Citalopram in Premenstrual Dysphoria
Abstract & Commentary
Synopsis: Citalopram is effective in treating premenstrual dysphoria. Intermittent dosing in the luteal phase is effective.
Source: Wikander I, et al. Citalopram in premenstrual dysphoria: Is intermittent treatment during luteal phases more effective than continuous medication throughout the menstrual cycle? J Clin Psychopharmacol 1998;18:390-398.
In this double-blind, flexible-dose, four-arm study, citalopram (Celexa, a recently approved SSRI) was evaluated for its possible effect on premenstrual dysphoria. One hundred twenty-three women completed daily self-ratings of irritability, tension, depressed mood, appetite changes, bloating, and breast tenderness using a visual analog scale for two consecutive menstrual cycles. Subjects were excluded from the study if they did not show more than a 100% increase in irritability or depressed mood five days preceding menstruation (the late luteal phase), compared to days 6-10 after the start of menstruation. Seventy-eight women were then randomly assigned to one of four treatment groups: 1) continuous citalopram treatment throughout the menstrual cycle; 2) low-dose citalopram in the follicular phase and a higher dose in the luteal phase; 3) citalopram in the luteal phase only with placebo in the follicular phase; and 4) placebo during all phases. All subjects were given three capsules per day, with the ability to titrate the dose from one to three pills as desired. Subjects were told that the recommended dosage was two pills. Each capsule contained either citalopram 10 mg or placebo. Therefore, the dosage range for patients in the active treatment group was between 10 mg and 30 mg per day of citalopram. Sixty-nine women completed the study, with dropouts due to side effects or inability to complete the daily rating scales. After three menstrual cycles of double-blind treatment, subjects were asked to give a global impression of symptoms before and during treatment with respect to their premenstrual complaints. On this subjective measure, there was significant improvement in both the continuous treatment and luteal phase only treatment groups compared to placebo (P = 0.02; P = 0.0001, respectively). Group number 2, which received low and then higher dose citalopram, did not statistically separate from placebo (P = 0.08). Irritability was the symptom most elevated prior to treatment for all four groups and was, therefore, the symptom used to measure treatment efficacy. A comparison of the visual analog scale for irritability during the late luteal phase (mean score of the 5 days before onset of menses) showed no difference in the four groups prior to treatment and a statistically significant difference between all groups vs. placebo during the three treatment cycles (P = 0.0008). In separate group comparisons, there was no difference between the group that received continuous citalopram treatment vs. placebo. The group that received increasing dosages during the luteal phase was significantly different from placebo during the first two treatment cycles. There was a highly significant difference between the group treated during the luteal phase only and the placebo group throughout all three treatment cycles. There was no correlation between serum drug concentration and clinical effect. Dosage correlated negatively in the semi-intermittent group with increased dosage during the luteal phase; however, in the other two groups, there was no correlation between dosage and response.
Comment By Lucy J. Puryear, MD
Eighty percent of women suffer some mood and/or physical symptoms in the week to two weeks prior to beginning a period. These symptoms are usually mild and do not interfere with daily functioning. In 6-8% of women, symptoms of irritability, depressed mood, and anxiety, along with physical symptoms of breast tenderness and bloating, can become severe enough that they interfere with normal functioning. Several studies to date conclude that serotonin reuptake inhibitors are effective in the treatment of premenstrual mood symptoms.1,2 It appears that serotonin may play a key role in treating this disorder. A study comparing the efficacy of the serotonergic antidepressant fluoxetine to the nonserotonergic antidepressant bupropion found a more robust response to fluoxetine.3 The current study attempts to assess the relative efficacy of citalopram administered in the luteal phase only, compared to continuous medication throughout the menstrual cycle. The results showed a global improvement in premenstrual symptoms vs. placebo for women in all treatment groups regardless of dosage or schedule of medication administration. Due to the unusual design of the study that allowed for multiple dosage regimens within each treatment group, it is difficult to say whether administering medication during the luteal phase only is more efficacious than continuous dosing or variable dosing. Wikander and associates speculate that, with exposure to citalopram throughout the entire cycle, there may be a slight but rapid development of tolerance. However, in other studies, when serotonin reuptake inhibitors have been used continuously throughout the menstrual cycle, the results do not support this hypothesis.1,2 The fact that antidepressant exposure only in the luteal phase has clinical efficacy is of scientific and clinical import. Studies of premenstrual mood disorders consistently suggest a rapid onset of response (within 1-2 days of starting treatment), as opposed to the longer onset of action typical of these same agents when used to treat Major Depressive Disorder. Intermittent medication is often preferred by patients.
References
1. Yonkers KA, et al. Paroxetine as a treatment for premenstrual dysphoric disorder. J Clin Psychopharmacol 1996;16:3-11.
2. Steiner M, et al. Fluoxetine in the treatment of premenstrual dysphoria. Canadian Fluoxetine/Premenstrual Dysphoria Collaborative Study Group. N Engl J Med 1995;332:1529-1534.
3. Pearlstein TB, et al. Comparison of fluoxetine, bupropion, and placebo in the treatment of premenstrual dysphoric disorder. J Clin Psychopharmacol 1997;17:261-266.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content