A multivariate approach to investigate the associations of electrophysiological indices with schizophrenia clinical and functional outcome.

BACKGROUND: Different electrophysiological (EEG) indices have been investigated as possible biomarkers of schizophrenia. However, these indices have a very limited use in clinical practice, as their associations with clinical and functional outcomes remain unclear. This study aimed to investigate the associations of multiple EEG markers with clinical variables and functional outcomes in subjects with schizophrenia (SCZs). METHODS: Resting-state EEGs (frequency bands and microstates) and auditory event-related potentials (MMN-P3a and N100-P3b) were recorded in 113 SCZs and 57 healthy controls (HCs) at baseline. Illness- and functioning-related variables were assessed both at baseline and at 4-year follow-up in 61 SCZs. We generated a machine-learning classifier for each EEG parameter (frequency bands, microstates, N100-P300 task, and MMN-P3a task) to identify potential markers discriminating SCZs from HCs, and a global classifier. Associations of the classifiers' decision scores with illness- and functioning-related variables at baseline and follow-up were then investigated. RESULTS: The global classifier discriminated SCZs from HCs with an accuracy of 75.4% and its decision scores significantly correlated with negative symptoms, depression, neurocognition, and real-life functioning at 4-year follow-up. CONCLUSIONS: These results suggest that a combination of multiple EEG alterations is associated with poor functional outcomes and its clinical and cognitive determinants in SCZs. These findings need replication, possibly looking at different illness stages in order to implement EEG as a possible tool for the prediction of poor functional outcome.

Dopamine DRD2 and DRD3 Polymorphisms Involvement in Nicotine Dependence in Patients with Treatment-Resistant Mental Disorders.

Patients affected by mental disorders smoke more than the general population. The reasons behind this habit are genetic, environmental, etc. This study aims to investigate the correlations between some polymorphisms and the smoking habits and nicotine dependence in patients with psychiatric disorders. We recruited 88 patients with treatment-resistant mental disorders, including 35 with major depressive disorder, 43 with bipolar spectrum disorder, and 10 with schizophrenia spectrum disorder. We carried out a clinical and psychometric assessment on current smoking habits, years of smoking, number of daily cigarettes, and level of nicotine addiction. The patients performed a peripheral blood sample for DNA analyses of different polymorphisms. We searched for correlations between the measures of nicotine addiction and analysed genotypes. The expression of the T allele of the DRD2 rs1800497 and DRD3 rs6280 polymorphisms significantly correlated with a lower level of nicotine dependence and lower use of cigarettes. We did not find significant correlations between nicotine dependence and OPRM1 rs1799971, COMT rs4680 and rs4633 polymorphisms, CYP2A6 rs1801272 and rs28399433, or 5-HTTLPR genotype. Concluding, DRD2 rs1800497 and DRD3 rs6280 polymorphisms are involved in nicotine dependence and cigarette smoking habits in patients with treatment-resistant mental disorders.

Pharmacogenomics-Guided Pharmacotherapy in Patients with Major Depressive Disorder or Bipolar Disorder Affected by Treatment-Resistant Depressive Episodes: A Long-Term Follow-Up Study.

Treatment-resistant depression (TRD) reduces affected patients' quality of life and leads to important social health care costs. Pharmacogenomics-guided treatment (PGT) may be effective in the cure of TRD. The main aim of this study was to evaluate the clinical changes after PGT in patients with TRD (two or more recent failed psychopharmacological trials) affected by bipolar disorder (BD) or major depressive disorder (MDD) compared to a control group with treatment as usual (TAU). We based the PGT on assessing different gene polymorphisms involved in the pharmacodynamics and pharmacokinetics of drugs. We analyzed, with a repeated-measure ANOVA, the changes between the baseline and a 6 month follow-up of the efficacy index assessed through the Clinical Global Impression (CGI) scale, and depressive symptoms through the Hamilton Depression Rating Scale (HDRS). The PGT sample included 53 patients (26 BD and 27 MDD), and the TAU group included 52 patients (31 BD and 21 MDD). We found a significant within-subject effect of treatment time on symptoms and efficacy index for the whole sample, with significant improvements in the efficacy index (F = 8.544; partial η² = 0.077, p < 0.004) and clinical global impression of severity of illness (F = 6.818; partial η² = 0.062, p < 0.01) in the PGT vs. the TAU group. We also found a significantly better follow-up response (χ² = 5.479; p = 0.019) and remission (χ² = 10.351; p = 0.001) rates in the PGT vs. the TAU group. PGT may be an important option for the long-term treatment of patients with TRD affected by mood disorders, providing information that can better define drug treatment strategies and increase therapeutic improvement.

Investigating the Relationships of P3b with Negative Symptoms and Neurocognition in Subjects with Chronic Schizophrenia.

Neurocognitive deficits and negative symptoms (NS) have a pivotal role in subjects with schizophrenia (SCZ) due to their impact on patients' functioning in everyday life and their influence on goal-directed behavior and decision-making. P3b is considered an optimal electrophysiological candidate biomarker of neurocognitive impairment for its association with the allocation of attentional resources to task-relevant stimuli, an important factor for efficient decision-making, as well as for motivation-related processes. Furthermore, associations between P3b deficits and NS have been reported. The current research aims to fill the lack of studies investigating, in the same subjects, the associations of P3b with multiple cognitive domains and the expressive and motivation-related domains of NS, evaluated with state-of-the-art instruments. One hundred and fourteen SCZ and 63 healthy controls (HCs) were included in the study. P3b amplitude was significantly reduced and P3b latency prolonged in SCZ as compared to HCs. In SCZ, a positive correlation was found between P3b latency and age and between P3b amplitude and the Attention-vigilance domain, while no significant correlations were found between P3b and the two NS domains. Our results indicate that the effortful allocation of attention to task-relevant stimuli, an important component of decision-making, is compromised in SCZ, independently of motivation deficits or other NS.

Current Clinical Psychopharmacology in Borderline Personality Disorder.

BACKGROUND: Patients with Borderline Personality Disorder (BPD) manifest affective and behavioral symptoms causing personal distress, relationship difficulties, and reduced quality of life with global functioning impairment, mainly when the disease takes an unfavorable course. A substantial amount of healthcare costs is dedicated to addressing these issues. Many BPD patients receive medications, mostly those who do not respond to psychological interventions. OBJECTIVE: Our aim was to assess the efficacy of the most used strategies of pharmacological interventions in BPD with a comprehensive overview of the field. METHODS: We searched the PubMed database for papers focused on the most used psychotropic drugs for BPD. We included randomized controlled trials and open studies in adult patients with BPD, focusing on the efficacy and tolerability of single classes of drugs with respect to specific clinical presentations that may occur during the course of BPD. RESULTS: Specific second-generation antipsychotics (SGAs) or serotonergic antidepressants can be effective for different core symptoms of BPD, mainly including mood symptoms, anxiety, and impulse dyscontrol. Some atypical antipsychotics can also be effective for psychotic and dissociative symptoms. Specific antiepileptics can be useful in some cases in treating different BPD symptoms, mainly including mood instability, impulsiveness, and anger. CONCLUSION: No medication is currently approved for BPD, and clinicians should carefully assess the benefits and risks of drug treatment. Further studies are needed to identify specific personalized treatment strategies, also considering the clinical heterogeneity and possible comorbidities of BPD.

International Expert Opinions and Recommendations on the Use of Melatonin in the Treatment of Insomnia and Circadian Sleep Disturbances in Adult Neuropsychiatric Disorders.

Introduction: Insomnia and circadian rhythm disorders, such as the delayed sleep phase syndrome, are frequent in psychiatric disorders and their evaluation and management in early stages should be a priority. The aim of this paper was to express recommendations on the use of exogenous melatonin, which exhibits both chronobiotic and sleep-promoting actions, for the treatment of these sleep disturbances in psychiatric disorders. Methods: To this aim, we conducted a systematic review according to PRISMA on the use of melatonin for the treatment of insomnia and circadian sleep disorders in neuropsychiatry. We expressed recommendations for the use of melatonin in psychiatric clinical practice for each disorder using the RAND/UCLA appropriateness method. Results: We selected 41 studies, which included mood disorders, schizophrenia, substance use disorders, attention deficit hyperactivity disorders, autism spectrum disorders, neurocognitive disorders, and delirium; no studies were found for both anxiety and eating disorders. Conclusion: The administration of prolonged release melatonin at 2-10 mg, 1-2 h before bedtime, might be used in the treatment of insomnia symptoms or comorbid insomnia in mood disorders, schizophrenia, in adults with autism spectrum disorders, neurocognitive disorders and during sedative-hypnotics discontinuation. Immediate release melatonin at <1 mg might be useful in the treatment of circadian sleep disturbances of neuropsychiatric disorders.

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.

Economic Impact of Schizophrenia from a Hospital and Social Security System Perspective in Italy.

BACKGROUND: Schizophrenia is one of the mental disorders with the highest economic and social costs, with an important burden on patients, caregivers, and society. OBJECTIVE: The objective of this study was to estimate the direct and social security costs of schizophrenia in Italy. As far as direct costs are concerned, those related to hospitalizations and pharmaceutical expenditure have been analyzed, while disability benefits (DBs) and incapacity pensions (IPs) have been considered for the social security costs. METHODS: In order to provide annual economic burden of schizophrenia using the real-world data, we analyzed the main regional and national databases related to hospitalizations and pharmaceuticals. Hospitalizations have been analyzed considering the Hospital Information System, which collects all the information regarding hospital discharges from all public and private hospitals (psychiatric wards or residential facilities have not been considered). Hospitalizations with a discharge date between 2009 and 2016, and with a primary or secondary diagnosis of schizophrenia (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 295.xx) were selected. Hospital costs have been estimated considering the national tariffs associated with each selected hospitalization. In addition, using the same inclusion criteria, the average DBs (for workers with reduced working capacity) and IPs (for workers without working capacity) provided each year have been analyzed from the social security benefit applications database. The estimate of pharmaceutical expenditure was prepared based on the OsMed 2018 Report (Italian Medicines Agency, latest issue 18 July 2019). A one-way deterministic sensitivity analysis was conducted to examine the robustness of the results. RESULTS: In Italy from 2009 to 2016, schizophrenia had an important economic impact from a social perspective. On average, 13,800 patients were hospitalized, with an average of 2.98 hospitalizations per patient. From a National Health Service (NHS) perspective and with specific reference to hospitalizations, the annual economic burden was €101.4 million, with an average cost per patient of €7338. On the other hand, pharmaceutical expenditure amounts to over €147 million each year, while residential, semi-residential, and specialist facilities amount to approximately €1 billion. Again, schizophrenia led to approximately 15,000 recipients of social security benefits (DBs and IPs) yearly from 2009 to 2015, with an average annual expenditure of €160.1 million (average cost per patient = €10,675). CONCLUSIONS: Our study estimates an economic burden of schizophrenia of €1250 million per year in direct costs, of which 20% is related to hospitalizations and pharmaceutical expenditure. With regard to social security benefits, an average annual expenditure of €160.1 million was calculated (average cost per patient = €10,675).

[Evaluation and management of insomnia in clinical practice and in the time of CoViD-19 in Italy: expert consensus and task-force recommendations from five scientific societies]. / Valutazione e trattamento dell'insonnia nella pratica clinica e ai tempi di CoViD-19 in Italia: raccomandazioni del panel di esperti e della task-force integrata di cinque società scientifiche.

Insomnia symptoms might affect about 60% of the Italian population. Insomnia is a "24 hours syndrome" and a risk factor for medical and mental disorders. It should always be assessed and treated in the clinical practice. Cognitive Behavioral Therapy for Insomnia is the first line treatment but its availability in Italy is scarce. Pharmacological options in Italy are: melatonin 2 mg prolonged release that should be the first choice in subjects ≥55 years old and used until 13 weeks; and for a short term use (≤4 weeks) Z-drugs or short-acting benzodiazepines (in subjects <65 years old) or a sedating antidepressant.

Expert Opinions and Consensus Recommendations for the Evaluation and Management of Insomnia in Clinical Practice: Joint Statements of Five Italian Scientific Societies.

BACKGROUND: Insomnia is the most commonly reported sleep problem in industrialized countries worldwide being present in about 36.8% of the general population. In Italy, such a percentage seems to be even higher. Although insomnia can be an independent disorder, it is most frequently observed as a comorbid condition and may precipitate, exacerbate, or prolong a broad range of comorbid conditions including physical and mental illnesses. Evaluating and targeting insomnia in the Italian clinical practice should be a priority. METHODS: The present expert options and recommendations development process was based on the RAND/UCLA Appropriateness Method for conceptualizing, designing, and carrying out the appropriateness of procedures for the diagnosis and treatment. Only available options in Italy were taken into considerations. RESULTS: We evaluated 12 international guidelines and 12 most recent systematic reviews for insomnia evaluation and treatment produced in the last 10 years. CONCLUSIONS: Our findings suggested that symptoms of insomnia must always be assessed in the Italian clinical practice by evaluating nocturnal and daytime symptoms, comorbid conditions and lifestyle. In a patient with chronic insomnia with and without comorbidity, insomnia treatment should be always initiated. CBT-Insomnia therapy should be the first option accordingly to availability. The choice of the drug should be based on different factors such as type of insomnia, age, comorbidities, and potential side effects. Melatonin 2 mg prolonged release should be the first choice in subjects >55 years. If the choice would be a Z-drug or a short-acting benzodiazepine (in subjects <65 years old) or a sedating antidepressant, the use should be in the short term (≤4 weeks) and then proceeds to tapering under clinical monitoring.

Long-Acting Injectable (LAI) Aripiprazole Formulations in the Treatment of Schizophrenia and Bipolar Disorder: a Systematic Review.

BACKGROUND: Several second-generation antipsychotics (SGAs) are available in long-acting injectable (LAI) formulations. OBJECTIVE: To systematically review the effects of the two formulations, Monohydrate and Lauroxil, of Aripiprazole LAI in patients with schizophrenia and bipolar disorder during an acute episode or during maintenance treatment. METHODS: On September 18, 2018, we adopted the following search strategy: (aripiprazole OR OPC-14597 OR Abilify) AND (long-acting OR depot OR LAI OR once monthly OR prolonged release OR monohydrate OR lauroxil) on PubMed, Cochrane, Scopus, CINAHL, PsycINFO, and Web of Science to identify randomised controlled trials. Furthermore, we searched the ClinicalTrials.gov site for possible additional studies. RESULTS: We included 28 papers dealing with randomised assignment of aripiprazole LAI formulations in schizophrenia and bipolar disorder in survival studies after stabilisation, in acute studies, and in head-to-head comparisons. Both monohydrate and lauroxil formulations reduced relapses/recurrences with respect to comparators (placebo or 50 mg once-monthly monohydrate) and improved symptomatology in acute schizophrenia. LIMITATIONS: Only a small number of studies were included in our review, with widely overlapping samples. While a high proportion of studies were wholly or partly industry-sponsored, their outcomes do not appear to have been affected. CONCLUSION: Aripiprazole LAI may to be efficacious in reducing relapse of schizophrenia and bipolar disorder in the long term in stabilised patients and in improving symptoms of schizophrenia during its acute phase, with both monohydrate and lauroxil formulations showing efficacy.

Drug Treatment of Trichotillomania (Hair-Pulling Disorder), Excoriation (Skin-picking) Disorder, and Nail-biting (Onychophagia).

BACKGROUND: Trichotillomania (TTM), excoriation (or skin-picking) disorder and some severe forms of onychophagia are classified under obsessive-compulsive and related disorders. There are different interacting neurotransmitter systems involved in the pathophysiology of impulse-control disorders, implicating noradrenaline, serotonin, dopamine, opioid peptides and glutamate, hence investigators focused on drugs able to act on these transmitters. Our aim was to critically review the efficacy of the drugs employed in impulse-control disorders. METHODS: We searched for controlled drug trials to treat TTM, excoriation, and/or nail-biting six databases (PubMed, Cochrane, Scopus, CINAHL, PsycINFO/PsycARTICLES, and Web of Science), using the search strategy: (trichotillomania OR "excoriation disorder" OR "face picking" OR "skin picking" OR "hair pulling" OR onychophagia OR "nail-biting") AND drug treatment on 12 March 2018 for all databases. We followed in our method of identifying relevant literature the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: SSRIs and clomipramine are considered first-line in TTM. In addition, family members of TTM patients are often affected by obsessive-compulsive spectrum disorders. Other drugs used in the treatment of TTM are lamotrigine, olanzapine, N-Acetylcysteine, inositol, and naltrexone. CONCLUSION: The treatment of TTM, excoriation disorder and nail-biting is still rather disappointing. Conjectures made from preclinical studies and the relative pathophysiological hypotheses found poor confirmations at a clinical level. There is a need for further studies and the integration of pharmacological and psychotherapeutic. Our results point to the need of integrating personalised medicine principles in the treatment of these patients.

Disorganization and cognitive impairment in schizophrenia: New insights from electrophysiological findings.

In subjects with schizophrenia (SCZ), the disorganization dimension is a strong predictor of real-life functioning. "Conceptual disorganization" (P2), "Difficulty in abstract thinking" (N5) and "Poor attention" (G11) are core features of the disorganization factor, evaluated using the Positive and Negative Syndrome Scale. The heterogeneity of this dimension and its overlap with neurocognitive deficits are still debated. Within the multicenter study of the Italian Network for Research on Psychoses, we investigated electrophysiological and neurocognitive correlates of disorganization and its component items to assess the heterogeneity of this dimension and its possible overlap with neurocognitive deficits. Resting state EEG was recorded in 145 stabilized SCZ and 69 matched healthy controls (HC). Spectral amplitude was averaged in ten frequency bands. Neurocognitive domains were assessed by MATRICS Consensus Cognitive Battery (MCCB). RAndomization Graphical User software explored band spectral amplitude differences between groups and correlations with disorganization and MCCB scores in SCZ. Correlations between disorganization and MCCB scores were also investigated. Compared to HC, SCZ showed increased delta, theta, and beta 1 and decreased alpha 2 activity. A negative correlation between alpha 1 and disorganization was observed in SCZ. At the item level, only "N5" showed the same correlation. MCCB neurocognitive composite score was associated with disorganization, "P2" and "N5". Our findings suggest only a partial overlap between disorganization and neurocognitive impairment. The association of alpha 1 with the "N5" item suggests that some aspects of disorganization could be underpinned by the impairment of basic neurobiological functions that are only partially evaluated using MCCB.

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.

Predictive factors of overall functioning improvement in patients with chronic schizophrenia and schizoaffective disorder treated with paliperidone palmitate and aripiprazole monohydrate.

BACKGROUND: Long-acting injectable (LAI) antipsychotics can improve medication adherence and reduce hospitalisation rates compared with oral treatments. Paliperidone palmitate (PAL) and aripiprazole monohydrate (ARI) LAI treatments were associated with improvements in global functioning in patients with schizophrenia. OBJECTIVE: The objective of this study was to assess the predictive factors of better overall functioning in patients with chronic schizophrenia and schizoaffective disorder treated with PAL and ARI. METHOD: Enrolled were 143 (97 males, 46 females, mean age 38.24 years, SD = 12.65) patients with a diagnosis of schizophrenia or schizoaffective disorder, whom we allocated in two groups (PAL and ARI treatments). We assessed global functioning, amount of oral medications, adherence to oral treatment, and number of hospitalisations before LAI introduction and at assessment time point. RESULTS: Longer treatment time with LAIs (p < .001), lower number of oral drugs (p < .001), and hospitalisations (p = .002) before LAI introduction, and shorter duration of illness (p = .038) predicted better Global Assessment of Functioning scores in the whole sample (R2  = 0.337). CONCLUSION: Early administration and longer duration of ARI or PAL treatments could play a significant role in improving global functioning of patients with schizophrenia and schizoaffective disorder. Better improvement in functioning could be achieved with ARI in young individuals with recent illness onset and PAL in patients at risk for recurrent hospitalisations.

Body Image and Eating Disorders are Common among Professional and Amateur Athletes Using Performance and Image Enhancing Drugs: A Cross-Sectional Study.

The use of performance and image enhancing drugs (PIEDs) is not uncommon in athletes and appears to be associated with several psychopathological disorders of unclear prevalence. In this multicenter, cross-sectional study, we aimed to evaluate the prevalence of body image disorders (BIDs) and eating disorders (EDs) in PIED-using athletes vs. PIED nonusers. We enrolled 84 consecutive professional and amateur athletes training in sport centers in Italy, who underwent semi-structured interviews (SCID-I, SCID-II) and completed the Body Image Concern Inventory (BICI) and the Sick, Control, One, Fat, Food Eating Disorder Screening Test (SCOFF). PIEDs were searched for in participants' blood, urine, and hair. Of these, 18 (21.4%) used PIEDs, the most common being anabolic androgenic steroids, amphetamine-like substances, coffee and caffeine derivatives, synthetic cathinones, and ephedrine. PIED users and nonusers did not differ in socio-demographic characteristics, but differed in clinical and psychopathological features, with PIED users being characterized by higher physical activity levels, higher daily coffee and psychotropic medication use (e.g., benzodiazepines), more SCID diagnoses of psychiatric disorders, especially substance use disorder, body dysmorphic disorder (BDD), EDs, and general anxiety disorder, higher BICI scores (indicating higher risk of BDD), and higher SCOFF scores (suggesting higher risks for BIDs and EDs).

Personal resources and depression in schizophrenia: The role of self-esteem, resilience and internalized stigma.

Depression in schizophrenia represents a challenge from a diagnostic, psychopathological and therapeutic perspective. The objective of this study is to test the hypothesis that resilience and self-stigma affect depression severity and to evaluate the strength of their relations in 921 patients with schizophrenia. A structural equation model was tested where depression is hypothesized as affected by resilience, internalized stigma, gender and negative symptoms, with the latter two variables used as exogenous covariates and the former two as mediators. The analysis reveals that low resilience, high negative symptoms, female gender were directly associated with depression severity, and internalized stigma acted only as a mediator between avolition and resilience, with similar magnitude. The cross-sectional study design and the variable selection limit the generalizability of the study results. The model supports a complex interaction between personal resources and negative symptoms in predicting depression in schizophrenia. The clinical implication of these findings is that personal resources could be a significant target of psychosocial treatments.

Lithium in Bipolar Disorder: Optimizing Therapy Using Prolonged-Release Formulations.

Lithium has been a gold standard in the treatment of bipolar disorder (BD) for several decades. Despite a general reduction in the use of lithium over the past several years, it is effective in the management of both manic and depressive episodes in BD and continues to be recommended as a first-line mood stabilizer. This review provides an overview of the pharmacology of lithium and highlights its clinical profile in the management of BD, focusing on the potential advantages of prolonged-release (PR) versus immediate-release (IR) formulations of lithium. A literature search using PubMed was performed to identify articles describing IR and PR lithium in BD using specific search terms like 'lithium', 'prolonged-release', 'sustained-release', 'extended-release', 'bipolar disorder', 'adherence' and 'compliance'. Relevant pharmacodynamic and pharmacokinetic data were also included. Several clinical trials suggested that lithium is effective in the treatment of acute mania and prophylaxis of BD and reduces the risk of suicide in patients with BD; it may also be used in combination with other drugs in the treatment of bipolar depression. Treatment with lithium must be monitored to avoid lithium-associated toxicity. The prolonged PR formulation of lithium has several advantages including consistent serum lithium concentrations, fewer adverse events and improved adherence to therapy. Although direct comparative studies between PR and IR formulations of lithium are primarily limited to pharmacokinetic studies, PR formulation of lithium provides potential advantages over IR formulation and can be effectively used in the management of BD with lesser adverse events.

Add-on high frequency deep transcranial magnetic stimulation (dTMS) to bilateral prefrontal cortex reduces cocaine craving in patients with cocaine use disorder.

INTRODUCTION: Cocaine dependence is a substantial public health problem. The aim of this study is to evaluate the effect of high frequency deep transcranial magnetic stimulation (dTMS) on craving in patients with cocaine use disorder (CUD). METHODS: Seven men (mean age, 48.71 years; standard deviation [SD], 9.45; range 32-60 years) with CUD and no concurrent axis 1 or 2 disorder save nicotine abuse, underwent three sessions of alternate day 20Hz dTMS in 20 trains delivered to the dorsolateral prefrontal cortex (DLPFC) preferentially to the left hemisphere, for 12 sessions spread over one month, added to unchanged prior drug treatment. We used a visual analogue scale (VAS) to measure cocaine craving the week before, each week during, and one month after dTMS treatment. RESULTS: DLPFC stimulation significantly reduced craving over time: within-subjects main effect of time of treatment (ANOVA, F[3,18]=46.154; p<0.001; η(2)=0.88). The reduction of craving from baseline was significant at two weeks (p<0.001), and four weeks (p<0.001) of treatment, and at the week eight, four weeks after treatment interruption (p=0.003), although the increase of craving was significant from week four and eight (p=0.014). CONCLUSION: dTMS over left DLPFC reduced craving in CUD patients in a small sample that is to be considered preliminary. However, maintenance sessions would be needed to maintain the achieved results. Our findings highlight the potential of noninvasive neuromodulation as a therapeutic tool for cocaine addiction.

Model of Management (Mo.Ma) for the patient with schizophrenia: crisis control, maintenance, relapse prevention, and recovery with long-acting injectable antipsychotics (LAIs).

INTRODUCTION: Schizophrenia is a severe mental disease that affects approximately 1% of the population with a relevant chronic impact on social and occupational functioning and daily activities. People with schizophrenia are 2-2.5 times more likely to die early than the general population. Non-adherence to antipsychotic medications, both in chronic and first episode schizophrenia, is one of the most important risk factors for relapse and hospitalization, that consequently contributes to increased costs due to psychiatric hospitalization. Atypical long-acting injectable (LAI) antipsychotics can improve treatment adherence and decrease re-hospitalization rates in patients with schizophrenia since its onset. The primary goals in the management of schizophrenia are directed not only at symptom reduction in the short and long term, but also at maintaining physical and mental functioning, improving quality of life, and promoting patient recovery. AIM: To propose a scientific evidence-based integrated model that provides an algorithm for recovery of patients with schizophrenia and to investigate the effectiveness and safety of antipsychotics LAI in the treatment, maintenance, relapse prevention, and recovery of schizophrenia. METHODS: After an accurate literature review we identified, collected and analyzed the crucial points in taking care schizophrenia patients, through which we defined the steps described in the model of management and the choice of the better treatment option. Results. In the management model we propose, the choice of a second generation long acting antipsychotic, could allow from the earliest stages of illness better patient management, especially for young individuals with schizophrenia onset, a better recovery and significant reductions of relapse and health care costs. LAI formulations of antipsychotics are valuable, because they help patients to remain adherent to their medication through regular contact with healthcare professionals and to prevent covert non-adherence. CONCLUSIONS: The proposed schizophrenia model of management could allow better patient management and recovery, in which the treatment with LAI formulation is a safe and effective therapeutic option. This new therapeutic approach could change the cost structure of schizophrenia by decreasing costs with efficient economic resource allocation guaranteed from efficient diagnostic and therapeutic pathways.