Best Medications for Premenstrual Dysphoric Disorder (PMDD)

Premenstrual Dysphoric Disorder responds to medications that enhance serotonin levels. It can be inferred that the cause relates to dropping serotonin levels as estrogen levels fall (since estrogen increases serotonin). Lowering serotonin levels only causes mood symptoms in women who have a genetic predisposition or previous history of depression.
Unlike depression, symptoms of PMDD respond fairly quickly to medication. Typical mood symptoms of PMDD are sad, tearful, feeling overwhelmed, irritability and being overly emotional.
Before deciding whether to use medication every day or just in the last 1-2 weeks of the cycle it is recommended that mood charts be kept for 2-3 cycles. This is primarily to evaluate mood in the first half of the cycle. It is believed that many women have mood symptoms all the time but they are worse during the premenstrual phase. It may be that the lesser degree of depression in the early cycle is normal (by comparison). PME or premenstrual exacerbation of mood symptoms is best treated with daily medication – though sometimes increasing the dose in the last 7-10 days is helpful.

For true PMDD there are several reasons that limiting medication to a few days is helpful. The biggest reason is avoidance of potential long term side effects, especially sexual side effects, possible weight gain and blunting of emotion and motivation. Other reasons include the cost, stigma, and the hassle.
When using medication just during the late luteal phase (last few days of cycle) my first choice is Effexor. Because Effexor is the quickest to cross the blood brain barrier (due to low protein binding) it can be taken for the shortest number of days. It frequently starts working the first day (usually 37.5mg is adequate but sometimes 75mg is needed). Once Effexor is discontinued – usually once menses starts – the Effexor is totally out of the system in 3 days. Most medications take one week to be out of the system. Prozac (fluoxetine) aka Sarafem takes six weeks to clear – i.e., it can’t be taken just during the PMS phase. My 2nd choice and the second fastest to work is Lexapro 5-10mg. Ironically it’s Prozac (Sarafem) and Zoloft (slowest to work) that pursued and received FDA indications.
Although Effexor and Lexapro may work the first day it’s usually better to start them 2-3 days before symptoms usually start – this of course requires using a calendar and keeping track of due dates. If you can tell when you ovulate it’s easy – 14 days later you will start your period.

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2 Responses to “Best Medications for Premenstrual Dysphoric Disorder (PMDD)”

  • Jessica says:

    How do you feel about Celexa for PMDD? Is it slower on the uptake?

    • Reply from Dr. Jones says:

      Celexa does work for PMDD – usually better than the meds that are formally approved (Prozac). The problem with Prozac is if you take one every 6 weeks it is always in your system because it takes six weeks to clear the system. Zoloft is 98% protein bound so only 2% crosses the blood brain barrier, which means it works slowly – you would have to start a few days before “showtime” which is any time the last 7 days before menses.

      Prozac and Paxil are over 90% protein bound. Celexa is only 80% protein bound and Lexapro is even faster at 56% protein binding, but it is pricier. Effexor XR is the fastest at <30% protein bound – it often works the first day. It was never studied or approved by the FDA however…bad decision by Wyeth Pharmaceutical. Pristiq and Cymbalta aren't as good because they have less serotonin effect, which is the main ingredient needed to help PMDD.

      Of course, I am assuming you are PMDD, and not PME which means premenstrual exacerbation of an ongoing mood disorder. Formal diagnosis of PMDD requires 2 cycles monitored prospectively, not retrospectively to show that symptoms are limited to the phase where dropping estrogen (which equals dropping serotonin), and sometimes dropping progesterone, causes increased anxiety and irritability. The medication then will have a calming effect.

      In general, for true PMDD, taking medication for just a few days 1-2, or up to 7-10 causes fewer side-effects and the lower doses continue to work. Dr. Wayne Jones