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Background Some data suggests that citalopram has more risk of corrected QT interval (QTc) prolongation than other selective serotonin reuptake inhibitors. Consequently the U.S. Food and Drug Administration distributed a safety warning limiting the maximum dose for citalopram. There is also a suggestion that bupropion may decrease QTc in patients on drugs that increase QTc. The goals of this cross-sectional study were to examine (1) effects on QTc of citalopram compared to sertraline, bupropion, and tricyclic antidepressants; (2) dose dependent effects of citalopram; and (3) effects of bupropion on citalopram-mediated changes in QTc. Methods Records of subjects who received an EKG while taking one of the specified antidepressants were reviewed to collect demographic information, antidepressant history, and information about other confounders. Linear regression was used to examine the relationship between QTc and antidepressants. Results 487 subjects provided 798 EKG records. The sample was 95% male with an average age of 61 years. No differences were found in QTc between citalopram and other antidepressants. No dose relationship was detected between citalopram and QTc. Bupropion did not affect the relationship between citalopram and QTc (coefficient = -3.4; 95%CI = -14.2, 7.5; p = 0.54). Limitations Observational study designs are prone to biases from retrospective data collection. Some data subsets had small numbers of subjects. Conclusions No effect of citalopram on QTc was found at therapeutic doses. Neither was there evidence of a “QTc-sparing” effect of bupropion. The risk of adverse cardiovascular effects from citalopram at doses of 60 mg per day or less appears minimal.

Fibromyalgia is a debilitating condition that is frequently misdiagnosed. It affects 2% of the population, with middle-aged women having the highest frequency. Fibromyalgia affects more women than men, and It becomes worse as you get older. Because medical treatment for fibromyalgia is typically only partial, health professionals must provide patients with ongoing assistance in order for them to become effective, active self-managers. There is no one-size-fits-all drug for fibromyalgia, but you do have a lot of options for treating your symptoms. However, Antidepressants in general such as “duloxetine” and Gabapentinoids drugs such as “pregabline” are the most used drugs. There is some evidence that NSAIDs may have a synergistic effect when combined with centrally active agents such as tricyclic antidepressants and anticonvulsants. Among non-pharmacological therapy, exercise and psychoeducational techniques have the most evidence of efficacy, but they must be personalized to the individual. In this review we will be looking at diagnosis and treatment of fibromyalgia.

Background The present study aimed to compare and evaluate the efficacy of antidepressants in remission of esophageal reflux symptoms. Methods A comprehensive literature review was performed including sources published on MEDLINE, EMBASE, the Cochrane Central Registry of Controlled Trials (Cochrane), Web of Science, China National Knowledge Infrastructure Database (CNKI), Chinese VIP Information Databases (VIP), Chinese Biology Medicine disc (CBM), and Wan-Fang databases for randomized controlled trials, published up to and including March 31, 2020. We analyzed relevant randomized, placebo-controlled trials reporting the effect of antidepressant therapy in relieving esophageal reflux symptoms ADDIS 1.16.8 was used to perform the network meta-analysis. Furthermore, we performed a split analysis to test inconsistency, and rank probability was complemented for comparison among antidepressants. Results A total of 10 randomized controlled trials (RCTs) examining the effects of antidepressants, selective 5-HT reabsorption inhibitor (SSRI), 5-HT 1A receptor agonist (5-HT1AA), tricyclic antidepressants (TCAs), and the complex of flupentixol-melitracen (FM) were included. Flupentixol-melitracen and SSRIs exhibited a significantly higher rate of remission than placebo. However, there was no statistically significant difference among different antidepressants compared. Rank probability showed that FM exhibited the highest probability of rank 1 compared with other antidepressants and placebo. Conclusion This network meta-analysis of RCTs supported the use of FM and SSRIs as a potentially effective regimen for symptom remission of gastroesophageal reflux. Furthermore, according to our analysis, FM represents the most efficient antidepressant with highest probability of symptom remission.

Our study aimed to determine the relationship of antidepressant medicine use with periodontal diseases, exploring the association of different pharmacological classes of antidepressant with observations of clinical attachment loss (CAL) and alveolar bone level (BL) in patients with periodontitis.Existing evidence on the impact of antidepressant medication on periodontal tissues has focused on some classes only and is still unclear. Therefore, this retrospective study evaluated the association of different antidepressant classes with clinical attachment loss (CAL) and alveolar bone level (BL).This study was carried out in a population of patients aged ≥ 30 years old with periodontitis who sought treatment at the University of Florida from 2014 to 2018. The following variables were obtained from patients' records; usage of antidepressant medications and their pharmacological classes (selective serotonin reuptake inhibitors [SSRI], serotonin-norepinephrine reuptake inhibitors [SNRI], tricyclic, atypical, and monoamine oxidase inhibitors [MAO]), age, gender, smoking habit, mild systemic diseases, CAL, and cement-enamel junction (CEJ) and alveolar bone crest (BC) distance, defined as BL, in the Ramfjord index teeth.Five hundred and eighty-two periodontitis patients were evaluated, of which 113 (19.4%) were antidepressant users. Antidepressant users exhibited significantly lower BL and fewer sites with severe CAL (≥5 mm), than non-users (p .05). Among all single-class antidepressant users, the SSRI users showed significantly less CAL and lower BL than non-users (p .05). Patients taking combinations of the different classes of antidepressants also showed better CAL and BL than non-users. Generalized linear models, including variables such as gender, age, systemic diseases, and smoking, demonstrated that antidepressant users were more likely to have lower mean BL and fewer sites with severe bone loss (i.e. BL 3 and5 mm) than non-users (p .05).Antidepressant medications were associated with higher alveolar bone level and less clinical attachment loss in patients with periodontitis. When the different classes of antidepressants were analyzed individually, only the SSRI class users and the multiple-class users showed significantly less periodontal breakdown than non-users.

Medical therapies for dizziness are aimed at vertigo reduction, secondary symptom management, or the root cause of the pathologic process. Acute peripheral vertigo pharmacotherapies include antihistamines, calcium channel blockers, and benzodiazepines. Prophylactic pharmacotherapies vary between causes. For Meniere disease, betahistine and diuretics remain initial first-line oral options, whereas intratympanic steroids and intratympanic gentamicin are reserved for uncontrolled symptoms. For cerebellar dizziness and oculomotor disorders, 4-aminopyridine may provide benefit. For vestibular migraine, persistent postural perceptual dizziness and mal de débarquement, treatment options overlap and include selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants and calcium channel blockers.

Smoking is highly prevalent in the psychiatric population, and hospital admittance usually results in partial or complete smoking cessation. Tobacco use is known to affect the metabolism of certain psychoactive drugs, but whether smoking influences the plasma concentration of tricyclic antidepressants (TCAs) remains unclear. This article investigates the possible effect of smoking on the plasma concentration of TCAs. A systematic review of the literature available on PubMed and EMBASE as of October 2020 was carried out using PRISMA guidelines. Studies reporting plasma concentrations of any TCA in both a smoking and a non-smoking group were included and compared. Ten eligible studies were identified and included. In the eight studies investigating the effect of smoking on amitriptyline and/or nortriptyline, five studies found no significant effect. Two studies investigating the effect of smoking on imipramine found a significant effect, and one study investigating the effect of smoking on doxepin found no significant effect. The majority of studies included in this review were influenced by small study populations and other methodical issues. The effect of smoking on the plasma concentration of TCAs is still not entirely clear. There is a possibility that smoking affects the distribution of TCA metabolites, but this is probably not of clinical importance.

Background/purpose Tricyclic antidepressants (TCAs) are still widely used and are available to purchase without prescription in some countries. Awareness of adverse cutaneous drug reactions is essential. Method We reported a case of photo-distributed hyperpigmentation due to imipramine and carried out a systematic search of the related articles using the search terms "tricyclic antidepressants" or "tricyclic antidepressive agents", and "hyperpigmentation" or "photosensitivity disorder". Fifty non-duplicate citations were identified of which 28 articles which were independently assessed in full. The review was registered in PROSPERO, CRD42018107338. Results The remaining 25 articles met our inclusion criteria. Photo-distributed hyperpigmentation tricyclic antidepressant-induced photosensitivity reactions (TIPs) was the most common presentation. In 21 cases, this presented as an asymptomatic discolouration of exposed sites. Imipramine (81%), amitriptyline (9.5%), desipramine hydrochloride (4.8%) and mirtazapine (4.8%) were reported to be the culprit drugs. Nineteen were female with a mean age at presentation of 55 years. Mean duration from commencing the culprit drug until the development of discolouration was 10.4 years. Mean daily dose was 222.7 mg for imipramine. Histology was characteristic with golden-brown or brownish granules deposited in dermis. Staining for Masson-Fontana and MEL-5 was positive in all cases. Phototesting had not been done in cases prior to ours (negative 3 months after discontinuation of imipramine). Three further reports of suspected TIP presented with non-specific and eczematous eruption. The two presentations were reported along with systemic problems (thrombocytopenia and hepatic injury). Conclusions This systematic review highlights the characteristic features of exposed site hyperpigmentation of TCA-induced photosensitivity occurring after prolonged drug exposure in many cases.

Administration of a rational and safe drug therapy is one of the most challenging issues for healthcare professionals. The frequency of hospitalizations due to the adverse drug reactions in the years 2000 — 2015 was estimated at 6.3 (3.3—11.0 %) for developed countries and 5.5 % (1.1—16.9 %) for developing countries. It is known that alcohol intake is a risk factor for many socially significant diseases, including arterial hypertension, coronary heart disease, chronic heart failure, etc., however, many doctors pay insufficient attention to the fact that many drugs, for example, beta-blockers, antidepressants, bezodisepines, calcium antagonists, can interact with alcohol when consumed simultaneously and, thus, increase the risks of adverse drug reactions. There are 2 main types of interactions between alcohol and drugs: pharmacokinetic (at the stage of absorption, distribution, metabolism and elimination) and pharmacodynamic (at the stage of effects and receptors). For example: the simultaneous intake of alcohol and paracetamol leads to the formation of toxic metabolites due to the induction of cytochrome P450 isoenzymes by alcohol. Another example is decrease in presystemic elimination and stimulation of the metabolism of tricyclic antidepressants; an increase in the elimination of imipramine and desipramine in patients with chronic alcoholism after detoxification therapy, and so on. In this article, the authors analyzed and systematized data from open literature sources in order to inform health care professionals about the possible risks associated with the interaction of alcohol and drugs and various pharmacological groups.

Glioblastoma multiforme (GBM) is known as the deadliest form of brain tumor. In addition, its high treatment resistance, heterogeneity, and invasiveness make it one of the most challenging tumors. Depression is a common psychological disorder among patients with cancer, especially GBM. Due to the high occurrence rates of depression in GBM patients and the overlap of molecular and cellular mechanisms involved in the pathogenesis of these diseases, finding antidepressants with antitumor effects could be considered as an affordable strategy for the treatment of GBM. Antidepressants exert their antitumor properties through different mechanisms. According to available evidence in this regard, some of them can eliminate the adverse effects resulting from chemo-radiotherapy in several cancers along with their synergistic effects caused by chemotherapy. Therefore, providing comprehensive insight into this issue would guide scientists and physicians in developing further preclinical studies and clinical trials, in order to evaluate antidepressants' antitumor potential. Considering that no narrative review has been recently published on this issue, specifically on these classes of drugs, we present this article with the purpose of describing the antitumor cellular mechanisms of three classes of antidepressants as follows: tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and monoamine oxidase inhibitors (MAOIs) in GBM.

Background: Tricyclic antidepressants (TCAs) toxicity continues to be a major problem and an important cause of morbidity and mortality from poisoning all over the world. Aim of the study: to compare the effectiveness of poison severity score (PSS), acute physiology and chronic health evaluation (APACHE II) score and rapid emergency medicine score (REMS) for prediction of the need for intensive care unit (ICU) admission and mechanical ventilation (MV) in cases with acute TCAs toxicity. Methods: This retrospective observational study was conducted on 109 TCAs poisoned cases who were admitted to Tanta University Poison Control Center during the period from the first of January 2017 to the end of December 2020. Three scoring systems (PSS, APACHE II and REMS) were calculated for all cases at admission. Discrimination was evaluated using receiver operating characteristics curve and calculating the area under the curve (AUC). Results: The results of this study revealed that twenty-five cases needed to be admitted to ICU and 8 cases needed MV. The median of the three scores was significantly higher in cases that needed both ICU admission and MV. Although the APACHE II score has the best AUC value for prediction of ICU admission and MV (0.956 and 0.943 respectively), there was no statistically significant difference between the three scores. The AUC value of REMS comes next (0.931 and 0.925 respectively). Conclusion: REMS is rapid and simple score that can be easily assessed in emergency situations, it is recommended to be used for outcome prediction in TCAs poisoning.

OBJECTIVES Tricyclic antidepressants (TCAs) are commonly used to treat disorders of gut-brain interaction (DGBI). However, these medications are often associated with side effects that lead to early treatment discontinuation. Research in other chronic medical conditions suggests that many TCA side effects may be caused by nocebo (negative placebo) effects. The current study tests a brief, verbal intervention aimed at improving tolerance of TCAs in DGBI by providing education about nocebo effects. MATERIALS AND METHODS This pilot randomized controlled trial was performed in a tertiary care gastroenterology clinic. Participants with DGBI were randomized "standard information," describing the benefits and risks of TCAs, or "augmented information," which included an additional

Objective: to compare depression treatment efficacy with and without antidepressants (ADs) in men and women with bipolar affective disorder (BAD).Patients and methods. We enrolled 100 patients with BAD (F31.3–F31.5 according to ICD-10), including 50 women aged 33.0 [23.0; 50.2] years and 50 men aged 37.5 [29.5; 47.2] years using prospective and retrospective methods. Various antidepressants, normothymics, antipsychotics combinations were used to treat depression. We performed a comparative analysis of treatment efficacy with and without antidepressants in men and women subgroups. Clinical assessment at the baseline and the end of 1, 2, 4, 6-th week of therapy (or at discharge) included a specially developed clinical examination chart and the following psychometric scales: Montgomery-Asberg Depression Rating Scale (MADRS), Clinical Global Impression – Severity of illness (CGI-S), Clinical Global Impression – Improvement (CGI-I).Results and discussion. Women tended to have a slower improvement in the condition compared to men. Maximum reduction in MADRS score and a CGI-I, CGI-S higher frequency of clinical improvement and remission was observed in men and women who did not receive antidepressants than patients who did not receive antidepressants. When BAD type was included in the analysis, in patients treated with antidepressants, transient symptoms of the opposite pole occurred in 24.7% of patients of both sexes with bipolar affective I disorder (BAD I) and in 16.8% with bipolar affective II disorder (BAD II). There were no significant gender differences in patients with BAD I, while women predominated in BAD II group (22.5% compared to 7.8% men). No significant treatment-emergent affective switch was observed with tricyclic antidepressants and selective serotonin and norepinephrine reuptake inhibitors in both groups (21; 16.7; 16.7% in men and 28; 21.8; 12.5% in women, respectively). The assessment of intermission revealed that women were significantly more likely to have shorter periods between phases (42% compared to 22% in men). In addition, women were significantly more likely to have shorter periods between phases (42% compared to 22% in men) when the intermission duration was included in the analysis. In some patients with severe depression and infective first-line therapy (anticonvulsants and atypical antipsychotics), antidepressants prescription can increase treatment effectiveness. However, several factors should be considered, such as BAD type and variant, depression severity, treatment-emergent affective switch in history, and gender.Conclusion. A decision about antidepressants' dosage and treatment duration requires a dynamic follow-up of the patient in order to discontinue the antidepressants as fast as possible and decrease the risk of treatment-emergent affective switch and shortening of remission period.

Premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) are characterized by somatic and psychologic symptoms that arise at the luteal phase of the menstrual cycle and subside with menstruation. For definitive diagnosis prospectively self-reported symptoms should demonstrate a cyclic pattern and other psychological pathologies and thyroid dysfunction, that may present with similar symptoms, should be excluded. Both entities affect millions of women at reproductive age as the prevalence of PMS is given as 10-98% while PMDD affects 2-8%. Sex steroids and neurotransmitters have a central role in the etiology. The role of vitamins and minerals in the etiology and treatment of PMS and PMDD is open to discussion. Drugs that suppress ovarian sex steroid production, such as combined oral contraceptives or selective serotonin re-uptake inhibitors enhancing central serotonin delivery are used for treatment. Life-style changes and regular exercise also have a positive effect in milder cases. Tricyclic antidepressants and gonadotropin-releasing hormone analogues can be used in selected cases.

Background Mobility is important for daily life functioning, with particular challenges regarding road safety under pharmacological treatment in patients with a psychiatric disease. Methods According to PRISMA guidelines, a systematic literature search on PubMed database (January 1970 to December 2020) was performed. Primary endpoints were driving performance in on-road tests, driving simulator performance, or psychomotor and visual perception functions assessed to estimate fitness to drive according to legal regulations in patient studies. Results Forty studies were identified (1533 patients, 38% female, median age 45 years), of which more than 60% were cross-sectional and open-label trials. Under steady-state medication, 31% (range 27%–42.5%) of schizophrenic or schizoaffective patients under antipsychotics and 18% (range 16%–20%) of unipolar and bipolar patients under antidepressants showed severe impairment in skills relevant for driving. Data point to an advantage of second-generation antipsychotics compared with first-generation antipsychotics as well as modern antidepressants over tricyclic antidepressants with respect to driving. Most patients significantly improved or stabilized in driving skills within 2–4 weeks of treatment with non-sedative or sedative antidepressants. Diazepam significantly worsened driving the first 3 weeks after treatment initiation, whereas medazepam (low dose), temazepam, and zolpidem did not impair driving. In long-term users of sedating antidepressants or benzodiazepines, impairments in on-road tests were not evident. Conclusion The available evidence suggests that psychopharmacologic medicines improve or at least stabilize driving performance of patients under long-term treatment when given on clinical considerations. To enhance treatment compliance, existing classification systems of medicinal drugs concerning impact on driving performance should also incorporate information about effects of long-term-treatment.

Background Inconsistent evidence suggests that use of certain antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), in patients using oral anticoagulants (OACs) might be associated with an elevated risk of bleeding. Objective This study aims to investigate the risk of bleeding associated with initiation of different types of antidepressants among atrial fibrillation (AF) patients on OAC therapy. Patients and methods A total of 30,336 AF patients (mean age 72.2 years; 54% female) on OAC therapy that started antidepressant treatment were identified from the Truven Health Analytics MarketScan Commercial and Medicare Databases for the period 2007–2015. Exposure was defined as filling a prescription for antidepressant, and categorized as SSRI, serotonin/norepinephrine reuptake inhibitors (SNRIs), serotonin reuptake inhibitors (SRIs), tricyclic antidepressants (TCAs), or other antidepressants. The primary outcome was incident hospitalized bleeding. Associations of antidepressant type with bleeding were assessed calculating hazard ratios (HRs) and 95% confidence intervals (CIs) with adjusted Cox models in pairwise propensity score-matched cohorts. Results During a mean follow-up of 21 months, we identified 1612 bleeding episodes. In pairwise comparisons, SSRI use was associated with an increased risk of bleeding when compared to most other antidepressants (HR 1.22, 95% CI 0.96–1.54 vs SNRI; HR 1.10, 95% CI 0.90–1.35 vs SRI; HR 1.03, 95% CI 0.82–1.30 vs TCA). SNRI use was associated with the lowest bleeding risk. Results did not differ by OAC type, age, and sex. Conclusions Among AF patients on OAC initiating antidepressants, risk of bleeding varied across antidepressant type. This information can inform treatment choices among patients receiving OAC. Supplementary Information The online version contains supplementary material available at 10.1007/s40801-021-00258-3.

Viloxazine has a long history of clinical use in Europe as an antidepressant, and has recently been repurposed into an extended-release form for the treatment of attention-deficit/hyperactivity disorder in the USA. An immediate-release formulation was approved for the treatment of depression in the UK in 1974, and was subsequently marketed there and in several European countries for 30 years with no major safety concerns. In contrast to first-generation antidepressants (e.g., tricyclic antidepressants, monoamine oxidase inhibitors), viloxazine was associated with a relatively low risk for cardiotoxicity. Gastrointestinal symptoms were the most commonly reported side effects. The therapeutic effects of viloxazine are thought to be primarily the result of its action as a norepinephrine reuptake inhibitor, although in vitro and preclinical in vivo animal data suggest that viloxazine may also impact the serotoninergic system. This review summarizes the evolving knowledge of viloxazine based on information from previously published preclinical and clinical investigations, and acquired unpublished historical study reports from both open-label and blinded controlled clinical trials. We review the chemical properties, mechanism of action, safety, and tolerability across these studies, and discuss the contemporary rationale for the development of this agent as an extended-release oral formulation for the treatment of attention-deficit/hyperactivity disorder.

This article provides a practical review of the diagnosis and management of angle closure induced by psychotropic agents, including tricyclic antidepressants, antipsychotics and anticonvulsants. Selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, monoamine oxidase inhibitors and antipsychotics may trigger angle closure by influencing pupil configuration through adrenergic, anticholinergic, serotonergic or dopaminergic mechanisms. Patients with narrow iridocorneal angles are at risk, and these are more common in people with hypermetropia (near-sightedness), older people and individuals with an Asian background. These patients may benefit from a laser peripheral iridotomy, either prophylactically or to relieve an acute angle-closure episode. An idiosyncratic reaction to medications such as topiramate may lead to angle closure through an alternate mechanism, leading to a uveal effusion. Ophthalmological review may be considered prior to commencing medications in high-risk patients.

In recent years, some progress has been achieved in elaborating the algorithms and standards for the treatment of many conditions accompanied by vertigo. The current possibilities of treating vestibular vertigo consist of a gradually expanding arsenal of symptomatic and pathogenetic drugs. Among the drugs used for the symptomatic treatment of vestibular vertigo, there are vestibular suppressants (antihistamines, benzodiazepines, and calcium antagonists) and antiemetics (dopamine antagonists and serotonin 5-HT3 receptor antagonists). The paper discusses the possibilities of using betahistine and vitamin D as pathogenetic agents for recurrent benign paroxysmal positional vertigo; diuretics, betahistine (including the new prolonged release formulation Betaserc® Long), glucocorticoids, and gentamicin for Meniere's disease; triptans, beta-blockers, tricyclic antidepressants, and anticonvulsants for vestibular migraine; glucocorticoids, antiviral agents, and drugs that accelerate vestibular compensation for acute unilateral peripheral vestibulopathy (vestibular neuritis and Ramsey Hunt syndrome).The emergence of new drugs, as well as the design of new dosage forms that enhance patient adherence to the prescribed treatment, can improve quality of life in patients suffering from diseases that have recently led to long-term disability or even incapacitation.

A 32-year-old woman with anorexia nervosa experienced ventricular tachycardia while on therapeutic-dose amitriptyline despite normal blood tests, imaging, and intracardiac recordings. Electrocardiograms over several years featured the Type 1 Brugada pattern. Careful electrocardiogram monitoring should be made if using high doses of amitriptyline, especially in those with low body weight. (Level of Difficulty: Intermediate.), Graphical abstract

Stroke is the leading cause of disability in adults. Depression after a stroke is detected in one third of patients, complicating physical rehabilitation, worsening functional outcome, increasing mortality rates. The question of the use of antidepressants in the treatment of post-stroke depression is currently not completely resolved, there is no consensus on the most optimal drug. The drugs of choice are selective serotonin reuptake inhibitors, the use of tricyclic antidepressants is possible. A number of clinical studies indicate the effectiveness of selective serotonin reuptake inhibitors in the treatment of post-stroke depression, including through mechanisms including increased neuroplasticity and stimulation of neurogenesis, while others disprove their effectiveness. The article presents a clinical case of the use of vortiroxetin in the patient’s neurorehabilitation in the early recovery period of a stroke, its safety and positive effect are shown.

Since the 1950s, the therapeutic arsenal against depression has grown considerably. From the discovery of mono-amine oxidase inhibitors (MAOIs) to the antidepressant effect of ketamine, several pharmacological breakthroughs made the history of psychiatry. These discoveries oriented the research about the pathophysiology of depression, which is one of the most disabling diseases worldwide affecting 10 to 20% of general population. In this article, we offer a short historical review of the various therapeutic options developed over the past century and the consequences of these innovations. We then review the discovery of the antidepressant effects of ketamine (and its S-enantiomer, esketamine), the lastest development in depression treatment. Ketamine's effects are spectacular both in terms of their very short onset time, and because they are observed even in treatment-resistant depression. Just as MAOIs and tricyclic antidepressants allowed the “monoaminergic hypothesis of depression” to emerge, unravelling the mechanisms of ketamine's antidepressant effects should highlight the role of glutamatergic system and neuro-inflammation in the neurobiology of depression. Ketamine might also help to refine our understanding of the cognitive pathophysiology of depression and to deeply transform the clinical representations of depressive disorder.

Objective: The primary indication for electroconvulsive therapy is medication-resistant major depression. There is some evidence that combining electroconvulsive therapy with an antidepressant, instead of electroconvulsive therapy monotherapy, might improve remission rates. However, data on this topic have not been systematically studied. We undertook a systematic review and meta-analysis to determine the effectiveness of an adjuvant antidepressant during electroconvulsive therapy for major depression. Methods: Embase, Medline Ovid, Web of Science, Cochrane Central, PsychINFO Ovid and Google Scholar were searched up to January 2019. Randomized controlled trials and cohort studies reporting on the influence of an adjuvant antidepressant on the efficacy of electroconvulsive therapy for major depression were included. Authors independently screened records, extracted data and assessed study quality. We reported this systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: Nine studies were included in the meta-analysis. The meta-analysis revealed a significant advantage of adjuvant antidepressants versus placebo. The overall effect size per category of antidepressant was as follows: tricyclic antidepressants: Hedges’ g 0.32 (95% confidence interval: [0.14, 0.51]) ( k = 6) with low heterogeneity ( I2: 4%, p = 0.39); selective serotonin reuptake inhibitors/serotonin noradrenaline reuptake inhibitors: Hedges’ g 0.27 (95% confidence interval: [0.03, 0.52]) ( k = 2) with a lack of heterogeneity ( I2: 0%, p = 0.89); and monoamine oxidase inhibitors: Hedges’ g 0.35 (95% confidence interval: [−0.07, 0.77]) with moderate heterogeneity ( I2: 43%, p = 0.17) ( k = 3). Conclusion: An adjuvant antidepressant enhances the efficacy of electroconvulsive therapy for major depression. Tricyclic antidepressants, selective serotonin reuptake inhibitors/serotonin noradrenaline reuptake inhibitors and monoamine oxidase inhibitors showed the same effect size. However, the effect sizes of tricyclic antidepressants and monoamine oxidase inhibitors are most likely underestimated, due to insufficient doses in most of the included studies. We recommend the routine use of an adequately dosed antidepressant during electroconvulsive therapy for major depression.

Chronic pain syndromes cost the US healthcare system over $600 billion per year. A subtype of chronic pain is neuropathic pain (NP), which is defined as "pain caused by a lesion or disease of the somatosensory system," according to the International Association for the Study of Pain (IASP). The pathophysiology of neuropathic pain is very complex, and more research needs to be done to find the exact mechanism. Patients that have preexisting conditions such as cancer and diabetes are at high-risk of developing NP. Many NP patients are misdiagnosed and receive delayed treatment due to a lack of a standardized classification system that allows clinicians to identify, understand, and utilize pain management in these patients. Medications like tricyclic antidepressants, serotonin-norepinephrine reuptake Inhibitor (SNRIs), and gabapentinoids are first-line treatments followed by opioids, cannabinoids, and other drugs. There are limited studies on the treatment of NP.

The article attempts to generalize the currently known pathogenetic mechanisms of antinociceptive effects of the most widely used antidepressants and to highlight the currently available data of experimental models of various pain disorders in laboratory animals and the results of clinical studies both in groups of patients with comorbid pain symptoms and in patients with pain symptoms of various origins without the presence of pronounced affective disorders. The article presents the results of evidence-based studies of the analgesic activity of tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRI), selective serotonin and norepinephrine reuptake inhibitors (SNRI) and drugs with a special receptor mechanism of action. The involvement of various neurotransmitters: serotonin, dopamine, norepinephrine, melatonin, enkephalin, GABA, glutamate, adenosine, etc. in the implementation of the analgesic effect of antidepressants has been examined. The most common side effects of mentioned antidepressants of frequent cause of patients refusing treatment were highlighted as well. Taking into account the considered features of the treatment of comorbid patients with pain, recommendations on the choice of the drug not only according to the severity of its antidepressant and antinociceptive actions, but also the possible development of undesirable effects of long-term therapy were made. New groups of antidepressants with an alternative mechanism of action deserve special attention.

Purpose/background The increased risk of type 2 diabetes mellitus (T2DM) among users of antidepressants (ADs) might be mediated by depression. We investigated whether ADs are associated with increased risk of T2DM in patients with depression. Moreover, the relationship between binding affinities of serotonin transporter (SERT) of ADs and the risk of T2DM is examined. Methods/procedures We conducted a retrospective nested case-control study using data from Taiwan's National Health Insurance Research Database between 2000 and 2013. A total of 3038 patients with depression, 1519 cases of T2DM, and 1519 controls matched for age, sex, and index date, were included. Exposure to ADs was categorized by type and SERT. The association between AD exposure and T2DM development was assessed using conditional logistic regression analysis. Findings/results No association between T2DM development and selective serotonin reuptake inhibitors (adjusted odds ratio [AOR], 1.01; 95% confidence interval [CI], 0.87-1.19; P = 0.962), serotonin-norepinephrine reuptake inhibitors (AOR, 1.13; 95% CI, 0.94-1.37; P = 1.196), tricyclic antidepressants (AOR, 1.01; 95% CI, 0.85-1.21; P = 0.906), or others (AOR, 0.88; 95% CI, 0.75-1.03; P = 0.104) was found. Alternatively, no association between individual ADs and potency of affinity to SERT and the risk of T2DM was found. Implications/conclusions No association between ADs and increase risk of T2DM was found in patients with depression. However, regular metabolic evaluations are recommended for patients with depression regularly taking ADs.

Novel tricyclic diacid (TCDA) and tetracyclic anhydride (TCAH) were synthesized from renewable furan to generate a series of bio-based polyesters via melt polymerization (MP) of TCDA with seven lin...

Topicality. Increase in the use of antipsychotics and antidepressants in many countries led to augmentation of acute poisoning amount with lethal cases. Among them, the main part is combined poisoning, including combination with other medicines, which significantly complicates the conduction of chemical-toxicological analysis.Aim. To conduct the analytical review of side effects and lethal cases of acute poisoning by antipsychotics and antidepressants, including combination with other medicines.Materials and methods. Analysis of websites and online literature sources such as: ehealthme.com, patientsville.com, Academia.edu, PubMed, ResearchGate, Scopus etc.Results and discussion. According to the results of sources analysis, in the period from 2013 to 2018, there were registered 5094 cases of side effects and 56 lethal poisonings with the use of the most commonly used antipsychotics of phenothiazine derivatives. Also 6013 cases of side effects and 675 lethal poisonings were registered with the use of tricyclic antidepressants. The main side effects and causes of fatalities have been identified. The combined use of antipsychotics and antidepressants and its simultaneous application with medicines from other pharmacological groups, increases the risk of poisoning. It greatly complicates the chemical and toxicological searches to determine the cause of poisoning.Conclusions. The conducted research determined the factors of deterioration the toxicological situation recently which has developed with the use of antipsychotics and antidepressants and substantiated feasibility of the development of methods of chemical-toxicological analysis for drugs that caused fatal poisoning.

Antidepressant treatment has been evolving and changing since the 1950s following the discovery of the classic antidepressant treatments including tricyclic antidepressants and monoamine oxidase inhibitors. The heterogeneity of the disorder became apparent in the beginning when individuals remained symptomatic despite medication compliance. This spurred further research in order to understand the neurobiology underlying the disorder. Subsequently, newer medications were designed to target specific neurotransmitters and areas of the brain involved in symptom development and maintenance. Our original review article looked at both classic and modern antidepressant medications used in the treatment of major depressive disorder. This manuscript is an update to the original review and serves to provide clinicians with information about novel antidepressant medications, augmentation strategies with atypical antipsychotics, over-the-counter medications, as well as nonpharmaceutical treatments that should be considered when treating each individual patient who remains symptomatic despite treatment efforts.

There is a huge need for pharmaceutical agents for the treatment of chronic Neuropathic Pain (NP), a complex condition where patients can suffer from either hyperalgesia or allodynia originating from central or peripheral nerve injuries. To date, the therapeutic guidelines include the use of tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors and anticonvulsants, beside the use of natural compounds and non-pharmacological options. Unfortunately, these drugs suffer from limited efficacy and serious dose-dependent adverse effects. In the last decades, the heptapeptide SP1-7, the major bioactive metabolite produced by Substance P (SP) cleavage, has been extensively investigated as a potential target for the development of novel peptidomimetic molecules to treat NP. Although the physiological effects of this SP fragment have been studied in detail, the mechanism behind its action is not fully clarified and the target for SP1-7 has not been identified yet. Nevertheless, specific binding sites for the heptapeptide have been found in brain and spinal cord of both mouse and rats. Several Structure-Affinity Relationship (SAR) studies on SP1-7 and some of its synthetic analogues have been carried out aiming to developing more metabolically stable and effective small molecule SP1-7-related amides that could be used as research tools for a better understanding of the SP1-7 system and, in a longer perspective, as potential therapeutic agents for future treatment of NP.

Thirty million office visits annually are the result of a mental health disorder, and 33% occur in an outpatient clinic. Depression, a common diagnosis in the primary care setting, is often treated with selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, and tricyclic and atypical antidepressants. However, withdrawal symptoms can occur with the abrupt cessation of the medication. This article discusses the clinical features associated with withdrawal syndrome and how to prevent them with an adequate taper of antidepressants.

Functional dyspepsia (FD) is one of the dysregulatory lesions of the upper digestive tract. This syndrome has fairly well-defined clinical manifestations that include borderline psychopathological disorders. Its diagnosis becomes a method for ruling out organic gastrointestinal and mental illnesses. Treatment for FD is complex and includes a behavioral component, prokinetics, myotropic spasmolytics, antisecretory drugs, and tricyclic antidepressants. The efficiency of therapy directly depends on a physician's ability to choose an individualized regimen.

Background Understanding how patients are treated in the real-world is vital to identifying potential gaps in care. We describe the current pharmacologic treatment patterns for the treatment of depression. Methods Patients with depression were identified from four large national claims databases during 1/1/2014–1/31/2019. Patients had ≥2 diagnoses for depression or an inpatient hospitalization with a diagnosis of depression. Patients were required to have enrollment in the database ≥1 year prior to and 3 years following their first depression diagnosis. Treatment patterns were captured at the class level and included selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors, tricyclic antidepressants, other antidepressants, anxiolytics, hypnotics/sedatives, and antipsychotics. Treatment patterns were captured during all available follow-up. Results We identified 269,668 patients diagnosed with depression. The proportion not receiving any pharmacological treatment during follow-up ranged from 29 to 52%. Of the treated, approximately half received ≥2 different classes of therapy, a quarter received ≥3 classes and more than 10% received 4 or more. SSRIs were the most common first-line treatment; however, many patients received an anxiolytic, hypnotic/sedative, or antipsychotic prior to any antidepressive treatment. Treatment with a combination of classes ranged from approximately 20% of first-line therapies to 40% of fourth-line. Conclusions Many patients diagnosed with depression go untreated and many others receive a non-antidepressant medication class as their first treatment. More than half of patients received more than one type of treatment class during the study follow up, suggesting that the first treatment received may not be optimal for most patients.

Introduction Drug-induced QT prolongation is associated with higher cardiovascular mortality. Material and methods We conducted a protocol-based comprehensive review of antidepressant-induced QT prolongation in people with mental disorders. Results Based on findings from 47 published randomized controlled trials (RCTs), 3 unpublished RCTs, 14 observational studies, 662 case reports of torsades de pointes, and 168 cases of QT prolongation, we conclude that all antidepressants should be used only with licensed doses, and that all patients receiving antidepressants require monitoring of QT prolongation and clinical symptoms of cardiac arrhythmias. Large observational studies suggest increased mortality associated with all antidepressants (RR = 1.62, 95% CI: 1.60-1.63, number of adults: 1,716,552), high doses of tricyclic antidepressants (OR = 2.11, 85% CI 1.10-4.22), selective serotonin reuptake inhibitors (OR = 2.78, 95% CI: 1.24-6.24), venlafaxine (OR = 3.73, 95% CI: 1.33-10.45, number of adults: 4,040), and nortriptyline (OR = 4.60, 95% CI: 1.20-18.40, number of adults: 5,298). Conclusions Evidence regarding the risk of QT prolongation in children is sparse.

Carbamazepine (CMZ) is a drug from the group of anticonvulsants, similar in chemical structure to tricyclic antidepressants. CMZ is widely used for mental disorders and neurological diseases. The lecture discusses the safety of CMZ in respect to personalized medicine, while considering the pharmacogenetic profile of the patient.The authors declare about the absence of conflict of interest with respect to this publication. All authors contributed equally to this article.

Current antipsychotic drugs are notably ineffective at addressing the cognitive deficits associated with schizophrenia. N-Desmethylclozapine (NDMC), the major metabolite of clozapine, displays muscarinic M1 receptor (M1) agonism, an activity associated with improvement in cognitive functioning. Preclinical and clinical data support that M1 agonism may be a desired activity in antipsychotic drugs. However, NDMC failed clinical phase II studies in acute psychotic patients. NDMC analogues were synthesized to establish a structure-activity relationship (SAR) at the M1 receptor as an indication of potential procognitive properties. In vitro evaluation revealed a narrow SAR in which M1 agonist activity was established by functionalization in the 4- and 8-positions in the tricyclic core. In vivo behavioral response profiles were used to evaluate antipsychotic efficacy and exposure in zebrafish larvae and peripheral side effect related M1 activity in adult zebrafish. The NDMC analogue 13f demonstrated antipsychotic activity similar to clozapine including M1 agonist activity. Cotreatment with trospium chloride, an M1 peripheral acting antagonist, counteracted peripheral side effects. Thus, the NDMC analogue 13f, in combination with a peripherally acting anticholinergic compound, could be suitable for further development as an antipsychotic compound with potential procognitive activity.

Tricyclic antidepressants (TCAs) were originally designed and marketed for treating depression, but over time they have been applied to a variety of conditions, mostly off-label. TCAs can serve as first-line or augmenting drugs for neuropathic pain, headache, migraine, gastrointestinal syndromes, fibromyalgia, pelvic pain, insomnia, and psychiatric conditions other than depression. This article reviews pharmacology, dosing, and safety considerations for these uses.

INTRODUCTION: Depression is one of the most prevalent psychological disorders. It affects all body systems including endocrinal,neurological and immune system. Additionally, it is thought to affect bone homeostasis. Antidepressants are the most commonly prescribeddrugs. They are classified into tricyclic and tetra cyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs) and selectiveserotonin-reuptake inhibitors (SSRIs). Fluoxetine, which is a selective serotonin-reuptake inhibitor, is used for the treatment of depression byselectively acting on serotonin (5-HT). Fluoxetine plays a major role in bone apposition and in maintaining the bone homeostasis.OBJECTIVES: To investigate the effect of selective serotonin-reuptake inhibitor (fluoxetine) on the structure of alveolar bone in rats withinduced depression.MATERIALS AND METHODS: Thirty adult male rats were divided as follows: Group I: (control group) which consists of 10 rats, Group II: (depression group) 10 rats were exposed to chronic unpredictable stress (CUS) to induce depression, Group III: (fluoxetine group) 10 ratswere exposed to chronic unpredictable stress (CUS) to induce depression and at the same time they were orally supplied with 10 mg/kg/day offluoxetine. After 3 months, the mandibles were dissected out and prepared for histological analysis using light microscope, scanning electronmicroscope (SEM) and energy dispersive x-ray microanalysis (EDX).RESULTS: In the control group, the alveolar bone surface showed a regular and smooth outline. In the depression group, there was a significantdisturbance in the bone architecture. The bone surface showed an irregular outline with multiple osteoclasts lying in How ship's lacunae. Deeplystained incremental lines were also evident. In the fluoxetine group, the bone surface restored its regular outline with multiple osteoblasts andosteocytes. The bone showed incremental lines indicating bone formation.CONCLUSIONS: Depression can lead to bone loss and osteoporosis. Fluoxetine is an effective drug in enhancing the bone condition andrestoring the normal architecture of the alveolar bone.

Hyperhidrosis occurs when sweating is excessive for thermoregulatory purposes, which may result in decreased quality of life and emotional stress for patients.1 Classified as primary and secondary, secondary hyperhidrosis is often related to an underlying cause.2 Certain medications have been reported to induce hyperhidrosis, including selective serotonin reuptake inhibitors, tricyclic antidepressants, and opioid agonists.2, 3, 4 We present the case of a woman with a history of opioid use disorder who experienced hyperhidrosis in the setting of partial opioid agonist and opioid antagonist therapy (buprenorphine-naloxone), who was treated successfully with oral oxybutynin 5 mg daily.

Background Many antidepressants are substrates of P-glycoprotein, an efflux transporter in the blood-brain-barrier encoded by the ABCB1 gene. Genetic variations might influence the transport rate of antidepressants and hence their pharmacological effects. This study investigates the influence of eight polymorphisms in the ABCB1 gene on antidepressant treatment response. Method 152 patients were included from psychiatric departments of the Mental Health Research Institute in Tomsk. The difference in Hamilton-Depression-Rating-Scale (HAMD-17)-scores between baseline and week two, week two and four, and baseline and week four was used to estimate timing of improvement of depression. Associations between the ABCB1 gene-polymorphisms and reduction in HAMD-17 score were assessed using independent t-test and multiple linear regression. Results Tricyclic antidepressants were associated with a higher reduction of HAMD-17 score when compared to SSRIs. The SNP rs2235040 A-allele had a significant positive influence on the Delta HAMD-17((0 -> 2W)) score but a significant negative influence on the Delta HAMD-17((2 -> 4W)) score. The rs4148739 G-allele had a significant negative influence on the Delta HAMD-17((0 -> 2W)) score but a significant positive influence on the Delta HAMD-17((2 -> 4W)) score. The SNP rs2235015 T-allele is significant negatively related to the Delta HAMD-17((2 -> 4W)) score. Conclusion ABCB1 Genetic variations appear to affect speed but not magnitude of antidepressant drug response.

Post-fundoplication dyspepsia is a common complication of gastric fundoplication surgeries. This can be attributable to the loss of fundal relaxation, decreased gastric accommodation, and/or alterations in gastric motility and sensitivity following fundoplication. The role of neuromodulators in the management of such symptoms is unknown. We retrospectively assessed the efficacy of neuromodulators such as tricyclic antidepressants, buspirone, and mirtazapine for the management of post-fundoplication dyspepsia.

To analyse the current therapeutic options for patients with premature ejaculation (PE) and highlight their mechanism(s) of action, effectiveness, advantages and limitations. A literature search was conducted using the PubMed database searching for articles exploring different PE treatment modalities. A Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) approach was used to report the results of the literature search. A total of 149 articles were included in this review. The currently available treatment methods for PE include behavioural therapy, local anaesthetics, tricyclic antidepressants, selective serotonin reuptake inhibitors, and selective phosphodiesterase inhibitors. Most PE treatments are either experimental or used off-label. New treatments are certainly warranted to overcome this exasperating sexual dysfunction. Abbreviations: AIPE: Arabic Index of Premature Ejaculation; CNS: central nervous system; CYP: cytochrome P450; ED: erectile dysfunction; FDA: United States Food and Drug Administration; H1: histamine receptors; 5-HT: 5-hydroxytryptamine; IELT: The intravaginal ejaculation latency time; IPE: Index of Premature Ejaculation; M1: muscarinic receptors; OCD: obsessive–compulsive disorder; PDE5: phosphodiesterase type 5; PE: premature ejaculation; PEP: Premature Ejaculation Profile; PRO: patient-reported outcome; RCT: randomised controlled trial; SS: Severance Secret (cream); SSRIs: selective serotonin reuptake inhibitors; TCAs: tricyclic antidepressants

Background: Obsessive-compulsive disorder (OCD) is a common chronic mental disorder with a high disability rate. Serotonin reuptake inhibitors (SRIs), including selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants, such as clomipramine, are the most common choices for the pharmacological treatment of OCD. Optimizing their use is pivotal in guiding clinical practice of OCD. However, there are few studies on the optimal dose of SRIs and there is controversy about their dose–response relationship and optimal target dose. Therefore, the objective of this study was to summarize the relationship between the dose and effect of SRIs, as well as the optimal dose of SRIs for OCD, as to propose future research directions.Methods: Medline, Embase, Biosis, PsycINFO, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and CINAHL were searched for relevant publications, and the search was up to February 22, 2020. We used a one-stage, robust error meta-regression (REMR) model to deal with the correlated dose–response data for SRIs from different studies. Doses of SRIs were converted to fluoxetine equivalents when performing dose–response analysis. Review Manager Program Version 5.3 and STATA software package (version 15.1) were applied to analyze data. The study protocol was registered with PROSPERO (number CRD42020168344).Results: Eleven studies involving 2,322 participants were included in final analysis. For SRIs, the dose–efficacy curve showed a gradual increase trend in the 0–40-mg dose range and then had a decreased trend in doses up to 100 mg fluoxetine equivalent. Dropouts due to adverse effects gradually increased throughout the inspected dose slope. The curve of dose of all-cause dropouts suggested no relationship between them. Sensitivity analysis proved that these results were robust.Conclusion: The systematic review found that the optimal dose for efficacy was about 40mg fluoxetine equivalent. Tolerability decreased with increased doses, and there was no significant correlation between acceptability and doses of SRIs. Therefore, the optimal dose of SRIs needs to consider effectiveness and tolerability.Systematic Review Registration: [PROSPERO], identifier [CRD42020168344].

Background Antidepressants are a lifesaver for many people worldwide, regardless of their age or gender. Antidepressant therapy has been the choice for patients with depression, anxiety, and schizophrenia. The gut-brain axis (GBA) is a bidirectional pathway illustrating the communication between the brain and the gut microbiota and vice versa. Many studies have demonstrated the establishing of gut dysbiosis status in major depressive disorder. Meanwhile, the impact of antidepressant treatments on gut microbiota composition remains underexplored. Interestingly, several classes of antidepressants drugs, including monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), N-methyl-d-aspartate (NMDA) receptor antagonists, and tricyclic antidepressants (TCAs), exhibit antibacterial activities. Hence, this systematic review explores the impact of antidepressants on gut microbiota and potential strategies to alleviate antidepressant-associated dysbiosis. Methods This systematic review was conducted based on the PRISMA guidelines. Predefined MeSH terms ‘antidepressants AND gut microbiome’; ‘antidepressants AND antimicrobial activity’ were used in three databases (Pubmed, Embase, ProQuest; from database inception to June 2021). Studies reporting on the gut microbiota variation and antidepressants action were included. Studies without antidepressants and/or gut microbiome data were excluded, including conference proceedings, reviews, systematic reviews, meta-analyses, and commentaries. Results According to the study’s inclusion criteria, twelve studies out of 300 articles were selected for the qualitative analysis. In the in-vivo studies, animals administrated with SSRIs had a decreased abundance of Firmicutes, Alphaproteobacteria, Bacteroides, Ruminococcus, Adlercreutzia, Turicibacter, and alpha diversity but an increase in Prevotella, Parabacteroides, Butyricimonas, and Alistipes. Besides, antidepressants were shown to exhibit significant in vitro antimicrobial activity against Akkermansia muciniphila, Bifidobacterium animalis, and Bacteroides fragilis, suggesting that the chronic use of antidepressants potentially causes adverse effects due to their antimicrobial effects and dysbiosis (IDDF2021-ABS-0164 Figure 1. Illustration of gut microbiota dysbiosis in response to antidepressants). Probiotics, prebiotics and fecal microbiota transplantation are shown to be promising strategies to ameliorate antidepressant-associated dysbiosis. Conclusions Understanding the interaction between antidepressants and gut microbiota, including dysbiosis as a consequence of treatment and potential side effects, is vital for the future development of better and personalized treatment. Supplementing the gut microbiome with prebiotics/probiotics could be an adjuvant treatment to improve the clinical efficacy of the current antidepressant therapies.

BACKGROUND: The majority of antidepressants inhibit serotonin reuptake and include the selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and the serotonin reuptake inhibiting tricyclic antidepressants. OBJECTIVE: The objective of this study was to investigate and describe the range and impact of reported adverse visual effects linked to serotonin reuptake inhibiting antidepressants. METHODS: Using data from a global database of patient spontaneous reports of drug adverse events, we systematically identified eligible reports of visual problems linked to the use of serotonin reuptake inhibiting antidepressants. We analyzed these data using simple descriptive statistics to present the range and impact. RESULTS: We identified 124 reports of visual problems. Reports originate from 18 countries and involve 11 different drugs. The most commonly reported symptoms were vision blurred/visual acuity reduced (n = 79, 63.7%), night blindness (n = 22, 17.7%), vitreous floaters (n = 21, 16.9%), photophobia (n = 19, 15.3%), diplopia (n = 15, 12.1%), palinopsia (n = 13, 10.5%), visual field defect (n = 12, 9.7%), photopsia (n = 11, 8.9%) and visual snow syndrome (n = 11, 8.9%). 74 patients indicated that the side effect was bad enough to affect everyday activities, 62 had sought health care, and 50 indicated that their work had been affected. 49 patients reported an enduring vision problem after discontinuation of treatment. CONCLUSIONS: The data suggest that serotonin reuptake inhibiting antidepressants can produce a range of adverse effects on vision that in some cases can be long-lasting after discontinuation of the drug. Further efforts are needed to understand the mechanisms involved, the incidence among those prescribed these medications, and identify any risk or mitigation factors.

Objectives Although many antidepressants are available, they are not always used appropriately. For appropriate use of antidepressants, the old concept of a linear dose–response relationship, in which the dose is linearly increased to achieve a sufficient antidepressant effect, should be reconsidered. Furthermore, there is ongoing debate on the safe and appropriate use of antidepressants in patients with bipolar depression. Antidepressants may be used under certain conditions in patients with bipolar depression. These neglected—but not negligible—aspects of antidepressants have been discussed herein. Methods A narrative qualitative review Results Dose–response relationships of antidepressants such as selective serotonin reuptake inhibitors (SSRIs) are not linear. They may be bell‐shaped, with efficacy initially increasing with an increase in dose but decreasing when the dose is increased beyond a certain point. Despite using international diagnostic criteria, uncertainty remains on whether operationally diagnosed depression is latent bipolar I depression, latent bipolar II depression, or true depression. Furthermore, operationally diagnosed bipolar II depression may be latent bipolar I depression, true bipolar II depression, or depression with false hypomanic episodes. Manic/hypomanic switches are most likely to occur in patients receiving tricyclic antidepressants, followed by those receiving serotonin and noradrenaline reuptake inhibitors and SSRIs, in that order. Also, these switches are most likely to occur in patients with bipolar I depression, followed by those with bipolar II depression and true depression, in that order. Conclusions Considering the diagnostic subtype of bipolar depression and antidepressant properties may help to determine the optimal treatment strategy., Considering the diagnostic subtype of (bipolar) depression and antidepressant properties may help to determine the optimal treatment strategy.

Psychopharmacologic therapies are beneficial in reducing symptoms when treating irritable bowel syndrome (IBS) and other disorders of gut-brain interaction (DGBI). Noradrenaline, serotonin, and dopamine are neurotransmitters of key importance in psychopharmacology and pain-reduction mechanisms. The first-line (tricyclic antidepressants, serotonin noradrenaline reuptake inhibitors, selective serotonin reuptake inhibitors) and second-line (atypical antipsychotics, delta-ligand agents, low-dose naltrexone) neuromodulator treatment options are recommended when IBS-associated abdominal pain is of moderate or severe intensity and is persistent. To understand the implementation strategy, the multidimensional clinical profile as a template is used for presenting 3 case scenarios involving painful IBS and DGBI of varying complexity.

There is an urgent need to find antidepressants that can be administered for long periods without inducing severe side effects to replace conventional antidepressants that control monoamine levels, such as tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), and selective serotonin reuptake inhibitors (SSRI). We sought to determine the antidepressant effects of Fraxinus rhynchophylla Hance (F. rhynchophylla Hance, FX) and its components on a reserpine-induced mouse model. One hour after oral administration of FX (30, 50, and 100 mg/kg), esculin (50 mg/kg), esculetin (50 mg/kg), fraxin (50 mg/kg), and fluoxetine (20 mg/kg), reserpine was delivered intraperitoneally to mice. Behavioral experiments were conducted to measure anxiety and depressive-like behaviors after 10 days of administration. FX and its components increased the number of entries into the center of an open field as well as distance traveled within it and decreased immobility duration in the forced swim and tail suspension tests. Reserpine-induced increases in plasma corticosterone concentrations were attenuated by the administration of FX and its components, which were also found to decrease the reserpine-induced enhancement of mRNA levels of interleukin (IL)-12 p40, IL-6, and tumor necrosis factor (TNF)-α, pro-inflammatory cytokines. Finally, the diminished expressions of hippocampal phosphorylated cAMP response element-binding protein (pCREB) and brain-derived neurotrophic factor (BDNF) by reserpine were increased by FX and its components. Our results suggest that FX and its components regulate anxiety and depressive-like behaviors through stress hormones, immune regulation, and the activation of neuroprotective mechanisms, further supporting the potential of FX and its components as antidepressants.

Tricyclic antidepressants, citalopram, venlafaxine and monoamine oxidase inhibitors are the most toxic antidepressants in overdose. Features include hypotension and arrhythmias that are best managed by aggressive correction of metabolic acidosis with sodium bicarbonate. Antipsychotic drugs differ in their chemical structure and specificity at dopamine receptors. Overdose produces a range of adverse effects including sedation and acute extrapyramidal reactions. Cardiovascular effects including hypotension, prolongation of the QT interval and, potentially, arrhythmias including torsade de pointes are also seen.

Objective: The aim of this repeated cross-sectional study was to compare patients from a psychiatric intensive care unit (PICU) over ≫30 years regarding their diagnostic and therapeutic characteristics. Method: Three samples including 100 consecutive inpatients each from the Viennese PICU were submitted to a chart review: sample no. 1 from the years 1985/86, no. 2 from 1995/96 and no. 3 from 2007/08. Results: Changes in referral modes were associated with a decrease of patients with substance induced disorders and an increase of patients with affective disorders over time. The rate of admissions after accidents and suicides was stable. The use of cranial MRI increased, while intravenous psychopharmacotherapy and parenteral nutrition decreased. Involuntary admission occurred in 43% and in 37% of patients physical restraints were necessary. We saw a shift from tricyclic antidepressants to SSRIs and SNRIs from sample 1 to 3. Likewise, we observed the emergence of atypical antipsychotics and a reduction of use of typical neuroleptics mainly from sample 2 to 3. The percentage of patients receiving benzodiazepines increased over time, while the mean dosage of benzodiazepines decreased. 7% of patients received electroconvulsive therapy. Conclusions: The changes over time in our samples reflect the medical progress made during the last decades. Future studies should focus on evaluation of efficacy of psychiatric intensive care using standardized measurements. Keywords: Mental health services, Intensive care, History, Psychopharmacology, Antidepressants, Antipsychotics

Pain is classified by various descriptions. Chronic pain has been described as being neuropathic (due to nervous system lesions), nociceptive (due to tissue damage), or mixed (a combination of neuropathic and nociceptive). The addition of the term nociplastic pain is used to describe patients who experience chronic pain without tissue damage or nervous system lesions. Chronic pain is often difficult to manage, particularly neuropathic pain. Evidence-based pharmacological treatment options include anticonvulsants and antidepressants. The choice of medication will depend on various factors, including patient profile, type of pain, and associated conditions. Medications with the best evidence of efficacy for first-line use in neuropathic pain are the gabapentinoids, carbamazepine, the tricyclic antidepressants, and the serotonin-noradrenaline reuptake inhibitors duloxetine and venlafaxine. The cannabinoids and ketamine are being actively investigated for use in chronic pain. Currently the cannabinoids’ potential benefit is outweighed by the adverse effects, and recommendations for the use of ketamine is limited by its parenteral route of administration and low evidence of efficacy in chronic pain.