Multicenter study comparing thioridazine with diazepam and placebo in elderly, nonpsychotic patients with emotional and behavioral disorders. Comparison of SCH-12679 and thioridazine in aggressive mental retardates. Alleviating agitation, apprehension, and related symptoms in geriatric patients: A double-blind comparison of a phenothiazine and a benzodiazepien. Remoxipride versus thioridazine in elderly psychotic patients. The Australian multicentre double-blind comparative study of remoxipride and thioridazine in schizophrenia. Efficacy of antipsychotic medications in behaviorally disturbed dementia patients. A double-blind comparative study of remoxipride and thioridazine in the acute phase of schizophrenia. Thioridazine improves affective symptoms in schizophrenic patients. Inadequate treatment response to des-enkephalin-gamma-endorphin compared with thioridazine and placebo in schizophrenia.
Thioridazine was compared with placebo or diazepam or both in 610 elderly, nonpsychotic inpatients in geriatric wards of state hospitals or nursing homes. All patients manifested disruptive and difficult-to-manage behavior that interfered with adjustment to their environment and with proper care and treatment of their medical and emotional problems. Target symptoms such as agitation, anxiety, tension, apprehension, depressed mood, and sleep disturbances showed consistently marked improvement throughout the four-week study, as measured by the modified Hamilton Anxiety Scale, the modified Nurses' Observation Scale for Inpatient Evaluation (NOSIE), and global ratings. Significantly greater improvement on all measures was achieved with thioridazine than with placebo. In addition, greater improvement in the majority of symptoms assessed by the Hamilton Anxiety Scale and NOSIE were seen in patients who received thioridazine than in those given diazepam. SCH-12679, a benzazepine derivative, was compared to thioridazine and to placebo on the aggressive behaviour of mentally retarded patients. After a three-week chlorpromazine (100 mg t.i.d.) standardizaton period, no significant differences between the three treatment groups were observed in their abnormal behaviour. During the comparative phase, patients treated with SCH-12679 became less hyperative and less agitated while those treated with thioridazine became more violent, more choleric and more provocative. The clinical investigator and the nursing staff found significant differences between the active drugs. As compared to the placebo, SCH-12679 improved the behaviour of the patients while thioridazine aggravated their condition. No important adverse reaction was found and the drugs did not interact with the sex of the patients and the presence of epilepsy. The results suggest that, in mental retardation, physical restraint of hyperactivity might induce aggressivity and that one should be cautious in using neuroleptics in nonpsychotic patients. A four-week, double-blind study compared the effectiveness of thioridazine and diazepam in 40 geriatric patients with various symptoms of senility. Patients' progress was evaluated with the Hamilton Anxiety Rating Scale, a Modified Nurses' Observation Scale for Inpatient Evaluation (NOSIE), a global rating of degree of illness, and a global rating of degree of overall change. The data indicate that thioridazine was superior to diazepam inrelieving troublesome symptoms of senility. A total of 18 hospitalized elderly psychotic patients in need of antipsychotic treatment took part in a double-blind exploratory study concerning the safety, tolerability and efficacy of remoxipride and thioridazine. Their median age was 78 years (range 66-90 years). Over the study period of 6 weeks, 9 patients received remoxipride and 9 thioridazine. Both drugs were given in a dosage range of 50-200 mg/day. The median total score on the Brief Psychiatric Rating Scale at the start of active treatment was 18 in the remoxipride group and 24 in the thioridazine group. The scores were reduced to 6 and 7, respectively, at the last rating. The Clinical Global Impression at last rating showed 4 of the 9 remoxipride patients to be very much improved compared to 1 of the 9 thioridazine patients. Apart from three reports of severe drowsiness in the thioridazine group, the incidence of treatment-emergent adverse effects was low in both groups. No clinically significant aberrations were seen in laboratory tests or cardiovascular data. In conclusion, remoxipride seemed to be well tolerated in this group of patients and its antipsychotic efficacy in the doses used is promising. A double-blind, randomized study of parallel group design comparing remoxipride and thioridazine (dose range 150-600 mg/day of either drug) was undertaken at 11 Australian centres. A total of 144 patients (remoxipride = 73, thioridazine = 71) with DSM-III-R schizophrenia or schizophreniform disorder commenced the study, and 89 patients (remoxipride = 45, thioridazine = 44) completed the 6 weeks of the trial. The mean daily doses at last rating were 404 mg (remoxipride) and 378 mg (thioridazine). Initial Brief Psychiatric Rating Scale scores decreased by a mean 8.7 points in both remoxipride and thioridazine groups. Equivalent treatment responses were also confirmed by Clinical Global Impression. During the study, sedatives or hypnotics were needed by 68% of the remoxipride patients and 51% of the thioridazine patients. Thioridazine was associated with more postural hypotension, drowsiness, increased sleep, headache, dizziness on rising, dry mouth, sexual dysfunction and weight gain, while remoxipride patients reported more insomnia. There were no differences between remoxipride and thioridazine on dystonia, hypokinesia, dyskinesia, rigidity and akathisia. The results indicate that remoxipride has similar antipsychotic efficacy to thioridazine but causes fewer side effects. This study compared the therapeutic efficacy of thioridazine, loxapine, and a placebo in the treatment of behavioral disturbances in nursing home patients with dementia. Antipsychotic medications were effective for the specific behavioral problems of anxiety, excitement, emotional lability, and uncooperativeness. Subjects with the most severe symptoms at baseline assessment derived the greatest benefit from treatment. Sedation, extrapyramidal symptoms, and decreased blood pressure were common side effects among patients treated with the antipsychotic drugs. The authors conclude that antipsychotic medication has a definite but limited therapeutic role in the treatment of behavioral disturbances in nursing home patients with dementia. Sixty-one patients with acute schizophrenia received either remoxipride (75-375 mg daily) or thioridazine (150-750 mg daily) for 6 weeks. There was no statistically significant between-drug difference in improvement in mental state, as measured by the Brief Psychiatric Rating Scale, although the trend favoured thioridazine; global assessment of illness severity at the last rating also favoured thioridazine. Sedation, anticholinergic effects, autonomic dysfunction, and weight gain were significantly more common in patients receiving thioridazine. Both drugs produced few extrapyramidal effects, but both were associated with cardiovascular changes in two patients; neither drug produced significant abnormalities in laboratory tests. Consenting schizophrenic patients ranging in age from 18 to 63 years were withdrawn from antipsychotics for at least 1 week and randomly assigned to receive identical capsules of thioridazine (n = 13), molindone (n = 10), or haloperidol (n = 12) for a minimum of 6 weeks. Compared with the molindone- and haloperidol-treated patients, the thioridazine-treated patients were significantly improved over time as measured by Brief Psychiatric Rating Scale (BPRS) and Hamilton Rating Scale for Depression (HAM-D) total scores. Improvement in BPRS scores was due largely to improvement in symptoms of anxiety and depression. Subjects did not differ significantly on other measures, with the important exception of weight. On average, molindone patients lost 5 pounds over the 6 weeks of treatment, whereas thioridazine patients gained 6 pounds. Haloperidol-treated patients had no significant weight changes. The possibility of an involvement of peptidergic systems in schizophrenia has been under investigation for a number of years. Studies of the efficacy of des-tyr-gamma-endorphin were equivocal; more recent studies with des-enkephalin-gamma-endorphin have reported some activity but the peptide has only been investigated as an adjunct to neuroleptic medication, apart from one very small active reference comparator study. In the multicentre study reported here, 96 patients suffering from schizophrenia (DSM-III with a current exacerbation if chronic) were allocated randomly to double-blind treatment with either des-enkephalin-gamma-endorphin (DE-gamma-E) (Org 5878) 10 mg given as a once daily intramuscular injection for 4 weeks, thioridazine 400 mg orally in 2 divided doses or placebo using a double-dummy technique to preserve blindness. There was a significant advantage for thioridazine compared with placebo registered on all measures at weeks 3 and 4. There was no difference between DE-gamma-E and placebo. There was a significant difference between thioridazine and DE-gamma-E at weeks 3 and 4 registered on the MSS and at week 3 registered on the BPRS. The lack of efficacy of DE-gamma-E suggests that the theories that the endorphins have an important role in schizophrenia have to be revised. The need for well designed placebo controlled studies for assessing efficacy in schizophrenia is emphasized.
Very limited data are available to support the use of thioridazine in the treatment of dementia. If thioridazine were not currently in widespread clinical use, there would be inadequate evidence to support its introduction.
The only positive effect of thioridazine when compared to placebo is the reduction of anxiety. When compared to placebo, other neuroleptics, and other sedatives, it has equal or higher rates of adverse effects.
Clinicians should be aware that there is no evidence to support the use of thioridazine in dementia, and its use may expose patients to excess side effects.