to diagnosis, gender, number of admissions, and social class

The present study of psychotic patients investigates the relationship of specific psychotic diagnoses (i.e., psychoactive-substance-induced psychosis, schizophrenia, bipolar disorder, other DSM-III Axis I psychotic disorders), social class, gender, and number of admissions to the rate of arrest in the community. All admissions with psychotic symptoms to hospitals providing inpatient psychiatric services in the Baltimore area were surveyed during a 6-year period. Study participants were assessed using a modified version of the Diagnostic Interview Schedule. During the course of the interview, patients were asked whether they had ever been arrested as a juvenile or as an adult. After adjusting for age, gender, number of admissions, and social class, we found that patients admitted for psychoactive-substance-induced psychosis were more likely to report having been arrested than patients with other psychotic diagnoses. Patients with schizophrenia were not more likely to have an history of arrest than patients with other psychotic disorders. Number of admissions and social class were independent predictors of history of arrest. The relationship between psychotic diagnosis and history of arrest was modified by gender. Psychotic patients with substance-induced diagnosis who were male were more likely to report a prior arrest in the community than their female counterparts. Our results suggest that type of psychotic diagnosis and social class, in addition to gender and number of admissions, are important predictors of differences in arrest-rate histories among psychotic patients. Gender appears to be an effect modifier of the relationship between psychotic diagnosis and history of arrest. Accepted: 12 December 1997     

Psychotic features and illness severity in combat veterans with chronic posttraumatic stress disorder.

BACKGROUND: Psychotic symptoms may be present in up to 40% of patients with combat-related posttraumatic stress disorder (PTSD). In this study, we hypothesized that severity of psychotic symptoms would also reflect severity of PTSD symptoms in patients with well-defined psychotic features. METHODS: Forty-five Vietnam combat veterans with PTSD but without a primary psychotic disorder diagnosis underwent a Structured Clinical Interview for DSM-III-R with Psychotic Screen, and the Clinician Administered PTSD Scale (CAPS). Patients identified as having psychotic features (PTSD-P), (n = 22) also received the Positive and Negative Syndrome Scale (PANSS) and the Hamilton Depression Rating Scale (HDRS). RESULTS: There was a significant positive correlation between the CAPS and PANSS global ratings (p < .001) and the HDRS and PANSS (p < .03) in the PTSD-P patients. Many CAPS and PANSS subscales also demonstrated significant intercorrelations; however, the CAPS-B subscale (reexperiencing) and the PANSS positive symptom scale were not correlated, suggesting that psychotic features may not necessarily be influenced or accounted for by more severe reexperiencing symptoms. Fifteen (68%) of the PTSD-P patients had major depression (MDD). Both CAPS and PANSS ratings were significantly higher in the PTSD-P patients with comorbid MDD. CONCLUSIONS: As postulated, patients with more severe psychosis ratings are likely to have more severe PTSD disease burden if psychotic features are present. This study further documents the occurrence of psychotic features in PTSD that are not necessarily due to a primary psychotic disorder, suggesting that this may be a distinct subtype; however, a significant interaction likely exists between PTSD, depression, and psychotic features.     

Familial aggregation of psychotic symptoms in Huntington's disease

OBJECTIVE: The mutation responsible for Huntington's disease is an elongated and unstable trinucleotide (CAG) repeat on the short arm of chromosome 4. Psychotic symptoms are more common in patients with Huntington's disease than in the general population. This study explored the relationship of psychosis in Huntington's disease patients with the number of CAG repeats and family history of psychosis. METHOD: Forty-four patients with Huntington's disease, 22 with and 22 without psychotic symptoms, were recruited from two university-affiliated medical genetics clinics in Seattle and Vancouver, B.C. Psychiatric assessments of the subjects were made through chart review, and diagnoses were validated by structured interviews in a subset of patients. The demographic and clinical characteristics of the psychotic and nonpsychotic patients were compared. RESULTS: The two groups did not differ in demographic and clinical characteristics, except that subjects with psychosis were significantly more likely than nonpsychotic subjects to have a first-degree relative with psychosis. In eight of nine families in which Huntington's disease probands with psychosis had a first-degree relative with psychosis, the relative's psychosis co-occurred with Huntington's disease. In the Huntington's disease probands with psychosis, the onset of psychosis correlated with the onset of the neurological symptoms of Huntington's disease, and the age at onset of psychosis was lower in probands with a higher number of CAG repeats. CONCLUSIONS: Patients with Huntington's disease and psychotic symptoms may have a familial predisposition to develop psychosis. This finding suggests that other genetic factors may influence susceptibility to a particular phenotype precipitated by CAG expansion in the Huntington's disease gene.     

Psychotic depression: advances in conceptualization and treatment.

Psychotic depression is a unique subtype of depressive illness in which mood disturbance is accompanied by delusions, hallucinations, or both. Once considered relatively uncommon, it is frequently encountered in clinical practice, particularly in treatment-resistant depressed patients. Psychotically depressed patients respond poorly to antidepressants, but remission is likely with neuroleptic-antidepressant combinations or electroconvulsive therapy. Psychotic depression may be unipolar or bipolar with early or late onset and may be more likely to occur in patients with a history of childhood psychic trauma. Much is known about the course and treatment response of obvious presentations of psychotic depression, but more must be learned about depressed patients who have intermittent, subtle, or mild psychotic symptoms and about the ways in which the capacity to become psychotic interacts with the capacity to become depressed to produce a syndrome greater than the sum of its parts.     

Psychotic symptoms in Parkinson’s disease

Psychotic symptoms are common in Parkinson’s disease (PD) and occur in at least 20% of medication-treated patients. Benign visual hallucinations usually appear earlier, while malignant hallucinations, confusional states, delusions, paranoid beliefs, agitation, and delirium become more frequent with disease progression. Virtually all antiparkinsonian drugs may produce psychotic symptoms. Cognitive impairment, increased age, disease duration and severity, depression, and sleep disorders have been consistently identified as independent risk factors for their development. Although the precise pathoetiologic mechanisms remain unknown, we review evidence that links ventral dopaminergic pathway dysfunction (overactivity) together with the involvement of other neurotransmitter system imbalances as likely contributors. The clinical importance of the proposed mechanism is that successful management of psychotic symptoms in PD may rely on a multitarget approach to restore neurotransmitter imbalances rather than focusing exclusively on the dopaminergic dysfunction.     

Diagnosing psychotic disorders in the emergency department in the context of substance use

OBJECTIVE: For patients who are actively using a substance and experience psychotic symptoms, determining whether the psychotic symptoms are due to a primary psychotic disorder or are substance induced is challenging, especially in emergency departments, where historical information is limited. This study examined the accuracy and subsequent treatment implications of emergency department diagnoses among substance-using patients who were having their first psychotic episode. METHODS: Emergency department diagnoses for 302 patients were compared with best-estimate longitudinal diagnoses (BELDs) based on research assessments at three time points (baseline, six months, and 12 months). RESULTS: Of the 223 patients whose symptoms were diagnosed in the emergency department as a primary psychotic disorder, one-quarter were determined by the BELD to have substance-induced psychosis or no psychosis. Overall, the diagnostic agreement was only fair (kappa=.32). Patients with an emergency department diagnosis of primary psychosis were significantly more likely than those with an emergency department diagnosis of substance-induced psychosis to be hospitalized, started on antipsychotic medication, and referred to mental health services instead of treatment for substance use (p<.001). Patients given an emergency department diagnosis of primary psychosis who were found by the BELD to have substance-induced psychosis or no psychosis were significantly more likely to be treated for a psychotic disorder rather than for substance-induced psychosis (p<.001) CONCLUSIONS: Clinicians in psychiatric emergency departments appear to have a tendency to attribute psychotic symptoms to a primary psychotic disorder rather than to concurrent substance use. Given that the diagnosis has significant implications for future management, it is important to improve diagnostic approaches in the emergency department.     

Psychosis in a pediatric mood and anxiety disorders clinic: phenomenology and correlates

OBJECTIVES: To examine the demographics and phenomenology of psychosis in a sample of children and adolescents referred to a mood and anxiety disorders clinic. METHOD: Patients (N = 2,031) were assessed with the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present Episode version and classified as definite, probable, or nonpsychotic. Clinical and demographic characteristics of the groups were compared,and symptoms of psychosis were analyzed using factor analysis. RESULTS: Definite psychotic symptoms were seen in approximately 90 (4.5%) patients: 80% of these reported hallucinations (mainly auditory), 22% delusions, and 3.3% thought disorder. Of the patients with definite psychotic symptoms, 24% had bipolar disorder, 41% had major depression, 21% had subsyndromal depression, and 14% had schizophrenia spectrum disorders (schizophrenia and schizoaffective disorders). Factor analysis of the definite psychotic symptoms yielded 4 factors: hallucinations, thought disorder, delusions, and manic thought disorder. Psychotic patients had a higher frequency of comorbid disorders and suicidal ideation than nonpsychotic patients. CONCLUSIONS: Outpatient youngsters with mood disorders frequently present with psychotic symptoms, in particular auditory hallucinations. These patients commonly have comorbid psychiatric disorders and suicidal ideation.     

The biology of psychosis in older people

The nosology, classification, and biological basis of psychosis in the elderly have been much debated. Psychotic features are seen in schizophrenia, affective illness, and dementia in the elderly. This article reviews evidence for the biological basis of psychosis in older people. In schizophrenia, there is evidence of gender differences in brain volume loss and dopamine receptor numbers, possibly linked to estrogen loss in women. Neuroimaging evidence of ventricular brain changes and more dopamine receptors have also been documented. In Alzheimer's disease, genetic factors such as PS1 and ApoE4 have been associated with psychotic symptoms, and histopathological studies have revealed differences in neuronal pathology. Radiological studies have shown right and left hemisphere differences in size, blood flow, and glucose metabolism between psychotic and nonpsychotic patients. In affective illnesses, there is evidence of structural brain changes in psychotic depression. Ample evidence suggests that biological substrates underlie many psychotic symptoms. More research will identify causal links between brain changes, symptom appearance, and the effects of psychosocial factors in their genesis.     

Psychotic late-life depression: a 376-case study.

The aim of the report was to study clinical differences between psychotic late-life depression and psychotic depression in younger patients, to determine if differences were age-related or specific for psychotic late-life depression. Three hundred seventy-six consecutive outpatients, presenting for treatment of unipolar or bipolar depression (with or without psychotic features), were assessed by means of the Structured Clinical Interview for DSM-IV, the Montgomery and Asberg Depression Rating Scale, and the Global Assessment of Functioning Scale. Results showed that psychotic late-life (50 years or more) depression, versus psychotic depression in younger patients, was associated with significantly higher age at study entry/onset, longer duration, and lower comorbidity. Psychotic depression versus nonpsychotic late-life depression, in late-life and in younger patients, was associated with significantly greater severity, lower comorbidity, more patients with bipolar I disorder, and fewer patients with unipolar disorder. Findings were related to psychosis or to age, and not to specific features of psychotic late-life depression. These results support a unitary view of psychotic depression.     

Psychotic symptoms in combat-related posttraumatic stress disorder

BACKGROUND: Posttraumatic stress disorder (PTSD) is known often to be comorbid with other anxiety, mood, and substance use disorders. Psychotic symptoms have also been noted in PTSD and have been reported to be more common in Hispanic veterans. However, the occurrence of psychotic symptoms, including the degree to which they are accounted for by comorbid disorders, have received limited systematic investigation. Our study objectives were to assess psychotic symptoms according to DSM-III-R criteria in patients with a primary diagnosis of combat-related PTSD and determine the associations of those symptoms with psychiatric comorbidity and ethnicity. METHOD: Fifty-three male combat veterans consecutively admitted to a PTSD rehabilitation unit were assessed for psychotic symptoms and Axis I disorders. Ninety-one percent were Vietnam veterans; 72% were white, 17% were Hispanic, and 11% were black. Associations between psychotic symptoms and comorbid depression, substance use disorders, and minority status were compared by chi-square analyses; associations between psychotic symptoms and both PTSD and dissociative symptom severity were compared by t test analysis. RESULTS: Forty percent of patients reported a psychotic symptom or symptoms in the preceding 6 months. These symptoms featured auditory hallucinations in all but 1 case. The psychotic symptoms typically reflected combat-themes and guilt, were nonbizarre, and were not usually associated with formal thought disorder or flat or inappropriate affect. Psychotic symptoms were significantly associated with current major depression (p < .02), but not with alcohol or drug abuse or with self-rated PTSD and dissociation severity. Psychotic symptoms and current major depression were more common in minority (black and Hispanic) than white veterans (p < .002). CONCLUSION: Psychotic symptoms can be a feature of combat-related PTSD and appear to be associated with major depression. The association with minority status may be a function of comorbidity.     

Antidepressants in the treatment of psychosis with comorbid depression in Parkinson disease

Psychotic symptoms are commonly associated with Parkinson disease and can be a source of significant morbidity. Depression has been reported as a comorbidity in patients with psychosis. We describe a patient with Parkinson disease with psychotic symptoms and comorbid depression whose treatment refractory delusions and hallucinations improved markedly only after antidepressant monotherapy was initiated. The phenomenology of the delusions was atypical for those found in Parkinson or in depression. Psychotic symptoms refractory or only partially responsive to conventional treatment should prompt a search for potential underlying psychiatric comorbidities. Given case reports of exacerbation of psychotic symptoms with antidepressants, we emphasize careful identification and active follow up of the comorbid depressive disorders in PD patients with psychosis. Potential mechanisms implicated in the response of psychosis to antidepressants are discussed.     

Epidemiology of and risk factors for psychosis of Alzheimer's disease: a review of 55 studies published from 1990 to 2003

OBJECTIVE: The authors reviewed studies published between 1990 and 2003 that reported the prevalence, incidence, and persistence of, as well as the risk factors associated with, psychosis of Alzheimer's disease. METHOD: PubMed and PsycINFO databases were searched by using the terms "psychosis and Alzheimer disease" and "psychosis and dementia." Empirical investigations presenting quantitative data on the epidemiology of and/or risk factors for psychotic symptoms in Alzheimer's disease were included in the review. A total of 55 studies, including a total of 9,749 subjects, met the inclusion criteria. RESULTS: Psychosis was reported in 41% of patients with Alzheimer's disease, including delusions in 36% and hallucinations in 18%. The incidence of psychosis increased progressively over the first 3 years of observation, after which the incidence seemed to plateau. Psychotic symptoms tended to last for several months but became less prominent after 1 year. African American or black ethnicity and more severe cognitive impairment were associated with a higher rate of psychosis. Psychosis was also associated with more rapid cognitive decline. Some studies found a significant association between psychosis and age, age at onset of Alzheimer's disease, and illness duration. Gender, education, and family history of dementia or psychiatric illness showed weak or inconsistent relationships with psychosis. CONCLUSIONS: Psychotic symptoms are common and persistent in patients with Alzheimer's disease. Improved methods have advanced the understanding of psychosis in Alzheimer's disease, although continued research, particularly longitudinal studies, may unveil biological and clinical associations that will inform treatments for these problematic psychological disturbances.     

Mirtazapine improves visual hallucinations in Parkinson's disease: a case report

Psychotic symptoms often occur as a complication in Parkinson's disease patients, and a set of criteria for Parkinson's disease with psychosis (PDPsy) has been established. Among these criteria, hallucinations are one of the specific symptoms, with visual hallucinations being the most common. While atypical antipsychotic agents are often used for the treatment of PDPsy, adverse effects, including extrapyramidal symptoms, often hinder its continuation or tolerance. There have been some reports and reviews indicating that antidepressants may be effective for PDPsy and other forms of dementia with psychosis. In this report, we present a patient with PDPsy who was treated with one of the new‐generation antidepressants, mirtazapine. Mirtazapine improved the patient's refractory psychotic symptoms, especially her visual hallucinations, without worsening her motor symptoms.     

Treating Psychotic Symptoms in Elderly Patients

Research has shown that elderly patients are especially at risk for the development of psychotic symptoms. A combination of factors contributes to the increased risk for psychosis in this patient population. Various DSM-IV diagnostic categories including delirium, schizophrenia, delusional disorder, mood disorders, dementia, substance abuse, and medical-neurologic conditions can be associated with psychotic symptoms. In general, medications are prescribed for specific target symptoms, started at low doses, and titrated gradually. Although buspirone, trazodone, valproic acid, and carbamazepine have been used with some success, antipsychotic medications have been the primary treatment of psychosis in the elderly. Because the atypical antipsychotics offer effective management of psychotic symptoms combined with low liability of extrapyramidal symptoms, these agents may be the current treatment of choice for psychotic symptoms in the elderly when used cautiously.     

Demographic, historical, and symptomatic features of the nonmanic psychoses

Consecutively admitted patients with nonmanic psychosis were more likely to meet Research Diagnostic Criteria (RDC) for schizoaffective disorder, depressed type (N = 47), than for psychotic major depression (N = 29) or schizophrenia (N = 21). Although the RDC duration requirements for these three disorders are quite similar, schizophrenics had already experienced much more chronicity as reflected in episode duration, psychosocial impairment during the preceding 5 years, marital status, and low likelihood of prior remission. Schizoaffective patients took intermediate positions in these measures in accord with the majority of follow-up studies comparing these disorders. Although the RDC specify the same array of psychotic symptoms for schizoaffectives and for schizophrenics, these symptoms were significantly more prominent among the schizophrenics. Conversely, although this system also specifies the same list of depressive symptoms for major depression and schizoaffective depression, symptoms of endogenous depression were significantly more prominent in the major depression group. Thus, among functionally psychotic patients, those with schizophrenia-like symptoms have milder and less typical depressive symptoms whereas those with depressive syndromes have fewer and milder schizophrenia-like symptoms.     

Parkinson’s disease psychosis 2010: A review article

Psychotic symptoms are common in Parkinson’s disease (PD), generally associated with the medications used to treat the motor symptoms. On rare occasion they occur in patients not taking medication for PD. Psychotic symptoms are usually hallucinations, typically visual, less commonly auditory, and rarely in other domains. Hallucinations are generally stereotyped and without emotional content. Initially patients usually have insight so that the hallucinations are benign in terms of their immediate impact but have poor prognostic implications, with increased risk of dementia, worsened psychotic symptoms and mortality. Delusions occur in about 5–10% of drug treated patients and are considerably more disruptive, being paranoid in nature, often of spousal infidelity or abandonment by family. Treatment of Parkinson’s disease psychosis (PDP) focuses on reducing the psychiatric symptom load while balancing the competing problem of mobility. Contributors to the psychotic symptoms should be searched for, such as systemic illness and other psycho-active medications. If none are identified or can be eliminated then the PD medications should be reduced to the lowest levels that allow tolerable motor function. Once this level has been reached there are two schools of thought on treatment, using either acetylcholinesterase inhibitors or atypical anti-psychotics. Only clozapine has level I evidence to support its use. Quetiapine is the only other anti-psychotic free of motor side effects, but it has failed double blind placebo controlled trials to demonstrate efficacy.     

The epidemiology of psychosis: the Suffolk County Mental Health Project.

This article describes the rationale, aims, and methodology of an epidemiological study of psychosis being conducted in Suffolk County, New York. A sample of first-admission patients is drawn from 10 inpatient and 25 outpatient facilities. Diagnostic psychosocial interviews are conducted shortly after admission to treatment, and at 6- and 24-month followup. Consensus diagnoses are made after each interview. Demographic and clinical background characteristics of the first 250 subjects enrolled over a 2-year period are presented here. The response rate was 76 percent. Based on the initial interview, 75 percent of subjects received a diagnosis involving psychosis. The three most common diagnoses were schizophrenia, bipolar disorder with psychotic features, and major depression with psychotic features. Among subjects with psychosis, 58 percent of males and 29 percent of females had a history of substance abuse/dependence. Gender differences were found on several background and clinical characteristics. Males were somewhat younger, less likely to have ever married, and had less education. Although the median length of hospitalization was the same for females and males (27 days), females were more likely to be hospitalized within 1 month of the occurrence of their first psychotic symptom (60% of females compared to 37% of males). Subjects with schizophrenia-related disorders were significantly more impaired on an assessment of negative symptoms than were affectively ill subjects, but clinical ratings of depression were not significantly different across diagnostic groups.     

Psychosis in geropsychiatric inpatients with and without dementia

Psychotic symptoms are commonly encountered in elderly patients both with and without dementia. The authors compared presentation and treatment response between these two groups. Of 206 consecutive admissions to an inpatient geropsychiatry unit, 52 (26%) had psychotic symptoms. Thirteen of these had dementia and 22 had a primary Axis I psychotic disorder without dementia. Both groups presented similarly, improved significantly from admission to discharge and demonstrated equivalent medication side-effect profiles. Elderly psychotic patients with and without dementia improve significantly on antipsychotics and tolerate their side-effects; however, those with dementia receive lower dosages of medication to treat their symptoms.     

Six-year outcomes in first admission adolescent inpatients: clinical and cognitive characteristics at admission as predictors

Persistent functional disability is common after even a single psychiatric admission in people with schizophrenia or bipolar disorder, but less is known about other conditions and about adolescent onset patients. This study examined clinical symptoms and cognitive performance at the time of the first admission for the prediction of 6-year outcomes. First admission adolescent patients with a variety of psychiatric diagnoses were assessed with comprehensive clinical ratings of psychopathology, a neuropsychological assessment, and received clinical diagnoses while experiencing their first psychiatric admission. They were contacted 6 years after discharge and examined with a structured assessment of psychiatric symptoms and functioning. Despite the low levels of overall impairment at follow-up, at least 20% of the variance in depression, psychosis, poor peer relationships and poor school attendance 6 years after the hospital admission were predicted by information collected during the hospitalization. Attentional deficits during admission predicted the presence of psychosis at follow-up more substantially than psychotic symptoms during admission, as well as predicting risk for relapse. Attentional deficits during a first psychiatric admission predicted risk for manifesting psychosis at 6-year follow-up to a more substantial degree than either a psychosis diagnosis or psychotic symptoms at admission. In contrast to psychosis, depression at follow-up was predicted by admission symptomatology, but not by cognitive deficits.