New trends of drug abuse in custodial settings: A systematic review on the misuse of over-the-counter drugs, prescription-only-medications, and new psychoactive substances.

The article presents a systematic literature review on the use and the psychiatric implications of over-the-counter drugs (OTC), prescription-only-medications (POM), and new psychoactive substances (NPS) within custodial settings. The searches wer carried out on 2 November 2022 on PubMed, Scopus, and Web of Science in line with PRISMA guidelines. A total of 538 records were identified, of which 37 met the inclusion criteria. Findings showed the most prevalent NPS and OTC and POM classes reported in prisons were synthetic cannabinoids receptor agonists (SCRAs) and opioids, respectively. NPS markets were shown to be in constant evolution following the pace of legislations aimed to reduce their spread. The use of such substances heavily impacts the conditions and rehabilitation of persons in custody, with consequent physical and mental health risks. It is important to raise awareness of the use and misuse of such substances in prisons (i) from an early warning perspective for law enforcement and policy makers (ii) to prompt doctors to cautiously prescribe substances that may be misused (iii) to improve and increase access to treatment provided (iv) to add such substances to routine toxicological screening procedures (v) to improve harm reduction programmes.

Investigating the Effectiveness of Brexpiprazole in Subjects with Schizophrenia Spectrum Illness and Co-Occurring Substance Use Disorder: A Prospective, Multicentric, Real-World Study.

BACKGROUND: Dual disorders (DDs) involve the coexistence of a substance use disorder (SUD) with another mental illness, often from the psychotic and affective categories. They are quite common in clinical practice and present significant challenges for both diagnosis and treatment. This study explores the effectiveness of brexpiprazole, a third-generation antipsychotic, in an Italian sample of individuals diagnosed with schizophrenia spectrum disorder and a comorbid SUD. METHODS: Twenty-four patients, diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and enrolled in several Italian hospitals, underwent a psychometric assessment at baseline (T0) and one month (T1) after starting brexpiprazole treatment administered at a mean dosage of 2 mg/day. RESULTS: Brexpiprazole demonstrated significant reductions in psychopathological burden (Positive and Negative Syndrome Scale/PANSS total score: p < 0.001). Positive (p = 0.003) and negative (p = 0.028) symptoms, substance cravings (VAS craving: p = 0.039), and aggression (MOAS scale: p = 0.003) were notably reduced. Quality of life improved according to the 36-item Short Form Health Survey (SF-36) subscales (p < 0.005). CONCLUSIONS: This study provides initial evidence supporting brexpiprazole's efficacy and safety in this complex patient population, with positive effects not only on psychopathology and quality of life, but also on cravings. Further studies involving larger cohorts of subjects and extended follow-up periods are needed.

Examining Lurasidone Efficacy in Patients with Schizophrenia Spectrum Illness and Concurrent Alcohol and Substance Use Disorder: A Prospective, Multicentric, Real-World Investigation.

Background: Dual disorders (DD) entail the coexistence of a substance use disorder (SUD) and another mental health condition, often within psychotic and affective disorders. This study aims to evaluate lurasidone, an innovative atypical antipsychotic, in individuals diagnosed with schizophrenia spectrum disorder and concurrent comorbidities of alcohol use disorder/substance use disorder (AUD/SUD). Methods: A cohort of 23 subjects diagnosed with schizophrenia spectrum disorder and comorbid AUD/SUD underwent psychometric assessments at baseline (T0) and one-month (T1) post-lurasidone initiation. Results: Lurasidone exhibited significant reductions in psychopathological burden, evidenced by decreased total PANSS scores (Z = 2.574, p = 0.011). Positive symptoms, substance craving (VAS Craving; Z = 3.202, p = 0.001), and aggressivity (MOAS scale; Z = 2.000, p = 0.050) were notably reduced. Clinical Global Impression (CGI) scores significantly improved (Z = 2.934, p = 0.003). Quality of life enhancements were observed in SF-36 subscales (energy, emotional well-being, and social functioning) (p < 0.05) and Q-LES-Q-SF scale (Z = -2.341, p = 0.021). A safety analysis indicated lurasidone's good tolerability, with only 8.7% reporting discontinuation due to side effects. Conclusions: This study offers initial evidence supporting lurasidone's efficacy and safety in dual diagnoses, highlighting positive effects on psychopathology, substance craving, and quality of life. These findings emphasize the need for tailored, comprehensive treatment strategies in managing the complexities of this patient population.

Efficacy of Psychosocial and Psychological Interventions in Addition to Drug Therapy to Improve Global Functioning of Inpatients with Schizophrenia Spectrum and Mood Disorders: A Real-World Observational Study.

Introduction and Aim: Psychotic and mood disorders are associated with significant functional impairment, premature mortality, physical morbidity, and great social and economic burden. The aim of this study is to evaluate the effectiveness of psychosocial, psychological, and rehabilitative interventions implemented in an Italian psychiatric inpatient facility, with a focus on patients with schizophrenia spectrum versus those with mood disorders. Methods: A retrospective observational study was conducted in the psychiatric hospital Villa Maria Pia in Rome, Italy, during 2022. Patients with an established diagnosis of schizophrenia spectrum and mood disorder (ICD-9-CM) were assessed on admission (T0) and at the end of treatment (T1), using the Brief Psychiatric Rating Scale (BPRS) and the Global Assessment of Functioning (GAF). Interventions involved a multidisciplinary team and included individual and group activities. The t-test for independent samples was used to compare continuous variables between groups and Spearman correlation coefficient to calculate correlations between variables. Results: The study sample consisted of 141 patients, the majority of them being adults (51.3 years ± 12.4) men (F/M= 68/73). Among them, 85 patients (60.3%) actively engaged in psychosocial and rehabilitative interventions and, compared to non-participating individuals, they showed lower functioning and symptoms at discharge (delta GAF was significantly higher among patients who had taken part in the psychosocial activities, t = -2.095; p = 0.038). Considering the index computed (n of interventions/days of hospitalization), the number of psychosocial activities was positively correlated with the improvement in patients' functioning in the sample taking part in activities (r = 0.272, p = 0.012), especially with psychotherapy and support groups (r = 0.202, p = 0.017 and r = 0.188, p = 0.025, respectively). Splitting the total sample into schizophrenia-spectrum disorder (N = 37) and mood disorder (N = 48) groups, the positive correlations between GAF improvement and participation in psychosocial activities were confirmed only in the schizophrenia-spectrum group. These correlations were not significant for symptomatology (BPRS) either in the total or the individual group. Conclusion: Evidence from our study suggests that inpatient rehabilitation can be effective and useful for people with severe mental disorders. Further investigations are needed to better understand its effectiveness on improving quality of life and social functioning in the long term.

Knowledge and Use of Over-the-counter Drugs in Italy: An Exploratory Survey-based Study in the General Population.

BACKGROUND: During the past decade, the misuse of over-the-counter (OTC) medicines has become a global public health concern, especially among young people. In this study, we aimed to explore the OTC consumption and related misuse in Italy and identify the demographic characteristics of people/individuals involved in this phenomenon, understanding eventual risk factors. METHODS: The study consisted of an anonymous online survey distributed by direct contact and via the Internet between June-November 2021 to the general population living in Italy. Descriptive statistics were reported, and binary regression analyses were performed to identify risk factors for lifetime misuse of OTC. The University of Hertfordshire approved the study (aLMS/SF/UH/02951). RESULTS: The final sample size was composed of 717 respondents. The sample was mainly represented by female (69.3%) students (39.9%) in the 20-25 years age group (30.0%). Based on the survey responses, study participants were divided into two groups according to the presence/absence of OTC abuse/misuse (127 versus 590), which were compared for possible predictors of OTC diversion. Multivariate regression showed that OTC abuse/misuse was associated with the knowledge of the effects of OTC [odds ratio/OR = 2.711, 95%Confidence Interval/CI 1.794-4.097, p <0.001]. On the contrary, the educational level appeared to be a protective factor [OR = 0.695, 95%CI 0.58-0.94, p = 0.016]. CONCLUSION: Although, according to our data, the phenomenon of OTC abuse appeared to be limited, increasing attention is needed because of possible underestimation and high-risk outcomes. Preventive strategies, including simplified access to information, may play a key role in limiting OTC misuse.

Ibogaine/Noribogaine in the Treatment of Substance Use Disorders: A Systematic Review of the Current Literature.

BACKGROUND: Ibogaine and noribogaine are psychedelic substances with dissociative properties naturally occurring in plants of the Apocynaceae family. Research has shown their efficacy in treating substance use disorders (SUD), particularly in opiate detoxification, but their efficacy and toxicity are still unclear. OBJECTIVE: This review aims to assess the anti-addictive role of ibogaine and evaluate its side effects. METHODS: A systematic literature review was conducted on the 29th of November 2021 using PubMed, Scopus and Web of Science databases through the following search strategy: ("Ibogaine" OR "Noribogaine") AND ("SUD" OR "substance use disorder" OR "craving" OR "abstinence" OR "withdrawal" OR "addiction" OR "detoxification") NOT animal NOT review NOT "vitro." The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was followed for data gathering purposes. Research methods were registered on PROSPERO (CRD42021287034). RESULTS: Thirty-one articles were selected for the systematic revision, and two were considered for analysis. The results were organised according to the type of study: case reports/case series, randomised- controlled trials (RCTs), open-label, survey and observational studies. The main outcomes were related to the anti-addictive effect of ibogaine and its cardiac toxicity. A meta-analysis of side effects was conducted using RevMan 5.4 software, showing a significant risk of developing headaches after ibogaine/noribogaine treatment. CONCLUSION: The results show some efficacy of ibogaine in the treatment of SUDs, but its cardiotoxicity and mortality are worrying. Further studies are needed to assess its therapeutic efficacy and actual safety.

Recreational Drug Misuse and Its Potential Contribution to Male Fertility Levels' Decline: A Narrative Review.

Recreational drug intake may be associated with a range of medical untoward consequences, including male infertility. However, as the related evidence is still limited, the main outcome of this review is to provide a better understanding of the existence of any association between recreational drug misuse and male fertility levels' decline. Whilst searching the MEDLINE/PubMed, a comprehensive overview of the literature regarding male infertility and substances of abuse (e.g., phytocannabinoids, opiates/opioids, stimulants, 'herbal highs', psychedelics, and 'novel psychoactive substances) was here undertaken. Due to the paucity of robust, high-quality, empirical, human studies, a narrative strategy was here preferred over a systematic approach. Relevant data are qualitatively analyzed and presented in a table. Although most available evidence is in support of a detrimental role of cannabis on human spermatogenesis, a few remaining studies failed to document any effect of this drug on seminal quality, and it is not clear to which extent this drug impacts fertility rates/time to pregnancy. The current understanding of the impact of opiate-, cocaine- and amphetamine/stimulant-misuse on human reproduction is widely unknown, and most studies dealing with this matter represent only an extrapolation of data derived from specific clinical circumstances. Although the message of 'no smoking, no alcohol and no street drugs' should always be offered as good health advice to all patients seeking medical help for fertility issues, robust scientific clinical evidence in support of a direct detrimental impact of recreational drugs on spermatogenesis is scant to date.

Atypical Antipsychotic Drugs in Dual Disorders: Current Evidence for Clinical Practice.

BACKGROUND: Concurrent disorder or dual diagnosis refers to a combination of substance use disorders and mental disorders that occur in the same patient simultaneously. These conditions pose significant clinical and healthcare impacts and are often underdiagnosed, undertreated, and complex to manage. OBJECTIVE: We assessed the quality of current pharmacological recommendations for the management of dual diagnosis, particularly by evaluating the use of second-generation antipsychotics (SGA). METHODS: A literature search was performed using the PubMed and Scopus databases for publications up to September 21, 2021, without any time restrictions. The following search strings were used: (aripiprazole OR brexpiprazole OR cariprazine OR paliperidone OR risperidone OR quetiapine OR clozapine OR olanzapine) AND (psychosis OR schizophrenia OR schizoaffective) AND ("substance use disorder" OR cocaine OR alcohol OR cannabis OR heroin OR "double diagnosis" OR "dual diagnosis")) NOT (animal OR rat OR mouse) NOT (review or meta-analysis). RESULTS: The search produced a final set of 41 articles. Most patients were males and were affected by schizophrenia, with cannabis the most abused substance, followed by alcohol. Aripiprazole was the most used drug, either orally or by long-acting formulations, followed by risperidone with oral and long-acting formulations, clozapine, olanzapine, and quetiapine. CONCLUSION: The findings highlight the use of SGA for the treatment of psychotic symptoms in comorbidity with substance use. Future studies on people with dual diagnosis and focused on long-term evaluations are warranted and need to investigate the efficacy of newly introduced molecules, such as partial D2 agonists and longacting injectable antipsychotics.

What role for cognitive remediation in the treatment of depressive symptoms? A superiority and noninferiority meta-analysis for clinicians.

BACKGROUND: Cognitive remediation (CR) is a promising technique in the treatment of the cognitive dimension of depression. The present study evaluated the potential of CR in treating depressive symptoms and provides practical information about its usefulness in clinical settings. METHODS: We performed two meta-analyses of published randomized (and nonrandomized) clinical trials, comparing CR to control conditions in subjects with current depressive symptomatology. The superiority meta-analysis aimed to determine the superiority of CR when compared with placebo/waiting list interventions and its efficacy when used as an augmentation therapy. The noninferiority meta-analysis determined whether CR had noninferior efficacy compared with standard antidepressant interventions. RESULTS: CR was found to significantly improve depressive symptomatology in the superiority meta-analysis (CR: n = 466, control n = 478). Moreover, CR seemed to be noninferior to standard antidepressant interventions (CR: n = 230, control n = 235). CR was more effective when addressing hot (vs. cold) cognition, when involving younger patients (i.e., <30 years), and in the case of mild-moderate (vs. severe) depression. CONCLUSIONS: CR should be considered an augmentation treatment to improve treatment outcomes in depressed subjects, especially among young individuals. Interventions addressing hot cognition seem to be the most promising.

Misuse of Anticholinergic Medications: A Systematic Review.

(1) Background: Over the last decade, misuse and diversion of medications has appeared to be increasingly concerning phenomena, including a range of different molecules. As current knowledge on the abuse of centrally acting anticholinergics is limited, the aim of the present study is to review the relevant published data, focusing on the following molecules: benztropine, biperiden, scopolamine, orphenadrine, and benzhexol/trihexyphenidyl (THP). (2) Methods: A systematic literature review was carried out using Pubmed, Scopus, and Web of Science databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Research methods were registered on PROSPERO (CRD42021257293). (3) Results: A total of 48 articles, including case reports, surveys, and retrospective case series analyses, were included. Most articles focused on benzhexol/THP (n = 25), and benztropine (n = 4). The routes of administration were mostly oral, and macrodoses together concomitant illicit drugs, e.g., cocaine, have been recorded. Toxidromes included both physical (e.g., tachycardia, tachypnoea, dilatated pupils, dry skin, urinary retention, ataxia, etc.) and psychiatric symptoms (e.g., anxiety, agitation, delirium, etc.). Fatal outcomes were very rare but reported. (4) Conclusion: Results from the present study show that anticholinergic misusing issues are both widespread worldwide and popular. Considering the potential adverse effects associated, healthcare professionals should be vigilant and monitor eventual misusing issues.

From a Cycle to a Period: The Potential Role of BDNF as Plasticity and Phase-Specific Biomarker in Cocaine Use Disorder.

Cocaine Use Disorder (CUD) is one of the diseases with the greatest social and health impact, due to the high cost of rehabilitation management and the high risk of dangerous behavior and relapse. This pathology frequently leads to unsuccessful attempts to interrupt the consumption, resulting in relapses and a vicious cycle of binge/intoxication, withdrawal/negative affect, and preoccupation/ anticipation (craving). The alternation of these phases in addiction was well illustrated by Koob and colleagues in the so-called "addictive cycle", which nowadays represents a landmark in the addiction field. Recently, there has been a surge of interest in the worldwide literature for biomarkers that might explain the different stages of addiction, and one of the most studied biomarkers is, without a doubt, Brain-derived Neurotrophic Factor (BDNF). In this perspective article, we discuss the potential role of BDNF as biomarker of the CUD phases described in the "Addictive Cycle", speculating about the close relationship between BDNF fluctuations and the clinical course of CUD. We also discuss BDNF's potential role as "staging" biomarker, predicting the progression of the disease. Finding valuable biomarkers of CUD severity and disease stage could shift clinicians' focus away from behavioral symptomatic treatment and toward a novel brain-based approach, allowing for the development of more effective and targeted therapeutic strategies, thus determining major benefits for CUD patients.

Hypomanic/manic switch after transcranial magnetic stimulation in mood disorders: A systematic review and meta-analysis.

BACKGROUND: Nowadays there is an increasing use of transcranial magnetic stimulation (TMS) both in neurological and psychiatric fields. After Food and Drug Administration approval of TMS for the therapy of treatment-resistant depression, TMS has been widely used in the context of mood disorders (MD). However, growing reports regarding the possibility of developing hypomanic/manic switch (HMS) have generated concern regarding its use in MDs. AIM: To investigate the actual risk of developing HMS due to TMS in the treatment of MD. METHODS: We led our research on PubMed, Scopus and Web of Science on March 22, 2020, in accordance to the PRISMA guidelines for systematic review. Only double blind/single blind studies, written in English and focused on the TMS treatment of MD, were included. A meta-analysis of repetitive TMS protocol studies including HMS was conducted using RevMan 5.4 software. The assessment of Risk of Bias was done using Cochrane risk of bias tool. This protocol was registered on PROSPERO with the CRD42020175811 code. RESULTS: Twenty-five studies were included in our meta-analysis: Twenty-one double blind randomized controlled trials (RCT) and four single blind-RCT (no. of subjects involved in active stimulation = 576; no. of subjects involved in sham protocol = 487). The most frequently treated pathology was major depressive episode/major depressive disorder, followed by resistant depression, bipolar depression and other MD. The majority of the studies used a repetitive TMS protocol, and the left dorsolateral prefrontal cortex was the main target area. Side effects were reported in eight studies and HMS (described as greater energy, insomnia, irritability, anxiety, suicidal attempt) in four studies. When comparing active TMS vs sham treatment, the risk of developing HMS was not significantly different between conditions. CONCLUSION: Applying the most usual protocols and the appropriate precautionary measures, TMS seems not to be related to HMS development.

Therapeutic Potentials of Ketamine and Esketamine in Obsessive-Compulsive Disorder (OCD), Substance Use Disorders (SUD) and Eating Disorders (ED): A Review of the Current Literature.

The obsessive-compulsive spectrum refers to disorders drawn from several diagnostic categories that share core features related to obsessive-compulsive disorder (OCD), such as obsessive thoughts, compulsive behaviors and anxiety. Disorders that include these features can be grouped according to the focus of the symptoms, e.g., bodily preoccupation (i.e., eating disorders, ED) or impulse control (i.e., substance use disorders, SUD), and they exhibit intriguing similarities in phenomenology, etiology, pathophysiology, patient characteristics and clinical outcomes. The non-competitive N-methyl-D-aspartate receptor (NMDAr) antagonist ketamine has been indicated to produce remarkable results in patients with treatment-resistant depression, post-traumatic stress disorder and OCD in dozens of small studies accrued over the past decade, and it appears to be promising in the treatment of SUD and ED. However, despite many small studies, solid evidence for the benefits of its use in the treatment of OCD spectrum and addiction is still lacking. Thus, the aim of this perspective article is to examine the potential for ketamine and esketamine in treating OCD, ED and SUD, which all involve recurring and intrusive thoughts and generate associated compulsive behavior. A comprehensive and updated overview of the literature regarding the pharmacological mechanisms of action of both ketamine and esketamine, as well as their therapeutic advantages over current treatments, are provided in this paper. An electronic search was performed, including all papers published up to April 2021, using the following keywords ("ketamine" or "esketamine") AND ("obsessive" OR "compulsive" OR "OCD" OR "SUD" OR "substance use disorder" OR "addiction" OR "craving" OR "eating" OR "anorexia") NOT review NOT animal NOT "in vitro", on the PubMed, Cochrane Library and Web of Science online databases. The review was conducted in accordance with preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. The use and efficacy of ketamine in SUD, ED and OCD is supported by glutamatergic neurotransmission dysregulation, which plays an important role in these conditions. Ketamine's use is increasing, and preliminary data are optimistic. Further studies are needed in order to better clarify the many unknowns related to the use of both ketamine and esketamine in SUD, ED and OCD, and to understand their long-term effectiveness.

New Psychoactive Substances and Suicidality: A Systematic Review of the Current Literature.

Background and Objectives: Over the past twenty years a large number of new psychoactive substances (NPS) have entered and modified the recreational drug scene. Their intake has been associated with health-related risks, especially so for vulnerable populations such as people with severe mental illness, who might be at higher risk of suicidality or self-injurious behavior. This paper aims at providing an overview of NPS abuse and the effects on mental health and suicidality issues, by performing a literature review of the current related knowledge, thereby identifying those substances that, more than others, are linked to suicidal behaviors. Materials and Methods: A comprehensive and updated overview of the literature regarding suicidality and NPS categories has been undertaken. An electronic search was performed, including all papers published up to March 2021, using the following keywords "NPS" OR "new psychoactive substances" OR "novel psychoactive substances" OR "synthetic cannabinoids" OR "phenethylamines" OR "synthetic cathinones" OR "tryptamines" OR "piperazines" OR "new synthetic opioids" OR "designer benzodiazepines" AND ("suicide" OR "suicidality") NOT review NOT animal on the PubMed, Cochrane Library, and Web of Science online databases. Results: Suicidality and self-injurious behavior appear to be frequently associated with some NPS such as cathinones, synthetic cannabinoids, and new synthetic opioids. The results are organized according to the substances recorded. Conclusion: The growing use of NPS has become a significant clinical issue, causing increasing concern and challenges for clinicians working in both mental health and emergency departments. Thus, considering the associations between NPS and suicidality or self-injurious behaviors, areas where suicide-prevention efforts and strategies might be focused are the early detection, monitoring, and restriction of NPS.

Focus on Over-the-Counter Drugs' Misuse: A Systematic Review on Antihistamines, Cough Medicines, and Decongestants.

Background: Over the past 20 years or so, the drug misuse scenario has seen the emergence of both prescription-only and over-the-counter (OTC) medications being reported as ingested for recreational purposes. OTC drugs such as antihistamines, cough/cold medications, and decongestants are reportedly the most popular in being diverted and misused. Objective: While the current related knowledge is limited, the aim here was to examine the published clinical data on OTC misuse, focusing on antihistamines (e.g., diphenhydramine, promethazine, chlorpheniramine, and dimenhydrinate), dextromethorphan (DXM)- and codeine-based cough medicines, and the nasal decongestant pseudoephedrine. Methods: A systematic literature review was carried out with the help of Scopus, Web of Science databases, and the related gray literature. For data gathering purposes, both the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and PROSPERO guidelines were followed (PROSPERO identification code CRD42020209261). Results: After completion of the selection, eligibility, and screening phases, some 92 articles were here taken into consideration; case reports, surveys, and retrospective case series analyses were included. Findings were organized according to the specific OTC recorded. Most articles focused here on DXM (n = 54) and diphenhydramine (n = 12). When specified, dosages, route(s) of administration, toxicity symptoms (including both physical and psychiatric ones), and outcomes were here reported. Conclusion: Results from the systematic review showed that the OTC misusing issues are both widespread worldwide and popular; vulnerable categories include adolescents and young adults, although real prevalence figures remain unknown, due to a lack of appropriate monitoring systems. Considering the potential, and at times serious, adverse effects associated with OTC misusing issues, healthcare professionals should be vigilant, and ad hoc preventative actions should be designed and implemented.

PON1 polymorphisms can predict generalized anxiety and depressed mood in patients with multiple chemical sensitivity.

Background: Multiple chemical sensitivity (MCS) is a chronic condition with somatic, cognitive and affective symptoms that follow contact with chemical agents at usually non toxic concentrations. We aimed to assess the role of genetic polymorphisms involved in oxidative stress on anxiety and depression in MCS. Materials & methods: Our study investigated the CAT rs1001179, MPO rs2333227, PON1 rs662 and PON1 rs705379 polymorphisms in MCS. Results: The AG genotype of the PON1 rs662 and the TT and CT genotypes of the PON1 rs705379 were involved in anxiety and depression. Discussion: These results are in line with existing evidence of PON1 involvement in MCS and suggest a further role of this gene in the exhibition of anxiety and depression in this disease.

Multiple Chemical Sensitivity Syndrome: A Principal Component Analysis of Symptoms.

Multiple Chemical Sensitivity (MCS) is a chronic and/or recurrent condition with somatic, cognitive, and affective symptoms following a contact with chemical agents whose concentrations do not correlate with toxicity in the general population. Its prevalence is not well defined; it mainly affects women between 40 and 50 years, without variations in ethnicity, education and economic status. We aimed to assess the core symptoms of this illness in a sample of Italian patients. Two physicians investigated different symptoms with a checklist compilation in 129 patients with MCS (117 women). We conducted a categorical Principal Component Analysis (CATPCA) with Varimax rotation on the checklist dataset. A typical triad was documented: hyperosmia, asthenia, and dyspnoea were the most common symptoms. Patients also frequently showed cough and headache. The CATPCA showed seven main factors: 1, neurocognitive symptoms; 2, physical (objective) symptoms; 3, gastrointestinal symptoms; 4, dermatological symptoms; 5, anxiety-depressive symptoms; 6, respiratory symptoms; 7, hyperosmia and asthenia. Patients showed higher mean prevalence of factors 7 (89.9%), 6 (71.7%), and 1 (62.13%). In conclusion, MCS patients frequently manifest hyperosmia, asthenia, and dyspnoea, which are often concomitant with other respiratory and neurocognitive symptoms. Considering the clinical association that is often made with anxiety, more studies are necessary on the psychosomatic aspects of this syndrome. Further analytical epidemiological studies are needed to support the formulation of aetiological hypotheses of MCS.

Placebo Effect in Obsessive-Compulsive Disorder (OCD). Placebo Response and Placebo Responders in OCD: The Trend Over Time.

BACKGROUND: Placebo response appears to be increasing in antidepressant, antipsychotic and various internal medicine trials. A similar trend has been reported for OCD during 1989-1999. Placebo response is generally considered as the extent to which placebo treatment is associated with core symptom improvement. In this analysis, we used Joinpoint regression to assess the time trend of both placebo response and placebo responder rates according to the year of publication with no time restriction in OCD drug trials. METHODS: We included drug and/or psychotherapy trials vs. placebo from PubMed, Embase, CINAHL, and PsycINFO retrieved through the search (placebo OR sham) AND (obsessive* OR OCD). We included studies through investigator consensus. We then performed on data of included studies log-linear joinpoint segmented regression models using a p<0.05 cutoff. RESULTS: We included 113 studies from 112 published papers. Placebo mean annual response rates in OCD studies significantly increased from 1991 to 2017 with an annual percent change (APC) of 0.66%, while placebo mean annual responder rates also significantly increased from 2010 to 2017, with an APC of 5.45%. Drug mean annual response rates in OCD studies significantly increased from 1987 to 2012 with an APC of 0.72%, while the corresponding responder rates did not show statistically significant APC changes between 1984 and 2017. CONCLUSION: We observed a tendency for placebo to increase both measures of response in OCD clinical drug trials through the years that tend to approximate the responses shown by drugs. Changes in the type of study (moving from classical head to head comparisons to add-on studies in treatmentresistant populations) and countries involved in experimentation may partially account for some portion of these results. It appears that placebo effects are becoming more elusive and out of control.