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

Abstract

Current treatment standards in psychiatry are oriented towards polypharmacy, that is, patients receive combinations of several antidepressants, antipsychotics, mood stabilizers, anxiolytics, hypnotics, antihistamines, and anticholinergics, along with other somatic treatments. In tandem with the beneficial effects of psychopharmacological drug treatment, patients experience significant adverse reactions which appear to have become more frequent and more severe with the rise of ubiquitous polypharmacy. In this study, we aimed to assess today’s acute inpatient treatment of depressive and schizophrenic disorders with focus on therapeutic strategies, medications, adverse side effects, time course of recovery, and efficacy of treatments. Of particular interest was the weighing of the benefits and drawbacks of polypharmacy regimens. We recruited a total of 320 patients hospitalized at three residential mental health treatment centers with a diagnosis of either schizophrenic (ICD-10: “F2x.x”; n = 94; “F2 patients”) or depressive disorders (ICD-10: “F3x.x”; n = 226; “F3 patients”). The study protocol included (1) assessment of previous history by means of 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 medications and adverse side effects through the Medication and Side Effects Inventory MEDIS; and (3) the collection of blood samples from which DNA and serum were extracted. Polypharmacy was by far the most common treatment regimen (85%) in this study. On average, patients received 4.50 ± 2.68 medications, consisting of 3.30 ± 1.84 psychotropic drugs, plus 0.79 ± 1.13 medications that alleviate adverse side effects, plus 0.41 ± 0.89 other somatic medications. The treating psychiatrists appeared to be the main determining factor in this context, while «previous history» and «severity at baseline» played a minor role, if at all. Adverse drug reactions were found to be an inherent component of polypharmacy and tended to have a 2–3 times higher incidence compared to monotherapy. Severe adverse reactions could not be attributed to a particular drug or drug combination. Rather, the empirical data suggested that severe side effects can be triggered by virtually all combinations of drugs, provided patients have a respective vulnerability. In terms of efficacy, there were no advantages of polypharmacy over monotherapy. The results of this study underlined the fact that polypharmacy regimens are not equally suited for every patient. Specifically, such regimens appeared to have a negative impact on treatment outcome and to obfuscate the “natural” time course of recovery through a multitude of interfering factors. Evidence clearly speaks against starting just every therapeutic intervention in psychiatry with a combination of psychopharmaceuticals. We think that it is time for psychiatry to reconsider its treatment strategies, which are far too one-sidedly fixated on psychopharmacology and pay far too little attention to alternative approaches, especially in mild cases where psychotherapy without concurrent medication should still be an option. Also, regular exercises and sports can definitely be an effective therapeutic means in a considerable number of cases. General practitioners (GPs) are particularly in demand here.

Pharmacological treatment of major depressive disorder according to severity in psychiatric inpatients: results from the AMSP pharmacovigilance program from 2001–2017

“…However, the extent of this presumed specificity is severely limited, because many drugs, especially APDs, act on a variety of different receptor systems (e.g., dopamine, histamine, serotonin, and acetylcholine) (Siafis et al 2018 ). Further overshadowing the potential benefits of this technique is the simple fact that polypharmacy is not considered more efficacious than monotherapy (Stassen et al 2021 ) and is also is a well-established risk factor for ADRs (Zopf et al 2008 ).…”

Analysis of Genetic Diversity in Patients with Major Psychiatric Disorders versus Healthy Controls: A molecular-genetic study of 1,698 subjects genotyped for 100 candidate genes (549 SNPs)

“…Data from patients and controls from five of our previous studies were (1) pooled, (2) coded in a standardized way, and (3) analyzed together. The study details can be found elsewhere [13][14][15][16][17][18]. Totally 1,698 subjects were genotyped for 100 genes 4 and 549 specifically selected SNPs at a missing data rate < 5% (96 autosomal genes; 1,431 psychiatric patients; 267 healthy controls, of which 141 (52.8%) were unaffected 1st degree relatives of the patients).…”

“…Among the exogenous factors, lifestyle, diet, consumption behavior, and physical activity play a prominent role. Inflammation is another major exogenous constituent explaining some 15-25% of the observed phenotypic variance [3][4].…”

“…Inevitably, analyses of genetic diversity bring up the question of biological ethnicity ("population stratification") [10][11][12], as it may well be that any differences between patients and healthy controls are due to population stratification rather than to the disorders under investigation. We tackled this problem in two different ways: (1) we aimed to recruit half of the healthy controls from the patients' unaffected first-degree relatives; and (2) with "unsupervised learning" methods 3 and 73 SNPs located within the CLOCK gene we aimed to develop a "natural" model of biological ethnicity. The CLOCK gene was chosen because it was deemed to contain distinctive adaptations of typical North-South and West-East specifics.…”

The pharmacogenetics of the new-generation antipsychotics – A scoping review focused on patients with severe psychiatric disorders

“…Another important aspect of pharmacogenetic research is the possibility of anticipating the consequences of concomitantly administering multiple drugs, which is far from being an isolated phenomenon in patients with SPDs. Polypharmacy was found in 85% of the hospitalized patients enrolled in a study ( N = 320 participants diagnosed with schizophrenia spectrum disorders (SSD) or depressive disorders ( 12 ). On average, these patients received 4.5 ± 2.7 medications, out of which 3.3 ± 1.8 were psychotropics ( 12 ).…”