Roland J. Branconnier

Comparison of Bupropion and Trazodone for the Treatment of Major Depression

Bupropion and trazodone were compared in a two-center, double-blind clinical trial of outpatients with moderate to severe major depression. After a 1-week placebo lead-in, 124 patients were randomly assigned to receive either bupropion (N = 63) or trazodone (N = 61) for 6 weeks; data from 111 patients were used in the efficacy analysis. Dosing ranged from 225 to 450 mg/day for bupropion and 150 to 400 mg/day for trazodone. The overall efficacy for each of the two drugs was similar; although improvement in the trazodone treatment group was significantly greater on day 7 because of the effects on sleep. At the end of treatment, 58% of the bupropion-treated patients and 46% of the trazodone-treated patients were considered much or very much improved. Weight measurements at the time of discontinuation indicated a 2.5-lb mean weight loss for the bupropion treatment group and a 1.2-lb mean weight gain for the trazodone treatment group. The adverse experience profiles for bupropion and trazodone were consistent with their known pharmacologic profiles (i.e., activating versus sedating). Anorexia and anxiety were reported significantly more often for the bupropion treatment group, whereas somnolence, appetite increase, and edema were reported significantly more often for the trazodone treatment group.

ACTH 4-10 in the amelioration of neuropsychological symptomatology associated with senile organic brain syndrome

Eighteen male and female volunteers over the age of sixty who exhibited mild senile organic brain syndrome were administered ACTH 4-10 (Org OI 63) (30 mg, s.c.) or saline in a 2×2 Latin square design. Subjects experienced a reduction in depression and confusion and an increase in vigor. This evidence of an increase in vigor was supported behaviorally by a delay in the onset of increased latency in reaction time. Data also indicated that retrieval from memory may be enhanced by this compound. The electroencephalogram evinced a shift to lower frequencies under ACTH 4-10, but this effect was primarily noted in the females who received drug followed by placebo. These effects of ACTH 4-10 are intriguing and suggest that further work in this area should be encouraged.

Recall and recognition as diagnostic indices of Malignant Memory loss in senile dementia: A bayesian analysis

The Benign Senescent Forgetfulness of normal aging and the Malignant Memory Loss of Senile Dementia of the Alzheimer Type (SDAT) each have a distinct symptomatology, course, and prognosis. The purpose of this study was to evaluate the discriminative validity and relative predictive values of recall and recognition as diagnostic screening tests for the Malignant Memory Loss of SDAT. Thirty-six patients with mild to moderate SDAT and 40 normal aged controls were studied. Both recall and recognition showed good discriminative validity. However, analysis of recall and recognition by Bayess Theorem revealed the relative predictive values as diagnostic screening instruments were 11% and 100% respectively. Thus, it was concluded that while both recall and recognition have discriminative validity under experimental conditions, a test of recognition is the preferred diagnostic instrument when screening for the Malignant Memory Loss of SDAT.

Amitriptyline selectively disrupts verbal recall from secondary memory of the normal aged

Amitriptyline, a frequently prescribed tricyclic antidepressant, is reported to produce an age-related impairment in anterograde memory. However, the locus of this adverse effect has never been described within the context of contemporary learning and memory theory. Fifteen normal elderly subjects were treated with 50 mg amitriptyline and placebo in a cross-over study. A computerized stage analysis of memory revealed that sensory and primary memory were not affected while verbal recall from secondary memory was markedly disrupted by amitriptyline. Further examination of secondary memory revealed that amitriptyline impaired recall, but not recognition. The profile of anterograde memory impairments observed with amitriptyline is similar to that previously reported for the antimuscarinic, scopolamine. Since amitriptyline at the dose employed in this study would be expected to exert marked central antimuscarinic effects, it appears likely that it is the pharmacologic blockade of central muscarinic receptors in the aged that results in the selective disruption of verbal recall in secondary memory.

Effects of Acute Administration of Trazodone and Amitriptyline on Cognition, Cardiovascular Function, and Salivation in the Normal Geriatric Subject

Trazodone, unlike amitriptyline, produced no impairment of psychomotor function or memory in normal geriatric subjects. Moreover, trazodone produced few cardiovascular effects. While drowsiness and a reduction in salivary flow were observed with trazodone, both are probably related to an α-blocking mechanism of action. Therefore, the unique pharmacological profile of trazodone offers a significant safety advantage over the tricyclic antidepressants in the geriatric patient.

Prediction of serum cortisol response to dexamethasone in normal volunteers: A multivariate approach

Dexamethasone (DEX, 0.5 mg orally at 11 PM) challenge was used for the assessment of hypothalamic-pituitary-adrenal (HPA) activity in 20 normal volunteers. Age and pre-DEX serum cortisol levels were thee evaluated as predictors of postDEX serum cortisol levels using step-wise multiple regression analysis. Both age and preDEX serum cortisol levels were significant predictors of postDEX serum cortisol levels. It is suggested that the adjustment for age and preDEX serum cortisol level could be useful for the interpretation of abnormal postDEX levels.

Sleep deprivation deficits and their reversal by d-and l-amphetamine

Vigilance performance, waking EEG patterns and mood were studied before and after one night of sleep deprivation in normal males. The effects of d-amphetamine 10 mg, l-amphetamine 10 mg and placebo on these measures were compared. Changes were found in all three measures after one night of sleep-deprivation. d-Amphetamine was more powerful than l-amphetamine in reversing sleep deprivation effects on vigilance and on waking EEG.

Electroencephalographic and Behavioral Changes Associated with Papaverine Administration in Healthy Geriatric Subjects

A double‐blind cross‐over procedure was used to evaluate the effects of papaverine hydrochloride on the electroencephalogram (EEG), cognition, mood and psychologic test performance of 10 healthy geriatric volunteers. During the two‐week period, each subject was tested four times: before and after receiving papaverine and before and after receiving placebo. Period analysis revealed that a 300‐mg dose of papaverine (Pavabid Plateau Caps) increased EEG alpha activity (8–13 cycles per second) and decreased the beta2 range (27–40 cps). Baseline values for six mood factors, short‐term memory, complex problem solving, and attention were not altered significantly by either drug or placebo. Results of the Subject Paced Digit Symbol Substitution Test indicated that papaverine may produce some improvement in simple cognitive functioning. No adverse effects were associated with the use of papaverine.

A Memory Assessment Technique for Use in Geriatric Psychopharmacology: Drug Efficacy Trial with Naftidrofuryl

This study was conducted to compare an automated test of paced stimulus material (Sperlings Perceptual Trace, SPT) with several other standard memory scales. Sixty patients with mild senile organic brain syndrome were divided into two groups of 30; one group was treated for 90 days with 300 mg daily of naftidrofuryl (Praxilene), and the other group received placebo. The patients were tested before treatment and at 30, 60 and 90 days after the beginning of treatment. The data indicated that the SPT indirectly assesses short‐term memory, is resistant to practice effects, and is drug‐sensitive. It is suggested that the SPT might become the test of choice in the indirect assessment of short‐term memory in the elderly.

Effects of chronic papaverine administration on mild senile organic brain syndrome.

Two groups of geriatric patients were treated with either 300 mg/day of papaverine hydrochloride (Pavabid) or placebo in a double‐blind study of two months’ duration. All patients (25 in each group initially) had mild to moderate senile organic brain syndrome but were ambulatory and treated on an outpatient basis. Neuropsychologic evaluations were made by means of the following six tests: Electroencephalographic Analysis (EEG), Profile of Mood States (POMS), Subject Paced Digit Symbol Substitution Test (SPDT), Continuous Performance Test (CPT), Peterson and Peterson Test (P & P) for Short‐Term Memory, and Clinical Global Impression (CGI). The tests were comparative with a baseline period and between treatment groups. There were positive responses from baseline to active‐drug treatment in four of the six evaluations—EEG, POMS, SPDT and CPT. Some side effects were noted in both drug and placebo groups, but these were not disabling and did not interrupt therapy. Positive responses were also observed between treatment groups. By the EEG criterion, the papaverine patients responded positively. By the P & P test for short‐term memory, the placebo group responded better than did the papaverine group. It is suggested that the pharmacodynamic action of papaverine in ameliorating the symptoms of senile organic brain syndrome may not be due to vasodilation but to dopamine receptor blockade.