What is the documentation for the use of selective serotonin re-uptake inhibitors (SSRI), especiall

Fråga: What is the documentation for the use of selective serotonin re-uptake inhibitors (SSRI), especially citalopram, for premenstrual syndrome? Are there other pharmacological treatment alternatives? A 27-year-old woman with a borderline personality disorder has a seriously elevated anxiety level the week before menstruation. She even becomes suicidal. The patient has previously been on venlafaxine for depression and anxiety. This had no effect on her premenstrual anxiety escalation. She switched to mirtazapine due to sexual side effects. Mirtazapine has good effect on her general anxiety, but not on her PMS. She is also on contraceptive medication with desogestrel 150 ug, ethinyl estradiol 30 ug (Desolett) 21 of 28 days.

Sammanfattning: PMS is a common condition with many suggested therapies, with selective serotonin reuptake inhibitors being the best documented pharmacological treatment.

Svar: Premenstrual syndrome (PMS), or the more severe variant premenstrual dysphoric disorder (PMDD), is not uncommon among fertile women and can cause much discomfort. The pathophysiology is unknown (1,2).

Serotonergic antidepressants have the best documentation for a beneficial effect in PMDD, with a response rate of 60-70%. Most studied are fluoxetine and sertraline, both of which are also approved by FDA for the treatment of PMDD (3). No SSRI has this indication approved by the Swedish MPA (4).

As PMS is a cyclic disorder, several studies have been conducted using intermittent administration of SSRI:s. For citalopram, there is one study in 69 women showing better response with luteal phase administration, than with continuous dosing. In this study sexual side effects decreased with time on intermittent medication with citalopram (5).

For other SSRI:s, when comparative studies have been made, comparable results have been shown with intermittent and continuous dosing. Adverse effects (gastrointestinal symptoms, insomnia, anxiety, decreased libido and anorgasmia) occur with both continuous and intermittent dosing. The frequency of side effects is similar between continuous and intermittent dosing studies. Sexual side effects occur in 9-16% of patients as compared with 36-43% in patients treated with SSRI due to depression. In responders, relief from symptoms typically comes rapidly (within a few days) and there are no or few withdrawal symptoms with intermittent dosing. Dosing is typically in the same order as for major depressive disorder (20-40 mg citalopram, 25-100 mg sertraline) (6).

In most studies there is no dose titration, but in the mentioned citalopram-study there was a 5-10-10-15-20mg titration beginning on cycle day 14 and a 20-10-0mg tapering from the first day of menstruation (5). In another small citalopram study showing efficacy in patients not responsive to other SSRI:s, there was no titration or tapering but sharp start and stop (7).

Treatments with vitamin B6 and contraceptive pills have been tried with uncertain effect (1,2). A meta-analysis gives some support to the use of vitamin B6 (8). There is one controlled clinical study suggesting a beneficial effect of an oral contraceptive pill containing drospirenon (Yasmin). The placebo response rate in this study was 43% (9). Spironolactone, at a dose of 100 mg during the last 14 days of the cycle, has also been reported to alleviate both physical and psychological symptoms of PMS (10). Progesterone deficiency during the late luteal phase has been suggested to cause the syndrome. Therefore, progesterone substitution has been tried. Cyclic progesterone administration, though, seems to worsen symptoms, why depot preparations or the use of GnRH-agonists has been suggested. However, the documentation for this is scarce (11). Some reports suggest a disturbed calcium homeostasis and therefore calcium supplementation has been tried. Approximately 500 women participated in a trial of 1200 mg elemental calcium daily compared to placebo. Forty-eight per cent of the calcium group had less symptoms compared to 30% of the placebo group (1).

In the present case, where premenstrual symptoms were not relieved by venlafaxine, which is also a serotonin reuptake inhibitor, it is perhaps less likely that the patient will respond to another SSRI. Fluvoxamine and fluoxetine should better be avoided, due to the risk for drug interactions with mirtazepine (4). A change in contraceptive regimen might be the therapy of choice in the present case.