resulting if treatment is not given due to suicide, poor
daily functioning and adverse family impact. The alleviation
of suffering, in our view, substantially outweighs a
few side effects. It is important that the physician be
attentive to and minimizes side effects.We see no violation
of the patient’s autonomy in the recommendation to
take medication or in the patient’s voluntary action to
take medication. We recognize that the physician has an
interest in treating depression and could over-value treatment
as opposed to doing nothing, and feel the physician
should guard against this. But by the same token, the
researcher has an interest in doing research and may
over-value the importance of research. An example from
the history of medicine is the case studies of an investigator
who failed to treat with penicillin because he felt that
a more systematic study of the natural history of syphilis
was needed. The fourth ethical principle is justice. Imagine
the hypothetical of a yet unborn medical ethicist
with full mental capacities and current knowledge but
not knowing whether they would suffer from depression.
We think they would wish to have antidepressants available,
which, upon becoming seriously depressed, they
could choose or not choose to take for themselves
depending on their own judgment. Another ethical test
to consider is does the availability of antidepressants,
which physicians may or may not recommend and
patients take or not take, produce harm to society in any
imaginable way? (An example of this is: widespread lying
and not keeping your word would harm society.) Since
Ioannidis condemns the use of behavioral and psychological
treatments as well as antidepressants, it is a question
of choice of one versus the other, as both can be
used. There are also societal aspects of justice. Depression
is an illness that results in suffering impacting the
patients and their significant others such as family,
friends, and coworkers. Moreover, poor vocational and
social deficits have societal costs. It is not so costly that
only the affluent can afford them.
Legal Perspective
Physicians also have a medical-legal obligation to try to
assuage the suffering and restore functioning through
interventions. Some have been sued and have lost litigation
when ideological reasons perpetuate unnecessary
suffering (see Osheroff v. Chestnut Lodge, Inc [76]). Dr.
Osheroff was a patient in a facility that offered psychoanalytic
psychotherapy for his severe depression for
months; when he was finally transferred elsewhere and
received antidepressants and antipsychotics, his depression
remitted quickly.
Anthropological Perspective
The underpinnings of cooperation, empathy, and many
similar mental functions are fundamental to human
society. All cultures have religious and ethical norms to
provide help to members of their society, including the
relief of suffering. To alleviate human suffering is a
moral imperative.
Summary
Ioannidis suggests the efficacy of antidepressants is a
myth and that same applies to behavioral interventions.
There is merit in many of his methodological concerns,
which apply to most pharmacotherapy, and behavior
intervention. We agree that science, like all empirical
knowledge is not perfect. It is important to note that failure
of drug companies to publish all their studies does
result in an inflated estimation of their efficacy. We agree
that this is important. However, we disagree that antidepressant
have no greater efficacy than placebo. He notes
that there have been over a thousand controlled trials,
yet he bases his argument on very little data, indeed just
a few meta-analyses. We present the efficacy from
approximately a hundred of trials in percent of patients
with a substantial clinical response (defined as 50%
improvement or more symptomatic reduction). These
meta-analysis find 42-70% of antidepressant improve
with drug and 21%-39% improve with placebo. The increment
with drug is 33%-11% greater than placebo. Ioannidis
argues that it would be vanishingly smaller because
systematic biasing in these clinical trials would reduce
the drug-placebo difference to zero. (To reduce to zero,
one would also have to postulate that some of the unpublished
studies do find placebo better than drug and substantial
systematic bias, without any evidence). His
argument that effect size vanishes, suffers from failures of
logic because Ioannidis does not present any evidence
that there are a large number of studies where placebo is
substantially more effective than drug. (To reduce to
zero, one would also have to postulate that some of the
unpublished studies do find placebo to be better than
drug). We also present the empirical evidence showing
that these methodological issues generally have the opposite
effect of what Ioannidis argues, suggesting that the
measured efficacy underestimates true efficacy. Our argument
is not that antidepressants are more effective than
measured, nor that the effect size is necessarily bigger
than Ioannidis’ effect size of 0.31, but rather that he
presents no credible evidence that antidepressants
have zero effect size. Our most important criticism is
the basic underlying argument that if the existing evidence
is imperfect and methods can be criticized, then
the findings are invariably wrong, proving the opposite of
efficacy, i.e. the drug has no efficacy. We note the similarities
of this to the creationist argument that evolution
cannot explain everything; therefore, one must postulate
intelligence, the opposite of evolution, i.e. intelligent
design is true. Depression causes great suffering, indeed
so great that 5-15% of depressed patients kill themselves
[6,7]. Depression leads to suffering of family and friends.
We find no ethical reason why therapists should not try
to help depressed patients with drugs and/or with psychotherapeutic/
behavioral treatments even though they
do not help everyone and our knowledge is not perfect.
The immense suffering of patients with major depression
leads to professional, ethical, and moral obligations to
treat patients with the best available tools at our disposal,
while diligently and actively monitoring for adverse
effects, and actively considering revisions of the treatment
components, whatever the modality employed.
Medical decisions should be shared decisions made with
the patients, respectful of the patients and families
experiences, intuitions, values, and autonomy.