Patients' response to Anti-Depressants

Monday 12 May 2003 12:00AM (view full episode)

For more than one third of people with depression, the first anti-depressants they try won't make them feel any better. Although there are many different medications for people with depression, it can take up to two months for a patient to show any signs of response. Researchers at the University of California, Los Angeles, are trying to cut down this time by measuring a patient's brain waves. they suggest that it might reduce the waiting time to a mere two days. Maryke Steffens has the story.


One of the problems with all anti depressants, old and new, is that they take a while to have an effect and sometimes they don't work that well. When that happens, you have to try a new one and wait another few weeks to see whether the doctor's got it right this time.

What's needed is a faster way to identify if the medication you're on is going to pay off. It'd save a lot of time and distress.

The Health Report's Maryke Steffens has been looking at this, and visited a lab at the University of California Los Angeles where they think they may have an answer.

Ken Steckla: The fortunate or unfortunate thing for me I think was that for years I didn't realise I was depressed. I thought that that's how everybody sort of lived their lives, that you had to get up in the morning and go like OK, showtime, and psych yourself up. Being diagnosed and finding out that there was a possibility that medication would help me, I was hopeful. And of course, like you think you're going to win the lottery, I thought Well, probably the first one will work. Well it didn't.

Ian Cook: Most anti depressants take at least two to four weeks before one sees much of a change, and a really definitive response often isn't seen until eight weeks in younger adults, and sometimes 12 weeks in older individuals. So you really have to wait quite a while before we can say Yes, this is a medication that's working for a person, or, No, this just isn't doing the trick correctly. About 35% or 40% of people don't respond to the first medication they try, and of course there are many other medicines that a person can then try in sequence. But many people do find it very frustrating to try a medication that perhaps has some side effects, and be left after many weeks of trying, still feeling awful.

Maryke Steffens: Professor Ian Cook from the University of California, Los Angeles, and before him, Ken Steckla, who was diagnosed with depression two years ago.

As Professor Cook said, it can be incredibly frustrating to wait two to three months to see if an anti-depressant is working or not. So wouldn't it be great if there was another way to tell, one that would only take a few days?

Well, Professor Cook is looking at brain waves. He says these waves are like a barometer for your mood.

Ian Cook: We chose to look at brain waves because the relationship between what the nerve cells do and the medications, is something that other people had reported in the past is measurable by monitoring brain waves. No-one previously had really been able to relate specific changes in brain activity with treatment outcome in the way that we were able to.

Maryke Steffens: Fifty-one patients diagnosed with depression took part in the study. Some took fluoxetine, also known as Prozac, some took venlafaxine, brand name Effexor, and some took placebo.

The researchers measured brain waves at two days, one week and eight week.

Ian Cook: We have them lie down on a hospital bed and connect an array of electrodes onto their scalp, and this allows us to sense the electrical activity in the various parts of the brain. Then we use a computer to do the analysis that compares the activity in these different areas, and gives us brain maps, or pictures, of the relative activity in different parts. And what we found was that individuals who would go on to respond to the medication they were prescribed, characteristically showed a change in the area of brain behind the forehead, the prefrontal cortex, and that this change emerged as early as two days, three days, but certainly by a week, and almost everybody who would go on to respond. At this point they weren't showing any clinical differences.

Maryke Steffens: By clinical changes you mean they didn't feel any better?

Ian Cook: Exactly. They still had all the symptoms. The other part of the equation is that people who would end up not responding to the medication failed to show these early changes in brain activity. So we have this nice coincidence of a change being predictive of a later clinical change, and the absence of that brain function changes being predictive of an absence of later clinical response. But also the amount of change was associated with the amount of clinical improvement. What we would hope to do with more research is to decide what this threshold should be, and say If you've exceeded this amount of change, then that is likely to be associated with a very good outcome, and if you're in another range, you'll have a so-so kind of an outcome, and maybe something else would be a better choice.

Maryke Steffens: Measuring brain wave changes wasn't entirely reliable. Because about 20% of patients who did respond to medication didn't show these changes at all. But what was really interesting was the response that some of the patients had to placebo. Their brain waves also changed, but not in the same way. They increased, while responders to anti depressants decreased.

Ian Cook: When a person's having a response to the biochemical changes from the medication, brain activity change is one way. When they are having a clinical response not produced through introduction of molecules but through other brain-mind interactions, whether it's belief in the possibility of getting better, trust in their caregiver, past experience with other medicines having been effective, lots of different factors, here their brain function also changes, but it turns out it's in the opposite direction from the people who respond to the medication. For many years people have asserted that placebo treatment is non-treatment, and while the treatment may be inactive, there are changes in physiology that accompany it nonetheless in people who show clinical response.

Maryke Steffens: It's important to remember this research is preliminary, and the method they're using is experimental. However, the results do give us a small insight into what physically happens to our brain when we take drugs like anti depressants, and why this makes us feel better.

Ian Cook: What we're doing now is to look at what happens with other medications, and we're trying to see whether the pattern that we saw with the other medicines, holds with these as well, or if a different pattern will emerge. The medicines that we looked at the first time, fluoxetine, or Prozac, and venlafaxine, or Effexor, tend to act largely through serotonin in the brain. We're now looking at other medicines that act through primarily dopamine or other major neuro transmitters in the brain. Or another one called substance P, which is involved in pain circuits as well as in mood disorders. I think a couple of important points of the work are that it demonstrates that depression is a brain disorder. Many people still have the lingering feeling that this is somehow or other a problem of one's upbringing or immoral failings, and if only a person would just be stronger in some way, that they would be able to overcome this. And I think this underscores the fact that depression, while it has many contributing factors to it, is at its root, a problem in brain chemistry, and brain function. And we need to treat it, like we treat other medical illnesses.

Ken Steckla: It has sort of evened me out. I'm no longer as upset as I was about minor things. I don't think there's that much danger I'm going to kill anyone from road rage any longer, but it's important to realise that you treat depression, you do need to adapt to the drug and it is a long processes.

Norman Swan: Maryke Steffens with that story.


Professor Ian Cook
University of California, Los Angeles


Dr Norman Swan
Brigitte Seega