Exploring psychotherapeutic issues and agents in clinical practice
Virtually all drugs used in psychiatry are classified according to their initial or main therapeutic indications rather than by their pharmacological profiles. Prescribers, clinicians, and patients generally refer to drugs as antidepressants (implying depression), antipsychotics (implying psychosis), anxiolytics (implying anxiety), and so on, regardless of why the drugs may be used. Because particular drugs can be and are used for different clinical reasons, such an indication-based nomenclature system may often confuse or mislead patients as well as other non-mental health prescribers and clinicians. For example, when an antipsychotic drug or lithium is being used to augment an antidepressant drug for the treatment of major depressive disorder (MDD), the patient or his or her primary care physician may mistakenly believe that the prescribing psychiatrist or nurse practitioner is treating the patient for schizophrenia or bipolar disorder. Lumping drugs together based on overly broad classifications without regard to their individual pharmacologies can also result in a misleading perception of their relative risks (Howland, 2014a,b).
In previous columns, I have emphasized the central importance of knowing the pharmacology of drugs as a way to understand their clinical profiles and ranges of use (Howland, 2008, 2012, 2014a). In this month’s column, I will describe a proposed multi-axial, pharmacologically driven classification system for psychotropic drugs (Zohar et al., 2014).
Proposal for an Updated Neuropsychopharmacological Nomenclature
Beginning in December 2008, a collaborative taskforce involving representatives from the European College of Neuropsychopharmacology (ECNP), the American College of Neuropsychopharmacology, the Collegium Internationale de Neuropsychopharmacologie, the Asian College of Neuropsychopharmacology, and the International Union of Basic and Clinical Pharmacology took on the complex mission of updating and formulating pharmacological nomenclature that would be relevant to brain disorders. This effort led to the development of a proposed multi-axial, pharmacologically driven nomenclature system (Zohar et al., 2014). This system would be used to reclassify existing psychotropic drugs and provide a framework for evaluating and classifying new drug compounds.
The proposed nomenclature template has five axes. Axis 1 will be used to identify the primary pharmacological target and relative mechanism of action for a drug. Axis 2 will list the drug’s family, reflecting the primary neurotransmitter(s) and relevant mechanism(s). Axis 3 will describe the drug’s known neurobiological activities, including its neurotransmitter effects, brain circuits, and physiological effects in animals and humans. Axis 4 will detail clinical observations about the drug, including its major known efficacy and side effects. Axis 5 will include only current approved indications, based on the U.S. Food and Drug Administration, the European Medicines Agency, or other similar regulatory agencies. In addition, a “Committee Note” section may be added as necessary for each drug listed. The Committee Note may include such information as potential new indications, special clinical issues, and other important considerations pertinent to the drug. Relevant references may also be included for each drug.
Multi-Axial Psychopharmacological Nomenclature for Mirtazapine
On the ECNP website (access http://www.ecnp.eu/projects-initiatives/nomenclature.aspx), a list of 109 drugs presented using the proposed nomenclature template can be found. To illustrate what a multi-axial nomenclature may look like, I will use the antidepressant drug mirtazapine (Remeron®) as an example (Table).
Example of a Multi-Axial Nomenclature for Mirtazapine
As can be seen from this example, information about mirtazapine is organized to include basic information about its complicated pharmacology, its various therapeutic and adverse clinical effects, and its formal therapeutic indication. A Committee Note and relevant references have been added, as they may supplement information included in the five axes.
Information from the five axes could be used in various ways to guide or help with prescribing decisions. Although mirtazapine has an approved indication only for MDD, which is listed on Axis 5, the drug can be used off-label for the treatment of insomnia or anxiety, which is noted in Axis 4. The two main strategies for treating patients with depression who do not respond to an antidepressant drug are switching medications or combining medications. The switch or combination typically involves drugs with different pharmacological properties. Using information from Axes 1, 2, and 3, a rational choice for switching or combining certain medications can be made. On the basis of pharmacological differences, either switching to or adding mirtazapine to other antidepressant drugs is justified for treatment nonresponders (Howland, 2008).
Classifying drugs not by their main therapeutic indications but rather by their pharmacological profiles provides a useful framework for explaining and describing their clinical profiles and ranges of use. This classification will encourage the exploration of potential new clinical uses for a drug, corresponding to developments in understanding the neuroscience of a drug and the pathophysiology of psychiatric disorders. Such a classification system will also provide a practical rationale for using certain strategic drug switches or combinations to improve patient outcomes. This type of system will make it easier to incorporate advances in pharmacogenomics. The proposed multi-axial system is a common sense but scientifically informed approach for classifying psychotropic drugs, designed to be practically useful for prescribers, clinicians, and patients. For example, as part of the initial phase of development, a beta version of a smartphone application has been created (Brauser, 2014). The proposed nomenclature is a work in progress, and interested readers can submit comments about the proposal on the ECNP website (access http://www.ecnp.eu/projects-initiatives/nomenclature.aspx).
- Brauser, D. (2014, November3). New psychotropic drug classification system unveiled. Medscape Medical News. Retrieved from http://www.medscape.com/viewarticle/834238
- Gillman, P.K. (2006). A systematic review of the serotonergic effects of mirtazapine in humans: Implications for its dual action status. Human Psychopharmacology, 21, 117–125. doi:10.1002/hup.750 [CrossRef]
- Howland, R.H. (2008). Understanding the clinical profile of a drug on the basis of its pharmacology: Mirtazapine as an example. Journal of Psychosocial Nursing and Mental Health Services, 46(12), 19–23.
- Howland, R.H. (2012). Off-label medication use. Journal of Psychosocial Nursing and Mental Health Services, 50(9), 11–13. doi:10.3928/02793695-20120807-05 [CrossRef]
- Howland, R.H. (2014a). Atypical antipsychotics are not all alike: Side effects and risk assessment. Journal of Psychosocial Nursing and Mental Health Services, 52(9), 13–15. doi:10.3928/02793695-20140820-01 [CrossRef]
- Howland, R.H. (2014b). Mortality risk of mirtazapine: Guilt by association?JAMA Psychiatry, 71, 585–586. doi:10.1001/jamapsychiatry.2013.4582 [CrossRef]
- Zohar, J., Nutt, D.J., Kupfer, D.J., Moller, H.J., Yamawaki, S., Spedding, M. & Stahl, S.M. (2014). A proposal for an updated neuropsychopharmacological nomenclature. European Neuropsychopharmacology, 24, 1005–1014. doi:10.1016/j.euroneuro.2013.08.004 [CrossRef]
Example of a Multi-Axial Nomenclature for Mirtazapine
|Relevant mechanism||Receptor antagonist|
|Family||Norepinephrine alpha-2 receptor antagonist; serotonin 5HT2 and 5HT3 receptor antagonist; histamine H1 receptor antagonist|
| Neurotransmitter effects||Alpha-2 autoreceptor antagonism increases norepinephrine; alpha-2 heteroreceptor antagonism increases serotonin; antagonist at histamine H1, serotonin 5HT2, and serotonin 5HT3 receptors|
| Brain circuits||Increase in extracellular norepinephrine and dopamine in prefrontal cortex|
| Physiological||Increase in mRNA of neurotrophins (e.g., BDNF, NGF, NT-3) and decrease of pro-apoptotic proteins (e.g., Bax, Bcl-xl, p53, Bad)|
|Efficacy and major side effects||Improves symptoms of depression and anxiety; promotes sleep; has low level of sexual dysfunction; highly sedating at the beginning of treatment; may stimulate appetite and increase body weight; can reduce nausea and vomiting associated with other conditions|
|Approved indications||Major depressive disorder|
|Committee Note||Unlikely to be associated with serotonin toxicity in an overdose or when combined with monoamine oxidase inhibitor drugs|
|References||Gillman, 2006; Howland, 2008|