A double-blind comparison of fluphenazine and haloperidol in outpatient schizophrenic children

A study is presented in which fluphenazine and haloperidol administered on a double-blind basis were evaluated in an outpatient group of 30 schizophrenic children, 6 to 12 years of age. The duration of treatment was 12 weeks. Mean dosage for both treatment groups was 10.4 mg/d, with a maximum dose of 16 mg/d. Both fluphenazine and haloperidol proved highly effective in our population of schizophrenic children, with the two drugs indistinguishable in overall efficacy. Both drugs were characterized by low incidence of side effects with a tendency for fluphenazine treatment to induce extrapyramidal symptoms with greater frequency than haloperidol. Side effects were easily managed by dose reduction or contramedication. No child had to be terminated due to an adverse reaction. It is suggested that these findings, as well as other reports in the literature, indicate that fluphenazine and haloperidol deserve consideration in the treatment of schizophrenic children.This study was supported by Grant MH 18180 from The National Institute of Mental Health, United States Public Health Service, and by a grant from McNeil Laboratories, Inc.     

Distinguishing Acute and Tardive Akathisia by Monitoring Microvibration: A Pilot Study

Abstract: One acute and one tardive akathisia patients, respectively, and 10 : neuroleptic-treated schizophrenic patients were injected with biperiden 5 : mg or saline and the response to anticholinergics was monitored by microvibration (MV) as an indicator of muscle tonus. These data were subjected to the Fast Fourier Transform and an averaged power spectrum was computed. The biperiden injection markedly reduced the power spectral values of MV in acute akathisia. In contrast with acute akathisia, the biperiden injection sigdlcantly increased the power spectral values of MV in tardive akathisia. The subjective feelings of akathisia patients were parallel to the power spectral values of MV. Control patients were not aflected by such treatment. The present findings show that the subjective symptoms of akathisia can be well defined by the objective, differential response to anticholinergics in a manner similar to the visible extrapyramidal symptoms (dystonia, dyskinesia) induced by neuroleptics.     

Case report of propranolol (Inderal) pharmacotherapy for neuroleptic-induced akathisia and tremor

This case report describes a schizophrenic patient who developed akathisia and tremor following neuroleptic pharmacotherapy with fluphenazine decanoate. The patient also suffered from familial (benign essential) tremor. The patient's neuroleptic-induced extrapyramidal side effects were not relieved by anticholinergic antiparkinson drugs or by phenobarbital. The patient was started on propranolol 10 mg b.i.d. She was also started on diazepam 5 mg t.i.d. for anxiety. The diazepam dose was held constant and propranolol was gradually increased to 40 mg q.i.d. The patient's extrapyramidal symptomatology gradually resolved over the course of one month, during which time the propranolol dose was being steadily increased. Propranolol also effectively controlled her familial tremor. After nine months as an outpatient, during which time the patient was neuroleptic-free, she developed psychotic decompensation for which she was treated with thiothixene. Akathisia or tremor did not develop, possibly because the patient was taking propranolol simultaneously. Propranolol may be useful for treating neuroleptic-induced akathisia. This requires systematic investigation with open and controlled trials.     

Drug refusal in schizophrenia: causes and prescribing hints.

Many discharged patients diagnosed as schizophrenic do not continue to take their prescribed antipsychotic medication. Reasons for reluctance to take drugs include the development of extrapyramidal symptoms, most notably akathisia and akinesia; a poor doctor-patient relationship; or the patient's preference to continue his schizophrenic existence. To improve drug compliance, the physician should ask the patient about his impressions of side-effects and should let the patient help determine the optimal dosage.     

Antipsychotic effects, side effects and effective dosis of the butyrophenone lenperone (AHR 2277)

Three open studies with Lenperone were performed. 50 hospitalized schizophrenic patients were treated 20-30 days with Lenperone. The therapeutic effective dose was 30-50 mg/day. The highest daily dosage was 90 mg. Patients were examined on fixed observation days and the findings were documented by means of the AMP system. AMP data were analyzed at symptom and syndrome level and compared using an analysis of covariance. In the described dosage Lenperone acted only little sedating, strong antipsychotic and caused only a few single extrapyramidal and little autonomic side effects. The dosage is limited because of the effect on heart and blood circulation. Lenperone caused a good improvement of depressive symptoms in the schizophrenic patients. Lenperone was well tolerated and slowed a rapid onset of its antipsychotic effect. It caused a steady improvement of productive schizophrenic symptoms. For better knowledge of the profile of the effects of Lenperone, a trial in depressive paranoid syndromes, for example schizoaffective psychoses, would be interesting; a double-blind trial in comparison to a well-known antipsychotic would be very useful.     

Double-blind comparison of haloperidol decanoate and fluphenazine decanoate effectiveness, side-effects, dosage and serum levels during a six months' treatment for relapse prevention

In this present study 31 schizophrenic patients were treated for six months for relapse prevention under double-blind conditions with either haloperidol decanoate (22) or fluphenazine decanoate (9). In respect of the prophylactic action, both depot neuroleptics proved to be equal during the comparatively short period of observation. In both groups a psychotic relapse occurred that could not be managed by increasing the depot dosage. No side-effects worth mentioning appeared in either group of patients; patients under haloperidol decanoate, however, only required half the quantity of anti-parkinson medication as compared with patients treated with fluphenazine decanoate, and also displayed extrapyramidal motor symptoms (EPMS) to a lesser degree. Patients received a mean monthly injection of 80 mg of Haloperidol, reaching steady-state serum levels of about 3 ng/ml in the third injection interval. Fluphenazine serum levels known so far for seven patients amount to 0.8 ng/ml after fluphenazine injections of 21 mg every 14 days.     

Akathisia variants and tardive dyskinesia

Eighty-two schizophrenic outpatients receiving maintenance antipsychotic medication were assessed for akathisia and tardive dyskinesia. Thirty-nine (48%) manifested patterns of nondyskinetic, restless movement characteristic of akathisia. On the basis of their clinical features, these patients were divided into three groups: "acute" akathisia (recent onset, related to an increase in antipsychotic drug dose); "pseudoakathisia" (motor signs but no subjective symptoms); and "chronic" akathisia (a mixed category including persistent acute akathisia and "tardive" akathisia with the pharmacologic characteristics of tardive dyskinesia). Coarse, jerky foot tremor was observed as an invariable accompaniment of acute akathisia. A significant association was found between choreoathetoid limb dyskinesias, orofacial dyskinesias, and the presence of chronic akathisia. Also, the findings suggested a possible relationship between pseudoakathisia, orofacial and limb dyskinesia, and the severity of negative schizophrenic symptoms.     

Pimozide versus fluphenazine in ambulatory schizophrenics: A 12-month comparison study.

In this study, chronic schizophrenic outpatients who had been maintained on various neuroleptics for an average of about 4 years had their previous medications (approximately equivalent to 695 mg of chlorpromazine per day) changed abruptly to either pimozide or fluphenazine given in single daily oral doses on a double-blind basis for a period of 52 weeks. Average daily doses were pimozide 9.6 mg and fluphenazine 12.5 mg. Measurements of the therapeutic effects of the two drugs were made immediately prior to starting the study, at the end of the 2nd and 4th weeks, and thereafter every 4th week to the end of the study. Three psychometric scales were used for evaluation: Brief Psychiatric Rating Scale (BPRS); Evaluation of Social Functioning (ESFR); and Clinical Global Impressions (CGI). In addition, patients participated in a Social Adjustment Inventory (SAI) evaluation. Statistical analysis with the use of several statistical techniques for between- and within-drug group comparisons revealed that pimozide and fluphenazine were equally effective in maintaining control of symptomatology of chronic schizophrenics at a level commensurate with or better than that provided by their previous medication. Side effects were characteristic of marketed neuroleptics, similar in severity and occurrence between study-drug groups, mainly extrapyramidal symptoms, and readily controlled with antiparkinsonian medication. Pimozide, slightly more potent than fluphenazine, proved to be equally effective for the long-term management of chronic schizophrenic patients.     

Cigarette smoking in schizophrenia: relationship to psychopathology and medication side effects.

OBJECTIVE: The authors' goal was to study the relationship between smoking status and clinical characteristics in schizophrenic patients. METHOD: Seventy-eight schizophrenic outpatients were assessed by a single rater using the Brief Psychiatric Rating Scale (BPRS), the Abnormal Involuntary Movement Scale, and the Simpson-Angus Scale for extrapyramidal symptoms. Current smokers (N = 58) were compared with nonsmokers (N = 20) on clinical variables by independent t tests and chi-square tests. Differences in outcome variables were tested by multiple analysis of covariance (ANCOVA) with smoking status and gender as factors and age, neuroleptic dose, and caffeine consumption as covariates. RESULTS: Seventy-four percent of patients were current smokers and reported a mean of 19 cigarettes smoked per day. Compared to nonsmokers, current smokers were significantly more likely to be men, to be younger, and to have had an earlier age at onset and a greater number of previous hospitalizations. Current smokers and nonsmokers received mean neuroleptic doses of 1160 and 542 mg/day (chlorpromazine equivalents); the difference was significant. Current smokers also displayed significantly less parkinsonism and more akathisia and had higher total scores on the BPRS. Overall multiple ANCOVA demonstrated a significant main effect for smoking status but not gender or the interaction between gender and smoking status. Univariate ANCOVAs demonstrated a significant main effect of smoking status only for the Simpson-Angus Scale score. CONCLUSIONS: Cigarette smokers receive significantly higher neuroleptic doses, in part because of a smoking-induced increase in neuroleptic metabolism. Smoking is also associated with significant reduction in levels of parkinsonism. Smoking status is a significant factor that should be considered in assessment of neuroleptic dose requirements and neuroleptic side effects.     

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.     

Risperidone augmentation of clozapine

OBJECTIVE: Atypical antipsychotics are frequently used as augmentation agents in clozapine-resistant schizophrenic patients. Risperidone (RIS) is the one most studied as a clozapine (CLZ) adjunct. The aim of this study is to critically review all published studies regarding the efficacy and safety of RIS as an adjunctive agent in CLZ-resistant schizophrenic or schizoaffective patients. METHODS: A MEDLINE search from January 1988 to June 2005 was conducted. Identified papers were examined against several clinical, pharmacological and methodological parameters. RESULTS: A total of 15 studies were found (2 randomized controlled trials, 3 open-label trials (OTs) and 8 case-studies (CSs)) comprising 86 schizophrenic or schizoaffective patients (mean age 38.4 years). Mean CLZ dosage during the combined treatment was 474.2 mg/day. Plasma CLZ levels were assessed in 62 patients (72.1%). RIS was added at a mean dosage of 4.6 mg/day for a mean of 7.9 weeks. Significant improvement in psychopathology was reported for 37 patients (43%). A lower RIS dosage and a longer duration of the trial seemed to be associated with a better outcome. Main side effects reported were: extrapyramidal symptoms or akathisia (9.3%), sedation (7%) and hypersalivation (5.8%). CONCLUSIONS: Existing evidence encourages the use of RIS as an adjunctive agent in CLZ-resistant schizophrenic or schizoaffective patients.     

Alcohol abuse in chronic schizophrenics: implications for management in the community

This study was designed to investigate the effects of regular alcohol consumption on chronic schizophrenic patients maintained on fluphenazine decanoate in the community. A group of patients who consumed more than 20 units of alcohol per week was compared with those who did not drink or did so only occasionally. It was found that patients in the alcohol group had a higher frequency of previous relapses, a greater severity of positive symptoms and a lower incidence of extrapyramidal side effects except tardive dyskinesia for which there was no difference. Serum fluphenazine levels were lower in this group (NS). It was concluded that patients who regularly consume alcohol tend to be clinically unstable, perhaps because of poor therapeutic control.     

Intramuscular ziprasidone, 2 mg versus 10 mg, in the short-term management of agitated psychotic patients

BACKGROUND: There is a clear need for effective, well-tolerated intramuscular (i.m.) agents for the acute control of agitated psychotic patients. Currently used agents, including conventional antipsychotics and/or benzodiazepines, may be associated with distressing side effects such as extrapyramidal side effects and excessive sedation. OBJECTIVE: The objective of this study was to evaluate the efficacy and tolerability of the rapid-acting i.m. formulation of the novel antipsychotic ziprasidone in the treatment of inpatients with psychosis and acute agitation (DSM-IV diagnoses). METHOD: In a 24-hour, double-blind, fixed-dose clinical trial, patients were randomly assigned to receive up to 4 injections (every 2 hours p.r.n.) of 2 mg (N = 54) or 10 mg (N = 63) of ziprasidone i.m. The Behavioral Activity Rating Scale measured behavioral symptoms at baseline and the response to treatment up to 4 hours after the first i.m. injection. RESULTS: Ziprasidone i.m., 10 mg, rapidly reduced symptoms of acute agitation and was significantly more effective (p < .01) than the 2-mg dose up to 4 hours after the first injection. Patients were calmed but not excessively sedated, and over half were classed as responders 2 hours after the 10-mg dose. No acute dystonia or behavioral disinhibition was reported. One patient who received the 10-mg dose experienced the extrapyramidal side effect akathisia. CONCLUSION: Ziprasidone i.m., 10 mg, is rapidly effective and well tolerated in the short-term management of the agitated psychotic patient. Comparison with a study of identical design comparing 2-mg with 20-mg doses in patients with similar levels of psychopathology suggests that efficacy with 10 mg or 20 mg of ziprasidone i.m. is significant and dose related.     

Low dose fluphenazine decanoate in maintenance treatment of schizophrenia

To test the clinical efficacy of low dose fluphenazine decanoate (1.25 mg to 5.0 mg biweekly), we carried out two separate experiments: (1) an open trial in 57 schizophrenic outpatients, lasting 6 months; (2) a double-blind, placebo-controlled discontinuation study in a subgroup of patients who maintained good remission throughout the entire 6-month open trial. The results suggest that lower doses of fluphenazine decanoate than those usually used may be effective in preventing psychotic relapse while keeping total cumulative dosage to a minimum.     

Treatment of neuroleptic-induced akathisia with the 5-HT2A antagonist trazodone

Akathisia is a common and distressful extrapyramidal adverse side effect usually resulting from the use of antipsychotic medications. Early management of akathisia is important because it may be associated with poor treatment response and medication noncompliance. Unfortunately many patients fail to respond to standard management of akathisia. In addition to dopaminergic mechanisms, it has been hypothesized that serotonin may play a prominent role in the pathophysiology of akathisia. Trazodone is an antidepressant agent demonstrating prominent serotonergic antagonistic properties. This open-label pilot study investigates the efficacy of trazodone in the management of akathisia. Nine female patients with a score of at least "mild akathisia" on the Barnes Akathisia Scale, and receiving a stable dose of antipsychotic medication, were administered trazodone, titrated up to a dosage of 100 mg/day over a period of 5 days. The patients demonstrated marked improvement in symptoms of akathisia. In addition, some improvement was noted in symptomatology of anxiety, depression, and psychosis. These observations suggest the use of trazodone as a beneficial and relatively safe medication for the treatment of antipsychotic medication-induced akathisia. Further study in the context of a double-blind, placebo-controlled trial is mandated to substantiate these preliminary findings.     

利培酮所致静坐不能临床研究

目的：了解利培酮所致静坐不能的发生率及其相关因素。方法：对128例单独服用利培酮治疗的精神分裂症患者采用修改的Simpson锥体外系反应量表评定静坐不能,进行为期8周的临床研究。结果：利培酮所致的静坐不能发生率为25．8％,多数发生于治疗的2周内,静坐不能的发生与利培酮剂量、入院时的阳性与阴性症状量表（PANSS）总分及加药速度有关。使用普萘洛尔及氯硝西泮治疗效果好。结论：利培酮所致静坐不能发生率虽较高,但若处理得当,不影响继续治疗。     

A single-blind, randomized comparison of olanzapine at a starting dose of 5 mg versus 20 mg in acute schizophrenia

Acute psychotic episodes represent critical situations during the course of schizophrenia. Olanzapine (OLZ), a second-generation antipsychotic, is efficacious in acute settings at dosages of 5 to 20 mg/d, and it can be considered a first-line treatment for patients with an acute episode of schizophrenia. The aim of this study was to evaluate the efficacy and tolerability of OLZ at a starting dose of 5 mg versus 20 mg in acute schizophrenic patients and to compare titration versus nontitration.Fifty-one schizophrenic inpatients were randomly assigned to receive OLZ at 5 mg/d (26 patients, group 1) or 20 mg/d (25 patients, group 2) as a starting dosage during an exacerbation phase. In group 1, the OLZ dosage was increased to a mean dosage of 10.55 (+/- 4.00) mg/d. Group 2 received OLZ at a fixed dose of 20 mg throughout the hospitalization period.Olanzapine was significantly and clinically effective on Brief Psychiatric Rating Scale (BPRS), Positive and Negative Syndrome Scale, PANSS positive symptoms, and Hamilton Rating Scale for Depression in both groups. There were no significant differences between groups 1 and 2 in the percent improvement in BPRS, Positive and Negative Syndrome Scale, PANSS positive symptoms, PANSS negative symptoms, or Hamilton Rating Scale for Depression; but group 2 was significantly superior in the mean percent improvement in the BPRS items of anxiety (P < 0.001) and suspiciousness (P < 0.05).In conclusion, the higher doses evidence more efficacy on anxiety and suspiciousness, so it seems to be useful to begin therapy with a full dose of the drug to obtain the maximum effect without any significant side effects.     

Risperidone versus zuclopenthixol in the treatment of acute schizophrenic episodes: a double-blind parallel-group trial

A double-blind, randomized, multi-center, parallel-group study was conducted in Finland to compare the efficacy and safety of risperidone with zuclopenthixol in patients with acute exacerbations of schizophrenia or schizophreniform disorder. Ninety-eight patients were randomly assigned to treatment with risperidone (n= 48) or zuclopenthixol (n= 50), in variable doses, for 6 weeks. The mean daily doses of risperidone and zuclopenthixol at the end of the trial were 8 mg and 38 mg respectively. Efficacy was assessed throughout by the Positive and Negative Syndrome Scale for schizophrenia and Clinical Global Impression. Safety assessments included the Extrapyramidal Symptom Rating Scale, UKU Side-Effect Rating Scale, vital signs, body weight and laboratory screening. The results indicate that risperidone is at least as effective as zuclopenthixol for the treatment of acute schizophrenic episodes, with a trend towards greater improvement in the overall severity of symptoms. The onset of action was significantly shorter with risperidone than with zuclopenthixol. Although the general tolerability of the two drugs was comparable, fewer patients experienced extrapyramidal symptoms with risperidone, so that significantly fewer risperidone-treated patients required antiparkinsonian medication.     

Improvement of schizophrenic patients with primary negative symptoms treated with amisulpride. Amisulpride Study Group

OBJECTIVE: The goal of this placebo-controlled study was to evaluate the efficacy and safety of low doses of amisulpride, an atypical antipsychotic of the benzamide class with high affinity for D2 and D3 dopamine receptors, in the treatment of schizophrenic patients with predominantly primary negative symptoms. METHOD: After completion of a 4-week washout period, schizophrenic patients with primary negative symptoms participated in a 12-week, multicenter double-blind trial of placebo (N = 83), amisulpride, 50 mg/day (N = 84), or amisulpride, 100 mg/day (N = 75). They were evaluated with the Scale for the Assessment of Negative Symptoms, the Scale for the Assessment of Positive Symptoms, the Brief Psychiatric Rating Scale, and the Montgomery-Asberg Depression Rating Scale. RESULTS: Both amisulpride treatment groups showed significantly greater improvement in negative symptoms than the placebo group. Positive symptom scores were low at baseline and changed minimally during the study, suggesting that the improvement in negative symptoms was independent of improvement in positive symptoms. The safety of amisulpride was comparable to that of placebo, and extrapyramidal symptoms were infrequent. Comparable efficacy and safety results were observed with either dose of amisulpride. CONCLUSIONS: These findings confirm and extend those of earlier placebo-controlled studies of low-dose amisulpride in the treatment of patients with predominantly negative symptoms of schizophrenia.     

A COMPARATIVE TRIAL OF FLUPHENAZINE DECANOATE AND FLUPENTHIXOL DECANOATE

A double-blind cross-over study is reported which compares the antipsychotic properties and the side effects of depot flupenthixol with fluphenazine decanoate in chronic schizophrenic inpatients. Special emphasis was laid on examining changes in the target symptoms of apathy/anergia and depression in which flupenthixol has been claimed to be particularly effective. No significant differences were found between treatments on schizophrenic symptoms, or as regards the extrapyramidal side effects produced by equipotent doses of the two drugs. Reasons for the essentially negative results are discussed against a background review of earlier optimistic studies of flupenthixol.