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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.
Prostate and breast cancer share many similarities: high lifetime prevalence, increasing frequency, role of environmental factors, long survival also in metastatic disease and possibility of screening. The aim of this work is to evaluate the characteristics related to the patients, disease and treatment which can affect HRQoL at the beginning and after radiotherapy.
since June 2009, we have recruited patients, providing informed consent, before radiotherapy (T0). We assess demographic characteristic (age, qualification, work, marital status…); neoplastic staging and grading; radiation dose and other antineoplastic treatment (hormonal/chemio-therapy or surgery); concomitant medical disease and pharmacological therapy. We evaluate HRQoL by EORTC-QLQ-C30 and EORTC-QLQ-PR25 (prostate-specific) or EORTC-QLQ-BR23 (breast-specific). The protocol also includes HADS, Paykel Life Events Scale and EPQ-R. The work is ongoing and implies a follow-up at 6 and 12 months (T1/T2).
The majority of men have a localized disease with Gleason score between 6 and 8 and the median pretreatment PSA is 10.52 ng/mL; 70% will undergo adjuvant-RT; median age is 69.30 years. Women have a median age of 58.46 years, all underwent surgery and all have a localized disease and positive receptorial status. Global QoL is lightly higher in the man sample; both groups report a major deficit at Emotional Function and high levels of Fatigue. The personological characteristic more represented is “Extravertion”.
The results show an association between worse QoL, “Nevroticism” and high Anxiety levels only in the men sample at T0. At the moment, there is no significant relation in the women sample.
To underline the importance of a correct diagnosis and management of catatonia and complications increasing its morbidity and mortality. Catatonia is a syndrome of altered motor behaviour, mainly classified as a form of schizophrenia. Recent literature suggests catatonia is an independent syndrome, frequent among patients diagnosed with mania/depression or accompanying many general medical conditions and neurological disorders.
We describe the case of a 58-year-old woman with NIDDM in antidiabetic oral therapy and history of schizophrenia, diagnosed when aged 20 and treated with Haloperidol (10 mg/day), Levomepromazine (100 mg/day) and Lorazepam (2.5 mg/day) who was admitted to our clinic for a condition characterized by mutacism, staring into space, muscular rigidity and bilateral arm cogwheeling, initially suggesting a neuroleptic malignant syndrome.
At hospitalization there was no fever, leukocytosis or CPK elevation. She quickly developed altered consciousness, autonomic dysfunction (hypertension, dysphagia, uncontrolled hyperglycaemia) and waxy flexibility finally recognized as a catatonic syndrome, according to DSM-IV-TR criteria. Multiple infections (urinary trait infection, teeth infections leading to sepsis) worsened her clinical condition. The first therapeutic strategy was suspending neuroleptics. Psychomotor symptoms, rated with the Catatonia Rating Scale (CRS), gradually resolved by intravenous administration of Lorazepam high doses (up to 12 mg/day). General medical conditions improved with specific antibiotic therapy, endovenous hydratation and parenteral nutrition. A physiatric rehabilitation program was started, with significative motricity improvement.
This report underlines the importance of the differential diagnosis between catatonia and similar conditions (such as NMS) and the fundamental role of multidisciplinary approach to complications.
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.
Long-acting injectable antipsychotics (LAI-APs) should be the first choice therapy in the treatment of schizophrenia, however their use in outpatient's psychiatric services remains limited.
Observational study in schizophrenic patients of the northwestern public health service.
To assess demographic and psychopathological features in patients treated with LAI haloperidol (H-LAI) and second-generation LAI antipsychotics (SG-LAI).
We recruited 105 schizophrenic patients upon LAI-APs treatment, and we assessed socio-demographic data, medical comorbidity, substances use, time from admission, treatment length, and per os augmentation therapies. All participants were assessed for global functioning and severity of illness by CGI-SCH and PSP, respectively.
Of all patients, 52% were treated by H-LAI, 48% by SG-LAI. No statistical differences (P > 0.05) were found between the 2 groups for age, gender, other demographic variables, substances use, somatic comorbidities. Both groups were homogeneous for severity of illness (CGI-SCH score = 4.20 in H-LAI vs. 4.38 in SG-LAI) and global functioning (PSP score = 49.1 in H-LAI vs. 54.4 in SG-LAI). Compared with the H-LAI group, SG-LAI-treated patients were characterized by shorter time from admission (>10 yrs) and treatment length (>1 yr), and less frequent anticholinergic drug co-prescription. We counted only 6 LAI-APs treatments started in the last year.
Despite of the literature support, LAI-APs treatment for schizophrenia is still limited in our service. Our data suggest that SG-LAI-APs are used as first choice of LAI-APs treatment, although maintained for short time, while H-LAI are reserved to long-standing patients and are burdened by side effects needing anticholinergic treatment.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
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