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Nomifensine, a tetrahydroisoquinoline antidepressant, was compared with imipramine in a 4-week multicenter double-blind study of depressed outpatients (100 on nomifensine, 56 on imipramine). Nomifensine was at least as effective as imipramine in reducing depressive symptoms at average doses of 150 mg/day. When significant differences did occur on Hamilton Depression Rating Scale scores, they favored nomifensine for improvement in cognitive symptoms and interest in work and activities. Early in treatment, nomifensine patients also showed a better relationship between clinical response and side effects. The proportions of patients experiencing at least one side effect or dropping out due to side effects were almost twice as high in the imipramine group. Dry mouth and sedating effects were 2-3 times more frequent among imipramine patients. Thus, nomifensine demonstrated clinical efficacy at least comparable with imipramine but with indications of a more favorable side effects profile.

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Eighty-two elderly subjects with significant cognitive impairment were randomly assigned to treatment with either hyperbaric oxygen, hyperbaric air, normobaric oxygen, or normobaric air. Treatment consisted of two 90-minute sessions a day for 15 consecutive days. Subjects were evaluated on measures of memory and intellectual capacity, as well as on psychiatric symptom rating scales. Results immediately after treatment and at one, two, three, and eight weeks following treatment did not show enhanced cognitive functioning or significantly greater symptom reduction in experimental subjects who received either normobaric or hyperbaric oxygen as compared to controls who received hyperbaric or normobaric air. There was also no evidence of differential treatment effects as a function of initial severity of illness, sex, response to a CO2 loading test, or presumed evidence of cerebrovascular disease.

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Recent research indicates a possible cholinergic involvement in memory processes and thus the possibility that acetylcholine deficiency may underlie memory impairment in senile dementia. Deanol (2-dimethylaminoethanol), which is assumed to increase brain acetylcholine, was given openly for 4 weeks to 14 senile outpatients, to determine the safety of the drug and whether or not it reduces cognitive impairment. The dosage was gradually increased to 600 mg three times daily during the first two weeks, with no adverse effects. Ten patients improved globally and 4 were unchanged (p less than .01). The total score on the Sandoz Clinical Assessment-Geriatric (SCAG) was lowered by the third week (p less than .01), primarily as a result of reduced depression, irritability and anxiety, and increased motivation-initiative. However, neither the clinical ratings nor an extensive pre- versus post-treatment series of cognitive tests revealed changes in memory or other cognitive functions. Since a similar separate study with a different compound produced no behavioral changes, it is unlikely that the improvement with deanol was due entirely to placebo effects. The results thus suggest that although deanol may not improve memory, it may produce positive behavioral changes in some senile patients.

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It was hypothesized that a central nervous system stimulant with relatively weak peripheral effects would facilitate test performance in the cognitively impaired aged. Twelve elderly subjects participated in a counter-balanced, crossover comparison of 10 mg methylphenidate, 30 mg methylphenidate and placebo. All treatments were administered double-blind as a single dose of oral medication. Neither dosage of active medication was found to effect psychomotor or psychological test performance, subjective report, heart rate or blood pressure. A subsequent open trial of 45 mg methylphenidate resulted in heart rate, blood pressure and subjective changes in two of eight subjects but no effects on test performance. The results suggest that cognitive performance in the moderately impaired aged is unimproved following administration of methylphenidate, and perhaps similar sympathomimetic amines, below a dosage level associated with clinically significant peripheral effects.

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Both simple and disjunctive reaction times (RT) are known to slow with aging but there is a paucity of information on RT changes in senility. Since disjunctive RT involves cognition in addition to the sensory-motor speed and attentional components of simple RT, it was hypothesized that disjunctive RT would be a reliable index of age-related mental decline. To test this prediction, simple and disjunctive RT were measured in matched groups of 20 normal and 20 cognitively impaired elderly. Simple RT was slower in the senile patients than in the normal subjects, but this difference was accounted for by differences in disjunctive RT. The senile patients showed a much larger performance decrement with respect to disjunctive RT than did the normal subjects--a difference which was not accounted for by differences in simple RT. In a discriminant function analysis, disjunctive RT alone correctly identified the senile patients and the normal subjects with 86% accuracy. Thus, this measure proved to be a reliable index of age-related mental decline. Preliminary data indicate that disjunctive RT slowing is correlated with non-memory mental decline, and that poor performance is related to the need for care and supervision.

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This study measured the levels of imipramine hydrochloride and desipramine hydrochloride (desmethylimipramine) in the plasma and cerebrospinal fluid (CSF) in 11 depressed patients. The oral doses correlated significantly with the plasma levels irrespective of different diagnostic categories. The CSF levels varied significantly. In the endogenous depressive group the CSF levels were significantly higher in responders as compared to nonresponders. The CSF levels of the nonresponders in the endogenous depressive group, and of both responders and nonresponders in the schizo-affective groups, were similar.

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A gas chromatographic-mass spectrometric determination of blood N,N-dimethyltryptamine in normal controls and schizophrenic patients was carried out with a sensitivity limit of 0.05 ng/ml whole blood. Although the results appear to suggest that the mean DMT level was higher in the total patient group, those patients with acute psychosis, female patients and patients with suspiciousness scores on the BPRS of 4 or over, the differences were not statistically significant.

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The polypeptide ACTH 4-10 has been shown to facilitate learning in animals, and possibly to improve attention and memory in normal human subjects. The purpose of this study was to assess the effects of ACTH 4-10 in cognitively impaired elderly subjects. In a double blind, cross over design, 24 cognitively impaired geriatric outpatients (mean age=71.4, 12 with mild and 12 with severe impairment) received injections of 30 mg or 15 mg ACTH 4-10 or matched placebo on 3 successive days. A cognitive test battery of memory and nonmemory tests was administered each day both before and after treatment. The 30 mg dosage produced a slowing of simple visual RT, a nonsignificant improvement trend in verbal associative memory, and significant, severity dependent facilitation or impairment in day later visual memory. The results suggest that the ACTH 4-10 effects on cognitively impaired elderly are dependent on the dosage and on the baseline cognitive level of the subjects.

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