How fast do antidepressants act? It depends what’s being treated. Premenstrual irritability responds within hours.

The standard wisdom has it that antidepressants take two weeks to work and four weeks to work well. But some women take medication only a few days a month, to regulate mood changes in response to the menstrual cycle. Can antidepressants provide help in such a brief timespan?

Mikael Landén and other researchers at the Karolinska Institute in Stockholm, Sweden, have performed a series of experiments to answer that question. The latest, reported this month as an advance online publication in Neuropsychopharmacology, involved 22 women who displayed premenstrual anger or irritability that had, in past trials, responded to Paxil.

Over the course of three menstrual cycles, Landén now had the women take either Paxil or an identical-looking placebo capsule. The women began the brief course of medication once they had felt irritable for two days, in the interval between ovulation and menstruation. Treatment continued until the third day of menstruation. (Each woman took Paxil during two cycles and placebo during one, based on random assignment; the placebo dosing might occur in any of the three months.) Every few hours, the women rated their irritability. By the fourth hour, women on the antidepressant began to feel less angry and upset; by the fourteenth hour, the change was statistically significant, when contrasted with the experiences of women on placebo. Most women could tell that they were on the active drug — by the fourth hour, they felt nausea that then faded — but the women who had no side effects from Paxil reported just as much sustained benefit.

The same research group has found that rats’ menstrual-cycle related irritability can be reduced within two hours by injecting antidepressant into the animals’ belly cavities. The new study also meshes well with observations that healthy huan subjects, without mental illness or premenstrual symptoms, can respond to Paxil with a quick decrease in hostility and other negative affects.

The theory is that antidepressants (like Paxil) whose main initial effect is on serotonin transmission — the SSRIs — cause rapid changes in the levels of neurotransmitters that bathe brain cells. What take time are other adaptations: the growth of new cells and changes in ways that receptors respond to transmitters. These slower effects are thought to account for improvements in the syndrome of major depression.

The current study offers only suggestive findings about how a broad range of premenstrual symptoms respond to Paxil. What these research subjects had in common was irritability. But average scores, combining reports of depressed feeling, mood swings, tension, bloating, breast tenderness, and changes in appetite, began separating at two hours and reached “significance” on the third day, with the medicated patients doing better than those on placebo.

The Landén study — it was underwritten by Glaxo SmithKline and the Swedish Research Council — offers additional support for practice of treating premenstrual symptoms with periodic doses of antidepressants.

For depressed patients on SSRIs whose symptoms worsen around their menses, doctors sometimes recommend a slight increase in dose on the relevant days. Finally, any claim about the precise mechanism of action of antidepressants is speculative. But it may be that the two sorts of improvement, in premenstrual symptoms and in depression, have different biological bases, one related to short-term fluctuations in neurotransmitter levels and one to slower and more chronic brain adaptations. Other early effects — I recently cited a report about rapid, subtle alterations in outlook in depressed patients — may also represent responses to immediate changes in brain cells’ exposure to serotonin.