Psichiatria per Professioni Sanitarie

Il presente manuale offre una preparazione psichiatrica per gli operatori delle professioni sanitarie. Considerata la grande prevalenza di disturbi psichiatrici nella popolazione, appare importante avere le basi dei disturbi psichiatrici, dei trattamenti, delle strutture che configurano l'attività psichiatrica e dei diversi approcci da tenere nei confronti di persone affette da patologie psichiatriche. Il manuale è diviso in capitoli specifici per consentire un rapido accesso alle informazioni necessarie

Polimorfizam gena za serotoninski transporter (5-HTTLPR) i učinkovitost selektivnih inhibitora ponovne pohrane serotonina – imamo li dovoljno dokaza za kliničku praksu

Depression pharmacotherapy can be described with weak predictability of individual response. Antidepressants are prescribed based on trial and error, as it is not possible to determine which patients will respond to antidepressants. It would appear that pharmacogenetics is the most promising path towards achieving the goal of individualized therapy. Today, the most commonly prescribed antidepressants are those from the group of selective serotonin reuptake inhibitors (SSRI). The most investigated genetic variations in the prediction and individualization of antidepressant therapy is the serotonin transporter gene (5-HTT LPR). The objective of this paper is to provide an overview of the research to date on 5-HTT LPR polymorphism in response to SSRI. This paper gives an overview of 35 studies investigating the efficacy of SSRI antidepressants in dependence of 5-HTT LPR polymorphism. The results of three meta-analyses examining this issue are discussed. Briefly, the great majority of studies conducted have shown that L-allele carriers have a faster and better response to SSRI antidepressants, if they are Caucasians. Studies with negative results included ethnically mixed populations, and it is known that there are different allele frequencies among ethnic groups and the consequence of this are the varying results of pharmacogenetic studies. Pharmacogenetic analysis of 5-HTT LPR polymorphism has proven to be economically cost-effective considering the recurrent course of the disease. It would appear that the response to SSRI antidepressants and the development of adverse reactions are associated with 5-HTT LPR polymorphism in Caucasians and this pharmacogenetic analysis could be one of the first in future clinical practice.Farmakoterapija depresije mogla bi se opisati slabom predvidljivosti individualnog odgovora. Antidepresivi se ordiniraju po načelu slučaj ili pogreška, jer kliničkim značajkama ne uspijevamo odrediti koji će bolesnik odgovoriti na antidepresive ili razviti nuspojave. Čini se da je farmakogenetika put koji najviše obećava kako bi se postigao zadani cilj, individualizirana terapija. Danas se najčešće primjenjuju antidepresivi iz skupine selektivnih inhibitora ponovne pohrane serotonina (SSRI). S druge strane, najistraživanija genetska varijanta u predviđanju i individualizaciji antidepresivne terapije je polimorfizam gena za serotoninski transporter (5-HTT LPR). Cilj ovoga rada je prikazati dosadašnja istraživanja polimorfizma 5-HTT LPR i odgovora na SSRI. U radu je prikazano 35 studija u kojima se istraživala učinkovitost antidepresiva SSRI u ovisnosti o polimorfizmu 5-HTT LPR. Prikazani su i rezultati 3 meta analize koje su istraživale navedenu problematiku. Ukratko, velika većina dosadašnjih studija je pokazala da nosioci L alela imaju brži i bolji odgovor na antidepresive SSRI ako su bijelci. Navedeno potvrđuju i 2 meta analize. Studije koje su bile negativne imale su etnički miješanu populaciju, a zna se da su frekvencije alela drugačije kod različitih etničkih skupina i posljedično tome i različiti rezultati farmakogenetskih istraživanja. Za Azijate rezultati su još proturječni. Farmakogenetska analiza polimorfizma 5-HTT LPR se pokazala i ekonomski isplativa ako se uračuna rekurentni tijek bolesti. Čini se da su odgovor na antidepresive SSRI i razvoj nuspojava povezani s polimorfizmom 5-HTT LPR u bijelaca i navedena farmakogenetska analiza bi mogla biti jedna od prvih u budućoj psihijatrijskoj kliničkoj praksi

Antipsychotic Response in the First Week Predicts Later Efficacy

Background and Aims: Time of onset of antipsychotic action is still a debated matter. We aimed to replicate and extend previous findings that early response can predict subsequent non-response. Methods: 86 acutely psychotic patients treated with haloperidol were studied. Results: A PANSS reduction = 23% at 1 week of treatment predicts response at 3 weeks, with a specificity of 84% and a sensitivity of 86%. Conclusion: Our results confirm that an early response to antipsychotic treatment accurately predicts the treatment effectiveness and extends it to a prediction performed as early as 1 week. Copyright (c) 2012 S. Karger AG, Base

Imputed expression of schizophrenia-associated genes and cognitive measures in patients with schizophrenia

Background: Cognitive dysfunction is a core manifestation of schizophrenia and one of the best predictors of long-term disability. Genes increasing risk for schizophrenia may partly act through the modulation of cognition.Methods: We imputed the expression of 130 genes recently prioritized for association with schizophrenia, using PsychENCODE variant weights and genotypes of patients with schizophrenia in CATIE. Processing speed, reasoning, verbal memory, working memory, vigilance, and a composite cognitive score were used as phenotypes. We performed linear regression models for each cognitive measure and gene expression score, adjusting for age, years of education, antipsychotic treatment, years since the first antipsychotic treatment and population principal components.Results: We included 425 patients and expression scores of 91 genes (others had no heritable expression; Bonferroni corrected alpha = 5.49e-4). No gene expression score was associated with cognitive measures, though ENOX1 expression was very close to the threshold for verbal memory (p = 6e-4) and processing speed (p = 7 e-4). Other genes were nominally associated with multiple phenotypes (MAN2A1 and PCGF3).Conclusion: A better understanding of the mechanisms mediating cognitive dysfunction in schizophrenia may help in the definition of disease prognosis and in the identification of new treatments, as the treatment of cognitive impairment remains an unmet therapeutic need

Challenging sequential approach to treatment resistant depression: Cost-utility analysis based on the Sequenced Treatment Alternatives to Relieve Depression (STAR⁎D) trial

In major depression, when a first antidepressant does not cause remission of symptoms (60%–75%), there are several options for continuing treatment in the next step. This study is a cost-utility analysis (CUA) of different second-line approaches. In a simulated trial outpatients with MDD were treated with citalopram for 13 weeks (level 1), then based on two alternative algorithms implemented from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Algorithm A: citalopram was continued until study endpoint (week 26). Algorithm B: patients who remitted during level 1 continued citalopram. Those who did not remit could opt for switching to another antidepressant (venlafaxine; sertraline) (b1) or adding bupropion to citalopram treatment (augmentation; b2). Algorithm B increased remission rate by 10.6% over Algorithm A (number needed to treat: 9.9; sensitivity range: 9.1–12.5). As a comparison, differences between active antidepressants and placebo are associated with NNT values of 6 to 8. In CUA Algorithm B was dominant with an ICER of $11,813 (sensitivity range=$1783 – $21,784), which is <1GDP per capita cost-effectiveness threshold (USA=$47,193). Among Algorithm B options, switching (b1) dominated Algorithm A with a smaller number of responders than augmentation approach (b2) (NNT 11 vs. 7.7), whereas ICER values were similar (b1: $14,738; b2:$15,458). However we cannot exclude a bias in selecting second treatment. This cost-utility analysis shows (in line with current guidelines) a benefit in modifying antidepressant treatment if response to first-line agent does not occur within 3 months, but not a clear-cut evidence in terms of NNT

NCAM1, TACR1 and NOS Genes and Temperament: A Study on Suicide Attempters and Controls

Suicide, one of the leading causes of death among young adults, seems to be plausibly modulated by both genetic and personality factors. The aim of this study was to dissect the potential association between genetics and temperament in a sample of 111 suicide attempters and 289 healthy controls. We focused on 4 genes previously investigated in association with suicide on the same sample: the nitric oxide synthase 1 and 3 (NOS1 and NOS3), the neuronal cell adhesion molecule 1 (NCAM1), and the tachykinin receptor 1 (TACR1) genes. In particular, we investigated whether a set of genetic variants in these genes (NOS1 : rs2682826, rs1353939, rs693534; NOS3 : rs2070744, rs1799983, rs891512; NCAM1 : rs2301228, rs1884, rs1245113, rs1369816, rs2196456, rs584427; TACR1 : rs3771810, rs3771825, rs726506, rs1477157) were associated with temperamental traits at the Temperament and Character Inventory (TCI). No strong evidence was found for the association between TCI personality traits and the polymorphisms considered in the 4 genes, with the exception of an association between reward dependence trait and the rs2682826 SNP in NOS1 in the healthy sample. However, this result could be plausibly interpreted as a false-positive finding. In conclusion, our study did not support the thesis of a direct modulation of these genes on temperament; however, further studies on larger samples are clearly required in order to confirm our preliminary findings and to exclude any possible minor influence. Copyright (C) 2011 S. Karger AG, Base

The dilemma of polypharmacy in psychosis: is it worth combining partial and full dopamine modulation?

Antipsychotic polypharmacy in psychotic disorders is widespread despite international guidelines favoring monotherapy. Previous evidence indicates the utility of low-dose partial dopamine agonist (PDAs) add-ons to mitigate antipsychotic-induced metabolic adverse effects or hyperprolactinemia. However, clinicians are often concerned about using PDAs combined with high-potency, full dopaminergic antagonists (FDAs) due to the risk of psychosis relapse. We, therefore, conducted a literature review to find studies investigating the effects of combined treatment with PDAs (i.e. aripiprazole, cariprazine and brexpiprazole) and FDAs having a strong D-2 receptor binding affinity. Twenty studies examining the combination aripiprazole - high-potency FDAs were included, while no study was available on combinations with cariprazine or brexpiprazole. Studies reporting clinical improvement suggested that this may require a relatively long time (similar to 11 weeks), while studies that found symptom worsening observed this happening in a shorter timeframe (similar to 3 weeks). Patients with longer illness duration who received add-on aripiprazole on ongoing FDA monotherapy may be at greater risk for symptomatologic worsening. Especially in these cases, close clinical monitoring is therefore recommended during the first few weeks of combined treatment. These indications may be beneficial to psychiatrists who consider using this treatment strategy. Well-powered randomized clinical trials are needed to derive more solid clinical recommendations. Copyright (C) 2022 The Author(s). Published by Wolters Kluwer Health, Inc

Genetica dei comportamenti impulsivo-aggressivi: possibile applicazione in psichiatria forense?

Impulsive-aggressive behavior was demonstrated to have a substantial genetic component, thus genetic variants affecting key neuro-modulators of aggressive behavior (in particular, serotonin, dopamine, sex steroids, glucocorticoids and arginin vasopressin) are putative biological markers of violent criminal behavior. From this scenario the hypothesis of engineering genetic tests for application in forensic psychiatry arose, with the aim to define a genetic risk profile which may represent an objective proof and affect chargeability.A number of studies investigated genes involved in the molecular pathways of the reported neuro-modulators, but results were mainly inconsistent or not replicated. Only some genes were quite consistently associated with impulsive-aggressive behavior (SLC6A4 and MAOA, which are pivotal for serotonin balance in the brain), but the explained variance was estimated not over 5% for the genetic variant with the highest evidence of association (5-HTTLPR). The described results reflect the complexity of human traits such as aggressiveness and impulsiveness, which show a biological liability due to multiple genetic variants but are subjected also to a critical influence from the environment (especially during childhood). In conclusion, biological liability due to genetic variants has not a deterministic value for violent criminal conducts. An integrated approach including biological, psychological and social variables seems the most appropriate for the investigation of human motivated behavior, even if the respective contribution of each variable and the best methodology for their investigation are still under discussion.La propensione a comportamenti impulsivo-aggressivi presenta una rilevante base di natura genetica, motivo per cui varianti genetiche riguardanti neuro-modulatori chiave coinvolti nel controllo dell’aggressività (in particolare, serotonina, dopamina, steroidi sessuali, glucocorticoidi e arginina vasopressina) rappresentano possibili marcatori biologici della predisposizione verso condotte criminali violente. Da tale scenario è nata l’ipotesi che fosse possibile realizzare test genetici applicabili in psichiatria forense, in grado di definire un profilo genetico di rischio che potesse rappresentare una prova oggettiva e influire sull’imputabilità.Numerosi studi hanno investigato i geni coinvolti nelle vie molecolari dei neuro-modulatori sopra riportati, ma i risultati ottenuti sono stati per lo più contraddittori o non replicati. Solo alcuni geni sono stati associati con condotte impulsivo-aggressive in modo piuttosto univoco (SLC6A4 e MAOA, che hanno un ruolo chiave nel controllo della neurotrasmissione serotoninergica cerebrale), ma la varianza spiegata è stimata non superiore al 5% per la variante genetica con la maggior evidenza di associazione (5-HTTLPR). I risultati descritti riflettono la complessità di tratti comportamentali quali aggressività ed impulsività, i quali sono caratterizzati da una labilità biologica legata a numerose varianti genetiche ma risentono in larga misura anche dell’influenza dell’ambiente (specialmente durante l’infanzia). In conclusione, i fattori predisponenti biologici non hanno un ruolo deterministico verso lo sviluppo di condotte criminali violente. Un approccio integrato comprendente variabili biologiche, psicologiche e sociali appare il più appropriato all’indagine del comportamento motivato umano, anche se il rispettivo contributo dei citati fattori e la metodologia più appropriata per la loro indagine sono tutt’oggi oggetto di dibattito