Low doses of the anti-anxiety drug Prozac may alleviate the misery of premenstrual syndrome (PMS), scientists have found.
Researchers at the University of Birmingham found that Prozac, known generically as fluoxetine, raises levels of a sex hormone that can drop sharply in women at the end of their menstrual cycle. This sudden drop is thought to cause the symptoms of PMS.
Millions of women around the world suffer the effects of PMS every month in the week before the start of their menstrual period. Symptoms can range from anxiety and irritability to headaches or joint and breast pain.
Not all women show symptoms, but around 75% are thought to experience PMS and, in up to 40% of cases, it can interfere with daily activities. Around 3% of women can experience a severe form of PMS, a psychiatric condition known as premenstrual dysphoric disorder.
Thelma Lovick, a neuroscientist at the University of Birmingham, thinks she has evidence that a 2mg daily dose of fluoxetine in the final week before menstruation could alleviate PMS. She presented her work at the British Science Festival in Birmingham today and her three-year study on rats, which were induced to have PMS-like symptoms, was funded by the Medical Research Council. Lovick now plans to submit her research to a scientific journal for peer review.
"We've got available to us a drug that is already in production, it's already gone through its safety tests, something we could use at very low dose to perhaps ameliorate the development of pre-menstrual syndrome in women," said Lovick.
Normally progesterone levels fall during the pre-menstrual period and this is when symptoms appear. "Progesterone is a hormone that circulates in the bloodstream and gets into the brain," said Lovick. "It breaks down into ALLO and it's this change in the ALLO concentration in the brain that causes excitability in the nerve circuits in parts of the brain that are involved in emotional behaviour."
Lovick thinks it is the sharp fall in the brain's ALLO levels that triggers PMS symptoms. "ALLO can alter the activity of nerve cells, thus it is described as a neuroactive steroid. It enhances the activity of GABA, one of the brain's inhibitory neurotransmitter chemicals, and in those parts of the brain that process emotional responses, ALLO normally produces calming effects."
When the levels of progesterone, and hence ALLO, in the brain drop during the final stages of the premenstrual period, that natural inhibition is turned off. "As a consequence these brain circuits become more excitable, leaving the individual more responsive to stress, which is often manifested behaviourally as anxiety and aggressive behaviour."
If ALLO levels could be allowed to fall gradually at the end of the monthly cycle, thought Lovick, PMS might not develop. She confirmed this idea by monitoring the hormone in rats' brains as they were administered fluoxetine.
"Millions of women take Prozac but the dose they take it in is relatively high. One of the effects of fluoxetine is that it acts on serotonin systems in the brain, that's why it's used as an antidepressant. One of the things it does in addition is increase ALLO concentrations in the brain and it does this at very low doses."
Tim Kendall of the Royal College of Psychiatrists, warned against self-medicating with fluoxetine. "Prozac is associated with a number of different side-effects. The most common is sexual dysfunction, it can lower libido and induce impotence. It can stop you sleeping and make you anxious and wound-up and affect appetite. And particularly in young people, under the age of 30, it can trigger suicidal thoughts and self-harm. I don't know if these side-effects would occur at low doses but it would strike me as unwise to start tipping drugs out of capsules."
Fluoxetine in sometimes prescribed as a treatment for PMS by some doctors in the US, but it is given at doses normally used in antidepressant therapy. Lovick said the standard antidepressant dose – 10-20mg per day – is inappropriate for PMS.
Her research team found that the dose required to produce a response was only a tenth of that found in the most commonly prescribed form of fluoxetine. "And you'd only be taking it for about a week so the side-effect issue should be non-existent," said Lovick.
The team now want to take their findings out of the lab and into clinical trials.
Kendall agrees that the use of low-dose fluoxetine in PMS needs more study. "PMS makes a lot of women quite miserable and if there is something we can do for them, that would be very good. But it is premature to say this is the thing."
