We Have Lost Track of the Natural History of Disease

You almost never hear about diseases having a beginning and an end anymore. It is as if all diseases are viewed as either acutely life threatening or inevitably chronic and requiring lifelong treatment.

Voltaire is credited with saying “The art of medicine consists in amusing the patient while nature cures the disease”. There is a lot of truth to that.

Some of the most common acute infections we treat in primary care, for example, are actually self limited, resolving on their own in the vast majority of cases. This is the case with strep throat, ear infections, many cases of “walking pneumonia” and even uncomplicated urinary tract infections.

Untreated strep throat, for example, very rarely becomes acutely life threatening. The reason we always prescribe antibiotics is to prevent late complications like rheumatic fever and glomerolunephritis, a kidney injury that was so common even with treatment when I trained that we always checked the urine after treating someone for strep. Now we hardly ever see this problem anymore, as if the strains of streptococcus have changed or evolved. Antibiotics can also help prevent peritonsillar abscess formation, which is quite rare.

Some diseases that we now think of as chronic and always requiring treatment are of course the lifestyle related ones like type 2 diabetes, hypertension and gastroesophageal reflux. We all know they can often be reversed in motivated people through changes in habits. So often these days, though, we prescribe medications early on, because it requires less effort on our part than counseling and monitoring change of patients’ daily habits.

Psychiatric diseases that we think of as obviously chronic include anxiety, depression and bipolar disease and even schizophrenia. But that is not always the case, and in some cases we may actually be turning transient diseases into chronic ones by the very treatments we prescribe for them.

Again going back to my Swedish medical education, I was taught that there were two kinds of depression; reactive where there was an identifiable external trigger like a major life event or endogenous where no trigger could be found. We Swedes only treated the latter form, whereas in the United States even the reactive form that we knew to usually be transient was treated with antidepressants – back then usually the tricyclic amitriptylene.

The American thinking was apparently that reactive depression could become chronic if left untreated, but many studies have now suggested that the opposite is true.

Several disturbing examples of this phenomenon are illustrated by author and journalist Roger Whitaker. His work, including his bestseller “Mad in America”, plowing through the scientific literature and contrasting that with pharmaceutical marketing and common psychiatric prescribing practices, is quite thought provoking:

A 1983 paper he quotes said this:

“Without antidepressant therapy, episodes of clinical depression last from 2 months to several years, with an average of around 5 to 6 months. One-third of the patients recover within a year; probably one out of four untreated episodes may last more than 2 years….Age and culture seem to influence the course of depression. In addition to the classified clinical depressions, there is a considerable prevalence in the general population of depressive symptomatology and dysphoric states, apparently related to genetic factors, age, and stress. Little is known about the course and indications for treatment of these latter conditions, which should be the target for more systematic study and research in the ever widening fields of the phenomenology and therapy of depression.”

Whitaker points out the shockingly disappointing results of some of the studies done on treating depression or not. He points out that the modern antidepressants, the selective serotonin reuptake inhibitors (SSRIs) were shown to increase levels of available serotonin at synapses, and the assumption was made that depressed patients had a deficit of serotonin, but this was actually never proven. He goes on to make the case that treatment with SSRIs may instead cause permanent changes in brain chemistry that induce chronic depression.

He quotes many leading academics who openly question the serotonin theory as a cause of depression.

Ironically, in our daily work, we are mandated (by our Federal payers) to screen for and offer treatment for depression – and SSRIs are the first line treatment. This brings us to the fundamental principles of medicine and “First, Do No Harm”. We should always ask ourselves these two questions:

What happens if I do nothing? and What’s the worst complication the treatment could cause? What does the literature say? Maybe we should take a closer look.

Are we in the same situation as the physicians who started wondering if bloodletting was really such a good idea. But it seemed like a frightening proposition to withhold what might be a patient’s only hope. Now we know that bloodletting actually made things worse.

In the case of SSRIs I certainly don’t know what’s what, but I do know that in this country at this point in time we are very quick to prescribe them, and I do know that we are not at all talking about the natural history of depression. I also know of an awful lot of patients who have had difficulty coming off SSRIs, so I do know they cause powerful, long lasting changes in how our brains work.

3 Responses to “We Have Lost Track of the Natural History of Disease”


  1. 1 Amanda (@changeiswelcome) October 12, 2019 at 4:57 am

    Thank You! From someone the antidepressants made much worse. I am having a very hard time getting off of them. I just wish more Drs would decide less is more.

  2. 2 Laura October 12, 2019 at 2:26 pm

    Some of the changes may have to do with changes in society. Few people can afford to take significant time off of work to care for themselves or a loved one, and thus the attraction of medication so people can get “back to their life”.

  3. 3 Andrew February 25, 2020 at 12:05 am

    So glad that you recognize and acknowledge the downsides and limitations of SSRIs. Mad In America is also a blog on psychology and social justice, with many MD contributors. The reality is that SSRI’s and other antidepressants are prescribed so widely and often without real, deep need, and too many people suffer from tremendous withdrawal symptoms and poor tapering instructions from doctors. Adequate training on SSRI tapering is so lacking in medical training, so I will say this here for anyone reading:

    Antidepressants must be tapered at a rate of 10% per month to reduce harm. This is corroborated by thousands on patient forums like SurvivingAntidepressants.org as well as by psychiatrists like Joseph Glenmullen, Peter Breggin, and new papers by Horowitz, Hengartner, and Davies. The brain requires such a slow rate of tapering (exponentially slow, in fact) in order to undergo the precise downregulation of receptors after the profound neuroremodeling induced by the drugs.


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