Full circle-old drugs prove more beneficial than newer agents for schizophrenia: a case report.

A 55-year-old female with a diagnosis of schizophrenia currently resides in an assisted living facility in a large metropolitan suburb. For approximately 25 years, the patient was relegated to a life of poor symptom control and social adjustment, largely due to nonadherence, relapse, and rehospitalization. The patient experienced a trial-and-error approach to drug therapy, which resulted in reliance on the older or first generation agents for symptom improvement. This case supports the assertion that the second-generation or atypical antipsychotics used to treat schizophrenia are no better than older drugs in terms of efficacy or tolerability.

Tardive dyskinesia and steady-state serum levels of thiothixene.

The purpose of this investigation was to determine the relationship between serum levels of the neuroleptic agent thiothixene and tardive dyskinesia in schizophrenics of a wide age range. Forty-one male schizophrenic subjects, 21 with tardive dyskinesia and 20 without, were given a fixed dosage of thiothixene hydrochloride (10 mg orally four times daily) after a drug-free period of one week. Higher steady-state serum levels of thiothixene (obtained after five days of a fixed-dosage schedule) were associated with greater degrees of tardive dyskinesia. This relationship was independent of the relationship between tardive dyskinesia and age.

Subjective response to antipsychotic drugs.

Sixty-three newly admitted schizophrenic patients were given a test dose of thiothixene and their subjective response was recorded by a technician blind to clinical ratings. All patients were then treated wih thiothixene in an active milieu setting. Patients varied widely in their subjective responses. An initial dysphoric response was a powerful predictor of both immediate and eventual drug refusal. Before treatment, dysphoric responders tended to be less symptomatic and did significantly better on the Continuous Performance Test. Dysphoric responders experienced significantly more extrapyramidal symptoms following the test dose. Some dysphoric responders did have a good outcome when treated with very low doses. We recommend that patients with a history of dysphoric response be given a very low dose initially.

Motility, Parkinsonism, and prolactin with thiothixene and thioridazine.

Clinical impressions suggest that thioridazine hydrochloride produces fewer extrapyramidal effects and more sedation than thiothixene. These drugs were given, each for three weeks, to 15 chronic schizophrenic outpatients in a counterbalanced, double-blind, crossover study. Spontaneous locomotion was recorded with an unobtrusive actometer toward the end of each three-week drug period. Surprisingly, patients were significantly more active with thioridazine, whereas parkinsonian scores, prolactin levels, and Brief Psychiatric Rating Scale scores remained about equal with the two drugs; thioridazine's extrapyramidal side effects were not "atypical." There are some explanations for why common clinical impressions and recent rodent studies have not predicted these results.

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.

Fever, tachycardia, and hypertension with acute catatonic schizophrenia.

Fever, tachycardia, and hypertension developed concurrently with the administration of thiothixene during an acute episode of agitation in a case of catatonic schizophrenia. No cause for the fever or hyperkinetic state was found, and the syndrome resolved spontaneously one week after antipsychotic drug therapy was halted. This case appears to be an example of "acute lethal catatonia" or the neuroleptic "malignant" syndrome, both of which may be due to disturbances of dopamine function within the CNS. Such cases are rare, but may be dramatic in their presentation; however, antipsychotic drugs must be withheld during the duration of the disorder.

The effects of neuroleptics on attention in adolescent schizophrenics.

In contrast to studies of adult psychiatric patients, there was no striking difference between vigilance task performance by 11 newly diagnosed, previously untreated adolescent schizophrenics and that of 58 nonpsychotic adolescent comparison subjects. Neuroleptic treatment failed to improve the performance of the schizophrenic subjects. Sedation, a frequent side effect, was associated with significant prolongation of reaction time and an increase in error rate. Attentional characteristics of adolescent schizophrenics appear to resemble those of other disturbed children. Their response to neuroleptics appears to be limited and the deleterious effects of sedation on attention may well outweigh any clinical benefit attributable to sedation. Findings are discussed in terms of methodology and age-related characteristics.

The effect of antipsychotic medication on relative cerebral blood perfusion in schizophrenia: assessment with technetium-99m hexamethyl-propyleneamine oxime single photon emission computed tomography.

Functional neuroimaging studies in schizophrenia have often been confounded by various factors including medication status. To explore the effects of antipsychotic medications on relative regional cerebral perfusion, we scanned a group of 33 persons with schizophrenia twice, while receiving a stable dose of antipsychotic and after being off antipsychotics for 3 weeks, using technetium-99m hexamethyl-propyleneamine oxime single photon emission computed tomography (Tc-99m HMPAO-SPECT. We found that antipsychotic significantly increased the mean relative cerebral perfusion in the left basal ganglia. Additionally, patients receiving thiothixene (n = 9) had a significantly greater increase in relative cerebral perfusion in the basal ganglia than patients receiving haloperidol (n = 12). These findings indicate that antipsychotics lead to regional increases in cerebral perfusion and that antipsychotic status must be controlled for in functional neuroimaging studies. Functional neuroimaging techniques such as SPECT may be useful in furthering our understanding of the mechanism of antipsychotics.

Drug-induced dystonia in young and elderly patients.

This retrospective study examined the common notion that neuroleptic-induced dystonia is less frequent in elderly patients. The hospital records of 45 young patients and 45 elderly patients were reviewed. Thirty-one percent of the young patients developed dystonia, compared to 2% of the elderly patients. This significant difference did not appear to be the result of types of neuroleptics used, dose, or concomitant administration of anticholinergic drugs.

Clinical comparison of thiothixene and thioridazine in schizophrenic adolescents.

Of 21 schizophrenic adolescents given thiothixene or thioridazine, many responded poorly or experienced sedation. Because sedation necessitates dose reductions, which limit therapeutic response, for schizophrenic adolescents high-potency neuroleptics may be preferable to the more sedating low-potency drugs.

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.

Drug-induced dystonia.

Among 1,152 psychiatric inpatients who received a phenothiazine, a butyrophenone, or a thioxanthene, 116 developed dystonia attributed to one or more of these drugs. The highest frequencies of dystonia occurred among recipients of haloperidol and the long-acting injectable fluphenazines. For all patients at risk, dystonia was more common in men and in younger patients. For chlorpromazine, high doses, male sex, and low age were each positively associated with dystonia.

Psychopharmacological correlates of post-psychotic depression: a double-blind investigation of haloperidol vs thiothixene in outpatient schizophrenia.

A 24-week double-blind study was conducted to compare haloperidol and thiothixene for efficacy and safety in 46 schizophrenic outpatients. In addition to the standard psychiatric rating scales, Brief Psychiatric Rating Scale (BPRS), Nurses' Observation Scale for Inpatient Evaluation (NOSIE), and Evaluation of Social Functioning Rating (ESFR), two scales more sensitive to the incidence of treatment emergent depression were utilized. They were the Hamilton Depression Scale (HPRSD) and the Zung Self-rating Depression Scale (ZUNG). On the BPRS factors, haloperidol was significantly superior to thiothixene in Thought Disturbance and Hostility-Suspiciousness, and in Total symptomatology. Haloperidol was also significantly superior to thiothixene in Cognitive Disturbance on the HPRSD. Results of global evaluations suggested haloperidol produced slightly more rapid relief of symptoms than did thiothixene. The inclusion of the depression scales was useful in following patients who exhibited depressive symptoms; clinically significant depression was seen in 5 patients receiving haloperidol and 3 receiving thiothixene. A high incidence of akathisia in the thiothixene group was responsible for a statistically significant difference between groups in the number of central nervous system symptoms. Mean doses of test drugs were 17.5 mg/day for haloperidol an 31.8 mg/day for thiothixene. The study showed that haloperidol was equal to and in some parameters superior to thiothixene in producing improvement in the symptoms of psychosis.

Urinary incontinence in patients receiving neuroleptics.

This paper presents a series of case reports making the observation of a possible association between neuroleptic drug therapy and urinary incontinence. The incontinence was limited and not of the overflow or stress variety. Anticholinergic compounds or drug action did not seem to influence or account for the findings. A central basis is postulated for consideration and warrants further study.

Haloperidol and thiothixene in the long-term treatment of chronic schizophrenic outpatients in an urban community: social and vocational adjustment.

Social and vocational adjustment are highly important--but frequently overlooked--measures of the effectiveness of psychotropic agents in therapeutic regimens involving chronic schizophrenic outpatients. This 24-week, double-blind study compared the effectiveness of haloperidol and thiothixene in facilitating social and vocational adjustment, as well as in controlling more traditionally studied psychopathological parameters, among 36 urban schizophrenic outpatients. Significant improvement favoring thiothixene was shown on physicians' ratings, ratings by relatives living in the same household as the patient, and patients' self-ratings. Side effects occurred with similar frequency in both drug groups; no patients were required to discontinue therapy because of side effects. There were no clinically significant abnormalities in laboratory values in either group.

The neuroleptic malignant syndrome.

The neuroleptic malignant syndrome (NMS) is an evidently underdiagnosed but potentially lethal consequence of treatment with potent neuroleptics. The author presents a detailed review of the clinical characteristics and differential diagnosis of the NMS as described in the world literature. Further studies of the incidence, etiology and pathogenesis of the NMS may enhance knowledge of neuroleptic pharmacology and produce more effective means of prevention and treatment.

Rapid tranquilization: a comparison of thiothixene with loxapine.

This 6-day study evaluated the efficacy of equivalent doses of loxapine and thiothixene for rapid tranquilization of acutely disturbed, psychotic patients. After initial tranquilization with intramuscular injections for 24 hours, 58 patients were treated for 5 days with oral medication. With both drugs, intramuscular treatment demonstrated clinically significant improvement from baseline on Clinical Global Impressions and Brief Psychiatric Rating scales; this improvement continued during the oral phase. Median time to tranquilization was significantly less with loxapine (60 minutes) than with thiothixene (95 minutes); during the oral phase, there were no significant differences between the two treatment groups. Side effects were minimal during the intramuscular phase; dystonia was most common during the oral phase.

Blood levels of neuroleptics: state of the art.

Difficulties in developing techniques to measure plasma levels of neuroleptic drugs have included the presence of metabolites, as well as cross-reactivity not only between these metabolites and the parent compound but between drugs (e.g., a phenothiazine and a tricyclic). Although newer techniques have minimized some of these problems, interpretation of published data must also recognize such design limitations as variable dose, small sample size, etc. The literature is reviewed on the relationship between therapeutic response and plasma levels of chlorpromazine, thioridazine, thiothixene, fluphenazine, butaperazine, and haloperidol. It is suggested that additional studies, carefully designed, on dosage and plasma levels could help in achieving the lowest possible therapeutic dosage and thus in minimizing side effects.

Cardiovascular side effects of long-term therapy with tricyclic antidepressants in the aged.

In a study to determine the nature and frequency of cardiac side effects during long-term administration of tricyclic antidepressant drugs in usual dosages in the aged, 32 geriatric patients were followed for an average of 36.6 weeks. Ten of them received amitriptyline in a daily dosage of 20-75 mg for 53 weeks (average); in 2, electrocardiographic side effects developed, viz, inversion of the T waves or evidence of acute coronary insufficiency. Imipramine was administered to 21 patients in a daily dosage of 20-100 mg (average, 66 mg) over a period of 40 weeks; in 3 instances major side effects developed--intermittent left bundle-branch block, acute coronary insufficiency with node dysfunction, or T-wave inversion with sinus tachycardia; in 1 instance there was a minor side effect, viz, tachycardia only. In 1 patient, acute myocardial infarction developed after two 10-mg doses of nortriptyline. Five of the 7 patients with cardiac side effects had prior organic heart disease. It was concluded that the incidence of cardiac side effects in aged persons given tricyclic antidepressant drugs in the usual therapeutic dosages for a prolonged period is great enough to warrant frequent careful monitoring of cardiac status during therapy.

Correlation of thiothixene serum levels and age.

Two experiments are reported in which acute single test dose levels of thiothixene (Navane) were correlated with age. In the first study 20 mg oral doses were given to 28 male subjects and serum levels were drawn 2 h later. Mean age was 30 and correlation of serum level with age was 0.43, P less than 0.02. In a second older group with a mean age of 41, 10 mg oral doses were given to 25 subjects. A correlation with age of 0.41, P less than 0.05 was obtained with age. In prior work such acute levels have been found to correlate with steady-state serum levels and with clinical response to the medication. Few side-effects were seen in these populations and no correlations were obtained between serum levels and any side-effects.