• It is clinically useful to have a table listing the equivalent doses of the various neuroleptics to a standard, such as chlorpromazine. This article derives such data by reviewing doubleblind controlled studies that used a flexible dosage schedule of neuroleptics in treating schizophrenic patients. Each neuroleptic is then converted to 100-mg chlorpromazine equivalents. This empirically derived dosage comparability table is compared with a similar table derived from the opinions of experts. Since these comparable doses produce equivalent amounts of antipsychotic activity, the cost to provide such medication was then calculated, and a table comparing the costs of the different neuroleptics was constructed. In absolute amounts, the cost differences between drugs are small. However, for any drug, large savings accrue when the largest possible capsule or tablet to achieve the desired dose is prescribed.

Comparative doses and costs of antipsychotic medication.

Hospital psychiatry has evolved from long-term "treatment" programs that were primarily custodial to the successful pharmacological treatment of acute psychotic episodes. Unfortunately, many patients still return to the hospital with relapses. This so-called revolving door syndrome draws attention to the critical importance of preventing as well as treating acute episodes. In the first part of this overview, the author reviews the clinical literature on prophylactic treatment of schizophrenia with maintenance antipsychotic drugs. The second part will review the literature on prophylactic treatment of affective disorders with lithium and tricyclics. In the opinion of the author these drugs provide the potential for truly preventive psychiatry.

Overview: maintenance therapy in psychiatry. I. Schizophrenia

We review evidence from randomized, placebo-controlled studies of patients with schizophrenia or schizoaffective disorder, which compared 2 or more doses of an antipsychotic to calculate the dose-response curve for each first-generation (typical) antipsychotic (FGA) or second-generation (atypical) antipsychotic (SGA) and as a group (based on dose equivalence). We identified the near-maximal effective dose (ED; ie, the threshold dose necessary to produce all or almost all the clinical responses for each drug). In randomized, fixed-dose studies of SGAs, the near-maximal efficacy dose for olanzapine may be greater than 16 mg; for risperidone, it is 4 mg; and for ziprasidone, it is 120 mg. Risperidone at 2 mg daily is 50% less efficacious than higher doses. Olanzapine at about 6 mg is approximately 33% less effective than higher doses. Aripiprazole at 10 mg daily was fully efficacious. Doses of clozapine well above 400 mg are necessary for optimal treatment of many schizophrenia patients. We found 3.3 to 10 mg haloperidol to be the near-maximal ED range. We find no evidence that doses higher than these are more effective. We failed to find that high doses of haloperidol (or all other first-generation comparison drugs converted to equivalent doses) were less effective than medium doses (3.3 to 10 mg). While high-dose FGAs are not less effective, we feel it is important not to avoid using high dose to avoid excessive toxicity.

/pdf/dose-response-and-dose-equivalence-of-antipsychotics-175oxp3lmy.pdf

Dose response and dose equivalence of antipsychotics.

A general introduction is given and followed by a review of recent literature under the following subheadings: electrodermal activity, cardiovascular activity, smooth pursuit eye movement, electroencephalogram, and evoked potentials. An attempt is made to assess the clinical significance of the findings reported in each area and to indicate directions for future investigation. The feasibility of defining homogeneous subgroups in schizophrenia using psychophysiological parameters is also considered. The review concludes with the recommendation that peripheral psychophysiological studies entailing (1) comprehensive recording of brain electrical activity and (2) behavioral experimentation on variables thought to be influenced by schizophrenia (e.g., sustained attentional ability) are promising directions for future research. Relationships between behavioral and psychophysiological variables determined by such studies (and possibly subgroupings) may then become the basis for neurophysiological-neurochemical investigations of specific abnormalities underlying such relationships and subgroups.

Recent Studies of Psychophysiology in Schizophrenia

/pdf/qualitative-and-quantitative-eeg-findings-in-schizophrenia-57iraw4ejq.pdf

Qualitative and Quantitative EEG Findings in Schizophrenia

Previous investigations have shown that some of the major neuroleptics, such as haloperidol and fluphenazine hydrochloride, have both central inhibitory and central stimulatory effects in animals and man, depending upon the dosage level (Kamenskaya PL Aleksandrovsky (1964), Himwich & Glissori (1967), Marinato Rr Leonardi (1960), Heinemann & Ztil (1970)). In recent all-night sleep investigations we have demonstrated that potent neuroleptic compounds, such as thiothixene, haloperidol, molindone, and fluphenazine, increase awakening states during low dosage treatment, but during high dosage treatment they decrease both awakening periods and very deep sleep stages (stage 4) ( I t i l et al. (1970 a, 1971 a, b, c ) ) . Since fluphenazine hydrochloride may have different clinical effects at different dosage levels, we set up a study to evaluate the psychopathological and quantitative EEG changes in two matched groups of chronic schizophrenics. Patients were treated simultaneously with two different dosage levels of fluphenazine hydrochloride. (Prolixin@, Squibb & Son, New Brunswick, N.J).

Clinical and quantitative eeg changes at different dosage levels of fluphenazine treatment

Changes in Somatosensory Evoked Potentials during Fluphenazine Treatment

Clinical, toxicological and electroencephalographic study with SCH-12,679 in chronic schizophrenics.

Quantitative EEG analysis of electrosleep using analog frequency analyzer and digital computer methods.

Quantitative EEG investigations, using an analog frequency analyzer and digital computer period analysis, were carried out following single parenteral injection of two long-acting fluphenazine derivatives, decanoate and enanthate. Both quantitative methods of analysis demonstrated that fluphenazine decanoate and enanthate produce significant EEG alterations which are similar to changes induced both by fluphenazine hydrochloride and by other known major tranquilizers (EEG profile of major tranquilizers). Maximum EEG changes occurred during the first week after enanthate, while they occurred during the second week following decanoate injection. These findings confirmed the metabolic and behavioral studies in animals regarding the long action of both compounds and, in particular, they demonstrated that the activity of fluphenazine decanoate is longer in duration than fluphenazine enanthate.

EEG changes after fluphenazine enanthate and decanoate based on analog power spectra and digital computer period analysis.

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