Does that mean that it is experimental? “Off label” is the term used when a medication is used in a manner that is not FDA approved. Does this mean the medication is experimental? No, absolutely not. This means simply that no studies have been sub-mitted 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 sub-mitted 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 his-tory. 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 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 to obtain FDA approval. The FDA requires that each medication target a specific diagnosis 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 overlap-ping 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.