For the treatment of premenstrual dysphoric disorder (PMDD), serotonin reuptake inhibitors (SRIs) are considered to be the first-line treatment of alternative. A big body of evidence, including quite a few double-blind, randomized controlled trials, supports the effectiveness of SRIs in reducing the emotional, in addition to physical, symptoms of PMDD. Generally, women reply to low doses of serotonin antidepressants, often at doses lower than typically used to treat major depressive disorder and anxiety disorders. As well as, treatment response to SRIs normally occurs rapidly, often inside several days.
While serotonin reuptake inhibitors represent an efficient treatment for PMDD, a good number of girls report unintended effects that interfere with long-term use. Sexual unintended effects, including decreased libido and anorgasmia, are a typical reason for discontinuing treatment. Other problematic unintended effects include fatigue.
Different dosing strategies may help to attenuate the danger of troublesome unintended effects. For instance, some women may elect to only take an SRI throughout the luteal phase–the last two weeks of their cycle–and to stop the SRI with the onset of menses.
Some women may profit from symptom-onset dosing, where the SRI is began with the onset of premenstrual symptoms and stopped when menses start. A recent article from Kimberly Yonkers and colleagues takes a better have a look at the effectiveness of this approach.
On this double blind, randomized, clinical trial, 184 women with PMDD were randomized to receive either sertraline (25-100 mg) or placebo. PMDD symptoms were measured using the Day by day Rankings of the Severity of Problems. Domains of functional impairment included (1) reduced productivity or efficiency at work, school, home, or each day routine; (2) interference with hobbies or social activities; and (3) interference with relationships.
Relationship Functioning Shows Biggest Improvement with Sertraline
On this study, women receiving sertraline experienced a greater reduction within the “interference” or overall impact of PMDD symptoms than those receiving placebo. On average, the anger/irritability subscale showed a greater decrease between baseline and end of second cycle within the sertraline group in comparison with placebo. Sertraline and placebo didn’t differ when it comes to impact on depressive symptoms or physical symptoms. Looking specifically at domains of functional impairment, only relationship functioning improved significantly with sertraline treatment between baseline and the top of the second cycle. (There have been no significant improvements in productivity/efficiency or participation in hobbies and social activities). An evaluation of potential mediating aspects suggested that most or the entire reduction in relationship interference with treatment could be explained by the reduction in anger/irritability symptoms.
While previous studies have shown that continuous treatment and luteal phase dosing with a serotonin reuptake inhibitor is related to improvements across multiple domains (i.e., physical symptoms, depressive symptoms, and anger/irritability), this study suggests that symptom-onset dosing could also be simpler for reducing anger/irritability than other symptoms seen with PMDD. Moreover, other studies have shown that improvements in functioning can also be impacted by dose and timing of administration.
Putting the Findings Right into a Clinical Context
Individuals with PMDD experience heterogenous symptoms that could be grouped into different symptom clusters. While PMDD with outstanding somatic symptoms is common, it’s PMDD with outstanding anger and irritability that seems to cause the best functional impairment and, not surprisingly, has the best impact on interpersonal relationships. This study and several other others suggest that, while most people with PMDD profit from treatment with serotonin reuptake inhibitors, dosage and timing of medication could also be essential considerations.
When initiating treatment with an SRI, we generally start with a comparatively low dose (for instance, fluoxetine at 10-20 mg or sertraline at 50 mg) and monitor symptoms for several consecutive cycles. Day by day charting of symptoms may be very helpful when it comes to tailoring treatment. The dosage and timing of medication can then be adjusted based on effectiveness and tolerability. If unintended effects are usually not tolerable, one may consider decreasing the dosage or changing to intermittent dosing (either starting at day 14 of the cycle or on the time of symptom onset). This can be a collaborative process, and, because symptoms are compared month to month, it will probably take a while to settle upon the most effective regimen.
Ruta Nonacs, MD PhD
References
Yonkers KA, Altemus M, Gilstad-Hayden K, Kornstein SG, Gueorguieva R. Does Symptom-Onset Treatment With Sertraline Improve Functional Impairment for Individuals With Premenstrual Dysphoric Disorder?: A Randomized Controlled Trial. J Clin Psychopharmacol. 2023 Jul-Aug 01;43(4):320-325.