Inflammatory processes linked to major depression and schizophrenic disorders and the effects of polypharmacy in psychiatry: evidence from a longitudinal study of 279 patients under therapy

Abstract

Over the past 2 decades, polypharmacy has become the de-facto standard of acute treatment in psychiatry where patients with psychiatric disorders receive a multiple medication regimen. There is growing evidence for a potential link between major psychiatric disorders and inflammatory processes. Combining these two aspects aims at avoiding polypharmacy attempts among patients with inflammatory activation through alternative treatment strategies. In this study, we addressed the following questions: (1) to what extent can polypharmacy be explained through the factors "diagnosis", "previous history", "severity at baseline", "age", "gender", and "psychiatrist in charge"; (2) what are the differences between polypharmacy and monotherapy regarding efficacy and side effect profiles; and (3) what amount of between-patient variance is explainable by the natural antibody immunoglobulin M (IgM) within each diagnostic group. This naturalistic longitudinal study was comprised of 279 patients under therapy with a clinical diagnosis of depressive (ICD-10: "F3x.x"; n = 195) or schizophrenic disorders (ICD-10: "F2x.x"; n = 84). The study protocol included (1) assessment of previous history by the SADS Syndrome Check List SSCL-16 (lifetime version); (2) repeated measurements over 5 weeks assessing the time course of improvement by the Hamilton Depression Scale HAM-D and the Positive and Negative Syndrome Scale PANSS, along with medication and unwanted side effects through the Medication and Side Effects Inventory MEDIS; and (3) the collection of blood samples from which DNA and serum were extracted. The association between inflammatory response system and psychiatric disorders was detailed by fitting multi-layer Neural Net (NN) models to the observed data ("supervised learning"). The same approach was used to set up prediction models of side effects. Our data showed that polypharmacy was omnipresent. Yet the various polypharmacy regimens had no advantage over monotherapy: we even found slightly larger baseline score reductions under monotherapy, independent of primary diagnoses and for comparable baseline severities. Most patients experienced unwanted side effects. The close link between side effects and treatment regimen was revealed by a linear model in which the mere number of drugs explained a significant (p < 0.001) proportion of the observed variance. As to the inflammatory response system: For the F2 patients, our NN model identified a 22.5% subgroup exhibiting a significant correlation of r = 0.746 (p = 0.0004) between global schizophrenia scores and IgM levels, along with a correct prediction of response of 94.4%, thus explaining 55.7% of the observed between-patient variance. For the F3 patients, our NN model identified a 19.6% subgroup exhibiting a significant correlation of r = 0.644 (p = 0.00003) between global depression scores and IgM levels, along a correct prediction of response of 89.6%, thus explaining 41.4% of the observed between-patient variance. Polypharmacy is omnipresent in today's acute treatment of psychi...

Detailing the effects of polypharmacy in psychiatry: longitudinal study of 320 patients hospitalized for depression or schizophrenia

“…We see the following implications for everyday clinical practice: (1) we have to accept that psychotropic drugs or combinations thereof are insufficiently effective in a larger proportion of patients; (2) polypharmacy does not solve this problem in any way-patients often have no benefits whatsoever, but only the burden of more severe adverse reactions; (3) consequently, all therapeutic options must be carefully considered in each individual case; (4) we have further to accept that psychiatric disorders, as they are manifest through the patients' clinical picture, are likely the result of etiologically very different pathologies, i.e., psychiatric disorders do not represent disease entities in terms of prognosis and therapy; (5) in light of this, it is principally quite unlikely that all patients will respond equally well to a particular therapy and, consequently, we have to think about alternatives, such as regular exercise and sports [30,31], or the inflammatory response system as targets for therapeutic intervention [cf. 6,20,[32][33][34][35]; (6) in contrast to everyday clinical practice, monotherapy and psychotherapy without concurrent psychopharmacological medications are by no means obsolete-empirical evidence speaks against starting just every therapeutic intervention in psychiatry with a combination of psychopharmaceuticals; (7) we should treat mild cases differently (e.g., mild depression with a HAM-D17 baseline score below 20) and consider to not use psychopharmaceuticals at all, or to opt for psychotherapy alone.…”

“…(5) To what extent can polypharmacy be explained through the factors clinical diagnosis, previous history, severity at baseline, age, and gender? (6) Which adverse side effects or combinations of adverse side effects are more common than others, and which are rare? (7) Which adverse side effects can be linked to specific drugs or drug combinations?…”

A Systematic Review of the Evidence on Inflammation in Depressive Illness and Symptoms, in Chronic and End Stage Kidney Disease

“…Inflammation may be an important mediator in developing mood disorders and research on antiinflammatories offer the potential for more precise treatment options, with fewer adverse effects or polypharmacy 88 . Furthermore, the presence of inflammation may help predict anti-depressant response.…”

Monitoring the effects of therapeutic interventions in depression through self-assessments

“…By contrast, in a recent longitudinal study of 279 inpatients, the patients received an average of 4.54±2.68 concurrent medications, composed of 3.30±1.84 psychotropic drugs, plus 0.81±1.13 drugs to reduce unwanted side effects, plus 0.43±0.89 other somatic drugs. The responder rate was 35% for major depression and 25% for schizophrenic disorders (Stassen et al ., 2021 ), which meant a general drop of about 40% compared to what was the standard 20 years ago. Among the patients suffering from major depression, monotherapy was a rare exception (12.7%), and only a small minority of patients under psychotherapy received psychotherapy alone (2.9%).…”

“…In tandem with the potentially beneficial effects of psychopharmacological treatments, patients experience significant adverse side effects. In a recent study, 85.7% of patients treated for major depression reported unwanted side effects (31.0% in severe form) and 81.7% of patients treated for schizophrenic disorders (33.1% in severe form) (Stassen et al ., 2021 ). There is no doubt that in many cases the beneficial effects of psychotropic drug treatment do not outweigh the associated risk of adverse side effects.…”