Using aripiprazole to resolve antipsychotic-induced symptomatic hyperprolactinemia: a pilot study

OBJECTIVE: To assess the effectiveness of substituting aripiprazole for other antipsychotic drugs taken by stable schizophrenic patients suffering from antipsychotic agent-induced symptomatic hyperprolactinemia. METHODS: Seven female schizophrenic patients with symptomatic hyperprolactinemia (167.6+/-58.0 microg/L) were recruited to take part in an 8-week open label trial of aripiprazole (10-20 mg/day) as a replacement for amisulpride or risperidone. Efficacy was assessed via PANSS and CGI-I scores. Serum prolactin levels were measured at baseline, week 4, and week 8. Data were collected from November, 2004 to May, 2005. RESULTS: At the end of weeks 4, serum prolactin levels were normalized (8.8+/-5.5 microg/L) and hyperprolactinemic symptoms were resolved in all patients. However, aripiprazole treatment was discontinued within 6 weeks for 2 of the 7 subjects due to aggravated auditory hallucinations. CONCLUSION: Results from this admittedly small-scale open-label study indicate that switching to aripiprazole may be useful for resolving antipsychotic-induced hyperprolactinemia and associated symptoms.     

Oculogyric crises: Etiology,pathophysiology and therapeutic approaches

Oculogyric crisis (OGC) describes the clinical phenomenon of sustained dystonic, conjugate and typically upward deviation of the eyes lasting from seconds to hours. It was initially observed in patients with postencephalitic parkinsonism, but since then a number of conditions have been associated with OGC. These include drug-induced reactions, hereditary and sporadic movement disorders, and focal brain lesions. Here, we systematically review the literature and discuss the spectrum of disorders associated with OGC in order to aid clinicians place this rare but distinctive clinical sign into the appropriate diagnostic context. We also provide a brief synthesis of putative pathophysiological mechanisms, as well as therapeutic recommendations based on the literature and our own experience.     

Prospective study of hallucinations and delusions in Parkinson's disease

OBJECTIVE: This study was undertaken to determine the prevalence of hallucinations and delusions in Parkinson's disease, to describe such symptoms phenomenologically, and possibly to determine factors associated with their development. In addition, the role of the visual system in relation to visual hallucinations was examined. METHOD: 102 consecutive patients diagnosed with strictly defined Parkinson's disease were examined for the presence of hallucinations and delusions and assessed for visual acuity, cognition, depression using the geriatric depression scale, disease severity as measured by the UPDRS, and other clinical variables. RESULTS: Of 102 consecutive patients, 29.4% (n=30) had hallucinations or delusions, four (3.9%) were determined to be psychotic due solely to delirium and were excluded from further analysis. Of the 98 remaining patients, 26.5% (n=26) had visual hallucinations. Among these, one patient also had delusions, two had auditory hallucinations, and one had gustatory hallucinations. Visual hallucinations were significantly associated with worse visual acuity, lower cognitive score, higher depression score, and worse disease severity. Hallucinations were not associated with history of psychiatric disease, dose or duration of levodopa or other antiparkinsonian medication treatment, or duration of illness. CONCLUSIONS: Visual hallucinations are common symptoms in Parkinson's disease and are most likely of multifactorial origin. Although higher doses of levodopa are known to be related clinically to hallucinations in individual patients, the results suggest that several underlying characteristics of patients with Parkinson's disease (disease severity, dementia, depression, worse visual acuity) may be more important determinants of which patients experience hallucinations. The data also provide preliminary evidence that abnormality of the visual system may be related to visual hallucinations in Parkinson's disease, as has been found in other disorders with visual hallucinations.     

Cabergoline-induced psychotic exacerbation in schizophrenic patients

INTRODUCTION: Hyperprolactinemia is a well-recognized side effect of antipsychotic treatment. Cabergoline, a dopamine agonist, has been introduced on the market to treat hyperprolactinemia, even secondary to antipsychotic use. CASE REPORT: In this article, we described two schizophrenic patients who received cabergoline to treat their antipsychotic-induced hyperprolactinemia and developed a subsequent psychotic exacerbation. The first patient received amisulpride as antipsychotic medication, and the second one took risperidone and fluoxetine for her psychotic and depressive symptoms, respectively. Both patients improved significantly their psychotic symptoms in 1 week without changing their former antipsychotic regimens. DISCUSSION: To the best of our knowledge, we found no previous report of cabergoline-induced psychotic exacerbation in schizophrenic patients who received antipsychotics. We brought up questions whether schizophrenic patients on amisulpride or with the addition of fluoxetine may have higher risk to experience psychotic worsening. We also highlighted the possible role of dose-dependent nature in cabergoline-induced psychotic exacerbation, suggesting that the single starting dose of 0.5 mg or higher might be unsafe in schizophrenic patients. CONCLUSION: These cases suggest that cabergoline, like other dopaminergic agents, should be used with caution in psychotic patients and the dose should be as low as possible.     

Antipsychotic induced weight gain in schizophrenia:mechanisms and management

The aim of the present paper was to describe the mechanisms and management of antipsychotic-induced weight gain in schizophrenia patients. A comprehensive literature review of all available articles on the mechanisms and management of antipsychotic-induced weight gain was done by searching databases PsychINFO and PubMed. A summary of the available guidelines for monitoring of antipsychotic-induced weight gain and metabolic syndrome is also provided. There has been a substantial increase in the number of studies investigating the mechanisms and management of antipsychotic-induced weight gain after 2002. These include advances in the understanding of pharmacogenomics of weight gain and several randomized controlled trials (RCTs) evaluating pharmacological and psychological treatments to promote weight loss. The most effective strategy for prevention of weight gain is the choice of antipsychotic medication with low weight gain potential. In individuals with established weight gain and metabolic issues, switching to an antipsychotic agent with lower weight gain potential and/or lifestyle modifications with physical activity are most effective in promoting weight loss. Pharmacological agents such as orlistat and sibutramine are effective in general obesity but have not been sufficiently evaluated in antipsychotic-induced weight gain. The case to prescribe routine pharmacological treatment to promote weight loss is weak. Long-term, pragmatic studies are required to inform clinical practice. Weight gain in schizophrenia is associated with significant physical and psychological morbidity. Achieving an optimal trade-off between effectiveness and side-effects of antipsychotic agents, although difficult, is achievable. This should be based on three main principles: (i) a shared decision-making model between the patient, clinician and carer(s) when choosing an antipsychotic; (ii) a commitment to baseline and follow-up monitoring with explicit identification of the responsible individual or team; and (iii) the adoption of clear structured protocols for clinicians to follow in case of clinically significant weight gain and metabolic issues, which should incorporate greater collaboration between various health professionals from psychiatric and medical specialist services.     

Status Epilepticus Manifesting as Reversible Wernicke''s Aphasia

Ictal aphasia in adults is a rare phenomenon, with the majority of reported cases showing a nonfluent Broca's or mixed aphasic speech pattern associated with disturbances of level of consciousness. There is usually only one prolonged episode of aphasia with evidence of lateralized neurological findings and structural pathology on CAT scan. We describe a patient with intermittent episodes over a 10-year period of a fluent Wernicke's aphasia associated with paroxysmal posterior temporoparietal spike-wave activity on the EEG. Interictally, the patient was clear of neurologic signs and symptoms. These episodes were repeatedly misdiagnosed as psychotic breaks and treated with antipsychotic medication and psychiatric hospitalization. Unless language performance is assessed, these cases of focal epilepsy may be diagnosed as schizophrenic "word-salad," leading to delay of appropriate treatment.     

Prevalence of mental illness in a community nursing home

A research psychiatrist using a standardized interview found that 94% of a random sample of residents at a large, intermediate-care nursing home had mental disorders according to DSM-III criteria. Primary degenerative dementia and multi-infarct dementia were the most common diagnoses. In addition, the majority of demented patients also had noncognitive symptoms such as delusions and hallucinations, and these residents were significantly more likely to have an associated behavioral disorder than were residents without delusions or hallucinations. Replications of these results would point out the need for major revisions in the funding and delivery of psychiatric care for nursing home residents.     

Visual hallucinations in a case of reversible hypertension-induced brain oedema

Visual hallucinations are commonly associated with seizures drug effects psychiatric disorders or visual loss as 'release' phenomena. We report the case of a previously healthy 65-year-old woman who was admitted to hospital with intermittent headache episodes accompanied by complex visual hallucinations. During these episodes the patient's blood pressure was 220/120 mm Hg. In between symptomatic episodes she had no complaints and felt healthy. The neurological and ophthalmological examinations were normal but cerebral magnetic resonance imaging (MRI) showed multiple white matter abnormalities in the parieto-occipital regions. Rapid reversal of the symptoms and imaging abnormalities occurred concurrently with lowering of blood pressure. The history and the findings were similar to those recently described in the clinicoradiological 'posterior leukoencephalopathy' syndrome. Different pathogenic mechanisms are discussed.     

A comparative study of psychiatric symptoms in dementia with Lewy bodies and Parkinson's disease with and without dementia

OBJECTIVES: To compare the frequency and clinical correlates of neuropsychiatric symptoms in patients with Parkinson's disease (PD) with and without dementia and in those with dementia with Lewy bodies (DLB). METHODS: Neuropsychiatric symptoms during the month prior to assessment were assessed in clinically diagnosed PD patients with dementia (PDD; n = 48) and without dementia (PDND; n = 83) and in 98 DLB patients (33% autopsy confirmed) using standardized instruments. RESULTS: Delusions and hallucinations were significantly more common in DLB (57% and 76%) than PDD (29% and 54%) and PDND (7% and 14%) patients (p < 0.001). In all groups, auditory and visual hallucinations and paranoid and phantom boarder delusions were the most common psychotic symptoms. Frequency of major depression and less than major depression did not differ significantly between the three groups. Clinical correlates of hallucinations in PD were dementia (odds ratio (OR) = 3.9; 95% confidence interval (CI) 1.5-10.4) and Hoehn-Yahr stage 3 or more (OR 3.4; 95% CI 1.0-12.0), whereas no significant clinical correlates of hallucinations were found in DLB patients. CONCLUSIONS: Delusions and hallucinations occur with increasing frequency in PDND, PDD and DLB patients, but the presentation of these symptoms is similar. These findings support the hypothesis that psychiatric symptoms are associated with cortical Lewy bodies or cholinergic deficits in the two disorders.     

Psychosis and antipsychotic medications in Alzheimer's disease: clinical management and research perspectives

Psychosis is common in patients with Alzheimer's disease (AD) and contributes substantially to patient morbidity and caregiver distress. Antipsychotic medications are used to treat psychosis and other psychiatric or behavioral symptoms in AD, although optimal treatment guidelines have been elusive. Choosing the most advantageous medication for an individual patient is challenging. This article provides an overview of clinical management principles and medication treatment strategies for patients with AD and psychosis. Effects of individual medications are also described. Medications in the conventional neuroleptic, atypical antipsychotic, cholinesterase inhibitor, and serotonergic classes have been shown to ameliorate psychosis and behavioral symptoms in patients with AD, although the evidence is not conclusive for many medications. Side effects vary substantially across medication classes and modestly among individual patients. Improvement in agitation, aggression, or other behaviors with antipsychotic medication treatment may not depend on distinct antipsychotic effects. In contrast, there is preliminary evidence that delusions and hallucinations may respond to treatment with medications outside the antipsychotic class. Many important clinical questions warrant further research study. In particular, studies to compare how individual symptoms respond to different medications, and to examine how to best manage overlapping symptoms or incomplete treatment response are needed.     

Psychiatric Disorder in Two Siblings with Hallervorden-Spatz Disease

Hallervorden-Spatz disease (HSD) is a rare autosomal-recessive hereditary disorder characterized by the early onset of progressive movement alterations, including dystonia, rigidity, choreoathetosis, and mental deterioration. HSD is also associated with a variety of psychiatric symptoms, primarily depression and mental deterioration. However, psychosis has rarely been reported as a major symptom of HSD. We report two siblings who presented psychiatric symptoms as major clinical presentations, accompanied by ataxic and spastic gait, dysarthria, and typical neuroimaging findings of HSD. A 14-year-old girl presented complex motor tics, stereotypic behavior and anxiety symptoms. Her older brother, a 16-year-old boy, presented prominent auditory hallucinations, persecutory delusions and social withdrawal symptoms. Psychiatric symptoms were improved after atypical antipsychotic treatment. HSD is a rare disease but should be carefully considered in the diagnosis of patients with both motor disorder and various psychiatric symptoms.     

Caregiver report of hallucinations and paranoid delusions in elders aged 70 or older

This study examined the demographic, medical, and psychiatric correlates of hallucinations and paranoid delusions reported by proxy informants for 822 elders aged 70 or older. This sample comprised people who were deemed unable to complete a direct interview in a large nationwide study of aging. Marital status, trouble with vision, and cognitive impairment were associated with report of both paranoid delusions and hallucinations. Depressive symptoms and stroke were associated with hallucinations only. These results suggest that inadequate external stimulation in the elderly leads to psychotic experiences.     

Levodopa-induced psychosis: a kindling phenomenon

Of 88 patients with idiopathic Parkinson's disease, without prior psychotic symptoms, and without significant dementia, nearly half had experienced vivid dreams, hallucinations, illusions, and nonconfusional as well as confusional psychoses as side effects of chronic levodopa therapy within the previous year of treatment. It was found that 61.3% of all hallucinations were associated with preexistent or concurrent vivid dream phenomena, that all psychotic states were associated with preexistent or concurrent vivid dreams and/or hallucinations, and that nonconfusional psychotic states tended to become confusional. These findings raise the possibility that chronic levodopa therapy may result in dopaminergic kindling and support the hypothesis that chronic dopaminergic agonism may, via such a kindling mechanism, play a role in the development of some types of psychoses.     

Visual hallucinations in patients with macular degeneration.

OBJECTIVE: This study was undertaken to determine the prevalence of visual hallucinations in patients with macular degeneration, describe such hallucinations phenomenologically, and possibly determine factors predisposing to their development. METHOD: Using a case-control design, the authors screened 100 consecutive patients with age-related macular degeneration for visual hallucinations. Each patient with visual hallucinations was matched to the next three patients without hallucinations. The patients and comparison subjects were compared in terms of scores on the Beck Depression Inventory, Eysenck Personality Questionnaire, Telephone Interview for Cognitive Status, and a structured questionnaire including demographic characteristics, family history, and medical and psychiatric history. Ophthalmologic data were obtained by chart review. RESULTS: Of the 100 patients, 13 experienced visual hallucinations. Four variables were significantly associated with having hallucinations: living alone, lower cognition score, history of stroke, and bilaterally worse visual acuity. Hallucinations were not associated with family or personal history of psychiatric disorder or with personality traits. In 11 (84.6%) of the 13 patients, the hallucinations had begun in association with an acute change in vision. CONCLUSION: These results indicate that visual hallucinations are prevalent among patients with macular degeneration. They appear unrelated to primary psychiatric disorder. The predisposing factors of bilaterally worse vision and living alone support an association with sensory deprivation, while history of stroke and worse cognition support a decreased cortical inhibition theory.     

Stability of psychotic symptomatology (delusions,hallucinations), affective syndromes,and schizophrenic symptoms (thought disorder,incongruent affect) over episodes in remitting psychoses

Summary A study was made on 140 schizophrenics, 40 schizoaffectives, 59 unipolar depressives, and 30 bipolar affective disorder patients in order to determine the quality of psychopathology over multiple episodes. The schizoaffectives were the most likely to have multiple episodes. Among the schizophrenics, there were few episodes that lacked psychotic symptoms, but almost half of the episodes for the schizoaffectives were asscociated with an absence of psychotic symptoms. Three-quarters of the patients with unipolar depression and bipolar illness showed no psychotic symptoms either congruent or noncongruent. There was a striking finding that all diagnoses were associated with a decrease in psychotic symptoms over time. These psychotic symptoms (delusions and hallucinations) became particularly more scarce among the schizoaffectives, unipolars, and bipolars. There was a 50% to 67% decrease of episodes with psychotic symptoms as more episodes occurred. For schizophrenia and schizoaffective disorder the first ten episodes were very similar to each other for affective syndromes, formal thought disorder and/or incongruent affect, and delusions and hallucinations. It was not until much time had passed that the symptom pictures changed.     

Psychopathology and narcolepsy

Twenty-eight patients with narcolepsy are compared to a sex- and age-matched control population with regard to the frequency of psychiatric symptoms. The occurrence of psychiatric syndromes in narcolepsy patients is also examined. The frequency of psychiatric illness in patients with cataplexy or hypnagogic/hypnopompic hallucinations is evaluated as well. Analysis with the Mann-Whitney test found a significant association between narcolepsy and the symptoms of schizophrenia. Premorbid history of organic brain disease was associated with mental illness, but was nonspecific for psychopathology.     

Differentiating the effects of pharmacological and psychosocial interventions in an intensive rehabilitation programme

Background It is of clinical importance to identify the contribution of the individual components in a composite intervention, but this is difficult in practice. The aim of this study was to differentiate the effects of pharmacological and psychosocial interventions in improving the symptoms of patients with schizophrenia undergoing an intensive rehabilitation programme. Method The Krawiecka Goldberg Vaughn scale was used to record the symptoms of 19 long-stay inpatients in the rehabilitation programme. Ratings were made every 2 weeks for periods of between 1 year and 20 months. Results Analysis of the time course of symptoms showed that substitution of a single novel antipsychotic for conventional antipsychotic regimes was followed by a significant reduction in delusions but no improvement in hallucinations or negative symptoms. However, hallucinations and negative symptoms reduced significantly over the whole period of the observations, indicating an effect of the composite psychosocial interventions in the programme. Conclusions For patients with persistent psychotic symptoms, changing from conventional to novel antipsychotic medication is likely to reduce delusions, whereas hallucinations and negative symptoms may be more responsive to a combination of psychosocial interventions.     

Telemetered EEG in schizophrenia: spectral analysis during abnormal behaviour episodes.

In an attempt to detect electroencephalographic (EEG) changes associated with characteristic clinical signs and symptoms of schizophrenia, power spectra were derived from scalp EEGs of schizophrenic patients recorded by telemetry during free behaviour on their psychiatric wards. Power spectra from EEG epochs coincident with psychomotor blocking, stereotyped automatism or hallucinations were compared with spectra derived during periods of relatively normal behaviour, during performance of specific tasks and spectra from control subjects. Ramp spectra, characterised by a smooth decline in power from lowest to highest frequencies, previously found in conjunction with subcortical spike activity of epilepsy were not found in any control subject, but appeared in spectra from schizophrenic patients during catatonic episodes, hallucinatory periods and visual checking. Schizophrenic patients also had more slow activity and less alpha activity in their EEGs than normal control subjects.     

Quetiapine for hypnogogic musical release hallucinations

Musical release hallucinations are complex auditory phenomena, affecting mostly the deaf geriatric population, in which individuals hear vocal or instrumental music. Progressive hearing loss from otosclerosis disrupts the usual external sensory stimuli necessary to inhibit the emergence of memory traces within the brain, thereby "releasing" previously recorded perceptions. Responses to conventional antipsychotic agents have been variable and extrapyramidal and other side effects have limited their use. We report the first case of hypnogogic release hallucinations successfully treated with the atypical antipsychotic quetiapine. The patient is an 88-year-old woman with progressive deafness who complained of hearing the piano, drums, or a full orchestra every time she was about to fall asleep. She accused her neighbor of hosting loud parties. Physical, neurologic, and psychiatric examination and work-up were unremarkable. She was treated with low-dose quetiapine affording near total resolution of hallucinations without adverse effects.     

Charles Bonnet syndrome: visual hallucination and multiple sclerosis

Multiple sclerosis (MS) is a fairly common condition that affects approximately 350,000 people in the United States. It is associated with various neuropsychiatric symptoms including cognitive and behavioral symptoms. However, visual hallucinations are rare in multiple sclerosis without the presence of cognitive deficits. We are describing the case of a 40-year-old married white female with isolated complex visual hallucinations compatible with the Charles Bonnet syndrome (CBS). The patient was successfully treated with the atypical antipsychotic olanzapine.