Mg Of Venlafaxine Research Articles

The influence of a single and chronic administration of venlafaxine on tramadol pharmacokinetics in a rabbit model.

The combined use of tramadol with selective serotonin and norepinephrine reuptake inhibitors e.g. venlafaxine may be associated with serotonin syndrome. No previous studies exist examining the influence of a weak CYP2D6 inhibitor venlafaxine on the pharmacokinetics of tramadol. Therefore, the aim of this study was to determine the effect of a single and chronic administration of venlafaxine on the pharmacokinetics of tramadol using a rabbit model. Adult New Zealand white rabbits of both sexes (n=21) were used. Animals received 100mg of tramadol per os (one slow release tablet) and 75mg of venlafaxine (one prolonged release capsule), and were divided into four groups: control group - a single dose of tramadol alone, 1day group - a single dose of tramadol and venlafaxine, 7 and 14days groups - seven and fourteen days administration of venlafaxine once daily plus a single dose of tramadol on the last day of the study. Venlafaxine administration over a period of 7 and 14days resulted in faster elimination of tramadol compared to the control group: significantly higher values of k el, and lower values of t1/2kel and MRT for the 7 and 14days group were observed. Although no differences in bioavailability of tramadol were obtained. Using a rabbit model, there is no evidence that the combined administration of tramadol and venlafaxine may increase the plasma exposure of tramadol and therefore increase the risk of serotonin syndrome.

The impact of the duration of an untreated episode on improvement of depression and somatic symptoms.

PurposeThe aim of this study was to investigate the impact of the duration of an untreated episode (DUE) on the improvement of depression and somatic symptoms among patients with major depressive disorder (MDD), after the patients had received 4 weeks of pharmacotherapy.MethodsIn this open-label study, there were 155 participants with MDD who were treated daily with 75 mg of venlafaxine for 4 weeks. DUE was defined as the interval between the onset of the index major depressive episode and the start of pharmacotherapy. The Depression and Somatic Symptoms Scale (DSSS), composed of the depression subscale (DS) and the somatic subscale (SS), was used. The SS included the pain subscale (PS) and the nonpain somatic subscale (NPSS). Multiple linear regressions were used to test the impacts of DUE on the improvement percentages (IPs) of depression and somatic symptoms.ResultsEighty-five subjects completed the 4-week treatment. The IPs of the DS, SS, and NPSS were significantly negatively correlated with DUE. A shorter DUE was related to higher IPs. DUE was an independent factor, predicting the IPs of the DS, SS, and NPSS. DUE <1 month was the most powerful time-point to predict the IPs of the DS, SS, and NPSS. However, DUE was unable to predict the IP of the PS at all time-points.ConclusionA shorter DUE might be one of the factors related to greater improvement of depression and somatic symptoms. DUE should be considered as an important factor when investigating the prognosis of depression and somatic symptoms.

Nystagmus as a discontinuation symptom after antidepressant therapy: a case report.

To the Editor: I present a patient with recurrent depression who experienced remission on a fixed daily dose of 150 mg of venlafaxine in the first episode and 15 mg of escitalopram in the second episode. Postural nystagmus appeared after discontinuation of treatment in each episode. Case report. Mr A, a 56-year-old married man, had a 6-year history of recurrent major depressive disorder (MDD) according to the DSM-5. His first episode had begun by January 2007 when he was 50 years old. His depressive symptoms began to appear slowly and were characterized by depressed mood, irritability, diminished interest and pleasure in his everyday activities, loss of appetite, lack of energy, poor concentration, early morning waking, and recurrent thoughts such as, “It is not interesting being alive.” These symptoms led to impaired work and social functioning. His parents and sister had a history of symptoms of depression. Extended-release venlafaxine was started with 37.5 mg/d and was increased gradually to 150 mg/d in 4 weeks with no adverse effects. The patient experienced important symptomatic relief by week 4 and reached remission in 8 weeks. Functionality was completely restored by August 2007. For the next 18 months, Mr A was on the same treatment regimen with full MDD remission. Remarkably, 10 days after completion of slow antidepressant discontinuation (ie, taper for 2 months), Mr A, who had no medical history of eye problems, started experiencing position vertical and lateral nystagmus, usually at its worst in the morning. The symptom was ameliorated during the day, almost disappearing by night. No other visual problem was related by the patient or detected. The symptom persisted for 3 weeks but disappeared slowly at the end of the fifth week. In January 2010, MDD reappeared, characterized by similar symptoms as previously described but with the emergence of symptoms of anxiety and fatigue (both severely worsening in the morning) and serious impairment of social functioning. Escitalopram was administered at 5 mg/d, reaching 15 mg/d in 3 weeks with no unwanted effects. After 6 weeks, depression had remitted. During follow-up (18 months), there was no relapse. After slow discontinuation of escitalopram for 6 weeks, the patient experienced nystagmus with the same characteristics as described earlier, disappearing by 4 to 5 weeks. The literature includes only 1 report of positional nystagmus associated with amitriptyline withdrawal.1 There is another case report of a patient who manifested signs of serotonin syndrome during an intravenous anesthetic with remifentanil and propofol. The patient displayed nystagmus, lower extremity clonus, and diaphoresis. At the time of surgery, the patient was being treated with 60 mg of fluoxetine for severe MDD. His symptoms resolved in the surgical care unit without incident. Investigators have shown that fluoxetine2,3 and sertraline4 can induce oculomotor abnormalities during sleep in depressed patients. It is suggested that these abnormalities are likely to be the result of increased availability of serotonin5,6 and secondary dopaminergic effects.7–9 As the use of antidepressants continues to increase, the incidence of withdrawal symptoms is also likely to increase. Patients treated with antidepressants should be questioned specifically during the discontinuation phase about the presence of this unwanted effect. It is important to recognize its clinical features as well as the benign course after a few weeks of follow-up.

PM.87 Unplanned Pregnancy in a Woman with Huntington’s Chorea

A 35 year old hospital worker was diagnosed with Huntington’s disease in the previous year after following a personality change.Her main symptoms reported was that of choriform movements and anxiety...

Pharmacoeconomic evaluation of venlafaxine compared with citalopram in generalized anxiety disorder

Pharmacoeconomic evaluation aims to investigate the selection and use of drugs to make patient medication efficient, safe and economical. In this study, a pharmacoeconomic evaluation was performed to assess two treatments for generalized anxiety disorder (GAD). A total of 100 outpatients with GAD were enrolled. The patients were divided into the following two groups according to treatment program: the venlafaxine group (n=50) and the citalopram group (n=50). The patients in the venlafaxine group received 75 mg of orally administered venlafaxine and 50 mg of sulpiride once a day for the first seven days and thereafter only 150 mg of venlafaxine once a day. The patients in the citalopram group received 10 mg of citalopram and 50 mg of sulpiride orally once a day for the first seven days and thereafter only 20 mg once a day. The treatment period for the two groups was three months. Follow-up was conducted at the end of weeks 2, 4 and 12 to evaluate drug efficacy, quality of life and drug side-effects. Moreover, the two groups were scored according to cost-effectiveness analysis. Using the SF-36 Scale, the quality of life score of the patients in the venlafaxine group was observed to be significantly higher compared with that of the patients in the citalopram group at the end of weeks 4 and 12 (P<0.05). The reduction rates of the Hamilton Anxiety (HAMA) scale show that the efficacy of venlafaxine was significantly better than that of citalopram by the end of week 12. The findings of this study suggest that venlafaxine is more cost-effective than citalopram in the treatment of outpatients with GAD.

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.

Uncontrolled Self-Medication with Venlafaxine in a Patient with Major Depressive Disorder

Antidepressants are known to have no significant ability to cause addiction. However, a recent study showed many individuals with mood disorders self-medicated with antidepressants to relieve symptoms. We report here a male physician, diagnosed five years ago with major depressive disorder, with insomnia, anxiousness, and chest heaviness. He began self-medicating with 150 mg of venlafaxine daily, without any monitoring. During his most recent severe depressive episode, he was taking up to 1,500 mg of venlafaxine daily. Without this medication, he experienced discontinuation syndrome, which included severe anxiety, chest heaviness, and breathing difficulty, and which he judged as indicating a more severely depressed state. He also experienced overdose symptoms, such as hypertension and tachycardia. He attempted suicide with drugs that he possessed. In conclusion, careful monitoring is needed when treating patients with venlafaxine, because its discontinuation syndrome is similar to symptoms of major depressive disorder, and suicidality may result from an overdose.

A Single-Blind Placebo Run-In Study of Venlafaxine XR for Activity-Limiting Osteoarthritis Pain

Osteoarthritis pain is a significant problem for our aging population. Non-steroidal anti-inflammatory drugs and opioids are effective treatments, but have significant adverse effects, so there is a need for alternative treatments. Selective norepinephrine-serotonin reuptake inhibitor antidepressants may provide a new treatment option for osteoarthritis pain. We performed a single-blind placebo run-in trial of 150-225 mg of venlafaxine in 18 subjects with activity-limiting osteoarthritis pain. Each subject received 2 weeks of placebo followed by 10 weeks of venlafaxine. The primary outcome was reduction in average pain intensity between 2 and 12 weeks. For subjects not completing the trial, their last observation was carried forward as an imputed outcome. Average pain on the Brief Pain Inventory (BPI) was 4.7 at baseline, 4.4 after the 2-week placebo run-in, and 3.3 at 12 weeks (25% decrease, P = 0.03). Nine subjects (50%) reported at least 30% pain reduction between weeks 2 and 12. The Western Ontario and McMasters University Osteoarthritis Index (WOMAC) pain score at baseline was 2.0, 1.8 after 2 weeks, and 1.7 after 12 weeks. This represented a 6% decrease in pain between weeks 2 and 12 (P = 0.42), with two subjects (11%) reported at least 30% pain relief between weeks 2 and 12 on the WOMAC. Effects on self-reported physical and role function and depression were marginal or non-significant, and observed physical function did not improve. Venlafaxine significantly reduced pain intensity on the BPI and marginally improved self-reported function. Venlafaxine should be investigated further in a larger randomized trial for the treatment of osteoarthritis pain.

Treatment with Venlafaxine in Six Cases of Children with Narcolepsy and with Cataplexy and Hypnagogic Hallucinations

Narcolepsy with cataplexy is a chronic neuropsychiatric disorder associated with inappropriate control of rapid eye movement (REM) sleep. The main symptoms are excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, and disturbed nocturnal sleep. Cataplexy is marked by episodes of muscular weakness and may cause the patient to collapse to the ground. So far, pharmacotherapy of cataplexy and hypnagogic hallucinations has been predominantly based on tricyclic antidepressants. Recently, new drugs that block the reuptake of norepineprine and serotonin (e.g., venlafaxine) have been suggested as first-line treatment. These drugs have become our choice in treating children with cataplexy and nightmares as a symptom in narcolepsy. We describe clinical case reports of venlafaxine treatment in 6 children aged 7-12 years old when diagnosed with narcolepsy-cataplexy. In 2 cases with up to 50 daily cataplectic attacks, an initial effect of 37.5 mg of venlafaxine was initially observed. However, during the first year, the dose had to be increased to 112.5 mg daily to avoid cataplexy. A third patient with partial cataplexy was treated with 75 mg of venlafaxine daily. In 2 cases, hypnagogic hallucinations, described by the patients as nightmares, were the most troubling symptom and were successfully treated with only 37.5 mg of venlafaxine daily. Side effects included an increase of disturbed nocturnal sleep when venlafaxine was taken after 2:00 p.m. No major aggressive or suicidal thoughts and no raised blood pressure were recorded. Venlafaxine has proven to be an effective treatment of cataplexy and hypnagogic hallucinations in 6 children with narcolepsy. No severe side effects were observed.

Effect of Desvenlafaxine on the Cytochrome P450 2D6 Enzyme System

The cytochrome P450 2D6 (CYP2D6) enzyme is responsible for metabolizing approximately 25% of pharmaceutical agents. Individuals with impaired CYP2D6 metabolism and those concomitantly receiving agents that inhibit CYP2D6 can have variations in concentrations of such medications and their metabolites. Five studies assessing the interaction between desvenlafaxine and CYP2D6 are reviewed. Study 1 compared desvenlafaxine area under the plasma concentration-versus-time curve (AUC) in CYP2D6 extensive metabolizers (EMs) and poor metabolizers (PMs) after administration of 100 mg of desvenlafaxine or 75 mg of venlafaxine extended release (ER). Studies 2 to 5 assessed the effect of concomitant administration of desvenlafaxine 100 mg (studies 2, 4, and 5) or 400 mg (study 3), paroxetine (20 mg, study 4), and duloxetine (30 mg twice daily; study 5) on the CYP2D6 probe desipramine. In study 1, there was no significant difference in mean desvenlafaxine AUC between the CYP2D6 EMs and PMs (-11%; P=0.641) who were administered desvenlafaxine. However, PMs receiving venlafaxine ER had significantly higher venlafaxine and lower desvenlafaxine AUCs compared with EMs (+350% and -74%, respectively; P<0.001 for each). In studies 2, 4, and 5, the mean increases in desipramine AUC with concomitant administration of desvenlafaxine 100 mg ranged from 17% to 36%; the increase with concomitant administration of desvenlafaxine 400 mg (study 3) was 90%. Paroxetine and duloxetine produced increases in mean desipramine AUC of 419% and 122%, respectively, which were significantly greater than the increases seen with desvenlafaxine 100 mg (P<0.001 for each comparison). Based on the findings presented here, desvenlafaxine is expected to have a low risk for variability in efficacy and safety/tolerability resulting from CYP2D6 polymorphisms or drug-drug interactions when coadministered with CYP2D6 substrates or inhibitors.

Safety and efficacy of venlafaxine in the treatment of premature ejaculation: a double-blind, placebo-controlled, fixed-dose, randomised study

Venlafaxine is a serotonin-noradrenaline reuptake inhibitor antidepressant. Two hundred and twenty-two married men (mean age, 34 years) with premature ejaculation (PE) were randomly assigned to receive 75 mg of venlafaxine extended release (n = 112) (group 1) or placebo (n = 110) (group 2) for 12 weeks. Pre-treatment evaluation included history and physical examination, geometric mean intravaginal ejaculatory latency time (IELT) and International Index of Erectile Function (IIEF). The efficacy of two treatments was assessed every 2 weeks during treatment, and at the end of study, using responses to IIEF, IELT evaluation, mean intercourse satisfaction domain, mean weekly coitus episodes and adverse drug effects. At the end of treatment period, the geometric mean IELT in venlafaxine and placebo group demonstrated 1.7-fold (95% CI: 0.76-1.96) and 1.6-fold (95% CI: 0.87-1.84) increase respectively (P = 0.1). The mean weekly intercourse episodes increased from pre-treatment values of 1.2 and 1.18 to 2.1 and 1.9 for venlafaxine and placebo respectively (P = 0.08). Baseline mean intercourse satisfaction domain values of IIEF 12 and 12 reached to 13 and 12 at 12-week treatment in groups 1 and 2 respectively (P = 0.07). Mean number of adverse events was 32 for venlafaxine and 8 for placebo (P = 0.02). Venlafaxine is not better than placebo in treatment of PE.

A 60-Year-Old Woman Who Has Felt Sad for Much of Her Life

DR DELBANCO: A 60-year-old unemployed widow, Ms A has felt sad much of her life. She graduated from high school, has 1 child, was married twice, and used to work as an aide in health care facilities. She lives in urban housing with her mother and has public insurance. For the past 30 years she has received care from a general internist practicing in an urban primary care practice. Dating back to her first memories, Ms A recalls a troubled family life that may have included various forms of abuse. She was married and divorced in the 1970s; her daughter had some difficulty during her teens and early adulthood, but is doing well now and is close to the patient. Ms A first felt seriously depressed in her 20s. Over the years she tried alprazolam, sertraline, bupropion, diazepam, amitriptyline, nortriptyline, and citalopram, reporting that these medications calmed her down at times, but did not really affect her depression. Despite her physician’s repeated recommendations for consultation and brief attempts on her part, she has chosen generally to stay away from psychiatry and social work. She married a second time in the late 1990s, but had a disastrous relationship and returned alone to her mother’s home in 2003. There, she contemplated suicide during uncontrolled periods of crying. This led to a 3-week hospitalization for depression, during which time she learned that her husband had suddenly died. During that hospitalization, there was no evidence of psychosis or dementia. After discharge with prescriptions for 150 mg of venlafaxine and 50 mg of trazodone at night, she accepted weekly psychotherapy in a community agency for 6 months. However, she has a mechanical aortic valve and became rather casual in following directions for monitoring her warfarin levels, fell, and was hospitalized for a cranial subdural hematoma and bleeding into her perisacral region. The subdural was drained through burr holes and she recovered without medical sequelae. Thereafter, she stopped taking the antidepressants. Currently, Ms A is refusing further psychotherapy and consultation and is applying for long-term disability. She is taking clonazepam intermittently under the guidance of her internist. She has never smoked, has had only a few drinks containing alcohol, and has not used illicit drugs. Her medical history is notable for surgery for congenital aortic valvular disease in the 1970s requiring anticoagulation for her mechanical aortic valve. Over the past 30 years, she has complained often of palpitations with several evaluations yielding normal cardiac rhythm and function. She has experienced recurrent migraines, had a 6-month period of unexplained abdominal pain that cleared without specific therapy, has passed kidney stones, and is treated for mild hypertension. Currently, she is bothered primarily by impaired recent memory that appears to be exacerbated by stress. On physical examination, Ms A looks well, younger than her stated age, and has full range of affect. She smiles readily, and her internist reports not feeling sad in the room with her. She is normotensive and in sinus rhythm. Her cardiac examination is unremarkable, save for sounds produced by the prosthetic aortic valve. There is no evidence for cardiac decompensation and none for neurological deficits. Her international normalized ratio is variable, and she has low-grade chronic anemia of uncertain etiology. Her current medications include clonazepam, atenolol, triamterene, hydrochlorothiazide, clopidogrel, warfarin, calcium, and esomeprazole for symptoms of gastroesophageal reflux disease.

Venlafaxine extended-release in patients older than 80 years with depressive syndrome

The aim of this evaluation was to assess the efficacy and safety of venlafaxine extended-release (ER) in very old primary care out-patients with depressive syndrome and associated anxiety symptoms. This was an observational, naturalistic, multicenter, prospective, open-label study in an outpatient population with a diagnosis of depressive syndrome with anxiety symptoms. Minimum scores of 17 and 10 on the Hamilton Rating Scale for Depression (HAM-D(17)) and Anxiety (HAM-A), respectively, were required. Daily doses of 75 mg to 225 mg of venlafaxine extended release (ER) were administered for 24 weeks. Effectiveness for depressive-anxious symptomatology was assessed using the HAM-D(17) and HAM-A scales. The 97 patients discussed in this report are a subgroup comprising all elderly patients, aged >or= 80 years, who were part of the larger observational, naturalistic, multicenter, prospective, open-label study and who had received venlafaxine ER for a maximum duration of 24 weeks. At endpoint, remission rates were 57.1% (HAM-D(17) <or=7), 66.2% (HAM-A <or= 7), and 52% (HAM-D(17) <or=7 and HAM-A <or= 7). Twenty patients (20.6%) dropped out or were withdrawn. Adverse events were reported by seven (7.2%) patients, none were reported as serious. Venlafaxine ER was shown to be an effective and safe drug for the treatment of very elderly primary care patients with depressive syndrome and associated anxiety symptoms.

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No Effect of a Selective Serotonergic/Noradrenergic Reuptake Inhibitor on Endurance Performance

The purpose of the present study was to examine the effects of a selective serotonin/noradrenaline (5-HT/NA) reuptake inhibitor (SNRI) on exercise performance. Seven well-trained male cyclists completed 2 time trials in a doubleblind randomized crossover design ingesting either placebo (PLAC) or 2 × 37.5 mg of Venlafaxine (VEN). Blood samples were collected for adrenocorticotropin hormone (ACTH), prolactin (PRL), cortisol, growth hormone (GH), beta-endorphins, and catecholamines and were taken at rest, at 30-min time intervals, at the end of exercise, and during recovery. Performance was not influenced by the SNRI (VEN: 92 min ± 3 min, PLAC: 92 min ± 1 min). Lactate concentrations, heart rate, and fatigue scores were not different between trials. All hormones increased during exercise in both trials. In the VEN trial, ACTH, beta endorphins, and NA concentrations were higher. The results from the present study demonstrate that a SNRI is not able to affect endurance performance in well-trained cyclists. However, it seems as though the hormonal response to the combination of the pharmacological manipulation and exercise is regulated more by the noradrenergic drive.

Postmortem tissue concentrations of venlafaxine

Venlafaxine is a phenethylamine antidepressant which inhibits both serotonin and norepinephrine reuptake and is structurally unrelated to the serotonin reuptake inhibitors (SSRIs). Its major metabolite, O-desmethylvenlafaxine (ODV), also inhibits serotonin reuptake. Although metabolized by the cytochrome P-450 (CYP) system, venlafaxine inhibits CYP 2D6 and 3A4 to a far lesser extent than do the SSRIs. Mechanisms of drug action are reviewed and evaluated in the investigation of 12 fatalities occurring over a 6-month-period where venlafaxine was detected. Venlafaxine and ODV were identified by liquid chromatography–mass spectrometry (LC–MS) using atmospheric pressure ionization (API) electrospray in positive mode following an n-butyl chloride extraction. Postmortem tissue concentrations studied in each of 12 postmortem cases for venlafaxine and ODV, were 0.1–36 and <0.05–3.5 mg/l (peripheral blood), <0.05–22 and <0.05–9.9 mg/kg (liver), <0.05–10 and <0.05–1.5 mg/l (vitreous), <0.05–53 and <0.05–6.8 mg/l (bile), <0.05–55 and <0.05–21 mg/l (urine), respectively, and 0.1–200 mg of venlafaxine in the gastric contents. Venlafaxine was typically present with other drugs, including other antidepressants, alcohol, and benzodiazepines. The potential for interaction with each drug is discussed. Over the 6-month-period of this study, there were no deaths ascribed solely to venlafaxine intoxication.

Critical Use of Venlafaxine Serology to Uncover Genetic Rapid Metabolism

Back to table of contents Previous article Next article LetterFull AccessCritical Use of Venlafaxine Serology to Uncover Genetic Rapid MetabolismJames L. Schaller, M.D., , and David Behar, M.D., James L. SchallerSearch for more papers by this author, M.D., Chester County Research Center, Chester Springs, PA, and David BeharSearch for more papers by this author, M.D., Eastern Pennsylvania Psychiatric Institute, Philadelphia, PAPublished Online:1 Feb 2001AboutSectionsView EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail SIR: A 17-year-old male with three serious overdose suicide attempts in two years and intractable major depression (MD) was successfully treated only with the high dose of 500 mg of venlafaxine per day. His experience illustrates the benefit of dual-action antidepressants, the critical utility of peak venlafaxine serum levels in selected patients, and the utility of knowing familial metabolic rates.Case ReportAn adolescent failed to improve from consecutive trials of 50 mg per day of fluoxetine and 200 mg of sertraline, each for months. Venlafaxine was started for its dual neurotransmitter action, possibly resulting in faster and fuller remission.1,2The youth's baseline Inventory to Diagnose Depression3 score (IDD) was 51 (0–10 is normal). He suffered daily suicidal ideation and profound anhedonia. He was titrated to 375 mg per day of venlafaxine over 2 weeks with only transient anorexia. He improved in 2 weeks, with a peak venlafaxine level of 310 ng/ml and an O-desmethylvenlafaxine (ODV) level of 210 ng/ml. In 3 weeks, he had an IDD of 24.After 5 weeks he worsened, in the absence of stressors. A prompt follow-up plasma venlafaxine level was only 79 ng/ml, with an ODV of only 170 ng/mg. The dose was increased to 425 mg/day in divided doses, with moderate improvement in his MD over 10 weeks. Plasma venlafaxine was 450 ng/mg, with ODV 480 ng/mg. Eventually the dosage was increased to 500 mg (slow-release form) in two doses, at which level the patient had only transient vivid dreams. After 2 months, his IDD scores were normal. Serum levels after 1 year were venlafaxine 650 ng/ml and ODV 590 ng/ml, approximately within the expected peak ranges.Eventually, his father began treatment and was also started on venlafaxine. He also initially had a therapeutic benefit on 200 mg per day, followed by a marked loss of benefit and a significant drop in baseline serum levels. Increasing his dose to 375 mg per day almost put him in full MD remission, with serum levels in the therapeutic range. Both pharmacokinetic and pharmacodynamic response may run in families. CommentReasonable laboratory standards for venlafaxine and ODV4,5 blood levels exist. It seems useful to use blood levels to confirm compliance, to monitor polypharmacy in treatment-resistant patients, and to assess patients with initial clear benefits that are suddenly lost, perhaps because of marked metabolism. Understanding this patient's rapid metabolism kept us from aborting a therapeutic medication and yielded meaningful remission in an otherwise treatment-resistant patient with a history of suicide attempts and severe MD.References1 Nelson JC, Mazure CM, Bowers MB, et al: A preliminary, open study of the combination of fluoxetine and desipramine for rapid treatment of major depression. Arch Gen Psychiatry 1991; 48:303–307Crossref, Medline, Google Scholar2 Silverstone PH, Ravindran AR: Once-daily venlafaxine extended release (xr) compared with fluoxetine in outpatients with depression and anxiety. J Clin Psychiatry 1999; 60:22–28Crossref, Google Scholar3 Zimmerman M, Coryell M, Corenthal C, Wilson S: A self-report scale to diagnose major depressive disorder. Arch Gen Psychiatry 1986; 43:1076–1086Google Scholar4 Clement EM, Odontiadis J, Franklin M: Simultaneous measurement of venlafaxine and its major metabolite, oxydesmethylvenlafaxine, in human plasma by high-performance liquid chromatography with coulometric detection and utilisation of solid-phase extraction. J Chromatography B 1998; 705:303–308Crossref, Medline, Google Scholar5 Hicks DR, Wolaniuk D, Russell A, et al: A high-performance liquid chromatographic method for the simultaneous determination of venlafaxine and O-desmethylvenlafaxine in biological fluids. Therapeutic Drug Monitoring 1994; 16:100–107Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited ByNone Volume 13Issue 1 February 2001Pages 112-a-113 Metrics History Published online 1 February 2001 Published in print 1 February 2001