The commentary of Drs Potter and Paul, on whether anti-depressants really work, is interesting and disturbing. I have great respect for both of these fine doctors. I believe that antidepressants have a role in clinical practice but they are grossly over-utilized. As a certified psychopharmacologist, practitioner of Whole Psychiatry (Functional Medicine and traditional psychiatry), and Clinical Professor of Psychiatry at Georgetown School of Medicine, I see several problems with the logic employed.
First, Drs Potter and Paul state that antidepressants (AD’s) work for “at least 20% of patients on an initial trial”. The challenge is to “separate patients who really need a drug from those who will respond to placebo”. This means that some part of this 20% is placebo response. Probably 30-50% in an average trial is placebo, according to Drs Potter and Paul. This means that the actual non-placebo responders are less than 20%--so, by implication closer to 10-15% of the people given an anti-depressant in an initial trial are non-placebo responders, meaning they are responding to the drug, not the placebo effect. That is a pretty small slice. There are ways of improving this number (therapy, thyroid augmentation, multiple drugs), but clearly the drugs are missing the mark for most of the people most of the time.
They go on to defend this state of affairs by saying that these numbers are “similar to that for many other classes of drugs”. I believe that is true, but that is not an excuse for antidepressants, but rather an indictment of our “one pill for every ill” society. We rely on drugs rather than deal with root causes, and the pills generally are not as effective as we would be led to believe by the pharmaceutical companies incessant ads and research (publically acknowledged as distorted in peer reviewed journals such as NEJM, Eric Turner, 2008). Nor are these drugs with out financial costs and side effects. The solution they suggest is to devote more research time and dollars to develop lab tests to predict who will respond to medications. That is a reasonable idea, but given this era of tight budgets, it seems like too little bang for the buck. At best, after much more research we will be able to identify the 10-15% of people who do respond to medication.
I suggest that the solution is to develop better assessments of the metabolic factors leading to the syndrome of depression. The psycho-social-spiritual risk factors are reasonably well spelled out, and we have excellent targeted psychotherapeutic techniques available now. However, Dr’s Potter and Paul have a case of what I call ‘neurocentric psychiatry’. The model Dr Potter and Paul live by is based on the assumption that the biological answers to depression reside within the brain. I suggest that the fact that the head and brain are connected to the body by something called the neck may be relevant. In fact, there is a great deal of basic science and a good deal of clinical science indicating the very significant role played in subjective and objective mental health by at least six metabolic systems: nutrition, gastrointestinal physiology, immune/inflammatory/infectious processes, methylation processes, oxidative stress, and all hormonal systems. This list excludes other factors such as circulatory problems, physical-structural problems, age, gender, and lifestyle factors.
Assessing these metabolic systems, and their mediators in a careful comprehensive manner, and re-establishing multi-system reserves not only helps depression with less medication, but at the same time reduces the side effect burden imposed by medication, and reduces the incidence of known co-morbidities such as diabetes, cardiovascular disease, osteoporosis, sexual dysfunction.
The challenge in this day and age is not to find a way to make the drugs work better, find better drugs, or find out who will respond to drugs but rather to take a broad picture of mood disorders, one that acknowledges the fact that depression is part of a web which reaches to all levels of physiology, family, and society. The depression epidemic (depression will be the leading cause of disability by 2020 according to the World Health Organization) will not be stopped by drugs.
The treatment of most of the chronic illnesses bankrupting our health care system, including but not limited to depression, is fundamentally the same: good nutrition; normalizing gastrointestinal physiology; treating immune/inflammatory/infectious dysfunction; diagnosing and treating methylation processes (which affect many neurotransmitter systems); normalizing oxidative stress and detoxification pathways; assessing and regulating hormonal systems. All of this needs to be done in the context of strong community and relational functioning. With limited resources approaching this comprehensive multi-faceted model should be our goal—not simply figuring out who will respond to which drug. Psychopharmacology is only one small tool in our toolbox. As Confucius once said, “To do good work, one must first have good tools.” Anti-depressants are somewhat useful tools; they are just not the best or the only ones. We have other tools at our disposal. Why not use them? Robert J. Hedaya, MD, DFAPA