Dose Of Venlafaxine Research Articles

Öyküsünde Alkol Ve Madde Kullanimi Bulunmayan Hastada Venlefaksin Bağimliliği: Bir Vaka Sunumu / Venlafaxine Addiction Without A History Of Alcohol And Substance Abuse: A Case Report

Venlafaxine addiction without a history of alcohol and substance abuse: a case report In this paper, the aim was to present a patient who had no history of drug or alcohol abuse but was prescribed venlafaxine because of her complaints of headache and increased its dosage by herself on the pretext of a decrease in efficiency. A 35 year-old female patient complaining of headache was prescribed 75 mg/day venlafaxine by a psychiatrist, and the dosage was increased to 225 mg/day by the same doctor, and then the drug dosage was increased to 2100 mg/day by the patient herself. The patient was hospitalized and venlafaxine dosage was gradually decreased and stopped in 10 weeks. This case shows that antidepressant dependence may develop in patients without a history of drug or alcohol abuse.

Patterns of cardiorespiratory coordination in young women with recurrent major depressive disorder treated with escitalopram or venlafaxine

Evidence from previous studies suggests autonomic dysregulation in patients with major depressive disorder (MDD). Antidepressant treatment may also affect central autonomic function. We investigated whether the type of antidepressant might be associated with the pattern of cardiorespiratory coordination in non-depressed women with recurrent MDD. Resting electrocardiograms and respiratory signals were simultaneously recorded from 38 euthymic women with recurrent MDD who were treated with either escitalopram (n=19) or venlafaxine (n=19) monotherapy and from 38 healthy women. Linear measures of heart rate variability were extracted to assess cardiac autonomic control. Sample entropy (SampEn) was computed to assess the complexity of heart rate and respiratory signals, and cross-SampEn was calculated to measure the nonlinear interaction of both signals. Significant decreases in the cardiovagal tone and cardiorespiratory coupling of women with recurrent MDD receiving venlafaxine, and tendencies toward lower cardiovagal tone and cardiorespiratory coupling in women with recurrent MDD receiving escitalopram were observed when compared with healthy controls. Effect sizes for these differences were large between women receiving venlafaxine and healthy controls. We found a positive association between cardiorespiratory decoupling and venlafaxine dose. Norepinephrine-enhancement, within a therapeutic dose range, seems to be closely associated with decreased vagal tone and reduced nonlinear coupling between heart rate and respiration in euthymic women with recurrent MDD. However, the effects of serotonin enhancement on cardiovagal tone should be considered. Our results suggest that the pharmacodynamic properties of antidepressants may affect autonomic regulation of women with recurrent MDD even in euthymic state.

Low-dose venlafaxine-induced severe rhabdomyolysis: a case report

Venlafaxine is a relatively new antidepressant with selective effects. Compared with traditional antidepressants, this agent has fewer adverse side effects. However, venlafaxine overdose has been reported with severe complications such as seizure, ventricular tachycardia, serotonin syndrome, neuroleptic malignant syndrome and rhabdomyolysis. We present a 21-year-old female with bipolar depression who took a low dose of venlafaxine, but subsequently developed severe rhabdomyolysis. Her plasma level of creatine kinase increased up to 18 711 U/L in few days. These findings may serve as a reminder to physicians to be alert to the possibility of rhabdomyolysis in patients who have only taken a low dose of venlafaxine.

Hypoglycaemia: A little known effect of Venlafaxine overdose

We report the case of a 39-year-old woman who presented with serotonin syndrome and hypoglycaemia likely due to intoxication with a very high dose of venlafaxine. This case of venlafaxine-associated hypoglycaemia was treated first by glucose perfusion, but despite large doses, hypoglycaemia recurred. Blood glucose normalized after injection of octreotide, eliminating the need for hypertonic glucose. Octreotide has been shown to decrease glucose requirements and the number of hypoglycaemic episodes in patients with sulfonylurea-induced hypoglycaemia but, to our knowledge, its ability to resolve hypoglycaemic episodes due to massive venlafaxine overdose has not yet been described.

Evaluation of antinociceptive/analgesic activity of SSRIs (fluoxetine and escitalopram) and atypical antidepressants (venlafaxine and mirtazapine): An experimental study

Objective: To evaluate the antinociceptive/analgesic action of selective serotonin reuptake inhibitors (SSRIs; fluoxetine, escitalopram) and atypical antidepressants (mirtazapine, venlafaxine) and to delineate their probable mechanism. Materials and Methods: The study was conducted on albino mice (25-35 g) and Wistar rats (80-100 g) of either sex. Different doses of morphine (0.5 and 1 mg/kg), fluoxetine (2, 5, and 10 mg/kg), venlafaxine (30, 40, and 50 mg/kg), mirtazapine (3, 5, and 7 mg/kg), and escitalopram (2.5, 5, and 10 mg/kg) were administered subcutaneously in order to ascertain their subanalgesic doses using tail flick analgesiometer and writhing method. Tail flick latencies were obtained at 15, 30, 60, and 120 min after drug administration. In another set of experiments, abdominal writhing was produced by employing 4% saline (1 ml/kg; i.p.) as irritant. Pretested sensitive rats were given test drugs 10 min before saline injection and abdominal writhing was noted between 30 seconds and 3 min of administering saline. Naloxone (1 mg/kg) was administered 10 min prior to test drug for testing antagonism in both sets of experiments. Results: In both sets of experiments, fluoxetine (5 and 10 mg/kg), mirtazapine (5 and 7 mg/kg), and venlafaxine (40 and 50 mg/kg) were found to have antinociceptive activity, but not at lower doses. Escitalopram failed to show antinociceptive activity at any of the doses used. The antinociceptive effect of all the drugs was antagonized by naloxone. Further, subanalgesic doses of fluoxetine, mirtazapine, and venlafaxine showed analgesic activity with suboptimal dose of morphine (0.5 mg/kg). Conclusion: Fluoxetine, mirtazapine, and venlafaxine have antinociceptive activity, whereas escitalopram does not have; their site of action seems to be the same as that of opioid analgesics (mu receptors). However, involvement of other pathways (cholinergic, histaminic, noradrenergic, GABAergic) cannot be excluded in mediation of their analgesic activity, which requires further elucidation.

Combined Treatments for Depression as for Other Medical Disorders

Back to table of contents Previous article Next article Communications and UpdatesFull AccessCombined Treatments for Depression as for Other Medical DisordersPierre Blier, M.D., Ph.D.Pierre BlierOttawaSearch for more papers by this author, M.D., Ph.D.Published Online:1 Jan 2012https://doi.org/10.1176/appi.ajp.2011.11071055AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: We read with great interest the article by Dr. Rush et al. on the Combining Medications to Enhance Depression Outcomes (CO-MED) study (1) and the editorial by Dr. Coryell (2) in the July 2011 issue of the Journal. The overall result of this large-scale trial is that a single antidepressant produced the same remission results as did combinations started 1 week after treatment initiation. Our main issue with CO-MED, apart from its not being a double-blind study, is the dosing of the antidepressants. The CO-MED study did not adhere to an important rule of combination treatment in medicine: use similar and/or effective dosages of both agents. For instance, when treating asthma, physicians should administer standard doses of both a β2-adrenergic agonist and an inhaled steroid, not lower doses. Physicians were aware of the dosages used throughout the study, and despite the use of a decision tree involving tolerability and response for titration, the dose of escitalopram was near the maximum in the monotherapy arm and was significantly lower when combined with bupropion. Consequently, the dosage issue has not been “credibly dismissed” in the CO-MED study (2).One possible explanation for the identical remission rates in the venlafaxine-mirtazapine arm and the escitalopram arm is that the combination arm was again underdosed. Several studies supporting the superiority of this combination consistently used higher dosages. The mean of the daily doses of mirtazapine was only 20 mg in the CO-MED study, which is below its minimal effective daily dose of 30 mg. The mean of the daily doses of venlafaxine was 192 mg, which is below its noradrenergic range of 225 mg/day (3). Rush et al. (1) point out that no difference in remission rates was observed between the 86 patients who reached the daily regimen of 225 mg of venlafaxine and 30 mg of mirtazapine and those who were in the escitalopram arm. However, the authors indicate that this regimen was achieved “at any time during treatment.” It is unclear how long these dosages were maintained. In two double-blind studies (4, 5), we doubled the remission rates using adequately dosed combinations of mirtazapine and other antidepressants, and the dropout rates were below 15%; no patients in the fixed venlafaxine (225 mg) and mirtazapine (30 mg) group dropped out because of side effects. The double-blind structure of our studies likely contributed to patients tolerating side effects because neither they nor the investigators knew if a dosage titration was used. On the one hand, the CO-MED study results may reflect the underdosing that can happen in a community sample. On the other hand, this approach limits our ability to validate the superiority of the venlafaxine-mirtazapine combination because most patients were on a dosage of venlafaxine that did not inhibit norepinephrine reuptake and a sedative/non-antidepressant dosage of mirtazapine during the trial.More studies on combining antidepressant drugs from treatment initiation are needed, especially those that keep in mind the above-mentioned pitfalls. Nevertheless, a crucial take-home message from the CO-MED study is that if patients are treated with a combination of antidepressants, they should be receiving adequate dosages because a single medication may do just as well.OttawaDr. Blier has received investigator-initiated research grants and/or honoraria for participating in advisory boards and delivering lectures from AstraZeneca, Biovail, Bristol-Myers Squibb, Eli Lilly, Euthymics, Janssen, Labopharm, Lundbeck, Merck, Organon, Pfizer, Pierre Fabre Medicaments, Takeda, and Wyeth.Accepted for publication in October 2011.

Response to Blier Letter

Back to table of contents Previous article Next article Communications and UpdatesFull AccessResponse to Blier LetterMadhukar H. Trivedi, M.D., A. John Rush, M.D., Ben T. Kurian, M.D., Andrew A. Nierenberg, M.D., Stephen R. Wisniewski, Ph.D., and Maurizio Fava, M.D.Madhukar H. TrivediDallasSearch for more papers by this author, M.D., A. John RushSingaporeSearch for more papers by this author, M.D., Ben T. KurianDallasSearch for more papers by this author, M.D., Andrew A. NierenbergBostonSearch for more papers by this author, M.D., Stephen R. WisniewskiPittsburghSearch for more papers by this author, Ph.D., and Maurizio FavaBostonSearch for more papers by this author, M.D.Published Online:1 Jan 2012https://doi.org/10.1176/appi.ajp.2011.11071055rAboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Dr. Blier raises two important issues in response to our findings from the Combining Medications to Enhance Depression Outcomes (CO-MED) study: the lack of a double-blind structure and the dosing of antidepressants. We are unable to confirm whether the presence of a double-blind structure would have allowed us to achieve a much higher dosage for the antidepressants, but the indirect evidence from the higher adverse events in the two combination arms suggests that higher doses would have increased dropout rates in these two groups. It is conceivable that significantly higher doses of individual antidepressants could increase the rates of remission; however, some major issues need to be considered.First, there are distinct differences in the treatment settings and participant population for the CO-MED study when comparing the results with Blier et al. (1); the CO-MED study was conducted in real-world primary and specialty care settings with minimal exclusion criteria (Tables 2 and 3 in our article [2]). For example, over 75% of the population had anxious depression, and unlike the Blier sample, which recruited around 75% with melancholic subtype of major depression disorder, less than 25% of CO-MED patients met criteria for the melancholic subtype. Furthermore, over 75% of CO-MED participants had at least one comorbid axis III disorder. Second, in the two combination arms of our study, a much higher rate of maximum side-effect burden (statistically higher for venlafaxine plus mirtazapine) was used when compared with monotherapy. Third, the daily doses of escitalopram, while slightly lower for those patients taking it in combination with bupropion (14.0 mg [SD=7.2] for single-blind escitalopram compared with 17.6 mg [SD=4.5] in the monotherapy arm), were not drastically different. Finally, while it is true that the Blier et al. study achieved slightly higher doses of mirtaza-pine and venlafaxine, the daily dose of fluoxetine was only 20 mg. The major difference in these findings stems from the fact that remission rates in the fluoxetine arm of the Blier et al. study were significantly lower (25%) relative to the sustained remission rates in the escitalopram monotherapy arm of the CO-MED trial (38.5%). In fact, Fava et al. (3, 4) have shown that increasing the daily dose of fluoxetine from 20 mg to 40–60 mg for partial responders or nonresponders further enhances response rates, indicating that the dosage of fluoxetine monotherapy in the Blier et al. study may have been suboptimal. In summary, while much higher daily doses of venlafaxine and mirtazapine may be theoretically interesting, it is difficult to argue in favor of its clinical utility in real-world clinical populations.DallasSingaporeDallasBostonPittsburghBostonThe authors' disclosures accompany the original article.Accepted for publication in October 2011.

P-1074 - Efficacy of venlafaxine compared with selective serotonin reuptake inhibitors (SSRI) in severe major depressive disorder (MDD): a retrospective pooled analysis

Introduction/objective There are no data on the comparative efficacy of venlafaxine to other SSRI's in severe MDD. Methods In a post hoc analysis, data were pooled from 8 double-blind active controlled studies in outpatients with a diagnosis of MDD. Patients randomly assigned to venlafaxine (dose range 75-225 mg) or SSRI (fluoxetine (20–80 mg/day), fluvoxamine (100 mg/day), or paroxetine (20 mg/day)) were included in the analysis. Severe MDD was defined as baseline HAM-D 17 >24 and alternatively as baseline MADRS≥ 31. Treatment groups were compared by mean improvement in the 17-item Hamilton Rating Scale for Depression (HAM-D 17 ) (and alternatively MADRS) scores from baseline to last observation carried forward (LOCF). Secondary outcomes included HAM-D 17 response (≥50% reduction in HAM-D 17 ) and remission (HAM-D 17 ≤7) rates, MADRS response (≥50% reduction in MADRS) and remission (MADRS≤10). Changes from baseline for the primary end point were evaluated using analysis of covariance with treatment, study, and baseline in the model. Results A total of 1503 patients were included in the analysis (venlafaxine n = 805; SSRI, n = 698); 649/1503 (43%) patients had severe depression (HAM-D 17 >24) at baseline. Venlafaxine improved HAM-D 17 scores vs. SSRI in patients with severe MDD (venlafaxine, −15.26 [0.73]; SSRI, −12.91 [0.81]; P = 0.003). Response and remission were significantly higher in venlafaxine compared with SSRI (Response: Venlafaxine = 63% vs SSRI= 53% (p = 0.004); Remission: 41% vs. 31% (p = 0.005)). The results of the analyses were similar when baseline severity was defined by MADRS scores. Conclusions In this retrospective pooled analysis, venlafaxine was superior to SSRI's in treating severe MDD.

Correlates and outcomes of depressed out-patients with greater and fewer anxious symptoms: a CO-MED report

The objective of this paper was to determine whether the presence of more vs. fewer anxious symptom features, at baseline, are associated with other clinical features and treatment outcomes in out-patients with major depressive disorder (MDD). This single-blind, randomized trial enrolled 665 MDD out-patients to compare the efficacy of two antidepressant medication combinations against escitalopram after 12-wk acute treatment and follow-up (total 28 wk). The sample was divided into those with greater (vs. fewer) anxiety features using the anxiety/somatization subscale of the baseline 17-item Hamilton Rating Scale for Depression. Baseline sociodemographic and clinical features, treatment features and outcomes compared these two groups. Overall, 74.7% of participants met the threshold for 'anxious features'. They were more likely to be female, have other concurrent anxiety disorders, more severe depression, more lethargic and melancholic features and poorer cognitive and physical functioning, quality of life and work and social adjustment. In acute treatment, participants with anxious features received comparatively higher doses of mirtazapine and venlafaxine and reported more side-effects. The groups with and without anxious features did not differ in treatment outcomes and side-effect burden. Despite being associated with a distinct clinical profile, baseline anxious features were not clinically useful in predicting acute treatment outcomes or differential treatment response.

Resilience as a predictor of treatment response in patients with posttraumatic stress disorder treated with venlafaxine extended release or placebo

This post-hoc analysis evaluated resilience as a predictor of treatment response in patients with posttraumatic stress disorder (PTSD). Data were pooled from two randomized, double-blind studies conducted with adult outpatients treated with flexible doses of venlafaxine extended release (ER) 37.5 to 300 mg/day or placebo. The 17-item Clinician-Administered Posttraumatic Stress Disorder Scale (CAPS-SX(17)) was the primary outcome measure. Baseline Connor-Davidson Resilience Scale (CD-RISC) scores for the 25-, 10-, and 2-item versions were used to predict changes in PTSD symptom severity at week 12 and symptomatic remission (CAPS-SX(17) ≤ 20). Analyses were conducted for the overall population and separately for the individual treatment groups. In total, pretreatment resilience predicted a positive treatment response. For the overall population, all versions of the CD-RISC predicted CAPS-SX(17) change scores and remission after controlling for variables such as treatment group and baseline symptom severity. For venlafaxine ER-treated patients, all versions of the CD-RISC were predictive of remission, but only the 10-item version was predictive of CAPS-SX(17) change score. Our results suggest that higher pretreatment resilience is generally associated with a positive treatment response. Future research may be warranted to explore the relationship between response to active treatment and the spectrum of resiliency.

Pharmacokinetics of Venlafaxine Extended Release 75 mg and Desvenlafaxine 50 mg in Healthy CYP2D6 Extensive and Poor Metabolizers

Genetically driven variations in the level of cytochrome P450 (CYP) 2D6 metabolic activity have been shown to significantly affect the pharmacokinetic behaviour of medications that are substrates of this enzyme. To evaluate the impact of CYP2D6 extensive metabolizer (EM) and poor metabolizer (PM) phenotypes on the pharmacokinetics of single doses of venlafaxine extended release (ER) and desvenlafaxine (administered as desvenlafaxine succinate). This study used a randomized, open-label, two-period, parallel-group, crossover design. The enrolled healthy subjects participated in the study for approximately 8 weeks, which included ≤ 6 weeks of screening procedures and two separate 1-week partial inpatient confinement periods (separated by a 4-day washout period), during which venlafaxine ER or desvenlafaxine was administered and blood samples were collected. Subjects were admitted to partial inpatient confinement in a laboratory setting for the two separate study periods where each study drug was individually administered. Blood samples for pharmacokinetic analyses were collected during the 120 hours following administration of each study drug. Plasma concentrations of the study drugs were measured by a third-party analyst using liquid chromatography-tandem mass spectrometry. Healthy subjects were recruited through newspaper advertisements and genotyped to determine their CYP2D6 metabolic phenotype (i.e. EM or PM) using internally developed and commercially available assays. Subjects were reimbursed for their participation in this study. Single, sequentially administered oral doses of the dual-acting, serotonin and norepinephrine reuptake inhibiting antidepressants venlafaxine ER (75 mg) and desvenlafaxine (50 mg) were administered. The main outcome measures were differences in the geometric means for area under the plasma concentration-time curve from time zero to infinity (AUC(∞)) and peak plasma concentration (C(max)) between EMs and PMs. Comparisons were made using a 2-tailed Wilcoxon exact test. No carryover effect was observed between treatment sequence groups. There was no statistically significant difference in either C(max) or AUC(∞) of O-desmethylvenlafaxine between PMs (n = 7) and EMs (n = 7) following administration of desvenlafaxine 50 mg. However, when subjects received venlafaxine ER 75 mg, the AUC(∞) and C(max) of O-desmethylvenlafaxine (the primary active metabolite) were 445% and 434% higher, respectively, in EMs compared with PMs (p ≤ 0.001), and the AUC(∞) and C(max) of venlafaxine were 445% and 180% higher, respectively, in PMs compared with EMs (p < 0.01). In addition, the ratios of O-desmethylvenlafaxine : venlafaxine AUC(∞) and C(max) for subjects receiving venlafaxine ER 75 mg were higher for EMs (6.2 and 3.3) than PMs (0.21 and 0.22; p ≤ 0.001 for both comparisons). In contrast to venlafaxine ER 75 mg, the pharmacokinetics of desvenlafaxine 50 mg is not significantly impacted by CYP2D6 genetic polymorphisms. PMs receiving venlafaxine ER 75 mg had significantly lower O-desmethylvenlafaxine and higher venlafaxine plasma concentrations.

P02-455 - Venlafaxine and CYP2D6 in clinical practice: An observational study

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.

Effect of Cytochrome P450 Enzyme Polymorphisms on Pharmacokinetics of Venlafaxine

This study examines the relationship between blood concentrations of venlafaxine and its active metabolite, O-desmethyl venlafaxine (ODV), and genetic variants of the cytochrome P450 enzymes CYP2D6 and CYP2C19 in human subjects. Trough blood concentrations were measured at steady state in patients treated with venlafaxine extended release in a clinical practice setting. CYP2D6 and CYP2C19 genotypes were converted to activity scores based on known activity levels of the two alleles comprising a genotype. After adjusting for drug dose and gender effects, higher CYP2D6 and CYP2C19 activity scores were significantly associated with lower venlafaxine concentrations (P < 0.001 for each). Only CYP2D6 was associated with the concentration of ODV (P < 0.001), in which genotypes with more active alleles were associated with higher ODV concentrations. The sum of venlafaxine plus ODV concentration showed the same pattern as venlafaxine concentrations with CYP2D6 and CYP2C19 genotypes with higher activity scores being associated with a lower venlafaxine plus ODV concentration (2D6 P = 0.01; 2C19 P < 0.001). Because allelic variants in both CYP2D6 and CYP2C19 influence the total concentration of the active compounds venlafaxine and ODV, both CYP2D6 and CYP2C19 genotypes should be considered when using pharmacogenomic information for venlafaxine dose alterations.

Study of antinociceptive activity of SSRI (fluoxetine and escitalopram) and atypical antidepressants (venlafaxine and mirtazepine) and their interaction with morphine and naloxone in mice

Objective:to study the probable site of antinociceptive action of SSRI (fluoxetine, escitalopram) and atypical antidepressants (mirtazapine, venlafaxine) and their interaction with morphine and naloxone.Materials and Methods:the study was conducted on albino mice (25-35 grams) of either sex. Different doses of morphine (0.5 and 1 mg/kg), fluoxetine (2, 5 and 10 mg/kg), venlafaxine (30, 40 and 50 mg/kg), mirtazapine (3, 5 and 7 mg/kg) and escitalopram (2.5, 5 and 10 mg/kg) were administered subcutaneously to obtain their subanalgesic doses using tail flick analgesiometer. Tail flick latencies were obtained at 15, 30, 60 and 120 min. after drug administration. Naloxone (1 mg/kg) was administered 10 minutes prior to test drug for testing antagonism.Observations:fluoxetine (5 and 10 mg/kg), mirtazapine (5 and 7 mg/kg) and venlafaxine (40 and 50 mg/kg) were found to have antinociceptive activity but not at lower doses. Escitalopram failed to show any antinociceptive activity at any of the doses used. The antinociceptive effect of all the drugs was antagonized by naloxone (1 mg/kg). Further, subanalgesic doses of fluoxetine, mirtazapine and venlafaxine showed analgesic activity with suboptimal dose of morphine (0.5 mg/kg).Result and conclusion:fluoxetine, mirtazapine and venlafaxine have antinociceptive activity whereas escitalopram doesn’t; their site of action seems to be the same as that of opioid analgesics (‘mue’ receptors). However, other pathways (cholinergic, histaminic, noradrenergic, GABAergic) may be involved in mediation of their analgesic activity, deserving further elucidation. Results apparently show that these drugs may be useful in the management of pain as monotherapy or in combination with other opioids.

Sustained release of venlafaxine from venlafaxine–montmorillonite–polyvinylpyrrolidone composites

Due to shorter half life of venlafaxine, it is a prime requirement to develop a formulation which could extend the release of venlafaxine in the human body and also eliminate daily multiple dosage of venlafaxine. Montmorillonite (MMT) was used as sustained release carrier for venlafaxine by preparing venlafaxine–MMT by ion exchange. Venlafaxine–MMT was coated with polyvinylpyrrolidone to delay the release of venlafaxine. In vitro releases of venlafaxine from the various formulations were carried out in simulated gastric and intestinal fluids in controlled environment. 50% of venlafaxine was released by intestinal fluid within 5h, >95% within 48h. Venlafaxine–MMT coated with PVP further decreased the release of venlafaxine.

Sleepwalking in Multiple Sclerosis: A Case Report

Back to table of contents Previous article Next article LETTERFull AccessSleepwalking in Multiple Sclerosis: A Case ReportH. Dilek Yalvac M.D.,Murat Emul M.D.,Rifat Karlidag M.D.,Cemal Ozcan M.D.,Suheyla Unal M.D.,H. Dilek Yalvac M.D.Search for more papers by this author,Murat Emul M.D.Search for more papers by this author,Rifat Karlidag M.D.Search for more papers by this author,Cemal Ozcan M.D.Search for more papers by this author,Suheyla Unal M.D.Search for more papers by this author,Published Online:1 Oct 2010https://doi.org/10.1176/jnp.2010.22.4.451.e32AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editors: Multiple sclerosis is an inflammatory demyelinating disease in which patches of damage called plaques or lesions predominantly appear in the cerebral white matter. Multiple sclerosis is frequently associated with psychiatric manifestations (e.g., patients with multiple sclerosis have more sleep disorders than the general population). 1 , 2 However, there has been no literature regarding somnambulism related to multiple sclerosis. Case Report A 33-year-old man with diagnoses of multiple sclerosis and anxiety disorder has been followed for 2 years. He was treated with interferon beta-1a, 22 mcg three times per week; venlafaxine, 225 mg/day; and tioridazin, 20 mg/day. He began to complain about sleepwalking during the first one-third of the night. The dosage of venlafaxine was decreased to 150 mg/day, and imipramine, 50 mg/day, was initiated. He complained of ataxic walking, increasing of ataxia, dizziness, imbalance, and fatigue. He had no epileptic seizure. On MRI, demyelinating plaques lining to corpus with vertical angle were seen in bilateral periventricular white matter, but they were also retained in the corpus callosum and left brachium pontis. There were increases of a few multiple millimetric signals at the level of pericallosal and semiovale, especially on the left and posterior side on T 2 -weighted imaging. There were a few millimetric signal increases in the pons in favor of demyelinating plaques. Discussion Sleepwalking is one of the most common parasomnias, and genetic, developmental, organic, and psychological factors have been proposed as causes. Sleepwalking episodes can be triggered by fever, medication with some drugs, stress, and major life events. 3 Neither sleepwalking in our patient’s family history or in his childhood period, nor epileptic history or fever, were detected in the present case. During non-REM sleep, PET studies have shown a net reduction in cerebral activity in the thalamic nuclei, brain stem (mesencephalon and tegmentum of pons), basal ganglia, hypothalamus, basal forebrain, the orbitofrontal and anterior cingulate cortical regions, the precuneus, and the right mediotemporal regions. 4 There were a few millimetric signal increases in the pons giving evidence for demyelinating plaques. It has been reported that the unilateral small lesion of the pontine tegmentum could be responsible for the parasomnia overlap disorder as in other rare lesional cases. 5 We considered such overlapping in our patient because demyelinating plaques lining to corpus with a vertical angle were seen in bilateral periventricular white matter, but they were retained in the corpus callosum and left brachium pons in imaging. Paroxetine and lithium may have triggered the episodes of somnambulism. 3 Until now, there have been no reports relating venlafaxine to somnambulism. Although the patient had been using venlafaxine for 2 years without parasomnia complaint, decreasing the dosage of venlafaxine did not affect the frequency of sleepwalking. Thus, we suggested that demyelinating plaque in the pons might be responsible for the sleepwalking as a neuropsychiatric symptom in multiple sclerosis. Department of Psychiatry, Menemen State Hospital, Izmir, TurkeyDepartment of Psychiatry, University Hospital of Afyon Kocatepe University, Afyonkarahisar, TurkeyDepartment of Psychiatry, Medical Centre of Turgut Ozal, University of Inonu, Malatya, TurkeyDepartment of Neurology, Medical Centre of Turgut Ozal, University of Inonu, Malatya, TurkeyDepartment of Psychiatry, Medical Centre of Turgut Ozal, University of Inonu, Malatya, Turkey

Reduced signal transduction by 5‐HT4 receptors after long‐term venlafaxine treatment in rats

The 5-HT(4) receptor may be a target for antidepressant drugs. Here we have examined the effects of the dual antidepressant, venlafaxine, on 5-HT(4) receptor-mediated signalling events. The effects of 21 days treatment (p.o.) with high (40 mg·kg(-1)) and low (10 mg·kg(-1)) doses of venlafaxine, were evaluated at different levels of 5-HT(4) receptor-mediated neurotransmission by using in situ hybridization, receptor autoradiography, adenylate cyclase assays and electrophysiological recordings in rat brain. The selective noradrenaline reuptake inhibitor, reboxetine (10 mg·kg(-1), 21 days) was also evaluated on 5-HT(4) receptor density. Treatment with a high dose (40 mg·kg(-1)) of venlafaxine did not alter 5-HT(4) mRNA expression, but decreased the density of 5-HT(4) receptors in caudate-putamen (% reduction = 26 ± 6), hippocampus (% reduction = 39 ± 7 and 39 ± 8 for CA1 and CA3 respectively) and substantia nigra (% reduction = 49 ± 5). Zacopride-stimulated adenylate cyclase activation was unaltered following low-dose treatment (10 mg·kg(-1)) while it was attenuated in rats treated with 40 mg·kg(-1) of venlafaxine (% reduction = 51 ± 2). Furthermore, the amplitude of population spike in pyramidal cells of CA1 of hippocampus induced by zacopride was significantly attenuated in rats receiving either dose of venlafaxine. Chronic reboxetine did not modify 5-HT(4) receptor density. Our data indicate a functional desensitization of 5-HT(4) receptors after chronic venlafaxine, similar to that observed after treatment with the classical selective inhibitors of 5-HT reuptake.

Chronic effects of venlafaxine on synaptophysin and neuronal cell adhesion molecule in the hippocampus of cerebral ischemic miceThis paper is one of a selection of papers published in this special issue entitled “Second International Symposium on Recent Advances in Basic, Clinical, and Social Medicine” and has undergone the Journal's usual peer review process.

Venlafaxine, a novel antidepressant, inhibits serontonin and norepinephrine reuptake in the presynaptic cleft. Unlike typical selective serontonin reuptake inhibitors (SSRIs), venlafaxine may have modulatory effects on nerve terminals and neuronal plasticity. Our preliminary data found that 5 mg.kg-1.d-1 of venlafaxine treatment prevented decreased synaptophysin (SYP) in the hippocampus, which results from chronic restrained stress in the rat model. The present study investigates whether venlafaxine regulates alterations of synaptophysin and neuronal cell adhesion molecule (NCAM) in a post-stroke depression mouse model. We compared the expression level of SYP and NCAM in the hippocampus of global cerebral ischemic (GCI) mice treated with different doses of venlafaxine using immunohistological and Western blot analysis. Pre-treatment with intraperitoneal injection of venlafaxine (2.5 and 5.0 mg.kg-1.d-1) for 14 days significantly prevented the decrease of SYP in the hilus area of the hippocampus in vehicle-treated GCI mice. NCAM was significantly higher in the hippocampus of vehicle-treated GCI mice, and pretreatment with venlafaxine prevented alterations of NCAM, with the high-dose venlafaxine group comparable with vehicle-sham mice. The results suggest the alteration of neuronal remodeling proteins in the hippocampus may be an underlying mechanism of venlafaxine in treating post-stroke depression.

Effect of venlafaxine on bone loss associated with ligature-induced periodontitis in Wistar rats

BackgroundThe present study investigated the effects of venlafaxine, an antidepressant drug with immunoregulatory properties on the inflammatory response and bone loss associated with experimental periodontal disease (EPD).Materials and MethodsWistar rats were subjected to a ligature placement around the second upper left molar. The treated groups received orally venlafaxine (10 or 50 mg/kg) one hour before the experimental periodontal disease induction and daily for 10 days. Vehicle-treated experimental periodontal disease and a sham-operated (SO) controls were included. Bone loss was analyzed morphometrically and histopathological analysis was based on cell influx, alveolar bone, and cementum integrity. Lipid peroxidation quantification and immunohistochemistry to TNF-α and iNOS were performed.ResultsExperimental periodontal disease rats showed an intense bone loss compared to SO ones (SO = 1.61 ± 1.36; EPD = 4.47 ± 1.98 mm, p < 0.001) and evidenced increased cellular infiltration and immunoreactivity for TNF-α and iNOS. Venlafaxine treatment while at low dose (10 mg/kg) afforded no significant protection against bone loss (3.25 ± 1.26 mm), a high dose (50 mg/kg) caused significantly enhanced bone loss (6.81 ± 3.31 mm, p < 0.05). Venlafaxine effectively decreased the lipid peroxidation but showed no significant change in TNF-α or iNOS immunoreactivity.ConclusionThe increased bone loss associated with high dose venlafaxine may possibly be a result of synaptic inhibition of serotonin uptake.

Correlation between SERT polymorphisms and Venlafaxine response in major depression patients

Major depression (MD) has a complex multifactorial aetiology with genetic and environmental factors contributing to this disorder. As with all antidepressant treatments, there is variability in drug response because of heredity, and this leads us to focus on the genetic polymorphism of the drug’s metabolising transporter genes. The serotonin transporter (5-HTT) gene is a particularly important candidate for genetic involvement in MD disorders owing to its key role in the regulation of serotonergic transmission and is therefore considered an interesting candidate in the mechanism of antidepressant drugs. Here, we studied the associations between genetic polymorphisms in two regions of the 5-HTT gene (5-HTTLPR and VNTR) to understand venlafaxine response. Venlafaxine was found to be effective in MD patients based on their HAM-D and CGI scores (p<0.05). Although the results did not yield a significant difference between the frequencies of the SS, LS, LL, 9/9, 10/10, 12/12 and 10/12 genotypes and venlafaxine response, venlafaxine dose was increased in patients with Stin2.12 and S alleles. These alleles might have a predisposition to mood disorders. Further studies with more patients are required to confirm this clinical association.