Determination of pollutants, antibiotics, and drugs in surface water in Italy as required by the third EU Water Framework Directive Watch List: method development, validation, and assessment.

In this paper, we report a study concerning the quantification of new emerging pollutants in water as a request from the third European Watch List mechanism. The EU Watch List compound was investigated by an internal method that was validated in terms of detection limits, linearities, accuracy, and precision in accordance with quality assurance criteria, and it was used to monitor several rivers from 11 Italian regions. The methodology developed was satisfactorily validated from 5 to 500 ng L-1 for the emerging pollutants studied, and it was applied to different river waters sampled in Italy, revealing the presence of drugs and antibiotics. Rivers were monitored for 2 years by two different campaigns conducted in 2021 and 2022. A total of 19 emerging pollutants were investigated on 45 samples. The most detected analytes were O-desmethylvenlafaxine and venlafaxine. About azole compounds, sulfamethoxazole, fluconazole, and Miconazole were found. About antibiotics, ciprofloxacin and amoxicillin were found in three and one samples, respectively. Moreover, statistical analyses have found a significant correlation between O-desmethylvenlafaxine with venlafaxine, sulfamethoxazole with venlafaxine, and fluconazole with venlafaxine.

Desvenlafaxina para el tratamiento de la depresión moderada a severa en pacientes con cáncer de mama usuarias de Tamoxifeno / Desvenlafaxine for the treatment of moderate to severe depression in patients with breast cancer who use Tamoxifen

INTRODUCCIÓN: En Perú, la prevalencia de la depresión en mujeres con cáncer de mama (estadío I o II) ha sido reportada en un rango de 21.9% a 25.6%, y por niveles en un 16.9% para síntomas leves, 6.3% moderado y 2.4% severo. El tratamiento antidepresivo usado en primera línea, como los Inhibidores selectivos de la recaptación de serotonina, inhiben la CYP2D6 en diferentes grados. Los nuevos agentes antidepresivos han mostrado un mejor perfil en su prescripción conjunta. Algunos recomiendan evitar fármacos como la paroxetina y fluoxetina para el tratamiento conjunto. La literatura sugiere que los antidepresivos más seguros son la Venlafaxina, Desvenlafaxina y Mirtazapina. CUADRO CLÍNICO: El tratamiento de la depresión, preferentemente moderada a severa, de primera línea es el uso de IRSS, así como nuevos agentes que han mostrado menor efecto adverso y mayor eficacia. En mujeres, el uso del Tamoxifeno puede inducir síntomas propios de la menopausia y se ha reportado eficacia de antidepresivos como la Venlafaxina para el tratamiento de los sofocos en conjunto con el Tamoxifeno. La coprescripción de la Desvenlafaxina y el Tamoxifeno se ha sugerido por su baja concentración en el plasma, aunque la evidencia no sea suficiente. TECNOLOGÍA SANITARIA: La Desvenlafaxina es el principal metabolito activo de la Venlafaxina, es un antidepresivo de la clase de los inhibidores de la recaptación de serotonina y norepinefrina. La desvenlafaxina inhibe la recaptación de neurotransmisores en los transportadores de serotonina, noradrenalina y dopamina. La Desvenlafaxina inhibe los transportadores de serotonina y con una afinidad 10 veces superior a la de los transportadores de noradrenalina y los transportadores de dopamina con la menor afinidad. Se puede utilizar para el tratamiento de depresión mayor en adultos y síntomas como el sofoco en mujeres pre y pos menopáusicas. Está formulado como un comprimido de liberación prolongada. OBJETIVO: Evaluar la eficacia y seguridad, así como documentos relacionados a la decisión de cobertura de la Desvenlafaxina en pacientes con cáncer de mama comparado a otros antidepresivos. METODOLOGÍA: Se realizó una búsqueda sistemática en las bases de datos bibliográficas: MEDLINE (PubMed), LILACS, Cochrane Library, así como en buscadores genéricos de Internet incluyendo Google Scholar. Así también, se hizo una búsqueda en agencias que realizan evaluación de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC). RESULTADOS: Se identificó un ensayo clínico abierto y dos GPC. No se encontraron ETS o Evaluaciones económicas en la región. CONCLUSIONES: La evidencia en relación a la interacción de la Desvenlafaxina y el uso del Tamoxifeno concomitante es insuficiente. Un único estudio de tipo farmacocinético, con el uso concomitante, no alteró la concentración minima, reciente y máxima de la Desvenlafaxina. Las guías de práctica clínica identificadas, en general, recomiendan el uso (o coprescripción) de la Desvenlafaxina en mujeres con cáncer de mama usuarias de Tamoxifeno por su nivel de eficacia semejante a otros Inhibidores de Recaptación de Noradrenalina y la baja concentración en plasma del endoxifeno. El nivel de concentración mínima reportada se sugiere como un parámetro, farmacocinético y farmacodinámico, a favor al momento de tomar la decisión de la elección del fármaco y su posología. Las guías de práctica clínica identificadas, en general, recomiendan el uso (o coprescripción) de la Desvenlafaxina en mujeres con cáncer de mama usuarias de Tamoxifeno por su nivel de eficacia semejante a otros Inhibidores de recaptación de Noradrenalina y la baja concentración en plasma del endoxifeno. Cuando sea posible, se recomienda el uso de Citalopram, Escitalopram, Venlafaxina y Desvenlafaxina, dosis bajas de Sertralina o Mirtazapina como antidepresivos de primera línea. Finalmente y de modo general, se recomienda no usar antidepresivos de forma rutinaria para el tratamiento de depresión leve o subclínica, más bien considerar el nivel de severidad, principalmente en el tratamiento de la depresión severa.

Avaliação da bioequivalência entre duas formulações de succinato de desvenlafaxina monoidratado ­ 50 mg comprimido revestido de liberação prolongada ­ administradas em jejum e pós-prandial em voluntários sadios de ambos os sexos / Bioequivalence evaluation of two desvenlafaxine succinate monohydrate formulations 50-mg extendedrelease coated tablet administered in fasted and fed conditions in healthy male and female volunteers

Objetivo: O objetivo deste trabalho foi avaliar a bioequivalência entre duas formulações de succinato de desvenlafaxina monoidratado 50 mg comprimido revestido de liberação prolongada, sendo a formulação teste produzida por Medley Farmacêutica Ltda. e a formulação referência (Pristiq™) comercializada por Wyeth Indústria Farmacêutica Ltda. Métodos: Os estudos foram conduzidos em voluntários sadios e as formulações administradas em dose única, sob o estado jejum e pós-prandial. Cada estudo foi conduzido de maneira independente, sendo ambos do tipo aberto, dois períodos, utilizando um delineamento do tipo crossover 2x2, envolvendo 48 voluntários, com intervalo de sete dias entre os períodos (washout). Resultados: Na administração em jejum, a razão entre a média geométrica da formulação teste e referência (T/R) de Cmáx foi 107,49%, com intervalo de confiança (IC) 90% de 100,81 a 114,60%. Para ASC0-t, a razão T/R foi de 104,90%, com IC 90% de 97,53 a 112,82%. Na administração pós-prandial, a razão T/R de Cmáx foi 103,17%, com IC 90% de 95,08 a 111,94%. Para ASC0-t, a razão T/R foi 103,40%, com IC 90% de 94,97 a 112,58%. Conclusões: As formulações teste e referência foram consideradas estatisticamente bioequivalentes em ambas as condições de administração, jejum e pós-prandial, de acordo com os critérios exigidos pela Agência Nacional de Vigilância Sanitária (Anvisa). A formulação teste foi o primeiro medicamento similar (Zodel®, 50 e 100 mg) registrado pela Anvisa nessa categoria e disponibilizado para comercialização, contribuindo assim com a ampliação da disponibilidade do tratamento para o transtorno depressivo maior e a redução de custos ao paciente.

Objective: The objective of this work was to evaluate the bioequivalence between two desvenlafaxine succinate monohydrate formulations 50-mg extended-release tablet, the test product manufactured by Medley Farmacêutica Ltd. and reference product (Pristiq™) commercialized by Wyeth Indústria Farmacêutica Ltda. Methods: The studies were performed in healthy volunteers and the formulations were administered in single-dose under fasted and fed conditions. Each study was conducted independently and performed of type open, two periods, using a 2x2 crossover design, involving 48 volunteers, with seven days of minimum interval between periods (washout). Results: In the fasted administration, the ratio between the geometrical mean of test formulation and reference (T/R) of Cmax was 107.49%, with confidence interval 90% (CI 90%) of 100.81 to 114.60%. For AUC0-t, the ratio T/R was of 104.90%, with CI 90% from 97.53% to 112.82%. In the fed administration, the ratio T/R of Cmax was 103.17% with CI 90% of 95.08 to 111.94%. For AUC0-t, the ratio T/R was 103.40%, with CI 90% of 94.97 to 112.58%. Conclusions: The test and reference formulations were considered statistically bioequivalent in the two administration conditions, fasted and fed, according to the requirements of Brazilian National Health Surveillance Agency (Anvisa). The test formulation was the first similar medicine (Zodel®, 50 e 100 mg) to be registered by Anvisa in this category and available to commercialization, thus contributing to increase the availability of treatment for major depressive disorder and the reduction of costs to the patient.

Análisis de costo-efectividad de los medicamentos utilizados para el tratamiento de pacientes con dolor neuropático en Colombia / Cost-effectiveness analysis of drugs used for the treatment of patients with neuropathic pain in Colombia

INTRODUCCIÓN: El análisis de costo-efectividad de ácido tióctico, acetaminofén y tramadol, acetaminofén e hidrocodona, tramadol, amitriptilina, imipramina, valproato, acetaminofén y codeína, buprenorfina, capsaicina, carbamazepina, parches de fentanyl, tapentadol, duloxetina, gabapentina, parches de lidocaína, oxcarbazepina, pregabalina para el tratamiento de pacientes con dolor neuropatico en Colombia, se desarrolla en el marco del mecanismo técnico-científico para la ampliación progresiva del plan de beneficios y la definición de la lista de exclusiones, establecido en el artículo 15 de la Ley 1751 de 2015. Estas tecnologías fueron seleccionadas por la Dirección de Beneficios, Costos y Tarifas del Aseguramiento en Salud del Ministerio de Salud y Protección Social (MinSalud), y remitidas al Instituto de Evaluación Tecnológica en Salud (IETS) para su evaluación. Con respecto a la condición de salud de interés, la asociación internacional para el estudio del dolor (IASP 2011) definió el dolor neuropático como dolor causado por consecuencia directa de una lesión o enfermedad del sistema nervioso somatosensitivo. El mecanismo generador del dolor neuropático se halla en cualquier sitio a lo largo del recorrido de las vías nociceptivas (las vías que conducen la información de tipo doloroso), sin estimular inicialmente a los nociceptores (los receptores de dolor), a diferencia de lo que sucede con el dolor nociceptivo o fisiológico. El dolor neuropático es causado por diversos trastornos que afectan el sistema nervioso central y perifér

[Economic evaluation of desvenlafaxine in the treatment of major depressive disorder in Spain]. / Evaluación económica de la desvenlafaxina en el tratamiento de la depresión mayor en España.

INTRODUCTION: The objective of this analysis was to evaluate the clinical and economic value of the use of 50mg-desvenlafaxine compared to the usual care (mix of duloxetine and venlafaxine) in the outpatient treatment of major depressive disorder after first line treatment failure (relapse) in Spain. MATERIALS AND METHODS: A Markov model was used to follow up a cohort of major depressive disorder patients for one year after failure of first-line treatment with a serotonin-specific reuptake inhibitor and estimate outcome measures (percentage remission and depression-free days) and accrued and direct costs incurred during outpatient treatment of major depressive disorder. In order to obtain the efficacy data related to the treatment alternatives, a literature review of clinical trials was performed. A panel of clinical experts validated the use of clinical resources employed in the estimation of economic outcomes together with model assumptions. The analysis was performed in 2014 from the perspective of the National Health System. RESULTS: Due to fewer discontinuations, initiating second line treatment with desvenlafaxine was associated with more depression-free days and a higher percentage of patients in remission versus usual care: 1.7 days and 0.5%, respectively. This was translated into lower drug and events management costs, and an overall cost reduction of €108 for the National Health System. CONCLUSIONS: In patients who have not responded to a first-line serotonin-specific reuptake inhibitor therapy, desvenlafaxine-50mg was clinically similar in effectiveness, but a less costly option, compared with a weighted average of duloxetine and venlafaxine for the second-line treatment of major depressive disorder patients from a payer (National Health System) perspective in Spain.

Management of Newer Antidepressant Medications in U.S. Commercial Health Plans.

BACKGROUND: Private health insurance plays a large role in the U.S. health system, including for many individuals with depression. Private insurers have been actively trying to influence pharmaceutical utilization and costs, particularly for newer and costlier medications. The approaches that insurers use may have important effects on patients' access to antidepressant medications. AIMS OF THE STUDY: To report which approaches (e.g., tiered copayments, prior authorization, and step therapy) commercial health plans are employing to manage newer antidepressant medications, and how the use of these approaches has changed since 2003. METHODS: Data are from a nationally representative survey of commercial health plans in 60 market areas regarding alcohol, drug abuse and mental health services in 2010. Responses were obtained from 389 plans (89% response rate), reporting on 925 insurance products. For each of six branded antidepressant medications, respondents were asked whether the plan covered the medication and if so, on what copayment tier, and whether it was subject to prior authorization or step therapy. Measures of management approach were constructed for each medication and for the group of medications. Bivariate and multivariate analyses were used to test for association of the management approach with various health plan characteristics. RESULTS: Less than 1% of health plan products excluded any of the six antidepressants studied. Medications were more likely to be subjected to restrictions if they were newer, more expensive or were reformulations. 55% of products used placement on a high cost-sharing tier (3 or 4) as their only form of restriction for newer branded antidepressants. This proportion was lower than in 2003, when 71% of products took this approach. In addition, only 2% of products left all the newer branded medications unrestricted, down from 25% in 2003. Multivariate analysis indicated that preferred provider organizations were more likely than other product types to use tier 3 or 4 placement. DISCUSSION: We find that U.S. health plans are using a variety of strategies to manage cost and utilization of newer branded antidepressant medications. Plans appear to be finding that approaches other than exclusion are adequate to meet their cost-management goals for newer branded antidepressants, although they have increased their use of administrative restrictions since 2003. Limitations include lack of information about how administrative restrictions were applied in practice, information on only six medications, and some potential for endogeneity bias in the regression analyses. CONCLUSION: This study has documented substantial use of various restrictions on access to newer branded antidepressants in U.S. commercial health plans. Most of these medications had generic equivalents that offered at least some substitutability, reducing access concerns. At the same time, it is worth noting that high copayments and administrative requirements can nonetheless be burdensome for some patients. IMPLICATIONS FOR HEALTH POLICY: Health plans' pharmacy management approaches may concern policymakers less than in the early 2000s, due to the lesser distinctiveness of today's branded medications. This may change depending on future drug introductions. IMPLICATIONS FOR FURTHER RESEARCH: Future research should examine the impact of plans' pharmacy management approaches, using patient-level data.

Prediction of antidepressant response to venlafaxine by a combination of early response assessment and therapeutic drug monitoring.

INTRODUCTION: Early assessment of a therapeutic response is a central goal in antidepressant treatment. The present study examined the potential for therapeutic drug monitoring and symptom rating to predict venlafaxine treatment efficacy (measured by overall patient response and remission). METHODS: 88 patients were uptitrated homogenously to 225 mg/day venlafaxine. Serum concentrations of venlafaxine (VEN) and its active metabolite O-desmethylvenlafaxine (ODV) were measured at week 2. Continuous psychopathometric ratings were measured for up to 6 weeks by independent study raters. RESULTS: An early improvement was significantly more common in venlafaxine responders than non-responders (χ(2); p=0.007). While ODV serum levels were significantly higher in responders (t test; p=0.006), VEN serum levels, sum level of VEN+ODV and the ratio of ODV/VEN levels were not. Moreover, patients who showed an early response combined with an ODV serum level above the median of 222 ng/mL were significantly more likely to achieve full response (binary logistic model; p<0.01). Sensitivity (84% for early response) and specificity (81% for combination of early response and therapeutic drug monitoring) were sufficient to qualify as a reasonable screening instrument. CONCLUSION: Our results indicate that early improvement and ODV serum concentration are predictive of therapeutic outcome and can thus be used to guide use of the antidepressant venlafaxine.

The comparison of brand-name and generic formulations of venlafaxine: a therapeutic drug monitoring analysis.

OBJECTIVE: Venlafaxine (VEN) is a widely used antidepressant drug, which is available in both brand-name and generic formulations. Bioequivalence studies indicate some pharmacokinetic variability. However, naturalistic therapeutic drug monitoring studies of different generic formulations are lacking. METHODS: In 2010, inpatients of the Department of Psychiatry, Psychosomatics, and Psychotherapy, University Hospital of Würzburg, were treated with either slow-release brand-name VEN (Trevilor) or slow-release generic VEN (Venlafaxin Hexal) depending on the respective inpatient ward. Routine therapeutic drug monitoring analyses of both groups were compared after matching samples regarding dose of VEN, gender, age, smoking habits, and evaluation of co-medication. RESULTS: Both groups did not differ in mean values of VEN, O-desmethyl-VEN (ODV), VEN + ODV serum concentrations, and ODV/VEN ratio. No difference in dose-corrected serum concentrations between generic and brand-name VEN was revealed for males, females, smokers, or nonsmokers. In both groups, Spearman Rho correlation between VEN dose and VEN + ODV serum concentration was moderate but significant (P < 0.001; generic: r = 0.554; brand name: r = 0.668). Within the generic subgroup, females had a significantly higher dose-corrected serum concentration of VEN (U test, P < 0.05), whereas within brand name, no gender influence was detected. Spearman Rho correlation of age and dose-corrected ODV (P < 0.05) and VEN + ODV (P < 0.05) was significant only in the generic group. In the brand-name sample, smokers had significantly lower dose-corrected serum concentrations of ODV (U test, P < 0.01) and VEN + ODV (P < 0.01). In the generic group, smoking habit was without any influence. DISCUSSION: No differences in serum concentrations in dependence of either VEN formulations suggest a safe and efficient treatment of patients using the evaluated generic VEN. However, differences within one formulation regarding gender, age, and smoking status suggest variability of serum concentrations and thus could endanger safety and efficacy of drug use.

Medical school gift restriction policies and physician prescribing of newly marketed psychotropic medications: difference-in-differences analysis.

OBJECTIVE: To examine the effect of attending a medical school with an active policy on restricting gifts from representatives of pharmaceutical and device industries on subsequent prescribing behavior. DESIGN: Difference-in-differences approach. SETTING: 14 US medical schools with an active gift restriction policy in place by 2004. PARTICIPANTS: Prescribing patterns in 2008 and 2009 of physicians attending one of the schools compared with physicians graduating from the same schools before the implementation of the policy, as well as a set of contemporary matched controls. MAIN OUTCOME MEASURE: Probability that a physician would prescribe a newly marketed medication over existing alternatives of three psychotropic classes: lisdexamfetamine among stimulants, paliperidone among antipsychotics, and desvenlafaxine among antidepressants. None of these medications represented radical breakthroughs in their respective classes. RESULTS: For two of the three medications examined, attending a medical school with an active gift restriction policy was associated with reduced prescribing of the newly marketed drug. Physicians who attended a medical school with an active conflict of interest policy were less likely to prescribe lisdexamfetamine over older stimulants (adjusted odds ratio 0.44, 95% confidence interval 0.22 to 0.88; P=0.02) and paliperidone over older antipsychotics (0.25, 0.07 to 0.85; P=0.03). A significant effect was not observed for desvenlafaxine (1.54, 0.79 to 3.03; P=0.20). Among cohorts of students who had a longer exposure to the policy or were exposed to more stringent policies, prescribing rates were further reduced. CONCLUSION: Exposure to a gift restriction policy during medical school was associated with reduced prescribing of two out of three newly introduced psychotropic medications.

Duloxetine versus other anti-depressive agents for depression.

BACKGROUND: Although pharmacological and psychological interventions are both effective for major depression, in primary and secondary care settings antidepressant drugs remain the mainstay of treatment. Amongst antidepressants many different agents are available. Duloxetine hydrochloride is a dual reuptake inhibitor of serotonin and norepinephrine and has been licensed by the Food and Drug Administration in the US for major depressive disorder (MDD), generalised anxiety disorder, diabetic peripheral neuropathic pain, fibromyalgia and chronic musculoskeletal pain. OBJECTIVES: To assess the evidence for the efficacy, acceptability and tolerability of duloxetine in comparison with all other antidepressant agents in the acute-phase treatment of major depression. SEARCH METHODS: MEDLINE (1966 to 2012), EMBASE (1974 to 2012), the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Central Register of Controlled Trials up to March 2012. No language restriction was applied. Reference lists of relevant papers and previous systematic reviews were hand-searched. Pharmaceutical company marketing duloxetine and experts in this field were contacted for supplemental data. SELECTION CRITERIA: Randomised controlled trials allocating patients with major depression to duloxetine versus any other antidepressive agent. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and a double-entry procedure was employed. Information extracted included study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy, acceptability and tolerability. MAIN RESULTS: A total of 16 randomised controlled trials (overall 5735 participants) were included in this systematic review. Of these, three trials were unpublished. We found 11 studies (overall 3304 participants) comparing duloxetine with one selective serotonin reuptake inhibitor (SSRI) (six studies versus paroxetine, three studies versus escitalopram and two versus fluoxetine), four studies (overall 1978 participants) comparing duloxetine with a newer antidepressants (three with venlafaxine and one with desvenlafaxine, respectively) and one study (overall 453 participants) comparing duloxetine with an antipsychotic drug which is also used as an antidepressive agent, quetiapine. No studies were found comparing duloxetine with tricyclic antidepressants. The pooled confidence intervals were rather wide and there were no statistically significant differences in efficacy when comparing duloxetine with other antidepressants. However, when compared with escitalopram or venlafaxine, there was a higher rate of drop out due to any cause in the patients randomised to duloxetine (odds ratio (OR) 1.62; 95% confidence interval (CI) 1.01 to 2.62 and OR 1.56; 95% CI 1.14 to 2.15, respectively). There was also some weak evidence suggesting that patients taking duloxetine experienced more adverse events than paroxetine (OR 1.24; 95% CI 0.99 to 1.55). AUTHORS' CONCLUSIONS: Duloxetine did not seem to provide a significant advantage in efficacy over other antidepressive agents for the acute-phase treatment of major depression. No differences in terms of efficacy were found, even though duloxetine was worse than some SSRIs (most of all, escitalopram) and newer antidepressants (like venlafaxine) in terms of acceptability and tolerability. Unfortunately, we only found evidence comparing duloxetine with a handful of other active antidepressive agents and only a few trials per comparison were found (in some cases we retrieved just one trial). This limited the power of the review to detect moderate, but clinically meaningful differences between the drugs. As many statistical tests have been used in the review, the findings from this review are better thought of as hypothesis forming rather than hypothesis testing and it would be very comforting to see the conclusions replicated in future trials. Most of included studies were sponsored by the drug industry manufacturing duloxetine. As for all other new investigational compounds, the potential for overestimation of treatment effect due to sponsorship bias should be borne in mind. In the present review no trials reported economic outcomes. Given that several SSRIs and the great majority of antidepressants are now available as generic formulation (only escitalopram, desvenlafaxine and duloxetine are still on patent), more comprehensive economic estimates of antidepressant treatment effect should be considered to better inform healthcare policy.

Assessment of infant dose through milk in a lactating woman taking amisulpride and desvenlafaxine for treatment-resistant depression.

This study presents the case of a 35-year-old breastfeeding mother who delivered her fourth child 5 months previously and was prescribed 100 mg amisulpride twice daily and 250 mg desvenlafaxine in the morning for treatment-resistant depression. Arriving at this regimen took approximately 2 months postbirth. Because she was keen to continue breastfeeding her infant, and published data on the use of amisulpride and desvenlafaxine were very limited, the clinical team sought assistance from the therapeutic drug monitoring laboratory to quantify infant dose-exposure to guide consideration of continuing breastfeeding. A sampling schedule for milk and plasma from mother and plasma from her infant was agreed and drug concentrations were measured by high-performance liquid chromatography. Absolute (theoretic) infant dose (µg/kg/d) was calculated as the product of the average concentration in milk and an assumed milk intake of 0.15 L/kg/day (294 mg/kg/day for desvenlafaxine and 183 mg/kg/day for amisulpride), and relative infant dose was estimated as absolute infant dose expressed as a percentage of the maternal dose in µg/kg/day (7.8% for desvenlafaxine and 6.1% for amisulpride). Consistent with the infant being partially breastfed, the ratio of drug in the infant's plasma to that in mother's plasma was lower at 1.7% for desvenlafaxine and 3.9% for amisulpride. A pediatric assessment of the infant found achievement of expected developmental progress for age and no detectable drug-related adverse effects. Assessing the safety of breastfeeding was difficult because it involved simultaneous use of two drugs for which there was limited previous experience. However, after discussion of the infant dose-exposure data and lack of adverse effects, the mother elected to continue partial breastfeeding for the next few months. The clinical team plans a reassessment of the infant's progress in 3 months.

Desvenlafaxine: application withdrawal. Desvenlafaxine: withdrawal of marketing application for depression also.

A welcome move! This psychoactive agent has an unfavourable risk-benefit balance in both hot flushes and depression.

An assessment of drug-drug interactions: the effect of desvenlafaxine and duloxetine on the pharmacokinetics of the CYP2D6 probe desipramine in healthy subjects.

A number of antidepressants inhibit the activity of the cytochrome P450 2D6 enzyme system, which can lead to drug-drug interactions. Based on its metabolic profile, desvenlafaxine, administered as desvenlafaxine succinate, a new serotonin-norepinephrine reuptake inhibitor, is not expected to have an impact on activity of CYP2D6. This single-center, randomized, open-label, four-period, crossover study was undertaken to evaluate the effect of multiple doses of desvenlafaxine (100 mg/day, twice the recommended therapeutic dose for major depressive disorder in the United States) and duloxetine (30 mg b.i.d.) on the pharmacokinetics (PK) of a single dose of desipramine (50 mg). A single dose of desipramine was given first to assess its PK. Desvenlafaxine or duloxetine was then administered, in a crossover design, so that steady-state levels were achieved; a single dose of desipramine was then coadministered. The geometric least-square mean ratios (coadministration versus desipramine alone) for area under the plasma concentration versus time curve (AUC) and peak plasma concentrations (C(max)) of desipramine and 2-hydroxydesipramine were compared using analysis of variance. Relative to desipramine alone, increases in AUC and C(max) of desipramine associated with duloxetine administration (122 and 63%, respectively) were significantly greater than those associated with desvenlafaxine (22 and 19%, respectively; P < 0.001). Duloxetine coadministered with desipramine was also associated with a decrease in 2-hydroxydesipramine C(max) that was significant compared with the small increase seen with desvenlafaxine and desipramine (-24 versus 9%; P < 0.001); the difference between changes in 2-hydroxydesipramine AUC did not reach statistical significance (P = 0.054). Overall, desvenlafaxine had a minimal impact on the PK of desipramine compared with duloxetine, suggesting a lower risk for CYP2D6-mediated drug interactions.

Desvenlafaxine: another "me too" drug?

OBJECTIVE: To compare desvenlafaxine with its parent drug, venlafaxine, to determine the usefulness of this new medication. DATA SOURCES: Information was obtained through a MEDLINE search (1966-June 2008) and from published abstracts. Search terms included desvenlafaxine, O-desmethylvenlafaxine, Pristiq, major depressive disorder, and venlafaxine. STUDY SELECTION AND DATA EXTRACTION: All English-language studies and abstracts pertaining to desvenlafaxine and venlafaxine were considered for inclusion. Preference was given to human data. DATA SYNTHESIS: Desvenlafaxine is a serotonin-norepinephrine reuptake inhibitor and is the active metabolite of the antidepressant venlafaxine. The recommended dose is 50 mg daily, based on the efficacy and safety data of 50, 100, 150, 200, and 400 mg of desvenlafaxine. The response and remission rates of depression at 8 weeks for the 50-mg dose are 51-63% and 31-45%, respectively. These rates are comparable with those seen with venlafaxine (58% and 45%, respectively). Adverse effects are also similar to those of venlafaxine, with the most common being insomnia, somnolence, dizziness, and nausea. The decreased potential of CYP2D6 activity with desvenlafaxine compared with the parent drug may be a potential advantage in patients on other medications metabolized via this enzymatic pathway. Also, desvenlafaxine tablets are less expensive than extended-release (XR) venlafaxine, which may decrease healthcare costs in the short term. However, venlafaxine XR is expected to go off patent in 2010. CONCLUSIONS: With the overall similarity between these 2 drugs and the potential lack of cost savings, the need for desvenlafaxine and its ultimate utility in treating major depressive disorder appears to be insignificant.

Quantification of venlafaxine and O-desmethylvenlafaxine in human serum using HPLC analysis.

We describe an isocratic reversed-phase liquid chromatographic method for the determination of venlafaxine (VLX) and its main active metabolite O-desmethylvenlafaxine (ODV) in serum, using haloperidol as internal standard and liquid/liquid extraction for sample preparation. VLX and ODV were separated on a C18 column with a mobile phase of acetonitrile/buffer (30/70, v:v) at 60 degrees C and a flow rate of 1.5 ml/min. The measurement of the native fluorescence signals of the eluted compounds were carried out at 227/300 nm (excitation/emission) without interference from endogenous components in serum. High linearities for VLX and ODV for concentrations between 20 and 500 microg/l were obtained (r = 0.9997). A large spectrum of routinely prescribed drugs did not interfere in the assay. The coefficients of variation for repeatability varied between 5.40% and 5.99% and for reproducibility between 9.43% and 21.63%. Absolute recoveries were more than 52% for both substances.