Eyal Shamir

Vitamin E (α-Tocopherol) in the Treatment of Tardive Dyskinesia: A Statistical Meta-Analysis

AbstractTardive dyskinesia is an involuntary movement disorder developing following treatment with neuroleptics. As many as 50% of chronic psychotic patients develop this disabling condition. No treatment has been found effective for tardive dyskinesia. This study was undertaken to meta-analyze the effects of vitamin E (α-tocopherol) reported in the last decade. All studies published since 1987, focusing on vitamin E and tardive dyskinesia are reviewed. Double-blind studies are analyzed using measures of effect and variance as described by secondary analysis of magnitude of effects in pooled data. A total of 223 patients received vitamin E treatment (400-1600 IU/day) for tardive dyskinesia, in 12 studies. A significant subgroup (28.3%) showed a modest improvement. Vitamin E was well tolerated, and only rarely did side effects occur-of no clinical significance. Vitamin E is a safe, well-tolerated compound that may provide some beneficial effects in patients suffering from neuroleptic-induced tardive dyskin...

Would a switch from typical antipsychotics to risperidone be beneficial for elderly schizophrenic patients? A naturalistic, long-term, retrospective, comparative study.

Elderly chronic schizophrenia patients are particularly difficult to treat because of aging-related changes, cognitive impairment, and comorbid physical illness. This article describes a naturalistic, retrospective study of typical antipsychotic treatment versus risperidone for elderly psychotic inpatients. Fifty-one patients, mean age 72.7 + 5.9 years, mean disease duration 33.1 + 12.0 years, who met the DSM-IV criteria for schizophrenia or schizoaffective disorder were treated by risperidone (n = 26) or typical antipsychotic treatment (n = 25) during acute exacerbation and followed up for 18 months. Patients were rated using the clinical global impression (CGI) scale and positive and negative symptom scale (PANSS), and their body weight was recorded at baseline, 6 months, and 18 months. Both treatment groups improved on all rating scales at 18 months. Levels of decrease in PANSS positive and total scores were more prominent in patients treated with risperidone (p < 0.01 and p < 0.05, respectively). The change in CGI scores reached significance only after 18 months and was more pronounced in the risperidone group (p < 0.01). Anti-Parkinsonian medications were used more frequently in the typical antipsychotic group, whereas benzodiazepines were used more frequently in the risperidone group. Body mass index increased minimally after 18 months in the risperidone group (+ 0.3 kg/m2), whereas a larger (+ 1.1 kg/m2), albeit not statistically significant, increase was recorded in the typical antipsychotic group. Emergence of side effects was less frequent in patients treated with risperidone (4/26 vs. 16/25 patients, p < 0.01). The results of this study demonstrate that in elderly chronic schizophrenic patients, switching from typical antipsychotics to risperidone is effective and well tolerated.

Olanzapine vs. haloperidol in the treatment of elderly chronic schizophrenia patients

OBJECTIVE Most of the data supporting the use of atypical antipsychotics (AA) is based on studies in young adult patients. The present study is an open-label naturalistic follow-up study of olanzapine treatment vs. haloperidol for elderly chronic schizophrenia patients. MEHTOD: 20 patients (mean age 72.7+/-5.9 years, mean disease duration 33.1+/-12.0 years) who met the DSM-IV criteria for schizophrenia were randomly assigned to olanzapine (n=10) or haloperidol (n=10) treatment during acute exacerbation. Primary outcome measure was rating on the Clinical Global Impression (CGI) scale and the Positive and Negative Symptom Scale (PANSS). RESULTS Between-group differences were computed using analysis of covariance. PANSS Total score decreased from 84 at baseline to 65 after treatment with olanzapine while decreased only from 79 to 74 with haloperidol treatment (F= 6.66, P=.02). PANSS Negative subscale decreased from 19 at baseline to 15 with olanzapine treatment while increased (deteriorated) from 18 to 20 with haloperidol treatment (F=23.37, P=.0003). CGI decreased from baseline with both olanzapine and haloperidol treatments (1.1 vs. 0.4) but the decrease in the olanzapine group was significantly greater (F=4.63, P=.05). Mean weight increased in both groups but without statistical difference between groups. CONCLUSIONS In elderly chronic schizophrenia patients, olanzapine treatment is superior to haloperidol in reducing negative symptoms as well as less induction of extrapyramidal symptoms (EPS).

First-night effect of melatonin treatment in patients with chronic schizophrenia.

The first-night effect (FNE) is the tendency for individuals to sleep worse than normal during their first night of polysomnographic sleep evaluation. FNE reflects the adaptive increase of alertness and perhaps the stress resulting from an unfamiliar sleeping environment. This effect is usually absent in patients with chronic schizophrenia. Melatonin (N-acetyl-5-methoxy-tryptamine), the hormone secreted by the pineal gland at night, has been found to improve sleep in elderly patients with insomnia and recently in patients with chronic schizophrenia. The authors used FNE as a marker to explore the neurobehavioral responses of patients with chronic schizophrenia to melatonin treatment. In a randomized, double-blind, crossover trial, 14 patients with chronic schizophrenia were administered melatonin (2 mg in a controlled-release formulation) or placebo for 3 weeks with a 1-week washout between treatment periods. Polysomnography was performed during the last two consecutive nights of each treatment period. The following significant FNEs were observed with melatonin treatment: (1) rapid eye movement sleep latency was longer; (2) sleep efficiency was lower; and (3) the duration of wakefulness during sleep was lower on the first night than on the second night. These effects were not found when the patients received a placebo. The FNE was manifested regardless of whether melatonin was administered before or after the placebo treatment period. For the first time, these results show that melatonin treatment exaggerates FNE in patients with chronic schizophrenia, thereby suggesting an improved ability of these patients to mobilize alertness in unfamiliar surroundings.

REM sleep latency and wakefulness in the first sleep cycle as markers of major depression: a controlled study vs. schizophrenia and normal controls.

INTRODUCTION REM sleep latency is a clinically significant sleep variable that is found to be decreased in several psychiatric disorders. However, it is not known whether alteration of REM sleep latency is similar across disorders. In order to test whether incorporation of wakefulness in the first sleep cycle has a different outcome on REM sleep latency in different clinical groups, the authors have investigated correlation between sleep variables in the first sleep cycle in 25 patients with major depression, 24 patients with chronic schizophrenia, and in 10 healthy subjects. RESULTS REM sleep latency correlates with the duration of wakefulness in the first cycle in patients suffering from chronic schizophrenia and in healthy subjects. This correlation does not hold true in patients suffering from major depression. CONCLUSION Wakefulness incorporated in the first cycle influences REM sleep latency in healthy subjects and in patients suffering from chronic schizophrenia but not in patients suffering from major depression. This finding further supports the evidence that reduced REM sleep latency is a nonflexible marker of depression.

Switching elderly chronic psychotic patients to olanzapine

The purpose of this study was to examine whether elderly chronic schizophrenia or schizoaffective disorder patients would clinically improve if switched to olanzapine from previous neuroleptic treatment. Twenty-one hospitalized patients, aged 6088 yr, with a diagnosis of chronic schizophrenia or schizoaffective disorder who were being treated with typical neuroleptic medication were switched to olanzapine. The Positive and Negative Symptom Scale (PANSS), Geriatric Depression Scale (GDS) and Clinical Global Impression Severity (CGI-S) Scale were completed while patients were on their previous medication regimen and again 6 months after the last patient had been started on olanzapine. The mean duration of treatment was 289 d (S.D.=139). Three patients discontinued the medication. Mean end dose of olanzapine was 12.9 mg (S.D.=5.7). Paired sample t tests were used to test change on PANSS Positive, Negative and Total scales, CGI, GDS and body weight. PANSS (Positive, p=0.002; Negative, p=0.003; General, p=0.003; and Total, p=0.000) and CGI (p=0.000) but not the GDS (p=0.67) demonstrated statistically significant improvement. There was no significant change in body weight (p=0.61). Elderly patients with aggravation of chronic schizophrenia showed improvement after being switched to olanzapine with no weight gain. Clinically meaningful change was observed in positive and negative psychotic symptomatology but not in depressive symptoms.

The magnocellular visual pathway and facial emotion misattribution errors in schizophrenia.

Many individuals with schizophrenia show impairment in labeling the emotion depicted by faces, and tend to ascribe anger or fear to neutral expressions. Preliminary research has linked some of these difficulties to dysfunction in the magnocellular (M) visual pathway, which has direct projections to subcortical emotion processing regions. The current study attempted to clarify these relationships using a novel paradigm that included a red background. Diffuse red light is known to suppress the M-pathway in nonpsychiatric adults, and there is preliminary evidence that it may have the opposite (stimulating) effect in schizophrenia-spectrum disorders (SSDs). Twenty-five individuals with SSDs were compared with 31 nonpsychiatric controls using a facial emotion identification task depicting happy, angry, fearful, and sad emotions on red, green, and gray backgrounds. There was a robust interaction of group by change in errors to the red (vs. green) background for misattributing fear expressions as depicting anger (p=.001, ή(2)=.18). Specifically, controls showed a significant decrease in this type of error with the red background (p=.003, d=0.77), while the SSD group tended to increase this type of error (p=.07, d=0.54). These findings suggest that the well-established M-pathway abnormalities in SSDs may contribute to the heightened misperception of other emotions such as anger, which in turn may cause social misperceptions in the environment and elicit symptoms such as paranoia and social withdrawal. As the ventral striatum plays a primary role in identifying anger and receives efferent input from the M-pathway, it may serve as the neuroanatomical substrate in the perception of anger.

Biometric parameters of the hand as an index of schizophrenia—A preliminary study

Since abnormalities in distal upper limb development are among the minor physical anomalies associated with schizophrenia we attempted to determine whether patients with schizophrenia can be identified on the basis of specific morphologic and dermatoglyphic features of the hand. Photographs and prints of the hands of 38 patients with schizophrenia and those of 42 control subjects were evaluated and graded on 13 biometric parameters. Results were statistically evaluated. A combination of three of the parameters was found to have good predicting abilities to distinguish between schizophrenics and controls. Subjects having high values in these three parameters were found to have a higher propensity to be defined as schizophrenics. In order to define a simple rule for classifying subjects we chose a criterion of having a value of 3 (in a scale from 1 to 3) in at least one of these three discriminating variables. This rule yielded an overall accuracy of 81.2%. Among controls, 85.7% of subjects did not fulfill such criteria, while 14.3% were defined as false positives. Among schizophrenics 76.3% achieved this condition while 23.7% were false negatives. The techniques objectivity and ease of application could facilitate the diagnosis of this disease.

Probing the magnocellular and parvocellular visual pathways in facial emotion perception in schizophrenia

Schizophrenia patients have well-established deficits in facial emotion perception, which contribute to their poor social functioning. A number of studies have related these deficits to a differential dysfunction in the magnocellular (M) versus parvocellular (P) visual pathway. We assessed 35 schizophrenia patients and 35 healthy individuals on an emotion identification task, in which facial stimuli were either unaltered (broad spatial frequency, BSF) or manipulated to contain only high (HSF) or low (LSF) spatial frequencies, thereby respectively biasing the visual system toward the P- or M- pathways. As expected, patients were less accurate and slower in recognizing emotions across all conditions, relative to controls. Performance was best in the BSF condition followed by the HSF and finally the LSF condition, in both groups. A significant group by spatial frequency interaction reflected a smaller magnitude of impairment in the HSF condition, compared to the other two conditions that preferentially engage the M-system. These findings are consistent with studies showing a differential M-pathway abnormality in schizophrenia with a less pronounced impairment in P-function. The current study suggests that patients have less difficulty extracting emotional content from faces when LSFs are attenuated and supports the need to remediate basic visual processing deficits in schizophrenia.

Do biometric parameters of the hand differentiate schizophrenia from other psychiatric disorders? A comparative evaluation using three mental health modules

The link between schizophrenia and anomalies in the distal upper limb is well documented. Preliminary studies have identified a number of biometric parameters of the hand by which schizophrenics can be distinguished from matched controls. The current study seeks to determine whether patients with schizophrenia can be singled out from a disparate group of other mental disorders by using the same parameters. We studied three groups, totaling 134 men: 51 diagnosed with schizophrenia, 29 with anxiety and mood disorders, and 54 comprising a control group. Seven parameters were studied: the proximal interphalangeal joint, the eponychia of the middle and ring digits, two dermatoglyphic features, and two constitutional factors. Examiners evaluated the parameters based on photographs and prints. An initial Mann Whitney comparison showed no significant difference between the control group and those identified with anxiety and mood disorders. We therefore accounted for them as a single group. In a discriminant analysis, an overall accuracy of 78.4% was established with a sensitivity of 80.4% (schizophrenics identified correctly) and a specificity of 77.1% (controls identified correctly). These results suggest that the biometric parameters employed may be useful in identifying patients with schizophrenia from a disparate group of other mental disorders.