Pharmacological and cognitive neuroenhancement refer to the non-medical use of prescription drugs, alcohol, illegal drugs, or the so-called soft enhancers, to enhance cognition, mood, work or school performance, or to promote pro-social behaviour. Literature on the topic is meagre, and available data only partially enlightens their use.

The aim of this paper is to review and comment on the available literature on pharmacological neuroenhancement and, secondary, on emotional enhancement.

A systematic review was conducted according to the PRISMA guidelines. Pubmed, Scopus, Embase, PsychInfo and Google Scholar databases were accessed to select English language articles, published from 1980 to April 2020. 11746 papers were initially selected and 123 papers were finally included.

Available literature indicates a widespread and increasing use of different kinds of substances, drugs and food supplements mainly with neuroenhancing purposes, especially amongst specific populations of young healthy subjects. The evidence regarding their efficacy is controversial. Further, a limited or no awareness regarding the possible consequences of their abuse/misuse emerges amongst users.

Despite the limited evidence that some substances may improve cognitive functions in healthy subjects and neglecting their detrimental side effects and potential risk of misuse, abuse and addiction, there is an increasing worldwide use of the so-called neuroenhancers, especially in some categories of individuals, such as university students. Further studies are needed to collect reliable data on the effects of neuroenhancers in healthy subjects. Neuroenhancement puts into question the concept of authenticity, so that the problem requires to be analyzed within a complex ethical conceptual frame.

No significant relationships.

Many psychotropic drugs can induce weight gain with differences in their metabolic risk profiles (i.e. high, medium or low-risk).

To compare the weight evolution of patients switching versus patients keeping their psychotropic drugs with different risk-profiles.

Data for patients switching or keeping the same drug were obtained from the Psyclin (from 2007 to 2015) and Psymetab (2007- 2019) cohort studies, conducted at the Lausanne University Hospital, Switzerland. Patients either switched from a high to a low-risk, a high to a medium-risk, a medium to a low-risk drug, or for a drug with the same risk category. Patients not switching either kept a high, medium or low-risk drug. The evolution of weight is currently being analyzed using a linear mixed-effect model.

Preliminary results showed that switching from a high to low-risk molecule had the strongest impact on weight changes. The analysis being ongoing, the quantitative results will be presented at the congress.

Switching from a high-risk to a low-risk molecule is likely to have the strongest impact on weight changes.

No significant relationships.

Paliperidone Palmitate 3-month (PP3M) formulation, introduced in Italy since 2017, is an effective and safety therapeutic option for patients with schizophrenia, clinically stable with 1-month formulation (PP1M). Only a few “Real World” studies investigated the clinical relevance of PP3M and the long-term clinical and health resource utilization outcomes.

The aim of this retrospective, mirror image study was to evaluate the efficacy of PP3M in terms of continuity of care and number of hospitalizations.

Fifty outpatients treated with Paliperidone Palmitate (PP) were recruited from a Community Mental Health Centre (CMHC) in Milan. Statistical analysis were conducted with SPSS 26. Frequencies of hospitalization 6 months before and after the start of PP3M were compared using the McNemar test, setting the significance to p<0.05.

This study involved 34 patients (68%) treated with PP1M and 16 (32%) treated with PP3M.The median time interval between PP1M and PP3M was 14 months. After the switch to PP3M, 69% of patients continued to visit the CMHC with an unchanged frequency (50% once/month, 6% more than once/month), while 31% with a decreased frequency (once/3 months). No patient increased the frequency of CMHC visits or started visiting it discontinuously. 44% of subjects had had at least one hospitalization prior to the switch and no hospitalizations after (p=0.016). Moreover, no patients showed increased hospitalizations

In this study PP3M clinical relevance was confirmed comparing pre-initiation and post-initiation 6-months time intervals: hospitalizations number significantly decreased, while the continuity of care was preserved. Further studies on a greater sample are necessary to support these preliminary data.

No significant relationships.

Urine Drug Screening (USD) is one of the most used techniques for drug testing. However, one of the main issues related to USD is the high frequency of cross-reactivity with other molecules. Amphetamines, because of their simple structures, are highly subjected to cross-reactivity with other molecules.

Our aim was to investigate and characterize the role of psychopharmacological drugs in the occurrence of false-positive amphetamine drug screening, by performing an international pharmacovigilance study through the Food and Drug Administration Adverse Event Reporting System (FAERS), in which user’s medication errors for drugs are reported in the form of Individual Case Safety Reports (ICSRs).

All ICSRs recorded between 2010 and 2020 with a positive screening for amphetamine reported as adverse reaction in patients with a psychiatric diagnosis were included in the study. Duplicated records and ICSRs with missing values for age and gender, were excluded from the study.

Among 249 ICSRs involving false-positive amphetamine drug screening, 109 ICSRs reported psychiatric disorders and/or psychiatric drugs. In 83 (76%) cases, drugs were known for cross-react. 66 cases reported drugs known as “suspect”. 24% of cases reported unknown false-positive reactions: acetaminophen (5%), duloxetine (5%) and oxycodone (5%).

The high cross-reactivity of psychotropic drugs with amphetamine testing in USDs may be linked to the neuromodulatory effect of these drugs, suggesting a similar molecular structure. In this perspective, antidepressants and amphetamines share a similar mechanism of action, maybe partially explaining why the most reported cross-reactions are with antidepressant (59%).

No significant relationships.

Bariatric surgery is considered an effective treatment against obesity. Psychiatric illness is relatively common in patients who have undergone bariatric surgery. Over one-third of these patients are prescribed psychotropic drugs, particularly antidepressants. Unlike medications for diabetes, hypertension or hyperlipidemia, which are generally reduced and at times discontinued, postsurgery psychotropic use is only slightly reduced. The surgical intervention and the subsequent weight loss can affect several pharmacokinetic parameters, leading to a possible need of dosing adjustment.

To review the influence of bariatric surgery on the use and pharmacokinetics of psychotropic drugs.

Non-systematic review of literature through search on PubMed/MEDLINE for publications from 2011 to 2021, following the terms psychotropic and bariatric surgery. Textbooks were consulted.

It is difficult to predict how psychotropics will be affected by bariatric surgery because of interindividual differences and limited data. Malabsorptive surgical procedures have a relatively greater potential to alter drug exposure. Medication disintegration, dissolution, absorption, metabolism and excretion have been found to be altered in postbariatric patients. Antidepressants are the best studied psychotropics in the bariatric population and their absorption is reduced. The risk of gastric bleeds with bariatric surgery will probably be increased by serotoninergic antidepressants. Antipsychotics and mood stabilisers are not well studied in these patients. Depot antipsychotics avoid the risk of reduced absorption after surgery. Lithium use requires particular close monitoring.

Close treatment monitoring and the ongoing monitoring of symptoms are needed after bariatric surgery. Many patients may not require significant changes to drug treatment after surgery.

No significant relationships.

Obsessive Compulsive Disorder (OCD) and Tic Disorder (TD) are two highly disabling, comorbid and difficult-to-treat conditions. DSM-5 acknowledged a new “tic-related” specifier for OCD, i.e., Obsessive-Compulsive Tic-related Disorder (OCTD), which may show poor treatment response.

The aim of the present study was to evaluate rates and clinical correlates of response, remission and resistance to treatment in a large multicentre sample of OCD patients with versus without tics.

398 patients with a DSM-5 diagnosis of OCD with and without comorbid TD was assessed from ten psychiatric departments across Italy. Treatment response profiles in the whole sample were analysed comparing the rates of response, remission and treatment-resistance as well as related clinical features. Multivariate logistic regressions were performed to highlight possible treatment response related factors.

Later ages of onset of TD and OCD were found in the remission group. Moreover, significantly higher rates of psychiatric comorbidities, TD, and lifetime suicidal ideation and attempts were associated to the treatment-resistant group, with larger degrees of perceived worsened quality of life and family involvement.

While remission was related to later ages of OCD and TD onset, specific clinical factors, such as early onset and presence of psychiatric comorbidities and concomitant TD, predicted a worse treatment response, with a significant impairment in quality of life for both patients and their caregivers. These findings suggest a worse profile of treatment response for patients with OCTD.

No significant relationships.

No significant relationships.

Studies have demonstrated that Ziprasidone use may be beneficial in children. Determining its potential risks and benefits when used in children is therefore important.

To examine the tolerability of Ziprasidone, an atypical antipsychotic, in children and adolescents.

We conducted a literature search of open label or randomized control trials that report on Ziprasidone use in children on three databases: Embase, PsychInfo and PubMed using the PRISMA guidelines of Systematic review and Meta-analysis. Out of 1690 articles, 11 studies met inclusion criteria. Outcome measures included adverse effects such as weight gain, increase in BMI, QTc prolongation, changes in metabolic parameters, sedation, and dizziness. We conducted a random effects meta-analysis and meta-regression of potential moderators. Publication bias was assessed with funnel plots.

Data from Eleven studies was meta-analyzed (Total n= 474, mean age=12.87 years, male= 68..37%) that reported the use of Ziprasidone in children and adolescents with Psychosis, Bipolar, Autism spectrum disorders and Tourettes syndrome. Mean Ziprasidone dose = 84.40 mg and mean study duration = 2.85 months). We found that Ziprasidone was not found to cause any significant weight gain (1.72, p>0.05) or change in BMI (0.58 , p>0.05). QTc prolongation was found to be significant (11.9 , p<0.05). Most common side effects were sedation (42.44%), Nausea(19.32%), Headache (22.92%), fatigue (16.67%) and Dizziness (16.96 %).

Results demonstrate that Ziprasidone does not cause significant weight gain, however QTc prolongation and sedation were found to be significant side effects of Ziprasidone use. Therefore, baseline EKG and thorough history must be obtained before prescribing Ziprasidone in children and adolescents.

No significant relationships.

Patients with severe mental disease have a considerably shorter lifespan than the general population. The majority of psychiatric drugs are metabolized by the liver. Cytochromes play a central role, interactions between drugs are expected. Neuroleptics are frequently associated with weight gain, steatosis development, elevation of liver enzymes and rare acute cytolytic hepatitis, particularly with clozapine and olanzapine. Mood stabilizers, like Valproate classically gives mitochondrial steatosis with potentially important damages, and also possible acute liver failure.

This case presents a 56-year-old patient, previously diagnosed of schizoaffective disorder, with chronic psychotic symptoms that showed high drug resistance. She had been treated in the past with most common antipsychotic drugs with no clinical response. While being in treatment with valproate and olanzapine, she was started on clozapine while olanzapine removed. Two weeks later she developed Acute Pharmacologic Hepatitis with mild liver failure.

Physical examination was normal. Mental exam revealed presence of delusion. Blood tests showed: hyperbilirubinemia and mil coagulopathy. Clozapine dose was reduced and valproate was suspended.

The patient showed a substantial improvement of hepatic damage. Delusions are active after 12 weeks of treatment with clozapine.

Psychiatric disorders and liver illnesses are entangled in multiple ways. Screening for liver diseases is essential in order to prevent liver complications in patients receiving psychotropic medications. Further investigation of combinations of agents such as mood stabilizers and atypical antipsychotics may yield valuable insights into the potential of combination therapies to enhance clinical outcomes in patients with Severe Mental Disease.

No significant relationships.

Brexpiprazole is a novel antipsychotic drug. It exerts antagonistic activity at the serotonin 5HT2A, 5HT2B, 5HT7 and noradrenaline alpha 1b/2c receptors; it also acts as partial agonist of serotonin 5HT1 and dopamine D2, D3 receptors. Brexpiprazole is approved for the treatment of schizophrenia and as an add-on therapy for major depression.

This pilot study aims at exploring efficacy and tolerability of Brexpiprazole in a small sample of patients diagnosed with either a psychotic or a mood disorder.

This observational study was conducted at our Acute Psychiatric Inpatient Unit. We included 7 patients (5 males, 2 females) hospitalized between 2020 and 2021, diagnosed with schizophrenia spectrum disorders or mood disorders with psychotic symptoms confirmed by Mini International Neuropsychiatric Interview. Patients who participated signed an informed consent. Information concerning diagnosis, demographic characteristics (age, sex, education, marital status) and pharmacological therapy were collected examining clinical records. The average lenght of hospitalization was 13.4 days. Psychopathology was assessed by means of the PANSS and the severity of the illness was evaluated with CGI severity scale (CGI-S), both on admission and discharge. We also administered the UKU scale to evaluate the tolerability profile.

.

Results can be seen in figures 1, 2, 3

Our study found a significant improvement in both positive and negative symptoms, with good tolerability. Limitations of our study are: small sample size and limited period of observation. These premises suggest that further research is needed in order to elucidate the exact mechanisms underlying Brexpiprazole’s action and the possible implication in mood disorders.

No significant relationships.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome refers to a cluster of clinical symptoms/signs related to drug hypersensitivity. The main clinical features include fever, skin rash, eosinophilia, enlarged lymph nodes, atypical lymphocytosis, and involvement of at least one internal organ. Clozapine-related DRESS syndrome has been rarely reported, but this may be due to a different clinical presentation pattern compared to DRESS for other culprit drugs.

We aimed to assess clusters of main clinical features of clozapine-related DRESS.

We ran a network analysis for clinical manifestations in the pooled sample of all previous published cases of clozapine-related DRESS.

We observed a triad of core symptoms (i.e., organ implication, fever, and eosinophilia) among DRESS criteria co-occurring in 59.3% (n=16) of 27 patients. The organs most likely to be involved in clozapine-related DRESS included lungs, liver, heart, and kidneys. Fever was also present in almost all cases (n=25 patients), while eosinophilia was observed in two thirds of the sample (n=18 patients).

Regarding clinical manifestations clozapine-related DRESS may differ from DRESS for other culprit drugs as skin reaction is not very typical; thus, clinicians need to consider DRESS as a potential diagnosis even in absence of a skin reaction. When managing clozapine-treated patients with the core triad of organ implication, fever, and eosinophilia clinicians should consider guidelines for DRESS treatment.

No significant relationships.

Clozapine, the first atypical antipsychotic, is a highly effective medication for patients with treatment-resistant schizophrenia. Robust evidence describes important risk for psychosis in immigrant population(2). Despite this, some studies suggest that immigrant patients are less treated and misdiagnosed due to cultural barriers(3,4). Clozapine and Electroconvulsive therapy tend to be less prescribed in immigrants(3). However, few studies assess differences in clozapine prescription between immigrants and non-immigrant psychotic inpatients.

To describe and compare clozapine prescription between psychotic patients and non-psychotic patients in a sample of Acute and Chronic inpatients.

Patients who have presented, according to DSM-V criteria, one or more non-affective psychotic episodes, were recruited in Acute and Chronic inpatients units leading to a total sample of 198 patients. Immigrant condition was defined as “a person who comes to live permanently in a foreign country”. Demographic characteristics of patients, clinical data and main pharmacological treatment were recorded through a questionnaire. Comparative analysis was performed with IBM SPSS Statistics using Chi-Square Test and t-Student test.

From a total of 198patients clozapine was prescribed to 31(15,7%). From the total immigrant sample only 7,1% had prescribed clozapine compared to 24,2% from the locals(p<0.005). Significant differences in diagnosis associated to clozapine were found between both groups : Schizophrenia(57,1%immigrants, 57,1%locals), Schizoaffective disorder(14,3%immigrants, 41,7%locals) and Non specific psychosis (28,3%immigrants, 8,3%locals).

According to our results, immigrant psychotic inpatients receive less clozapine prescription compared to non-immigrant psychotic patients. There results should be considered to study barriers for clozapine prescription in this population and offer a treatment based in equality.

No significant relationships.

Despite the widespread use of long-acting injectable (LAI) antipsychotics in schizophrenia and other disorders, there is a lack of longitudinal studies evaluating prescription trends and the usefulness of therapeutic drug monitoring (TDM) to inform dosing. Indeed, LAI prescription varies greatly among different areas of the world and over the years.

Assess trends in LAI prescription in 2013-2020 at the Psychiatry Department of Bozen, Italy, and (2) analyze the correlation between dose of prescribed LAIs and blood levels measured via TDM.

Parametric statistics.

LAIs were administered to 471 patients (x̅ age±SD=47.2±16.3 years; 56.3% men). The pie chart shows LAI treatment duration, i.e., from 1 to 7 consecutive years. The most used LAIs were haloperidol in 2013-2104 (26.5-31.8%) and paliperidone in 2015-2020 (22.5-25.7%). Dose adjustments were rather frequent, whereas the switch between LAI, due to moderate-to-side effects or unsatisfactory improvement of clinical status, was infrequent (41 cases/8 years). LAI interruption for the same reasons or non-compliance was even more infrequent (10 cases), but in 8 cases it happened for opposite reasons, i.e., achievement of patients’ stabilization and good compliance. The Table shows doses and plasma levels of LAIs. Correlations between doses and plasma levels were: haloperidol: r=-0.037, p=0.620; paliperidone: r=0.290; p=0.000; risperidone: r=0.219, p=0.006; fluphenazine r=0.358, p=0.000; aripiprazole: r=-0.051, p=0.610; olanzapine: r=-0.090, p=0.634.

Haloperidol and paliperidone were the most used LAIs. Drug prescription trends and doses were stable over time. A significant positive correlation between dose and plasma level was found for paliperidone, fluphenazine, and aripiprazole.

No significant relationships.