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Biomedical subjects

W C Wirshing

Publications and source records attributed to W C Wirshing.

At least 19 recordsLinked to original sources

Two-year outcome of social skills training and group psychotherapy for outpatients with schizophrenia.

OBJECTIVE: The authors evaluated the effectiveness of behaviorally oriented social skills training and supportive group therapy for improving the social adjustment of schizophrenic patients living in the community and for protecting them against psychotic relapse. METHOD: Eighty male outpatients with schizophrenia were stabilized with a low dose of fluphenazine decanoate (5 to 10 mg every 14 days), which was supplemented with oral fluphenazine (5 mg twice daily) or a placebo when they first met criteria for a prodromal period. (Half of the patients did so at some time during the study.) Patients were randomly assigned to receive either social skills training or supportive group therapy twice weekly for 6 months and then weekly for the next 18 months. Rates of psychotic exacerbation were monitored, as were scores on the Social Adjustment Scale II. RESULTS: There were significant main effects favoring social skills training over supportive group therapy on two of the six Social Adjustment Scale II cluster totals examined (personal well-being and total) and significant interactions between psychosocial treatment and drug treatment for three items (external family, social and leisure activities, and total). In each case, these interactions indicated that the advantage of social skills training over supportive group therapy was greatest when it was combined with active drug supplementation. Social skills training did not significantly decrease the risk of psychotic exacerbation in the full group, but an advantage was observed (post hoc) among patients who received placebo supplementation. CONCLUSIONS: These findings suggest that social skills training resulted in greater improvement in certain measures of social adjustment than supportive group therapy. The greatest improvement in social outcomes occurred when social skills training was combined with a pharmacological strategy of active drug supplementation at the time prodromal worsening of psychotic symptoms was first observed. However, these improvements were modest in absolute terms and confined to certain subgroups of patients.

Adult

Predictive value of eosinophilia for neutropenia during clozapine treatment.

BACKGROUND: Myelotoxicity continues to hinder the widespread use of clozapine in the United States. It has been theorized that eosinophilia predicts later agranulocytosis and that agranulocytosis occurs due to an immunologic mechanism. Our study compares the rates of these dyscrasias in clozapine-treated patients and a control group. METHOD: Forty-one patients taking clozapine and 29 patients taking haloperidol were monitored for a period of 6 months. Rates of eosinophilia and neutropenia were compared between the two treatment groups. RESULTS: Treatment-emergent eosinophilia occurred frequently in both haloperidol- and clozapine-treated patients. No significant difference was seen between groups in the incidence of eosinophilia and neutropenia. CONCLUSION: We find no statistical difference between the rates of eosinophilia or neutropenia in haloperidol- and clozapine-treated patients. This study does not support the use of eosinophilia as a reliable predictor of neutropenia.

Adult

Fluphenazine vs placebo supplementation for prodromal signs of relapse in schizophrenia.

BACKGROUND: We studied the effectiveness of treating patients with low doses of fluphenazine decanoate and supplementing them with oral fluphenazine when there was evidence of prodromal symptoms of psychotic exacerbations. METHODS: Eighty schizophrenic patients who were receiving 5 to 10 mg of fluphenazine decanoate every 2 weeks were monitored for prodromal symptoms using an idiosyncratic prodromal rating scale. When patients met our criteria for a prodromal episode, they were randomly assigned to a double-blind comparison of oral fluphenazine hydrochloride (5 mg twice daily) or a placebo for the current and future prodromal episodes. We compared rates of psychotic exacerbations in the two treatment groups. RESULTS: Thirty-six patients (45%) met the criteria for a prodrome at some point during the trial and were randomized to drug or placebo. Using survival analysis during the entire 2 years, we did not find a significant difference between fluphenazine and placebo in the likelihood that a prodrome would continue to an exacerbation. Survival analysis beginning at the start of the second year of treatment did indicate a significant reduction in exacerbation risk for patients receiving drug supplementation (P = .032). Similarly, there was no difference between the two groups in the proportion of time at risk spent in exacerbation during the first year, but patients receiving active drug supplementation spent less time in an exacerbated state in the second year (P = .05). CONCLUSIONS: Our treatment strategy appeared to be effective for some patients, particularly those who were able to remain in the study beyond the first year. Although the occurrence of a prodrome was a fairly good marker that a patient was at high risk of ultimate exacerbation with our low-dose maintenance protocol, prodromes were not highly sensitive indicators of imminent exacerbation.

Acute Disease

Repetitive and compulsive behavior in frontal lobe degenerations.

The authors review the relationship of repetitive behaviors to frontal lobe degenerations and report the repetitive and compulsive behaviors, radiologic imaging findings, and neuropathology of 3 patients with dementia secondary to frontal lobe degeneration. These 3 patients and 78% of 46 proven pathologic cases of frontal lobe degeneration described in the literature demonstrate repetitive behaviors ranging from motor stereotypies to complex obsessive-compulsive disorder. This review suggests that combined damage to the frontal lobe, caudate nucleus, and globus pallidus may account for the repetitive behaviors seen in frontal lobe degenerations, idiopathic obsessive-compulsive disorder, and other neuropsychiatric diseases.

Adult

Clinical perspectives of some neuroleptics through development and application of their assays.

Attempts to investigate relationships between plasma levels of neuroleptics and therapeutic outcome in schizophrenic patients have been hampered due to such factors as the chemical nature of these drugs, their metabolism, and the very heterogeneous nature of the disease states. Two clinical studies are described that investigate the relationship between plasma levels of fluphenazine (FLU) and its metabolites and therapeutic outcome in schizophrenic patients. In the first of these studies the levels of FLU and fluphenazine sulfoxide (FLUSO) in schizophrenics receiving either 5 or 25 mg of fluphenazine decanoate (FLUD) intramuscularly every 2 weeks were monitored. Patients given 25 mg of FLUD required 3 months to reach plasma level steady state. The results suggest that such patients, when being switched from the oral to the depot formulation of FLU, should continue to receive oral supplementation during the 1st 3 months after conversion. The relationship between log-transformed plasma levels at 26 and 38 weeks with subsequent psychotic exacerbation was investigated with the use of logistic regression and survival analysis. Both demonstrated significant relationships between FLU plasma levels and a risk of psychotic exacerbation at 26 and 38 weeks. The possibility of any correlations between neurological side effects and plasma concentrations were also investigated, with statistically significant correlations between FLU levels and akinesia found at 2 and 26 weeks. In the second of these studies the levels of FLU, FLUSO, 7-hydroxyfluphenazine (7-OHFLU), and fluphenazine N4'(-)-oxide (FLUNO) in schizophrenics receiving 5, 10, or 20 mg of oral fluphenazine dihydrochloride daily for 4 weeks were monitored. The relationships between log-transformed plasma levels, disabling side effects, and global improvement were examined by logistic regression for the 4-week period. The study showed a significant correlation between increases in both plasma levels and disabling side effects such that at a plasma level of 2.7 ng/ml, approximately 90% of acutely ill patients experienced disabling side effects. Conversely, the study also showed that at a plasma level of 0.67 ng/ml, 48% of patients experienced improvement without the development of disabling side effects. When relationships between metabolite levels, disabling side effects, and global improvement were examined by logistic regression, a stronger correlation between disabling side effects and FLUNO levels than between side effects and FLU levels was found.(ABSTRACT TRUNCATED AT 400 WORDS)

Antipsychotic Agents

Schizophrenia.

The pharmacologic treatment of the schizophrenic patient has remained substantively unchanged during the last 35 years. It is evident that as our knowledge of neuropharmacology has grown--the notion of schizophrenia being merely caused by a hyperdopaminergic state may be too simplistic. Multiple neurotransmitter systems may be involved in the manifestations of this illness. Conventional neuroleptics--the mainstay of antipsychotic treatment--have proved to be only partially effective and their untoward side effects have led to notorious patient noncompliance and iatrogenic morbidity. The demonstration that clozapine possesses both increased efficacy and reduced neurotoxicity, however, has forever altered the conventional wisdom that held all antipsychotics to be equally efficacious and uniformly neurotoxic. The pharmacologic legacy of clozapine promises to provide clinicians with biologic therapies that are at once safe, effective, and easy to administer.

Antipsychotic Agents

Technique for training schizophrenic patients in illness self-management: a controlled trial.

OBJECTIVE: To determine whether schizophrenic outpatients receiving low-dose neuroleptic therapy could learn and retain complex information and skills related to self-management of their illness, a novel technique of teaching, using cognitive and behavioral methods, was designed to compensate for the patients' learning disabilities. METHOD: The subjects were 41 patients with DSM-III-R schizophrenia who were receiving constant maintenance neuroleptic drug therapy. They were randomly assigned to structured, modularized skills training or to supportive group psychotherapy. RESULTS: The patients who received skills training made significant gains in each of the areas taught, while those participating in group therapy did not. The skills learned during training were retained without significant erosion over a 1-year follow-up period. CONCLUSIONS: The effectiveness of modularized teaching of illness self-management skills to schizophrenic patients appears to be largely independent of baseline psychology and symptom improvement. Such an approach is useful for overcoming or compensating for the enduring cognitive and information processing deficits commonly found in schizophrenia.

Activities of Daily Living

Acquisition and retention of skills training methods in chronic schizophrenic outpatients.

Forty-one DSM-III-R schizophrenic subjects on constant, low-dose maintenance neuroleptic drug therapy (5-10 mg of fluphenazine decanoate intramuscularly every 2 weeks) were randomly assigned to structured and modularized skills training or to supportive group psychotherapy. The skills training was designed by using cognitive and behavioral methods to compensate for the learning disabilities that plague many schizophrenic patients. Skill acquisition was assessed by using quantified performance on standardized role-play tests. Subjects who received skills training made significant gains in each of the areas taught, whereas those who participated in the control psychotherapy group did not. The knowledge and skills learned during training were retained without significant erosion over a 1-year followup period. These results suggest that the use of structured principles of learning and cognitive therapy can effectively train schizophrenics in skill areas pertinent to the self-management of their illness.

Adult

Organic mental disorders associated with bupropion in three patients.

Bupropion hydrochloride is a phenylaminoketone antidepressant whose clinical pharmacology is poorly understood. Part of bupropion's action may be attributed to inhibition of dopamine reuptake that may induce organic mental disorders in certain susceptible patients. We report three cases of organic mental disorders in patients receiving bupropion hydrochloride for treatment of the depressed phase of their bipolar-type mood instability. The organic mental disorders that occurred in these patients were characterized largely by visual disturbances--visual hallucinations and visual illusions--although one patient also experienced auditory hallucinations. The patients' use of concomitant medications and potential drug interactions are carefully evaluated and the literature on bupropion's ability to induce organic mental disorders is reviewed. We suggest a number of possible mediating mechanisms for these syndromes including dose-related dopaminergic augmentation, accumulation of toxic metabolites, predisposition to psychosis, and drug interactions.

Adult

Patterns of manual dominance in patients with neuroleptic-induced movement disorders.

To explore the association between patterns of manual dominance and extrapyramidal symptoms we examined 32 chronic schizophrenic inpatients at Camarillo State Hospital for signs of tardive dyskinesia (TD) and neuroleptic-induced parkinsonism (NIP) using clinical rating scales (Abnormal Involuntary Movement Scale and Columbia Unified Parkinsons Disease Rating Scale) and specialized electromechanical instruments. Manual dominance was assessed using an eight-item hand preference demonstration test. Patients were divided into dextral (consistent use of right hand) and nondextral (any use of the left hand) groups. Dextrals showed a higher prevalence of TD than nondextrals on clinical rating measures (p less than 0.01). Orofacial ultrasound measures of TD revealed a similar association between TD and handedness. The two handedness groups did not differ on either the clinical or electromechanical measures of NIP. Interestingly, 28 of the 32 patients showed greater left than right facial movement. It is hypothesized that patients with more standard patterns of manual dominance may be at higher risk for TD than those with atypical patterns.

Adult

Neuroleptic plasma levels.

There is enormous variation in plasma levels of most neuroleptics in patients on the same dose. Much of the past research on the relation between plasma levels of antipsychotic drugs and clinical change, however, has been difficult to interpret. It does appear that decreased bioavailability, at least in public institutions, is rarely the cause of treatment failure. Aberrantly low plasma levels are more likely due to surreptitious noncompliance or drug interactions with enzyme inducers such as carbamazepine. Therapeutic plasma level ranges, in which good antipsychotic effect occurs without undue side effects, have been tentatively identified for perphenazine, haloperidol, fluphenazine, and chlorpromazine. The extent to which aberrantly high plasma levels are associated with inferior antipsychotic response is unclear. Antipsychotic plasma levels may be most useful when the distinction between side effects and worsening psychosis is unclear. The utility of high neuroleptic plasma levels in the treatment-resistant patient is unclear.

Antipsychotic Agents

Electromechanical characteristics of tardive dyskinesia.

Fifty patients with mild-to-moderate tardive dyskinesia (TD), who were devoid of other clinically apparent movement abnormalities, and 70 neurologically normal controls were assessed with a battery of instruments developed to measure and analyze the hyperkinetic movements of TD directly, objectively, and noninvasively. The electro-mechanical features that most consistently characterized and differentiated the TD group were a greater variability of all movements, increased energy in the 1-2 Hz frequency band in hand and foot movements, and a marked increase in movements during distracting tasks. This instrumentation promises to be useful in quantitating abnormal involuntary movements, in prospectively following individual patients to scan for small deviations from an instrument-established baseline, and in examining patients with combined movement abnormalities.

Adult

Early prediction of relapse in schizophrenia: an application of receiver operating characteristic (ROC) methods.

We compared different methods of identifying prodromal periods with regard to their ability to predict relapse in schizophrenia. Fifty stabilized schizophrenic patients, who received a low dose of schizophrenic patients, who received a low dose of fluphenazine decanoate (5 to 10 mg every 2 weeks) were monitored with weekly evaluations to determine whether they met criteria for nonpsychotic prodromal episodes. We evaluated three different scales: (1) the Anxious-Depression subscale of the Brief Psychiatric Rating Scale (BPRS); (2) a modification of the patient self-report Early Signs Questionnaire and (3) the Idiosyncratic Prodromal Scale (IPS). We used receiver operating characteristic (ROC) methods for comparing the different instruments as methods for predicting whether patients would or would not demonstrate a psychotic exacerbation in the 4 weeks following the assessment. Both the IPS and the BPRS cluster scores were better than chance at correctly identifying periods of vulnerability to psychotic exacerbation. The ROC analyses suggest that relatively small changes in the signs and symptoms of chronic schizophrenic patients in maintenance treatment may be clinically meaningful.

Humans