Improving pharmacological treatment for patients with severe mental illness

Background information

People with severe mental illness (SMI) die 10-20 years earlier than the general population [1]. This excess mortality is primarily due to death by natural causes. In line with this, people with SMI have a higher prevalence of physical comorbidities than the general population. This increased morbidity is partly explained by social factors and lifestyle [2]. However, to a large extent this excess morbidity results from a lower quality of medical care [3], including poor medication control [4].

One part of medication control encompasses the monitoring and prevention of adverse medication effects. People with SMI often experience side effects of psychopharmacologic treatment. Antipsychotic medications have serious adverse effects, for instance increased risk of heart arrhythmia. A nationwide Danish study of unexplained sudden cardiac death in individuals < 40 years revealed that 24% had two or more psychiatric prescription drugs in their blood at the time of death [5]. Moreover, metabolic disturbances such as weight gain, diabetes, and dyslipidemia are common adverse effects of antipsychotic medication. However, this may only be the tip of the iceberg: trials on antidepressants have been shown to be an unreliable source for quantifying adverse effects due to selective reporting, misclassification and underreporting of harms [6]. To our knowledge, no studies have investigated, in a rigorous manner, the adverse effects of other psychopharmacologic treatments and therefore it remains unknown how harmful these drugs are.

A second aspect of medication control includes pharmacological over- and under-treatment. Among people with SMI, physical diseases are often not diagnosed at all or they are pharmacologically undertreated [4, 7]. Still, patients with SMI are often treated with multiple medications at the same time. In medical terms, this is referred to as polypharmacy. Polypharmacy is a natural consequence of adhering to recognized guidelines for treatment. However, polypharmacy increases the risk of drug-drug and/or disease-drug interactions that may alter the balance between desired and adverse effects for the individual medications [8-10]. In this way, concurrent treatment with several medications often leads to unwanted adverse effects and sometimes to hospital admission and even death [8, 11].

For people with SMI the challenges of adverse medication effects and over- and under-treatment, are often complicated by limited personal and socioeconomic resources [12]. People with SMI often have uncharacteristic physical complaints and may not succeed in identifying adverse effects of the medical treatment and communicating them to healthcare professionals. Thus, physical disorders and adverse medication effects are often not recognized. In fact, part of the pharmacological treatment regime can be treatment of medication-induced adverse effects, which have been unnoticed as such [13].

A third aspect of medication control involves compliance. Compliance is the ability of a patient to follow a treatment as prescribed. The few personal resources in combination with complex treatment regimens often results in low compliance in people with SMI [14].
The complex interplay between all these factors in the clinical care of patients with SMI highlights the need for a new approach to detect adverse effects, monitor polypharmacy and improve compliance, taking into account under- and over-treatment, preferences and values of patients, and cooperation with the existing healthcare system [15].
Personal health technology (PHT) may provide tools for handling the challenges of improving the pharmacological treatment and also increasing the involvement of patients and their networks in care [16].


Project objectives

  • to get an overview of existing PHT tools to record side effects and increase compliance and medication control
  • to describe patterns of polypharmacy in patients with SMI in Denmark and to identify the most common and most hazardous clinically relevant drug/drug and drug/disease interactions in patients with SMI
  • to provide input for a new PHT care platform, which can engage patients and their networks in the process of adhering to the pharmacological treatment, report side effects, and at the same time assist the general practitioner and psychiatrists in optimizing the pharmacological treatment for the individual patient


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  2. Henderson, D.C., et al., Pathophysiological mechanisms of increased cardiometabolic risk in people with schizophrenia and other severe mental illnesses. Lancet Psychiatry, 2015. 2(5): p. 452-64.
  3. Laursen, T.M., et al., Somatic hospital contacts, invasive cardiac procedures, and mortality from heart disease in patients with severe mental disorder. Archives of General Psychiatry, 2009. 66(7): p. 713-20.
  4. De Hert, M., et al., Physical illness in patients with severe mental disorders. II. Barriers to care, monitoring and treatment guidelines, plus recommendations at the system and individual level. World Psychiatry, 2011. 10(2): p. 138-51.
  5. Bjune, T., et al., Post-mortem toxicology in young sudden cardiac death victims: a nationwide cohort study. Europace, 2018. 20(4): p. 614-621.
  6. T, S., Effects of selective serotonin reuptake inhibitors ( SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) on suicidality, violence, and quality of life, in Faculty of Medicine. 2018, University of Copenhagen.
  7. Laursen, T.M., et al., Cardiovascular drug use and mortality in patients with schizophrenia or bipolar disorder: a Danish population-based study. Psychol Med, 2014. 44(8): p. 1625-37.
  8. Spinewine, A., et al., Appropriate prescribing in elderly people: how well can it be measured and optimised? Lancet, 2007. 370(9582): p. 173-84.
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  11. Gnjidic, D., et al., Polypharmacy cutoff and outcomes: five or more medicines were used to identify community-dwelling older men at risk of different adverse outcomes. J Clin Epidemiol, 2012. 65(9): p. 989-95.
  12. Smith, S.M., et al., How to design and evaluate interventions to improve outcomes for patients with multimorbidity. 2013, 2013. 3(1): p. 8.
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  14. Velligan, D.I., et al., The expert consensus guideline series: adherence problems in patients with serious and persistent mental illness. J Clin Psychiatry, 2009. 70 Suppl 4: p. 1-46; quiz 47-8.
  15. Mercer, S.W., et al., Managing patients with mental and physical multimorbidity. Bmj, 2012. 345: p. e5559.
  16. Bardram, J.E. and M. Frost, The Personal Health Technology Design Space. IEEE Pervasive Computing, 2016. 15(2): p. 70-78.

Photo by Sharon McCutcheon on Unsplash


Catrine Bakkedal
PhD Student
University of Copenhagen
10 DECEMBER 2023