Potent Serotonin Reuptake Inhibitor Research Articles

Impact of selective serotonin receptor inhibitors on gastric histopathology in patients with depression

Objective: Antidepressant medications such as Selective Serotonin Reuptake Inhibitors (SSRI) and Serotonin and Norepinephrine Reuptake Inhibitors (SNRI) are used in the psychopharmacological treatment for various types conditions. This study aimed to investigate whether SSRIs and SNRIs could reduce gastric intestinal metaplasia. Material Methods: A total of 212 patients who underwent upper gastrointestinal endoscopy plus biopsy in our clinic and were using selective serotonin reuptake inhibitors and other potent serotonin reuptake inhibitors were included in the study. A control group was created with a total of 230 age and gender matched patients who underwent upper gastrointestinal endoscopy plus biopsy but had no SSRI or SNRI usage. Patients’ endoscopic and pathologic findings were recorded retrospectively and compared between the groups. Results: The patient group consisted of 180 (84.9%) male and 32 (15.1%) female patients, while the control group included 175 (76.1%) male and 55 (23.29%) female patients. There was a statistically significant difference between the groups in terms of gender (p=0.020). The rates of erythematous antral gastritis (p<0.001), peptic ulcer (p=0.019), erosive gastropathy (p=0.001) and duodenitis (p=0.002) were statistically significantly lower in the patient group compared to the control group. The rates of H.Pylori(p=0.002), intestinal metaplasia (p=0.013), neutrophil activity (acute inflammation) (p<0.001) and chronic inflammation (p<0.001) were lower in the case group compared to the control group. Conclusion: SSRIs/SNRIs may potentially be used in treating gastrointestinal inflammation and metaplasia. However, further prospective randomised studies with larger series are needed to support our findings.

Exposure to Morphine and Cocaine Modify the Transcriptomic Landscape in Zebrafish Embryos

Morphine and other opioid analgesics are the drugs of election to treat moderate-to-severe pain, and they elicit their actions by binding to the opioid receptors. Cocaine is a potent inhibitor of dopamine, serotonin, and noradrenaline reuptake, as it blocks DAT, the dopamine transporter, causing an increase in the local concentration of these neurotransmitters in the synaptic cleft. The molecular effects of these drugs have been studied in specific brain areas or nuclei, but the systemic effects in the whole organism have not been comprehensively analyzed. This study aims to analyze the transcriptomic changes elicited by morphine (10 uM) and cocaine (15 uM) in zebrafish embryos. An RNAseq assay was performed with tissues extracts from zebrafish embryos treated from 5 hpf (hours post fertilization) to 72 hpf, and the most representative deregulated genes were experimentally validated by qPCR. We have found changes in the expression of genes related to lipid metabolism, chemokine receptor ligands, visual system, hemoglobins, and metabolic detoxification pathways. Besides, morphine and cocaine modified the global DNA methylation pattern in zebrafish embryos, which would explain the changes in gene expression elicited by these two drugs of abuse.

Formulation and Development of Oral Fast-Dissolving Films Loaded with Nanosuspension to Augment Paroxetine Bioavailability: In Vitro Characterization, Ex Vivo Permeation, and Pharmacokinetic Evaluation in Healthy Human Volunteers.

Paroxetine (PX) is the most potent serotonin reuptake inhibitor utilized in depression and anxiety treatment. It has drawbacks, such as having a very bitter taste, low water solubility, and undergoing extensive first pass metabolism, leading to poor oral bioavailability (<50%). This work aimed to develop and optimize palatable oral fast-dissolving films (OFDFs) loaded with a paroxetine nanosuspension. A PX nanosuspension was prepared to increase the PX solubility and permeability via the buccal mucosa. The OFDFs could increase PX bioavailability due to their rapid dissolution in saliva, without needing water, and the rapid absorption of the loaded drug through the buccal mucosa, thus decreasing the PX metabolism in the liver. OFDFs also offer better convenience to patients with mental illness, as well as pediatric, elderly, and developmentally disabled patients. The PX nanosuspension was characterized by particle size, poly dispersity index, and zeta potential. Twelve OFDFs were formulated using a solvent casting technique. A 22 × 31 full factorial design was applied to choose the optimized OFDF, utilizing Design-Expert® software (Stat-Ease Inc., Minneapolis, MN, USA). The optimized OFDF (F1) had a 3.89 ± 0.19 Mpa tensile strength, 53.08 ± 1.28% elongation%, 8.12 ± 0.13 MPa Young’s modulus, 17.09 ± 1.30 s disintegration time, and 96.02 ± 3.46% PX dissolved after 10 min. This optimized OFDF was subjected to in vitro dissolution, ex vivo permeation, stability, and palatability studies. The permeation study, using chicken buccal pouch, revealed increased drug permeation from the optimized OFDF; with a more than three-fold increase in permeation over the pure drug. The relative bioavailability of the optimized OFDF in comparison with the market tablet was estimated clinically in healthy human volunteers and was found to be 178.43%. These findings confirmed the success of the OFDFs loaded with PX nanosuspension for increasing PX bioavailability.

Recent Advances in the Synthesis of the Antidepressant Paroxetine.

Paroxetine is a potent inhibitor of serotonin reuptake and is widely prescribed for the treatment of depression and other neurological disorders. The synthesis of paroxetine and the possibility to prepare derivatives with a specific substitution pattern that may allow their use as biological probes is an attractive topic especially for medicinal chemists engaged in neurosciences research. Considering the extensive work that was developed in the last decade on the total synthesis of paroxetine, this review summarizes the most important contributions in this field, organized according to the reagent that was used as a starting material. Most of the methods allowed to prepare paroxetine in 4-9 steps with an overall yield of 9-66%. Despite the progress made in this area, there is still room for improvement, searching for new eco-friendly and sustainable synthetic alternatives.

Effectiveness of duloxetine for remnant pain relief in patients with rheumatoid arthritis despite remission

Rheumatoid arthritis (RA) is a chronic inflammatory disorder that causes swelling and pain in the joints. Pain management for RA becomes easier if patients are in clinical remission, although some may experience remnant pain despite adequate disease control. Duloxetine, a potent serotonin and norepinephrine reuptake inhibitor, has demonstrated pain relief effects in patients with osteoarthritis; however, the effectiveness of duloxetine for pain in patients with RA in clinical remission has not been investigated. The purpose of this study was to evaluate the efficacy of duloxetine for remnant pain in patients with RA in clinical remission This retrospective study included RA patients from a single institute in Japan from January 2011 to September 2019. Patients with RA who had a visual analog scale (PS-VAS) score > 30 mm and Clinical Disease Activity Index (CDAI) score ≤ 2.8 were selected and were grouped depending on whether duloxetine was administered (G-D) or not (G-C). Variables such as PS-VAS, patient’s global assessment (PGA), C-reactive protein (CRP), CDAI, Simplified Disease Activity Index (SDAI), modified Health Assessment Questionnaire (mHAQ), and quality of life (QOL) score were measured at the initiation of duloxetine and at the first CDAI remission in the G-D and G-C groups, respectively. Thereafter, the variables were measured at week 12. Changes in PS-VAS were compared as a primary outcome using the one-sample t test for each group. Differences between the two groups were evaluated using the Mann–Whitney U test. A total of 306 patients (G-C = 238; G-D = 68) were evaluated. PS-VAS, mHAQ, and QOL scores in both groups improved at week 12 from baseline, in which these scores in the G-D group demonstrated significantly higher improvements than those observed in the G-C group. At week 12, although CDAI scores significantly increased from baseline in both groups, patients were considered to have low disease activity. Duloxetine treatment in patients with RA in clinical remission appears to have comparable effectiveness on relieving remnant pain, improving activities of daily living and maintaining QOL. Duloxetine is not expected to have any effects on disease activity control.

The effect of duloxetine on penicillin-induced epileptiform activity in rats

ABSTRACTAim: Previous studies showed the existence of a relationship between epilepsy and depression. Duloxetine is a potent and selective inhibitor of serotonin and norepinephrine reuptake (SNRI) used in the treatment of the major depressive disorder. The aim of the present study was to investigate the effect of duloxetine on penicillin-induced epileptiform activity in an experimental rat model of acute partial epilepsy.Method: In this study, 35 male rats weighing 200–240 g were used. Under urethane anesthesia, tripolar electrodes were placed for electrocorticography (ECoG) recording. Duloxetine, at 1, 5, 10 or 30 mg/kg rates, was administered intraperitoneally 30 minutes after intracortical penicillin (500 IU) injection.Results: Duloxetine administrations of 1, 5, 10 and 30 mg/kg increased the mean frequency of epileptiform activity 10 minutes after Duloxetine injection compared to the control group (p < 0.05) without changing amplitude in all groups (p > 0.05).Conclusion: The results showed proconvulsant effect of duloxetine in penicillin-induced epileptiform activity and indicated that it could pose complications risk for people with partial epilepsy.

Enantioselective Disposition of Venlafaxine and its Metabolite O-Desmethylvenlafaxine in Rats

Aim: The study was conducted to understand enantioselective pharmacokinetic of venlafaxine (VEN) and o-desmethylvenlafaxine (ODV) using enantioselective HPLC method. The R-enantiomer of VEN is a potent inhibitor of both serotonin and noradrenaline reuptake, whereas the S-enantiomer is more selective in inhibiting serotonin reuptake. Enantiomers of ODV also inhibit noradrenaline and serotonin reuptake. Materials &amp; methods: Study was carried out in wistar rats after oral administration of 120 mg/kg dose of racemic VEN. Results: Plasma concentrations of S (+) VEN were found to be higher than those of R (-) VEN. Plasma concentrations of S (+) ODV were found to be higher than those of R (-) ODV. Conclusion: A significant difference in most of the pharmacokinetic parameters was observed between the enantiomers of VEN in rat plasma.

Evaluation of the analgesic effects of ammoxetine, a novel potent serotonin and norepinephrine reuptake inhibitor.

The selective serotonin (5-HT) and norepinephrine (NE) reuptake inhibitors (SNRIs) are commonly used for the treatment of neuropathic pain and fibromyalgia. Ammoxetine ((±)-3-(benzo[d] [1,3]dioxol-4-yloxy)-N-methyl-3-(thiophen-2-yl)propan-1-amine) has been identified as a novel potent SNRI. In this study, we evaluated the acute analgesic properties of ammoxetine in different animal models of pain, and examined the involvement of monoamines in its analgesic actions. The analgesic effects of ammoxetine were assayed using models of acetic acid- and formalin-induced pain in mice, neuropathic pain induced by sciatic nerve injury (SNI), chronic constriction injury (CCI) and reserpine-induced fibromyalgia pain in rats. The contents of 5-HT and NE in brain regions of fibromyalgia rats were measured using HPLC-ECD. In all the experiments, duloxetine was used as a positive control drug. Oral administration of ammoxetine (0.625-10 mg/kg) or duloxetine (2.5-40 mg/kg) dose-dependently decreased the number of acetic acid-induced writhing and formalin-induced first phase and second phase paw licking time in mice. Oral administration of ammoxetine (2.5-10 mg/kg) or duloxetine (10 mg/kg) alleviated mechanical allodynia in SNI and CCI rats and thermal hyperalgesia in CCI rats. The antiallodynic effect of ammoxetine in CCI rats was abolished by pretreatment with para-chlorophenylalanine methyl ester hydrochloride (PCPA, a 5-HT synthesis inhibitor) or α-methyl-para-tyrosine methylester (AMPT, a catecholamine synthesis inhibitor). Oral administration of ammoxetine (30 mg/kg) or duloxetine (50 mg/kg) significantly attenuated tactile allodynia in rats with reserpine-induced fibromyalgia. In the fibromyalgia rats, administration of ammoxetine (10, 30 mg/kg) or duloxetine (30, 50 mg/kg) dose-dependently increased the levels of 5-HT and NE, and decreased the metabolite ratio of 5-HT (5-HIAA/5-HT) in the spinal cord, hypothalamus, thalamus and prefrontal cortex. Ammoxetine effectively alleviates inflammatory, continuous, neuropathic and fibromyalgia-related pain in animal models, which can be attributed to enhanced neurotransmission of 5-HT and NE in the descending inhibitory systems.

Rapid-Onset Hyponatremia Induced by Duloxetine in an Elderly Patient

Duloxetine is a potent serotonin and noradrenaline re-uptake inhibitor that is used for the management of major depressive disorder and diabetic neuropathic pain. The common adverse effects are nausea, dry mouth, fatigue, dizziness, somnolence, anorexia, constipation, and hyperhidrosis. The cases of hyponatremia induced by duloxetine have rarely been reported. Here, we present the case of a 75-year-old male patient who developed rapid-onset and severe hyponatremia after low-dose duloxetine treatment. In the result of laboratory investigations syndrome of inappropriate antidiuretic hormone was diagnosed and then duloxetine treatment was discontinued. Serum sodium normalized within 5 days. We suggest that elderly patients treated with duloxetine should be closely monitored for hyponatremia during duloxetine treatment particularly in the first days of treatment.

Role of Serum Cholesterol Level in Pathogenesis of OCD

Etiology and pathophysiology of obsessive compulsive disorder remains inconclusive till today. Multiple converging lines of evidence suggest that neurobiology plays a significant role in the etiology of obsessive compulsive disorder (OCD). Certain brain areas frequently involved in symptomatology of OCD, analyzed by neuroimaging studies. The strongest pharmacologic evidence concerns the serotonergic system and the well-established efficacy of potent serotonin reuptake inhibitors in the treatment of OCD. Cholesterol forming the vital component of neurons regulates neurochemical activity. Reduced serum cholesterol level causes hyperactivity of serotonin reuptake receptor activity precipitating symptoms of OCD.

Efficacy and safety of vilazodone in major depressive disorder: a randomized, double-blind, placebo-controlled trial.

Vilazodone is a potent serotonin (5-HT) reuptake inhibitor and 5-HT₁A receptor partial agonist approved by the US Food and Drug Administration for the treatment of major depressive disorder (MDD) in adults. This study evaluated the efficacy and tolerability of vilazodone in the treatment of MDD. This 8-week, randomized (1:1), double-blind, placebo-controlled, parallel-group, fixed-dose study conducted from January 2012 to February 2013 compared vilazodone 40 mg/d with placebo in outpatients with DSM-IV-TR-diagnosed MDD. The primary efficacy measure was Montgomery-Asberg Depression Rating Scale (MADRS) total score change from baseline to week 8 analyzed by a mixed-effects model for repeated measures on the intent-to-treat population (placebo = 252, vilazodone = 253). Secondary efficacy outcomes were Clinical Global Impressions-Severity of Illness (CGI-S) Scale score change from baseline and MADRS sustained response rate (total score ≤ 12 for at least the last 2 consecutive double-blind visits). Approximately 83% of patients completed the study. Least squares mean differences (95% CI) were statistically significant for vilazodone versus placebo on MADRS (-5.117 [-6.886 to -3.347], P < .00001) and CGI-S (-0.622 [-0.845 to -0.399], P < .00001) change from baseline; statistically significant improvements versus placebo occurred at week 2 and persisted for the study duration. The MADRS sustained response rate was 17% for placebo and 27% for vilazodone (P < .01). Patients taking vilazodone versus placebo had higher rates of diarrhea and nausea; most incidences were mild in severity. Weight increase and sexual dysfunction adverse events were low in both groups. A large and significant treatment effect on the MADRS and statistically significant improvement on the CGI-S demonstrated meaningful depressive symptom improvements. Vilazodone was generally well tolerated. ClinicalTrials.gov identifier: NCT01473394.

Determination of duloxetine in human plasma with proven lack of influence of the major metabolite 4-hydroxyduloxetine

ObjectivesMinimizing the impact of major or unstable metabolites on the determination of a drug substance represents a leading task in the development and validation of bioanalytical methods. “Incurred samples reanalysis” provides relevant information too late; therefore, carefully selected tests on known metabolites should precede the pharmacokinetic studies. Design and methodsThis paper describes a simple and rapid HPLC-UV method for the determination of duloxetine, a potent serotonin and norepinephrine reuptake inhibitor, in the presence of its major metabolite, i.e. 4-hydroxyduloxetine glucuronide. Analyte and fluoxetine (internal standard) were extracted from human plasma by liquid–liquid extraction. ResultsNo influence of the major metabolite was observed on the reliability of the new method. There was also lack of evidence of the major metabolite back-conversion to the parent drug substance. The validation demonstrated high precision of the new method. All validation parameters met the acceptance criteria of bioanalytical regulations. ConclusionsThe new method enabled the reliable determination of duloxetine in the presence of its major metabolite in the human plasma. The method might be applied to pharmacokinetic studies in humans, including bioequivalence and therapeutic drug monitoring.

A randomized, double-blind, placebo-controlled study of flexible doses of levomilnacipran ER (40–120 mg/day) in patients with major depressive disorder

Objective:Levomilnacipran ER is a potent and selective serotonin and norepinephrine reuptake inhibitor (SNRI) approved for the treatment of major depressive disorder (MDD). Efficacy and safety have been evaluated in five Phase II/III studies, four of which met the pre-specified primary efficacy outcome. Results of the negative trial (ClinicalTrials.gov NCT00969150) are reported here.Methods:A Phase III randomized, double-blind, placebo-controlled trial comparing flexible-dose levomilnacipran ER 40–120 mg/day with placebo was conducted in outpatients with MDD. Patients met the DSM-IV-TR criteria for MDD, had a current episode of depression of at least 4 weeks’ duration, and a Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥30. The study comprised a 1-week, single-blind, placebo lead-in, 8-week double-blind treatment, and a 2-week down-taper. The primary and secondary efficacy measures were change from baseline to Week 8 in MADRS and Sheehan Disability Scale (SDS) total scores, respectively, analyzed using a mixed-effects model for repeated measures approach. Safety outcomes included adverse events (AEs), laboratory and vital sign measures, the Columbia-Suicide Severity Rating Scale, and the Arizona Sexual Experiences Scale (ASEX).Results:Three hundred and fifty-five patients received the study drug and had ≥1 post-baseline MADRS total score assessment (ITT Population); 81.9% of placebo and 77.1% of levomilnacipran ER patients completed the study. For levomilnacipran ER vs placebo, MADRS (−15.7 vs −14.2) and SDS (−8.8 vs −8.2) total score improvements, and rates of MADRS response (38.5% vs 34.8%) and remission (25.3% vs 23.8%) were numerically greater but differences were not statistically significant. Levomilnacipran ER was generally well tolerated. More levomilnacipran ER patients vs placebo reported AEs; the most common AEs for levomilnacipran ER were nausea (17%) and headache (16%). Mean changes in most safety measures were small and similar between groups. There were no meaningful differences in total ASEX scores between groups.Limitations:Short duration of treatment, inclusion and exclusion criteria, and lack of an active comparator.Conclusion:Numerical improvements for levomilnacipran ER vs placebo were detected in this study, but the differences were not statistically significant; levomilnacipran ER was generally well tolerated.

The evaluation of analgesic effects of milnacipran and sertraline in tail-flick test

Antidepressant drugs are used in the treatment of pain as an adjuvant or alone. It has been shown that antidepressant drugs have analgesic effects in various diseases (diabetic neuropathy, low back pain, cancer pain etc.) Sertraline is a potent serotonin re-uptake inhibitor. Some antidepressant drugs inhibited both of the reuptake of serotonin and of noradrenaline. These drugs are called serotonin-noradrenaline re-uptake inhibitors (SNRIs). Milnacipran is a serotonin-noradrenaline re-uptake inhibitor. We have studied the analgesic effects of sertraline and milnacipran after acute and chronic application in tail-flick test in mice. The analgesic effects of milnacipran (10, 30, 50 mg/kg) and sertraline (10, 20, 50 mg/kg) were measured after acute and chronic application in tail flick test. The analgesic effects of milnacipran (30 mg/kg) or sertraline (50 mg/kg) were evaluated after the application of L-NAME (10 mg/kg), naloxone (5 mg/kg), prazosin (1 mg/kg), ondansetron (0.1 mg/kg) in tail flick test. Milnacipran (30 mg/kg) and sertraline (50 mg/kg) produced statistically significant analgesic effect compared to their control values after acute and chronic application in tail-flick test. The analgesic effects of both milnacipran (30 mg/kg) and sertraline (50 mg/kg) in the presence of L-NAME (10 mg/kg), naloxone (5 mg/kg), ondansetron (0.1 mg/kg) and prazosin (1 mg/kg) were inhibited in tail-flick test. These results indicate that the analgesic effects of milnacipran and sertraline are related to nitrergic, opioidergic, serotonergic and adrenergic system (Fig. 8, Ref. 23).

Vilazodone lacks proarrhythmogenic potential in healthy participants: a thorough ECG study

Vilazodone is a potent serotonin reuptake inhibitor and 5-HT1A receptor partial agonist approved for the treatment of major depressive disorder (MDD) in adults. The effect of clinical and supratherapeutic doses of vilazodone on cardiac repolarization was determined in healthy volunteers. In this Phase 1, randomized, doubleblind, placebo- and active-controlled, 3-arm, parallel, single-center study, healthy subjects received placebo; moxifloxacin 400 mg; or vilazodone (sequentially escalated every 3 days) 10, 20, 40, 60, and 80 mg/day. The primary endpoint was the time-matched change from baseline in the QT interval corrected for heart rate (QTc) using an individual correction method (QTcI). Placebo-corrected time-matched analysis of the QTcI duration for the vilazodone treatment effect indicated that no vilazodone dose had an upper bound that approached or exceeded 10 ms, demonstrating no signal for a significant vilazodone effect on cardiac repolarization. Vilazodone had no significant effect on heart rate, PR, or QRS interval duration. The pharmacokinetic/pharmacodynamic model showed that the QTcI slope for vilazodone was not different from 0.0 and that the predicted increase from baseline in the QTc at Cmax for the highest therapeutic dose (156 ng/ml after 40 mg/day) was < 1 ms. The incidence of adverse events (AEs) was higher in the vilazodone group (57.6%) than in the moxifloxacin (37.0%) and placebo (35.6%) groups, though AEs were generally mild to moderate in severity and resulted in few discontinuations. Vilazodone had no significant effect on cardiac repolarization, heart rate, PR or QRS interval duration, or ECG morphology in healthy adult participants.

Stereoselective Synthesis and Dissolution Studies on Enteric Coated Pellets of (S)-Duloxetine Hydrochloride

The enantioselective hydrogenation of 2-bromo-1-(thiophen-2-yl)ethanone and further elaboration of thr cyclic carbamate derived from γ-aminoalcohol to provide a facile synthesis of (S)-duloxetine, a potent dual inhibitor of serotonin and norepinephrine reuptake, is described. Enteric coated pellets with polymer load 25% and 30% failed to provide required acid resistant to the pellets but very insignificant amount of drug was leached from the coated tablets in acid phase with polymer load 35% and 40% in the acidic phase whereas almost the whole amount of drug was released in the buffer phase. The results generated in this study showed that proper selection of polymeric materials based on their physicochemical properties as well as polymer load is important in designing delayed release pellets dosage form with acceptable dissolution profile. DOI: http://dx.doi.org/10.3126/jncs.v28i0.8110 Journal of Nepal Chemical Society Vol. 28, 2011 Page:74-79 Uploaded Date: May 24, 2013

Pharmacokinetic Analysis of Two Different Doses of Duloxetine Following Oral Administration in Dogs

Duloxetine is a potent and balanced dual inhibitor of serotonin and norepinephrine reuptake that is being investigated for the treatment of depression and urinary incontinence. The purpose of this study was to investigate the pharmacokinetic properties of duloxetine in 20 beagle dogs following a single oral administration of a 30- or 60-mg enteric-coated pellet in a capsule (Cymbalta). Following the administration of 30 or 60 mg of Cymbalta to 20 beagle dogs, the plasma concentration of duloxetine was measured using LC-MS/MS. Pharmacokinetic parameters were analyzed using both noncompartmental and compartmental approaches. The values of C max and AUC increased in proportion to the dose of duloxetine. The one compartment model with first-order absorption and a lag time was used successfully for pharmacokinetic analysis of duloxetine following a single oral administration of Cymbalta 30 mg or 60 mg. The studies described here are the first to report the pharmacokinetics of oral duloxetine in dogs, and these findings provide important information for pharmaceutical formulation research of duloxetine using dogs.

Lamotrigine Augmentation of Serotonin Reuptake Inhibitors in Severe and Long-Term Treatment-Resistant Obsessive-Compulsive Disorder

The treatment recommendations in obsessive-compulsive disorder (OCD) after lack of response to selective serotonin reuptake inhibitors (SSRIs) include augmentation with other drugs, particularly clomipramine, a more potent serotonin reuptake inhibitor (SRI), or antipsychotics. We present two cases of response to lamotrigine augmentation in treatment-refractory OCD; each received multiple SRI trials over a >10-year period. The first patient had eleven years of treatment with multiple combinations including clomipramine and SSRIs. She had a >50% decrease of Y-BOCS (from 29 to 14) by augmenting paroxetine (60 mg/day) with lamotrigine (100 mg/day). The second patient had 22 years of treatment with multiple combinations, including combinations of SSRIs with clomipramine and risperidone. She had an almost 50% decrease of Y-BOCS (from 30 to 16) and disappearance of tics by augmenting clomipramine (225 mg/d) with lamotrigine (200 mg/day). These two patients were characterized by lack of response to multiple treatments, making a placebo response to lamotrigine augmentation unlikely. Prospective randomized trials in treatment-resistant OCD patients who do not respond to combinations of SSRIs with clomipramine and/or antipsychotics are needed, including augmentation with lamotrigine. Until these trials are available, our cases suggest that clinicians may consider lamotrigine augmentation in such treatment-resistant OCD patients.

Acute Dystonia after Using Single Dose Duloxetine: Case Report

Duloxetine is a balanced and potent serotonin and noradrenaline reuptake inhibitor which is known to be effective in depression and anxiety disorders. The common adverse effects include dry mouth, nausea, insomnia, somnolence, dizziness and constipation. Reported adverse effects of the extra pyramidal symptoms (EPS) are rare. In this case, a patient who suffered from acute dystonia, after only one dose of 30 mg duloxetine is presented.

Evidence for the use of vilazodone in the treatment of major depressive disorder

Introduction:Major depressive disorder (MDD) is characterized by dysfunction in cognition, behavior, and physical functioning, and is associated with a chronic clinical course. There are barriers to successful treatment, which often result in early discontinuation and relapse. Adverse effects (AEs) remain the most commonly cited reason for discontinuation of treatment with conventional antidepressants, particularly early on in therapy. This often translates into relapse of symptoms or recurrence of the depressive episode. The delay to therapeutic response also has a meaningful implication for treatment adherence.Areas covered: This article focuses on the implications of a novel entity for the treatment of depression; the first new molecule developed for this indication in the last 10 years. Vilazodone is a novel dual-acting serotonergic antidepressant, which is a selective and potent inhibitor of serotonin reuptake, as well as a selective partial agonist of the 5-HT1A receptor.Expert opinion: The data available in the literature so far indicate clinical efficacy over placebo and a rather benign adverse event profile. Whether the early onset of clinical efficacy observed in one of the two pivotal studies represents a true or only a chance phenomenon, only future studies can tell. Adverse effects are mostly mild–moderate and most GI type AEs disappear in about one week, at a time when all patients are still on a clinically suboptimal daily dosage (10 mg/d during the first week). Sexual AEs did not differ from placebo. Vilazodone represents an interesting addition to the arsenal of available antidepressants.