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Venlafaxine (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.
We 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.
We expect to find out a correlation between CYP2D6-genotype, Venlafaxine dose and clinical response to treatment.
We 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.
The 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.
Of 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).
Preliminary 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.
We 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).
Venlafaxine 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.
To evaluate the impact of CYP2D6 phenotype on the efficacy of Venlafaxine XR in depressed patients.
This 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.
Most 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.
In our sample, CYP2D6 metabolizer status does not seem to affect treatment response nor adverse events related to Venlafaxine.
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