Does off-label medication for depression treatment means it is experimental?
"Off label" is
used when a medication is used in a manner that is not Food and Drug
Administration (FDA) approved. Does this mean the medication is
experimental? No, absolutely not. This means simply that no studies have
been submitted to the FDA for approval of the medication for that
particular use. It does not mean that no studies have been done. Many
studies may not have been submitted or may have been submitted and
approved by European governments. It does not mean that the medication is
not widely prescribed for a use other than what the FDA approved. It does
not mean that doses under or over the recommended range approved by the
FDA are neither effective nor safe. It does not mean that the medication
is not safe in age groups younger or older than what the FDA approved. It
merely means that when the company submitted the medication for approval
to the FDA it submitted studies that specified a diagnosis, a dosage
range, and an age group that their study subjects reflected.
Drug research and development have a fascinating history. Psychiatric
drugs are often discovered serendipitously. Most drugs have multiple
effects on the body, and focusing on one particular action to the
exclusion of another is often as much a matter of marketing as it is drug
action. For example, the first antipsychotic medication was developed and
tested by a trauma surgeon who was specifically interested in finding a
medication that could prevent surgical shock, a condition with a high
mortality rate at the time. It was only through clinical observation that
it was discovered to have antipsychotic effects as well as a variety of
other effects on the body. The company that originally introduced it to
the United States did not believe that there would be a market for it as
an antipsychotic and thus released it to the public as an antiemetic.
Only through multiple physician-driven lectures were psychiatrists in the
United States comfortable enough to try it on patients suffering from
schizophrenia. Perhaps even odder is the fact that the first
antidepressant effects were observed in medications developed to treat
tuberculosis. Only later was it discovered that these medications
inhibited, or blocked, monoamine oxidase, an enzyme that breaks down
norepinephrine, serotonin, and dopamine at the synaptic cleft.
To call any particular medication an antihypertensive, an antipsychotic,
an antidepressant, or an anticonvulsant is actually a misnomer and really
reflects the target population that a particular medication is geared
toward when released to the public, and not the broad range of effects of
which the medication is capable. It also reflects the expense that the
companies go through in order to obtain FDA approval. The FDA requires
that each medication target a specific diagnosis in order to receive
approval. This is a hugely expensive enterprise for one diagnosis, which
is exponentially greater for multiple diagnoses. Therefore, it is
unlikely drug companies will submit studies for approval for more than
one or two diagnoses, unless they can see some return on investment. As a
result, clinical practice is often very different from what the
Physicians' Desk Reference (a standard reference of all FDA approved
prescription medications) publishes. Clinical practice moves at a much
faster pace than clinical trials and publications can keep up with.
Although clinical trials are considered to be the definitive evidence of
any particular medication's efficacy, astute clinical observations are
what brought the biggest drug discoveries to the world and cannot be
discounted simply because no study has yet to be published.
There are two broad reasons why off-label use makes sense in psychiatry.
First, psychiatric diagnoses do not fit into the neat little categories
that the DSM-IV-TR attempts to define. They generally have many
overlapping symptoms. For example, anhedonia, or loss of interest, can be
seen in a number of conditions that include depression, schizophrenia,
and frontal lobe damage. Many psychiatrists believe that medications
should be prescribed to target the particular neurochemicals underlying
such specific symptoms regardless of the DSM diagnosis. Off-label use is
practiced with a clear rationale for another reason as well. Human nature
defies categories. Although there may be broad similarities between two
individuals suffering from depression, it is doubtful that any one
individual is suffering in exactly the same way as another from both a
biochemical standpoint and a psychological standpoint. Thus, one may
respond to one particular therapy or antidepressant and not another, and
the reasons are due to the therapies' and antidepressants' biochemical
differences, not their similarities. For these reasons, off-label use in
psychiatry is more the rule than the exception. As an example of
observation trumping scientific studies: a man sought out a cardiologist
because he noticed getting palpitations from one particular brand of cola
and not another. The cardiologist dismissed him outright. The man sought
another cardiologist who agreed to perform a stress test after he
ingested the different brands; sure enough, the man experienced premature
ventricular beats with one particular brand of cola and not another.
Never underestimate the power of one.
