Applying complexity theory to psychotropic medication polypharmacy: a typology proposal

Journal of Psychiatry Reform vol. 10 #12, November-December 2023

Abraham (Rami) Rudnick, MD, PhD, FRCPC, DFCPA

Clinical Director, Nova Scotia Health Authority Clinic, Nova Scotia Health Authority

Professor, Departments of Psychiatry and Bioethics and School of Occupational Therapy

Dalhousie University, Nova Scotia, Canada

Email: [email protected]


Psychotropic medication polypharmacy (PMP) is commonly prescribed yet it poses increased safety risks and is not sufficiently evidence based; it is also arguably not based on a coherent theoretical approach, which is challenging too. To ground PMP in a sufficiently coherent theoretical approach, the application of a key tenet (non-linearity) of complexity theory to PMP is hereby explored. This article proposes a related typology and illustrates it with the example of PMP for posttraumatic stress disorder (PTSD). It concludes by addressing implications for practice and related policy and suggests further theoretical inquiry and empirical research.

Key words: complexity, medication, polypharmacy, psychotropic, theory

Psychotropic medication polypharmacy (PMP) can be simply defined as prescribing more than one psychotropic medication at a time for a person.  It is often prescribed for various mental disorders of various clinical populations across the age range, yet it poses increased safety risks and is not sufficiently evidence based1. Furthermore, and arguably as importantly, it does not seem to be grounded in a coherent theoretical approach to inform its research, practice, education and policy making (such as setting clinical guidelines), although such grounding has been helpful in other areas of mental health inquiry2. For example, some of its current classification distinguishes same-class, multi-class, adjunctive, augmentation and other (such as total) PMP1. This classification seems to address various categories, such as same-class PMP vs multi-class PMP and adjunctive PMP vs augmentative PMP. Some of these categories seem incoherent, as some psychotropic medications belong to more than one class. The distinction between adjunctive PMP and augmentative PMP seems coherent as presumably adjunctive treatment refers to adding treatment with an expected effect that is not related to the effect of the core treatment, whereas augmentative treatment refers to adding treatment that enhances the effect of the core treatment.

To ground PMP in a coherent theoretical approach, exploration of complexity theory is helpful. In this article, I explored the application of non-linearity as a key tenet of complexity theory to PMP and implications for practice and related policy; I chose non-linearity as my focus for this article as its application to PMP seems particularly suitable such as for a typology of PMP, recognizing that other tenets of complexity theory such as emergent properties, self-organization and more may be pertinent too. I selectively used peer reviewed literature to illustrate this, using posttraumatic stress disorder (PTSD) as an example.

Complexity theory has been described as “the study of phenomena which emerge from a collection of interacting objects”3. Complexity refers to systems whose behaviours in some or all circumstances are not fully explained by their components. For example, complex systems manifest some properties that are not the properties of any of their components; this applies to both animate and inanimate systems, such as consciousness being a property of persons whose nervous and other biological systems do not manifest consciousness and anomalous aspects of the solid state of water (ice) being a property of hydrogen and oxygen that do not separately manifest such anomalous physical behaviour. Complexity also refers to systems that self-organize in that they determine their own structure and function, at least within a (limited) range of parameters. For example, some mineral crystals manifest self-organization of their structure within a range of chemical concentration and other physical variable, and homeostasis is physiological self-regulation of living systems’ function within a range of temperature and other physical variables; indeed, health – and related pharmacology – is arguably such biopsychosocial (dynamic) balance4,5.

In the context of PMP, complexity theory can be interpreted as referring, among other things, to effects that result from prescribing more than one psychotropic medication at a time for a person. In particular, non-linear effects often occur according to complexity theory3. Non-linearity means that effects are not additive (arithmetically summative) but rather result from other types of (hopefully quantifiable) interactions. For example, a non-additive effect could be catalytic, such as occurs when enzymes are added to suitable proteins and other types of substrate molecules, resulting in activation or de-activation of these substrate molecules; these enzymes are not otherwise active. Another type of non-additive effect could be augmentative, such as occurs when one molecule enhances the effect of another molecule while producing an effect of its own. Yet another type of non-additive effect could be synergistic, such as occurs when two or more molecules are augmentative of each other. And yet another type of non-additive effect could be adjunctive, where two or more molecules have separate effects but their cumulative effect is more beneficial and/or harmful than each of their effects separately (a special case of this are linear effects where the cumulative effect is as beneficial and/or harmful as the sum of each of the effects separately). Thus, a typology of PMP can be generated coherently using the non-linearity tenet of complexity theory (recognizing that the typology described above may not be exhaustive).

An example of this application of complexity theory’s non-linearity tenet to PMP is the combination of antipsychotic medication with antidepressant medication for refractory posttraumatic stress disorder (PTSD). This is still an emerging rather than an established practice that has mixed results. For example, some antipsychotic medications such as risperidone demonstrate (small size) positive effects when combined with antidepressant medications such as selective serotonin reuptake inhibitors (SSRIs) for PTSD that does not improve sufficiently with SSRIs (and trauma focused psychotherapies)6. In particular, these effects seem to improve PTSD’s common symptomatology of anxiety6, for which this medication combination may be considered either augmentative or adjunctive (rather than only augmentative as it is currently considered, recognizing that the term augmentation may be used more generally in this literature). To clarify which of these two types of effects is occurring in this example, further analysis of separate as well as cumulative effects of the combination of these two types of medication on anxiety related to such PTSD is needed, the results of which may change practice and related policy such as clinical guidelines (as if this is an adjunctive rather than an augmentative effect, lower risk adjunctive treatments – rather than antipsychotic medications – may be preferred).

To conclude, applying complexity theory’s non-linearity tenet to PMP facilitates a theoretically coherent approach that generates an apparently useful typology of PMP. This is demonstrated by the example of PMP for PTSD. Both practice and policy may be positively impacted by such an application, preferably integrating it with person-centered mental health care7. Further theoretical inquiry in addition to empirical research of complexity and its theory is important to pursue and support in relation to PMP and arguably more generally in relation to psychopharmacology, such as addressing emergent properties and self-organization as well as non-linearity.


  1. Kukreja S, Kalra G, Shah N, Shrivastava A. Polypharmacy in psychiatry: a review. Mens Sana Monogr 2013;11(1):82-99. doi: 10.4103/0973-1229.104497
  2. Rudnick A. Psychiatric leisure rehabilitation: conceptualization and illustration. Psychiatric Rehabilitation Journal 2005;29(1):63-65. doi: 10.2975/29.2005.63.65
  3. Johnson N. Simply complexity: a clear guide to complexity theory. New York: Simon and Schuster, 2009, p. 1.
  4. Rudnick A. The notion of health: a conceptual analysis. Israel Medical Association Journal 2002;4(2):83-85
  5. Rudnick A. Health as balance: a conceptual study. Health 2017;9(7):1000-1006. doi: 10.4236/health.2017.97072
  6. Hoskins MD, Bridges J, Sinnerton R, Nakamura A, Underwood JFG, Slater A, Lee MRD, Clarke L, Lewis C, RobertsNP, Bisson JI. Pharmacological therapy for post-traumatic stress disorder: a systematic review and meta-analysis of monotherapy, augmentation and head-to-head approaches. Eur J Psychotraumatol 2021; 12(1):1802920. doi: 10.1080/20008198.2020.1802920
  7. Akhtar N, Forchuk C, McKay K, Fisman S, Rudnick A. Handbook of person-centered mental health care. Boston: Hogrefe, 2021.


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