Bone density measurement in major depression.

1. Disturbances in cortisol secretory patterns and excessive secretion of cortisol after a variety of neuroendocrine stimulation tests indicate excessive activity of the hypothalamic-pituitary-adrenocortical axis in depression. 2. Peripheral indicators of hypercortisolemia have also been observed (e.g. enlarged adrenal glands, glucocorticoid insensitivity and insulin intolerance). 3. Excessive cortisol production may also result in altered bone metabolism and bone architecture, and a recent study by Michelson et al. (1996) found slightly lower bone density in depressed women with hypercortisoluria versus healthy controls. 4. In this study, the authors examined bone mineral density (BMD) using dual energy radiographic absorptometry (DEXA) technique in 6 depressed patients (3 with and 3 without hypercortisoluria) with a mean (+/- SD) age of 41 +/- 13 years, and in 5 healthy, controls with mean age 38 +/- 4 years). 5. DEXA images of the lumbar vertebrae (L1 to L4) for BMD were acquired over a 5-minute interval. 6. Overall, the authors observed no difference in mean BMD values between patients and controls, nor were differences observed between patients with and without hypercortisoluria.

Once- versus twice-daily venlafaxine therapy in major depression: a randomized, double-blind study.

BACKGROUND: Psychotropic drug dosing regimens are often based on the pharmacokinetic elimination half-life of the compound. This implies that the pharmacokinetic half-life of the drug may be the critical or sole determinant of pharmacodynamic half-life. In the present study, we examined the safety and efficacy of once- versus twice-daily dosing regimens of the immediate-release formulation of venlafaxine, a serotonin and norepinephrine reuptake site blocker with a short elimination half-life. METHOD: Forty-eight patients with a diagnosis of DSM-IV major depressive episode were randomly assigned to once-daily (N = 25) versus twice-daily (N = 23) venlafaxine. Venlafaxine was started at 37.5 mg daily with specified increments up to 225 mg daily. Efficacy was rated using the Hamilton Rating Scale for Depression (HAM-D), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Clinical Global Impressions scale (CGI). RESULTS: Twenty-one patients in each group completed 6 weeks of treatment. We observed a significant reduction in mean weekly HAM-D and MADRS scores at weeks 1 through 6 for both dosing groups (p < .001). There were no statistically significant differences in mean HAM-D or MADRS scores between dosing groups at any time point. There was, however, a nonsignificant trend for a more rapid reduction in the mean HAM-D score at week 2 (p < .06) and in the mean MADRS score at week 1 (p < .07) and week 2 (p < .09) in the b.i.d. dosing group. Similarly, there was a significant decrease in the CGI score at week 2 (p < .02) in the b.i.d. dosing group. The rate of adverse events was similar between treatment groups; the most common adverse events were transient nausea and headaches. CONCLUSION: These results indicate that the immediate-release formulation of venlafaxine may be safe and effective in some patients when used in a once-daily dose regimen. Moreover, the present results suggest that the short elimination half-life of immediate-release venlafaxine should not be the sole determinant for multiple daily dosing and that antidepressant activity may be more profoundly influenced by a drug's pharmacodynamic half-life than by its pharmacokinetic half-life.

Suppression of herpes simplex virus infections with oral lithium carbonate--a possible antiviral activity.

In vitro studies have shown an inhibitory effect of lithium salts on herpes simplex virus (HSV) replication by mechanisms that interfere with viral DNA synthesis. Moreover, clinical studies have shown that oral lithium carbonate and topical lithium succinate can suppress genital HSV infections in humans. We conducted a randomized, double-blind, placebo-controlled trial of oral lithium carbonate in 11 healthy subjects age 28-65 years (mean +/- SD age 38 +/- 11 years) who had at least four recurrent HSV infections in the year preceding the study. Six patients completed at least 5 months of lithium therapy at a mean (+/-SD) average daily lithium dose of 437 +/- 185 mg (range, 150-900 mg) and an average serum lithium level of 0.56 +/- 0.20 mmol/L. Overall, lithium treatment resulted in a consistent reduction in the mean number of episodes/month, the average duration of each episode, the total number of infection days/month, and the maximum symptom severity. In contrast, treatment with placebo resulted in an increase in three out of the four severity measures. Although the comparisons between the treatment groups did not achieve statistical significance due to the limited sample size, there was a clear "trend" for a reduction in the total monthly duration of all HSV infections with lithium (p = 0.08). Lithium treatment was well tolerated and produced no deleterious effects on renal or thyroid function. These observations lend support to prior observations of an antiviral activity of lithium, and suggest the possibility that oral lithium may represent a safe prophylactic agent in patients with recurrent HSV infections.

A computational model of pulmonary gas transport incorporating effective diffusion.

A computational model of gas transport in the lung is described which remedies many of the deficiencies of previous models, as listed by Chang and Farhi (1973), in that it allows for fluctuating lung dimensions, gas exchange, simultaneous convection and diffusion, and the enhanced effective diffusion that occurs when convective flow is also present. The results of calculations using the model are presented, showing the maximum effect of Taylor diffusion. The actual magnitude of Taylor diffusion, suitably modified to allow for the disturbed conditions within the lung, is considered in the light of recent experiments.