Polypharmacy in psychiatry and weight gain: longitudinal study of 832 patients hospitalized for depression or schizophrenia, along with data of 3180 students from Europe, the U.S., South America, and China.

Epidemiologic data indicate that overweight and obesity are on the rise worldwide. Psychiatric patients are particularly vulnerable in this respect as they have an increased prevalence of overweight and obesity, and often experience rapid, highly undesirable weight gain under psychotropic drug treatment. Current treatment strategies in psychiatry are oriented towards polypharmacy, so that the information on drug-induced weight gain from earlier monotherapy studies is of very limited validity. We have analyzed the longitudinal data of 832 inpatients with ICD-10 diagnoses of either F2 (schizophrenia; n = 282) or F3 (major depression; n = 550) with the goal of ranking treatment regimens in terms of weight gain, side effects, and response to treatment. The patient data were complemented by the data of 3180 students aged 18-22 years, with which we aimed to identify factors that enable the early detection and prevention of obesity and mental health problems. After 3 weeks of treatment, 47.7% of F2 patients and 54.9% of F3 patients showed a weight gain of 2 kg and more. Major predictive factors were "starting weight" (r = 0.115), "concurrent medications" (r = 0.176), and "increased appetite"(r = 0.275). Between 11 and 30% of the observed variance in weight gain could be explained by these factors, complemented by sex and age. The comparison between monotherapy (n = 409) and polypharmacy (n = 399) revealed significant drawbacks for polypharmacy: higher weight gain (p = 0.0005), more severe side effects (p = 0.0011), and lower response rates (F2: p = 0.0008); F3: p = 0.0101). The data of 3180 students made it clear that overweight and obesity often begin early in life among those affected, and are interconnected with personality traits, while increasing the risk of developing psychosomatic disturbances, mental health problems, or somatic illnesses. Although the available data did not readily lead to a comprehensive, clinically applicable model of unwanted weight gain, our results have nevertheless demonstrated that there are ways to successfully counteract such weight gain at early stages of treatment.

Analysis of genetic diversity in patients with major psychiatric disorders versus healthy controls: A molecular-genetic study of 1698 subjects genotyped for 100 candidate genes (549 SNPs).

BACKGROUND: This study analyzed the extent to which irregularities in genetic diversity separate psychiatric patients from healthy controls. METHODS: Genetic diversity was quantified through multidimensional "gene vectors" assembled from 4 to 8 polymorphic SNPs located within each of 100 candidate genes. The number of different genotypic patterns observed per gene was called the gene's "diversity index". RESULTS: The diversity indices were found to be only weakly correlated with their constituent number of SNPs (20.5 % explained variance), thus suggesting that genetic diversity is an intrinsic gene property that has evolved over the course of evolution. Significant deviations from "normal" diversity values were found for (1) major depression; (2) Alzheimer's disease; and (3) schizoaffective disorders. Almost one third of the genes were correlated with each other, with correlations ranging from 0.0303 to 0.7245. The central finding of this study was the discovery of "singular genes" characterized by distinctive genotypic patterns that appeared exclusively in patients but not in healthy controls. Neural Nets yielded nonlinear classifiers that correctly identified up to 90 % of patients. Overlaps between diagnostic subgroups on the genotype level suggested that (1) diagnoses-crossing vulnerabilities are likely involved in the pathogenesis of major psychiatric disorders; (2) clinically defined diagnoses may not constitute etiological entities. CONCLUSION: Detailed analyses of the variation of genotypic patterns in genes along with the correlation between genes lead to nonlinear classifiers that enable very robust separation between psychiatric patients and healthy controls on the genotype level.

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

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 history¼ and «severity at baseline¼ 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.

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.

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 psychiatric disorders. Given the large proportion of patients with unwanted side effects and the strong correlation between side effects and the number of drugs, polypharmacy approaches are not equally suited for every patient. In terms of efficacy, there are no advantages of polypharmacy over monotherapy. Most notably, our study appears to have cleared the way for the reliable identification of a subgroup of patients for whom the inflammatory response system is a promising target of therapeutic intervention.

[Community-based crisis home programme. Cost-efficient alternative to psychiatric hospitalization]. / Gemeindenahe psychiatrische Akutbehandlung in Gastfamilien. Kostengünstige Alternative zum Klinikaufenthalt bei hoher Patientenzufriedenheit.

BACKGROUND: Over recent decades, institutional psychiatric care has shifted its focus from traditional inpatient treatment to a variety of more advanced outpatient services. Within this context, a new "crisis home" programme (CHP) was launched in Zurich on 1 January 2005. With this programme, mentally ill patients can avoid hospitalization by living with a host family for a certain time period while receiving standard outpatient care. In this study we addressed the question of whether the quite substantial financial advantages of the Zurich CHP over traditional inpatient care are achieved at the expense of a reduced quality of care. SAMPLE AND METHODS: Between 1 January 2005 and 30 June 2007, a total of 33 patients enrolled in the Zurich CHP with an average stay of 19 days at host families. The vast majority of the patients (85%) were moderately to severely ill at study entry. Of these patients data were collected in a standardized way on the basis of five rating instruments. The statistical data analysis included cross-comparisons with corresponding inpatient data. RESULTS: Results showed that (1) the CHP works well in a routine setting and provides cost-efficient interventions for patients in acute crises; (2) the financial advantages of the Zurich host family programme over traditional inpatient care do not lead to a reduced quality in patient care; (3) patients suffering from severe mental illnesses clearly benefit from this programme, thus avoiding hospitalization. CONCLUSIONS: The Zurich CHP is a cost-efficient alternative to traditional inpatient treatment. Specifically, our results suggest that this type of acute crisis intervention should be established as a standard psychiatric care service.

Brain imaging in psychiatry - a study of 435 psychiatric in-patients at a university clinic.

OBJECTIVE: The use of brain imaging in psychiatry still lacks clear guidelines. We investigated the referral practice, outcome and predictive factors of neuroimaging in a Swiss psychiatric university clinic. METHOD: Medical files were reviewed retrospectively for 435 consecutively hospitalized patients who were subjected to neuroimaging. The association between the sociodemographic and clinical characteristics and the scan results was analyzed using bivariate and multivariate analyses. RESULTS: Of overall examinations, 69.4% were normal, 16.3% equivocal and 14.3% abnormal; 2.9% of scans ordered for screening only showed pathology. Neurologic signs and advanced age of patients predicted abnormal scan findings, whereas other variables such as EEG results showed no significant association. CONCLUSION: Our results support the need for clear indications for using brain imaging in psychiatric in-patients. Focal neurologic signs and advanced patient age seems to predict abnormal scan results. However, these criteria are not sufficiently sensitive to predict significant scan findings in all patients.

Ethnicity-independent genetic basis of functional psychoses: a genotype-to-phenotype approach.

The functional psychoses schizophrenia, schizoaffective disorder, and bipolar illness represent complex clinical syndromes that are characterized by phenotypic heterogeneity. Yet evidence from numerous studies suggests that (1) the prevalence of schizophrenia and bipolar illness is with 1% very similar across ethnicities, and (2) a strong genetic component is involved in the disorders' pathogenesis. Using data from different US-American ethnicities (77 families with a total of 17 unaffected and 170 affected sib pairs; 276 marker loci), we searched for ethnicity-independent oligogenic susceptibility loci for which the between-sib genetic similarity in affected sib pairs deviated from the expected values. Specifically, we addressed the question of the extent to which genetic risk factors and their interactions constitute multigenic inheritance of functional psychoses across populations and might constitute universal targets for treatment. Our novel multivariate genotype-to-phenotype search strategy was based on a genetic similarity function that allowed us to quantify the inter-individual genetic distances d(x(i), x(j)) between the allelic genotype patterns x(i), x(j) of any two subjects i, j with respect to n loci l(1), l(2), em leader l(n). Thus, we were able to assess the between-ethnicity, the within-ethnicity, and the within-family genetic similarities. The problem of ethnicity-independent vulnerability was addressed by treating the Afro-American families as "training" samples, while the non-Afro-American families served as independent "test" samples. We evaluated the between-sib similarities, which were expected to deviate from "0.5" in affected sib pairs if the region of interest contained markers close to vulnerability genes. The reference value "0.5" was derived from the parent-offspring similarities that are always 0.5, irrespective of the affection status of parents and offspring. We found 12 vulnerability loci on chromosomes 1, 4, 5, 6, 13, 14, 18, and 20, that were reproducible across the two samples under comparison and therefore, likely to constitute an ethnicity-independent, oligogenic vulnerability model of functional psychoses. The elevated vulnerability appeared to be unspecific and to act in such a way that exogenous factors become more likely to trigger the onset of psychiatric illnesses.

Development of specific social skills training programmes for schizophrenia patients: results of a multicentre study.

OBJECTIVE: The efficacy of three newly developed cognitive social skills training programmes for residential, vocational and recreational functioning (experimental groups) were compared with a traditional social skills training programme (control group) referring to cognitive and social abilities, psychopathology and generalisation effects. METHOD: One hundred and five patients with a diagnosis of schizophrenia or schizoaffective disorder according to ICD-10 criteria were selected and assigned to the different treatment groups, using a matching procedure. The treatment phase lasted 6 months. A follow-up assessment was carried out after 1 year. RESULTS: Higher global therapy effects were obtained on almost all dependent variables in the experimental groups. Analyses of variance and covariance indicated higher symptom reduction for the experimental groups, but significantly greater improvements in some cognitive variables for the control group. Correlation analysis suggested associations between improvement of social behaviour with symptom reduction and improvements of cognitive skills. CONCLUSION: In view of these favourable effects, the developed cognitive social skills training programmes might facilitate the abilities of schizophrenia patients for their integration in the community.

[Treatment of panic disorder with combination of SSRI and cognitive-behavioral therapy]. / Kombinationsbehandlung einer Panikstörung mittels SSRI und kognitiver Verhaltenstherapie.

GOAL: Various forms of treatment of panic disorder with and without agoraphobia have shown good results. We examined the combination of cognitive-behavioral psychotherapy and treatment with an SSRI. METHODS: Case report and literature review. RESULT: The combination treatment shows a faster onset of therapeutic effects than cognitive-behavioral psychotherapy. However, final outcomes are comparable. CONCLUSIONS: The addition of a SSRI to cognitive-behavioral psychotherapy accelerates the onset of therapeutic effects. It does not interfere with the cognitive restructuring aimed at cognitive-behavioral psychotherapy.

[Diagnostic principles for differential therapy of psychoses]. / Diagnostische Grundlagen für eine differenzielle Therapie der Psychosen.

The pharmacotherapy of psychotic disturbances is not limited on neuroleptics, but includes Clomethiazol and Benzodiazepines (e.g. to treat delirium) or antidepressants (e.g. to treat psychotic depression) too. Even more divergent is the psychosocial treatment of different psychotic states. In this overview the diagnostic principles, needed for a differential therapy of psychotic disorders, are described.

[Drug treatment of functional psychotic disorders]. / Medikamentöse Behandlung funktioneller psychotischer Störungen.

Psychotic symptoms occur in different psychiatric disorders. The principles of antipsychotic drug treatment of various non-organic psychotic disorders are discussed. In particular, the role of the so-called atypical antipsychotics is highlighted.

Schizophrenia and smoking: evidence for a common neurobiological basis?

Several previous investigations have suggested that the gene for the alpha 7-nicotinic receptor may play a role in the pathogenesis of schizophrenia and may be responsible for the heavy smoking among schizophrenic patients. In a study of 129 healthy controls and 127 schizophrenic, schizoaffective, and bipolar patients we have aimed 1) to confirm the potential association between schizophrenia and the alpha 7-nicotinic receptor, 2) to test the diagnostic specificity of alpha 7-receptor subunits with respect to psychiatric diagnoses, and 3) to investigate potential receptor differences between smokers and nonsmokers in the general population. Our analysis included the two dinucleotide polymorphisms D15S1360 and L76630 that are localized in a genomic fragment containing the alpha 7-nicotinic receptor gene CHRNA7. Highly significant differences (P < 0.0001) between the allele distributions of patients and controls were detected for these two markers with all three diagnostic subgroups contributing to the discrimination. An independently ascertained replication sample of 24 patients confirmed this finding. Our results suggested an unspecific vulnerability that depended on the severity of overall psychopathology in terms of the co-occurrence of psychopathology with no clear-cut boundary between the diagnostic entities. In comparison with healthy controls, this vulnerability was lowest among schizophrenics, intermediate among bipolars, and highest among schizoaffectives. As to the question of alpha 7-receptor differences between smokers and nonsmokers among the healthy control subjects, our analysis revealed no significant differences, thus indicating that the differences between patients and controls are more than just a smoker/nonsmoker distinction. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:173-177, 2000.

[Acute life-threatening catatonia]. / Akute lebensbedrohliche Katatonie.

Malignant catatonia is a rare, life-threatening syndrome that occurs in connection with somatic as well as psychiatric disorders, in particular with functional psychosis. Key symptoms are catatonic features combined with elevated muscle tone, hyperthermia, vegetative instability, and pathological laboratory values. Benzodiazepines, dantrolene, and ECT have been reported to be an effective treatment of malignant catatonia, whereas classic neuroleptics and anticholinergic drugs are contraindicated. If antipsychotic treatment is required, clozapine is generally used. In this article we describe a case of malignant catatonia in a 52 year old female patient and discuss the clinical picture, the treatment, and the time course of the syndrome.

[Acute life threatening catatonia--clinical significance and therapeutic possibilities]. / Akute lebensbedrohliche Katatonie (ALK)--klinische Bedeutung und therapeutische Möglichkeiten.

Malignant catatonia, associated with different somatic and psychiatric disorders, is a rare, life-threatening syndrome. Immediate recognition and adequate treatment are essential and may be life-saving. We describe a case of malignant catatonia and discuss the clinical implications. Additionally, we review the recent literature regarding epidemiology, nosology, current pathophysiological concepts, differential diagnosis, and treatment recommendations.