Predicting Antidepressant Response with EEG

One of the limitations of antidepressants is that they don't always work. Worse, they don't work in an unpredictable way. Some people benefit from some drugs, and others don't, but there's no way of knowing in advance what will happen in any particular case - or of telling which pill is right for which person.

As a result, drug treatment for depression generally involves starting with a cheap medication with relatively mild side-effects, and if that fails, moving onto a series of other drugs until one helps. But since it can take several weeks for any new drug to work, this can be a frustrating process for patients and doctors alike.

Some means of predicting the antidepressant response would thus be very useful. Many have been proposed, but none have entered widespread clinical use. Now, a pair of papers(1,2) from UCLA's Andrew Leuchter et al make the case for prediction using quantitative EEG (QEEG).

EEG, electroencephalography, is a crude but effective way of recording electrical activity in the brain via electrodes attached to the head. "Quantitative" EEG just means using EEG to precisely measure the level of certain kinds of activity in the brain.

Leuchter et al's system is straightforward: it uses six electrodes on the front of the head. The patient simply relaxes with their eyes closed for a few minutes while neural activity is recorded.

This procedure is performed twice, once just before antidepressant treatment begins and then again a week later. The claim is that by examining the changes in the EEG signal after one week of drug treatment, the eventual benefit of the drug can be predicted. It's not an implausible idea, and if it did work, it would be rather helpful. But does it?

Leuchter et al say: yes! The first paper reports that in 73 depressed patients who were given the antidepressant escitalopram 10mg/day, QEEG changes after one week predicted clinical improvement six weeks later. Specifically, people who got substantially better at seven weeks had a higher "Antidepressant Treatment Response Index" (ATR) at one week than people who didn't: 59.0 ± 10.2 vs 49.8 ± 7.8, which is highly significant (p less than 0.001).

In the companion paper, the authors examined patients who started on escitalopram and then either kept taking it or switched to a different antidepressant, bupropion. They found that patients who had a high ATR after a week of escitalopram tended to do well if they stayed on it, while patients who had a low ATR to escitalopram did better when they switched to the other drug.

These are interesting results, and they follow from ten years of previous work (mostly, but not exclusively, from the same group) on the topic. Because the current study didn't include a placebo group, we can't say that the QEEG predicts antidepressant response as such, only that it predicts improvement in depression symptoms. But even this is pretty exciting, if it really works.

In order to verify that it does, other researchers need to replicate this experiment. But they may find this a little difficult. What is the Antidepressant Treatment Response Index use in this study? It's derived from an analysis of the EEG signal, and we're told that you get it from this formula:

Some of the terms here are common parameters that any EEG expert will understand. But "A", "B", and "C" are not. They're constants, which are not given in the paper. They're secret numbers. Without knowing what those numbers are, no-one can calculate the "ATR" even if they have an EEG machine.

Why keep them secret? Well...

"Financial support of this project was provided by Aspect Medical Systems. Aspect participated in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation and review of the manuscript."

Aspect is a large medical electronics company who developed the system used here. Presumably, they want to patent it (or already have). We're told that

"To facilitate independent replication of the work reported here, Aspect intends to make available a limited number of investigational systems for academic researchers. Please contact Scott Greenwald, Ph.D... for further information."

All very nice of them, but if they'd told us the three magic numbers, academics could start trying to independently replicate these results tomorrow. As it is, anyone who wants to do so will have to get Aspect's blessing, which, with the best will in the world, means they will not be entirely "independent".

[BPSDB]

Leuchter AF, Cook IA, Gilmer WS, Marangell LB, Burgoyne KS, Howland RH, Trivedi MH, Zisook S, Jain R, Fava M, Iosifescu D, & Greenwald S (2009). Effectiveness of a quantitative electroencephalographic biomarker for predicting differential response or remission with escitalopram and bupropion in major depressive disorder. Psychiatry research PMID: 19709754

Leuchter AF, Cook IA, Marangell LB, Gilmer WS, Burgoyne KS, Howland RH, Trivedi MH, Zisook S, Jain R, McCracken JT, Fava M, Iosifescu D, & Greenwald S (2009). Comparative effectiveness of biomarkers and clinical indicators for predicting outcomes of SSRI treatment in Major Depressive Disorder: Results of the BRITE-MD study. Psychiatry research PMID: 19712979