Spyridon Siafis

Technische Universität München | TUM · Section for Evidence Based Medicine in Psychiatry and Psychotherapy

Aim: Recent data suggest that antidepressants are associated with incident diabetes but the possible pharmacological mechanism is still questioned. The aim of the present study was to evaluate antidepressant's risk for reporting diabetes using disproportionality analysis of the FDA adverse events spontaneous reporting system (FAERS) database and t...

Background There is still no approved medication for the core symptoms of autism spectrum disorder (ASD). This network meta-analysis investigated pharmacological and dietary-supplement treatments for ASD. Methods We searched for randomized-controlled-trials (RCTs) with a minimum duration of seven days in ClinicalTrials.gov, EMBASE, MEDLINE, PsycIN...

Background The Z-drugs are indicated for the short-treatment of insomnia, but they are associated with abuse, dependence and side-effects. There are only sparse data about Z-drug prescribing in Greece. Methods We analyzed data from the Greek prescription database, considering prescriptions for the available Z-drugs in Greece, i.e., zolpidem and zo...

Antipsychotic drugs differ in their propensity to cause extrapyramidal side-effects (EPS), but their dose-effects are unclear. Therefore, we conducted a systematic review and dose-response meta-analysis. We searched multiple electronic databases up to 20.02.2023 for fixed-dose studies investigating 16 second-generation antipsychotics and haloperido...

Background: Bipolar depression constitutes a major public health problem due to its substantial burden of disease. Although pharmacological interventions are available, guidelines required updated evidence synthesis to improve their current recommendations. In order to inform evidence-based prescribing, we investigated the comparative efficacy and...

Background The relative treatment effects estimated from network meta-analysis can be employed to rank treatments from the most preferable to the least preferable option. These treatment hierarchies are typically based on ranking metrics calculated from a single outcome. Some approaches have been proposed in the literature to account for multiple o...

Background Exercise can play an important role in reducing symptom severity and improving functional impairment in patients with posttraumatic stress disorder (PTSD). However, the precise mechanisms underpinning the effect of exercise in PTSD management are not fully understood. This living systematic review aims to synthesize and triangulate the e...

Background: Anhedonia is a key symptom of depression, and it has been suggested as a potential target for future individualised treatments. However, much is unknown about how interventions enhancing dopaminergic pathways may affect anhedonia symptoms in the context of depression. Methods: We will perform independent searches in multiple electronic...

Background: There is an urgent need to develop more effective and safer antipsychotics beyond dopamine 2 receptor antagonists. An emerging and promising approach is TAAR1 agonism. Therefore, we will conduct a living systematic review and meta-analysis to synthesize and triangulate the evidence from preclinical animal experiments and clinical studie...

Objective Clozapine is considered as the standard treatment for this subgroup, but the evidence is not unequivocal. There are several potential alternatives being used because of the possible adverse effects of clozapine. We aimed to examine the efficacy and adverse events of different antipsychotics in treatment-resistant schizophrenia by performi...

Background and hypothesis: Long-acting injectable antipsychotic drugs (LAIs) are mainly used for relapse prevention but could also be advantageous for acutely ill patients with schizophrenia. Study design: We conducted a systematic review and meta-analysis of randomized-controlled-trials (RCTs) comparing the second-generation long-acting injecta...

In anxiety, depression and psychosis, there has been frustratingly slow progress in developing novel therapies that make a substantial difference in practice, as well as in predicting which treatments will work for whom and in what contexts. To intervene early in the process and deliver optimal care to patients, we need to understand the underlying...

Antipsychotic-induced akathisia is severely distressing. We aimed to investigate relationships between antipsychotic doses and akathisia risk. We searched for randomised controlled trials that investigated monotherapy of 17 antipsychotics in adults with acute schizophrenia until 06 March 2022. The primary outcome was the number of participants with...

Despite the clear rationale for applying shared decision-making in the context of the preference sensitive decision for or against antipsychotics and the upswing of patient decision aids (pDAs) to support this process, there is still a lack of knowledge regarding which key features are crucial for pDAs in schizophrenia treatment. A scoping review a...

Background There is evidence that antipsychotic drugs differ in their effect on the cognitive symptoms of schizophrenia. So far, there is no comprehensive systematic review available that would enable providers and patients to make informed choices regarding this important aspect of treatment. With a large number of substances available, convention...

Objectives: Decision aids (DAs) are promising tools to foster evidence-based shared decision-making between practitioners and service users. Nevertheless, it is still obscure how an evidence-based DA for people with severe mental illness, especially psychosis, should look in an inpatient treatment setting to be useful and feasible. Therefore, we c...

The agreement between treatment effects measured by clinician- and caregiver-ratings of repetitive-restricted behaviors (RRBs) is important for clinical practice and research but is still unclear. Therefore, we conducted a post-hoc meta-analysis of placebo-controlled randomized-controlled trials (RCTs) investigating pharmacological and dietary-supp...

Background: Predicting relapse for individuals with psychotic disorders is not well established, especially after discontinuation of antipsychotic treatment. We aimed to identify general prognostic factors of relapse for all participants (irrespective of treatment continuation or discontinuation) and specific predictors of relapse for treatment di...

Introduction Guidelines recommend clozapine for treatment-resistant schizophrenia. However, meta-analysis of aggregate data (AD) did not demonstrate higher efficacy of clozapine compared with other second-generation antipsychotics but found substantial heterogeneity between trials and variation between participants in treatment effects. Therefore,...

Network meta-analysis (NMA) usually provides estimates of the relative effects with the highest possible precision. However, sparse networks with few available studies and limited direct evidence can arise, threatening the robustness and reliability of NMA estimates. In these cases, the limited amount of available information can hamper the formal...

Previous late-stage randomized controlled trials (RCTs) failed to identify effective medications for the core symptoms of autism spectrum disorder (ASD), i.e., social- communication difficulties and repetitive behaviors, and as a consequence, there is still no approved medication. Thus, I conducted a systematic review of 203 RCTs with 12111 partici...

Metabolic side effects of antipsychotic drugs can have serious health consequences and may increase mortality. Although persons with schizophrenia often take these drugs for a long time, their mid‐ to long‐term metabolic effects have been studied little so far. This study aimed to evaluate the mid‐ to long‐term metabolic side effects of 31 antipsyc...

Background: In recent years it could be shown that psychosocial working conditions and mental health of employees are closely correlated. One well-established instrument to measure psychosocial stress at work is the COPSOQ (Copenhagen Psychosocial Questionnaire, German Standard Version). It is an 84 item self-rating instrument addressing several d...

Background: Antipsychotic drugs are the mainstay treatment for schizophrenia, yet they are associated with diverse and potentially dose-related side effects which can reduce quality of life. For this reason, the lowest possible doses of antipsychotics are generally recommended, but higher doses are often used in clinical practice. It is still uncl...

Background Multiple sclerosis (MS) is a lifelong deteriorating disease characterized by multiple heterogeneous symptoms. Being an autoimmune disease of the central nervous system, mainly affecting the myelin sheath of the nerves ordinarily results in neurological symptoms.GABA has numerous effects on the immune cells, altering cytokine production,...

Background: To what extent the COVID-19 pandemic and its containment measures influenced mental health in the general population is still unclear. Purpose: To assess the trajectory of mental health symptoms during the first year of the pandemic and examine dose–response relations with characteristics of the pandemic and its containment. Data Sour...

Background: In clinical practice, different antipsychotics can be combined in the treatment of people with schizophrenia (polypharmacy). This strategy can aim at increasing efficacy, but might also increase the adverse effects due to drug-drug interactions. Reducing polypharmacy by withdrawing one or more antipsychotics may reduce this problem, bu...

Antipsychotics are a class of psychotropic drugs that improve psychotic symptoms and reduce relapse risk. However, they may cause side effects (SE) that impact patients' quality of life and psychosocial functioning. Therefore, there is a need for practical tools to identify them and possibly intervene. The objective of the present study was to tran...

Background Choosing an antipsychotic medication is an important medical decision in the treatment of schizophrenia. This decision requires risk-benefit assessments of antipsychotics, and thus, shared-decision making between physician and patients is strongly encouraged. Although the efficacy and side-effect profiles of antipsychotics are well-estab...

Antipsychotic drugs are the mainstay of treatment of schizophrenia, and are known to reduce acute symptoms of the disorder. An original version of the current review, published in 2012, examined whether antipsychotics are effective for relapse prevention, compared to withdrawing these agents for people with schizophrenia or schizophrenia-like psych...

Background Adverse events can occur after antipsychotic discontinuation but evidence from antipsychotic drug trials is scarce. We aimed to estimate the occurrence of adverse events after discontinuing antipsychotics. Methods For this two-stage individual participant data meta-analysis, we searched the Yale University Open Data Access Project's dat...

Background Weight gain is among the most important side-effects of antipsychotics. It is, however, unclear whether it is associated with antipsychotic doses. We aimed to fill this gap with a dose-response meta-analysis. Methods We searched multiple electronic databases (last update search June 2021) for all fixed-dose studies that investigated 16...

Background Schizophrenia is a common, severe, and usually chronic disorder. Maintenance treatment with antipsychotic drugs can prevent relapse but also causes side-effects. We aimed to compare the efficacy and tolerability of antipsychotics as maintenance treatment for non-treatment resistant patients with schizophrenia. Methods In this systematic...

Background Family interventions are efficacious for relapse prevention in schizophrenia. Multiple different models have been developed. We aimed to compare the efficacy, acceptability, and tolerability of family interventions for relapse prevention in schizophrenia. Methods In this systematic review and network meta-analysis, we searched for rando...

Introduction The high efficacy of atypical antipsychotics (AAP) in treating diverse psychiatric disorders has been partly attributed to their capacity to curb neuroinflammation, a shared aspect of these diseases. These immunomodulatory properties of AAP have lately been explored in the context of multiple sclerosis (MS), an autoimmune demyelinating...

A recent increase in the literature regarding the evidence base for clozapine has made it increasingly difficult for clinicians to judge “best evidence” for clozapine use. As such, we aimed at elucidating the state-of-the-art for clozapine with regard to efficacy, effectiveness, tolerability, and management of clozapine and clozapine-related advers...

In Reply Replication is the essence of science. It is therefore important that Højlund and colleagues,¹ who used a different meta-analytic method and slightly different inclusion criteria from ours, had similar findings in that standard doses (in our analysis, 5 mg risperidone equivalent) were more effective than lower ones (also see our Supplement...

Prolactin increase is a common side effect in antipsychotic treatment of schizophrenia, which crucially impacts drug choice and treatment compliance. As previous reviews by our group on this topic have included only few Chinese studies, we aimed to compare and rank antipsychotics based on broader evidence. This systematic review pooled data of 92 i...

Background Many psychosocial and psychological interventions are used in patients with schizophrenia, but their comparative efficacy in the prevention of relapse is not known. We aimed to evaluate the efficacy, acceptability, and tolerability of psychosocial and psychological interventions for relapse prevention in schizophrenia. Methods To conduc...

Objective: The present study aims to identify potential safety signals of chloroquine (CQ) and hydroxychloroquine (HCQ), over the period preceding their repurpose as COVID-19 treatment options, through the analysis of safety data retrieved from the FDA Adverse Event Reporting System (FAERS) pharmacovigilance database. Materials and methods: We p...

Importance The doses of antipsychotic drugs needed for relapse prevention in schizophrenia is a debated issue. Objective To examine dose-response findings in a meta-analysis of randomized clinical trials. Data Sources Studies were identified through the Cochrane Schizophrenia Group’s Study-Based Register of Trials (March 9, 2020), PubMed (January...

Background The magnitude of the superiority of antipsychotics over placebo is debated. One reason is that the effect-size index which is usually used in meta-analyses is in standard deviation units. Many other indices, some of which are more intuitive, exist. Methods We explain the formulae, advantages, and limitations of 13 effect-size indices: M...

Background Antipsychotic drugs and especially the newer compounds are known to cause metabolic side effects. However, a comprehensive comparison of the different substances regarding their propensity to cause metabolic side effects in medium- to long-term treatment of schizophrenia is lacking. Methods We will conduct a systematic review and networ...

Introduction: Response to treatment, according to Clinical Global Impression-Improvement (CGI-I) scale, is an easily interpretable outcome in clinical trials of autism spectrum disorder (ASD). Yet, the CGI-I rating is sometimes reported as a continuous outcome, and converting it to dichotomous would allow meta-analysis to incorporate more evidence...

Background Increased prevalence of depression has been observed among patients with multiple sclerosis (MS) and correlated with the elevated levels of proinflammatory cytokines and the overall deregulation of monoaminergic neurotransmitters that these patients exhibit. Antidepressants have proved effective not only in treating depression comorbid t...

Introduction: The latest decade, an emerging issue has been the abuse potential of the gabapentinoids pregabalin and gabapentin. The aim of our study was to assess this safety signal combining two different methods of surveillance: search analytics big data and the FDA spontaneous reporting system database. Methods: Analysis of big data and the FAE...

Aim: While the efficacy of disease-modifying therapies (DMTs) for patients with multiple sclerosis (MS) is established, little is known about their long-term safety. Cancer-risk after DMT use remains unclear. This study aimed to investigate whether the prescription of DMTs for patients with MS increases the risk of reporting cancer. Methods: Dat...

Background: Multiple sclerosis (MS) is a chronic inflammatory and immune-mediated disease, whose current therapeutic means are mostly effective in the relapsing-remitting form of MS, where inflammation is still prominent, but fall short of preventing long term impairment. However, apart from inflammation-mediated demyelination, autoimmune mechanis...

Background Psychomotor agitation is a common condition in patients with psychotic disorders. One treatment possibility is intramuscular (IM) second-generation antipsychotics. Yet their efficacy in this formulation and for this aim is unclear. This network meta-analysis aims to evaluate the efficacy of short-acting IM second-generation antipsychotic...

In the last decade there has been a revolution in terms of genetic findings in neurodevelopmental disorders (NDDs), with many discoveries critical for understanding their aetiology and pathophysiology. Clinical trials in single-gene disorders such as fragile X syndrome highlight the challenges of investigating new drug targets in NDDs. Incorporatin...

Antipsychotic drugs are commonly prescribed, mainly for the treatment of schizophrenia and other psychotic disorders. Disproportionality analysis of pharmacovigilance data from national and international databases have been recently utilized to investigate the side-effect profiles of antipsychotics and have provided unique insights of their safety....

The second-to-fourth digit ratio (2D:4D) is an indirect, retrospective, non-invasive measure that correlates negatively with intrauterine exposure to testosterone. The present meta-analysis aimed to evaluate if 2D:4D differs between patients with psychiatric disorders and controls. In September 2019, we searched in Web of Knowledge, PsycINFO, Embas...

An association between antipsychotic drugs and pneumonia has been demonstrated in several studies; however, the risk for pneumonia caused by specific antipsychotics has not been extensively studied. The underlying mechanism is still unknown, and several receptor mechanisms have been proposed. Therefore, using a combined pharmacovigilance-pharmacody...

Objective: To estimate current prevalence of multiple sclerosis (MS) in Greece using administrative data from the nationwide medicine prescription database. Methods: Prescription records of a 24-month period (June 2017-May 2019) were analyzed in order to identify cases of MS. Sex, age, and place of residence were recorded for each identified case....

Background The present study aimed at answering three research questions: (a) Does shared decision making (SDM) yield similar effects for patients with involuntary admission or incidents of aggression compared to patients with voluntary admission or without incidents of aggression? (b) Does SDM reduce the number of patients with incidents of aggres...

Background Placebo response in autism spectrum disorder (ASD) might dilute drug-placebo differences and hinder drug development. Therefore, this meta-analysis investigated placebo response in core symptoms. Methods We searched ClinicalTrials.gov, CENTRAL, EMBASE, MEDLINE, PsycINFO, WHO-ICTRP (up to July 8, 2018), and PubMed (up to July 4, 2019)...

Background: The symptoms and signs of schizophrenia have been linked to high levels of dopamine in specific areas of the brain (limbic system). Antipsychotic drugs block the transmission of dopamine in the brain and reduce the acute symptoms of the disorder. An original version of the current review, published in 2012, examined whether antipsychot...

Objective: The second-to-fourth digit ratio (2D:4D) is an indirect, retrospective, non-invasive measure that correlates negatively with intrauterine exposure to testosterone. The present meta-analysis aimed to evaluate if 2D:4D differs between patients with psychiatric disorders and controls. Methods: In September 2019, we searched in Web of Knowle...

Background Antipsychotic drugs are the mainstay of the pharmacological treatment of schizophrenia, used in the acute episode of the disorder and for prevention of relapses. Unfortunately, antipsychotics cause side effects. Weight gain is one of the most prominent side effects. In line with weight gain, also alterations of lipid- and glucose homeost...

Background Weight gain is an important side effect of antipsychotics. Meta-analyses of randomized controlled trials indicate differences between the multiple antipsychotics in propensity to cause weight gain. However, antipsychotic-associated weight gain, in randomized controlled trials as well as in real life situations, might also depend on popul...

This study sought to detect a potential safety signal of mirtazapine abuse by combining two different sources of surveillance, specifically Google Analytics (Google, Inc., Mountain View, CA, USA) and the FDA Adverse Event Reporting System database. Data from the first quarter of 2004 to the second quarter of 2017 were collected and analysed. The se...

Purpose The aim of this systematic review was to evaluate current evidence on the efficacy and safety of levetiracetam as migraine prophylaxis in adult patients suffering from migraine attacks. Methods PubMed, Scopus, Cochrane Central Register of Controlled Trials, and International Web of Science were searched (last search in August 2018) for stu...

Antipsychotic drugs: from ‘major tranquilizers’ to Neuroscience-based-Nomenclature - Spyridon Siafis, John M. Davis, Stefan Leucht

Objective: The dose-response relationships of antipsychotic drugs for schizophrenia are not well defined, but such information would be important for decision making by clinicians. The authors sought to fill this gap by conducting dose-response meta-analyses. Methods: A search of multiple electronic databases (through November 2018) was conducte...

Background Comparisons of antipsychotics with placebo can be biased by unblinding due to side effects. Therefore, this meta-analysis compared the efficacy of antipsychotics for acute schizophrenia in trials using barbiturates or benzodiazepines as active placebos. Methods Randomized controlled trials (RCTs) in acute schizophrenia with at least 3 w...

Introduction: A recent meta-analysis of seven case-controls studies suggested a positive association between cataract development and antidepressant use [1]. Aim of the present study was to evaluate the risk for cataract among individual antidepressants using a disproportionality analysis. Methods: A disproportionality analysis was conducted in t...

Background: Antipsychotic drugs are the cornerstone of schizophrenia treatment but are also indicated for other psychotic and mood disorders. Different antipsychotic drugs and their formulations are available, though liquid forms have been overlooked. Methods: Herein the added value of liquid antipsychotics is reviewed, with a focus on the recen...

Objective Cannabis is reported to be the most common illicit substance used among medical students; however, the number of related studies is limited and their results are not systematically reviewed. The aim of our study was to analyze the prevalence of lifetime and current use of cannabis among medical students worldwide. Methods A systematic re...

rev_supplementary_xyz9610434e3d4a – Supplemental material for Prevalence of Cannabis Use Among Medical Students: A Systematic Review and Meta-analysis

Nonmedical use of prescription medications is a growing health problem including not only the opioid painkiller overdose epidemic but also benzodiazepine and stimulants misuse. Medical students express considerable high percentages of prescription drug misuse but also of illicit drug use, with cannabis being the frequently used illicit drug. We rep...

Patient: Female, 30 Final Diagnosis: Depression Symptoms: — Medication: Mirtazapine Clinical Procedure: — Specialty: Psychiatry Objective Unusual or unexpected effect of treatment Background The pharmacological term tachyphylaxis is used to describe rapidly occurring response desensitization, a situation where the biological response to a given d...

Background: Antipsychotic-induced metabolic side effects are major concerns in psychopharmacology and clinical psychiatry. Their pathogenetic mechanisms are still not elucidated. Methods: Herein, we review the impact of neurotransmitters on metabolic regulation, providing insights into antipsychotic-induced metabolic side effects. Results: Ant...