On Depression

by Siegfried Othmer | July 14th, 2005

The current issue of Biological Psychiatry offers a trenchant study titled “Are There Differences in the Symptoms that Respond to a Selective Serotonin or Norepinephrine Reuptake inhibitor?” by Jay Craig Nelson, Laura Portera, and Andrew C. Leon (Volume 57(12), June 15, 2005, 1535-1542).

Remarkably, in two sequential, independent, randomized controlled large-scale studies (253 and 168 subjects) no significant differences were found in the response of major depression to reboxetine and fluoxetine. Symptom change was assessed with the Hamilton Depression Rating Scale (HAMD).

First of all, these results fly in the face of the core belief system of modern psychiatry, namely that of specificity not only with regard to diagnosis but with regard to pharmacological remedy. It also undermines the chemical deficiency model of depression. That model all along has had little more than the presumptive “specific efficacy” of selective serotonin reuptake inhibitors in evidence. Now that tall pole in the tent is gone.

It is truly ironic that the hegemony of the SSRIs has lasted for the entire duration of the Prozac patent. The superiority of SSRIs vis-à-vis the earlier medications that targeted the norepinephrine system as well (the tricyclics) seemed to be established beyond question. In truth, the driving force has all along been more a question of side effects rather than raw efficacy, with SSRIs being “cleaner” and freer of dietary restrictions than the tricyclics. This paper will make it easier to propose that the clinically effective drugs serve mainly to “reregulate” the system rather than to resolve a putative neurotransmitter deficit.

Neurofeedback for ADHD: A Review Paper

The latest issue (June 2005) of the Applied Psychophysiology and Biofeedback Journal features A White Paper Review of the prior research on neurofeedback for ADHD:

Monastra, V. J., Lynn, S., Linden, M., Lubar, J. F., Gruzelier, J., &
LaVaque, T. J. (2005). Electroencephalographic Biofeedback in the
Treatment of Attention-Deficit/Hyperactivity Disorder. Applied
Psychophysiology & Biofeedback, 30(2), 95-114.

The paper focuses on research performed with three of the standard protocols:
1) SMR Enhancement with Theta suppression;
2) SMR Enhancement with Beta-2 Suppression
3) Beta-1 Enhancement with Theta Suppression

The Kaiser-Othmer study on 1089 subjects is included in the review. However, the work is lumped under Protocol 1 (with variation). Unfortunately, the essence of the protocol is thereby lost. First of all, the protocol combined all three of the above. It provided standardly for the inhibition of both theta and beta-2 bands (22-30 Hz). And it provided for both SMR (12-15 Hz) and beta-1 (15-18 Hz) reinforcement according to the demands of the situation. Most individuals received both kinds of training.

Hence the review gives the impression that a standard protocol was used as with the other studies. And the essential feature of balancing right- and left-hemisphere training with hemisphere-specific parameters (SMR on the right; beta-1 on the left) was submerged.

It is difficult not to get the impression that the introduction of variability into protocol-based training is considered in some way a deviation from the ideal. Nevertheless, the White Paper is to be welcomed. Unfortunately, the paper came too soon to include the just-published replication by Tom Rossiter. Looking further back in history, the Cartozzo controlled study could not be included since it was kept out of the literature. And unfortunately the large-scale study we sponsored back in 1994-95 at Cal Poly Pomona never got written up. This was due to the fact that Barkley thoroughly intimidated the authors of that study when they surfaced their preliminary results at the 1995 APA meeting in Los Angeles. Perhaps there is a way to include such data in a future meta analysis.

And when it comes to outcome studies, there is Tamsen Thorpe’s dissertation, in which she quantified and analyzed the results from a number of practices that were using C3beta and C4SMR training with common instrumentation.

There is continuing controversy about whether training effects necessarily show up in the stationary EEG measures. The authors report on Lubar’s work with protocol 3 with some 17 children. 6 of these did not show change in EEG variables, whereas 11 showed change consistent with the design protocol. “Although the association between learning to control cortical activation and degree of clinical response was not assessed,” the authors nevertheless press the “importance of directly assessing neurophysiological indicators of learning in any evaluation of efficacy.” Remarkable. One can also relate this back to item one in the newsletter. If such criteria had been applied to the SSRI’s–i.e. they would be applied only in the case of a demonstrated deficit, and then only if the deficit is successfully remediated–then Prozac would never have gotten off the ground.

In both cases, that of depression and of ADHD, we are facing a yawning deficit in the understanding of the dynamics and complexity of neuroregulation. We must go back to a different point of departure entirely, one that sees regulation as a matter of the dynamic interaction of a variety of regulatory systems. It is impossible to intervene unilaterally with such a system. Once that is recognized we can go beyond overly specific models of deficits and over-constrained remedies to deal with them.

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