M. Deuschle et al., PULSE-DOSING AND CONVENTIONAL APPLICATION OF DOXEPIN - EFFECTS ON PSYCHOPATHOLOGY AND HYPOTHALAMUS-PITUITARY-ADRENAL (HPA) SYSTEM, Journal of clinical psychopharmacology, 17(3), 1997, pp. 156-160
It has been shown that a single pulse-dosing (PD) dose of clomipramine
improves depressive symptoms. However, so far PD and conventional (CO
NV) application of antidepressants have never been directly compared f
or an extended period. We performed a double-blind study of PD and CON
V application of doxepin (DOX) in depressed patients. After a 1-week p
lacebo treatment, nine patients in the PD group received 250 mg of DOX
every 6 days and placebo on the other days until day 39. Ten patients
in the CONV group received increasing dosages of DOX until day 7 and
250 mg DOX on the other days for 39 days. Three dexamethasone (DEX)-su
ppression/corticotropin-releasing hormone (CRH)-stimulation tests were
completed: (1) during the initial placebo period; (2) on day 9; and (
3) on day 21. In the PD group, scores on the Hamilton Rating Scale for
Depression (HAM-D) differed from baseline only after day 36 (17.1 +/-
7.0 vs. 22.7 +/- 2.8, p < 0.03). In the CONV group, however, HAM-D sc
ores improved significantly after 2 days (22.8 +/- 7.2 vs. 26.5 +/- 5.
7, p < 0.02) and continued to improve until day 39 (7.3 +/- 5.8). From
day 25 to 39, there were significant differences between the HAM-D sc
ores of the two groups. In the PD group, the decline of cortisol after
DEX pretreatment was nonsignificant (NS) at both follow-up test occas
ions (35.9 +/- 40.7 vs. 24.0 +/- 20.7 vs. 23.6 +/- 26.6 mu g/mL). In t
he CONV group, a significant decrease was observed at the second test
(61.8 +/- 61.9 vs. 10.7 +/- 4.2 vs. 19.8 +/- 19 mu g/mL, p < 0.05, res
pectively, NS). The area under-the-curve cortisol response after CRH w
as attenuated in the PD group (5,667 +/- 2,910 vs. 1,883 +/- 2,178 vs.
2,239 +/- 2,583 [arbitrary unit], p < 0.01, respectively, p < 0.01) a
nd in the CONV group (5,710 +/- 4,734 vs. 1,267 +/- 2,053 vs. 445 +/-
1,016 [arbitrary unit], NS, respectively, p < 0.02). We conclude that
CONV application of DOX is clinically superior compared with PD and th
at both modes of application have attenuating effects on hypothalamus-
pituitary-adrenal system activity.