Comparison of quality of life with standard of living in schizophrenic out-patients.

Standard of living reflects the objective dimension of how well the basic needs of life are met, while quality of life is the patient's own subjective view of well-being and satisfaction with her/his life. Sixty-one schizophrenic out-patients completed self-report inventories and participated in interviews about quality of life and standard of living. When living standards were met by a well functioning social service system, patients' perceptions of their quality of life and their standard of living appeared to be independent. Subsequent analyses revealed that 'inner experiences' was one quality-of-life domain frequently reported as unsatisfactory. Moreover, differences in quality of life were found across patients' age, education, and work status.

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.

Tardive dyskinesia in schizophrenic patients: correlation with negative symptoms.

The relationship between severity of tardive dyskinesia (TD) and the prominence of negative symptoms was assessed in 25 right-handed, medicated schizophrenic patients. TD was quantified using ultrasound detectors and frequency measurement techniques as well as with observer rating scales. Electromechanical studies revealed a systematic relationship between TD severity and negative symptoms; TD was more severe in patients with fewer negative symptoms. The correlation was small in magnitude.

Comparison of electromechanical measures and observer ratings of tardive dyskinesia.

Thirty-three patients with tardive dyskinesia (TD) were studied with multiple-observer consensus ratings of videotaped examinations, ultrasound counts of movement, and electromechanical frequency measures of the movements. There were statistically significant correlations between orofacial ultrasound measures and TD severity determinations made by observers. Clinical ratings did not correlate with frequency measures. Ultrasound measures substantiate observer rating scales, whereas frequency measures appear to provide information not available from clinical rating scale scores.

Low- and conventional-dose maintenance therapy with fluphenazine decanoate. Two-year outcome.

We evaluated the effectiveness and the side effects of what we defined as low (5-mg) and conventional (25-mg) doses of fluphenazine decanoate administered every two weeks in a double-blind comparison. Subjects were 66 patients who fulfilled DSM-III criteria for schizophrenic disorder. Evaluation of the survival with each dose revealed no significant difference at one year, but significantly better survival was seen with the 25-mg dose (64%) than the 5-mg dose (31%) at two years. There was no significant difference in survival when the clinician was permitted to make a dosage adjustment up to 10 mg in the low-dose group and 50 mg in the higher-dose group when the patient demonstrated evidence of a symptomatic exacerbation. Patients assigned to the higher dose appeared to feel more uncomfortable during the early months of the study, as indicated by significantly higher scores on subscales of the Hopkins Symptom Checklist-90R and higher side effect scores for retardation and akathisia. Implications for clinical practice are discussed.

The sulfoxidation of fluphenazine in schizophrenic patients maintained on fluphenazine decanoate.

Highly sensitive radioimmunoassays were applied to study the sulfoxidation of fluphenazine in 30 schizophrenic patients maintained on either 5 mg or 25 mg fluphenazine decanoate by intramuscular injection every 14 days over a period of 6 months. The presence of the sulfoxide metabolite was detected in all but one of the patients, such that 97% of the 340 plasma samples analysed contained the metabolite. Interpatient variations in plasma levels of fluphenazine, fluphenazine sulfoxide, and in drug to metabolite plasma level ratios were several fold higher than the corresponding intrapatient variations at both dosages. There were statistically significant tendencies for mean plasma fluphenazine levels to rise and mean plasma sulfoxide levels to fall over the 6-month period of study among patients on the high dose, consistent with our previously reported observation that it takes 3-6 months to establish a steady state of fluphenazine with this dosage regimen. By contrast, there were no statistically significant changes in mean plasma levels of either fluphenazine or its sulfoxide in patients on the low dose. Nevertheless, there was a significant rise in fluphenazine to fluphenazine sulfoxide mean plasma level ratios in both dosage groups. It is difficult to assess the significance of the changes in the drug to metabolite ratios with time, since there are no kinetic data on the phase II metabolism (conjugation) of fluphenazine or fluphenazine sulfoxide. This study shows that sulfoxidation is an important major pathway in the metabolism of intramuscularly-administered fluphenazine, and implies that metabolic sites other than gut wall are also involved in the process.

Benefits and limitations of neuroleptics--and other forms of treatment--in schizophrenia.

Neuroleptic drugs are of proven value in schizophrenia for both the treatment of acute psychotic states and for the prevention of relapse in patients who have recovered from psychosis. However, these drugs have a number of important limitations: they are not effective for all patients, they have a number of serious adverse effects, and they are limited in what they can do. Some of the more serious side effects, particular tardive dyskinesia, require that clinicians use these drugs only in situations when they are demonstrably effective, and at the lowest effective dose. For most schizophrenic patients, neuroleptics should be only one part of a treatment program which will also include appropriate psychosocial treatment.

Fluphenazine plasma levels in patients receiving low and conventional doses of fluphenazine decanoate.

Plasma fluphenazine concentrations (FLU) were measured in 45 patients with schizophrenic disorders who participated in a double-blind comparison of 5 and 25 mg fluphenazine decanoate (FD). The rise in plasma level of FLU 24 h after a "test dose" was significantly correlated with steady state FLU concentration at 12 weeks (for 5 mg patients, r = 0.45, P = 0.04; for 25 mg, r = 0.78, P = 0.005). Patients who had low FLU at baseline required nearly 6 months to reach a steady state when they received 25 mg. Patients who received 5 mg and had low FLU at baseline continued to demonstrate relatively low plasma levels for the entire 1st year. Although the mean FLU at 6 months was lower for patients who relapsed during the subsequent 18 months (0.57 ng/ml for relapsers vs 1.01 ng/ml for nonrelapsers), this difference was not statistically significant. When plasma levels from both dosage groups were combined, FLU at 12 weeks correlated significantly with factor scores for akinesia (r = 0.52, P = 0.002) and BPRS cluster scores for retardation (r = 0.52, P = 0.002). These results indicate that the measurement of fluphenazine plasma levels may be useful in determining when patients treated with FD are receiving drug doses which are likely to cause discomforting side effects.

Therapeutic monitoring of chlorpromazine I: Pitfalls in plasma analysis.

Pooled plasma from healthy volunteers was spiked with pure, synthetic chlorpromazine (CPZ), chlorpromazine sulfoxide (CPZSO), or chlorpromazine N-oxide (CPZNO), and then made alkaline with either sodium hydroxide or sodium carbonate. The samples were allowed to stand at room temperature for various timed intervals before extraction with organic solvent. It was found that CPZNO was reduced to CPZ in plasma made alkaline with sodium hydroxide, but not in protein-free buffer solution at high pH nor in plasma made alkaline with sodium carbonate. The reaction appears to take place through reducing equivalents generated by the action of sodium hydroxide on plasma proteins. Thus, apparent concentrations of CPZ in plasma from patients were elevated by as much as 343% when sodium hydroxide was used compared with concentrations in aliquots of the same plasma samples alkalinized with sodium carbonate. The amount of CPZ produced from CPZNO depends on the type of extraction procedure employed as well as on the quantity of sodium hydroxide added to the plasma. By contrast, no interconversion between CPZ and CPZSO or CPZNO and CPZSO was observed in plasma alkalinized and extracted under any of the conditions tested.

Akathisia with haloperidol and thiothixene.

We studied the incidence of akathisia in two populations of newly admitted schizophrenic patients: one group was treated with haloperidol and the other group was treated with thiothixene hydrochloride. Within six hours after taking a 5-mg test dose of haloperidol, 40% of the patients experienced akathisia; during maintenance treatment with 10 mg of haloperidol taken at bedtime, 75% of the patients experienced akathisia by the seventh day. With thiothixene hydrochloride (0.22-mg/kg test dose; 0.44-mg/kg maintenance dose), the respective percentages were 20% and 46%. The akathisia experienced after administration of the test of haloperidol dose was not mild or inconsequential; 28% of the patients experienced moderate, 17% of the patients experienced severe, and 22% of the patients experienced very severe akathisia. Akathisia with haloperidol could not be suppressed completely in half of the patients. Treatment-resistant akathisia was experienced as anxiety and depression. We believe these tallies to be important because akathisia causes much misery and often goes undiagnosed.

Costs and benefits of two doses of fluphenazine.

The relative costs and benefits of low- and conventional-dose neuroleptic maintenance therapy were evaluated in a double-blind comparison of 5 and 25 mg of fluphenazine decanoate administered every two weeks. Subjects were 50 patients fulfilling DSM-III criteria for schizophrenic disorder who had been successfully maintained with 25 mg or less of fluphenazine decanoate. A one-year survival analysis disclosed that there were no statistically significant differences between the two doses insofar as preventing relapse. Patients receiving the higher dose appeared to feel more uncomfortable, as indicated by higher scores on subscales of the Hopkins Symptom Checklist-90. In addition, patients receiving the higher dose had higher side-effect scores. These findings suggest that a substantial proportion of patients who are presently maintained with 25 mg or less of fluphenazine decanoate every two weeks will do just as well with as little as 5 mg.

Response to antipsychotic medication: the doctor's and the consumer's view.

The subjective response to antipsychotic medication was systematically evaluated in two samples of schizophrenic patients, one treated with haloperidol, the other with thiothixene. For both groups, a dysphoric response to the first dose was found to be a powerful predictor of noncompliance. A persisting dysphoric response was associated with a poor clinical outcome. Dysphoric responses were powerfully associated with akathisia. Patients' subjective responses were consistent throughout therapy, and there was moderate agreement between the patients' evaluation of the medication and the staff's ratings of improvement. The authors suggest that the subjective response to antipsychotic medication should not be dismissed and that dysphoric responses should be acknowledged.

A step forward in research on psychotherapy of schizophrenia.

The Boston group have devoted 10 years to a thoughtful, comprehensive, and much needed study that will undoubtedly become a classic reference in the field. If the emphasis is placed on differences that reached statistical significance, the major finding is minimal outcome differences between exploratory, insight-oriented (EIO) and reality-adaptive, supportive (RAS) therapies with, if anything, significant advantages to RAS in recidivism and performance. Selective beneficial effects for EIO gain only very weak support. The results should contribute to a climate wherein we may move on to study how psychotherapy and pharmacotherapy can be combined to achieve optimal results and minimize toxic effects.

Plasma levels of thiothixene by radioreceptor assay: clinical usefulness.

Thirty-four newly admitted schizophrenic patients were treated with a fixed dose of thiothixene (0.44 mg/kg) for 4 weeks. Thiothixene and its active metabolites were measured by a new radioreceptor assay. Improvement occurred over the entire range of recorded plasma levels, but the chances of substantial improvement appear greater above 40 neuroleptic units (n.u.). The data do not support the notion of a "therapeutic window", in that higher plasma levels were not associated with side effects or clinical deterioration (although at extreme plasma levels this must of course be so). In 11 nonresponders dosage could not be increased because of side effects. If a non-responder with troublesome side effects has a low plasma level (less than 40 n.u.), it would seem prudent to switch to another antipsychotic drug.