Interaction with a Biomolecule Facilitates the Formation of the Function-Determining Long-Lived Triplet State in a Ruthenium Complex for Photodynamic Therapy.

TLD1433 is the first ruthenium (Ru)-based photodynamic therapy (PDT) agent to advance to clinical trials and is currently in a phase II study for treating nonmuscle bladder cancer with PDT. Herein, we present a photophysical study of TLD1433 and its derivative TLD1633 using complex, biologically relevant solvents to elucidate the excited-state properties that are key for biological activity. The complexes incorporate an imidazo [4,5-f][1,10]phenanthroline (IP) ligand appended to α-ter- or quaterthiophene, respectively, where TLD1433 = [Ru(4,4'-dmb)2(IP-3T)]Cl2 and TLD1633 = [Ru(4,4'-dmb)2(IP-4T)]Cl2 (4,4'-dmb = 4,4'-dimethyl-2,2'-bipyridine; 3T = α-terthiophene; 4T = α-quaterthiophene). Time-resolved transient absorption experiments demonstrate that the excited-state dynamics of the complexes change upon interaction with biological macromolecules (e.g., DNA). In this case, the accessibility of the lowest-energy triplet intraligand charge-transfer (3ILCT) state (T1) is increased at the expense of a higher-lying 3ILCT state. We attribute this behavior to the increased rigidity of the ligand framework upon binding to DNA, which prolongs the lifetime of the T1 state. This lowest-lying state is primarily responsible for O2 sensitization and hence photoinduced cytotoxicity. Therefore, to gain a realistic picture of the excited-state kinetics that underlie the photoinduced function of the complexes, it is necessary to interrogate their photophysical dynamics in the presence of biological targets once they are known.

String-Attached Oligothiophene Substituents Determine the Fate of Excited States in Ruthenium Complexes for Photodynamic Therapy.

We explore the photophysical properties of a family of Ru(II) complexes, Ru-ip-nT, designed as photosensitizers (PSs) for photodynamic therapy (PDT). The complexes incorporate a 1H-imidazo[4,5-f][1,10]-phenanthroline (ip) ligand appended to one or more thiophene rings. One of the complexes studied herein, Ru-ip-3T (known as TLD1433), is currently in phase II human clinical trials for treating bladder cancer by PDT. The potent photocytotoxicity of Ru-ip-3T is attributed to a long-lived intraligand charge-transfer triplet state. The accessibility of this state changes upon varying the length (n) of the oligothiophene substituent. In this paper, we highlight the impact of n on the ultrafast photoinduced dynamics in Ru-ip-nT, leading to the formation of the function-determining long-lived state. Femtosecond time-resolved transient absorption combined with resonance Raman data was used to map the excited-state relaxation processes from the Franck-Condon point of absorption to the formation of the lowest-energy triplet excited state, which is a triplet metal-to-ligand charge-transfer excited state for Ru-ip-0T-1T and an oligothienyl-localized triplet intraligand charge-transfer excited state for Ru-ip-2T-4T. We establish the structure-activity relationships with regard to changes in the excited-state dynamics as a function of thiophene chain length, which alters the photophysics of the complexes and presumably impacts the photocytotoxicity of these PSs.

Effectiveness and cost effectiveness of a stress management training for leaders of small and medium sized enterprises - study protocol for a randomized controlled-trial.

BACKGROUND: Leaders in small and medium-sized enterprises (SMEs) are exposed to increased stress as a result of a range of challenges. Moreover, they rarely have the opportunity to participate in stress management trainings. Therefore, KMU-GO (ger: Kleine und mittlere Unternehmen - Gesundheitsoffensive; en: small and medium-sized enterprises - health campaign) aims at conducting and evaluating such a stress management training. The focus of evaluation does not only lie on the effects on leaders participating but also on their employees. METHODS: The study is planned as a 2 × 3 mixed design with two groups (intervention and waiting control group) as a between factor and point in time (at baseline, 6 and 12 months later) as a within factor. We aim at collecting data from N = 200 leaders. Based on the results of a preceding assessment, an already successfully implemented stress management training was adapted to SME needs and now serves as the framework of this intervention. The stress management training comprises one and a half days and is followed by two booster sessions (each 180 min) about 3 and 6 months after the training. The main focus of this intervention lies on specifying leaders stress reactivity while at the same time investigating its effects on employees' mental health. Further dependent variables are leaders´ depression and anxiety scores, effort-reward imbalance, sick days and psychophysiological measures of heart rate variability, hair cortisol, and salivary alpha-amylase. Cost-effectiveness analyses will be conducted from a societal and employers' point of view. DISCUSSION: Stress management is a highly relevant issue for leaders in SMEs. By providing an adequate occupational stress management training, we expect to improve leaders´ and also employees` mental health, thereby preventing economic losses for SMEs and the national economy. However, collecting data from employees about the success of a stress management training of their leader is a highly sensitive topic. It requires a carefully planned proceeding ensuring for example a high degree of transparency, anonymity, and providing team incentives. TRIAL REGISTRATION: The KMU-GO trial is registered at the German Clinical Trial Register (DRKS): DRKS00023457 (05.11.2020).

Passive elimination of correlated amplitude fluctuations in ultrabroadband supercontinua from highly nonlinear fibers by three-wave mixing.

The nonlinear transformation of fluctuations by frequency broadening is found to produce strong anti-correlations in the spectral output. This effect is investigated by dispersive Fourier transform measurements. We exploit the anti-correlations in order to cancel the intensity noise in a subsequent sum-frequency mixing step. This principle allows for the generation of tunable visible pulses by cascaded nonlinear mixing whilst maintaining the same intensity noise performance as the input pulses. In addition, we demonstrate that the power fluctuations occurring in the process of passive stabilization of the carrier-envelope phase locking via difference frequency generation may be cancelled by an analogous strategy.

Intracellular Photophysics of an Osmium Complex bearing an Oligothiophene Extended Ligand.

This contribution describes the excited-state properties of an Osmium-complex when taken up into human cells. The complex 1 [Os(bpy)2 (IP-4T)](PF6 )2 with bpy=2,2'-bipyridine and IP-4T=2-{5'-[3',4'-diethyl-(2,2'-bithien-5-yl)]-3,4-diethyl-2,2'-bithiophene}imidazo[4,5-f][1,10]phenanthroline) can be discussed as a candidate for photodynamic therapy in the biological red/NIR window. The complex is taken up by MCF7 cells and localizes rather homogeneously within in the cytoplasm. To detail the sub-ns photophysics of 1, comparative transient absorption measurements were carried out in different solvents to derive a model of the photoinduced processes. Key to rationalize the excited-state relaxation is a long-lived 3 ILCT state associated with the oligothiophene chain. This model was then tested with the complex internalized into MCF7 cells, since the intracellular environment has long been suspected to take big influence on the excited state properties. In our study of 1 in cells, we were able to show that, though the overall model remained the same, the excited-state dynamics are affected strongly by the intracellular environment. Our study represents the first in depth correlation towards ex-vivo and in vivo ultrafast spectroscopy for a possible photodrug.

A bacterial Argonaute with noncanonical guide RNA specificity.

Eukaryotic Argonaute proteins induce gene silencing by small RNA-guided recognition and cleavage of mRNA targets. Although structural similarities between human and prokaryotic Argonautes are consistent with shared mechanistic properties, sequence and structure-based alignments suggested that Argonautes encoded within CRISPR-cas [clustered regularly interspaced short palindromic repeats (CRISPR)-associated] bacterial immunity operons have divergent activities. We show here that the CRISPR-associated Marinitoga piezophila Argonaute (MpAgo) protein cleaves single-stranded target sequences using 5'-hydroxylated guide RNAs rather than the 5'-phosphorylated guides used by all known Argonautes. The 2.0-Å resolution crystal structure of an MpAgo-RNA complex reveals a guide strand binding site comprising residues that block 5' phosphate interactions. Using structure-based sequence alignment, we were able to identify other putative MpAgo-like proteins, all of which are encoded within CRISPR-cas loci. Taken together, our data suggest the evolution of an Argonaute subclass with noncanonical specificity for a 5'-hydroxylated guide.

Unusually Short-Lived Solvent-Dependent Excited State in a Half-Sandwich Ru(II) Complex Induced by Low-Lying 3MC States.

A ruthenium complex with a half-sandwich geometry ([(p-cymene)Ru(Cl)(curcuminoid)]) was synthesized, characterized, and investigated regarding its ultrafast photophysics. These photophysical investigations of the complex revealed a weak and short-lived emission from the initially populated 1MLCT state and solvent-dependent photoinduced dynamics, where the secondarily populated 3MC state is stabilized by nonpolar solvents. Overall the decay of the 3dd-MC state to the ground state is completed within picoseconds. This short excited-state lifetime is in stark contrast to the typically observed long-lived 3MLCT states with lifetimes of nanoseconds or microseconds in unstrained, octahedral ruthenium complexes but is in good agreement with the findings for distorted octahedral complexes. This is pointing to the half-sandwich geometry as a new and easy approach to study these otherwise often concealed dd states.

[Quality of life among older informal caregivers of people with dementia]. / Lebensqualität älterer pflegender Angehöriger von Demenzerkrankten.

BACKGROUND: In Germany, informal caregiving becomes an increasingly important issue especially for people with dementia. Spouses often provide nursing care due to the limited daily living skills of people with dementia. This leads to a wide range of caregiver burden and decreased quality of life (QoL). Analyses on the relation between QoL and caregiver burden of older informal caregivers in Germany are rare. OBJECTIVE: The following research questions were assessed: (1) Does caregivers' QoL differ from that of the older general population?; (2) Which sociodemographic, health- and care-related characteristics affect caregivers' QoL? MATERIAL AND METHODS: For this study, two samples (aged 60 years and older) were recruited: informal caregivers (n = 119) and a representative sample of older non-caregivers in the general population (n = 1133). Linear regression analyses were applied to examine the effects of sociodemographic, health and care-related variables on the QoL of older informal caregivers of people with dementia. RESULTS: Older informal caregivers reported a significantly lower QoL compared to older non-caregivers in the general population. Especially the domains autonomy, activities in the past, the present and the future as well as intimacy were negatively associated with caregivers' QoL. CONCLUSION: The results of the study highlighted caregivers' need for assistance. Due to demographic changes, tailored support services should be based on older caregivers' needs.

Excited State Properties of Heteroleptic Cu(I) 4H-Imidazolate Complexes.

The excited state properties of three heteroleptic copper(I) xantphos 4H-imidazolate complexes are investigated by means of femtosecond and nanosecond time-resolved transient absorption spectroscopy in dichloromethane solution. The subpicosecond spectral changes observed after excitation into the MLCT absorption band are interpreted as intersystem crossing from the singlet to the triplet manifold. This interpretation is corroborated by DFT and TD-DFT results, indicating a comparable molecular geometry in the ground state (and hence the nonrelaxed singlet state) and the excited triplet state. Population of the triplet state is followed by planarization of the N-aryl rings of the 4H-imidazolate ligand on a 10 ps time scale. The planarization strongly depends on the substitution pattern of the N-aryls and correlates with the reduced moment of inertia for the planarization motion. The triplet state subsequently decays to the ground state in about 100 ns. These results demonstrate that the excited state processes of copper(I) complexes depend on the specific ligand(s) and their substitution pattern. Thus, the work presented points to a possibility to design copper(I) complexes with specific photophysical properties.

Excited State Dynamics of a Photobiologically Active Ru(II) Dyad Are Altered in Biologically Relevant Environments.

In this study femtosecond and nanosecond time-resolved transient absorption spectroscopy was used to investigate the influence of ionic strength and complexity on the excited state dynamics of a Ru(II)-based metal-organic dyad. The bis-heteroleptic complex [Ru(bpy)2(ippy)]2+ (1), where bpy = 2,2'-bipyridine and ippy = 2-(1-pyrenyl-1H-imidazo[4,5-f][1,10]phenanthroline, is a potent photosensitizer for in vitro photodynamic therapy (PDT) and photodynamic inactivation (PDI) of microorganisms owing to a long-lived triplet excited state derived from a metal-to-ligand charge-transfer (3MLCT) state that is equilibrium with an intraligand (3IL) state. The prolonged lifetime provides ample opportunity for bimolecular quenching of this state by oxygen; thus singlet oxygen (1O2) sensitization is very efficient. In simple aqueous solution, fast cooling within the 3MLCT manifold is followed by energy transfer to an 3IL state, which is facilitated by rotation of a pyrenyl unit about the imidazo-pyrenyl (ip) coannular bond. For solutions of 1 in high ionic strength simulated biological fluid (SBF), a more physiologically relevant solvent that contains a complex mixture of ions at pH 7.4, femtosecond studies revealed an additional excited state, possibly based on an ion-ligand interaction. This new state appearing in high ionic strength SBF was not observable in water, simple buffers, or low ionic strength SBF. These photoinduced dynamics were also affected by the presence of biomolecules such as DNA in simple buffer, whereby relaxation on the picosecond time scale was accelerated from 39 to 18 ps with DNA intercalation by 1. The increased rate of coplanarization of the pyrene and the imidazole units was attributed to DNA-induced conformational restriction of the pyrenyl unit relative to the ip bond. Quantitative changes to excited state decay rates of 1 in solutions of high ionic strength were also observed when probed on the microsecond time scale. Notably, the thermalized excited state decay pathways were altered substantially with DNA intercalation, with access to some states being completely blocked. Experimentally, this manifested in the absence of the slowest microsecond decay channel, which is normally observed for 1 in solution. The quantitative and qualitative observations from this study highlight the importance of employing biologically relevant solvents and potential biomolecule targets when the excited state dynamics and photophysical properties (under cell-free conditions) responsible for the potent photobiological effects are assessed in the context of photodynamic therapy and photodynamic inactivation.

Constructed wetlands and solar-driven disinfection technologies for sustainable wastewater treatment and reclamation in rural India: SWINGS project.

SWINGS was a cooperation project between the European Union and India, aiming at implementing state of the art low-cost technologies for the treatment and reuse of domestic wastewater in rural areas of India. The largest wastewater treatment plant consists of a high-rate anaerobic system, followed by vertical and horizontal subsurface flow constructed wetlands with a treatment area of around 1,900 m2 and a final step consisting of solar-driven anodic oxidation (AO) and ultraviolet (UV) disinfection units allowing direct reuse of the treated water. The implementation and operation of two pilot plants in north (Aligarh Muslim University, AMU) and central India (Indira Gandhi National Tribal University, IGNTU) are shown in this study. The overall performance of AMU pilot plant during the first 7 months of operation showed organic matter removal efficiencies of 87% total suspended solids, 95% 5-day biological oxygen demand (BOD5) and 90% chemical oxygen demand, while Kjeldahl nitrogen removal reached 89%. The UV disinfection unit produces water for irrigation and toilet flushing with pathogenic indicator bacteria well below WHO guidelines. On the other hand, the AO disinfection unit implemented at IGNTU and operated for almost a year has been shown to produce an effluent of sufficient quality to be reused by the local population for agriculture and irrigation.

[Home Treatment]. / Home Treatment.

Home Treatment (HT) means acute psychiatric treatment in the patient's usual environment. Conceptually, HT is to be differentiated from other home-based services: It is limited with regard to duration and multiprofessional (e. g. psychiatrist plus psychiatric nursing staff plus social worker); the "24/7"-accessibility is frequently provided by the corresponding background hospital infrastructure. Target group are acutely mentally ill persons with an indication to inpatient treatment, who are willing to cooperate, and absence of endangerment to self and others. In contrast to the Scandinavian and many Anglophone countries where nationwide HT services are delivered, there are not many HT sites in Germany so far. Consequently, empirical data concerning HT in Germany is scarce. In summary, international studies show equivalent effects on psychopathological measures compared to inpatient treatment, reductions with regard to inpatient days, higher patient satisfaction and a trend towards cost-effectivity.

Promoting physical health in severe mental illness: patient and staff perspective.

OBJECTIVE: To explore physical health problems and their causes in patients with severe mental illness, as well as possibilities for prevention and treatment from the patients' and staff's perspectives. METHOD: We conducted six focus groups with patients and staff separately, from three out-patient clinics treating patients with schizophrenia or substance-use disorder comorbid to another psychiatric disorder. Focus groups were audio-recorded, transcribed verbatim and analysed using a template approach. RESULTS: Paramount physical health problems are weight issues, cardiovascular diseases and poor physical shape. Main causes are lifestyle, the mental disorder and organisational issues. Patients and staff expressed similar opinions regarding physical health problems and their causes. Possibilities for prevention and treatment includes a case manager and binding communities with like-minded, as well as management support and implementation of physical health into daily psychiatric practice. Although patients and staff suggested different possibilities for prevention and treatment, they support one strategy: less fragmentation of the treatment system and cooperation between psychiatric and somatic healthcare. CONCLUSION: To prevent and treat physical health problems in patients with severe mental illness, support in daily structure and lifestyle changes is needed. Management support is needed to change daily practice and implement routines regarding physical health.

A systematic review of controlled interventions to reduce overweight and obesity in people with schizophrenia.

OBJECTIVE: Overweight and obesity are generally found among patients with schizophrenia. This may lead to serious implications for health and wellbeing. The aim was to review controlled intervention studies on reducing overweight/obesity and/or reducing physical illness in patients with schizophrenia. METHOD: A systematic literature search was carried out in the bibliographic databases PubMed (MEDLINE), Embase (Ovid), PsycInfo (Ovid) and Cinahl (Ebsco). We included all randomised and non-randomised clinically controlled studies that compared a non-pharmacological intervention, aimed at weight reduction and/or reducing physical illness, with standard care for patients with schizophrenia. RESULTS: All 1713 references were evaluated for inclusion in the review. Twenty-three met the inclusion criteria and were categorised into four subgroups according to tested interventions: diet, exercise and cognitive behavioural therapy, or mixed combinations of the three. In this review, interventions showed efficacy in reducing weight and improving physical health parameters confirming that physical health improvement was possible in patients with schizophrenia. CONCLUSION: The included studies indicate that the interventions reduced weight and improved physical health parameters in patients with schizophrenia.

[Decentralized outpatient teams in community-based psychiatric care: comparison of two Bavarian rural catchment areas]. / Dezentrale ambulante Teams in der gemeindenahen psychiatrischen Versorgung : Zwei bayerische ländliche Regionen im Vergleich.

BACKGROUND: Psychiatric outpatient clinics (PIAs) are an indispensable care service for crisis intervention and multidisciplinary treatment of people suffering from severe and persistent mental disorders. The decentralization of outpatient clinics can be understood as a further step in the deinstitutionalization process. METHODS: This cross-sectional study (n=1,663) compared the central outpatient clinic with the decentralized teams for the year 2010 by means of analyses of variance, χ(2)-tests and robust multivariate regression models. The longitudinal assessment (descriptively and by means of Prais-Winsten regression models for time series) was based on all hospitalizations for the two decentralized teams (n = 6,693) according to partial catchment areas for the time period 2002-2010 in order to examine trends after their installation in the year 2007. RESULTS: Decentralized teams were found to be similar with respect to the care profile but cared for relatively more patients suffering from dementia, addictive and mood disorders but not for those suffering from schizophrenia and personality disorders. Decentralized teams showed less outpatient care costs as well as psychopharmacological expenses but a lower contact frequency than the central outpatient clinic. Total expenses for psychiatric care were not significantly different and assessed hospitalization variables (e.g. total number of annual admissions, cumulative length of inpatient-stay and annual hospitalizations per patient) changed slightly 3 years after installation of the decentralized teams. The number of admissions of people suffering from schizophrenia decreased whereas those for mood and stress disorders increased. DISCUSSION: Decentralized outpatient teams seemed to reach patients in rural regions who previously were not reached by the central outpatient clinic. Economic figures indicate advantages for the installation of such teams because care expenses are not higher than for patients treated in centralized outpatient clinics and because hospitalization figures for the whole catchment area did not increase.

[Involuntary psychiatric hospital admissions: a comparison between five hospitals in three German federal states]. / Psychiatrische Unterbringungspraxis : Ein Vergleich von fünf Kliniken in drei Bundesländern.

BACKGROUND: There is considerable variance in involuntary psychiatric hospital admission rates both in Europe and Germany. In a prospective comparison between five hospitals in three German federal states we assessed and analyzed involuntary psychiatric hospital admissions, including the patient's perspective. MATERIAL AND METHOD: All involuntarily admitted patients were assessed by an independent researcher. Clinical data, patient and psychiatrist views were documented with different instruments including the McArthur admission experience survey. RESULTS: In this study 104 out of 244 involuntarily admitted patients gave informed consent. We found considerable differences between study centres concerning involuntary admission quotas (3.2-25.8% of all hospital admissions) and involuntary admission rates (16.6-97.6 per year per 100,000 inhabitants). Hospitals in the state of Baden-Württemberg had the lowest involuntary admission rates while they were highest in Bavaria. In Baden-Württemberg involuntarily admitted patients were more likely to suffer from chronic schizophrenia, they were more severely ill and experienced the involuntary hospital admission as more strenuous. There were no differences between centres concerning frequency of dangerous behavior or self-harm. CONCLUSION: We found a high variance across regions concerning the reasons for, frequencies and legal basis of involuntary hospital admissions. Regional differences of legal frameworks and service organization can explain this only to a limited amount. Transparency, legal certainty and reflection of stakeholder roles are a future necessity. Furthermore, there is a need for stringent compliance with legal regulations and coherent documentation.

Potential of nature-based solutions to reduce antibiotics, antimicrobial resistance, and pathogens in aquatic ecosystems. a critical review.

This comprehensive scientific review evaluates the effectiveness of nature-based solutions (NBS) in reducing antibiotics (ABs), combating antimicrobial resistance (AMR), and controlling pathogens in various aquatic environments at different river catchment levels. It covers conventional and innovative treatment wetland configurations for wastewater treatment to reduce pollutant discharge into the aquatic ecosystems as well as exploring how river restoration and saltmarshes can enhance pollutant removal. Through the analysis of experimental studies and case examples, the review shows NBS's potential for providing sustainable and cost-effective solutions to improve the health of aquatic ecosystems. It also evaluates the use of diagnostic indicators to predict NBS effectiveness in removing specific pollutants such as ABs and AMR. The review concludes that NBS are feasible for addressing the new challenges stemming from human activities such as the presence of ABs, AMR and pathogens, contributing to a better understanding of NBS, highlighting success stories, addressing knowledge gaps, and providing recommendations for future research and implementation.

[Service structure and cooperation in mental health care]. / Struktur und Kooperation in der Versorgung psychisch Kranker.

BACKGROUND: This study assesses exemplarily the regional structure of mental health services and the practice of cooperation of mental health service providers. The aim is to identify starting points for improving mental health care. METHOD: (1) Mapping of mental health services in four exemplary regions (urban/rural, East/West Germany) using the European Service Mapping Schedule. (2) Analysis of the practice of cooperation in mental health care using focus groups and a postal survey of psychiatrists and psychotherapists working in private practice. RESULTS: All surveyed regions have a well-developed and complex service system available. Cooperation in mental health care takes place in flexible networks rather than in fixed relationships. An explicit concept of cooperation does not exist. Time and resources promote cooperation. Psychiatrists and psychotherapists working in outpatient care mainly cooperate among themselves and rarely on an interdisciplinary basis. In particular psychotherapists are usually not part of cooperation networks. CONCLUSIONS: Improvements in mental health care are more likely to be achieved through improving cooperation rather than just developing additional services. Starting points for improvements include-beyond the increase of resources for cooperation - the training of medical students and psychiatrists in cooperation practice, reimbursement of cooperation and coordination and the implementation of systematic coordination of service networks.

Effects of polypharmacy on outcome in patients with schizophrenia in routine psychiatric treatment.

OBJECTIVE: Evaluating the effects of different types of psychotropic polypharmacy on clinical outcomes and quality of life (QOL) in 374 patients with schizophrenia and schizoaffective disorder in routine care. METHOD: Psychotropic regimen, clinical outcomes, and QOL were assessed before discharge and after 6, 12, 18, and 24 months. Data were analyzed by mixed-effects regression models for longitudinal data controlling for selection bias by means of propensity scores. RESULTS: At baseline 22% of participants received antipsychotic monotherapy (APM) (quetiapine, olanzapine, or risperidone), 20% more than one antipsychotic drug, 16% received antipsychotics combined with antidepressants, 16% antipsychotics plus benzodiazepines, 11.5% had antipsychotics and mood stabilizers, and 16% psychotropic drugs from three or more subclasses. Patients receiving APM had better clinical characteristics and QOL at baseline. Patients receiving i) antipsychotics plus benzodiazepines or ii) antipsychotics plus drugs from at least two additional psychotropic drug categories improved less than patients with APM. CONCLUSION: Combinations of antipsychotics with other psychotropic drugs seem to be effective in special indications. Nevertheless, combinations with benzodiazepines and with compounds from multiple drug classes should be critically reviewed. It is unclear whether poorer outcomes in patients with such treatment are its result or its cause.

Psychotropic drug treatment, clinical characteristics and cognitive processing speed in patients with schizophrenia: results from the ELAN study.

INTRODUCTION: Psychotropic drug combinations (PDC) are common in the treatment of patients with schizophrenia but there is little research regarding the effects of PDC on cognition. OBJECTIVE: The aim of this study was to analyse the effects of antipsychotic monotherapy and various types of PDC on cognitive processing speed (CPS). METHODS: ELAN is a 24-month multi-site prospective observational controlled trial following up 374 patients with schizophrenia under routine treatment conditions following discharge from inpatient treatment. The propensity score method, multinomial logistic regression analyses and mixed effects regression models were used. RESULTS: CPS correlated significantly with PANSS and GAF scores and improved over time in the monotherapy group. Negative effects of some PDC (antipsychotics + tranquilizers/antipsychotics+at least 2 other psychopharmacological subclasses, sedative/anticholinergic drugs/high adjusted antipsychotic dose) lost significance after controlling for clinical characteristics. DISCUSSION: Indications for PDC should be examined with care although, in the present study, effects on cognition were small.