Number Of Schizophrenic Patients Research Articles

Effectiveness of aripiprazole in a patient with presumed idiopathic Parkinson's disease and chronic paranoid schizophrenia

SEVERAL CASES OF the coexistence of schizophrenia and idiopathic Parkinson's disease (IPD) have been reported and the management of concurrent psychosis and parkinsonism has been considered as quite difficult as even atypical antipsychotics may worsen parkinsonism; conversely L-dopa may worsen psychosis.1, 2 To my knowledge, this is the first case report of successful treatment with aripiprazole in a schizophrenic patient with comorbid IPD. A 71-year-old woman with chronic schizophrenia was admitted to our department. She was diagnosed with schizophrenia at age 28. She had auditory hallucinations with voices conversing with each other and persecutory delusions but did not have mood symptoms. After brief admission at age 48, her condition was stable on thioridazine 40 mg/day and sulpiride 200 mg/day. However, at age 61, she noted the resting tremor of her left arm. She discontinued all antipsychotics for several years. But, thereafter, she experienced resting tremor of the right extremities, rigidity and postural instability. At age 69, she was diagnosed as having IPD and L-dopa/carbidopa was commenced. The treatment improved parkinsonism but exacerbated her psychosis. In addition she complained of various side-effects such as nausea and consequently discontinued it after 3 months. On admission, she had no obvious cognitive deficits (the Mini-Mental State Examination = 28/30). The results of laboratory tests and the findings of cranial magnetic resonance were normal. In 123I-metaiodobenzylguanidine myocardial scintigraphy, the average count per pixel in heart to mediastinum (H/M) ratio was decreased [H/M (early) = 1.854, H/M (late) = 1.350]. Her score on the Brief Psychiatric Rating Scale (BPRS) was 79, her stage on the Hoehn–Yahr scale was IV, and her activities-of-daily-living (ADL) rating on the Barthel index was 35. However, after she started taking aripiprazole 6 mg/day, we sometimes saw her walking by herself. Therefore, we gradually increased aripiprazole over 4 weeks to 18 mg/day. Then, her psychosis gradually improved and she wanted to be more mobile. She underwent physical therapy with successful discharge after 3 months. Her psychotic symptoms, motor function and ADL all improved without antiparkinsonian medications (BPRS = 37, Hoehn–Yahr stage = III, Barthel index = 65). She continues to do well on aripiprazole 6 months post-discharge. The number of schizophrenic patients with comorbid IPD will increase in aging patients with schizophrenia. This case suggests that aripiprazole may be useful in treating such patients (especially when L-dopa cannot be administered due to its side-effects) because aripiprazole, a dopamine D2 partial agonist, theoretically may improve hypodopaminergic activity in the nigrostriatal pathway in patients with IPD. In addition, the present patient was able to undergo physical therapy safely because aripiprazole rarely induces sedation and orthostatic hypotension due to extremely weak antagonism at α1 and H1 receptors. However, several case reports of aripiprazole in patients with psychosis associated with IPD indicate that aripiprazole worsens motor function,3, 4 partly because aripiprazole appears to bind to D2 receptors by competing with dopamine replenished by L-dopa because the binding affinity to dopamine D2 receptors of aripiprazole is higher than that of dopamine.5 It is necessary to note this when administering aripiprazole with L-dopa.

Cebus apella, a nonhuman primate highly susceptible to neuroleptic side effects, carries the GLY9 dopamine receptor D3 associated with tardive dyskinesia in humans.

Tardive dyskinesia (TD) is a severe side effect of traditional neuroleptics affecting a considerable number of schizophrenic patients. Accumulating evidence suggests the existence of a genetic disposition to TD and other extra pyramidal symptoms (EPS) most strongly linked to a ser/gly polymorphism in position 9 of the D3 dopamine receptor gene (DRD3). The Cebus apella monkey is the favored animal model to study TD and other EPS because of its high susceptibility to side effects of neuroleptics. We therefore determined the sequence of the DRD3 gene in this species and compared it with that of humans. We found that the highly TD susceptible C. apella monkey (n=21) carries the gly9/gly9 DRD3 genotype that has been associated with TD in humans. Contrarily, C. apella did not carry the ser23 5HT2C allele that has been reported to increase TD susceptibility in humans.

Trends in Danish research on crime and mental health (1970–94): A review

This is a review of the last 25 years' research on forensic psychiatry in Denmark. Thirty studies are reviewed. The studies are categorized on the basis of the types of population they investigate: 1) the background population; 2) criminals; 3) psychiatric patients; 4) forensic patients; and 5) others. The main results are 1) the number of schizophrenic patients under psychiatric treatment orders has increased dramatically; 2) criminal recidivism is common among forensic patients, 3) more than 50% of the forensic patients have a dual diagnosis (substance abuse and psychosis); and 4) the number of homicides committed by schizophrenics has increased. It is concluded that research on forensic psychiatry is a prerequisite for explaining the etiology of the changes in numbers and types of patients and for evaluating and improving forensic examination and treatment.Denmark, Forensic psychiatry, Mentally ill offenders, Review article.

Combined electroconvulsive therapy and clozapine in schizophrenia

Although clozapine is effective in treating about one third to one half of schizophrenic patients refractory t0 conventional antipsychotie agents, there is still a substantial number of schizophrenic patients who do not respond adequately to clozapine. Treatment options for such patients currently are limited; supplementing clozapine with a course of electrocnnvulsive therapy (ECT) has been suggested as one possible approach. Specifically, investigators have questioned the utility, safety, and efficacy of ECT augmentation in combination with clozapine in treatment-refractory schizophrenia. To assess the efficacy and safety of this combination, we evaluated the effects of combining clozapine and ECT in 14 schizophrenic inpatients (SADS/RDC and DSM-III-R). All these patients were on treatment with clozapine at the time that ECT was considered. All these patients had significant symptomatology despite clozapine treatment; the range of symptoms included disorganization, positive symptoms, catatonia, and negative symptoms. The sample consisted of nine male and five female patients. Bilateral ECT was utilized in all patients; the number of treatments ranged from 8-18. The dose of clozapine ranged from 200-800 mg/day. Five patients showed marked and sustained clinical improvement, five patients showed transient improvement followed by relapse, and four patients showed no response. One patient of the group that showed u'ansient improvement followed by relapses received maintenance ECT but relapsed despite maintenance ECT, Except fnr one patient who experienced significant tachycardia (which continued after discontinuation of ECT), we saw no adverse effects in connection with the combination of ECT and clozapine. Supplementing clozapine with a course of bilateral ECT appears to be safe and is effective in some patients with refractory schizophrenia. More systematic trials are indicated.

Depressive Symptoms in Schizophrenic Outpatients

AbstractPatients with schizophrenia suffer from a variety of depressive symptoms, but the prevalence and significance of these symptoms is not fully understood. Using a self-rated symptom checklist, 140 schizophrenic outpatients and 137 outpatients with affective disorder were compared on the frequency and severity of depressive symptomatology. As expected, patients with major depressive disorder had a significantly higher prevalence of depressive symptoms than the schizophrenic patients. However, there was a substantial number of schizophrenic patients who indicated severe distress from a variety of depressive symptoms including neurovegetative type symptoms. Though no actual suicides were reported a rather ominous finding was that 14% of the schizo-phrenicpatients reported having suicidal plans. This article discusses the implications of these findings in terms of diagnostic precision and therapeutic strategies.

The use of eye movement dysfunctions in exploring the genetic transmission of schizophrenia

Eye movement dysfunctions have been found in a large number of schizophrenic patients and in about half of their first-degree relatives. The distribution of these traits within the families of schizophrenic patients suggests a model of genetic transmission that fits an autosomal dominant model, which we have called the "genetic latent trait model." The model, with seven parameters, was fitted to a U.S. population and the model was cross-validated on an independent Norwegian sample. Although the model does not invalidate other, more conventional solutions to the puzzle of schizophrenic transmission, such as multifactorial transmission, the latent trait model does more easily permit linkage studies and therefore will allow refutation or support from the use of molecular genetics techniques.

Neuroleptics, Dopamine, and Schizophrenia

Neuroleptic drugs have provided not only the most efficacious form of treatment for schizophrenia but also a unique pharmacologic probe for discerning its pathophysiology. The link between the antipsychotic effects of neuroleptics and dopamine systems continues to be supported by current research. Recent preclinical and clinical studies suggest that time-delayed changes in DA neuronal function may more closely relate to the therapeutic effects of neuroleptics than does their relatively immediate effect of DA receptor blockade. The use of levels of plasma HVA as a noninvasive reflector of DA function provides a research strategy for longitudinal studies of neuroleptic effects in schizophrenia. Preliminary evidence suggests that neuroleptic-induced changes in levels of plasma HVA may be of value as an in vivo marker for neuroleptic antipsychotic effects. The recent identification and characterization of the mesocortical DA system, which links the midbrain to frontal areas of the cerebral cortex, represents a significant development in the neurobiology of CNS DA systems. The behavioral implications of the functional neuroanatomy of the mesocortical system, its relative unresponsiveness to neuroleptic agents, and the possibility of modulatory effects on the mesolimbic DA system render the mesocortical system a particularly important area of research with etiologic and pharmacotherapeutic implications for schizophrenia. The accumulating evidence indicating structural brain abnormalities in a significant number of schizophrenic patients has renewed interest in classical neuropathologic approaches to understanding its etiology. Although current evidence does not uniformly support the hypothesis of two schizophrenia types reflecting DA and non-DA forms of the illness, the postulate is useful as an attempt to integrate recent findings into a conceptual framework. Better understanding of the biochemical basis for heterogeneity of neuroleptic response and systematic data relating this responsivity to morphologic brain changes constitute an important direction for schizophrenia research.

Clinical, biochemical, and hormonal aspects of treatment with des-tyr 1-gamma-endorphin in schizophrenia

Des-tyr 1- y-endorphin (DT yE) was administered intramuscularly in a dose of 1 mg/day for 10 days to 18 neuroleptic-free schizophrenic patients in a double-blind crossover design. Six patients showed either a slight or no antipsychotic response; seven patients showed a moderate antipsychotic response; and the remaining five patients showed a marked antipsychotic response. DT yE led to a decrease of plasma prolactin levels in patients treated with DT yE in the first period of experimental treatment as compared to those treated with placebo. Neither plasma levels of growth hormone and cortisol nor cerebrospinal fluid concentrations of homovanillic acid, 5-hydroxyindoleactic acid, and 3-methoxy-4- hydroxyphenylglycol were affected by DT yE. Patients suffering from a hebephrenic or paranoid type of schizophrenia and those presenting relatively fewer negative symptoms were most susceptible to treatment with DT yE. These data confirm and extend previous findings that DT yE has antipsychotic properties in a number of schizophrenic patients.

(Des-tyrosine 1)-gamma-endorphin in schizophrenia: Clinical, biochemical, and hormonal aspects

The neuropeptide (des-tyrosine 1)-γ-endorphin (DTγE; β-LPH 62–77) was given to 10 schizophrenic patients who had been free of neuroleptic medication for at least 3 weeks. DTγE was injected intramuscularly in a dose of 1 mg daily for 10 days following a double-blind placebo-controlled crossover design. In 4 of the 10 patients a pronounced antipsychotic effect was observed; in 3 a temporary or slight reduction of psychotic symptoms occured; and in 3 no response was noted. DTγE led to decreased plasma levels of prolactin and in some patients to increased concentrations of homovanillic acid in cerebrospinal fluid (CSF). Neither plasma levels of growth hormone and cortisol nor CSF concentrations of 5- hydroxyindoleacetic acid were affected by DTγE. These data confirm that DTγE has antipsychotic properties in a number of schizophrenic patients and suggest an interaction between DTγE and central dopaminergic systems.

A Method for Monitoring the Treatment of Schizophrenics in the Community

A trial was carried out over twelve months of a method for monitoring the care of a large number of schizophrenic patients in the community. The method has been demonstrated to be practical in use, economical of resources and potentially relevant to a number of chronic disorders.