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BACKGROUND: Venlafaxine (V) is a serotonin-norepinephrine selective reuptake inhibitor, mainly metabolized by cytochrome P4502D6 (CYP2D6). CYP2D6 polymorphisms result in a variety of phenotypes: poor (PMs), intermediate (IMs), extensive (EMs), and ultrarapid metabolizers (UMs). PMs usually show poor tolerance to drugs metabolized by CYP2D6, while UMs need greater doses. The aim of this study was to evaluate the impact of CYP2D6 genotype on V dosage, therapeutic response, and side effects in a clinical outpatient setting. METHODS: 47 patients with Major Depressive Disorder, treated with V 75 - 300 mg/day, underwent CYP2D6 genotyping using the INFINITI-CYP2D6 assay. Duration of treatment and clinical outcome (Clinical Global Impression [CGI] effectiveness index) were assessed. RESULTS: CGI assessment was performed after 6 weeks, 6 months, and 1 year of treatment with a V median dose of 150 mg/day. CYP2D6 genotyping resulted in 1 PM, 3 IMs, 42 EMs, and 1 UM. The UM took the greatest V dose (375 mg) without side effects; IMs/PMs took moderate/high doses of V (150 - 300 mg) without adverse effects; EMs displayed high response variability. CONCLUSIONS: PM/IM patients responded to V differently than expected according to genotype. However, the UM patient responded to a dosage higher than the usual therapeutic range and without developing side effects, suggesting an association between CYP2D6 gene duplication and the therapeutic efficacy of venlafaxine. The CYP2D6 genotyping may thus provide clinicians with a potential explanation for those patients requiring greater doses of CYP2D6 substrates in order to obtain the same therapeutic efficacy.

Background Frontotemporal dementia (FTD) may present with psychiatric symptoms, usually together with neurological ones and in cases with a family history of dementia. We describe the case of an FTD behavioural variant with a psychiatric presentation and a normal neurological examination, due to a C9Orf72 gene mutation. Case presentation The patient was a 57 years-old Caucasian woman with a recent onset of bizarre behaviours and mystic delusions. She had a negative clinical history for previous psychiatric disorders and treatments and this was her first admission to a Psychiatry Ward. A careful assessment was performed including, beyond psychiatric evaluation, the following: blood sampling, neurological examination (including electroencephalogram, electroencephalogram with zygomatic electrodes, Positron Emission Tomography, Cerebrospinal Fluid Analysis), carotid artery Doppler ultrasound, brain Magnetic Resonance Imaging – angio Magnetic Resonance Imaging. Blood sampling for the genetic assessment of mutations associated to primary dementias was performed as well: the genes investigated were FUS, C9Orf72, PSEN-1, PSEN-2. Conclusions Serological tests were negative, neurological examination was normal, instrumental examinations showed theta waves in the posterior temporal areas bilaterally and frontotemporal cortical atrophy bilaterally. The genetic assessment of mutations associated revealed she carried a GGGGCC hexanucleotide repeat expansion (at least 80 repeats) in C9Orf72 intron 1. Patients carrying the C9Orf72 mutation are likely to receive a psychiatric diagnosis (mainly mood disorder or schizophrenia) prior to correct diagnosis; this may be particularly problematic for those patients with no neurological signs to orientate diagnosis. Understanding the manner in which such FTD variant may present as a psychiatric syndrome, with a negative neurological examination, is essential to provide the best treatment for patients, as soon as possible, especially when the behavioural anomalies interfere with their care.

Purpose The annual global suicide mortality rate is 16 per 100,000 and suicide attempts are 20 times more frequent. We aimed at comparing patients referring to the emergency room (ER) for self-inflicted injury vs those needing psychiatric consultation for other reasons, in order to assess possible predictors of self-injury. Methods Determinants of ER psychiatric consultations were studied prospectively during the period 2008–2011 at the ‘Maggiore’ Hospital in Novara. A multivariate analysis was performed using a logistic regression in order to assess the potential predictors of self-injury behaviors. Results are expressed as Odds Ratio (OR) with 95% Confidence Intervals (95%CI). Statistical significance was set at p≤0.05. Results In a sample of 1888 psychiatric consultations, 280 (14.8%) were due to self-inflicted injuries . Female gender (OR: 1.51; p=0.005) was found to positively correlate with attempted suicides, whereas unemployment (OR: 0.68; p=0.013) and being in the colder months of the year (OR: 0.75; p=0.043) were found to be negative correlated. A positive trend without statistical significance was observed for foreign nationality, being not married and living with parents/own family vs a negative trend was found for history of psychiatric disorders. Conclusions In accordance with other studies, we observed the female gender positively correlates with attempted suicides and sunlight may act as a trigger. In contrast with literature, individuals with a permanent job would be at higher risk of self-injury behaviours, whereas having a history of psychiatric disorders and being under the care of a psychiatrist might be a protective predictor.

Introduction Suicidal behaviours are major public health concerns, associated with many risk factors that vary with sociodemographical features. Objectives To compare the differences between patients visiting the emergency room (ER) for self-inflicted injury vs those needing psychiatric consultation for other reasons, as far as their occupational and accommodation status are concerned. Aims To evaluate the influence of the economic scenery on suicidal behaviours. Methods Determinants of ER psychiatric consultations were studied prospectively from 2008 to 2011 at the “Maggiore” Hospital in Novara. Comparison of qualitative data was performed by means of the x 2 test, or the Fisher’s Exact test in case of expected frequencies less than 5. All tests were two-sided and a P value less than 0.05 was considered as statistically significant. Results In a sample of 1888 psychiatric consultations, 281 (14.9%) were due to self-inflicted injuries. The preliminary analysis of socio-demographical features showed that self-harm behaviours are significantly more frequent among employed vs unemployed or disabled subjects (20.1% vs 13.2%; p=0.0005) and among those living in their immediate or own family vs those living alone or in therapeutic facilities (17.0% vs 13.0% vs 8.4%; p=0.012). Conclusions In contrast to current literature, our study shows that individuals living in more favourable conditions are at greater risk of attempting suicide. These results might be associated to the current Italian economic scenery, and to emerging difficulties as far as keeping an income to adequately maintain a family are concerned.

IntroductionVenlafaxine is a serotonin-norepinephrine inhibitor, mainly metabolized by CYP2D6 to its active metabolite ODV. Depending on CYP2D6 activity, patients may be identified as Poor, Intermediate, Extensive or Ultrarapid Metabolizers. There is some evidence that a PM phenotype is associated with poor tolerance more often than an EM; while a UM patient would only respond to a greater dose of Venlafaxine1.ObjectivesTo evaluate the impact of CYP2D6 phenotype on the efficacy of Venlafaxine XR in depressed patients.MethodsThis observational study evaluated 27 Caucasian adult patients (F = 18, M = 9), satisfying DSM-IV criteria for Major Depressive, Bipolar Disorder or Personality Disorder receiving treatment with Venlafaxine 75–300 mg/die.CYP2D6 alleles were evaluated with INFINITI CYP2D6 assay, which employs AutoGenomics proprietary film-based microarray technology.ResultsMost patients were identified as EMs, 4 as PMs, while only one was identified as UM. The only statistically significant difference between Extensive and Poor Metabolizers was, in contrast with current literature, the need of a greater mean dose of Venlafaxine in the second group (225 mg/die vs 159.38 mg/die, t student: p = 0.01).Likewise, in contrast with literature, the UM patient was responsive to average doses of Venlafaxine.On the contrary, we found no statistically significant differences as far as efficacy, adverse events or duration of treatment are concerned.ConclusionsIn our sample, CYP2D6 metabolizer status does not seem to affect treatment response nor adverse events related to Venlafaxine.

ObjectivesThe immigrant population in Italy is currently increasing, particularly, foreigners in East Piedmont raised by 16,8 % last year. We aim to compare immigrant and Italian patients’ Emergency Room (ER) admissions due to psychiatric symptoms.ResultsOf the 658 admissions we observed, 13.1 % of ER contacts concerned immigrants mostly coming from Russia, Albania, Morocco and Romania, consistently with migration streams in East Piedmont. Compared to the Italians, immigrant patients were younger (35.70; SD = 10.56 versus 44.78; SD = 16.57) and more frequently admitted for alcohol and substance abuse/withdrawal. Italians had a higher probability of having a psychiatric history including previous hospitalizations and contacts with Mental Health Services (OR = 2.60; CI 95 %: 1.64-4.12). The presence of social/relational problems associated with admission was significantly lower among the Italians (OR = 0.55; CI 95 %: 0.35-0.88).ConclusionsPreliminary data suggest that ER utilisation by immigrants may represent their main way to primary health care. Monitoring ER contacts may provide relevant information for the development of culturally sensitive Mental Health Services.MethodsWe considered Italian and immigrant patients with psychiatric symptoms who were admitted to the ER Department of Novara during a period of 13 months. We compared sociodemographic (gender, age, education, occupational history, marital status, living circumstances) clinical-anamnestic (history of psychiatric illness, presentation symptoms, previous contacts with Substance Abuse/Mental Health Services, social/relational problems) and admission (type of admission, intervention and discharge) characteristics of the two groups (Italians versus immigrants).

ObjectiveVenlafaxine (V) is a SNRI metabolized primarily by the highly polymorphic cytochrome P4502D6 enzyme (CYP2D6) in O-desmethylvenlafaxine (ODV), the main active metabolite. Four CYP2D6 metabolizer phenotypes have been identified: poor (PM), intermediate (IM), extensive (EM) and ultrarapid (UM). Approximately 5-10% Caucasians are PMs; in these individuals metabolism of substrate is decreased and adverse clinical effects may be expected. The effectiveness of pharmacogenetic tests is controversial because the association between plasma levels of V/ODV and side effects is not attested.We discuss the association between CYP2D6-genotype and Venlafaxine clinical effects.MethodsWe will recruit Caucasian patients aged 18 to 65, eligible for Venlafaxine treatment, satisfying DSM-IV criteria for major depressive episode, dysthymia or depressive adjustment disorder. Exclusion criteria will be: pregnancy, acute suicidality, alcohol/substance abuse, concomitant/prior antidepressive treatment in the previous 3 months. We will assess patients’ age, gender, DSM-IV diagnosis, Venlafaxine dose, concomitant pharmacological treatment, BMI, BP, tobacco use, liver and kidney functionality. Clinical response and side effects will be monitored using CGI, HAM-D and SIDE at T0 (onset), T1 (1 week later) and T2 (6 weeks later).The patients will be analyzed for the presence of 16 CYP2D6-genotype variants by INFINITITTM CYP2D6 assay which utilizes AutoGenomics proprietary film-based microarray technology.ResultsWe expect to find out a correlation between CYP2D6-genotype, Venlafaxine dose and clinical response to treatment.ConclusionsWe will investigate whether a pharmacogenetic test prior to treatment can be useful in clinical practice to detect a proper Venlafaxine dosage or to switch to a different drug.

Background Suicidal behaviours are major public health concerns worldwide. They are associated with risk factors that vary with age and gender, occur in combination, and may change over time. The aim of our study was to investigate how frequently patients visiting a hospital emergency room (ER) require a psychiatric consultation for attempted suicide, and to outline the characteristics of this population. Methods Determinants of emergency room visits for psychiatric reasons were studied prospectively from 2008 to 2011 at the “Maggiore” Hospital in Novara. Results 280 out of 1888 patients requiring psychiatric consultation were referred to the ER because of suicide attempt. Suicide attempters were more often female. The rate of suicide attempters among Italian people was 14.2%, compared to 19.5% in foreigners. Subjects living with parents or own family and those having a permanent job had a higher frequency of suicide attempt. Suicide attempts were more frequent among patients with a history of psychiatric disorders; nonetheless, suicide attempts were more common among those who had not previously been hospitalized in a psychiatric ward or were not under the care of a psychiatrist. The multivariate analysis found that female gender was a risk factor for suicide attempt, while being in the colder months of the year and, surprisingly, unemployment were protective factors. Conclusions A better understanding of patients referring to the ER due to attempted suicide may allow the identification of at-risk subjects and the implementation of targeted treatment approaches.