A comparison of the therapeutic and toxic effects of thioridazine and chlorpromazine in chronic schizophrenic patients

Waldrop, Francis N.; Robertson, Robert; Vourlekis, Alkinoos

doi:10.1016/s0010-440x(61)80026-6

Cited by 32 publications

(7 citation statements)

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“…Thioridazine is an effective antipsychotic agent and causes only minor extrapyramidal side effects [Waldrop et al, 1961;Bowers, 19751 . Other investigators have found that it antagonises the hypermotility induced by low doses of apomorphine (0.25-1 .O mg/kg) but not by higher doses (1.0-5.0 mg/kg) [Buus Lassen, 19771 .…”

Section: Discussionmentioning

confidence: 99%

Behavioural effects of chronic treatment with apomorphine in combination with neuroleptic drugs

Kenny

Leonard

1980

J of Neuroscience Research

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Groups of male Wistar rats were injected with either apomorphine alone twice daily for one week or with apomorphine in combination with chlorpromazine or thioridazine. The neuroleptics were administered once daily so that it was possible to assess their duration of effect on the apomorphine responses. Other groups were injected with saline (controls) chlorpromazine or thioridazine. The nature and time of onset and duration of the stereotyped response following apomorphine injection was determined twice daily. In addition, the behaviour of the rats on the hole board apparatus was also assessed after seven days of drug treatment. Apomorphine was found to induce either a "sniffing/burrowing" or a "fighting" stereotypy. Chlorpromazine increased the latency and reduced the duration of both types of stereotypy. In contrast thioridazine only increased the latency and reduced the duration of response the "fighting" group. On the hole board apparatus, both neuroleptics reduced the ambulation and rearing scores of the "fighting groups alone. It is suggested that the different types of stereotypy induced by chronic apomorphine administration, and their sensitivity to the two neuroleptics, are mediated by different types of dopamine receptors.

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Section: Discussionmentioning

confidence: 99%

Behavioural effects of chronic treatment with apomorphine in combination with neuroleptic drugs

Kenny

Leonard

1980

J of Neuroscience Research

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“…Against the hypothesis that extrapyramidal side-effects are necessary for therapeutic efficacy it has been argued that the drugs chlorpromazine and thioridazine are approximately equipotent in diminishing the symptoms of acute schizophrenia (Cole et al, 1964), but thioridazine causes significantly fewer extrapyramidal sideeffects (Waldrop et al, 1961;Herman & Pleasure, 1963). Thioridazine is also a less potent blocker of amphetamine-induced turning behaviour, an index of central dopaminergic activity, in rats with unilateral nigro-striatal lesions (Crow & Gillbe, 1973.…”

Section: Discussionmentioning

confidence: 99%

The coincidence of schizophrenia and Parkinsonism: some neurochemical implications

1976

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SynopsisThe hypothesis has recently been advanced that increased activity of central dopaminergic mechanisms underlies the symptomatology of the schizophrenias. The evidence that dopaminergic transmission in the corpus striatum is impaired in Parkinson's disease suggests that observations on the relationship between Parkinson's disease and schizophrenia may illuminate the pathophysiology of the latter disease. Four cases are reported in which an illness with schizophrenic features developed in the setting of longstanding Parkinson's disease; attention is drawn to earlier reports of schizophrenic illnesses occurring as.postencephalitic sequelae in the presence of a parkinsonian syndrome. These observations appear to conflict with the view that increased dopamine release in the striatum is necessary for the expression of schizophrenic psychopathology, but do not exclude the possibility that increased transmission may occur at other dopaminergic sites in the brain, for example the nucleus accumbens, tuberculum olfactorium or cerebral cortex. Similarly the dopamine receptor blockade hypothesis of the therapeutic effects of neuroleptic drugs cannot be maintained with respect to an action in the striatum in view of the differences between the actions of thioridazine and chlorpromazine in this structure, but may be tenable for actions at extra-striatal sites.

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“…of Psychiatry! University of pathy on very high dosage (39,20) akathisia) which is generally (12,16,30) but not invariably ( 17,38) much less frequent than with other phenothiazines. Epileptic seizures were reported by Barsa (4) in two of 100 chronic adult schizophrenic patients, neither of whom had been known to have seizures before and who had tolerated equal doses of chlorpromazine.…”

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confidence: 98%

“…Hypotension (35), inhibitionof ejaculation (33) and rarely, subclinical jaundice (5), granulopenia (3,36), and thrombocytopenia (1), have occurred. Waldrop et al (38) reported blurring of vision, dryness of the mouth, nausea and/or vomiting more commonly with thioridazine than with chlorpromazine; the contrary was the case with lactation, nasal congestion, syncope, dermatitis and photo-sensitivity. Sauter (30) reported the hypnotic effect of thioridazine to be greater than chlorpromazine and also described disturbances of accommodation, diarrhea and urinary incontinence.…”

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confidence: 98%

“…Epileptic seizures were reported by Barsa (4) in two of 100 chronic adult schizophrenic patients, neither of whom had been known to have seizures before and who had tolerated equal doses of chlorpromazine. Waldrop et aJ (38) reported grand mal seizures in two of 71 chronic schizophrenic patients but Pauig (25), using the drug in 100 epileptic patients, of whom an unstated number were children, reported a reduction in the number of seizures, attributed to the control of emotional factors. Hypotension (35), inhibitionof ejaculation (33) and rarely, subclinical jaundice (5), granulopenia (3,36), and thrombocytopenia (1), have occurred.…”

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confidence: 99%

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A Controlled Study of the Use of Thioridazine in the Treatment of Hyperactive and Aggressive Children in a Children's Psychiatric Hospital

Alderton

Hoddinott²

1964

Canadian Psychiatric Association Journal

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It is now well recognized that the pa-that if an investigation is worth undertient response associated with the admini-taking there is no point in encouraging srration of medication has many deter-unlimited bias. minants. These include the staff involve-A second vital consideration in the dement and optimism which may be part sign of experiments into the effects of a of a drug investigation, the non-pharm-drug is the need for adequate, objective, acologically derived effect of the med-repeatable and quantifiable measures of ication (the so-called "placebo" effect), change. c?anges in the patient's interp~rsonal.enMuch current drug research is poorly vIronmentwhe0er at home or In hosl;">Ital, designed. Dunham and Howard (7) surwhether -occurrIng by ch~nc: or delIb.er-veyed six psychiatric journals for the fisately .t~rough therapeutI~mtervennon cal years 1957 and 1960 for articles rea~d clinical changes ;:flectII~g the natural porting research on the therapeutic value history of the condition being treated.of energizing and tranquillizing drugs. Gralnick (10) has pointed to the dan-They found that while the total number gers arising from a failure to take these of articles had increased by 36% in 1960, factors into account. Uncritical and ex-"most of the articles in both years and aggerated claims for a new treatment practically all of the increase fall at the method are likely to be followed by an lower levels of methodological adeequally uncritical rejection of the metho? quacy". Collaborative interdisciplinary as a whole, including any real value It research involving trained research workmight have. He warns that the same may ers was highly desirable in psychopharhappen with the new drugs unless they macology, in the authors' view. are subjected to thorough search and Thioridazine, first reported on, clinitudy a.n~unl~ss the treatment approach cally, in 1958 by Fleesan et «1 (8) and IS multidimensional from t?e start.Cohen (6) has since been the subject of !he use of the dou?le-bh~d procedure many reports. Doub.le-blind stud~es comUSIng placebo makes It poss~ble for most paring the drug with placebo In adult of these factors to be taken Into acco.unt, psychiatric patients (8, 14, 15, 29, 31, 1, since their influence will tend to contmue 11, 13) have all shown thioridazine to be whether the patient is taking placebo or more effective than placebo with few drug.side effects. The first five studies includNash (21), in his balanced appraisal of ed adequate objective measures of the double-blind procedure, emphasizes change. Further investigations employing the necessity for the investigator to "an-such measures, but without placebo, (23, ticipate damage to the experiment by fac-34, 37) concluded the drug was effective tors impeding attainment of double-blind and safe. Comparison with other phenoconditions, and to adapt his procedure to thiazines using placebo (8,9,11,14,31)

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A comparison of the therapeutic and toxic effects of thioridazine and chlorpromazine in chronic schizophrenic patients

Cited by 32 publications

References 5 publications

Behavioural effects of chronic treatment with apomorphine in combination with neuroleptic drugs

Behavioural effects of chronic treatment with apomorphine in combination with neuroleptic drugs

The coincidence of schizophrenia and Parkinsonism: some neurochemical implications

A Controlled Study of the Use of Thioridazine in the Treatment of Hyperactive and Aggressive Children in a Children's Psychiatric Hospital

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