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1. Setiptiline maleate (SPT) was administered orally to 45 subjects aged 22-86 years and steady state plasma levels were determined by mass fragment chromatography (GC-MF) to examine the effect of aging on those values. 2. There was a significant correlation between the plasma levels and daily dose. However, there was a wide interindividual variability. 3. Dose-corrected plasma level (DC-PL), or values corrected by dividing the plasma level by daily dose/body weight, was used as the systemic drug clearance parameter. 4. DC-PL was compared among 7 age groups of the subjects distributed in 10-year-intervals. DC-PL showed no difference among groups of subjects between the > 29 years bracket to the 70 years bracket, but showed significantly higher values in those in the > 80 bracket compared to all age groups and subjects in the < 79 bracket. 5. There was a significant correlation between the age of patients and DC-PL according to polynomial response curve analysis. Regression analysis yielded the equation y = -52.72 + 7.05 x -0.17 x2 + 0.01 x3 (n = 45, r = 0.49, p < 0.01).

We examined the efficacy and safety of electroshock therapy (EST) under general anesthesia in 26 depressed patients (9 males, 17 females, age range 55-79). The scores of the Hamilton Psychiatric Rating Scale for depression were significantly decreased after EST and clinical symptoms such as depressive mood. psychomotor retardation, anxiety, agitation, suicidal tendencies, hypochondria and sleeplessness improved in all of the patients. Complications included amnesia (16/26), delirium (3/26) and transient arrhythmia (1/26) after EST, but neither lethal nor lasting complications were observed. In summary, EST was an effective and convenient method of treatment for senile depression.

1. The effects of bromocriptine (BC) on choreiform movement were compared with those of bromperidol (BP) and fluphenazine (FLZ) in a patient with Huntington disease. The patient (male, 42 years old) was treated with BP (15 mg/day, 4 weeks), FLZ (3 mg/day, 4 weeks), low dose of BC (5 mg/day, 4 weeks) and relatively high dose of BC (10 mg/day, 8 weeks). The CSF content of homovanilic acid (HVA) was assayed at last day of the each drug trial. The efficacy of the drugs was evaluated by electromyography. 2. Although BP and FLZ did not succeed to ameliorate the choreiform movement, both low dose and high dose BC showed rapid improvement of the involuntary movement. The CSF HVA concentration was 35.0 ng/ml before beginning treatment. Whereas FLZ and high dose of BC substantially increased the levels of HVA after the dosage (49.3 and 53.1 ng/ml, respectively), moderate increase of HVA (41.5 ng/ml) was observed when the low dose of BC was administered. These observations suggest that increase of CSF HVA might be necessary for clinical improvement of choreiform movement but not correlate with the degree of improvement and dopamine agonists could be useful drug for the treatment of choreiform movement which is refractory to the administration of neuroleptics.

The effects of once a day dose of sulpiride efficacy and safety was evaluated in patients with major depressive disorder. The patients received sulpiride once a day in the morning or in the evening. There were no significant differences between two groups in the mean measures of efficacy. Side effects were rare and all of a mild degree. The most common side effects were sedation, constipation, and dryness of mouth. Out of regard for the administrative and psychological advantage of the once a day dosage this form should be preferred in the treatment of major depression.

Concentrations of the neuroleptics haloperidol, bromperidol, fluphenazine, chlorpromazine and its metabolites nor-1- and nor-2-chlorpromazine, thioridazine and its metabolites mesoridazine, sulforidazine, and northioridazine, and promazine were estimated in serum and brain of rats by high performance liquid chromatography (HPLC) with electrochemical detection following 5 days of chronic administration of drug at typical doses (haloperidol, bromperidol, and fluphenazine 1 mg/kg/day; chlorpromazine, promazine, and thioridazine 25 mg/kg/day). The observed ratio of brain-to-serum concentration of drug varied widely (0.18-62.5) among neuroleptics studied. High potency agents had more favorable brain-to-blood distribution than low potency agents, and a strong correlation (r = 0.734, p < 0.05) was observed between the brain-to-serum ratios of the neuroleptics and standard clinical doses of drug. This finding suggests that drug distribution is a significant determinant of clinical potency. For most neuroleptics, including drugs with high (fluphenazine, haloperidol) and low potency (thioridazine) such as dopamine D2 antagonists, concentration of drug in the brain was similar. If the results are applicable to patients, they suggest that the degree of dopamine D2 blockade achieved during treatment may vary by drug. Chlorpromazine and promazine were notable for producing high concentrations of drug in the brain at typical doses, suggesting that optimal doses might be lower than those in common use. These results may be important in designing and interpreting studies of the effects of neuroleptic drugs in animals and patients.

After a single dose of the butyrophenone neuroleptic haloperidol, behavioral effects and detectable drug levels in rat brain can last for several weeks. To determine if such persistence is a general property of neuroleptics, we compared drug levels and effects after IP administration of two butyrophenones (haloperidol and bromperidol), a high potency (fluphenazine) and a low potency (chlorpromazine) phenothiazine. Drug levels in brain tissue were measured by high pressure liquid chromatography and behavioral effects monitored as inhibition of apomorphine-induced stereotypy. Estimated near terminal elimination half-lives (t 1/2) from brain for acutely administered chlorpromazine (20 mg/kg) and fluphenazine (1 mg/kg) were 0.41 and 0.62 days, respectively, and neither drug was detectable after 4 days. Fluphenazine given daily for 5 days showed an only slightly slower elimination (t 1/2 = 1.1 days). In contrast, near-terminal elimination half-lives from brain for haloperidol and bromperidol (both at 1 mg/kg, IP) were much longer (6.6 and 5.8 days, respectively), and each was detectable for 21 days after dosing. Inhibition of apomorphine-induced stereotypy correlated highly (r = 0.95) with brain levels of haloperidol. For fluphenazine, given once or repeatedly, early inhibition was replaced within 1 week by supersensitivity to apomorphine which persisted for up to 3 weeks. These findings, indicating marked differences in clearance and recovery times after dosing with butyrophenones and phenothiazines, have clear implications for studies of the effects of neuroleptic drugs in rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma neuroleptic levels in 41 patients (21 men, 20 women, aged 18 to 74) on haloperidol therapy were examined in relation to their age by means of radioreceptor assay. There was no significant difference among three age groups (below 45 years, 46 to 60 years, over 60 years) in the ratio of the plasma neuroleptic level to daily dose (nM/mg/kg), but a significant difference in the plasma neuroleptic level was found between the average values in parkinsonian (19.1 +/- 8.5 nM, M +/- SD) and nonparkinsonian (5.5 +/- 3.0 nM, M +/- SD) patients. There was, however, no significant difference in the incidence of parkinsonian symptoms between the young (below 60 years) and the old (over 60 years) age groups. These results suggest that in contrast to the previously reported study with chlorpromazine, the plasma neuroleptic level of haloperidol is not altered with aging and that parkinsonian symptoms induced by haloperidol occur simply in a plasma-neuroleptic-level-dependent manner.

Plasma neuroleptic levels of 31 elderly psychiatric patients (8 males and 23 females, age 80.1 +/- 8.95 years) on chronic propericiazine therapy and with multimorbidity were measured by means of radioreceptor assay. There was no significant correlation between the daily dose and the plasma neuroleptic level. Nor was there any significant correlation between the patients' age and the ratio of plasma neuroleptic level to the daily dose. On the other hand, the immobility score of patients (GBS scale) had a high correlation with the ratio of the plasma neuroleptic level to the daily dose. Furthermore, patients with positive C-reactive protein (CRP) had an average ratio value 3-fold higher than the CRP negative group. The results suggest that the plasma neuroleptic level of propericiazine in elderly patients is raised by morbidity and immobility rather than chronological age per se.