Off-label prescribing is a central and common source of treatment throughout medicine, particularly psychiatry. Lack of FDA indication does not equate to lack of evidence. It is therefore important to distinguish between supported and unsupported off-label prescribing practices. Supported off-label prescribing is the use of medications for a non-FDA-approved indication with clinical literature to support their use and the expectation based on scientific evidence that the benefits with outweigh the risks. Unsupported off-label prescribing does not have clinical literature to support the use and involves use that is suppositional or even investigative. In unsupported prescribing, there isn’t certainty that the benefits will outweigh the risks.
Off-label prescribing is a hot issue when it comes to antipsychotic medications. While many are approved for the treatment of schizophrenia and bipolar disorder, they are often also used off-label for aggression, impulsivity, and behavioral dysregulation. There are clinical situations when this can be considered supported off-label prescribing.
Elements involved in supported off-label prescribing include:
- A thorough clinical assessment including of co-morbid mental health and substance use issues
- Assessment of the level of impairment of the presenting symptoms
- Trials of appropriate non-medication treatments and medications with safer profiles
- A careful discussion with the patient and family about the potential risks and benefits and alternatives for the proposed treatment.
It is important that the provider make a thoughtful decision about prescribing off-label versus making the decision rashly because there is a sense of urgency to prescribe. It is also important that the off-label use of a medication be limited to as short of a time as possible, so that it is helpful during the acute period when not treating would have greater consequences but also to limit exposure to longer-term adverse effects, including metabolic effects and unknown effects on brain development.
In the case of antipsychotic medications, there is some good evidence based on clinical studies and neuroscience to support the idea of this class of medication to treat aggressive behavior. Antipsychotic antagonism of dopamine (D2) and serotonin (5-HT2a) receptors has been linked to reductions in aggressive behavior.
One thing to keep in mind is that antipsychotics to treat aggression represent a symptom-based approach to treatment rather than targeting the underlying cause, whether it is ADHD or depression or anxiety, etc. So at times, the symptom-based use of antipsychotics can lead to inappropriate and unsupported prescribing, if coupled with an incomplete assessment and a sense of urgency to prescribe.
The decision to prescribe off-label is complicated and involves a lot of thought. It is our hope that this information is helpful in the primary care setting when faced with these clinical decisions.