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Introduction and aim. 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. Materials and methods. 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. Results. 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. Conclusions. 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.

Introduction: Major depression is a worldwide problem and often remains undetected and untreated. Given the low rates of detection plus the need to intervene in a short time, it is important to identify factors which are likely to improve treatment outcomes. Methods: STIMA-D was designed to provide the profile of patients with major depression in Italy (focusing on pathway to care, patient characteristics, drug therapy and treatment outcomes). The patients enrolled (M/F, aged between 18 and 65) experienced single/multiple episodes of major depression (DSM-IV-TR). Patients with lifetime or current bipolar syndrome or other mental disorders were excluded. Results: 44 of the 50 invited centers sent data concerning 1 140 patients. The majority of patients were women. Among working individuals, 52.5% of them were absent from work due to depression in the previous 6 months. Recurrent episodes of major depression were very common and were associated with persistence of residual post-episodic symptoms, a family history of mood disorders and presence of anxiety. 59.6% of the patients were treated with monotherapy (SSRI or SNRI), while 19.2% of them were treated with SSRI plus SNRI. Only the 25.5% on monotherapy had a complete response compared to 12.4% of patients on dual therapy. Discussion: Poor outcomes in major depression have profound implications on patients’ quality of life and cost burden. New pharmacological approaches with novel modes of action are therefore urgently needed.

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RIASSUNTO. Scopo. Il trattamento del disturbo ossessivo-compulsivo (DOC) prevede l’utilizzo di inibitori della ricaptazione della serotonina (IRS) e della terapia cognitivo-comportamentale (TCC).La revisione si propone di discutere se: a) la terapia combinata ab initio sia una strategia più efficace rispetto alle singole monoterapie; e b) la terapia sequenziale sia efficace nel trattare pazientiresponder con sintomiresidui, e nell’indurre una risposta clinica nei non responder.Metodi. Sono stati utilizzati gli archivi elettronici MEDLINE/PubMed e libri di testo scientifici prendendo in considerazione tutti gli studi clinici controllati randomizzati scritti in inglese.In assenza di questi,sono stati considerati gli studi naturalistici in aperto. Sono stati revisionati 9 studi randomizzati e/o controllati riguardo l’utilizzo della terapia combinata ab initio versusTCC da sola; 6 tra trattamento combinato e IRS da soli. Per il trattamento sequenziale,sono stati considerati 2 studi con pazienti responder e 7 con campioni di pazienti non responder. Risultati. Dei 9 studi, 7 non ne hanno rilevato alcun vantaggio rispetto alla solaTCC, 1 ha evidenziato una maggiore efficacia in pazienti bambini e adolescenti e 1 in pazientiseveramente depressi.Rispetto alla sola farmacoterapia, 4 lavori non hanno rilevato una maggiore efficacia della terapia combinata, mentre 2 studi erano positivi.Tutti glistudisul trattamento sequenziale erano positivi. Discussione. La combinazione ab initio non rappresenta una valida strategia di trattamento in prima istanza nel DOC, a eccezione di pazienti adultiseveramente depressi e pazienti bambini o adolescenti.Al contrario,l’integrazione sequenziale delle due strategie di prima linea è efficace sia nel portare a remissione completa i pazienti con sintomiresiduisia nel determinare una risposta clinica nei pazienti resistenti.

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Objective. The aim of the present study is to analyse the frequency of the different types of insomnia (early, middle and late insomnia) in a sample of patients with Obsessive-Compulsive Disorder (OCD). It also intends to determine whether the presence of a comorbid depressive disorder influences frequency and type of insomnia. Methods. All patients with a primary diagnosis of OCD, consecutively referred to the Mood and Anxiety Disorder Unit, Department of Neuroscience, University of Turin, from January 2000 to December 2004, were recruited. Frequency and severity of the different types of insomnia were evaluated on the basis of the Hamilton Depression Rating Scale (HDRS) specific items scores (item 4-5-6). Aim. Two different analyses were performed with regard to insomnia: 1) OCD patients without any comorbid depressive disorder vs OCD patients with any comorbid depressive disorder; 2) OCD patients without any comorbid depressive disorder vs OCD patients with a comorbid Major Depressive Episode (MDE). Results. The sample included 141 patients. 58.2% suffered from any type of insomnia, especially early insomnia (46.1%). The presence of any comorbid depressive disorder increased the frequency of insomnia up to 67.7% (p=0.041). The presence of a comorbid MDE significantly increased the frequency of late insomnia up to 33.3% (p=0.021). Conclusions. Insomnia, especially the early one, is a common symptom in OCD patients with or without comorbid depressive disorders. Late insomnia is typical of OCD with comorbid major depression.

Per ipomania farmacoindotta si intende un quadro psicopatologico caratterizzato da abnorme elevazione del tono dell’umore ed altri sintomi ipomaniacali determinato da un agente farmacologico. A parte le sostanze psicoattive euforizzanti (quali gli amfetaminici o la cocaina, ad esempio), un quadro ipomaniacale può essere temporalmente in relazione con l’impiego di farmaci quali gli antidepressivi oppure agenti con diverso meccanismo d’azione ma che sono in grado di interferire anche sulle funzioni neurotrasmettitoriali (ad esempio i cortisonici o l’interferone). Sia sul piano clinico che nosografico, l’ipomania farmacoindotta costituisce una questione aperta. Due sono i punti principali non definitivamente chiariti su cui si è accentrata l’attenzione dei ricercatori negli ultimi anni e che tuttavia appaiono ancora oggetto di discussione: 1. i criteri diagnostici per definire tale quadro clinico, in particolare per quanto concerne la differenziazione rispetto alla mania (discorso che vale in generale per tutti i quadri ipomaniacali, anche non in relazione con l’impiego di farmaci), e 2. più specificamente per l’ipomania farmacoindotta, se si tratti di una condizione peculiare in cui il farmaco è a tutti gli effetti l’elemento causale ovvero se si tratti di un quadro di ipomania in cui il farmaco ha al massimo il ruolo di fattore scatenante.

Objective: Obsessive-compulsive disorder (OCD) is a common psychiatric illness with a lifetime prevalence in the general population of approximately 2-3%. Serotonin reuptake inhibitors (SRIs) and cognitive-behavioral 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 very common and the evaluation of next-step treatment strategies is highly relevant. The purpose of this paper is to review available data on treatment-resistant OCD and to build a treatment algorithm for those patients who fail to respond to a first SRI trial. Method: We carried out a search on MEDLINE/PUBMED database, selecting meta-analyses, systematic reviews and randomized controlled studies written in English on treatment-resistant OCD. We also considered open-label studies and case series and/or reports, written in English. We reviewed the available evidence for different strategies and tried to delineate an evidence-based treatment algorithm for clinicians. Results: Antipsychotic addition to SRIs and CBT augmentation of drug treatment both are supported by a number of double-blind studies, although differences between antipsychotics seem to exist and the effectiveness of routinely delivered CBT as an adjunct to medication in real world OCD patients with incomplete response to medication need to be replicated. The switch to IV administration of clomipramine may be clinically useful in some cases, although the return to oral formulation often is associated with a relapse. Switching to other first-line agents or to other compounds (such as venlafaxine) is supported by open-label studies or by double-blind studies without a placebo arm. Conclusions: Several evidence-based effective strategies are available to clinicians in case of treatment-resistant OCD. Strengths and limitations of each of the effective strategies are still under study and will be the focus of future comparative trials. There is also a strong need for alternative therapeutic options for OCD patients.

This multisite study was conducted to compare the efficacy and tolerability of combination treatment with clozapine plus aripiprazole versus combination treatment with clozapine plus haloperidol in patients with schizophrenia who do not have an optimal response to clozapine. Patients continued to take clozapine and were randomly assigned to receive daily augmentation with aripiprazole or haloperidol. Physicians prescribed the allocated treatments according to usual clinical care. Withdrawal from allocated treatment within 3 months was the primary outcome. Secondary outcomes included severity of symptoms on the Brief Psychiatric Rating Scale and antipsychotic subjective tolerability on the Liverpool University Neuroleptic Side Effect Rating Scale. A total of 106 patients with schizophrenia were randomly assigned to treatment. After 3 months, we found no difference in the proportion of patients who discontinued treatment between the aripiprazole and haloperidol groups (13.2% vs 15.1%, P = 0.780). The 3-month change of the Brief Psychiatric Rating Scale total score was similar in the aripiprazole and haloperidol groups (-5.9 vs -4.4 points, P = 0.523), whereas the 3-month decrease of the Liverpool University Neuroleptic Side Effect Rating Scale total score was significantly higher in the aripiprazole group than in the haloperidol group (-7.4 vs -2.0 points, P = 0.006). These results suggest that augmentation of clozapine with aripiprazole offers no benefit with regard to treatment withdrawal and overall symptoms in schizophrenia compared with augmentation with haloperidol. However, an advantage in the perception of adverse effects with aripiprazole treatment may be meaningful for patients.

BackgroundDespite depressive disorders being very common there has been little research to guide primary care physicians on the choice of treatment for patients with mild to moderate depression.AimsTo evaluate the efficacy of interpersonal counselling compared with selective serotonin reuptake inhibitors (SSRIs), in primary care attenders with major depression and to identify moderators of treatment outcome.MethodA randomised controlled trial in nine centres (DEPICS, Australian New Zealand Clinical Trials Registry number: ACTRN12608000479303). The primary outcome was remission of the depressive episode (defined as a Hamilton Rating Scale for Depression score 7 at 2 months). Daily functioning was assessed using the Work and Social Adjustment Scale. Logistic regression models were used to identify moderators of treatment outcome.ResultsThe percentage of patients who achieved remission at 2 months was significantly higher in the interpersonal counselling group compared with the SSRI group (58.7% v. 45.1%, P = 0.021). Five moderators of treatment outcome were found: depression severity, functional impairment, anxiety comorbidity, previous depressive episodes and smoking habit.ConclusionsWe identified some patient characteristics predicting a differential outcome with pharmacological and psychological interventions. Should our results be confirmed in future studies, these characteristics will help clinicians to define criteria for first-line treatment of depression targeted to patients' characteristics.

AB Background: An autoimmune hypothesis has been suggested for a subtype of Obsessive-Compulsive Disorder (OCD); this hypothesis was investigated particularly in children, while only two studies assessed samples of adult patients. Aim of the study: To evaluate in a sample of adult OCD patients: a) the proportion of subjects with antibodies directed towards neuronal structures; b) with high ASLO titers and/or with markers of autoimmunity measured in the practice of neurology and internal medicine. Materials and methods: 74 OCD patients consecutively referred to the Mood and Anxiety Disorders Unit, Department of Neuroscience, University of Turin were recruited; as control group, 44 patients with a current major depressive episode consecutively referred to the same Unit were recruited. Structured and semi-structured interviews were used to collect data. Anti-brain antibodies were tested by immunohistochemistry and western-blotting methods. Results: 5.4% of the OCD sample resulted positive for anti-brain antibodies and there was an association with an earlier onset of symptoms. 10.3% of OCD subjects had high mean ASLO titers and this was correlated with a pre-pubertal onset of symptoms. No other significant differences in antibody parameters were found. Conclusions: In a small proportion of OCD patients autoimmune reactions towards neuronal structures are present. Further investigations are needed to demonstrate a possible autoimmune etiopathogenesis in this subtype of OCD, in order to open new therapeutic scenarios.

The "Remission Project" proposed the concept of symptom remission to the community of Italian psychiatrists to test the degree of its acceptance and to edit a National consensus document on the concept's validity and criteria in the Italian clinical context. During some meetings, the scientific Committee addressed the project's teaching material (literature review, handbook for working remission criteria, a DVD containing six clinical interviews aimed at assessing remission criteria) (Table I). During a first stage, such material has been discussed and shared with other 54 psychiatrists and, at a second stage, presented by these psychiatrists to more than 500 Italian psychiatrists in 20 different locations widely distributed in the national territory (Table II). The "Remission Project" represented an initiative of great impact at the teaching level, showing the need for continuous updating of the italian scientific community on issues that would have important research and clinical implications. Participants' attitudes were characterised by attention focused on the proposed contents, active participation in discussion, and critical, constructive observations (Tables III, IV). Update programmes focused on symptom remission, and social and cognitive functioning, could represent the ideal continuation of the initiative.