A five-day gradual reduction regimen of chlormadinone reduces premenstrual anxiety and depression: a pilot study.

BACKGROUND: Anxiety and depression commonly occur in premenstrual dysphoric disorder (PMDD). The PMDD symptomatology disappears once the menstrual cycle reinitiates, resembling a withdrawal syndrome. METHODS: The present study is a pilot, controlled, double-blind study exploring the effectiveness of a premenstrual 5-day gradual reduction regimen of chlormadinone acetate on PMDD. Volunteers received an initial dose of 10 mg (five 2-mg tablets) on the 24(th) day of the menstrual cycle and one-fifth of the dose less (one tablet) each day until a dose of 2 mg (one 2-mg tablet) was reached on the 28(th) day of the menstrual cycle. The control group received placebo with a similar regimen. RESULTS: The 5-day gradual reduction regimen of chlormadinone significantly improved (F(3.76) = 3.29, p <0.02) the daily symptoms report (DSR) scores by the third month of treatment. The resulting relative risk was 4.09 (confidence interval: 1.15-14.57, p <0.005, 95% CI). Compared to placebo, chlormadinone clinically and statistically reduced the severity of depression, anxiety, food cravings, mood swings and cramps. A statistical reduction of symptoms such as poor coordination, irritability, feeling out of control, hopelessness, decreased interest and headache was detected but was not clinically relevant. No changes occurred in concentration difficulties, tiredness, insomnia, swelling, breast tenderness and aches. As side effects, 30% of the volunteers showed changes in the length of the menstrual cycle, and 15% experienced dyspepsia. CONCLUSIONS: A 5-day gradual reduction regimen of chlormadinone improves some of the discomforting ailments associated with PMDD, namely, depression and anxiety.

Differential progesterone effects on defensive burying and forced swimming tests depending upon a gradual decrease or an abrupt suppression schedules.

A single dose of progesterone reduces the cumulative time in the defensive burying test and the immobility in the forced swim test, whereas the abrupt suppression of repeated doses increases the anxiety indicators. Whether anxiety and despair indicators reduce by a gradually decreased schedule of progesterone is unknown. Therefore, we subjected adult ovariectomized Wistar rats to open field, defensive burying and forced swim tests. One group received a constant schedule of progesterone (0.50 mg, daily), abruptly suppressed (AS) after five days. Another group received a gradual reduction schedule of progesterone (GR: 0.84, 0.67, 0.50, 0.33, 0.17 mg, each day). Control group received vehicle (VEH). The GR group displayed similar crossing in the open field test as the VEH group (F(2,19) = 8.78, p < 0.002), but also the shortest cumulative time in defensive burying (F(2,28) = 13.3, p < 0.0001) and the shortest time in freezing (F(2,24) = 6.39, p < 0.006). In the forced swim test, the GR group displayed the shortest immobility time (F(2,19) = 12.1, p < 0.0005), the lowest number of immobility periods (F(2,19) = 4.26, p < 0.03) and the longest latency to the first period of immobility (F(2,1) = 4.06, p < 0.03). It is concluded that a gradually reduced schedule of progesterone reduces anxiety and despair in the Wistar rat.