Henry Silver

The impact of side-effects of antipsychotic agents on life satisfaction of schizophrenia patients: a naturalistic study

This study compared the impact of side-effects of antipsychotic treatment, clinical and psychosocial factors on the subjective quality of life (QOL) of hospitalized patients. We surveyed 161 patients meeting DSM-IV criteria for schizophrenia stabilized on conventional and atypical antipsychotic drugs using standardized measures of adverse events, psychopathology, psychosocial variables, and perceived QOL. We found that patients with adverse events reported less satisfaction with life domains of subjective feelings and general activities than asymptomatic patients. Patients treated with conventional and novel antipsychotic agents had comparable QOL ratings. Multiple regression analysis showed total variance in QOL ratings as follows: psychosocial factors, 20.9%; clinical symptoms and associated distress, 10.1%; adverse effects, 3.2%. Thus, medication side-effects influence subjective quality of life of schizophrenia inpatients significantly less than other clinical and psychosocial factors. Patients subjective response to these events rather than their number is more predictive of QOL.

Perception of happy and sad facial expressions in chronic schizophrenia: Evidence for two evaluative systems

BACKGROUND Persons suffering from schizophrenia have impaired perception of emotional expressions, but it is not clear whether this is part of a generalized deficit in cognitive function. AIM To test for existence of emotion-specific deficits by studying the effects of valence on recognition of facial emotional expressions. METHODS 24 male subjects suffering from chronic schizophrenia were examined with two tests of perception of emotion: the Penn Emotion Acuity Test (PEAT 40) and the Emotion Differentiation Task (EMODIFF). Clinical state was assessed with the Scale for the Assessment of Negative Symptoms (SANS) and Scale for the Assessment of Positive Symptoms (SAPS), visual memory with the Benton Visual Retention Test (BVRT) and motor function with the finger tapping test. RESULTS Identification of happy facial expressions showed significant negative correlation with age, cumulated time in hospital and length of current hospitalization; positive correlations were found with visual retention and finger tapping scores. Identification of sad facial expressions showed significant correlation only with cumulated time in hospital while identification of neutral facial expressions showed no significant correlations. Discrimination between degrees of happy but not sad facial expression showed a positive correlation with negative symptoms. CONCLUSION Perception of happy and sad emotion relates differently to significant illness parameters. This differentiability supports the existence of an emotion-specific deficit in perception of emotions in schizophrenia and of separate channels for processing positive and negative emotions.

Brief emotion training improves recognition of facial emotions in chronic schizophrenia. A pilot study

Impaired emotional communication may be an important contributing factor to poor social function in schizophrenia. This pilot study examined the effect of emotion training exercises on the perception of facial emotional expression. Twenty male chronic schizophrenia patients underwent three training sessions using a computerized Emotion Training program, developed for teaching autistic children, which was adapted to the clinical setting. Patients were assessed before and after training with validated tests of identification of facial emotions (PEAT, ER40), differentiation of facial emotions (EmDiff) and working memory. In comparison to baseline, patients performed significantly better on the PEAT and ER40 tests after training. No change was observed in EmDiff or in cognitive test performance. Brief Emotion Training can improve recognition of facial emotional expressions in chronic schizophrenia patients. This may be due to increased patient awareness of emotional aspects of stimuli and/or improvement in specific emotional perceptual skills. Further studies of Emotion Training as a potential treatment modality are warranted.

Fluvoxamine augmentation of antipsychotics improves negative symptoms in psychotic chronic schizophrenic patients: a placebo-controlled study

&NA; The efficacy and safety of adding fluvoxamine to antipsychotic treatment in schizophrenic patients with mixed positive and negative symptoms was examined. Fifty‐three patients selected for persistent negative and positive symptoms who were receiving antipsychotic treatment were randomly allocated to additional fluvoxamine (50‐100 mg / day) or placebo in a double‐blind manner. Fluvoxamine was associated with significant improvement in negative symptoms (Scale for the Assessment of Negative Symptoms) compared to placebo. The combination was well tolerated. Fluvoxamine augmentation of antipsychotics is safe in chronic schizophrenic patients with mixed positive and negative symptoms and may ameliorate negative symptoms in such patients.

Animal-Assisted Therapy Ameliorates Anhedonia in Schizophrenia Patients

Background: Anhedonia, a component of the negative symptom dimension and a core phenomenon in schizophrenia, is associated with poor social functioning and is resistant to treatment. We tested the hypothesis that animal-assisted therapy (AAT) may improve anhedonia. Objective: To compare the effect of psychosocial treatment sessions in which a dog was an active participant (AAT) with comparable sessions without a dog, using a controlled protocol. Method: The hedonic tone of 10 chronic schizophrenia patients who participated in 10 weekly interactive sessions of AAT was compared to a control group treated without animal assistance. The hedonic tone was measured with the Snaith-Hamilton Pleasure Scale. Subjective quality of life variables and clinical symptoms were also assessed. Results: The AAT group showed a significant improvement in the hedonic tone compared to controls. They also showed an improvement in the use of leisure time and a trend towards improvement in motivation. Conclusion: AAT may contribute to the psychosocial rehabilitation and quality of life of chronic schizophrenia patients.

Perception of facial emotions in chronic schizophrenia does not correlate with negative symptoms but correlates with cognitive and motor dysfunction

BACKGROUND Appropriate expression of emotions and correct perception of emotional expression in others are important social skills which may be impaired in schizophrenia and contribute to poor social adjustment. We examined the relationship between expression of emotions as measured by affective flattening and other negative symptoms and their perception. We compared performance on tests of perception of facial emotions with that in other cognitive areas. METHODS 36 chronic schizophrenic patients on stable doses of atypical antipsychotics were assessed using tests of identification (FID) and discrimination (FDIS) of facial emotional expressions, visual retention (BVRT) and general cognitive function (Mini Mental State Examination, MMSE). Clinical symptoms were assessed with scales for the assessment of negative symptoms (SANS) and positive symptoms (SAPS). Motor symptoms were assessed with side effects (SA) and AIMS scales and Finger Tapping Test. RESULTS Negative symptoms showed no relation to FID or FDIS. FID showed significant correlation with Visual Retention and Finger Tapping but not MMSE. CONCLUSION The ability to identify facial emotional expressions is not related to negative symptoms in chronic schizophrenia and shares common mechanisms with visual reproduction and ability to make rapid motor movements. This suggests common defects in perceptual, timed processes consistent with postulated dysfunction of cortico-subcortical circuits.

Selective serotonin re-uptake inhibitor augmentation in the treatment of negative symptoms of schizophrenia.

Negative symptoms are core features of schizophrenia that respond poorly to first-generation antipsychotics and present a major obstacle in rehabilitation. Patients may be somewhat more responsive to clozapine and second-generation antipsychotics but even then, considerable impairment remains. This paper reviews the use of selective serotonin re-uptake inhibitor (SSRI) augmentation of antipsychotics in the treatment of negative symptoms in schizophrenia. Important methodological issues particular to the study of negative symptoms are also discussed. Current evidence indicates that at least two SSRIs, fluvoxamine and fluoxetine, can ameliorate primary negative symptoms in chronic schizophrenic patients treated with first-generation antipsychotics. Onset of improvement may be detected within 2 weeks of starting treatment. The combination is well-tolerated, although as antipsychotic drug concentrations may rise, close monitoring of drug doses and possibly drug concentrations is needed. So far, evidence regarding SSRI augmentation of second-generation antipsychotics is limited and in view of the increasing use of these newer agents, controlled studies are urgently needed. SSRI augmentation may be a useful addition to the treatment of schizophrenic patients with persistent negative symptoms. The paradoxical findings that both clozapine, a serotonin antagonist, and an SSRI antidepressant added to antipsychotics, can improve negative symptoms suggests that these pharmacologically distinct treatments may share common final mechanisms. A better understanding of these mechanisms can shed light on the pathogenesis of negative symptoms and provide new targets for drug development.

Fluvoxamine Augmentation of Olanzapine in Chronic Schizophrenia: Pharmacokinetic Interactions and Clinical Effects

Olanzapine is a substrate of the cytochrome P450 enzyme (CYP) 1A2. In this study, pharmacokinetic interactions and clinical effects of adding the CYP1A2 inhibitor fluvoxamine to steady-state olanzapine was examined in patients suffering from schizophrenia. Eight patients had been treated for at least 3 months with 10 to 20 mg/day olanzapine. Fluvoxamine (100 mg/day) was added (week 0) to the olanzapine treatment and continued for 8 weeks. Concentrations of olanzapine and its metab-olite N-desmethylolanzapine and of fluvoxamine were analyzed at weeks 0, 1, 4, and 8. Addition of fluvoxamine resulted in a 12% to 112% (p < 0.01) increase of olanzapine from 31 ± SD 15 ng/mL (week 0) to 56 ± 31 ng/mL (week 8) in all patients. N-desmethylolanzapine concentrations were not significantly changed (p > 0.05). Fluvoxamine concentrations were 48 ± 26 ng/mL on week 1 and 83 ± 47 ng/mL on week 8. It is concluded that fluvoxamine affects olanzapine degradation and thus increases olanzapine concentrations. Although the combination was well tolerated in this sample and the negative symptom response appeared to be favorable in at least five patients, the combination therapy of olanzapine and fluvoxamine should be used cautiously and should be controlled by therapeutic drug monitoring to avoid olanzapine-induced side effects or intoxications.

Neuroendocrine responses in chronic schizophrenia: Evidence for serotonergic dysfunction

Neuroendocrine and mood responses to a 60 mg oral dose of the serotonin-releasing agent, fenfluramine, were assessed in ten neuroleptic-free, chronic schizophrenic patients and in age- and sex-matched normal control subjects. The prolactin (PRL) response to fenfluramine was significantly blunted in the schizophrenic subjects. Growth hormone and cortisol levels were not differentially affected by the challenge. There was no significant effect of fenfluramine on mood in either group. The blunted PRL response in the schizophrenic group suggests serotonergic dysfunction; possible mechanisms of this finding and implications for treatment are considered.

Fluvoxamine augmentation in clozapine-resistant schizophrenia: an open pilot study

Clozapine often improves refractory schizophrenia but is not always effective. Since Silver and Nassar (1992) first demonstrated that add-on fiuvoxamine improved primary negative symptoms in chronic schizophrenics evidence has accumulated that serotonin reuptake blocker (SSRI) augmentation may improve neuroleptic effectiveness (Goff et al 1995; Silver et al 1995). Here we report a study of fluvoxamine augmentation in patients resistant to both typical antipsychotics and subsequently clozapine.