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Psychiatric drugs have primacy for off-label prescribing. Among those, selective serotonin reuptake inhibitors (SSRIs) are highly versatile and, therefore, widely prescribed. Moreover, they are commonly considered as having a better safety profile compared to other antidepressants. Thus, when it comes to off-label prescribing, SSRIs rank among the top positions. In this review, we present the state of the art of off-label applications of selective serotonin reuptake inhibitors, ranging from migraine prophylaxis to SARS-CoV-2 antiviral properties. Research on SSRIs provided significant evidence in the treatment of premature ejaculation, both with the on-label dapoxetine 30 mg and the off-label paroxetine 20 mg. However, other than a serotoninergic syndrome, serious conditions like increased bleeding rates, hyponatremia, hepatoxicity, and post-SSRIs sexual dysfunctions, are consistently more prominent when using such compounds. These insidious side effects might be frequently underestimated during common clinical practice, especially by nonpsychiatrists. Thus, some points must be addressed when using SSRIs. Among these, a psychiatric evaluation before every administration that falls outside the regulatory agencies-approved guidelines has to be considered mandatory. For these reasons, we aim with the present article to identify the risks of inappropriate uses and to advocate the need to actively boost research encouraging future clinical trials on this topic.

Despite that it is commonly accepted that migraine is a disorder of the nervous system with a prominent genetic basis, it is comorbid with a plethora of medical conditions. Several studies have found bidirectional comorbidity between migraine and different disorders including neurological, psychiatric, cardio- and cerebrovascular, gastrointestinal, metaboloendocrine, and immunological conditions. Each of these has its own genetic load and shares some common characteristics with migraine. The bidirectional mechanisms that are likely to underlie this extensive comorbidity between migraine and other diseases are manifold. Comorbid pathologies can induce and promote thalamocortical network dysexcitability, multi-organ transient or persistent pro-inflammatory state, and disproportionate energetic needs in a variable combination, which in turn may be causative mechanisms of the activation of an ample defensive system with includes the trigeminovascular system in conjunction with the neuroendocrine hypothalamic system. This strategy is designed to maintain brain homeostasis by regulating homeostatic needs, such as normal subcortico-cortical excitability, energy balance, osmoregulation, and emotional response. In this light, the treatment of migraine should always involves a multidisciplinary approach, aimed at identifying and, if necessary, eliminating possible risk and comorbidity factors.

A considerable body of literature reports that individuals with psychotic disorders often suffer from sexual dysfunctions (SDs), with these representing a major unmet need. Long-term antipsychotic drug treatment may be the main cause for SDs in psychotic patients, through a plethora of different mechanisms, including prolactin dyscrasia, histamine-mediated sedation, and serotonin-induced sexual demotivation. However, a few pieces of evidence treat sexuality in patients at risk or the onset of psychosis. For this purpose, we systematically reviewed literature of the last 10 years in order to investigate sexuality in ultra-high risk (UHR) for psychosis and first-episode psychosis (FEP). We included in our review 34 articles fitting our research criteria on SDs in UHR and FEP. Evidence of SDs in the transition from UHR to FEP emerges through the selected studies. In FEP, sexuality is affected by the severity of the psychotic symptoms and, in some cases, by the iatrogenic effects of psychopharmacological treatment. Further experimental and clinical studies should systematically investigate the role of sexual functioning in the transition from UHR to FEP and, consequently, clarify whether or not SDs could be considered a possible marker for the onset of psychosis in at-risk populations. Moreover, psychiatrists and clinical psychologists should take into consideration the role of sexual life in young people with prodromal mental symptoms or at the onset of psychosis. Focusing on a thorough sexual evaluation might be a major challenge that could break down barriers of mental health promotion among young people with schizophrenia-spectrum disorders and therefore achieve better clinical outcomes.

Purpose To develop a comprehensive next-generation sequencing panel assay that screens genes known to cause developmental eye disorders and inherited eye disease and to evaluate its diagnostic yield in a pediatric cohort with malformations of the globe, anterior segment anomalies, childhood glaucoma, or a combination thereof. Design Evaluation of diagnostic test. Participants Two hundred seventy-seven children, 0 to 16 years of age, diagnosed with nonsyndromic or syndromic developmental eye defects without a genetic diagnosis. Methods We developed a new oculome panel using a custom-designed Agilent SureSelect QXT target capture method (Agilent Technologies, Santa Clara, CA) to capture and perform parallel high-throughput sequencing analysis of 429 genes associated with eye disorders. Bidirectional Sanger sequencing confirmed suspected pathogenic variants. Main Outcome Measures Collated clinical details and oculome molecular genetic results. Results The oculome design covers 429 known eye disease genes; these are subdivided into 5 overlapping virtual subpanels for anterior segment developmental anomalies including glaucoma (ASDA; 59 genes), microphthalmia–anophthalmia–coloboma (MAC; 86 genes), congenital cataracts and lens-associated conditions (70 genes), retinal dystrophies (RET; 235 genes), and albinism (15 genes), as well as additional genes implicated in optic atrophy and complex strabismus (10 genes). Panel development and testing included analyzing 277 clinical samples and 3 positive control samples using Illumina sequencing platforms; more than 30× read depth was achieved for 99.5% of the targeted 1.77-Mb region. Bioinformatics analysis performed using a pipeline based on Freebayes and ExomeDepth to identify coding sequence and copy number variants, respectively, resulted in a definitive diagnosis in 68 of 277 samples, with variability in diagnostic yield between phenotypic subgroups: MAC, 8.2% (8 of 98 cases solved); ASDA, 24.8% (28 of 113 cases solved); other or syndromic, 37.5% (3 of 8 cases solved); RET, 42.8% (21 of 49 cases solved); and congenital cataracts and lens-associated conditions, 88.9% (8 of 9 cases solved). Conclusions The oculome test diagnoses a comprehensive range of genetic conditions affecting the development of the eye, potentially replacing protracted and costly multidisciplinary assessments and allowing for faster targeted management. The oculome enabled molecular diagnosis of a significant number of cases in our sample cohort of varied ocular birth defects.

Background: The COVID-19 pandemic, due to its disproportionated higher morbidity and mortality rates in the older age, has been considered to be a “geropandemic.” Several studies, however, have found that older age is associated with lower psychological distress in relation to the COVID-19 outbreak and related lockdown measures.Aim: To explore the role of Resilience as a mediator between stressful COVID-19 related life events and depressive and, anxiety symptoms and perceived stress, and to ascertain the role of age as a moderator of the mediator's effect.Methods: An on-line survey was spread through social networks during the first lockdown in Italy. Depressive and anxiety symptoms and perceived stress were measured using the Italian version of the Patient Health Questionnaire-9 (PHQ-9), the Generalized Anxiety Disorder Questionnaire-7 (GAD-7) and the Perceived Stress Scale (PSS). Resilience was measured using the Italian version of the Resilience Scale for Adults (RSA). Stressful COVID-19 related life events were explored using a checklist of events derived from the International Adjustment Disorder Questionnaire (IADQ). After a preliminary panel of linear regressions, mediation was tested using Structural Equation Modeling and inspecting the bootstrapped indirect effects. Afterwards, age was introduced as a mediator of the indirect effect in a moderated mediation analysis.Results: Twenty one thousand three hundred and thirty four subjects completed the questionnaire, 17,178 (80.52%) were female, 748 (3.5%) were >60 years old. In the whole sample, the presence of any stressful event was associated with depressive and anxiety symptoms and perceived stress. Resilience mediated the effects of stressful COVID-19-related events on depressive and anxiety symptoms and perceived stress. The moderated mediation analysis revealed that age moderated the mediation effect of Resilience between the presence of a stressful event and the selected outcomes.Conclusion: Taken together, our results show that age moderates the mediating effect of Resilience in the relationship between COVID-19-related stressful events and depressive and anxiety symptoms and perceived stress. Older adults' Resilience was less influenced by stressful events, and this could be one of the reasons accounting for the better mental health outcomes observed in the older age.

Background and purpose Stroke-associated pneumonia (SAP) affects 10 to 38% of patients in the acute phase of stroke. Stroke patients diagnosed with dysphagia have an 11-fold higher risk of developing SAP. Thus, identifying dysphagic patients through a highly accurate screening tool might be crucial in reducing the incidence of SAP. We present a case–control study designed to evaluate efficacy in reducing the risk of SAP between two swallowing screening tools, the classic water swallow test (WST) and a recently validated tool such as the GLOBE-3S (the Sapienza GLObal Bedside Evaluation of Swallowing after Stroke), which is a highly sensitive swallowing screening tool particularly accurate in detecting silent aspiration as well. Methods We analyzed the occurrence of dysphagia in 100 acute stroke patients distributed in two groups: half were screened with WST and the other half with GLOBE-3S. Results Dysphagia was diagnosed in 28 patients. The main result is that, among patients who passed the dysphagia screenings, none of those screened with the GLOBE-3S method developed pneumonia compared to 31.82% in the WST group. Discriminant function analysis (DFA) showed that NIH Stroke Scale (NIHSS) score and the dysphagia screening method (i.e., GLOBE-3S vs. WST) were the two main factors in the SAP’s predicting model and the only significant ones per se. Conclusions The new GLOBE-3S screening test can reduce the risk of SAP compared to WST.

Introduction: Medical comorbidities (MCs) represent a significant burden in terms of more frequent hospitalizations and overall lower life expectancy among people with severe mental disorders, such as schizophrenia and related psychotic disorders (SZ) and bipolar disorder (BD). The present article aims to compare the prevalence of MCs and to examine the associated characteristics as marital status, job occupation, level of education, and living arrangements, between BD and SZ patients.Methods: One-hundred-eight-one patients with MCs (85/47% had BD and 96/53% had SZ) were recruited retrospectively from the Acute Inpatients Psychiatry Unit of Policlinico Tor Vergata, Rome, between January-2017 and December-2020. MCs were: cardiovascular diseases (CVD), bacterial infections, mycoses, viral diseases, neoplasms, musculoskeletal, respiratory tract, urological and male genital, gynecological, neurological, gastrointestinal, metabolic syndrome, nutritional, and metabolic diseases.Results: BD had more MC than SZ (36.2 vs. 28.2%, respectively, p = 0.04). CVD and metabolic MC were more common among BD (51.8 vs.34.4%; 51.8 vs.35.3%; p = 0.018; p = 0.039; respectively), while viral diseases were more frequent in SZ (13.5 vs.3.5%, p = 0.035). Hypertension was common in both psychiatric illnesses (81.8% BD vs. 65.6% SZ, p = 0.18). Obesity was the most frequent metabolic disease in both BD and SZ (75% BD vs. 73.5% SZ, p = 0.91), followed by diabetes mellitus (52.3% BD vs. 55.9% SZ, p = 0.93), metabolic syndrome (54.5% BD vs. 47.1% SZ, p = 0.67) and dysthyroidism (47.7% BD vs. 25.7% SZ, p = 0.093). After performing a binary logistic regression analysis, only two MCs showed a statistically significant association: patients with SZ had an OR of 2.01 [CI 95% (1.00–4.01)] for CVD compared to BD; on the other hand, patients with BD had an OR of 16.57 [CI 95% (3.58–76.77)] for gynecological diseases compared to SZ patients.Conclusions: MCs are common among people with severe mental illness, especially CVD and metabolic diseases, highlighting the need for a more collaborative relationship between general medical providers and psychiatrists.

Focal repetitive muscle vibration (fMV) is a safe and well-tolerated non-invasive brain and peripheral stimulation (NIBS) technique, easy to perform at the bedside, and able to promote the post-stroke motor recovery through conditioning the stroke-related dysfunctional structures and pathways. Here we describe the concurrent cortical and spinal plasticity induced by fMV in a chronic stroke survivor, as assessed with 99mTc-HMPAO SPECT, peripheral nerve stimulation, and gait analysis. A 72-years-old patient was referred to our stroke clinic for a right leg hemiparesis and spasticity resulting from a previous (4 years before) hemorrhagic stroke. He reported a subjective improvement of his right leg's spasticity and dysesthesia that occurred after a30-min ride on a Vespa scooter as a passenger over the Roman Sampietrini (i.e., cubic-shaped cobblestones). Taking into account both the patient's anecdote and the current guidelines that recommend fMV for the treatment of post-stroke spasticity, we then decided to start fMV treatment. 12 fMV sessions (frequency 100 Hz; amplitude range 0.2-0.5 mm, three 10-min daily sessions per week for 4 consecutive weeks) were applied over the quadriceps femoris, triceps surae, and hamstring muscles through a specific commercial device (Cro®System, NEMOCOsrl). A standardized clinical and instrumental evaluation was performed before (T0) the first fMV session and after (T1) the last one. After fMV treatment, we observed a clinically relevant motor and functional improvement, as assessed by comparing the post-treatment changes in the score of the Fugl-Meyer assessment, the Motricity Index score, the gait analysis, and the Ashworth modified scale, with the respective minimal detectable change at the 95% confidence level (MDC95). Data from SPECT and peripheral nerve stimulation supported the evidence of a concurrent brain and spinal plasticity promoted by fMV treatment trough activity-dependent changes in cortical perfusion and motoneuron excitability, respectively. In conclusion, the substrate of post-stroke motor recovery induced by fMV involves a concurrently acting multisite plasticity (i.e., cortical and spinal plasticity). In our patient, operant conditioning of both cortical perfusion and motoneuron excitability throughout a month of fMV treatment was related to a clinically relevant improvement in his strength, step symmetry (with reduced limping), and spasticity.

The present overview was aimed at presenting the state of the art of the clinical use of Transcranial Magnetic Stimulation (TMS) protocols in the treatment of anxiety disorders. Available evidence shows that TMS therapeutic protocols over the prefrontal cortex, with excitatory stimulation at the left side and/or inhibitory stimulation of the right side, are effective and well tolerated to reduce anxiety symptoms in Panic Disorder and Generalized Anxiety Disorder. To date, the level of evidence is, however, relatively low regarding the clinical use of TMS therapeutic protocols in anxiety disorders. Future investigation, with an improvement both in methodological issues and in study design, will reveal the real usefulness of TMS therapeutic protocols in the treatment of anxiety disorders.

Background and purpose Dysphagia occurs in up to 50% of all patients with acute stroke. There is debate regarding which is the most effective screening tool in identifying aspiration in patients with acute stroke. We assessed the accuracy of the Sapienza Global Bedside Evaluation of Swallowing after Stroke (GLOBE-3S), which combines the Toronto Bedside Swallowing Screening Test (TOR-BSST©) with oxygen desaturation and laryngeal elevation measurement during swallowing. Methods We prospectively enrolled consecutive patients with stroke within 72 h of symptom onset. All patients with stroke firstly underwent a standard neurological examination, then the GLOBE-3S evaluation and finally the fiberoptic endoscopic evaluation of swallowing (FEES). Two different assessors, a neurologist and a speech pathologist, blind to both the clinical data and each other's evaluation, administered the GLOBE-3S and FEES examination. We assessed the accuracy of the GLOBE-3S in detecting post-stroke swallow impairment with aspiration using the FEES as the standard. Results We enrolled 50 patients with acute stroke, 28 of whom (56%) had swallowing impairment with aspiration at FEES evaluation. A total of 33 patients (66%) failed the GLOBE-3S evaluation. The GLOBE-3S reached a sensitivity of 100% and a specificity of 77.3% (negative predictive value, 100%; positive likelihood ratio, 4.34). The median time required for the GLOBE-3S to be performed was 297 s. Conclusions GLOBE-3S is quick to perform at the bedside and can accurately identify aspiration in patients with acute stroke. By including the measurement of laryngeal elevation and monitoring of oxygen desaturation, it could represent a highly sensitive instrument to avoid the misdiagnosis of silent aspirators.

IntroductionThe deficiency of polyunsaturated fatty acids (PUFAs) and an alteration between the ratio of omega-6 and omega-3 PUFAs may contribute to the pathogenesis of depressive disorders.ObjectivesTo investigate the levels of omega-3 and omega-6 in red cell membranes (mPUFAs) and plasma (pPUFAs) of patients with treatment-resistant (TRD) and non-treatment resistant depression (non-TRD).MethodsTRD and non-TRD consisted of 75 patients enrolled at the Psychiatric and Clinic Psychology Unit of the University of Rome Tor Vergata, Rome, Italy, and met the DSM-IV criteria for major depressive disorder (MDD). A group of healthy controls (HC) matched for agender and age was enrolled. All blood samples were performed in conditions of an empty stomach between 07:00 am and 09:00 am. For each subject were obtained 5 ml of whole blood with the use of tubes for plasma with EDTA as an anticoagulant. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) for omega-3 and arachidonic acid (AA) for omega-6 were measured.ResultsLevels of pPUFAs did not differ between the three groups. The mPUFAs were altered in the MDD. TRD and non-TRD had lower EPA and AA values respect to the HC. DHA in red cell membranes was lower in TRD than non-TRD and HC.ConclusionsChanges in levels of PUFAs in red cell membranes, but not in plasma, may be an important factor to evaluate the resistance to the pharmacological treatment.

Repetitive focal muscle vibration (rMV) is known to promote neural plasticity and long-lasting motor recovery in chronic stroke patients. Those structural and functional changes within the motor network underlying motor recovery occur in the very first hours after stroke. Nonetheless, to our knowledge, no rMV-based studies have been carried out in acute stroke patients so far, and the clinical benefit of rMV in this phase of stroke is yet to be determined. The aim of this randomized double-blind sham-controlled study is to investigate the short-term effect of rMV on motor recovery in acute stroke patients. Out of 22 acute stroke patients, 10 were treated with the rMV (vibration group–VG), while 12 underwent the sham treatment (control group–CG). Both treatments were carried out for 3 consecutive days, starting within 72 h of stroke onset; each daily session consisted of three 10-min treatments (for each treated limb), interspersed with a 1-min interval. rMV was delivered using a specific device (Cro®System, NEMOCO srl, Italy). The transducer was applied perpendicular to the target muscle's belly, near its distal tendon insertion, generating a 0.2–0.5 mm peak-to-peak sinusoidal displacement at a frequency of 100 Hz. All participants also underwent a daily standard rehabilitation program. The study protocol underwent local ethics committee approval (ClinicalTrial.gov {"type":"clinical-trial","attrs":{"text":"NCT03697525","term_id":"NCT03697525"}}NCT03697525) and written informed consent was obtained from all of the participants. With regard to the different pre-treatment clinical statuses, VG patients showed significant clinical improvement with respect to CG-treated patients among the NIHSS (p < 0.001), Fugl-Meyer (p = 0.001), and Motricity Index (p < 0.001) scores. In addition, when the upper and lower limb scales scores were compared between the two groups, VG patients were found to have a better clinical improvement at all the clinical end points. This study provides the first evidence that rMV is able to improve the motor outcome in a cohort of acute stroke patients, regardless of the pretreatment clinical status. Being a safe and well-tolerated intervention, which is easy to perform at the bedside, rMV may represent a valid complementary non-pharmacological therapy to promote motor recovery in acute stroke patients.

IntroductionAmongst different subtypes of Conversion Disorder (CD), DSM-V lists the Psychogenic Non-epileptic seizures (PNES). PNES are defined as episodes that visually resemble epileptic seizures but, etiologically, they are not due to electrical discharges in the brain.ObjectivesOur study aims to explore the differences between PNES and other CDs. In particular, we studied the suicidality and its correlations with dissociation and alexithymia.MethodsPatients, recruited from the Psychiatry and Clinical Psychology Unit of the Fondazione Policlinico Tor Vergata, Rome, Italy, were diagnosed with PNES (n=22) and CD (n=16) using the DSM-5 criteria. Patients underwent the following clinical assessments: HAM-D, BDI, DES, BHS, TAS, CTQ.ResultsPNES showed significantly higher scores than CD in all assessments, except for BDI-somatic (p=0.39), BHS-feeling (p=0.86), and the presence of childhood trauma. PNES also showed significantly higher suicidality (p = 0.003). By controlling for the confounding factor “depression”, in PNES suicidality (and in particular the BHS-loss of motivation) appears to be correlated with DES-total score (p = 0.008), DES-amnesia (p = 0.002) and DES -derealization-depersonalization (p = 0.003). On the other hand, in CDs, the BHS-total score shows a correlation with the TAS-total score (p = 0.03) and BHS-Feelings with TAS-Externally-Oriented Thinking (p = 0.035), while only the BHS-Loss of motivation appears correlated with DES-Absorption (p = 0.011).ConclusionsOur study shows significant differences between PNES and CD, in several symptomatologic dimensions, including suicidality. Indeed, in PNES suicidality appears to be related to dissociation, while in CDs it appears mainly to be correlated with alexithymia.