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In Italy, Public Law n. 81/2014 promotes innovative, recovery-oriented, rehabilitative treatment for people with mental disorders who have committed a criminal offense, without criminal intention, but who are, nonetheless, regarded as socially dangerous. A relevant innovation was in the transfer of responsibilities and management of care from the Ministry of Justice to the Ministry of Health. The reduction of the number of beds during the transition from Forensic Psychiatric Hospitals (OPG) to Residences for the Execution of Security Measures (REMS) led to a waiting list; the intention to carry out community projects on patients who already had a REMS entry order led to friction between the legal system and the health system. Based on the experience in the Piedmont Region concerning the handling of mentally disordered offenders, the factors influencing the contrasts between the legal system and the health system have been examined: management of facilities by the regional health system and governance of the security measures by the Judiciary, extensive use of diminished responsibility, functions of the old OPGs not passed on to the REMS. The experience of managing the waiting list in Piedmont has revealed ways of dealing with these critical issues, but there is still a need for further organizational and, above all, legislative innovations.

The closing of six forensic psychiatric hospitals (OPG-Ospedali Psichiatrici Giudiziari) in Italy completed the long transition to a psychiatric community model of treatment. From 2014 to 2017, 20-bed, secure, community forensic residential facilities (REMS) were built and activated by regional health authorities in Italy, where people with mental disorders who committed a criminal offense, without criminal responsibility but still considered socially dangerous, must be treated. The REMS are health facilities where healthcare workers encourage inpatients to participate in a recovery-oriented rehabilitation project in order to return them to local services as soon as possible. Many difficulties obstruct the road to rehabilitation: interaction between the judicial and the healthcare sectors and among healthcare workers inside and outside the REMS; characteristics of the inmates and their level of collaboration; and lack of a penal code befitting the new situation. In this chapter, the authors describe the risks of violent behavior and the manner in which it must be avoided and managed in the two REMS of the Piedmont region. Following a request by the healthcare workers, an internal, unarmed guard was added to the staff. This guard participates in rehabilitation activities with the patients, reducing risk of injuries in the forensic residential facilities.

The essential feature of generalized anxiety disorder (GAD) is excessive anxiety and worry (apprehensive expectation) about a number of events or activities associated with other psychological and physical symptoms (see DSM-5 criteria). Diagnostic criteria for generalized anxiety disorder (GAD) (DSM-5): A.Excessive anxiety and worry (apprehensive expectation), occurring more days than not for at least 6 months, about a number of events or activities (such as work or school performance). B.The individual finds it difficult to control the worry. C.The anxiety and worry are associated with three (or more) of the following six symptoms (with at least some symptoms having been present for more days than not for the past 6 months): Note: Only one item is required in children. 1) Restlessness or feeling keyed up or on edge; 2) being easily fatigued; 3) difficulty concentrating or mind going blank; 4) irritability; 5) muscle tension; 6) sleep disturbance (difficult falling or staying asleep, or restless, unsatisfying sleep). D.The anxiety, worry, or physical symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. E. The disturbance is not attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication) or another medical condition (e.g., hyperthyroidism). F. The disturbance is not better explained by another mental disorder (e.g., anxiety or worry about having panic attacks in panic disorder, negative evaluation in social anxiety disorder [social phobia], contamination or other obsessions in obsessive-compulsive disorder, separation from attachment figures in separation anxiety disorder, reminders of traumatic events in posttraumatic stress disorder, gaining weight in anorexia nervosa, physical complaints in somatic symptom disorder, perceived appearance flaws in body dysmorphic disorder, having a serious illness in illness anxiety disorder, or the content of delusional beliefs in schizophrenia or delusional disorder).

Atypical antipsychotics (AAs) may play a role in the treatment of anxiety disorders, obsessive-compulsive disorder (OCD), and trauma-related disorders. No reviews on their differential use in these different disorders have been performed recently. The aim of this systematized review was to obtain data on efficacy and comparative effectiveness of AAs as a treatment of anxiety disorders, OCD, and trauma-related disorders to provide guidance for clinicians on when and which AA to use. We searched on PubMed, Psychnet, and Cochrane Libraries from inception to July 2015. Search results were limited to randomized, placebo-controlled trials of adult patients. Evidence of efficacy was considered the presence of positive results in two or more double-blind placebo-controlled studies. Our systematized search identified 1298 papers, of which 191 were subjected to a full-text review and 56 were included. Quetiapine extended-release showed a role in both acute and maintenance treatment of uncomplicated generalized anxiety disorder, whereas more studies are needed before drawing practical recommendations on the use of olanzapine and risperidone; aripiprazole and risperidone are effective in resistant OCD as augmentation treatments. Risperidone and olanzapine add-on may have a role in resistant or chronic post-traumatic stress disorder patients, although only risperidone addition can be recommended on the basis of the criterion of two or more positive placebo- controlled trials. This systematized review supports the evidence that only a few AAs are effective in only a minority of the off-label conditions in which they are currently used and confirms that AAs are not all the same. Their use should be on the basis of a balance between efficacy and side effects, and the characteristics as well as the preference of the patient.

La depressione maggiore rappresenta una categoria diagnostica molto eterogenea, in cui convergono quadri clinici che possono essere molto diversi tra loro. Questa eterogeneità rappresenta una sfida per il clinico (che di fronte alla diagnosi di disturbo depressivo maggiore necessita di ulteriori sottotipizzazioni per poter correttamente identificare la strategia terapeutica più efficace), ma rappresenta anche un grave impedimento per il ricercatore, nel momento in cui si cercano di identificare fattori di rischio (genetici e ambientali), fattori scatenanti e fattori protettivi per lo sviluppo di tale disturbo. Questa mancanza di specificità della diagnosi deriva in parte dalla storia della nosografia del concetto di depressione unipolare (creato in antitesi a quello del disturbo bipolare, DB), e ha determinato la spinta a ricercare aspetti clinici e/o di decorso che potessero indirizzare la scelta tra gli antidepressivi. Sono così stati recuperati indicatori clinici (ad esempio la presenza di quadri sintomatologici intraepisodici specifici), che il DSM-5 chiama specificatori, con la speranza di identificare sottogruppi più omogenei di pazienti responsivi a specifici trattamenti antidepressivi e/o caratterizzati da una prognosi diversa (ad esempio ad aumentato rischio suicidario). Molti dei sottotipi di depressione proposti derivano da un’ampia e storica letteratura (vedasi la depressione con caratteristiche melanconiche o atipiche); per alcuni dei sottotipi vi è maggiore consenso circa l’opportunità di indirizzi terapeutici specifici (ad esempio associazione tra antidepressivo e antipsicotico per la depressione maggiore con caratteristiche psicotiche) così come per altri vi è un consenso generale sul significato clinico prognostico (ad esempio depressione maggiore con ansia associata ad aumentato rischio suicidario; depressione maggiore con caratteristiche miste associata ad aumentato rischio suicidario e di conversione a DB franco nel follow-up). La ricerca di sottotipi e/o di caratteristiche specifiche che possano indirizzare la scelta dell’antidepressivo e/o portare luce sui meccanismi patogenetici della depressione prosegue, con alcune recenti acquisizioni che non sono ancora recepite dai sistemi classificatori attualmente in uso: ad esempio, la recente attenzione posta alla depressione con sintomi cognitivi rilevanti rappresenta un progresso per il clinico nel momento in cui indirizza la scelta di antidepressivi con azione specifica su tale componente sintomatologica. La vortioxetina, antidepressivo ad azione multimodale, si è rivelata estremamente efficace, in particolar modo su tale sottotipo di depressione.

Background: second-generation (“atypical”) antipsychotics are widely used for the treatment of bipolar disorder, although they may be associated, to a different degree, according to the specific antipsychotic, with metabolic side effects. The aim of this study is to review the available literature on clinical and therapeutic strategies to manage metabolic syndrome in patients with bipolar disorder. Subjects and methods: a PubMed/Medline research was performed on papers with regards to metabolic adverse events induced by second-generation antipsychotics in bipolar disorder. Articles published from 1st January 1990 to 31st January 2015 were selected. Results: the following issues were discussed: a) identification of patients at risk for developing metabolic side effects (the following clinical features were found associated with an increased risk: young males, older subjects at baseline, and patients in treatment with olanzapine or risperidone both in the short and long-term); b) monitoring metabolic parameters such as cholesterol, triglycerides, glycated hemoglobin, body mass index, waist circumference, weight: bipolar patients taking atypical antipsychotics should be monitored more carefully in the first year of treatment; c) managing the antipsychotic treatment with regard to metabolic side effects (e.g. switching strategies); non-pharmacological interventions aimed at promoting regular lifestyles, in particular ABCDE approach promoted by Johns Hopkins Hospital. Conclusions: psychiatrists or general practitioners may consider the aforementioned strategies in order to limit the metabolic side effects induced by atypical antipsychotics in patients with bipolar disorder. Future researches should try to identify genetic risk factors associated with the onset of metabolic side effects in order to predict the onset of this phenomenon.

Introduction: Obsessive-Compulsive Disorder (OCD) is a common psychiatric illness with lifetime prevalence in the general population of approximately 2-3%. Serotonin Reuptake Inhibitors (SRIs) and CognitiveBehavioral Therapy (CBT) in the form of Exposure and Response Prevention (ERP) both represent first-line treatments for OCD. However, unsatisfactory response to these treatments is common and the evaluation of next-step treatment strategies is highly relevant. Antipsychotic augmentation is the most studied pharmacological strategy. The purpose of this review is to provide guidance regarding the choice of antipsychotic medication on the basis of current evidence. Material and Methods: We carried out a search on MEDLINE/PUBMED database, selecting meta-analyses, systematic reviews and randomized controlled studies written in English on antipsychotic augmentation of treatment resistant OCD. We also considered open-label studies and case series, written in English. We reviewed the available evidence for antipsychotic use in treatment-resistant-OCD. Results: Antipsychotic addition to SRI treatment is supported by a positive number of double-blind studies although differences between them seem to exist. Fourteen double blind, randomized, placebo controlled trials investigating quetiapine (N=5), risperidone (N=3), olanzapine (N=2), aripiprazole (N=2), haloperidol (N=1), paliperidone (N=1) were identified. Significant efficacy was identifiable for risperidone and aripiprazole but not for quetiapine and olanzapine. Results regarding haloperidol and paliperidone were inconsistent. Discussion: Overall, about 50% of SRI-resistant-OCD patients benefited from augmentation strategy with antipsychotic. Risperidone and aripiprazole can be considered as the agents of first choice and should be preferred to the others antipsychotic. In our opinion, olanzapine may be a valid alternative to risperidone. Further trials are required to optimize pharmacological treatment for SRI-resistant-OCD.

Riassunto Introduzione Nei pazienti affetti da disturbo ossessivo-compulsivo (DOC) la comparsa di manifestazioni psicopatologiche di tipo bipolare costituisce un rilevante problema clinico con importanti conseguenze a livello sia prognostico sia terapeutico, con tassi di comorbilita tra i due disturbi che arrivano fino al 30%. Lo scopo del presente studio e quello di evidenziare le differenze sociodemografiche e cliniche tra i pazienti affetti da DOC con e senza disturbo bipolare associato, con l’obiettivo di identificare possibili predittori che orientino nelle scelte terapeutiche. Materiali e metodi Il campione, composto da pazienti con diagnosi principale di DOC, viene suddiviso per il confronto in un gruppo con DOC “puro” e in uno con associato disturbo bipolare. Risultati Il campione e costituito da 290 pazienti affetti da DOC, di cui 259 senza disturbo bipolare associato e 31 con disturbo bipolare. Il profilo sociodemografico e clinico dei pazienti che presentano disturbo bipolare in associazione a DOC e caratterizzato da maggiore frequenza nel sesso maschile, piu rilevante familiarita per disturbi dell’umore, piu frequenti ossessioni sessuali e di accumulo e compulsioni di ripetizione e accumulo. Inoltre, emerge come significativa l’associazione con disturbo da uso di sostanze e, per quanto riguarda la comorbilita di Asse II, con disturbo ossessivo-compulsivo di personalita. Conclusioni I risultati emersi evidenziano specifiche differenze tra i soggetti affetti da DOC con o senza disturbo bipolare in comorbilita e indirizzano verso la possibile identificazione di sottogruppi di pazienti DOC con caratteristiche specifiche, con possibili differenti basi eziopatogenetiche e per i quali e necessario studiare specifici approcci terapeutici.

Background Lithium is recommended as a first-line treatment for Bipolar Disorder (BD). Thyroid and renal alterations are well known lithium side-effects, while effects on parathyroids are less studied. The aim of this case-control cross-sectional study is to compare parathyroid hormone (PTH) and calcium levels in lithium-exposed bipolar patients and in subjects who had never been exposed to lithium. Methods 112 BD patients were enrolled, 58 on lithium since at least 1 month (mean exposure 60.8±74.8 months) and 54 in the control group. Blood exams included complete blood count, PTH, total and ionized calcium, TSH, T3 and T4, creatinine, urea, sodium and potassium, and lithium serum levels. The Student's t-test and the Pearson's Chi-square test were used for bivariate analyses. A linear regression model was used to analyze the relationship between the duration of exposure to lithium and PTH and calcium levels. Results PTH and ionized calcium levels were significantly higher in lithium-exposed patients; the proportions of subjects with hyperparathyroidism (8.6%) and hypercalcaemia (24.1%) were significantly greater in lithium-exposed patients. The linear regression analyses showed a significant effect of exposure to lithium in months on ionized calcium levels but not on PTH levels. Limitations Given the cross-sectional design of the study we could not identify the exact time of occurrence of hyperparathyroidism. Conclusions Our results indicate that lithium-associated stimulation of parathyroid function is more common than assumed to date. Among parameters to be evaluated prior to lithium implementation and during long-term lithium maintenance, calcium (and eventually PTH) should be added.

Background Recent evidence indicates the possible involvement of adenosine and the purinergic system in the pathophysiology of bipolar disorder (BD). The aim of this study is to compare serum uric acid (UA) levels in a large group of BD patients (in mania, depression and euthymia) vs. a control group of patients with different psychiatric disorders. Methods 150 BD (SCID-I; DSM-IV) patients were compared to 150 age- and gender-matched subjects with MDD, OCD, or Schizophrenia. Mean serum UA values were compared with the ANOVA, with Bonferroni׳s post-hoc tests. Results Mean serum UA levels (5.06±1.45 vs. 4.17±1.05 mg/dL) and rates of hyperuricaemia (30.7% vs. 6.7%) were significantly higher in the bipolar than in the control group. No differences were detected between bipolars in different phases of illness, with all three groups (manic, depressive and euthymic bipolars) showing significantly higher UA levels as compared to controls. No correlations were found between UA levels and YMRS or HAM-D scores. Mean UA levels were also higher in bipolars never exposed to mood stabilizers vs. controls (5.08±1.43 vs. 4.17±1.05 mg/dL), with no differences compared to other bipolars. Limitations Our study suffers from the lack of a healthy comparison group; moreover, longitudinal data are missing. Conclusions Our study provides further evidence of a purinergic dysfunction associated with BD, in all phases of the illness. It is possible that increased UA levels are a trait marker of higher vulnerability to bipolar disorder, and are even more increased during mania (mostly in the first manic episode of drug-naive patients).

Background Specific dysfunctional beliefs have been identified as candidate endophenotypes for Obsessive–Compulsive Disorder (OCD). Rector, Cassin, Richter, and Burroughs (2009) investigated cognitive vulnerability for OCD and their results support both the notion of familial-based origin of obsessive beliefs, and the hypothesis that inflated responsibility/overestimation of threat, could represent candidate endophenotypes for OCD. Aims The primary aim of this study was to replicate previous findings of a familial cognitive vulnerability for OCD. The secondary purpose was to test the hypothesis that obsessive beliefs of patients with OCD and those of their first-degree relatives (FDRs) are correlated, supporting dysfunctional beliefs as candidate endophenotypes for OCD. Method 65 patients with DSM-IV-TR (SCID-I) OCD were included together with one healthy FDR. 77 non-affected FDRs of patients with Bipolar Disorder were enrolled as a control group. Obsessive beliefs were measured with the OBQ-44. Results First-degree relatives of subjects with OCD scored significantly higher than controls on the total score and on the domain tapping inflated responsibility and overestimation of threat. There was no significant correlation between each obsessive belief in patients with OCD and their non-affected FDRs. Conclusions Our study provides evidence of a specific cognitive vulnerability for OCD in FDRs of probands with OCD.

Lithium is recommended by all treatment guidelines for bipolar disorder (BD) as a first-line maintenance treatment. However, the potential side effects and risks associated with long-term lithium use may at times make the implementation of these recommendations in daily practice challenging. The aim of the study is to review available literature on potential long-term side effects of lithium.A PubMed/Medline search was performed on papers dealing with long-term treatment with lithium and side effects. Articles published from January 1980 to February 2013 were selected.Long-term lithium treatment is associated with a reduced urinary concentrating ability, with subsequent polyuria and polidypsia and nephrogenic diabetes insipidus (in 10-40% of patients). Lithium also reduces glomerular filtration rate, and increases risk of renal failure, although the absolute risk is small (0.5% of patients). Lithium treatment is associated with significant higher TSH levels, with a 6-fold greater risk of hypothyroidism in lithium-treated than in control subjects. Less known is the increase of PTH and calcium levels induced by lithium. An exacerbation of psoriasis is also frequently associated with lithium treatment.Lithium remains a fundamental tool for the treatment of BD. Clinicians should know potential side effects (renal, endocrine and dermatological) associated with long-term treatment with lithium, for a correct management of the patient. A specialist referral is often necessary; the question is how to deal with long-term side effects more than whether or not withdrawing lithium. This decision should remain a psychiatrist's competence.

Riassunto Obiettivi Il disturbo ossessivo-compulsivo (DOC) presenta un’eterogeneita clinica con sottotipizzazioni proposte sulla base della sintomatologia prevalente, del decorso (episodico vs cronico), dell’eta d’esordio (precoce vs tardiva) e della comorbilita (tic, disturbo bipolare). Anche il genere e stato proposto come sottotipizzazione. Scopo del presente studio e valutare le differenze sociodemografiche e cliniche legate al genere in un ampio campione di pazienti. Materiali e metodi 415 pazienti con diagnosi principale di DOC sono stati inclusi e valutati tramite intervista semistrutturata. La valutazione clinica e stata effettuata mediante: Y-BOCS; HAM-D; HAM-A; scala di Paykel; SCID-II. Le variabili sociodemografiche e cliniche sono state confrontate tra i due sessi. Risultati I maschi, 217 (52,3%), avevano un esordio piu precoce dei sintomi e una comorbilita maggiore per disturbo bipolare. Inoltre avevano un’associazione significativa con ossessioni sessuali e compulsioni di ripetizione. Le femmine, invece, presentavano sintomi di tipo “washer”, maggiore comorbilita con depressione minore, con disturbi del comportamento alimentare e, infine, un’associazione significativa tra la presenza di un evento di vita stressante e l’esordio dei sintomi ossessivo-compulsivi. Discussione I dati, confermati da altri studi, suggeriscono che il DOC assume caratteristiche tipiche nei due sessi, ma le differenze non supportano l’idea di tipizzare il DOC in base al genere. Le differenze sembrano riferibili ad altri elementi (eta d’esordio) che, in futuro, potrebbero essere piu utili a identificare fattori genetici e ambientali predisponenti e strategie terapeutiche specifiche.

Riassunto Introduzione Il disturbo bipolare (DB) e una patologia cronica che puo alterare significativamente il funzionamento e la qualita di vita di chi ne e affetto e di coloro che se ne prendono cura. Poiche la terapia farmacologica con stabilizzatori del tono dell’umore, trattamento di prima scelta per questo disturbo, non e sempre sufficiente a garantire il raggiungimento di un completo recupero sintomatico e funzionale, negli ultimi anni sono stati proposti e validati interventi psicosociali di varia natura da associare a tale intervento terapeutico. Materiali e metodi Il presente articolo effettua una revisione sistematica degli studi, pubblicati tra il 1984 e il 2010, relativi a modelli di intervento psicosociale che si sono dimostrati efficaci in associazione alla terapia farmacologica nel trattamento del DB. Risultati Gli interventi psicosociali specifici per il trattamento del DB hanno mostrato una documentata efficacia nel ridurre, a lungo termine, il numero delle ricorrenze. L’effetto specifico sulle ricorrenze maniacali o depressive varia a seconda del tipo di intervento: gli interventi psicoeducazionali individuali sono efficaci nel ridurre il numero di ricorrenze maniacali e non depressive; gli interventi focalizzati sulla famiglia e la terapia cognitivo-comportamentale sembrano maggiormente efficaci nel ridurre la sintomatologia depressiva; gli interventi psicoeducazionali di gruppo, infine, sembrano efficaci nel ridurre le ricorrenze di entrambe le polarita.

Umberto Albert,1 David De Cori,1 Andrea Aguglia,1 Francesca Barbaro,1 Fabio Lanfranco,2 Filippo Bogetto,1 Giuseppe Maina3 1Anxiety and Mood Disorders Unit, Rita Levi Montalcini Department of Neuroscience, University of Turin, Torino, Italy; 2Division of Endocrinology, Diabetology and Metabolism, Department of Medical Sciences, University of Turin, Torino, Italy; 3Department of Mental Health, San Luigi-Gonzaga Hospital, University of Turin, Orbassano, Italy Objective: The aim of this retrospective longitudinal naturalistic study was to evaluate the effects of maintenance lithium treatment on parathyroid hormone (PTH) and calcium levels. Methods: A retrospective longitudinal naturalistic study design was used. Data were collected from the database of a tertiary psychiatric center covering the years 2010–2014. Included were bipolar patients who had never been exposed to lithium and had lithium started, and who had PTH, and total and ionized calcium levels available before and during lithium treatment. Paired t-tests were used to analyze changes in PTH and calcium levels. Linear regressions were performed, with mean lithium level and duration of lithium exposure as independent variables and change in PTH levels as dependent variable. Results: A total 31 patients were included. The mean duration of lithium treatment was 18.6±11.4 months. PTH levels significantly increased during lithium treatment (+13.55±14.20 pg/mL); the rate of hyperparathyroidism was 12.9%. Neither total nor ionized calcium increased from baseline to follow-up; none of our patients developed hypercalcemia. Linear regressions analyses did not show an effect of duration of lithium exposure or mean lithium level on PTH levels. Conclusion: Lithium-associated stimulation of parathyroid function is more common than assumed to date. Among parameters to be evaluated prior to lithium implementation, calcium and PTH should be added. Keywords: bipolar disorder, follow-up study, lithium side-effects&nbsp