Italian guidance on Dementia Day Care Centres: A position paper.

Dementia Day Care Centres (DDCCs) are defined as services providing care and rehabilitation to people with dementia associated with behavioural and psychological symptoms (BPSD) in a semi-residential setting. According to available evidence, DDCCs may decrease BPSD, depressive symptoms and caregiver burden. The present position paper reports a consensus of Italian experts of different disciplines regarding DDCCs and includes recommendations about architectural features, requirements of personnel, psychosocial interventions, management of psychoactive drug treatment, prevention and care of geriatric syndromes, and support to family caregivers. DDCCs architectural features should follow specific criteria and address specific needs of people with dementia, supporting independence, safety, and comfort. Staffing should be adequate in size and competence and should be able to implement psychosocial interventions, especially focused on BPSD. Individualized care plan should include prevention and treatment of geriatric syndromes, a targeted vaccination plan for infectious diseases including COVID-19, and adjustment of psychotropic drug treatment, all in cooperation with the general practitioner. Informal caregivers should be involved in the focus of intervention, with the aim of reducing assistance burden and promoting the adaptation to the ever-changing relationship with the patient.

Italian psychiatrists' perception on cognitive symptoms in major depressive disorder.

OBJECTIVE: Differently than Schizophrenia, the investigation of cognitive impairment in bipolar disorder and major depressive disorder (MDD) attracted the interest of research only recently. Therefore, it is worth understanding clinicians' perception about cognitive dysfunction in MDD and raising awareness about this issue. METHODS: Between December 2014 and January 2015, 128 Italian psychiatrists participated in an on-line survey aiming at understanding psychiatrists' perception about cognitive symptoms in MDD. The questionnaire comprised three sections: the first investigating psychiatrists' socio-demographic profile, the second assessing cognitive symptoms relevance without mentioning that they represented the study focus and the third explicitly investigating cognitive symptoms. RESULTS: Cognitive symptoms were considered as a relevant dimension of MDD and appeared among the most frequently cited residual symptoms influencing patients' work and relapse risk. About 70% of psychiatrists declared that cognitive symptoms significantly influence antidepressant choice. However, in the second questionnaire section cognitive symptoms appeared less frequently considered for antidepressant choice. CONCLUSIONS: Results revealed a clear understanding of cognitive symptoms relevance in MDD. Nevertheless, the discrepancy between psychiatrists' perception and their therapeutical choices underlines the presence of an unmet-need that should be addressed increasing the awareness about the positive effects on cognitive symptoms of existing drugs, which could allow a more symptom-oriented therapeutical intervention. Key points Major depressive disorder (MDD) is a common mental disorder often associated with deficits in cognitive function. Psychiatrists considered cognitive symptoms among the most relevant residual symptoms in MDD patients that compromise patients working and influence the relapse risk. The importance given to residual cognitive symptoms seemed not to be reflected by psychiatrists' therapeutical choice. There is a gap between what psychiatrists know and what psychiatrists apply to their clinical practice reflecting the feeling of a therapeutical unmet need.

Discriminative hypomania checklist-32 factors in unipolar and bipolar major depressive patients.

BACKGROUND: Although manic or hypomanic episodes define bipolar disorder (BD), most patients show a predominance of depressive symptomatology, often associated with delayed or disregarded BD diagnosis. The Hypomania Checklist-32 (HCL-32) has therefore been developed and tested internationally to facilitate BD recognition. SAMPLING AND METHODS: Five hundred seventy-one (563 eligible) patients diagnosed with a major depressive episode according to DSM-IV criteria were consecutively enrolled in a cross-sectional, multicenter, observational study (Come To Me). Lifetime manic or hypomanic features were assessed by the HCL-32, and severity of depressive and anxious symptomatology was assessed using the Zung's self-report questionnaires for depression and anxiety. RESULTS: Among the patients diagnosed with BD (n = 119), either type I or type II, the occurrence of (hypo)manic symptoms was significantly higher compared to major depressive disorder (MDD) symptoms according to HCL-32 total and subscale scores obtained using a score of 14, which ensured an optimal discrimination between BD and MDD with a sensitivity of 0.85 and a specificity of 0.78. CONCLUSIONS: Although some false positives might occur, the HCL-32 was confirmed to be a useful instrument in the detection of past hypomania in MDD patients, finally contributing to proper therapeutic choices.

Unexplained somatic symptoms during major depression: prevalence and clinical impact in a national sample of Italian psychiatric outpatients.

BACKGROUND: The aim of this study was to explore the prevalence and impact of unexplained somatic symptoms during major depression. SAMPLING AND METHODS: A total of 560 consecutive outpatients with a major depressive episode according to the DSM-IV (text revision) were evaluated in 30 psychiatric facilities throughout Italy. 'Unexplained' somatic symptoms were evaluated using the 30-item Somatic Symptoms Checklist (SSCL-30). Somatic symptoms were considered explained if they were best accounted for as coming from a concomitant physical illness or side effects. Patients evaluated their own mood symptomatology using the Zung questionnaires for depression and anxiety and the Hypomania Checklist-32. RESULTS: According to the SSCL-30, only 90 subjects (16.1%) had no unexplained somatic symptoms, while 231 (41.3%) had 1-5 unexplained symptoms and 239 (42.7%) had more than 5. Asthenia was the most commonly observed unexplained somatic symptom (53% of patients). Unexplained somatic symptoms were more common in females and among those suffering from major depression and depression not otherwise specified rather than in patients with recurrent major depression and bipolar disorders. No relationship between unexplained somatic symptoms and hypomanic features was observed. CONCLUSIONS: The presence of a large number of unexplained somatic symptoms is associated with more severe depression and higher rates of misdiagnosis and inappropriate treatment.

[Lamotrigine in bipolar disorder: preventing depression to treat the disease]. / Lamotrigina nel disturbo bipolare: prevenire la depressione per curare la malattia.

PURPOSE: The aim of this paper is to critically ascertain the effectiveness of lamotrigine (LTG) as a key strategy for the treatment of bipolar I disorder. METHODS: PubMed and Cochrane Library databases were searched using the following keywords: "lamotrigine" AND "bipolar disorder", "psychotic" or "mood disorder". RESULTS: Lamotrigine, has shown significant efficacy in preventing or delaying the onset of depressive episodes in bipolar disease. The standard final dose is 200 mg/day to be achieved with slow titration. The concomitant use of LTG and valproic acid requires a reduction of the standard final dosage of LTG to 100 mg/day in order to prevent the occurrence of adverse reactions, while an increase in the dosage of LTG (up to a maximum of 400 mg/day) is required in the case of concomitant use of enzyme inducers, such as carbamazepine. Lamotrigine is well tolerated and has a relatively low risk of side effects. Slow titration and accurate monitoring in the first weeks of treatment are necessary in order to reduce the risk of adverse events, such as severe skin rash, whose onset is however rare in the adult population (0.1%). It is possible to use LTG during pregnancy, breastfeeding or in subjects with liver or kidney disorders, following a preliminary assessment of the risk-benefit ratio. CONCLUSIONS: Lamotrigine is suitable for preventing or delaying the onset of depressive episodes in patients with bipolar I disorder, and has a high level of tolerability. Prevention of depression determines stabilization of bipolar disease and may contribute to a better overall outcome in patients with predominantly depressive episodes. In patients with a clinical history characterized by severe and repeated manic episodes, it is advisable to combine LTG with an antimanic agent (e.g. lithium or second generation antipsychotic) even in the maintenance phase. Lamotrigine is a valid therapeutic option in the long-term prevention and stabilization of the depressive phases in patients with bipolar I disorder.

[Personalized medicine with extended-release trazodone and/or once-a-day trazodone: from research trials to clinical practice]. / Medicina personalizzata con trazodone a rilascio prolungato e/o trazodone "once-a-day": dai trial di ricerca alla pratica clinica.

AIM: This paper belongs to a series of three manuscripts examining the clinically relevant evidence about the use of trazodone in major depressive disorder (MDD). One of the papers provides general clinical guidance for the use of trazodone MDD. Another paper evaluates the clinically relevant evidence pertaining to the use of trazodone in MDD with insomnia, and the present manuscript evaluates the properties of prolonged release trazodone (T-RP) and trazodone once-a-day (T-OAD), to identify the characteristics of patients that may benefit from the use of one of the formulations. METHODS: PubMed and Cochrane Library were searched for English language papers by using combinations of the following key words: trazodone, once-a day, prolonged release, extended release, slow release. United States, European and Italian Medicine Agency prescribing information for trazodone were consulted as well. RESULTS: Trazodone is a multifunctional drug, characterized by different affinities for specific receptors and transporters. Clinical efficacy on specific symptoms is influenced by pharmacokinetic aspects and variables such as the dose and the formulation that is prescribed and taken. T-RP can be particularly useful in the treatment of patients with mild or moderate depression, who show sleep disturbance and/or moderate or severe anxiety symptoms and who can benefit - in particular periods of the day or night (e.g. in the phase of falling asleep or during periods of increased anxiety-agitation), of peak blood concentration, which are higher than those of T-OAD. T-OAD appears particularly indicated for patients with moderate or severe depression, who show mild or moderate sleep and/or anxiety disorders, who have late insomnia (insomnia in the final part of sleep, i.e. early morning awakening), and who can benefit from the possibility of starting the drug at a dose that is already potentially effective (150 mg) for depressive symptoms. This dose can be then increased to 300 mg, and prescribed in the evening and once a day, which potentially improves treatment adherence. DISCUSSION: The different formulations of trazodone allow a personalization of the treatment, which may be targeted to the specific needs of each patient.

Clinical guidance for the use of trazodone in major depressive disorder and concomitant conditions: pharmacology and clinical practice.

AIM: To provide a review of the clinically relevant evidence pertaining to the use of trazodone in major depressive disorder. METHODS: Medline and Cochrane Library searches were searched using the keywords 'trazodone' AND 'depression', to identify the most relevant literature pertinent to the pharmacological properties of trazodone and its use in clinical practice. Articles that were selected included basic pharmacology papers, clinical trials, clinical practice guidelines, and reviews. Related references were cross checked. European and United States prescribing information was reviewed as well. An effort was made to give weight to the information that was most relevant for daily clinical practice. RESULTS: Trazodone is an antidepressant with a mechanism of action that remains innovative and with a favorable profile for the treatment of depression. The appropriate antidepressant doses are usually 150-300 mg/day and are often higher than the doses that are used when trazodone is prescribed to augment the antidepressant effect of another medication, for instance when trazodone is prescribed to address insomnia in a patient treated with an SSRI. Trazodone is usually well tolerated and has a low risk of anticholinergic side effects, weight gain and sexual side effects. DISCUSSION: Trazodone is an established medication that is efficacious for the treatment of a broad array of depressive symptoms, including symptoms that are less likely to respond to other antidepressants (e.g. SSRI), such as insomnia. As an antidepressant, trazodone has proven as efficacious as the tricyclic and second-generation antidepressants and is tolerated relatively well. Trazodone may be helpful for patients with major depression and comorbid insomnia, anxiety or psychomotor agitation. CONCLUSIONS: Trazodone is efficacious antidepressants with a relatively low risks of side effects such as weight gain, sexual or anticholinergic effects (such as constipation, urinary retention, dry mouth). In addition to being able to control a wide range of depressive symptoms, trazodone may improve sleep and be particularly helpful for patients whose symptoms of depression include insomnia.

[123I]FP-CIT SPET imaging in drug-induced Parkinsonism.

We assessed the status of dopamine nerve terminals in patients treated with dopamine receptor blocking agents (DRBAs) who had developed drug-induced parkinsonism (DIP). We performed [(123)I]FP-CIT SPET in 32 consecutive patients who were on DRBAs for at least 6 months and developed extrapyramidal signs. The UPDRS-III was used to assess clinical severity. Twenty-six age- and sex-matched healthy subjects served as control group. Putamen [(123)I]FP-CIT SPET binding was reduced in 14 and normal in the remaining 18 patients. There was no difference between the two groups for age, duration of DRBAs treatment, UPDRS III, tremor, rigidity, and bradykinesia subscores for upper and lower limbs. Conversely, symmetry of parkinsonian signs and presence bucco-linguo-masticatory dyskinesias were more frequent in individuals with normal tracer binding. Imaging of the dopamine transporter may help to identify subjects with DIP secondary to a loss of dopamine nerve terminals.

[Managing insomnia in the elderly patient: from pharmacology to subthreshold depression]. / La gestione dell'insonnia nel paziente anziano: dalla farmacologia alla depressione sottosoglia.

Insomnia is the most common and widespread sleep disorder. Managing insomnia in the elderly patient becomes a difficult challenge for the presence of a multi-disease and multi-drug condition. An organic and functional background that becomes even more fragile when the picture is complicated by psychomotor agitation and cognitive impairment. From the contribution of four experts of different fields and disciplines, stems the need to share an integrated vision that starts from the pharmacological basis of hypnotic drugs, delineates the features of depression in the elderly, addressed the delicate issue of chronic use/abuse of benzodiazepines and ultimately arrives to the management of behavioral disturbances. The pathway includes studies of clinical pharmacology and investigates the potential properties of trazodone, a multifunctional drug capable of acting on different biochemical and neurotransmitter pathways.

Targets, attitudes, and goals of psychiatrists treating patients with schizophrenia: key outcome drivers, role of quality of life, and place of long-acting antipsychotics.

PURPOSE: This survey of Italian psychiatrists was conducted to better define drivers of schizophrenia treatment choice in real-life practice, particularly for use of long-acting injectable (LAI) antipsychotics. METHODS: Between October 15 and December 15, 2014, 1,000 surveys were sent to psychiatrists who treat schizophrenic patients; 709 completed questionnaires were analyzed (71% response rate). RESULTS: The two most important factors determining therapy success were efficacy (75% of responses) and tolerability (45%) followed by global functioning (24%) and quality of life (17%). LAI antipsychotics were most often used to facilitate regular treatment monitoring (49%), and 41% of psychiatrists thought that patients with low adherence who had failed oral therapy were well-suited for LAI antipsychotics. Only 4% of respondents saw LAI antipsychotics as appropriate for patients without other therapeutic options. CONCLUSION: Although efficacy and tolerability were the most common factors used to evaluate treatment success in schizophrenia, psychiatrists also consider QoL and global functioning to be important.

Efficacy and safety of novel antipsychotics: a critical review.

Efficacy and safety of novel antipsychotic (AP) drugs (amisulpride, olanzapine, quetiapine, ziprasidone and zotepine) have been reviewed. Data on their antipsychotic efficacy and side effects profile have been evaluated only on the basis of controlled trials so far published. Overall, all these drugs have shown an antipsychotic efficacy on positive symptoms of schizophrenia similar to that of the conventional AP drugs. On negative symptoms, all novel AP drugs, except quetiapine and ziprasidone, demonstrated a better efficacy than haloperidol. Long-term efficacy of these AP drugs in the maintenance treatment of schizophrenia needs to be explored by further, better-designed, epidemiological studies. The safety profile shows that the novel AP drugs are generally well-tolerated and induce significantly less acute extrapyramidal side effects in comparison with haloperidol. Some methodological flaws in the experimental design of the clinical trials analysed are discussed. Although these novel AP drugs have potential clinical advantages, a number of relevant questions still remain to be addressed, in order to establish the impact of these drugs in the overall treatment of schizophrenia. Copyright 2000 John Wiley & Sons, Ltd.

Cost-effectiveness of asenapine in the treatment of patients with bipolar I disorder with mixed episodes in an Italian context.

INTRODUCTION: Bipolar disorder is a chronic disease characterized by periods of mania or hypomania, depression, or a combination of both (mixed state). Because bipolar disorder is one of the leading causes of disability, it represents an important economic burden on society. Asenapine (ASE) is a new second-generation antipsychotic developed and approved for the treatment of manic or mixed episodes associated with bipolar disorder. The objective of the present study was to assess the cost-effectiveness of ASE compared to olanzapine (OLA) in the treatment of patients experiencing mixed episodes associated with bipolar I disorder in the context of the Italian National Health Service (NHS). METHODS: A pharmacoeconomic model was developed to simulate the management of Italian bipolar I patients with mixed episodes over a 5-year time horizon by combining clinical parameters with resource utilization. An expert panel of Italian psychiatrists and health economists was responsible for adapting a UK model to the Italian context. The primary outcome measure of the economic evaluation was the incremental cost effectiveness ratio, where effectiveness is measured in terms of quality adjusted life-years gained. Scenario analyses, sensitivity analyses, and a probabilistic sensitivity analysis were performed to test the robustness of the model. RESULTS: This pharmacoeconomic model showed that ASE resulted to be dominant over OLA; in fact, ASE was associated with lower direct costs (derived largely by the savings from hospitalizations avoided) and also generated a better quality of life. Results were robust to changes in key parameters; both scenario analyses and sensitivity analyses demonstrated model reliability. CONCLUSIONS: Results from this study suggest that the management of bipolar I patients with mixed episodes using ASE as alternative to OLA can lead to cost saving for the Italian NHS and improve patients quality of life.

Prevalence and diagnostic distribution of medically unexplained painful somatic symptoms across 571 major depressed outpatients.

OBJECTIVE: To assess the prevalence and distribution of medically unexplained painful somatic symptoms (PSSs) versus nonpainful somatic symptoms (NPSSs) in patients diagnosed with major depressive episode (MDE). METHOD: A total of 571 outpatients diagnosed with MDE according to DSM-IV-TR criteria were consecutively enrolled into a cross-sectional, multicentric, observational study over a period of 7 months. Subjects were evaluated by means of the ad hoc validated 30-item Somatic Symptoms Checklist (SSCL-30) and Zung's questionnaires for depression and anxiety. The 32-item Hypomania Checklist (HCL-32) was also administered in order to explore any eventual association of PSSs or NPSSs with sub-threshold (DSM-IV-TR [Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision] not recognized) bipolar disorder (BD). RESULTS: In our sample, just 183 patients (32%) did not report painful somatic symptoms (NPSSs). Of these, 90 patients (15.76%) had no somatic symptoms at all. The remaining 388 (68%) had at least one PSS being subdivided as follows: 248 (43%) had one or two PSSs, while 140 (25%) experienced two or more. Patients with at least one PSS also reported a greater number of nonpainful somatic symptoms than NPSS. Bipolar patients (associated with higher HCL-32 scores) were less represented across PSS cases than NPSS subjects. Conversely, females were more prone to having a higher number of total somatic symptoms (and bipolar features). CONCLUSION: PSSs are common in patients with MDE, especially among those patients reporting fewer somatic symptoms in general as opposed to those patients who exhibit more somatic symptoms (both PSSs and NPSSs) with lower relative number of PSSs. A major therapeutic implication is that antidepressant monotherapy could be used with more confidence in unexplained PSS patients than in NPSS patients because of the latter group's lower frequency of (sub)-threshold bipolar features.

Are "social drugs" (tobacco, coffee and chocolate) related to the bipolar spectrum?

BACKGROUND: Across all ages and cultures, mankind has always used substances in order to induce pleasurable sensations or desirable psychophysical states. These substances, notably caffeine, tobacco, alcohol and chocolate, can be labeled 'social drugs'. METHODS: We analyzed the social drug habits of 562 patients suffering from mood disorders, according to DSM-IV-R criteria (major depressive episode, recurrent depression, bipolar type I and II disorders and depression not otherwise specified). The sample was also divided into bipolar and non-bipolar according to Hypomania Check-list 32 (HCL-32), which proposes a broader concept of hypomania and soft bipolarity, comprising the spectrum of bipolar disorders proper, along with other, "softer" expressions of bipolarity intermediate between bipolar disorder and normality. RESULTS: Using HCL-32 criteria, but DSM-IV-R criteria, a link was confirmed between bipolar spectrum and substance use including social drugs such as tobacco and coffee. LIMITATION: Observational correlational study. CONCLUSION: This study is in support of earlier theoretical formulations within the framework of the Pisa-San Diego collaboration.