Hippocratic Psychopharmacology

by | Jun 16, 2023 | Education

Hippocratic psychiatry

 NOT “First, do no harm”

It’s a lie:  Hippocrates never said, “First, do no harm.” That phrase was invented by a 19th century English physician and falsely attributed to Hippocrates.

Here’s the truth:  Hippocrates said, “As to diseases, try to help, or at least not harm.”

There’s a huge difference between the two statements. “First, do no harm” implies a general conservatism about treatment: Be conservative, don’t use many drugs.

“As to diseases, try to help, or at least not harm” implies that you should first try to identify diseases; you have to take the disease concept seriously; if you deny it, then you cannot help anyone as a doctor.  Then, if you do not identify any disease, at least don’t harm.

At least!  That’s the key phrase, not at most, not initially, not primarily: At least.  You focus on not harming when you don’t have anything else to do, when you have concluded that there is no disease present, or at least no disease that you can treat.

At most: you should identify diseases, that is the job of the doctor – and you should treat those diseases to the best of your knowledge.  And if that means very harmful treatments – even chemotherapies that make you bald and weak – then you should give those treatments if they cure the disease, or improve it markedly.

So now that you know that Hippocratic medicine has nothing to do with the false idea of just not harming people, let’s look in more detail into what Hippocratic ideas really are.

Nature heals 

The principles of psychopharmacology follow from the principles of medicine, among which the Hippocratic approach is one perspective, oft-quoted but frequently misunderstood.  Hippocrates’ view of medicine, in contrast to other schools, was that disease comes from nature: it is not unnatural. Thus, it is not something to fight against, but rather a natural process which nature itself can heal.  The job of the physician is to help guide nature towards health, using measures such as diet and exercise, rather than to engage in combat with nature through medicines and toxins.  Thus,   the key Hippocratic idea is that nature heals, and doctor is only to handmaiden into nature. Nature cures, the doctor assists.

Many, if not most, illnesses improve naturally, and our role is to not get in the way of nature, but to help nature along.  Hence, the Hippocratics divided diseases into the self-limited, the treatable, and the incurable.  In the first and third cases, treatments in general are unnecessary and often harmful; in the second case, they are needed.  The art of medicine is to distinguish between these three cases.

So, the famous Hippocratic maxim, of first do no harm, is not an abstract ethical ideal, but rather it grows of out of this basic philosophy of disease.

 Non-Hippocratic psychiatry

It is my view that most psychiatrists practice non-Hippocratically.  We think we need to treat everyone who enters the doors of our offices.  There is precedent for this view in the founder of American Psychiatry, Benjamin Rush, who directly attacked the Hippocratic philosophy of treatment and who was a strong advocate of active intervention to treat all kinds of illnesses, including mental illness, mainly through bleeding. The Hippocratic approach was long forgotten in the Middle Ages and into the modern era.  In the US, the Hippocratic philosophy was resurrected  in the late 19th century by Oliver Wendell Holmes and William Osler.

Based on their writings, PL has derived two rules that should help clinicians engage in Hippocratic psychopharmacology:

Rules for a Hippocratic Psychopharmacology

Holmes’ Rule:   Medications are guilty until proven innocent.  Prescribe based on benefits first, and risks second; NOT vice versa.

Osler’s Rule: Treat diseases, not symptoms.


Holmes’ Rule stated

The first rule is derived from the physician and writer Holmes, who said in 1861:  “Presumptions are of vast importance in medicine, as in law.  A man is presumed innocent until he is proved guilty.  A medicine…should always be presumed to be hurtful. It always is directly hurtful; it may sometimes be indirectly beneficial.  If this presumption were established…we should not so frequently hear…that, on the whole, more harm than good is done with medication.  Throw out opium, which the Creator himself seems to prescribe, for we often see the scarlet poppy growing in the cornfields, as if it were foreseen that wherever there is hunger to be fed there must also be pain to be soothed; throw out a few specifics which our art did not discover, and is hardly needed to apply; throw out wine, which is a food, and the vapors which produce the miracle of anesthesia, and I firmly believe that if the whole materia medica, as now used, could be sunk to the bottom of the sea, it would be all the better for mankind, – and all the worse for the fishes.”

Holmes’ Rule explained

Thus, Holmes’ Rule is that there must be empirical proof that a treatment is effective so as to outweigh the presumption against the use of a medication. If clinicians followed this rule, they would avoid treatment with medications whose efficacy has not been proven at least to some degree.  As Osler put it, all medications are toxic; it is only the indication and the dosing that makes them effective.  Thus, before using any medication, we must presume harm; the burden of proof is on the medication to be shown effective, not on anyone to show that the medication is not harmful. Our risk-benefit calculations should begin, not on the risk side, but on the benefit side. Otherwise we end up with a kind of “gabapentin syndrome”—giving people safe, though ineffective, drugs (or alternatively, widely using drugs effective only for a few conditions).

Example of Holmes’ Rule: Antidepressants in bipolar illness

For example, in  the case of antidepressants for bipolar disorder, clinicians have been breaking Holmes’ rule egregiously.  We have engaged in the extensive long-term use of antidepressants despite two decades of randomized maintenance data demonstrating that they are ineffective, on the whole, in the prevention of depressive episodes in bipolar disorder.  Recent data are supporting that view even with newer generation antidepressants.

We should be surprised how often clinicians say that they want more evidence to stop using antidepressants.  If they were practicing Hippocratic medicine, and following Holmes’ rule, they would want evidence to start using medications, not to stop them.   The burden of proof is not that medications should be used unless proven ineffective and unsafe, but that they should not be used unless proven effective and safe.  With antidepressants, for some reason, we have gotten it backwards.

Osler’s Rule stated

The second rule is derived from the father of modern medicine, William Osler, who urged thus in 1895 (reprinted in his classic collection of essays, called Aequanimitas): “A man cannot become a competent surgeion without a full knowledge of human anatomy and physiology, and the physican without physiology and chemistry flounders along in an aimless fashion, never able to gain any accurate conception of disease, practising a sort of popgun pharmacy, hitting now the malady and again the patient, he himself not knowing which.”

Osler’s rule explained

Osler emphasized that we need to learn first about diseases before we can really do much about treatment.  Thus, Osler’s Rule is that we should treat syndromes (based on underlying diseases), not symptoms.  Symptoms are not what need to be treated; they are signs which point to the disease (or diagnosis), which is what needs to be identified and treated.  If clinicians followed this rule, they would avoid using drugs for multiple symptoms, which leads to a haphazard polypharmacy.   Thus, in treating bipolar disorder, patients often receive antidepressants for depressive symptoms, antipsychotics for manic symptoms, anxiolytics for anxiety symptoms, sedatives for insomnia, and mood stabilizers for mood swings.  This symptom-oriented approach to treatment is prescientific rather than scientific, 19th century-based rather than up to date, and anti-Hippocratic.  The Oslerian approach would be to focus on the diagnosis (not the symptoms),  which is bipolar disorder, and emphasize mood stabilizers, as much as possible by themselves, as the only class of treatment that treats the whole illness (acute depression, acute mania, and prophylaxis of mood episodes).    In cases where the disease is not well-identified, or where perhaps no disease exists, then treatment is symptomatic, of a band-aid nature, and the risk-benefit ratio for medication treatment would become more unfavorable to extensive prescription of such treatments.  Such is not the case with bipolar disorder, however, a diagnosis that has been well described since the Roman physician Arateus of Cappadocia (2nd century AD) and whose biological basis is reasonably well-established.

This need not mean that we should never use medications merely to relieve symptoms. It does mean that this approach goes against the Hippocratic view of medicine, and we should take it only in the short-term, reluctantly, and for immediate relief of symptoms.  In psychiatric populations where diseases are either poorly understood (as in children and the elderly), there is rampant symptomatic polypharmacy.  And many psychiatrists consider this state of affairs to be acceptable.  Osler’s Rule would give us pause.


To paraphrase the great German psychiatrist, Karl Jaspers, most of our mistakes and disagreements stem from our beliefs and concepts, rather than science or research.  Readers who have picked up this book to better diagnose or treat mood disorders will not gain much benefit unless they first think about their conceptual assumptions about psychiatric treatment.   In the past, we avoided medications too much: psychoanalysis was seen as the solution.  Now I believe we use medications too much:  we practice a symptom-oriented psychopharmacology that belongs in the 19th century.  We need to be clear about what we need to do:  we should prescribe medications primarily for diseases, not symptoms, and not even for all diseases; we should avoid prescribing them by habit, only doing so when proof of benefit exists and far outweighs risks.  With that basic philosophy, we can then turn to studies and research and data, leading to a scientific Hippocratic psychopharmacology.  Otherwise, in the PL view, the science and the data will be twisted by doctors and patients to their own whims, producing that eclectic mish-mash which is contemporary psychiatry.