Tetracyclic Antidepressants Research Articles

An audit on prescribing practice and risk of serotonin syndrome among patients with chronic pain

AimsTo determine the incidence of prescribing practice with associated risk of serotonin toxicity among patients with chronic pain conditions.BackgroundSerotonin syndrome is a potentially life-threatening condition caused by excessive serotonergic activity, usually from drug interactions. Concurrent use of antidepressants is strongly linked to serotonin syndrome, with recent data revealing record numbers of NHS prescribed antidepressants in 2019. Antidepressant medications are also used in chronic pain management for their anti-neuropathic pain properties. However, it is well-recognised that a significant number of chronic pain patients suffer from anxiety and depression. This cohort of patients is therefore vulnerable to being exposed to multiple concurrent antidepressant agents, and thus at relatively higher risk of serotonin syndrome compared to other patient groups. Additionally, these patients are likely to be exposed to the concurrent use of antidepressants and certain analgesic agents particularly phenylpiperidine derivatives which increases serotonin toxicity risk.MethodMedications of patients presenting to a secondary care pain clinic within the last year were looked into. Patients were selected at random by pain management secretaries. Concurrent use of multiple antidepressant agents including Selective Serotonin Reuptake Inhibitors (SSRIs), Serotonin Noradrenaline Reuptake Inhibitors (SNRIs), Tricyclic Antidepressants (TCAs) or Tetracyclic Antidepressant (TeCA) was noted. Additionally, concurrent use of any of these antidepressant agents and phenylpiperidine derivatives such as Fentanyl and Tramadol was noted.ResultData on medications of 97 patients were collected. A total of 28 patients (28.8%) were observed to have at-risk medication combinations. Out of these, five patients were on both SSRI and TCA. Two patients were on both TCA and TeCA. Four other patients were on either a combination of SSRI and SNRI, SNRI and TCA, SSRI and TeCA, or TCA and TCA. Three patients were on both Fentanyl patches and an antidepressant. Fourteen patients were on both an antidepressant and Tramadol. None of these patients were diagnosed with serotonin syndrome; however, it is unclear as to whether these patients experienced milder symptoms of the syndrome.ConclusionA considerable number of patients in this group were on medication combinations putting them at risk of serotonin syndrome. Despite no documented patient harm, there is an urgent need for an increased awareness among prescribers on drug interactions which may lead to this syndrome and a subsequent change in prescribing practice.

New generation antidepressants for depression in children and adolescents: a network meta-analysis.

New generation antidepressants for depression in children and adolescents: a network meta-analysis.

How often are antidepressants prescribed off-label among older adults in Germany? A claims data analysis.

To estimate the extent of off-label prescribing of antidepressants in older adults and to characterize patients with off-label vs on-label prescriptions of antidepressants using a large German health claims database. Using data from the German Pharmacoepidemiological Research Database (GePaRD), we conducted a cross-sectional study in adults aged 65 years or older with a dispensation of an antidepressant between 1 January 2009 and 31 December 2015 after a period of 365 days without such a dispensation. We assessed the overall and annual proportion of off-label prescriptions of antidepressants by class and individual substance. Among 263 276 incident users of antidepressants, the proportion of off-label prescribing was 43.6% (95% CI 43.4-43.8%) with little variation between 2009 and 2015 (42.2-44.4%). The proportion of off-label use was higher in men (49%) than women (41%). While the proportion of off-label prescriptions was highest for tri- and tetracyclic antidepressants with 56.2% (amitriptyline 54.6%, maximum 65.9% for trimipramine), it amounted to 41.8% for selective serotonin reuptake inhibitors (citalopram 41.6%, maximum 46.0% for escitalopram) and was 51.2% for mirtazapine. Indicators of overall morbidity were similar in both groups, eg, pain was coded in 72% of off-label users vs 77% of on-label users (insomnia 20% vs 24%). Our study suggests a high prevalence of off-label antidepressant use among older adults in Germany, which was not restricted to certain classes of antidepressants or individual antidepressants. Given the unclear risk-benefit ratio, studies investigating the safety of off-label use among older adults for individual antidepressants are urgently needed.

POSSIBLE COMPLICATIONS OF ANTIDEPRESSANTS AND THEIR CORRECTION

Depression and the complications of its pharmacotherapy remain relevant issues in modern medicine. Since the advent of the first antidepressants, more than 60 years ago, to the present, their arsenal has expanded significantly. On the one hand, the emergence of new antidepressants is a great achievement in psychopharmacology, and on the other hand, due to their specificity, antidepressants cause many complications. In addition, in recent years, the list of diseases in which off label (outside the instructions) use these drugs has expanded significantly, and given the fact that for these diseases, anti-depressants are prescribed in combination with other drugs, so the risk of developing side effects increases significantly . This article analyzes the frequently encountered side effects of antidepressants, the mechanisms of their occurrence when using both first-generation antidepressants (three and tetracyclic antidepressants, monoamine oxidase inhibitors) and newer drugs from the group of selective serotonin reuptake inhibitors. The conditions for the rational use of antidepressants are also presented, which allows to optimize their use and the safety of pharmacotherapy for depression. Thus, today it is necessary to create new safer antidepressants that selectively inhibit the reuptake of one of monoamines (for example, serotonin) and third-generation drugs with a “double” effect, i. e. selectively and equipotentially inhibiting the reuptake of serotonin and norepinephrine.

Mirtazapine reduces the expression of cocaine-induced locomotor sensitization in male and female Wistar rats

BackgroundEpidemiological studies have described that women are more vulnerable to the reinforcing effects of cocaine. In animals, the findings are similar: female rats show higher levels of cocaine self-administration and increased cocaine-induced locomotor activity. In contrast, women with depression respond better to treatment with antidepressants, however their therapeutic response to tetracyclic antidepressants is lower. Several studies have shown that mirtazapine—a tetracyclic antidepressant—decreases the behavioral effects of cocaine in male rats. The objective of this study was to evaluate the efficacy of daily dosing of mirtazapine on cocaine-induced locomotor activity and sensitization in naive female rats compared to male rats. MethodsMale and female Wistar rats were daily dosed with 10 mg/kg of cocaine. During extinction, cocaine was withdrawn and the groups received daily mirtazapine (30 mg/kg, i.p.) or saline. Tamoxifen was administered during the antagonism phase. After each administration, locomotor activity for each animal was recorded for 30 min in transparent Plexiglass activity chambers. ResultsIn this study, a higher cocaine locomotor response was found in females than in males and the mirtazapine was equally effective in decreasing cocaine-induced locomotor activity and the expression of locomotor sensitization in male and female rats. In addition, co-administration of mirtazapine and tamoxifen enhanced the efficacy of mirtazapine in female rats. ConclusionThe results suggest that mirtazapine may be considered an effective therapeutic option for the treatment of cocaine use disorder in men and women.

New generation antidepressants for depression in children and adolescents: a network meta-analysis

New generation antidepressants for depression in children and adolescents: a network meta-analysis

The impact of β-cyclodextrin on biological and chemical properties of mianserin hydrochloride in aqueous solution

Mianserin hydrochloride (MIA), a drug, which belongs to a group of tetracyclic, noradrenergic and specific serotonergic antidepressants, is one of the commonly used psychotropic drugs. Despite its important uses and having a number of other potential utilizations, MIA has quite significant side effects on a patient health, including some cytotoxicity. The MIA toxicity could be reduced by drug encapsulation inside a non-toxic carrier, like β-cyclodextrin molecules (β-CD). Cyclodextrins are cone shaped supramolecules with hydrophobic interior, where hydrophobic parts of molecule can be included, and with hydrophilic rims consisting of primary and secondary hydroxyl groups, which can interact with water molecules. This study investigated the characteristic and mechanism for interaction of MIA with β-CD, and evaluated the effects of complexation on MIA cytotoxicity. Chemical shift differences for protons in mianserin hydrochloride and β-cyclodextrin molecules, induced by the formation of the inclusion complexes, have been determined by proton nuclear magnetic resonance spectroscopy. The other chemical properties of mianserin hydrochloride in aqueous solution in the presence of β-cyclodextrin has been examined at 298.15 K with the use of mass spectrometry and circular dichroism. The results showed that interaction of MIA with β-CD occurred through incorporation of MIA aromatic rings inside probably more than one β-CD molecules. The effects of β-cyclodextrin, mianserin hydrochloride and complexes thereof on the viability of Chinese hamster cells were investigated in order to estimate the cytotoxicity of the drug. The viability of B14 cells treated with MIA + β-CD is higher than with MIA and the protective effect is the highest for complexes of MIA:β-CD in a 1:4 ratio.

Psychotropic Medication Effects on Seizure Threshold and Seizure Duration During Electroconvulsive Therapy Stimulus Titration.

Decisions about psychotropic medication administration before electroconvulsive therapy (ECT) are central to management of a very psychiatrically ill patient population. Given that many psychotropic medications are thought to either promote or prevent seizures, there is ongoing concern about concurrent psychotropic medication and ECT administration. This study examined the effect of psychotropic medications on seizure threshold and duration during ECT stimulus titration. The study sample consisted of 550 patients receiving ECT stimulus titration at a single site during a 27-month period. Systematic chart review provided clinical data, including patients' demographics, psychiatric diagnoses, medications administered in the 48 hours before ECT, and information on the ECT procedure. Referring psychiatrists were advised to discontinue lithium before ECT but otherwise managed psychotropic medications as clinically indicated. A fixed charge titration schedule was used to estimate seizure threshold. Electroconvulsive therapy motor seizure duration was estimated by the cuff method, and electroencephalogram seizure duration was estimated by review of a 2-lead strip. Administration of psychotropic medications, including benzodiazepines, antiepileptics, selective serotonin reuptake inhibitors, tricyclic and tetracyclic antidepressants, bupropion, and stimulants, was not associated with seizure threshold as estimated by electrical charge eliciting a generalized seizure or duration during the initial ECT titration. Tricyclic and tetracyclic antidepressant dosage was associated with seizure threshold. Psychotropic medications may have little effect on seizure threshold and duration during titration of electrical dose at ECT initiation. Integrating this work with other literature supports making recommendations for medication discontinuation before ECT on an individual basis.

Analysis of Antidepressant Agonist Activity at LPA1, LPA2 and LPA3 lysophosphatidic acid receptors

Besides inhibiting monoamine reuptake, antidepressants have been shown to affect a number of neurotransmitter receptor systems, at which they most often act as antagonists. We have previously shown that in neuronal and non‐neuronal cells different antidepressants, predominantly belonging to the tricyclic and tetracyclic classes, activate the LPA1 lysophosphatidic acid (LPA) receptor to induce proliferative and prosurvival signaling. In the present study we further characterize this unique agonist activity of antidepressants by examining their ability to activate two additional members of the LPA receptor family, LPA2 and LPA3, which display high sequence similarity to LPA1. The human LPA receptors were stably transfected in HEK293 cells (HEK293‐LPA1–3 cells), and their activation was monitored by measuring the phosphorylation/activation of ERK1/2 by Western blot. Exposure to LPA caused a concentration‐dependent increase of phospho‐ERK1/2 levels with EC50 values of 145, 210 and 45 nM in HEK293‐LPA1, ‐LPA2 and ‐LPA3 cells, respectively. As previously observed in other cell types endogenously expressing LPA receptors, amitriptyline, imipramine, clomipramine, desipramine, mianserin and mirtazapine effectively increased ERK1/2 phosphorylation in HEK293‐LPA1 cells. In HEK293 cells stably transfected with a LPA1 mutant (Q3.29A), which was unresponsive to LPA, the stimulatory effects of amitriptyline, clomipramine and mianserin were greatly suppressed, indicating the dependence on receptor structural integrity. Tricyclic antidepressants failed to stimulate ERK1/2 phosphorylation in HEK293‐LPA2 cells, whereas the tetracyclic compounds mianserin and mirtazapine displayed agonist activity, although with relative efficacies lower than those showed in HEK293‐LPA1 cells. Conversely, both tricyclic and tetracyclic antidepressants induced ERK1/2 activation in HEK293‐LPA3 cells. These data demonstrate that some classes of antidepressants can exert agonist activity at more than one LPA receptor, thus extending their spectrum of pharmacological activity. In particular, the present finding that antidepressants can activate LPA3, which is expressed in human hippocampus, amygdala, frontal cortex and in different peripheral tissues, suggests that this receptor can be a potential target for the therapeutic and adverse effects of these drugs.Support or Funding InformationUniversity of Cagliari FIR 2019

Risk of Extrapyramidal Syndromes Associated With Psychotropic Polypharmacy: A Study Based on Large-Scale Japanese Claims Data.

Psychotropic polypharmacy is common in clinical practice although supporting evidence is limited. Extrapyramidal syndromes (EPS) are adverse events associated with use of psychotropic drugs, especially antipsychotics. There are quite a few reports that suggest association between each psychotropic drug and EPS; however, the risk of EPS associated with their polypharmacy has not been fully evaluated. This study aimed at examining the influence of psychotropic polypharmacy on EPS occurrence by drug category (anxiolytics, hypnotics, antidepressants, and antipsychotics). Sequence symmetry analyses were conducted using a large-scale Japanese health insurance claims database. This method assessed asymmetry in the distribution of EPS occurrence defined as both a diagnosis of EPS and a prescription for antiparkinsonian drugs before and after initiation of psychotropic drugs. The adjusted sequence ratio (ASR) and its 95% confidence interval (CI) were calculated. All categories of psychotropic drugs (anxiolytics, hypnotics, antidepressants, and antipsychotics) were significantly associated with EPS, and the tendency was stronger in polypharmacy associated with them. A clearer association between polypharmacy of BZs and EPS was indicated. In the analyses by subclasses of drugs, BZs, tetracyclic antidepressants, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, typical and atypical antipsychotics were significantly associated with EPS. The ASR of atypical antipsychotics (ASR 11.3, 95% CI 7.95-16.4) was higher than that of typical ones (ASR 2.96, 95% CI 2.06-4.33). The association between psychotropic polypharmacy and EPS was indicated. Further investigation is needed to confirm these findings because of the pharmacoepidemiologic nature of this study.

Update on pharmacotherapy in psychodermatological disorders

Psychodermatological (PD) conditions encountered in dermatologic practice include primary psychiatric conditions such as delusions of parasitosis or secondary psychiatric conditions such as anxiety and depression due to dermatologic disease. The psychotropics include antipsychotic agents, anti-anxiety agents, antidepressants, and miscellaneous drugs such as anti convulsants. Anti psychotics are further divided into first-generation and second-generation drugs. Currently, second-generation drugs e.g., risperidone are preferred over first-generation drugs e.g., pimozide in delusional infestation owing to the side effect profile of the latter. Anti-anxiety agents include benzodiazepines used in acute anxiety and buspirone in chronic anxiety disorders. They are frequently prescribed along with antidepressants. Although dependence and necessity of tapering is a problem with benzodiazepines, delayed onset of action is a feature of buspirone. The commonly used antidepressants in dermatology include selective serotonin reuptake inhibitors (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline), selective serotonin norepinephrine reuptake inhibitors (venlafaxine, desvenlefaxine, and duloxetine), norepinephrine dopamine reuptake inhibitors (bupropion), tricyclic antidepressants (doxepin, amitriptyline, imipramine, and clomipramine), and tetracyclic antidepressants (mirtazapine). Miscellaneous drugs include anticonvulsants such as gabapentin and pregabalin, naltrexone, and N-acetyl cysteine. The principles of PD treatment are first establish the psychiatric diagnosis, followed by initiating drug treatment. The choice of drugs is dependent on multiple factors such as side-effect profile, drug interactions, and co-morbid conditions. Usually, drugs are started at a low dose and gradually increased. A literature search was done in Pubmed, Google Scholar, and Medline databases, and articles on treatment were analyzed.

Fourier Transform Infrared Spectroscopic Characterisation of Some Common Antidepressans in Pharmaceutical Preparations

The objective of this study was to analyse some common antidepressants in pharmaceutical preparations. The antidepressants taken for analysis were Selective Serotonin Reuptake Inhibitors [SSRIs]. SSRIs were associated with the significantly lower risk of toxicity, but large number of deaths from SSRIs has occurred in combination with other drugs specifically tricyclic and tetracyclic antidepressants. There has been a lot of work in the characterisation of antidepressants in pharmaceutical preparations but still a rapid and reliable positive qualitative identification of SSRIs needs to be developed. In the present investigation, Fourier Transform Infra Red [FTIR] spectrophotometer in transmission and Attenuated Total Reflectance [ATR] mode was used to qualitatively identify pharmaceutical preparation consisting of Proxetine, Sertraline, Escitalopram, Fluvoxamine. The results suggested that both the modes provided greater sensitivity but the ATR mode has great potential for the characterisation of SSRIs.

EFFECT OF FLUOXETINE ON THE STRUCTURE OF ALVEOLAR BONE IN RATS WITH DEPRESSION

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.

Pharmacotherapy of borderline personality disorder: what has changed over two decades? A retrospective evaluation of clinical practice

BackgroundThe purpose of this study was to assess the pharmacological treatment strategies of inpatients with borderline personality disorder between 2008 and 2012. Additionally, we compared pharmacotherapy during this period to a previous one (1996 to 2004).MethodsCharts of 87 patients with the main diagnosis of borderline personality disorder receiving inpatient treatment in the University Medical Center of Goettingen, Germany, between 2008 and 2012 were evaluated retrospectively. For each inpatient treatment, psychotropic drug therapy including admission and discharge medication was documented. We compared the prescription rates of the interval 2008–2012 with the interval 1996–2004.Results94% of all inpatients of the interval 2008–2012 were treated with at least one psychotropic drug at time of discharge. All classes of psychotropic drugs were applied. We found high prescription rates of naltrexone (35.6%), quetiapine (19.5%), mirtazapine (18.4%), sertraline (12.6%), and escitalopram (11.5%). Compared to 1996–2004, rates of low-potency antipsychotics, tri−/tetracyclic antidepressants and mood stabilizers significantly decreased while usage of naltrexone significantly increased.ConclusionsIn inpatient settings, pharmacotherapy is still highly prevalent in the management of BPD. Prescription strategies changed between 1996 and 2012. Quetiapine was preferred, older antidepressants and low-potency antipsychotics were avoided. Opioid antagonists are increasingly used and should be considered for further investigation.

Efficacy of Antidepressants in the Treatment of Obstructive Sleep Apnea Compared to Placebo. A Systematic Review with Meta-Analyses.

To establish the efficacy of oral antidepressants compared to placebo in improving obstructive sleep apnea (OSA) as measured on a polysomnography study. Secondary outcomes included self-reported sleepiness. Authors identified prospective randomized placebo-controlled studies from MEDLINE through PubMed, Web of Science, the Cochrane Library and EMBASE up to February 2019 in English language. Antidepressants included tricyclic antidepressants (TCA), tetracyclic antidepressants (TeCA), selective serotonin reuptake inhibitors (SSRI), and serotonin receptor modulators (SRM). Studies were assessed for inclusion and exclusion criteria, as well as risk of bias based on the Cochrane handbook. The initial search yielded 254 unduplicated references ultimately reduced to 8 relevant studies, in which 198 OSA participants were included. Patients with an average baseline AHI of 26.7 events/hour taking 15-45mg mirtazapine had a statistically significant reduction in apnea-hypopnea index compared to placebo by -10.5 events/hour (p<0.001), apnea index by -3.6 events/hour (p=0.001) and hypopnea index by -5.9 events/hour (p=0.037). In one study, patients taking 100mg trazodone 1 night improved significantly in AHI compared to placebo group (p<0.001). Arousal index, sleepiness, and sleep efficiency were not statistically significantly reduced with any antidepressant medication compared to placebo (p>0.05). Of the five antidepressant medications studied, only mirtazapine and trazadone showed a statistically significant reduction in AHI in the treated groups but not in sleepiness scale nor an increase in sleep efficiency. In this review, the total sample sizes were small, adverse side effects of some of the antidepressant medications were clinically significant, overall risk of bias of the studies was high or unclear, and overall quality of the evidence was low. Based on the evidence available at this time, we cannot recommend the antidepressants studied in the treatment of OSA.

Two-Dimensional Tandem Mass Spectrometry in a Single Scan on a Linear Quadrupole Ion Trap.

A two-dimensional tandem mass spectrometry (2D MS/MS) scan has been developed for the linear quadrupole ion trap. Precursor ions are mass-selectively excited using a nonlinear ac frequency sweep at constant rf voltage, while simultaneously, all product ions of the excited precursor ions are ejected from the ion trap using a broad-band waveform. The fragmentation time of the precursor ions correlates with the precursor m/z value (the first mass dimension) and also with the ejection time of the product ions, allowing the correlation between precursor and product ions. Additionally, the second mass dimension (product ions' m/z values) is recovered through fast Fourier transform of each mass spectral peak, revealing either intentionally introduced "frequency tags" or the product ion micropacket frequencies, both of which can be converted to product ion m/z through the classical Mathieu parameters, thereby revealing a product ion mass spectrum for every precursor ion without prior isolation. We demonstrate the utility of this method for analyzing a broad range of structurally related precursor ions, including chemical warfare agent simulants, fentanyls and other opioids, amphetamines, cathinones, antihistamines, and tetracyclic antidepressants.

Epidemiology of pharmaceutically treated depression and treatment resistant depression in South Korea.

BackgroundThe epidemiology of pharmaceutically treated depression (PTD) and treatment resistant depression (TRD) is largely unknown in South Korea. The aim of this study was to develop a greater understanding of the characteristics of PTD and TRD in nearly the entire adult population in South Korea using the Health Insurance Review and Assessment Service (HIRA).MethodDiagnostic codes and prescription data for South Korean adults were extracted from the HIRA. Subjects were included in the PTD cohort if they received at least one prescription for antidepressants and were diagnosed with depression. TRD was defined as PTD having two or more regimen failures of antidepressants or antipsychotics.ResultsIn 2012, there were 41,256,396 adults in South Korea with 834,694 meeting the criteria for PTD (2.0%). Among subjects with PTD, 57% stopped treatment in less than 28 days of antidepressant supply. Tricyclic and tetracyclic antidepressants were the most frequently used antidepressants as a first-line regimen for PTD (44.3% of PTD) followed by selective serotonin reuptake inhibitors (32.1% of PTD). Results also indicated that 34,812 subjects developed TRD (4.2% of PTD). Median PTD and TRD durations were 28 and 623 days respectively. Proportions of psychiatric and non-psychiatric comorbidities were higher in TRD cases than in PTD cases that were not treatment resistant.ConclusionsDespite a small proportion of patients with TRD, the prolonged duration of illness and higher comorbidity implies the need for better treatment.

The Effect of Cyp2d6 Gene Polymorphism on the Efficacy and Safety of Mirtazapine in Patients with Depressive Disorders Comorbid with Alcohol

Background: Alcohol dependence is often combined with affective disorders, in particular, depressive disorder, which adversely affects the prognosis of the course of both diseases. For the treatment of a depressive disorder, drugs from the group of tetracyclic antidepressants, of which mirtazapine is a representative, are used. Therapy with mirtazapine is associated with the risk of undesirable drug reactions and pharmacoresistance.&#x0D; Aim: To study the effect of CYPD6 isoenzyme activity on the efficacy and safety of mirtazapine therapy in patients with depressive disorders comorbid with alcoholism.&#x0D; Methods: The study was conducted on 109 Russian patients with a depressive disorder, comorbid with alcohol dependence. For the correction of depressive disorders within the framework of cyclothymia, mirtazapine was prescribed to patients at a dosage of 1545 mg/day. CYP2D6*4 genotyping (1846G A, rs3892097) was carried out using Real-time polymerase chain reaction with allele-specific hybridization. Efficacy and safety were assessed using validated psychometric scales and an assessment of the severity of adverse drug reactions.&#x0D; Results: By the 9th day of the study, the severity of depressive symptoms on the HAMD scale was significantly different in patients with different genotypes: (GG) 7.0 [6.0; 8.0], (GA) 4.0 [3.8; 5.0] (p0.001), safety indicator, estimated on a UKU scale: (GG) 3.0 [3.0; 3.0], (GA) 4.0 [4.0; 5.0] (p0.001). The presence of differences persisted on the 16th day: (GG) 5.0 [3.0; 6.0], (GA) 1.5 [0.8; 3.2] (p0.001), safety indicator, estimated on a UKU scale: (GG) 6.0 [6.0; 7.0], (GA) 8.5 [8.0; 10.0] (p0.001).&#x0D; Conclusion: In this study, the effect of CYP2D6 gene polymorphism on the efficacy and safety of therapy with mirtazapine was demonstrated. Carrying a minor allele A is associated with an increased risk of adverse drug reactions, but improving performance profile performance.

Antidepressants and the Risk of Hemorrhagic Stroke in the Elderly: a Nested Case–Control Study

Selective serotonin reuptake inhibitors (SSRIs) are frequently prescribed in the elderly due to a more favorable risk profile than other antidepressants (ADs). However, SSRIs are associated with an increased risk of gastrointestinal bleeding, while evidence on the risk of hemorrhagic stroke (HS) is limited. Therefore, we compared the risk of HS associated with the use of ADs in the elderly. Based on data from the German Pharmacoepidemiological Research Database (GePaRD), a case-control study matched on age, sex, and health insurance provider, nested in a cohort of incident users of ADs ≥ 65years of age was performed. Cases were identified from hospital discharge diagnoses, and exposure was identified from outpatient prescriptions. Multivariable conditional logistic regression was used to estimate adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Based on 4059 cases and 40,590 controls, an increased risk of HS was found in current use of SSRIs (OR 1.39, 95% CI 1.22-1.58), selective serotonin and noradrenaline reuptake inhibitors (1.69, 1.35-2.11), noradrenergic and specific serotonergic ADs (1.44, 1.22-1.69), and noradrenaline reuptake inhibitors (3.81, 1.54-9.43) compared with tri- and tetracyclic antidepressants. An increased risk of HS was seen in patients with a high baseline risk of bleeding and in patients with depression. The risk of HS varied between individual ADs. Our study shows that the use of medications inhibiting serotonin and/or noradrenaline reuptake increases the risk of HS in patients aged 65years and older and that the risk varies across individual ADs.

Abstract TMP44: Gender and Race/ethnic Disparities in Psychotropic Medication Prescription at Discharge Among TIA and Mild/moderate Stroke Patients in the Discharge Educational Strategies for Reduction of Vascular Events (DESERVE) Study

Depression and anxiety are common after stroke. Little is known about the factors associated with prescription of antidepressants (AD) and anti-anxiety (AA) medications post-stroke. The study used data from DESERVE, a randomized educational trial to reduce vascular risk in a multi-ethnic cohort of TIA and mild/moderate stroke patients in New York City. The study outcome was any AD or AA prescription at discharge, including selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic and tetracyclic antidepressants, norepinephrine-dopamine reuptake inhibitors, serotonin antagonist and reuptake inhibitors, anxiolytics, and benzodiazepines. Chi-square, Fisher’s exact, and Wilcoxon rank sum tests were used to examine the association between patient characteristics and AD/AA prescription. Factors associated with the outcome at p&lt;0.10 in bivariate analysis were examined using multiple logistic regression. Of the 236 patients with medication information, 21.2% were prescribed an AD or AA, most commonly SSRIs/SNRIs (82.0%) and benzodiazepines (31.4%). In the adjusted model, males (OR=0.37 95% CI: 0.16, 0.84) and Non-Hispanic black/other race patients (OR=0.08, 95% CI: 0.03, 0.24) had significantly lower odds of AD/AA prescription. Probable depression pre-discharge (Center for Epidemiologic Studies-Depression scale ≥ 16) (OR=4.11, 95% CI: 1.46, 11.55) and prior psychiatry history (OR=2.82, 95% CI: 1.02-7.83) were associated with greater odds of AD/AA prescription. Non-significant differences in AD/AA prescription were noted on the basis of stroke severity, modified Rankin scale, and Hispanic ethnicity (Table 1). Prescription of ADs/AAs at stroke discharge was common and associated with gender and race/ethnicity independent of other factors. Further research is needed to better understand disparities in post-stroke psychotropic medication prescription.