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.

Gray and white matter trajectories in patients with bipolar disorder.

OBJECTIVES: Findings on brain structural abnormalities in patients with bipolar disorder (BP) are inconsistent and little is known about age-related evolution of these changes. We employed a cross-sectional, case-control study to compare structural age-related brain trajectories in patients with BP and healthy control subjects (HC) over a period of approximately 50 years. The primary aim was to understand whether white (WM) and gray matter (GM) abnormalities are present from the beginning of the illness and how they change over time. METHODS: Seventy-eight patients with BP and 78 HC matched for age, gender, and educational level underwent a high-resolution structural magnetic resonance imaging protocol. A voxel-based morphometry (VBM) analysis was used to capture GM and WM differences between subjects with BP and HC. Factorial analysis of covariance was used to compare brain volume alterations at different ages between the groups. RESULTS: We found an age-related atrophy in GM and WM volumes both in patients with BP and HC. A main effect of diagnosis emerged in the posterior cingulate cortex bilaterally, in the right thalamus, in the cerebellum bilaterally, and in the left posterior limb of the internal capsule. No interaction between diagnosis and age emerged, indicating that the volumes of these areas were permanently reduced in subjects with BP throughout the entire age range under investigation. CONCLUSIONS: Brain alterations in patients with BP are present from the beginning of the illness and remain stable over time. All the affected areas are involved in mood and psychomotor control process. This suggests a possible neurodevelopmental involvement in the mechanism of BP.

Italian psychiatrists' perception on cognitive symptoms in major depressive disorder.

OBJECTIVE: Differently than Schizophrenia, the investigation of cognitive impairment in bipolar disorder and major depressive disorder (MDD) attracted the interest of research only recently. Therefore, it is worth understanding clinicians' perception about cognitive dysfunction in MDD and raising awareness about this issue. METHODS: Between December 2014 and January 2015, 128 Italian psychiatrists participated in an on-line survey aiming at understanding psychiatrists' perception about cognitive symptoms in MDD. The questionnaire comprised three sections: the first investigating psychiatrists' socio-demographic profile, the second assessing cognitive symptoms relevance without mentioning that they represented the study focus and the third explicitly investigating cognitive symptoms. RESULTS: Cognitive symptoms were considered as a relevant dimension of MDD and appeared among the most frequently cited residual symptoms influencing patients' work and relapse risk. About 70% of psychiatrists declared that cognitive symptoms significantly influence antidepressant choice. However, in the second questionnaire section cognitive symptoms appeared less frequently considered for antidepressant choice. CONCLUSIONS: Results revealed a clear understanding of cognitive symptoms relevance in MDD. Nevertheless, the discrepancy between psychiatrists' perception and their therapeutical choices underlines the presence of an unmet-need that should be addressed increasing the awareness about the positive effects on cognitive symptoms of existing drugs, which could allow a more symptom-oriented therapeutical intervention. Key points Major depressive disorder (MDD) is a common mental disorder often associated with deficits in cognitive function. Psychiatrists considered cognitive symptoms among the most relevant residual symptoms in MDD patients that compromise patients working and influence the relapse risk. The importance given to residual cognitive symptoms seemed not to be reflected by psychiatrists' therapeutical choice. There is a gap between what psychiatrists know and what psychiatrists apply to their clinical practice reflecting the feeling of a therapeutical unmet need.

Is nocturnal eating in restless legs syndrome linked to a specific psychopathological profile? A pilot study.

The purpose of the study was to evaluate psychological comorbidity in drug-naive or drug-free primary restless legs syndrome (p-RLS) patients with nocturnal eating disorder (NED), and to analyze the association of comorbid p-RLS and NED with obsessive-compulsive, mood and anxiety symptoms, and personality. Participants comprised 20 consecutive female outpatients with p-RLS, 10 without NED and 10 with NED, and 10 female controls matched for age. Both patients and controls were evaluated by the Hamilton Depression and the Anxiety Rating Scales, the State-Trait Anxiety Inventory, the Maudsley Obsessive Compulsive Inventory and the temperament and character inventory-revised. Compared to controls, p-RLS patients without and with NED had higher trait anxiety and current anxiety and obsessive-compulsive symptoms. p-RLS patients with NED also had significantly higher doubting compared to p-RLS patients without NED. Furthermore, groups differed for harm avoidance (HA), with p-RLS patients with and without NED having higher scores than controls. Untreated p-RLS patients, particularly those with nocturnal eating, report anxiety and obsessive-compulsive symptoms, perceive stressful situations as dangerous and threatening and tend to respond with anxiety to such situations. They have higher tendency to respond intensely to aversive stimuli, inhibiting behavior to avoid punishment, novelty, and frustrative omission of expected rewards. We hypothesize that higher levels of HA, a biologically determined personality trait, might constitute a diathesis predisposing individuals to display obsessive-compulsive symptoms, namely increasingly severe compulsive nocturnal eating.

Are 5-HT3 antagonists effective in obsessive-compulsive disorder? A systematic review of literature.

OBJECTIVE: The purpose of this literature database search-based review was to critically consider and evaluate the findings of literature focusing on efficacy and safety of 5-HT3 antagonists in the treatment of obsessive-compulsive disorder (OCD), so as to test whether preclinical data match clinical therapeutic trials. DESIGN: The PubMed database has been searched for papers on 5-HT3 antagonists and OCD in humans and for animal models of OCD and 5-HT3 receptors. RESULTS: Of the clinically tested 5-HT3 receptor antagonists, ondansetron has been used to treat OCD in five therapeutic studies, whereas granisetron only in one recent trial. Both showed some efficacy in open studies and superiority to placebo in double-blind studies, along with fair safety. No animal OCD model directly implicated 5-HT3 receptors. CONCLUSIONS: Overall, results indicate some utility, but the available literature is too scanty to allow for valid conclusions to be drawn. The mismatch between animal models of obsessive-compulsive disorder and clinical data with 5-HT3 antagonists needs more clinical data to ensure that it is not an artefact.

Chinese patients with major depression: Do concomitant pain symptoms affect quality of life independently of severity of depression?

OBJECTIVE: This study investigated whether painful physical symptoms (PPSs) influenced quality of life (QoL) when adjusting for severity of depression. METHODS: Severity of depression, QoL and PPSs were assessed at baseline and 3 months among the Chinese cohort (n = 300) of a 3-month observational study of major depressive disorder (MDD) in East Asia. The presence of PPS was defined as 'a mean score of ≥2 on the Somatic Symptom Inventory pain-related items'. Regression analyses determined predictors of QoL at 3 months, adjusting for age, sex, depressive symptoms, overall severity and QoL at baseline. RESULTS: PPSs were present (PPS+) at baseline in 35.3% of patients. Over 3 months, in the whole sample, EuroQoL visual analogue scale (EQ-VAS) score improved from 45.5 (standard deviation [SD]: 20.9) to 81 (SD: 16.7), and EuroQoL 5-Dimension Questionnaire (EQ-5D) score improved from 0.52 (SD: 0.31) to 0.89 (0.16). At 3 months, mean EQ-VAS was 75.9 (SD: 17.7) for PPS+ versus 83.7 (SD: 15.6) for PPS-, and mean EQ-5D was 0.83 (SD: 0.17) versus 0.92 (SD: 0.14). PPS+ at baseline was a significant predictor of QoL at 3 months after adjusting for socio-demographic and baseline clinical variables. CONCLUSIONS: PPSs were associated with less improvement in QoL in patients receiving treatment for MDD, independent of severity of depression.

Impact of painful physical symptoms on depression outcomes in elderly Asian patients.

ABSTRACT Background: Painful physical symptoms (PPS) are prevalent among elderly patients with depression. We describe the impact of PPS on depression outcomes and quality of life (QOL) of elderly Asian patients with major depressive disorder (MDD). Methods: This post hoc analysis of data from a three-month prospective observational study of East Asian MDD in- or out-patients focused on elderly patients aged ≥60 years. Depression severity was evaluated using the Hamilton depression (HAMD-17) and clinical global impression of severity (CGI-S) scales, while QOL was measured using EuroQOL (EQ-5D and EQ-VAS) instruments. PPS were rated using the modified somatic symptom inventory (SSI). Results: At baseline, depression was moderate to severe and 49% of the 146 elderly patients were painful physical symptom positive (PPS+). Bivariate analysis showed significant correlations between PPS and depression severity and QOL at baseline. Linear regression models showed the baseline factor most significantly associated with depression severity at three months was baseline PPS status. PPS+ patients had a mean increase of 2.87 points in their HAMD-17 rating and 0.77 points in their CGI-S score. Response and remission were significantly lower in PPS+ patients; response was 60% and remission was 40% in PPS+ patients while 82% and 66% in painful physical symptom negative (PPS-) patients. QOL at endpoint was lower in PPS+ patients. Conclusions: PPS are common in elderly Asian patients with MDD and negatively influence depression outcomes and QOL. Patients with PPS had lower QOL at baseline, lower response and remission rates, higher severity of depression, and lower QOL after three months of treatment.

Effectiveness of short-term olanzapine in patients with bipolar I disorder, with or without comorbidity with substance use disorder.

OBJECTIVES: Prognosis of comorbid bipolar disorder (BD) and drug abuse is poor. We assessed the efficacy of olanzapine in manic or mixed BD patients, with (SUD) or without (N-SUD) comorbidity with substance use disorder (SUD) and its effect on drug abuse, days of abuse, and craving. METHODS: Eighty patients with BD-I (40 SUD) were hospitalized for a manic or mixed episode and received add-on olanzapine. Assessments were conducted at admission, discharge, and 4 and 8 weeks after discharge. Primary outcome was the proportion of responders and remitters in each group. We used a logistic regression model to adjust for possible confounders. We assessed craving and drug-abuse days with a visual analog scale and the Timeline Follow-Back. RESULTS: SUD and N-SUD were similar on response and remission, adjusted for sex, age, years ill, age at first episode, first episode depressive, number of hospitalizations, and duration of hospitalization (odds ratio, 1.09; 95% confidence interval, 1.02-2.29). Mood rating scores dropped significantly from baseline to end point in both groups. Timeline follow-back decreased in SUD from 22.5 to 7.3 at 8 weeks postdischarge, whereas craving dropped from 8.3 to 5.1 (P < 0.03). CONCLUSIONS: The effectiveness of short-term olanzapine in BD-I mania or mixed mania did not differ according to SUD comorbidity. Treatment was followed by less substance use/abuse and craving in comorbid bipolar-SUD patients.

Changes in adherence and treatment costs following initiation of oral or depot typical antipsychotics among previously non-adherent patients with schizophrenia.

OBJECTIVE: This study assessed the impact of depot formulations on adherence and treating costs in the naturalistic treatment of previously non-adherent outpatients with schizophrenia. METHODS: Data were taken from the European Schizophrenia Outpatient Health Outcomes (SOHO) study. Medication adherence and treating costs during an 18-month follow-up were assessed and compared for non-adherent patients initiated on depot typical (n = 262) or oral typical antipsychotics (n = 169) as monotherapy at the index visit. Multivariate analyses were employed to adjust for differences between the two groups at the index visit. RESULTS: Of the previously non-adherent patients, more than half of patients initiated on depot typicals (55%) remained adherent to medication during follow-up, whereas the equivalent was 39% for patients initiated on oral typicals. Logistic regression also showed higher odds of being adherent among the former group (Odds ratio = 1.84; 95% CI = 1.19-2.85). In addition, total costs incurred by this group during 18 months were only half those incurred by patients initiated on oral typicals (£3645 vs £7817, p < 0.05) CONCLUSIONS: Depot formulations of typical antipsychotics appeared to improve medication adherence and reduce treatment costs, compared with oral formulations, in the treatment of non-adherent patients. LIMITATION: adherence was assessed by the treating psychiatrist using a single-item.

Prevention of relapse with maintenance electroconvulsive therapy in elderly patients with major depressive episode.

OBJECTIVES: To evaluate the effectiveness and safety of maintenance electroconvulsive therapy (mECT) in elderly patients with treatment-resistant Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition major depressive episode. METHODS: Seven elderly patients with treatment-resistant major depressive episode were treated with a complete ECT cycle. Thereafter, they received one monthly ECT session as maintenance for 1 year. Response to treatment was defined as at least a 50% drop from baseline on the Hamilton Depression Rating Scale (HamD) and remission as not meeting criteria for major depression, a HamD score of 7 or less, and Clinical Global Impressions-Severity of Illness score of 1. We compared their response with the response of 7 elderly patients with treatment-resistant major depression who were treated with a full cycle of ECT but did not receive mECT (non-mECT). We compared the 2 groups for the number of relapses or recurrences of major depressive episodes after remission was achieved; a relapse or a recurrence occurred when HamD scores were 14 or higher, or when Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision major depressive episode criteria were met, or when Clinical Global Impressions-Severity of Illness score was 3 or higher and increased by at least 2 points from response/remission. RESULTS: The mECT group (4 women and 3 men; mean age, 73 years) had significantly less mean relapses/recurrences (0 vs 1.57) and hospitalizations (0 vs 1) and received less drug treatment than the nonMECT group (similar for age and sex composition) during the 12-month follow-up period. All patients with mECT improved during treatment and did not relapse. CONCLUSIONS: Maintenance ECT protected elderly patients from recurrent depressive episodes from relapsing/recurring more than standard ECT.

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.

Clinical consequences of switching from olanzapine to risperidone and vice versa in outpatients with schizophrenia: 36-month results from the Worldwide Schizophrenia Outpatients Health Outcomes (W-SOHO) study.

BACKGROUND: With many atypical antipsychotics now available in the market, it has become a common clinical practice to switch between atypical agents as a means of achieving the best clinical outcomes. This study aimed to examine the impact of switching from olanzapine to risperidone and vice versa on clinical status and tolerability outcomes in outpatients with schizophrenia in a naturalistic setting. METHODS: W-SOHO was a 3-year observational study that involved over 17,000 outpatients with schizophrenia from 37 countries worldwide. The present post hoc study focused on the subgroup of patients who started taking olanzapine at baseline and subsequently made the first switch to risperidone (n=162) and vice versa (n=136). Clinical status was assessed at the visit when the first switch was made (i.e. before switching) and after switching. Logistic regression models examined the impact of medication switch on tolerability outcomes, and linear regression models assessed the association between medication switch and change in the Clinical Global Impression-Schizophrenia (CGI-SCH) overall score or change in weight. In addition, Kaplan-Meier survival curves and Cox-proportional hazards models were used to analyze the time to medication switch as well as time to relapse (symptom worsening as assessed by the CGI-SCH scale or hospitalization). RESULTS: 48% and 39% of patients switching to olanzapine and risperidone, respectively, remained on the medication without further switches (p=0.019). Patients switching to olanzapine were significantly less likely to experience relapse (hazard ratio: 3.43, 95% CI: 1.43, 8.26), extrapyramidal symptoms (odds ratio [OR]: 4.02, 95% CI: 1.49, 10.89) and amenorrhea/galactorrhea (OR: 8.99, 95% CI: 2.30, 35.13). No significant difference in weight change was, however, found between the two groups. While the CGI-SCH overall score improved in both groups after switching, there was a significantly greater change in those who switched to olanzapine (difference of 0.29 points, p=0.013). CONCLUSION: Our study showed that patients who switched from risperidone to olanzapine were likely to experience a more favorable treatment course than those who switched from olanzapine to risperidone. Given the nature of observational study design and small sample size, additional studies are warranted.

Risk factors for suicide behaviors in the observational schizophrenia outpatient health outcomes (SOHO) study.

BACKGROUND: To identify risk factors for suicide using data from a large, 3-year, multinational follow-up study of schizophrenia (SOHO study). METHODS: Baseline characteristics of 8,871 adult patients with schizophrenia were included in a logistic regression post-hoc analysis comparing patients who attempted and/or committed suicide during the study with those who did not. RESULTS: 384 (4.3%) patients attempted or committed suicide. Completed suicides were 27 (0.3%). The significant risk factors for suicide behaviors were previous suicidality, depressive symptoms, prolactin-related adverse events, male gender and history of hospitalization for schizophrenia. CONCLUSIONS: In view of the observational design of the study and the post-hoc nature of the analysis, the identified risk factors should be confirmed by ad-hoc specifically designed studies.

Neurocognition, psychopathology, and subjective disturbances in schizophrenia: a comparison between short-term and remitted patients.

Patients with schizophrenia present deficits in multiple domains of cognition. The study of the relationship between cognitive performance and symptoms of schizophrenia has yielded heterogeneous results. The purposes of this study were to examine the extent of the relationship between psychopathologic symptoms, cognitive function, and subjective disturbances in a group of patients affected by schizophrenia spectrum disorders and to compare short-term with remitted patients. Seventy-nine patients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for schizophrenia, schizophreniform disorder, and schizoaffective disorder were assessed through the Positive and Negative Syndrome Scale, the Frankfurt Complaint Questionnaire, and a neuropsychologic battery exploring the 7 Measurement and Treatment Research to improve Cognition in Schizophrenia cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition) plus executive control. Neuropsychologic and psychopathologic variables were compared and correlated. Treatment groups did not differ in neuropsychologic and psychopathologic measures. The cognitive factor of the Positive and Negative Syndrome Scale correlated with worse performance on cognitive tasks and with higher scores on the Frankfurt Complaint Questionnaire 24 in the short-term, remitted, and combined groups. Subjective disturbances correlated with impaired executive control, reasoning and problem solving, and social cognition but not during the short-term phase. Both "objective" and subjective psychopathology are intertwined with cognitive function, suggesting some common underlying neural bases. The condition of being in a short-term or a remitted phase of the illness influences this interrelationship, regardless of the type of antipsychotic medication taken.

Antipsychotic monotherapy and polypharmacy in the treatment of outpatients with schizophrenia in the European Schizophrenia Outpatient Health Outcomes Study.

This post hoc study used data from the naturalistic Schizophrenia Outpatient Health Outcomes study, assessing the factors associated with starting antipsychotic monotherapy and the annual rate and duration of antipsychotic monotherapy among patients initiating atypical antipsychotics (N = 6866). Descriptive and regression analyses were used. Factors associated with starting antipsychotic monotherapy at baseline were antipsychotic treatment for the first time, shorter duration of illness, less severe illness, and better social functioning. Baseline monotherapy was maintained throughout 12 months by 63.2% of patients and was significantly greater for olanzapine (66.8%) than for risperidone (62.8%), quetiapine (43.4%), or amisulpride (52.6%) (all p ≤ 0.01). The predicted mean number of days on baseline monotherapy was significantly longer for olanzapine than for risperidone, quetiapine, or amisulpride (all p < 0.01). Initiation of antipsychotic monotherapy at baseline is associated with select baseline patient characteristics. Olanzapine was found to have the highest monotherapy rate and the longest duration of maintained monotherapy, followed by risperidone, amisulpride, and quetiapine.

Duloxetine in the treatment of elderly people with major depressive disorder.

INTRODUCTION: The elderly population is more frequently subjected to depressive mood compared to the general population and show peculiarities affecting responsiveness; furthermore, aged people need also special care. Duloxetine is a relatively new antidepressant that proved to be effective in adult depression, but has received little attention in elderly population heretofore. AIM: To review the evidence of duloxetine in late-life major depressive disorder (MDD). METHOD: A systematic review of studies focusing on the use of duloxetine in MDD in the elderly has been carried out through the principal specialized databases, including PubMed, PsycLIT, and Embase. RESULTS: Only a handful of papers were specifically dedicated to this issue. Duloxetine was found to be effective and safe in old-age MDD, to be better than placebo on many clinical measures in all studies, and to better differentiate from placebo with respect to selective serotonin reuptake inhibitors. Compared to placebo, its side-effect profile is slightly unfavorable and its drop-out rate is slightly higher. Furthermore, when pain is present in old-age MDD, duloxetine is able to reduce it. CONCLUSIONS: The efficacy and safety of duloxetine in old-age depression are similar to those encountered in adult MDD. There is a relative lack of comparative studies other than with placebo. The special needs of elderly patients with MDD must be addressed with close patient contact to avoid the perils of inappropriate dosing.

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.

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).