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Three kinds of vinyl hydrogels with a-aminoacid residues have been considered as potential platforms for the deliver of several therapies (pain, diabetes, and mood) when loaded with appropriate drugs. The presence of ionizable groups of the L-valine, L-phenylalanine and L-histidine residues is able to modify the swelling properties of the hydrogel on the basis of its pKa values. A greater basicity constant of the functional groups improves a greater loading of the drug and a longer sustained-release pattern due to a strong polymer-drug ionic interaction. This occurs for the insulin and the paroxetine loaded on carboxylate hydrogels, and diclofenac loaded on zwitterionic hydrogels. The pH stimulation improves the swelling of the hydrogel and increases ‘on demand’ the drug availability. A further remote stimulus based on alternating magnetic fields (AMF) on hydrogels containing embedded magnetic nanoparticles (CoFe2O4) allows a greater release rate of insulin and paroxetine for several pulses at physiological pH.

Trazodone is a serotonin antagonist/reuptake inhibitor, approved for treating major depressive disorder (MDD). Oral formulations are widely studied and marketed in several countries worldwide while there is little evidence to support use of parenteral formulation. Our narrative review summarizes pharmacological properties and clinical data concerning use of parenteral trazodone in mood disorders. PubMed and Web of Science were used to identify the most relevant literature. The main evidence concerns four studies evaluating efficacy in major depressive disorder and indicates that trazodone was well tolerated and effective. Off-label use in agitation associated with bipolar disorder is also reported in three studies, although prescription of concomitant treatment, as a confounding factor, may have influenced outcome measures. The limited available evidence supports parenteral trazodone use in major depressive disorder and suggests that trazodone is a suitable option in patients at high risk of treatment-emergent mania (TEM).

Objective: : Intramuscular medications are widely used to treat psychomotor agitation (PMA) in uncooperative patients. We evaluated knowledge and attitude towards guidelines and the prescribing patterns in a sample of Italian psychiatrists., Methods: : A structured 28-item questionnaire was submitted to psychiatrists of Italian Departments of Mental Health. We considered 8 clinical scenarios of PMA. For comparing two qualitative variables Chi-square tests were performed., Results: : One hundred thirty-four psychiatrists completed the survey. The use of a monotherapy is significatively higher ( p ＜ 0.05) over a dual therapy in all clinical scenarios except PMA due to Mood Disorder and Psychotic Disorders, whereas the use of a polytherapy is significatively higher ( p ＜ 0.05) in PMA due to Mood Disorders and Psychotic Disorders. The use of second-generation antipsychotic (SGAs) as monotherapy over first-generation antipsychotics (FGAs) is significantly higher ( p ＜ 0.05) in PMA due to Central Nervous System (CNS) stimulants. The use of SGAs over FGAs in polytherapy is significantly higher ( p ＜ 0.05) in PMA due to CNS stimulants. Knowledge of guidelines results 67.1% and significatively higher ( p ＜ 0.05) among those who prefer SGAs as monotherapy rather than FGAs in PMA due to Intellectual Disability, CNS depressants and Delirium. Knowledge of guidelines results significatively higher ( p ＜ 0.05) among those who prefer SGAs rather than FGAs in polytherapy in PMA due to Mood disorders., Conclusion: : This survey reports variation in prescribing patterns for medication used to treat PMA. While SGAs are often prescribed as first choice following the more recent guidelines, FGAs and multi-drug solutions seem to be still a popular solution.

Paroxetine and Sertraline are the only medications approved in posttraumatic stress disorder (PTSD). However, about 60% of traumatized patients fail to show an adequate clinical response. Second generation antipsychotics are recommended as second-line monotherapy or third-line augmentation strategies and quetiapine appears as one of the most used and promising agents. Up to date, no reviews assessed the efficacy of quetiapine in the treatment of PTSD. We aimed to assess the effectiveness and general safety of quetiapine on PTSD. A systematic review was conducted following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and Cochrane guidelines, selecting studies that evaluated the efficacy of quetiapine on global or specific PTSD symptomatology. Ten studies (n = 894) were considered eligible for qualitative synthesis: one case report, one case series, one prospective cohort study, 3 open-label trials, 3 retrospective studies, one randomized controlled trial. Quetiapine was effective on global PTSD symptomatology assessed in 6 studies as well as on re-experiencing (4/4 studies), avoidance (4/3 studies) and hyperarousal (4/4 studies), flashbacks (2/2 studies), depressive (4/4 studies), anxiety (1/1 studies), psychotic (3/3 studies), insomnia (4/5 studies), nightmares (3/3 studies) specific symptoms and PTSD domains. Sedation was among the most frequently observed adverse effects and the main cause of drug discontinuation. Preliminary findings support the efficacy of quetiapine in ameliorating symptoms relative to PTSD and its overall safety. However, quetiapine use in PTSD cannot be recommended yet as studies mainly rely on open-label, retrospective studies or case series.

Anxiety symptoms and anxiety disorders are frequent in patients with schizophrenia and are associated with greater severity of both positive and negative symptoms, cognitive impairment, poorer functioning and quality of life. Accumulating evidence suggests that atypical antipsychotics may have a role in treating comorbid anxiety symptoms. A systematic review was conducted following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and Cochrane guidelines, selecting randomized control trials (RCTs) that evaluated efficacy of olanzapine on anxiety symptoms in patients diagnosed with schizophrenia and included anxiety evaluation scales. We searched PubMed and Web of Science databases for articles in English language available until September 2021. We selected 7 studies (3 with primary data analysis, 4 with secondary data analysis) regarding the use of olanzapine in patients with schizophrenia. In fours studies olanzapine was superior to haloperidol in improving anxiety symptoms. Four studies compared olanzapine versus risperidone: in two of them risperidone was superior to olanzapine, although one study was limited by a relatively small sample size. In the other two there were no significant differences between olanzapine and risperidone-treated patients. One study found that olanzapine and clozapine were comparable in terms of efficacy. Although olanzapine was superior to haloperidol in treating anxiety, this symptom was a secondary outcome measure in most of the considered studies. Future RCTs comparing different antipsychotics and larger sample sizes may allow to develop more solid treatment strategies.

Objectives: An observation of the Emergency Room (ER) admissions during the lockdown. Methods: We monitored admissions to the ER requiring psychiatric evaluation during the 2020 lockdown (March 9 th -May 3 rd , 2020) compared to the same period of 2019, in four sites of Northern Italy (ASST Lariana, AUSL Modena, ASU Friuli Centrale and AUSL Romagna). Number of admissions, baseline demographic and clinical variables were extracted from the clinical databases. Results: A 20.0% reduction of psychiatric referrals was observed across the sites (24.2% in ASST Lariana, 30.5% in AUSL Modena, 12.0% in ASU Friuli Centrale and 14.5% in AUSL Romagna). This reduction peaked at 41.5% in the first month of the lockdown. Being homeless as well as with a dual diagnosis (OR 1,67, CI: 1.02-2.74), while living in a residential facility and admission for a depressive episode Being homeless (OR 2.50, CI: 1.36-4.61) and having a dual diagnosis (OR 1,67, CI: 1.02-2.74) were significantly associated with an increase in ER admission, while living in a residential facility (OR 0.48, CI: 0.31-0.74), having a depressive episode (OR 0.36, CI: 0.18-0.73) and a diagnosis of anxiety disorder (OR 0.60, CI: 0.36-0.99) were significantly associated with a decrease. Conclusions: During lockdown, a decrease in psychiatric referrals was observed.

Since decades, lithium and valproate remain the pharmacological cornerstone to treat bipolar disorder. Different response patterns occur according to the phases of illness. At same time, individual pretreatment variables may concur to determine a specific drug-response. Our narrative review focuses on these two key clinical aspects to summarize the state of art. Information from i) clinical trials and ii) the most relevant international guidelines is collected to assess the clinical and preclinical factors that may guide the use of lithium rather than valproate. Lithium may be effective in treating acute mania, and lithium efficacy is maximized when used to prevent both manic and depressive episodes. Lithium may be a better treatment choice in patients with: positive family history for bipolar disorder, mania-depression-interval pattern, few previous affective episodes/hospitalizations, high risk for suicide, no comorbidities. Valproate may be more effective as antimanic rather than prophylactic agent. Valproate might be a better choice in patients with many previous affective episodes/hospitalizations and psychiatric comorbidities. Finally, neither lithium nor valproate are suggested for the treatment of acute mixed states or bipolar depression. To consider clinical and preclinical factors may thus be useful to select the best treatment strategy.

Purpose: The aim of our study is to evaluate the number and the features of admissions to the emergency room (ER) requiring psychiatric consultation, in the period between May 4th and August 31st 2020., Methods: We carried out a retrospective longitudinal observational study examining the 4 months following the initial lockdown imposed during the COVID-19 outbreak (May 4th and August 31st 2020). More specifically, the ER admissions leading to psychiatric referral were reviewed at all seven public hospitals of AUSL Romagna (Emilia Romagna region, Italy). Socio-demographic variables, history of medical comorbidities or psychiatric disorders, reason for ER admission, psychiatric diagnosis at discharge, and actions taken by the psychiatrist were collected., Results: An 11.3% (p = 0.007) increase in psychiatric assessments was observed when compared with the same period of the previous year (2019). A positive personal history of psychiatric disorders (OR:0.68, CI: 0.53-0.87) and assessments leading to no indication for follow-up (OR: 0.22, CI: 0.13-0.39) were significantly less frequent, while there was a significant increase of cases featuring organic comorbidities (OR: 1.24, CI: 1.00-1.52) and suicidal ideation/self-harm/suicide attempt (OR: 1,71, CI: 1.19-2.45) or psychomotor agitation (OR: 1.46, CI: 1.02-2.07) as reason for admission., Conclusions: Our results showed an increase in ER psychiatric consultations compared to the previous year, underlying the increased psychological distress caused by the lockdown., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Objectives: An observation of the admissions to the emergency room (ER) requiring psychiatric evaluation during the lockdown and investigation of the demographic and clinical variables., Methods: Retrospective longitudinal observational study of ER accesses for psychiatric evaluation was performed, comparing two periods (9 March-3 May 2020 vs. 9 March-3 May 2019). Data (number of admissions, key baseline demographic and clinical variables) were extracted from the ER databases of referral centres in a well-defined geographic area of North-Eastern Italy (Cesena, Ravenna, Forlì, and Rimini)., Results: A 15% reduction of psychiatric referrals was observed, together with a 17% reduction in the total number of patients referring to the ER. This reduction was most evident in the first month of the lockdown period (almost 25% reduction of both referrals and patients). Female gender (OR: 1.52: 95%, CI: 1.12-2.06) and being a local resident (OR: 1.54: 95%CI: 1.02-2.34) were factors associated with the decrease., Conclusions: Lockdown changed dramatically health priorities in the local population, including people with mental health. We speculate that our observations do not only refer to the confinement due to the lockdown regime but also to fear of contagion and adoption of different coping strategies, especially in women.Key-pointsDuring lockdown 15% reduction of psychiatric visits and >17% reduction in the number of psychiatric patients referring to the ER was observed.in the first four weeks of the lockdown almost 25% reduction of both visits and patients was observedFemale gender and being a local resident were factors associated with the decrease.

Polyelectrolyte hydrogels bearing l-phenylalanine (PHE), l-valine (AVA), and l-histidine (Hist) residues were used as scaffolds for the formation of silver nanoparticles by reduction of Ag⁺ ions with NaBH₄. The interaction with the metal ion allowed a prompt collapse of the swollen hydrogel, due to the neutralization reaction of basic groups present on the polymer. The imidazole nitrogen of the hydrogel with Hist demonstrated greater complexing capacity with the Ag⁺ ion compared to the hydrogels with carboxyl groups. The subsequent reduction to metallic silver allowed for the restoration of the hydrogel's degree of swelling to the starting value. Transmission electron microscopy (TEM) and spectroscopic analyses showed, respectively, a uniform distribution of the 15 nm spherical silver nanoparticles embedded on the hydrogel and peak optical properties around a wavelength of 400 nm due to the surface plasmonic effect. Unlike native hydrogels, the composite hydrogels containing silver nanoparticles showed good antibacterial activity as gram+/gram- bactericides, and higher antifungal activity against S. cerevisiae .

Introduction: Few studies have investigated the effects of efficacious psychotherapy on structural alterations of discrete brain regions associated with posttraumatic stress disorder (PTSD). We therefore proposed to evaluate the neurobiological effects of eye movement desensitization and reprocessing (EMDR) on 19 patients with drug-naïve PTSD without comorbidity, matched with 19 untreated healthy controls., Methods: We administered the Clinician Administered PTSD Scale (CAPS) and conducted brain MRI measurements (with Optimized Voxel-Based Morphometry). Patients received 12 EMDR sessions over three months. Then patients and controls were reassessed., Results: At baseline, grey matter volume (GMV) differed significantly between patients and controls (F 1,35 =3.674; p=.008; η 2=.298). Analyses of 3-month scans showed no changes for controls, while significant changes were highlighted for patients post-EMDR, with a significant increase in GMV in left parahippocampal gyrus, and a significant decrease in GMV in the left thalamus region. The diagnosis of PTSD was effectively eliminated in 16 of 19 patients, reflected in a significant improvement on the CAPS (t(35)=2.132, p<.004)., Discussion and Conclusions: Results indicated post-EMDR changes for patients in brain morphology. We discuss whether EMDR’s mechanism of action may work at the level of the thalamus, an area implicated in PTSD pathology.

Some vinyl hydrogels containing α-amino acid residues (l-phenylalanine, l-valine) were used as polyelectrolyte platforms for the evaluation of the controlled release of two antidepressants (paroxetine and duloxetine). The closer acidity constant (pKa) values of the two drugs show a closer release profile in physiological phosphate buffered saline (PBS) buffer (pH 7.40) and for long periods of time. The great electrostatic interaction forces between the COO - group of the hydrogel and the protonated secondary amino nitrogen of the drug are the main factor improving the release kinetics; this release was found to be slower compared to that of two structurally related drugs bearing the tertiary amino nitrogen atom (citalopram and trazodone). Moreover, at the lower value of pH 4.60, paroxetine showed a flatter release profile from the hydrogel containing the l-phenylalanine residues that, after six days, is half of that shown by duloxetine. Further effects due to steric and hydrophobic interactions may contribute to the different release profile. A further stimulation with alternating magnetic fields (AMF) of low frequency (20 kHz/50 W) enhanced the release of the drug at pH 7.40 from the hydrogel containing magnetic nanoparticles. Both AMF and PBS solution at pH 7.40 were used to trigger the 'on-demand' pulsatile paroxetine release from the nanocomposite hydrogel.

Background: Research evidence on the effects of integrated multifaceted lifestyle interventions for depression is scanty. The aim of the present study is to report on the development, acceptability and efficacy of a standardized healthy lifestyle intervention, including exercise, eating habits, sleep hygiene and smoking cessation in preventing relapses., Methods: One hundred-sixty outpatients with recurrent unipolar depression or bipolar disorder were recruited after achieving full remission or recovery from the most recent depressive episode. Patients were randomized to 3-months of usual care or to an intervention aimed at promoting a healthy lifestyle (HLI), as an augmentation of pharmacological maintenance treatment. Usual care consisted of clinical management visits. At the end of the intervention, follow-up visits were scheduled at 3,6,9 and 12 months., Results: During the intervention phase, 1 relapse occurred in the HLI group and 4 in the control group. Over the 12 months of follow-up, relapses were 5 in the HLI group and 16 in control group. Using an intent-to-treat approach, the overall percentage of relapses was 6/81 (7.4%) in the HLI group vs. 20/79 (25.3%) in the control group.. In a Kaplan-Meier survival analysis the risk of relapse was significantly lower in patients receiving the HLI intervention (log-rank test, p=0.003) over the 60 weeks of observation. The majority of patients assigned to HLI adhered to the program, and were highly motivated throughout the intervention., Limitations: The retention rate was low because patients were recruited during the maintenance phase and the 1-year follow-up was relatively short to detect a long-term effect of HLI., Conclusions: The HLI program proved to be efficacious in preventing relapses. Given the absence of contraindications and its cost-effectiveness in routine practice, the use of HLI should be encouraged to promote the well-being of patients with recurrent depression., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Although trazodone is approved and marketed in most countries worldwide for the sole treatment of Major Depressive Disorder, the use for this medication is very common for many other conditions, such as primary or secondary insomnia, Generalised Anxiety Disorder, Panic Disorder, Post-Traumatic Stress Disorder and Obsessive- Compulsive Disorder. Other, not officially approved, uses of trazodone include: the treatment of bulimia, benzodiazepine and/or alcohol dependence or abuse, fibromyalgia, degenerative diseases of the central nervous system such as dementia and other organic disorders, schizophrenia, chronic pain, and diabetic neuropathy. In addition, due to its 5HT2A receptor antagonistic action, trazodone may be used to prevent the occurrence of initial and long-term side effects of SSRI, such as anxiety, insomnia and sexual dysfunction. Despite the favorable clinical experience and the encouraging results from the studies that have tested the efficacy of trazodone for some of its off-label indications, it is paramount that large, randomized and controlled clinical trials be conducted in the near future to evaluate which of the many off-label indications are supported by a strong scientific evidence.

Sexual dysfunctions may have a significant effect on the quality of life, but are unreported and under-diagnosed. A review of recent literature highlights the correlation between dysfunction and a decreased quality of life in people with psychiatric comorbidity, and explores several aspects impacting care, from following the patient to pharmacological and non-pharmacological treatments. Sexual dysfunctions (SD) have been shown to be prevalent, but under-diagnosed and un-dertreated because of communication barriers between patients and physicians. Pharmacogenic and morbogenic causes of sexual problems are often difficult to differentiate. Psychiatric diseases may increase the risk of SD, and SD may further exacerbate psychiatric problems, suggesting a bi-directional relationship. Their effective treatment frequently involves combination of elements from psychotherapy, and behavioral along with pharmacotherapeutic intervention, if needed. The persistence of sexual problems has significant negative impact on patient's satisfaction and adherence with the treatment, quality of life and partnership. Routine assessment of sexual functioning needs to be integrated into ongoing care to identify and address problems early. If sexual dysfunction is ignored it may maintain the psychiatric disorder, compromise treatment outcome and lead to non-adherence and compromise treatment outcome.

Objectives: The overlap between symptoms of PTSD and MDD is substantial. PTSD symptoms arise after a traumatic experience and the trauma is present in all of the diagnostic clusters. In individuals who have experienced a trauma a long time before, it is difficult to establish the exact moment of onset of their symptoms in relation to the trauma suffered. We proposed to raise awareness among operators who may encounter this problem, with the aim of providing them with valuable help in order to achieve a correct differential diagnosis., Methods: A sample of subjects suffering from PTSD without comorbidity was assessed to confirm the diagnosis and the severity of post-traumatic symptoms. The Kruskal-Wallis test was used to compare any modifications in the parameters analyzed through the Davidson Trauma Scale with the presence and severity of depressive symptoms as evaluated by the Hamilton-D scale., Results: Half of the PSTD patients recruited showed values of HAM-D > 18, although an active Major Depressive Episode was clinically excluded. Symptom of "numbing", despite being different from the apathy experienced in depression, is identified as a depressive symptom by the HAM-D., Conclusions: Giving prevalence to depressive symptoms may be misleading for diagnosis and may ultimately result in inappropriate treatment.

Objectives: Seasonal trends were demonstrated in reproduction and sexual activity. Through the secretion ofmelatonin the pineal gland plays an important role in the neuroendocrine control of sexual function and reproductive physiology. We hypothesized that inhibition of the pineal gland activity through a light treatment may favorably affect sexual function., Methods: We recruited 24 subjects with a diagnosis of hypoactive sexual desire disorder and/or primary sexual arousal disorder. The subjects were randomly assigned to either active light treatment (ALT) or placebo light treatment (L-PBO). Participants were assessed during the first evaluation and after 2 weeks of treatment, using the Structured Clinical Interview for Sexual Disorders DSM-IV (SCID-S) and a self-administered rating scale of the level of sexual satisfaction (1 to 10). Repeated ANOVA measures were performed to compare the two groups of patients. Post-hoc analysis was performed by Holm-Sidak test for repeated comparisons. Results. At baseline the two groups were comparable. After 2 weeks the group treated with Light Therapy showed a significant improvement in sexual satisfaction, about 3 times higher than the group that received placebo, while no significant improvement was observed in the group L-PBO. Conclusions. Our results confirm a potentially beneficial effect of Light Therapy on primary sexual dysfunction. In the future, we propose to correlate clinical findings with testosterone levels pre/post treatment.