Computerized EEG as a predictor of drug response in treatment resistant schizophrenics

Thirteen chronic schizophrenics were identified who failed to improve with physician's choice medication and 1 year of systematic treatment with a long acting phenothiazine. These patients were considered to be treatment resistant. Computer analyzed electroencephalogram (CEEG) or these treatment resistant schizophrenics was characterized by a large amount of alpha activity and less fast activity, in comparison with previous results from therapy responsive schizophrenics. The therapy resistant subjects did not display the typical neuroleptic CEEG profile following test dosages of four neuroleptics, and instead displayed CEEG profiles which more closely resembled the typical profile for psychostimulants. These findings may point to an altered metabolism, neurotransmitter defect, or other problem which alters the physiological and clinical response of therapy resistant schizophrenics to neuroleptic medication.     

Abnormal EEG patterns in treatment-resistant schizophrenic patients.

This study was conducted in order to compare the EEG patterns of schizophrenics who do not respond to typical neuroleptics with those who do respond under typical neuroleptic medication and a group of controls. Absolute (AP) and relative power (RP), and inter- and intrahemispheric correlations were calculated. Nonresistant schizophrenics showed lower delta RP, higher alpha 1 AP and RP and higher correlation between prefrontal areas than the resistant ones and controls. Resistant schizophrenics showed lower alpha 2 RP, lower beta 1 and beta 2 in temporal but higher beta 2 AP and RP in occipital derivations, and higher intrahemispheric correlation between Fp2 and F4 and lower between F8 and T4 than the nonresistant and controls. The resistants also showed a higher antero-posterior beta 1 and beta 2 index than the controls. We concluded that the EEG pattern showed by the nonresistants may be associated with their good neuroleptic response that was not present in the resistant schizophrenics.     

Smooth pursuit eye movements in schizophrenia: influences of neuroleptic treatment and the question of specificity

The authors investigated smooth pursuit eye movements (SPEMs) in 66 schizophrenic and 40 major affective patients and 39 healthy controls. The results showed significant differences of both patient groups as compared to the controls. Schizophrenics with neuroleptic treatment in the preceding 2 years were significantly more disturbed than the controls, the affective patients and the untreated schizophrenics. Acute neuroleptic medication and neuroleptic treatment of a duration of 4-6 weeks appear not to significantly influence the quality of SPEMs.     

Is interval medication a successful treatment regimen for schizophrenic patients with critical attitudes towards treatment?

In neuroleptic long-term medication, only part of the patients accept regular intake of neuroleptic drugs. The question is whether an interval medication regimen as opposed to continuous medication can help to reduce drop outs in patients with critical attitudes towards long-term medication. In a 2-year prospective study, 122 patients were randomised to an interval and 164 to a continuous neuroleptic medication regimen. The drop out rates were 62.5% in the interval and 53.7% in the continuous medication group. Drop outs generally show more negative attitudes towards treatment. Patients with negative attitudes do not do better under interval medication. Moreover, this regimen even requires more cooperation and trust in terms of the necessity of medication on the part of the patient compared to the continuous medication regimen. Interval medication therefore is a strategy which can only be successful in highly cooperative, but not in treatment-reluctant patients.     

Attitudes towards neuroleptic treatment: reliability and validity of the attitudes towards neuroleptic treatment (ANT) questionnaire

Non-compliance problems may rise to 50% among patients undergoing neuroleptic treatment. There are no direct measures available to predict compliance, if previous non-compliance is not taken into account. Attitudes towards neuroleptic treatment and insight into psychotic symptoms may vary during the course of the treatment process. It would be relevant to evaluate these items before taking any clinical action and later reassess the degree of change. The instrument thus far available has been the Drug Attitude Inventory. It has limitations for use with first-episode-patients and their follow-up. Its statements are dichotomous, which makes it difficult to determine the variation of attitudes e.g. during maintenance treatment, and most of the items concentrate on the subjective state of the patient, leaving attitudes as a minority in the scale.In this study, we report the new Attitudes towards Neuroleptic Treatment (ANT) questionnaire for the quantitative assessment of attitudes. We developed 10 statements for attitudes and two items for insight in the Visual Analogue Scale form (0-100 points). These were compared with the Drug Attitude Inventory 10 Questionnaire (DAI-10) (Hogan, T. P., Awad, A.G., Eastwood, R., 1983. A self-report scale predictive of drug compliance in schizophrenics: reliability and discriminative validity. Psychol. Med. 13, 177-183.) among 106 subjects receiving neuroleptic medication.The 12 Visual Analogue Scales showed a high inter-item consistency and fair test-retest validity. The results were in accordance with the DAI-10. The scales comprised three factors: general attitudes, subjective feeling and expectations and insight.Attitudes towards neuroleptic treatment and insight into psychotic symptoms are different dimensions and can be measured quantitatively. The Attitudes towards Neuroleptic Treatment scale is useful in assessing the state of attitudes before starting medication and for follow-up among patients receiving neuroleptic medication.     

Open withdrawal of antiparkinson drugs in the neuroleptic- induced Parkinson syndrome.

The study was finished according to schedule with 32 of the 49 examined patients, i.e. without changes in neuroleptic medication. The antiparkinson medication had been suddenly withdrawn in all patients. No patient had to be given another antiparkinson treatment due to reappearing Parkinson symptoms. Slight and constant deterioration in their condition occurred in four patients within 1-3 weeks following withdrawal of the antiparkinson medication; this fact justified recommencement of the antiparkinson therapy. All but seven patients had been given antiparkinson drugs for more than 1 year. All patients were on neuroleptic drugs. The neuroleptic dose was increased in seven patients, a slight transient deterioration of the Parkinson symptoms occurring in two cases. Investigation into the longitudinal course of the diseases revealed that the intensity of symptoms is not always steady, but that certain variations occur. An equable course was observed in paranoid schizophrenics. In cases of catatonia and hebephrenia variations in the symptoms and their intensity must be expected. However, these variations need not inevitably call for recommencement of the antiparkinson treatment. Thus, our results confirm similar available studies in that the incidence of relapses in cases of neuroleptically conditioned Parkinson's disease is very low in patients who had been receiving antiparkinson medication for long periods; this incidence of relapses amounts to 8% in our study. Our figures are lower than those referred to in literature up to now. Within 1-3 weeks following withdrawal it becomes obvious whether another antiparkinson therapy will be necessary or not. Within the scope of our study, we cannot comment on the statement that antiparkinson drugs may be withdrawn, without any risk of a relapse, after 3-month administration.     

Eye movement research with schizophrenic patients and normal controls using corneal reflection-pupil center measurement

Summary The eye movements of 20 partially remitted outpatient schizophrenics (ICD 9), for the most part receiving neuroleptic maintenance medication, and 20 normal controls were recorded using corneal reflection-pupil center measurement. Performance was investigated on the basis of widely varied measurement parameters during a fixation task and a visual search task (list of letters). Psychopathological data were additionally recorded for the group of patients by means of self and observer ratings, current social adjustment, and neuroleptic dosage. The schizophrenic patients showed the tendency to perform more poorly than the normal controls in the eye movement parameters recorded, and there was marked variation in performance within the group of schizophrenic patients. In particular, various abnormalities in fixation performance were connected differentially with individual psychopathological syndromes and neuroleptic dosage. Connections between fixation performance and search performance were found only within the group of patients. They are interpreted as an indicator of disturbed interhemispheric coordination in schizophrenics. Based upon specific pupillary findings one concludes that the processing load imposed on the attentional system by the search task is different for various schizophrenic subgroups.     

Loss of the Kamin blocking effect in acute but not chronic schizophrenics.

Differences between research diagnostic criteria (RDC)-diagnosed acute and chronic schizophrenics and normal controls were studied using a Kamin blocking procedure. Blocking is an established animal learning procedure, thought by some researchers to reflect selective attention; decreased blocking indicates increased processing of irrelevant stimuli. It was predicted that this pattern would be obtained in acute schizophrenics, tested soon after admission, for two reasons: (1) evidence from previous clinical studies indicates that acute schizophrenics are more aware of nonsalient aspects of their environment than controls; and (2) blocking is disrupted in animals in a hyperdopaminergic state and restored by neuroleptic medication. This was the case: acute, but not chronic, schizophrenics showed disrupted blocking. This disruption was especially clear in those acute schizophrenics tested within 2 weeks of hospital admission. By the second test session (in a cross-over design), there was some evidence of normalization in performance in the acute schizophrenics. These findings are considered with regard to the dopamine hypothesis of schizophrenia.     

Dopamine D2 receptors in substantia nigra in schizophrenia

Dopamine D2 receptors were assessed in samples of substantia nigra from controls and schizophrenics. Specific [3H]spiperone binding was significantly increased in both neuroleptic-free and neuroleptic-treated schizophrenics. This supports our previous suggestion that the increase in D2 receptors observed in striatum of schizophrenics is not wholly due to neuroleptic medication.     

The effect of neuroleptics and tardive dyskinesia on smooth-pursuit eye movement in chronic schizophrenics

We sought to determine whether such state-related factors as neuroleptic treatment and facio-oral tardive dyskinesia (TD) influence smooth-pursuit eye movement (SPEM) in chronic schizophrenics. The design involved 100 schizophrenics, 64 of whom showed "abnormal" eye tracking. Experimentally drug-withdrawn patients, some of whom were clinically relapsed, were compared with control patients who continued taking medication in prewithdrawal and postwithdrawal SPEM tests. All groups showed a slight worsening in eye-tracking performance on two postwithdrawal tests, but significant group-by-test session "interactions" were not demonstrable. We also determined that patients with TD tend to substitute large, nontracking saccades for SPEM to a significantly greater extent than nondyskinetic patients. Our findings strengthen the supposition that impaired SPEM is a trait in many schizophrenics but suggest that patients with TD be excluded in future studies of SPEM addressed to trait issues.     

Neuroleptic-induced Tardive Tourette treated with clonazepam: a case report and literature review

Tardive Tourette syndrome has been reported as a rare complication of neuroleptic treatment. This report describes the first case of neuroleptic-induced tardive Tourette syndrome in the Latin Americas and supports the successful treatment of this disorder with clonazepam. The syndrome developed in a female schizophrenic patient who discontinued medication after 8 years of continuous neuroleptic therapy. Symptoms were unresponsive to increased doses of typical antipsychotics and treatment with an atypical antipsychotic. Significant, sustained improvement occurred with clonazepam. In this report all cases of adult-onset tardive Tourette are reviewed.     

Decreased serotonin S2 and increased dopamine D2 receptors in chronic schizophrenics

Serotonin S2 and dopamine D2 receptors in the prefrontal cortex and caudate nucleus of postmortem brains of chronic schizophrenics were studied using 3H-ketanserin and 3H-spiperone, respectively. In the prefrontal cortex of schizophrenics, we found a significant decrease in the maximum number of 3H-ketanserin binding sites (Bmax), with no change in the dissociation constant (Kd). Conversely, both Bmax and Kd of 3H-spiperone binding to the caudate nucleus were significantly increased in the schizophrenic patients. There were no differences in receptor indices between patients who were taking neuroleptics until their death and those who had taken none for 2 months or more prior to death. These findings suggest that alterations in S2 receptors in the prefrontal cortex may reflect the disease process, per se, and that the increase in the number of D2 receptors in the caudate nucleus of schizophrenics is not due solely to neuroleptic medication.     

Social aspects of therapy with depot neuroleptics in the Federal Republic of Germany

The authors compare 76 patients (50% paranoid schizophrenics, 30% residual psychotics) successively treated with oral and depot neuroleptics: the mean number of rehospitalizations has dropped from 2.5 to 0.8, while the mean duration of hospital treatment has dropped from 34 to 8 weeks (t test significant). The relationship between the type of treatment and sociodemographic data was analyzed by means of correlation coefficients and variance analyses. There was no relation of age, sex, age of onset, school background, social class and professional achievement, but a significant superiority of depot medication in single patients. The choice of the depot preparation depends on habits, scientific attitudes and year: in 1976-1977, fluphenazine decanoate was prescribed in 70% of all cases; but penfluridol, fluspirilene and to a lesser extent flupentixol decanoate were also administered. Depot forms make for 32% of all neuroleptics. There is no evidence as to whether long-term neuroleptic medication has a prophylactic effect on relapses beyond the third year of treatment; but, without these drugs, it would have been impossible to return many patients to their environment; social psychiatry has received a new impetus from depot neuroleptics; the size of psychiatric hospitals could be reduced by one-third.     

Visuomotor performance of schizophrenic patients and normal controls in a picture viewing task

The eye movements of 20 partially remitted schizophrenic outpatients (ICD-9) under neuroleptic maintenance medication and those of 20 normal controls were recorded using corneal reflection pupil-center measurement. The visuomotor performance during a 1-min picture viewing task was studied on the basis of several eye movement parameters. Clinical evaluation comprised self-ratings (Frankfort Complaint Questionnaire) and observer ratings (BPRS, CGI, GAS), as well as recording of current daily neuroleptic dosage (mg CPZ). The main results are that schizophrenics differ from normals in their correlational pattern of fixation- and movement-related parameters, reflecting two opposite viewing styles in schizophrenics: staring and extensive scanning. Both styles are differently related to clinical symptomatology. There was no strongly marked relationship with neuroleptic dosage.     

精神分裂症病程与结局十二年随访

目的了解我国精神分裂症长期结局。方法按世界卫生组织提供的方法及评定工具，于１９９４年对１９８２年调查的８个地区的８９例精神分裂症患者进行随访。结果直接随访的５８例在症状总体功能和社会缺陷总体功能评定中，分别有２８例（４８％）为结局好及较好者。结论近半数的患者为结局好或较好，可能与近年来普遍使用精神药物有关；同时，仅４０％的患者接受常规治疗，提示精神分裂症患者的社区康复工作仍有待加强。     

Neuroleptic withdrawal with remitted schizophrenics: a naturalistic follow-up study

Despite proven efficacy of maintenance pharmacotherapy in schizophrenia, indefinite neuroleptic treatment may not be optimal for all patients. It is uncertain how long maintenance therapy should be continued and how to identify those patients who can withdraw eventually from neuroleptics. Prospective randomized controlled studies are the ideal approach for evaluation of medication, however they are inevitably for the short term and may not be suitable for addressing the above-mentioned issue. In this study, we naturalistically followed up 30 remitted schizophrenics for 10.7 years on average and examined factors that might affect the outcomes. Of 30 remitted patients, 8 cases (26.7%) ceased neuroleptic use completely for more than 2 years. The details of clinical courses of those 8 cases were described as case reports in this report. Importantly, 4 of 8 withdrawal cases required 2 or more trials in order for neuroleptic withdrawal to reach a drug-free state. Factors which significantly affected successful withdrawal involved the mode of onset and the ages at first neuroleptic withdrawal trial. Our results suggest that approximately one-fourth of completely remitted patients could withdraw neuroleptics, but certain cases may need withdrawal trials at least a few times to accomplish the drug-free state.     

The effect of fluphenazine upon social and vocational functioning in remitted schizophrenics.

Thirty-six remitted schizophrenics who participated in an outpatient study of fluphenazine decanoate or oral fluphenazine vs placebo given for a year were examined for the effect of drug treatment upon social and vocational functioning. Only the period prior to any clinical relapse was evaluated. We found no difference between those on drug or placebo, and conclude that antipsychotic drugs, at least in the context of an aftercare clinic offering a rich spectrum of nonpharmacological services, and when combined with antiparkinson medication, do not interfere with social and vocational functioning.     

Changes in plasma homovanillic acid concentrations in schizophrenic patients following neuroleptic discontinuation.

Changes in plasma levels of the dopamine metabolite homovanillic acid have been reported to correlate with changes in the severity of schizophrenic symptoms during neuroleptic administration and after neuroleptic discontinuation. This study examined the effects of discontinuation of neuroleptic treatment on plasma homovanillic acid levels in 23 patients with chronic schizophrenia. It was hypothesized that clinical decompensation would be associated with increased plasma homovanillic acid levels. Plasma homovanillic acid was measured during administration of neuroleptic medication and during a subsequent 6-week drug-free period. Nine patients decompensated during the drug-free period and 14 patients did not. Following drug discontinuation, plasma homovanillic acid concentrations were higher in schizophrenic patients who decompensated than in those who did not. Furthermore, peak plasma homovanillic acid elevation after discontinuation of neuroleptic medication was significantly correlated with peak Brief Psychiatric Rating Scale increase. The data suggest that, in some schizophrenic patients, symptomatic decompensation after discontinuation of neuroleptic treatment is associated with increases in dopamine turnover.     

Abnormal phosphatidylinositol-cycle of platelet membrane in schizophrenia--a preliminary study

Phosphatidylinositol (PI)-cycle in the platelet membrane was examined in eight untreated patients with psychotic symptoms. A defect of PI-cycle in the transformation from 1,2-diacylglycerol into phosphatidic acid was found in three patients, who were diagnosed as having Schizophrenic Disorders or Schizophreniform Disorder according to the DSM-III criteria. Two out of the three patients were reexamined while undergoing neuroleptic medication, and they showed the same abnormality in PI-cycle. Further studies were required to determine the nature of the abnormality in PI-cycle in the platelets of schizophrenics.     

Outcome of schizophrenia in a non-industrialized society: comparative study between Bali and Tokyo

OBJECTIVE: The aim of the present study was to contrast the outcome of schizophrenic patients between Bali and Tokyo, the former being a non-industrialized society and the latter an industrialized society in Asia. METHOD: A total of 51 Balinese schizophrenics and 40 schizophrenics in Tokyo were evaluated by five outcome measures at a 5-year follow-up. RESULTS: No significant difference was found in the mean scores of the Positive and Negative Syndrome Scale, Eguma's Social Adjustment Scale and the re-admission rates between the subjects in the two sites. The cumulative length of stay in hospital during the 5-year period was significantly shorter in Bali. The percentage of subjects on psychiatric medication at the follow-up was significantly lower in Bali than that in Tokyo. CONCLUSION: Although the clinical outcome of schizophrenics in Bali was not superior to that in Tokyo, the subjects in Bali tended to be able to live in society without neuroleptic medication.