In patients with severe mental illness (SMI), a high prevalence of metabolic risk factors (1–3) contribute to their poor cardiovascular health, largely contributing to a reduced life expectancy of at least 7–20 years compared to the general population (4–6). Besides a sedentary lifestyle (7–10), side effects of psychotropic medication (such as weight gain, dyslipidemia, diabetes mellitus, and direct and indirect harm to the vascular system) are associated with these cardiovascular health issues (11–14). Polypharmacy, higher dosages, and longer-term use are associated with higher risk for most of these side effects and somatic diseases (11, 12, 15). A study in people diagnosed with schizophrenia showed that both no exposure as well as high exposure to antipsychotics were associated with higher cardiovascular mortality than either low or moderate exposure (16). Unfortunately, polypharmacy is very prevalent among people with SMI (15, 17) and the dosage of antipsychotic medication has only increased during the last decades for long-term hospitalized patients (18, 19). Alongside this psychotropic medication, patients use antihypertensive, lipid-lowering, antihyperglycemic and other additional drugs if cardiovascular health issues (whether or not caused by psychotropic medication) are too severe (20–24).

Nowadays, there is more focus on the lowest effective dose, on the avoidance of inappropriate polypharmacy to minimize the side effect of antipsychotics (25–28), and on supporting a healthy lifestyle (29–32). Despite an increased number of studies showing benefits of lifestyle interventions in people with SMI, there is a lack of evidence to support the long-term effectiveness of such interventions in hospitalized patients (33, 34). Moreover, to the best of our knowledge, studies evaluating lifestyle interventions in inpatients did not analyze changes in medication use. Recently, improved physical activity and metabolic health were shown after 18 months in this group of patients receiving a multidisciplinary lifestyle enhancing treatment for inpatients with SMI (MULTI) (35). MULTI was pragmatically implemented in a group of inpatients whose psychotropic medication was already critically reviewed prior to its implementation; hence, dose reduction was not a specific goal. The treatment focused on decreasing sedentary behavior, increasing physical activity, and improving dietary habits in the context of daily treatment.

Because the (side) effects of medications are associated with cardiometabolic health issues, we hypothesized that we might observe changes in medication use after lifestyle changes, in addition to improvements in physical health. Therefore, the present study aimed to retrospectively study whether 18 months of MULTI was associated with changes in medication use, as compared with patients that continued treatment as usual (TAU) and to explore whether changes were mediated by increased physical activity as an essential component of MULTI.

Table 1 shows the baseline characteristics of patients receiving MULTI and TAU. None of the included 114 patients dropped out. On average, patients receiving MULTI were younger (M = −6.45 years, 95% CI: −10.27 to −2.64), had a higher baseline illness severity (M = 0.63, 95% CI: 0.17 to 1.08) and were more frequently diagnosed with schizophrenia or other psychotic disorders (X² = 21.98, p < 0.001) than patients receiving TAU.

In the current study, we observed a significant dose reduction in psychotropic medications after 18 months of MULTI, compared to TAU. Although the dose reduction in somatic medication was in favor of MULTI too, it was not significant. When these main groups were split into subgroups, there was a lack of power for corrected between-group analyses. However, the first steps in gaining more detailed insight into dose reductions by using within-group analyses showed interesting leads, for example, in the reduction of medication for diabetes and the respiratory system, which is in line with previously reported physical health improvements within MULTI (35). It also showed clearly the remarkable dose reductions in TAU. It is not likely that this is a time effect, as there was no change of policy in the organization regarding the dosage of medication during these 18 months. The reductions might, however, be a disruptive effect caused by a change in medical staff during the 18 months of this study. The psychiatrist responsible for the majority of the patients within TAU retired and was replaced by a younger colleague, who critically reviewed medication policies. Nevertheless, such a critical review had already been done on the wards receiving MULTI prior to its implementation, so dose reduction was not a specific goal within MULTI. Therefore, the significant decrease in the dose of psychotropic medication is even more striking. One explanation could be that this may be caused partly by decreased psychotic symptoms, but earlier results of the MULTI study showed no significant changes in these symptoms, as compared with TAU, after 18 months (35). Another explanation may be that the psychiatrists reduced the dose of medication based on observed improvements in psychosocial functioning in people who received MULTI (42). It is, however, challenging to clarify specific mechanisms with regard to dose reduction, as there are many variables involved (e.g., interactions between different medications; changes in and preferences of the staff; etc.).

Our findings are somewhat in line with the only other study known to us that evaluated medication use after a lifestyle focused program in patients with SMI (43). In that naturalistic study, Højlund et al. found a decrease in the use of antipsychotics in patients, although they found no specific association between these changes and the degree of participation in the intervention they delivered. However, their reported proportions of patients who used psychotropic co-medication (N categories except for N05) showed little change at follow-up, which is not in line with our observations. Differences may be caused by a different population, as their study was conducted in outpatients with a substantially shorter history of illness, who were relatively young and of whom only a minority used psychotropic co-medication. Also, the absence of a comparison group without lifestyle support makes it difficult to compare results. Indicating decreases in medication use after lifestyle improvement is however very relevant for clinical practice. The ideal situation would be to have medication that addresses the symptoms of psychosis with minimal side effects. However, due to a lack of fundamental innovation in psychopharmacology during recent decades, we still have to work with antipsychotics with a range of motor, metabolic, and cognitive side effects (28, 44). Moreover, as there is still an overall favorable benefit-to-risk ratio for the use of antipsychotics (45), addressing lifestyle is of importance to help minimize such side effects. Besides previously reported improvements in physical health (35), current results show that an integrated multidisciplinary approach is associated with a decrease in the dose of medication. Thereby, it potentially reduces (the risk for) those side effects, which are partly dose-dependent (11, 46). Additionally, because many but not all side effects are reversible, it suggests that lifestyle improvements could contribute to the prevention of irreversible effects, e.g., motor side effects. The reductions found are also promising from the patient's point of view, as side effects and negative attitudes toward medication use are associated with non-adherence, distress, and life impact (47–50).

Our explorative mediation analysis showed that the increase in physical activity observed in patients receiving MULTI after 18 months (35) did not mediate the association between MULTI and change in psychotropic medication use in this same period of time. This indicates that the decrease of psychotropic mediation was not a result of just increasing physical activity. We hypothesize that, with an organizational culture change as a base, multiple components that complement physical activity contribute to improvements, including focus on dietary habits, psycho-education, personal tailoring, and support by peers and qualified participating staff, in line with recent studies advocating the use of such elements (29, 30, 51–53). Such a holistic approach, in which patients are encouraged to do any activities instead of none (i.e., decreasing sedentary behavior), may be more feasible and beneficial in the longer term for inpatients with SMI. While previous studies have shown that structured exercise is feasible in those with SMI in general (31), sedentary behavior (as distinct from physical inactivity) is highly prevalent and associated with cardiometabolic risks that are largely independent of time spent in structured exercise (7, 8). Thus, controlled trials are needed to examine further the feasibility and effects of interventions targeting sedentary behavior.

Limitations in this study mainly arise from the naturalistic and observational design. In this design, we were not able to randomize patients (e.g., the TAU wards treated fewer patients with psychotic disorders) and control for treatment settings in advance (e.g., the continuity of psychiatrists). In addition, although dose reduction was not a specific goal of MULTI, psychiatrists were not blinded for patients' treatment condition (i.e., receiving MULTI or not), which might have affected observed dose reductions. Although this observational study seems the first indicating a possible effect of lifestyle improvements on medication use in inpatients with SMI, future well-designed trials are needed to study the efficacy of lifestyle changes on medication use. Regarding the participation of patients in MULTI, we have no specific data on (the degree of) their adherence. It was intended that all patients were doing some activities in the morning and afternoon, tailored to the particular ward and patients' abilities and interests. However, data on adherence to these individualized day-to-day programs including more detailed data on participation (e.g., frequency and intensity of activities) would make it possible to study the association between the (degree of) adherence and treatment outcomes. Also, our analyses depended on the availability of data within the cohort. Nevertheless, by using multilevel analyses adjusting for differences between MULTI and TAU, we aimed for robust results. However, more data will be needed to have sufficient power for adequate between-group analyses within subgroups of medication, whereby we could gain more detailed insight into specific reductions as indicated by within-group analyses (e.g., drugs for diabetes or obstructive airway diseases). This would provide the opportunity to control for possible differences between groups such as age, which can affect the prescribed dosages of medication (54–56). Furthermore, we used a simple mediation model to explore the influence of a change in physical activity, as an essential element of MULTI, on the association between MULTI and change in medication use. However, the main limitation of this is that by measuring all variables within the mediation analyses nearly simultaneously, we assumed that the association between change in total activity and change in medication use between our pre (T1) and post measurement (T2) would be the same as we would have measured between T2 and a (theoretical) third time point. To study if physical activity mediates associations between lifestyle interventions and medication use, in general, it would be the best to measure physical activity as a middle time-point to study the effect of a change in physical activity over time. Finally, we did not include pro necessitate medication (i.e., to be given as needed) because we cannot specify if and to what extent patients took these medications. The strength of this study is that it is the first study to report detailed dose-specific data on changes in both somatic and psychotropic medication use in inpatients with SMI after lifestyle changes. Despite the limitations, first steps were taken to analyze associations between lifestyle improvements and medication use in these patients, who are suffering from severe physical health problems and receive high dosages of medication. The naturalistic setting of the study improves the generalizability of the results and meets the need for observational studies to supplement randomized controlled trials in order to improve the external validity, such that clinicians treating patients in real-world settings have relevant evidence on which to base their clinical decisions (57). Regarding the impact of critically reviewing medication use that was most likely observed in TAU, it is a strength in favor of MULTI that medication was already critically reviewed on these wards before its implementation, so dose reduction was not a specific goal within MULTI. This suggests that lifestyle improvement has added value with regard to decreasing the dose of medication in inpatients with SMI. Above all, this strengthens the fact that we compared it with TAU. Otherwise, we would only have observed the improvements in MULTI without any context. Moreover, by analyzing possible mediation by total activity, we took a first step to gaining more insight into the contribution of different elements of MULTI to the observed improvements. Finally, by including baseline measures in this analysis, our mediation analysis is mathematically in line with a covariance approach, which was the recommended method for mediation analyses (58, 59).

In summary, in addition to previously reported improvements in physical activity and metabolic health after 18 months of MULTI, we observed a significant decrease in dose of psychotropic medication as compared with TAU. We encourage further longitudinal controlled research to gain more insight into the relationship between lifestyle changes and possible dose reductions to improve health outcomes in inpatients with SMI.

Data are available from the corresponding author on reasonable request and with permission of GGz Centraal.

JD: obtaining funding, study design, retrieving, processing and analyzing data, drafting the manuscript; DT: study design, supporting retrieving, processing and analyzing data; HvD: retrieving, processing and supporting analyzing data; IH: supporting analyzing data; DT and PvH: supporting grant applications; All authors critically revised the manuscript and approved the final version.