Tricyclic Research Articles

Prescribing patterns in patients with obsessive-compulsive disorder: Retrospective, single-center study.

Obsessive-compulsive disorder (OCD) is marked by a high rate of treatment resistance. Patients are often left trialing medications within multiple drug classes with little response, causing heterogeneity to emerge in prescribing patterns. This analysis seeks to investigate the selection and dosing of the pharmacotherapy utilized, to portray an overview of prescribing trends in the United States. This retrospective, single center, review of electronic medical records investigated the pharmacotherapy utilization of patients with a primary diagnosis of OCD. Two hundred and ninety-five patients who received OCD treatment at an urban, academic medical center were included in the study. Patients were included in the review if they were at least eighteen years of age and were assigned a diagnosis of OCD according to DSM-5 criteria. Psychotropic pharmacotherapy was integrated into the care of 93% of patients. Selective serotonin reuptake inhibitors were the most utilized medication class at 85% followed by benzodiazepines (47%) and second-generation antipsychotics (37%). Tricyclic antidepressants and first-generation antipsychotics were the two medication classes utilized the least at 13% and 2% respectively. Additionally, mood stabilizers and serotonin-norepinephrine reuptake inhibitors were utilized at rates of 8% and 16%, respectively. Evidence-based treatment guidelines are being followed with varying augmentation strategies widely prevalent, thus displaying the heterogeneity in treating OCD. A high rate of benzodiazepine utilization highlights a practice trend with potential ties to clinical factors, such as the latency to treatment effect of other first-line pharmacotherapies. Future prospective studies are required to determine the cultural, pharmacoeconomic and pharmacogenomic factors that contribute to the variation in prescribing practices and whether these variations influence treatment outcomes.

Central Neuromodulators in Irritable Bowel Syndrome: Why, How, and When.

Irritable bowel syndrome (IBS) is responsive to treatments using central neuromodulators. Central neuromodulators work by enhancing the synaptic transmission of 5-hydroxytryptamine, noradrenalin, and dopamine, achieving a slower regulation or desensitization of their postsynaptic receptors. Central neuromodulators act on receptors along the brain-gut axis, so they are useful in treating psychiatric comorbidities, modifying gut motility, improving central downregulation of visceral signals, and enhancing neurogenesis in patients with IBS. Choosing a central neuromodulator for treating IBS should be according to the pharmacological properties and predominant symptoms. The first-line treatment for pain management in IBS is using tricyclic antidepressants. An alternative for pain management is the serotonin and noradrenaline reuptake inhibitors. Selective serotonin reuptake inhibitors are useful when symptoms of anxiety and hypervigilance are dominant but are not helpful for treating abdominal pain. The predominant bowel habit is helpful when choosing a neuromodulator to treat IBS; selective serotonin reuptake inhibitors help constipation, not pain, but may cause diarrhea; tricyclic antidepressants help diarrhea but may cause constipation. A clinical response may occur in 6-8 weeks, but long-term treatment (usually 6-12 months) is required after the initial response to prevent relapse. Augmentation therapy may be beneficial when the therapeutic effect of the first agent is incomplete or associated with side effects. It is recommended to reduce the dose of the first agent and add a second complementary treatment. This may include an atypical antipsychotic or brain-gut behavioral treatment. When tapering central neuromodulators, the dose should be reduced slowly over 4 weeks but may take longer when discontinuation effects occur.

Assessing the prevalence of Beers medication utilization in the Medicare Part D population in 2020.

Medication utilization has been increasing in the U.S. year-over-year for several decades. As older adults take more medications, there is a higher risk of them being exposed to drug-drug or drug-disease interactions. The American Geriatrics Society in 2019 updated their Beers Criteria for Potentially Inappropriate Medication (PIM) Use in Older Adults. The objective of this study was to assess the prevalence of utilization of medications included in the 2019 Beers Criteria. An analysis was conducted using the Medicare Part D Provider Utilization and Payment Data Public Use File for calendar-year 2020. Medications identified in the 2019 Beers Criteria were applied to the analysis. Two categories of medications were assessed: (1) "Avoid" and (2) "Use With Caution." In 2020, 56 million prescriptions were dispensed to Medicare patients 65 years and older that are recommended to be avoided without exception (4.7% of all prescriptions) totaling $957 million in medication costs. The most utilized medication classes in this category were benzodiazepines (25,949,994 prescriptions), "Z-drugs" (6,204,909 prescriptions), long-acting sulfonylureas (5,306,577 prescriptions), 1st-generation antihistamines (5,049,289 prescriptions), and tricyclic antidepressants (4,190,062 prescriptions). Additionally, 135 million prescriptions were dispensed to Medicare beneficiaries 65 years and older for medications which the Beers Criteria states to use caution (11.3% of all prescriptions) exceeding $2.85 billion in medication costs. The most utilized medications for this category were diuretics (74,599,126 prescriptions), selective serotonin reuptake inhibitors (30,033,121 prescriptions), serotonin and norepinephrine reuptake inhibitors (11,858,968 prescriptions), tramadol (11,450,878 prescriptions), and mirtazapine (5,737,304 prescriptions). Even with the existence of the AGS Beers Criteria for PIM Use in Older Adults and its continued updated versions, 16% of medications dispensed to Medicare Part D were potentially inappropriate. Future studies are needed to assess if this has led to worsened outcomes among older adults who utilized these PIM.

Acupuncture versus tricyclic antidepressants in the prophylactic treatment of tension-type headaches: an indirect treatment comparison meta-analysis

BackgroundAcupuncture showed better improvement than sham acupuncture in reducing attack frequency of tension-type headache (TTH), but its effectiveness relative to first-line drugs for TTH is unknown, which impedes the recommendation of acupuncture for patients who are intolerant to drugs for TTH. We aimed to estimate the relative effectiveness between acupuncture and tricyclic antidepressants (TCAs) through indirect treatment comparison (ITC) meta-analysis.MethodsWe searched Ovid Medline, Embase, and Cochrane Library from database inception until April 13, 2023. Randomized controlled trials of TCAs or acupuncture in the prevention of TTH in adults were included. The primary outcome was headache frequency. The secondary outcomes were headache intensity, responder rate, and adverse event rate. Bayesian random-effect models were used to perform ITC meta-analysis, and confidence of evidence was evaluated by using the GRADE approach.ResultsA total of 34 trials involving 4426 participants were included. Acupuncture had similar effect with TCAs in decreasing TTH frequency (amitriptyline: mean difference [MD] -1.29, 95% CI -5.28 to 3.02; amitriptylinoxide: MD -0.05, 95% CI -6.86 to 7.06) and reducing TTH intensity (amitriptyline: MD 2.35, 95% CI -1.20 to 5.78; clomipramine: MD 1.83, 95% CI -4.23 to 8.20). Amitriptyline had a higher rate of adverse events than acupuncture (OR 4.73, 95% CI 1.42 to 14.23).ConclusionAcupuncture had similar effect as TCAs in reducing headache frequency of TTH, and acupuncture had a lower adverse events rate than amitriptyline, as shown by very low certainty of evidence.

Effectiveness of Vortioxetine in Patients with Major Depressive Disorder Associated with Chronic Pain: An Observational Study in a Spanish Population.

Chronic pain (CP) and depression/anxiety often coexist, worsening each other's symptoms. Treating this comorbidity is challenging. Tricyclic antidepressants and serotonin noradrenaline reuptake inhibitors are the first-line treatment options for this comorbidity, although sometimes they are not effective and/or well tolerated by patients, and there is little clinical evidence that selective serotonin reuptake inhibitors are useful for controlling CP. The antidepressant vortioxetine, with a multimodal mechanism that may help reduce pain, has proven clinical efficacy in patients with major depressive disorder (MDD). This study investigated vortioxetine's effectiveness for MDD and CP in clinical practice. This was a 3-month, multicenter, prospective, open-label, non-interventional pharmacoepidemiologic study. Patients (n = 64) with MDD (9-item Patient Health Questionnaire [PHQ-9] score ≥ 15) and CP (visual analogue scale [VAS] score ≥ 4) were treated with vortioxetine for 3months (initiated with 10mg/day, with flexible dosing thereafter [5-20mg/day]). VAS, Clinical Global Impression (CGI), and Patient Global Impression (PGI) scales were used at baseline and at 1 and 3months. Brief Pain Inventory (BPI), PHQ-9 scale, and Satisfaction with Medicines Questionnaire (SATMED-Q) were used at baseline and at 3months. Adverse Events (AEs) were recorded. Descriptive statistics, chi-square tests, and Student's t-tests were used for paired data. MDD patients showed a statistically significant improvement in VAS from baseline (mean [standard deviation (SD)]: 7.42 [0.69]) to 1month (mean [SD]: 6.1 [0.81], P < 0.001) and 3months (mean [SD]: 5.09 [1.26], P < 0.0001). Similarly, BPI and PHQ-9 scores showed significant improvement from baseline (mean [SD]: 6.20 [0.80] and 16.63 [1.47], respectively) to 3months (mean [SD]: 4.73 [0.98] and 7.30 [2.60], P < 0.0001, respectively). Patients showed clinical improvement with CGI and PGI scales and reported being satisfied with the treatment in the SATMED-Q. A few mild EAs were registered. Vortioxetine can relieve depressive and pain symptoms, with a good safety profile, in patients with MDD and CP.

Risk factors for inadequate bowel preparation before colonoscopy: A meta-analysis.

This meta-analysis aimed to comprehensively explore the risk factors for inadequate bowel preparation (IBP). We searched the Embase, PubMed, Web of Science, and The Cochrane Library databases up to August 24, 2023, to identify observational studies and randomized controlled trials (RCTs) that examined risk factors for IBP. A random effects model was used to pool the adjusted odds ratios and 95% confidence intervals. A total of 125 studies (91 observational studies, 34 RCTs) were included. Meta-analyses of observational studies revealed that three preparation-related factors, namely, characteristics of last stool (solid or brown liquid), incomplete preparation intake, and incorrect diet restriction, were strong predictors of IBP. The other factors were moderately correlated with IBP incidence, including demographic variables (age, body mass index, male sex, Medicaid insurance, and current smoking), comorbidities (diabetes, liver cirrhosis, psychiatric disease, Parkinson's disease, previous IBP, poor mobility, inpatient, and Bristol stool form 1/2), medications (tricyclic antidepressants, opioids, antidepressants, narcotics, antipsychotics, and calcium channel blockers), and preparation-related factors (preparation-to-colonoscopy interval not within 3 to 5/6h, nonsplit preparation, and preparation instructions not followed). No colonoscopy indications were found to be related to IBP. Meta-analyses of RCTs showed that education, constipation, stroke/dementia, and discomfort during preparation were also moderately associated with IBP. Most of the other findings were consistent with the pooled results of observational studies. However, primarily due to imprecision and inconsistency, the certainty of evidence for most factors was very low to moderate. We summarized five categories of risk factors for IBP. Compared to demographic variables, comorbidities, medications, and colonoscopy indications, preparation-related elements were more strongly associated with IBP. These findings may help clinicians identify high-risk individuals and provide guidance for IBP prevention.

Neuropathic pain: Evidence based recommendations

Neuropathic pain continues to be a significant problem that lacks effective solutions for every single patient. In 2015, international guidelines (NeuPSIG) were published, while the French recommendations were updated in 2020. The purpose of this minireview is to provide an update on the process of developing evidence-based recommendations and explore potential changes to the current recommendations.Primary treatments for neuropathic pain include selective serotonin-norepinephrine reuptake inhibitors (SNRIs) such as duloxetine and venlafaxine, gabapentin, tricyclic antidepressants, as well as topical lidocaine and transcutaneous electrical nerve stimulation, which are specifically suggested for focal peripheral neuropathic pain. Pregabalin is a first line treatment according to international guidelines but second-line in the more recent French guidelines, due to lower efficacy seen in more recent studies and misuse risk. Additionally, tramadol, combination therapies, and psychotherapy as adjuncts are proposed second line; high-concentration capsaicin patches, and botulinum toxin A are proposed specifically for focal peripheral neuropathic pain.In cases where primary and secondary treatments prove insufficient, third-line options come into play. These include high-frequency repetitive transcranial magnetic stimulation (rTMS) targeting the motor cortex, spinal cord stimulation, and the use of strong opioids when no alternative is available.To ensure optimal management of neuropathic pain in real-life situations, it is imperative to disseminate these recommendations widely and secure the acceptance of practitioners. By doing so, we can bridge the gap between theory and practice, and enhance the overall care and treatment of individuals suffering from neuropathic pain.

Tricyclic antidepressants: An update

Tricyclic antidepressants (TCAs) are a class of psychotropic medications primarily used in the treatment of major depressive disorders, although their indications extend to a variety of psychiatric and neurological conditions. This class of medications was one of the first to be developed for the treatment of depression, marking a revolution in the management of this condition in the mid-20th century. The aim of this study is to present a narrative review in the form of an update on the pharmacokinetic properties, pharmacodynamics, indications, and side effects of tricyclic antidepressants. For this purpose, a narrative review in the format of an update was carried out, which analyzed 42 manuscripts. TCAs have various pharmacological and therapeutic properties, low cost, but their major limitation is their side effects. Since the clinical trials for this class were conducted well before the launch of new antidepressants, new research is needed to allow comparison of these groups within the same methodology and with more up-to-date statistics.

Optimizing clozapine-loaded nanostructured lipid carriers through central composite design for enhance bioavailability in antipsychotic therapy

Clozapine (CLZ), a tricyclic dibenzodiazepine antipsychotic drug employed for the treatment of Schizophrenia. However, CLZ's significant first-pass effect, poor water solubility, and low oral bioavailability (27%) limit its potential for therapeutic use. The present investigation aimed to prepare CLZ-loaded nanostructured lipid carriers (NLCs) to improve its solubility, bioavailability, and therapeutic efficacy. The NLCs were prepared using an ultrasonic probe sonication technique using selected solid lipids (Gelucire 44/14), liquid lipids (Labrafil M 1944), and surfactants (Monoemul 80). A central composite design approach was adopted to optimize the NLCs. The optimized CLZ-loaded NLCs were evaluated in terms of particle size, zeta potential, surface morphology, crystallinity, drug loading, and in-vitro CLZ release studies. The optimized CLZ-loaded NLCs showed a particle size, zeta potential, and entrapment efficiency of 115.1 ± 2.48 nm, −17 mV and 96.74 ±1.82%, respectively. The morphology revealed the coarsely spherical shape of NLCs. Fourier transform infrared spectroscopy indicated the physical interaction between the CLZ and lipids rather than chemical interaction. The results of powder X-ray diffraction and differential scanning calorimetry showed the conversion of crystalline to amorphous form of CLZ and distributed molecular level in lipid matrix. In the in-vitro release study, pure CLZ showed 14±1.86% release, whereas CLZ-loaded NLC showed initial burst release (20.0±0.56%) followed by sustained release (69.0±1.03%) up to 24 hours. Collectively, results revealed that the developed novel CLZ-loaded NLCs could be a potential formulation to improve efficacy by increasing solubility and prolonging CLZ release and bioavailability with enhanced patient compliance and reduced side effects.

Brachioradial Pruritus Caused by Cervical Disc Herniation Precipitated by Trauma Treated with Anterior Cervical Discectomy and Fusion: Report of Two Cases and Review of the Literature

AbstractBrachioradial pruritis (BRP) is a rare form of dermatomal pruritis that appears to be caused both by cervical radiculopathy and exposure to ultraviolet-light, although the exact pathophysiology for the manifestation of these symptoms remains to be determined. A diagnosis of BRP is typically confirmed with the “ice-pack” test and evidence of cervical spine pathology using magnetic resonance imaging. Treatment options consist of application of ice, reduction in sun exposure, and topical capsaicin, antiepileptics, or tricyclic antidepressants. Patients with refractory symptoms and cervical spine pathology may be candidates for surgical decompression, particularly at the C5 and C6 levels. However, there are currently no established guidelines to treat BRP, or surgical procedures that have shown to be superior. Here, we report two cases of cervical disc herniations after traumatic events that presented as BRP. Both cases were successfully treated with anterior cervical discectomy and fusion with complete resolution of symptoms.

Decrypting the multifaceted peripheral neuropathy based on molecular pathology and therapeutics: a comprehensive review.

Peripheral neuropathy (PN) is a multifaceted complication characterized by nerve damage due to oxidative stress, inflammatory mediators, and dysregulated metabolic processes. Early PN manifests as sensory changes that develop progressively in a "stocking and glove" pattern. A thorough review of literature has been done to find the molecular pathology, clinical trials that have been conducted to screen the effects of different drugs, current treatments and novel approaches used in PN therapy. Diabetic neuropathy occurs due to altered protein kinase C activity, elevated polyol pathway activity in neurons, and Schwann cells-induced hyperglycemia. Other causes involve chemotherapy exposure, autoimmune ailments, and chronic ethanol intake. Symptomatic treatments for neuropathic pain include use of tricyclic antidepressants, anticonvulsants, and acetyl-L-carnitine. Patients will have new hope if clinicians focus on novel therapies including gene therapy, neuromodulation techniques, and cannabidiol as an alternative to traditional medications, as management is still not ideal.

A systematic review and meta-analysis of randomized controlled head-to-head trials of recommended drugs for neuropathic pain

Abstract Neuropathic pain is a challenging chronic pain condition. Limited knowledge exists regarding the relative effectiveness of pharmacological treatments, and differences in trial design and impact of the placebo response preclude indirect comparisons of efficacy between drug classes. The purpose of this systematic review and meta-analysis of head-to-head trials was to compare the efficacy and tolerability of drugs recommended for neuropathic pain. We conducted a systematic review and meta-analysis of direct-comparison double-blind randomized trials. Primary outcomes were mean change in pain intensity and number of responders with a 50% reduction in pain intensity. Secondary outcomes encompassed quality of life, sleep, emotional functioning, and number of dropouts because of adverse events. We included 30 trials (4087 patients), comprising 16 crossover and 14 parallel-group design studies. All studies were conducted in adults, and the majority were investigator-initiated trials. We found moderate-quality evidence for equivalence (no clinically relevant difference) between tricyclic antidepressants (TCA) and gabapentin/pregabalin with a combined mean difference in pain score of 0.10 (95% CI −0.13 to 0.32). We could not document differences between TCA and serotonin–noradrenaline reuptake inhibitors (SNRI), between SNRI and gabapentin/pregabalin, or between opioids and TCA (low quality of evidence). We found more dropouts because of adverse events with SNRI and opioids compared with TCA (low quality of evidence). We did not identify any studies that included topical treatments. This systematic review of direct-comparison studies found evidence for equivalence between TCA and gabapentin/pregabalin and fewer dropouts with TCA than SNRI and opioids.

Antidepressant use in relation to dementia risk, cognitive decline, and brain atrophy.

We aimed to assess the effect of antidepressant use on dementia risk, cognitive decline, and brain atrophy. In this prospective cohort study, we included 5511 dementia-free participants (Mini-Mental State Examination [MMSE]>25) of the Rotterdam study (57.5% women, mean age 70.6 years). Antidepressant use was extracted from pharmacy records from 1991 until baseline (2002-2008). Incident dementia was monitored from baseline until 2018, with repeated cognitive assessment and magnetic resonance imaging (MRI) every 4 years. Compared to never use, any antidepressant use was not associated with dementia risk (hazard ratio [HR] 1.14, 95% confidence interval [CI] 0.92-1.41), or with accelerated cognitive decline or atrophy of white and gray matter. Compared to never use, dementia risk was somewhat higher with tricyclic antidepressants (HR 1.36, 95% CI 1.01-1.83) than with selective serotonin reuptake inhibitors (HR 1.12, 95% CI 0.81-1.54), but without dose-response relationships, accelerated cognitive decline, or atrophy in either group. Antidepressant medication in adults without indication of cognitive impairment was not consistently associated with long-term adverse cognitive effects. Antidepressant medications are frequently prescribed, especially among older adults. In this study, antidepressant use was not associated with long-term dementia risk. Antidepressant use was not associated with cognitive decline or brain atrophy. Our results support safe prescription in an older, cognitively healthy population.

Efficacy of patient education and duloxetine, alone and in combination, for patients with multisystem functional somatic disorder: Study protocol for the EDULOX trial

BackgroundMultisystem functional somatic disorder is characterized by specific patterns of persistent physical symptoms with a complex biopsychosocial etiology. The disorder can lead to disability and personal suffering. Current treatment options require specialized settings, therefore patients often wait a long time to receive specific treatment.Patient education is considered important in most treatment programs, but has only been investigated sparsely as a stand-alone treatment. Pharmacological treatment is limited to tricyclic antidepressants in low doses with no antidepressant properties. Duloxetine has been found effective in single organ functional disorders. As a treatment for multisystem functional somatic disorder, duloxetine could reduce symptoms and treat comorbid anxiety and depression. It may furthermore enhance the effect of patient education through a hypothesized effect on cognitive functioning. The purpose of the EDULOX trial is to study psycho-EDUcation and duLOXetine alone and in combination. MethodsThis is a nested study design. The parent trial “EDULOX1” (n = 424) will compare a patient education program with enhanced usual care in an open-labelled, randomized controlled trial. In addition to this, eligible participants will furthermore receive either duloxetine or active placebo in the nested, double-blinded, randomized controlled trial, “EDULOX2” (n = 212). Patient and clinician reported outcomes will be collected through questionnaires. ConclusionThe EDULOX trial may establish evidence for treatments applicable for the majority of patients with multisystem functional somatic disorder. If effective, duloxetine would be a more tolerable pharmacological treatment option that can target comorbid depression and anxiety, and potentially boost the effect of patient education.Trial registration numberThe study is registered at www.clinicaltrials.gov (NCT06232473) and the internal list of research projects at the Region of Central Denmark (Case number 1-16-02-305-23). Approval from the Danish Medical Research Ethics Committees (Case number: 2212291) and the Danish Medicines Agency was obtained under EudraCT Number: 2022-002780-30 and Sponsor's Protocol Code Number: 9515.

Intramolecular Hydrogen Bonds Assisted Construction of Planar Tricyclic Structures for Insensitive and Highly Thermostable Energetic Materials.

Safety is fundamental for the practical development and application of energetic materials. Three tricyclic energetic compounds, namely, 1,3-di(1H-tetrazol-5-yl)-1H-1,2,4-triazol-5-amine (ATDT), 5'-nitro-3-(1H-tetrazol-5-yl)-2'H-[1,3'-bi(1,2,4-triazol)]-5-amine (ATNT), and 1-(3,4-dinitro-1H-pyrazol-5-yl)-3-(1H-tetrazol-5-yl)-1H-1,2,4-triazol-5-amine (ATDNP), were effectively synthesized through a simple two-step synthetic route. The introduction of intramolecular hydrogen bonds resulted in excellent molecular planarity for the three new compounds. Additionally, they exhibit regular crystal packing, leading to numerous intermolecular hydrogen bonds and π-π interactions. Benefiting from planar tricyclic structural features, ATDT, ATNT, and ATDNP are insensitive (IS > 60 J, FS = 360 N) when exposed to external stimuli. Furthermore, ATNT (Td = 361.1 °C) and ATDNP (Td = 317.0 °C) exhibit high decomposition temperatures and satisfying detonation performance. The intermolecular hydrogen bonding that produced this planar tricyclic molecular structure serves as a model for the creation of innovative multiple heterocycle energetic materials with excellent stability.

An Overview of Degradation Strategies for Amitriptyline.

Antidepressant drugs play a crucial role in the treatment of mental health disorders, but their efficacy and safety can be compromised by drug degradation. Recent reports point to several drugs found in concentrations ranging from the limit of detection (LOD) to hundreds of ng/L in wastewater plants around the globe; hence, antidepressants can be considered emerging pollutants with potential consequences for human health and wellbeing. Understanding and implementing effective degradation strategies are essential not only to ensure the stability and potency of these medications but also for their safe disposal in line with current environment remediation goals. This review provides an overview of degradation pathways for amitriptyline, a typical tricyclic antidepressant drug, by exploring chemical routes such as oxidation, hydrolysis, and photodegradation. Connex issues such as stability-enhancing approaches through formulation and packaging considerations, regulatory guidelines, and quality control measures are also briefly noted. Specific case studies of amitriptyline degradation pathways forecast the future perspectives and challenges in this field, helping researchers and pharmaceutical manufacturers to provide guidelines for the most effective degradation pathways employed for minimal environmental impact.

Antineuropathic Pain Management After Orthopedic Surgery: A Systematic Review.

The opioid crisis has become a present concern in the medical field. In an effort to address these complications, antineuropathic pain medications have been considered as alternatives to prescribed opioids. This review focuses on the analgesic effects of neuromodulators, such as gabapentin, duloxetine, and pregabalin, that provide room for less dependence on narcotic analgesics following orthopedic surgery. During the database searches, 1,033 records were identified as a preliminary result. After duplicates were removed, an initial screen of each article was completed which identified records to be removed due to absence of a full-text article. Articles were excluded if they were not either prospective or retrospective, showcased an irrelevant medication (such as tricyclic antidepressants) which are not pertinent to this review, or deemed to be unrelated to the topic. Ultimately, 19 articles were selected. Three different drugs, gabapentin, pregabalin, and duloxetine, were analyzed to compile data on the effectiveness of preventing opioid overuse and addiction following hand surgery. This review identifies potential evidence that peri-operative gabapentin, pregabalin, and duloxetine administration decreases post-operative pain and lowers opioid dependency. Gabapentin, pregabalin, and duloxetine have potential to further decrease post-operative pain and lower opioid dependency. This review creates an opening for further research in hand surgery to assess an updated protocol for pain management to reduce opioid dependency.

Current Understanding of Compulsive Sexual Behavior Disorder and Co-occurring Conditions: What Clinicians Should Know about Pharmacological Options.

Compulsive sexual behavior disorder (CSBD) has recently been recognized as a psychiatric disorder. Pharmacological treatments for CSBD have received little study and thus have limited empirical support. The main objective of the present work is to review existing literature on the efficacy of different drugs on the symptomatology of CSBD, including the subtype of problematic pornography use (PPU). The main pharmacological approaches to treating CSBD have included opioid antagonists (naltrexone and nalmefene), selective serotonin reuptake inhibitors (paroxetine, citalopram, fluoxetine, and sertraline), mood stabilizers (topiramate), tricyclic antidepressants (clomipramine), serotonin antagonist and reuptake inhibitors (nefazodone), and N-acetylcysteine. Since people with CSBD may experience different co-occurring disorders, these should be considered when choosing the best pharmacological treatment. Pharmacological therapy for CSBD/PPU has been suggested as an adjunct to psychological therapies, which, for the moment, have the most empirical evidence. However, to evaluate the efficacy of most of the drugs presented in this narrative review, data to date have only been available from case studies. Thus, empirical support is scant and generalizability of results is limited, highlighting the need for more research in this area.

Precision dosing for patients on tricyclic antidepressants.

We aim to develop a personalized dosing tool for tricyclic antidepressants (TCAs) that integrates CYP2D6 and CYP2C19 gene variants and their effects while also considering the polypharmacy effect. The study first adopted a scoring system that assigns weights to each genetic variant. A formula was then developed to compute the effect of both genes' variants on drug dosing. The output of the formula was assessed by a comparison with the clinical pharmacogenetics implementation consortium recommendation. The study also accounts for the effect of the co-administration of inhibitors and inducers on drug metabolism. Accordingly, a user-friendly tool, Clinical Dosing Tool ver.2, was created to assist clinicians in dosing patients on TCAs. The study provides a comprehensive list of all alleles with corresponding activity values and phenotypes for both enzymes. The tool calculated an updated area under the curve ratio that utilizes the effects of both enzymes' variants for dose adjustment. The tool provided a more accurate individualized dosing that also integrates the polypharmacy effect. To the best of our knowledge, the literature misses such a tool that provides a numerical adjusted dose based on continuous numerical activity scores for the considered patients' alleles and phenoconversion.

(259) Comparison of Dapoxetine vs Paroxetine vs Clomipramine for Premature Ejaculation Patients

Abstract Introduction Premature ejaculation (PE) is a common male sexual dysfunction. The International Society for Sexual Medicine (ISSM) defines PE as the inability to delay ejaculation during all or nearly all vaginal penetrations with latency time before or within 1 minute of penetration for lifelong PE and within 3 minutes for acquired PE and negative personal consequences such as distress, bother, frustration. The introduction of Selective Serotonin reuptake inhibitors (SSRIs) and Tricyclic antidepressants (TCA) revolutionized the treatment of PE. However not many studies have compared the efficacy and safety of these drugs in a single study. Objective To compare the clinical efficacy and safety of Dapoxetine, Paroxetine, and Clomipramine for the oral pharmacotherapy of PE. Methods Men presenting with self-reported PE were evaluated with full medical/sexual history, comorbidities, focused physical examination, assessment for Erectile function, any investigations suggested by these findings. IELT was determined by stopwatch method for every intercourse attempt. IELT were recorded before and after using the above medications in each group. ISSM definition of PE formed basis of diagnosis. All patients were married potent men in a stable relationship for at least 6 months and possible sexual intercourse equal or greater than one per week. None of the patients had received other treatment for PE for at least 4 weeks before the start of the study. All subjects gave their written informed consent before entering the study. Standardized assessment measures such as validated questionnaires &amp; Patient Reported Outcomes (PRO) used as adjunct for assessment. Results 48 Patients with PE were recruited in this study. Patients were randomly assigned to receive 60 mg Dapoxetine ‘on-demand’(group 1, n = 24), or 20 mg Paroxetine daily (group 2, n = 12) or 50 mg Clomipramine (group 3, n = 12) orally daily during a 12-week period for each agent. After 12 weeks of treatment with Dapoxetine, Paroxetine and Clomipramine, the IELT was increased from the pretreatment mean of 35 seconds to 184 seconds, from 32 seconds to 178 seconds and from 34 seconds to 169 seconds, respectively (P = 0.01 in group 1 and 2,P = 0.02 in group 3). Baseline and 12-week mean intercourse satisfaction domain values of the IIEF were 10, 11, 10 and 14, 15, 13 in groups 1, 2, and 3 respectively. The mean number of coitus per week pretreatment and at 12-week treatment were 1.4, 1.3 and 1.3/week which rose to 2.4, 2.3 and 2.2 for Dapoxetine, Paroxetine and Clomipramine, respectively. The most common adverse effects of each drug were nausea, diarrhea, headache and perspiration. Conclusions Oral SSRIs &amp; TCA are safe and effective treatments for PE. Dapoxetine, although approved, does Not appear to be widely used; cost could be an issue. Its use can result in better QoL for the patient and their sexual partner. Paroxetine has the advantage of improving IELT with well-tolerated side effects. It has good efficacy in the treatment of PE. Higher dose of Clomipramine results in a longer IELT without higher risk of adverse events. Larger studies with different dosages and treatment regimens are required to yield more credible outcomes. Disclosure No.