ABSTRACT
QUESTION: Tricyclic antidepressants are used to treat depression worldwide, but the adverse effects have not been systematically assessed. Our objective was to assess the beneficial and harmful effects of all tricyclic antidepressants for adults with major depressive disorder. STUDY SELECTION AND ANALYSIS: We conducted a systematic review with meta-analysis and trial sequential analysis. We searched CENTRAL, MEDLINE, Embase, LILACS and other sources from inception to January 2023 for randomised clinical trials comparing tricyclic antidepressants versus placebo or 'active placebo' for adults with major depressive disorder. The primary outcomes were depressive symptoms measured on the 17-item Hamilton Depression Rating Scale (HDRS-17), serious adverse events and quality of life. The minimal important difference was defined as three points on the HDRS-17. FINDINGS: We included 103 trials randomising 10 590 participants. All results were at high risk of bias, and the certainty of the evidence was very low or low. All trials only assessed outcomes at the end of the treatment period at a maximum of 12 weeks after randomisation. Meta-analysis and trial sequential analysis showed evidence of a beneficial effect of tricyclic antidepressants compared with placebo (mean difference -3.77 HDRS-17 points; 95% CI -5.91 to -1.63; 17 trials). Meta-analysis showed evidence of a harmful effect of tricyclic antidepressants compared with placebo on serious adverse events (OR 2.78; 95% CI 2.18 to 3.55; 35 trials), but the required information size was not reached. Only 2 out of 103 trials reported on quality of life and t-tests showed no evidence of a difference. CONCLUSIONS: The long-term effects of tricyclic antidepressants and the effects on quality of life are unknown. Short-term results suggest that tricyclic antidepressants may reduce depressive symptoms while also increasing the risks of serious adverse events, but these results were based on low and very low certainty evidence. PROSPERO REGISTRATION NUMBER: CRD42021226161.
Subject(s)
Antidepressive Agents, Tricyclic , Depressive Disorder, Major , Humans , Antidepressive Agents, Tricyclic/adverse effects , Antidepressive Agents, Tricyclic/therapeutic use , Depressive Disorder, Major/drug therapy , Adult , Quality of Life , Randomized Controlled Trials as TopicABSTRACT
BACKGROUND: There are no approved pharmacotherapies for methamphetamine use disorder. Two preliminary phase 2 randomised controlled trials have found mirtazapine, a tetracyclic antidepressant, to be effective in reducing methamphetamine use. The proposed Tina Trial is the first phase 3 placebo-controlled randomised trial to examine the effectiveness and safety of mirtazapine as an outpatient pharmacotherapy for methamphetamine use disorder. METHODS: This is a multi-site phase 3 randomised, double-blind, placebo-controlled parallel trial. Participants are randomly allocated (1:1) to receive either mirtazapine (30 mg/day for 12 weeks) or matched placebo, delivered as a take-home medication. The target population is 340 people aged 18-65 years who have moderate to severe methamphetamine use disorder. The trial is being conducted through outpatient alcohol and other drug treatment clinics in Australia. The primary outcome is measured as self-reported days of methamphetamine use in the past 4 weeks at week 12. Secondary outcomes are methamphetamine-negative oral fluid samples, depressive symptoms, sleep quality, HIV risk behaviour and quality of life. Other outcomes include safety (adverse events), tolerability, and health service use. Medication adherence is being monitored using MEMS® Smart Caps fitted to medication bottles. DISCUSSION: This trial will provide information on the safety and effectiveness of mirtazapine as a pharmacotherapy for methamphetamine use disorder when delivered as an outpatient medication in routine clinical practice. If found to be safe and effective, this trial will support an application for methamphetamine use disorder to be included as a therapeutic indication for the prescription of mirtazapine. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12622000235707. Registered on February 9, 2022.
Subject(s)
Amphetamine-Related Disorders , Clinical Trials, Phase III as Topic , Methamphetamine , Mirtazapine , Randomized Controlled Trials as Topic , Humans , Mirtazapine/therapeutic use , Double-Blind Method , Amphetamine-Related Disorders/drug therapy , Amphetamine-Related Disorders/psychology , Methamphetamine/adverse effects , Methamphetamine/administration & dosage , Adult , Middle Aged , Adolescent , Male , Young Adult , Aged , Female , Treatment Outcome , Multicenter Studies as Topic , Australia , Time Factors , Medication Adherence , Antidepressive Agents, Tricyclic/therapeutic use , Antidepressive Agents, Tricyclic/adverse effectsABSTRACT
Tianeptine is an opioid receptor agonist that is prescribed as an antidepressant in many countries. In the United States, tianeptine is not approved for medical use because of its potential for abuse and addiction. Nonetheless, products containing tianeptine are easily obtainable and are marketed as dietary supplements. There are increasing reports of adverse effects and fatal toxicities resulting from tianeptine use among adolescents and adults. This emerging public health threat could escalate the opioid epidemic and drive increased newborn perinatal exposure. The impact of in utero exposure to tianeptine has not been studied, and to our knowledge, the authors of only 1 report have documented possible neonatal effects. Here, we describe a case of chronic prenatal exposure to tianeptine in the setting of maternal dependence on dietary supplements. This infant developed signs of severe withdrawal shortly after birth that were refractory to treatment with oral phenobarbital but responded to subsequent oral morphine therapy. On further questioning, the mother revealed the use of a tianeptine-containing dietary supplement. We did not perform confirmatory toxicology testing because tianeptine is not assayed by usual urine drug screening tests. For infants with clinical signs of opioid withdrawal without known etiology, we suggest that the maternal interview should inquire about the use of neurotropic over-the-counter drugs.
Subject(s)
Neonatal Abstinence Syndrome , Thiazepines , Adult , Infant , Infant, Newborn , Pregnancy , Female , Adolescent , Humans , United States , Analgesics, Opioid/adverse effects , Antidepressive Agents, Tricyclic/adverse effects , Neonatal Abstinence Syndrome/diagnosis , Neonatal Abstinence Syndrome/etiology , Thiazepines/adverse effects , Vitamins , Dietary Supplements/adverse effectsABSTRACT
The use of antidepressants with anticholinergic effects has been associated with an increased risk of dementia. However, the results published are contradictory. The aim of the study is to compare the risk of developing dementia in elderly who were prescribed tricyclic antidepressants (TCA) versus those who were prescribed selective serotonin reuptake inhibitors (SSRIs) and other antidepressants (OA). A prospective population-based cohort study was performed using the Spanish Database for Pharmacoepidemiological Research in Primary Care (BIFAP) data (from 2005 to 2018). The cohort study included 62,928 patients age ≥ 60 without dementia and with antidepressant long-term monotherapy. Patients were divided into exposure antidepressant groups based on ATC system [TCA, SSRIs users and OAs users]. The risk of dementia was calculated by Cox regression models, providing hazard ratios (HR) and 95 % confidence intervals. The Kaplan-Meier model was used for survival analysis. Chi2 test was used as association test. The results showed SSRI users had higher dementia risk than TCA users (HR = 1.864; 95%CI = 1.624-2.140). Moreover, OA users had also significant risk of dementia (HR = 2.103; 95%CI = 1.818-2.431). Several limitations are the variation of the trend in the prescription of antidepressants, the small number of patients that use some antidepressants, the lack of information related to the dose, or socioeconomic characteristics, the use of antidepressant drugs for other indications, or the therapeutic compliance. Our findings showed that older users of SSRI and OA have more risk of developing dementia than TCA elderly users. However, additional studies would be needed.
Subject(s)
Dementia , Selective Serotonin Reuptake Inhibitors , Humans , Aged , Cohort Studies , Prospective Studies , Spain/epidemiology , Antidepressive Agents/adverse effects , Antidepressive Agents, Tricyclic/adverse effects , Dementia/chemically induced , Dementia/epidemiologyABSTRACT
Imipramine is a tricyclic antidepressant typically reserved for patients with treatment-resistant mood disorders. A rare side effect of long-term use of imipramine is a slowly progressive melanin-associated, slate gray-blue hyperpigmentation of the skin in a photo-distributed pattern. We report a case of imipramine-induced hyperpigmentation developing 50 years after initiating imipramine therapy, whose lesions were essentially devoid of melanin on histopathological exam. This differs from all other reported cases of imipramine-induced hyperpigmentation in two notable respects. First, the time between initiating imipramine therapy and the onset of pigmentation changes was nearly 30 years longer than prior case reports. Second, the lack of melanin in our samples suggests a divergence from the hypothesized melanin-imipramine complex mechanism of hyperpigmentation. Instead, we propose a novel pathogenesis of imipramine-induced hyperpigmentation that is unrelated to melanin.
Subject(s)
Hyperpigmentation , Imipramine , Humans , Imipramine/adverse effects , Melanins , Hyperpigmentation/chemically induced , Hyperpigmentation/pathology , Antidepressive Agents, Tricyclic/adverse effects , Skin/pathologyABSTRACT
Various antidepressants have introduced in clinical practice for pain management, but it is important to understand how to properly use them. We therefore performed a systematic review and network meta-analysis to compare and rank the efficacy and safety of antidepressants for patients with chronic back pain. We identified eligible randomized controlled trials (RCTs) that investigated the efficacy and safety of antidepressants for chronic back pain from PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov, searching from inception to May 2023. Six categories of antidepressants for the treatment of chronic back pain were included, and the surface under the cumulative ranking probabilities was applied to rank the treatment strategies. Overall, we selected 19 RCTs recruiting 2903 patients for the meta-analysis. Tricyclic antidepressants presented the best relative effects for relief in pain score (surface under the cumulative ranking, 84.4%). The results of pairwise comparison analyses found the use of serotonin-noradrenaline reuptake inhibitors (SNRIs) significantly reduced pain score and low disability score compared with placebo, irrespective of treatment duration. Noradrenaline-dopamine reuptake inhibitors (relative risk [RR], 2.80; 95% confidence interval [CI], 1.30-6.03; P = .008) and SNRIs (RR, 1.17; 95% CI, 1.07-1.27; P < .001) significantly increased the risk of adverse events. SNRIs were associated with an increased risk of withdrawal due to adverse events (RR, 2.37; 95% CI, 1.64-3.43; P < .001). This study found that antidepressants are more efficacious than placebos for treating chronic back pain, and tricyclic antidepressants are the most likely medications that lead to pain relief.
Subject(s)
Antidepressive Agents, Tricyclic , Serotonin and Noradrenaline Reuptake Inhibitors , Humans , Antidepressive Agents, Tricyclic/adverse effects , Network Meta-Analysis , Antidepressive Agents/adverse effects , Selective Serotonin Reuptake Inhibitors , Norepinephrine , Pain/drug therapyABSTRACT
PURPOSE: The association between antidepressant use and the risk of seizures remains controversial. Therefore, this meta-analysis examined whether antidepressant use affects the risk of seizures. METHODS: To identify relevant observational studies, we conducted systematic searches in PubMed and Embase of studies published through May 2023. Random-effects models were used to estimate overall relative risk. RESULTS: Our meta-analysis included eight studies involving 1,709,878 individuals. Our results showed that selective serotonin reuptake inhibitors (SSRI) (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.32-1.66; P < 0.001) and selective noradrenalin reuptake inhibitors (SNRI) (OR 1.65, 95% CI 1.24-2.19; P = 0.001), but not tricyclic antidepressants (TCA) (OR 1.27, 95% CI 0.84-1.92; P = 0.249), were associated with an increased risk of seizures. Subgroup analyses revealed an OR of 2.35 (95% CI 1.7, 3.24; P < 0.001) among short-term (< 30 days) antidepressant users. CONCLUSIONS: The findings of this meta-analysis support an increased risk of seizures in new-generation antidepressant users, expanding previous knowledge by demonstrating a more pronounced risk in short-term users.
Subject(s)
Antidepressive Agents , Selective Serotonin Reuptake Inhibitors , Humans , Antidepressive Agents/adverse effects , Selective Serotonin Reuptake Inhibitors/adverse effects , Seizures/chemically induced , Seizures/epidemiology , Antidepressive Agents, Tricyclic/adverse effects , RiskSubject(s)
Antidepressive Agents, Tricyclic , Intracranial Hypertension , Mirtazapine , Humans , Mirtazapine/adverse effects , Intracranial Hypertension/chemically induced , Intracranial Hypertension/diagnosis , Female , Antidepressive Agents, Tricyclic/adverse effects , Intracranial Pressure/drug effects , AdultABSTRACT
ABSTRACT: Tianeptine is an atypical antidepressant that is not approved for use in the United States and has a significant potential for abuse. In recent years, illicit use and misuse of tianeptine have become increasingly common. Symptoms caused by illicit use and withdrawal from tianeptine have become an emerging public health concern. Nurses should be aware of serious or even fatal opiate-like intoxication or withdrawal symptoms, which may present in the absence of a positive urine drug screen or in cases where withdrawal does not follow expected patterns. The associated health effects of tianeptine exposure and misuse include neurologic, cardiovascular, and gastrointestinal symptoms, which manifest in a similar manner to opioid toxicity and opioid withdrawal syndrome. People who illicitly use or misuse tianeptine should be educated regarding the risks associated with this drug. In addition, nurses should promote screening, intervention, and referral to treatment for this and other substance use disorders. Nurses should also support efforts to control access to products containing tianeptine.
Subject(s)
Substance Withdrawal Syndrome , Substance-Related Disorders , Humans , United States , Analgesics, Opioid/therapeutic use , Antidepressive Agents, Tricyclic/adverse effects , Substance-Related Disorders/drug therapy , Substance Withdrawal Syndrome/drug therapyABSTRACT
BACKGROUND: Idiosyncratic drug-induced liver injury (IDILI) is common in hepatology practices and, in some cases, lethal. Increasing evidence show that tricyclic antidepressants (TCAs) can induce IDILI in clinical applications but the underlying mechanisms are still poorly understood. METHODS: We assessed the specificity of several TCAs for NLRP3 inflammasome via MCC950 (a selective NLRP3 inhibitor) pretreatment and Nlrp3 knockout (Nlrp3-/-) BMDMs. Meanwhile, the role of NLRP3 inflammasome in the TCA nortriptyline-induced hepatotoxicity was demonstrated in Nlrp3-/- mice. RESULTS: We reported here that nortriptyline, a common TCA, induced idiosyncratic hepatotoxicity in a NLRP3 inflammasome-dependent manner in mildly inflammatory states. In parallel in vitro studies, nortriptyline triggered the inflammasome activation, which was completely blocked by Nlrp3 deficiency or MCC950 pretreatment. Furthermore, nortriptyline treatment led to mitochondrial damage and subsequent mitochondrial reactive oxygen species (mtROS) production resulting in aberrant activation of the NLRP3 inflammasome; a selective mitochondrial ROS inhibitor pretreatment dramatically abrogated nortriptyline-triggered the NLRP3 inflammasome activation. Notably, exposure to other TCAs also induced aberrant activation of the NLRP3 inflammasome by triggering upstream signaling events. CONCLUSION: Collectively, our findings revealed that the NLRP3 inflammasome may act as a crucial target for TCA agents and suggested that the core structures of TCAs may contribute to the aberrant activation of NLRP3 inflammasome induced by them, an important factor involved in the pathogenesis of TCA-induced liver injury. Video Abstract.
Subject(s)
Chemical and Drug Induced Liver Injury , Inflammasomes , Mice , Animals , NLR Family, Pyrin Domain-Containing 3 Protein , Antidepressive Agents, Tricyclic/adverse effects , Nortriptyline/adverse effects , Furans , Sulfonamides , Inflammation , Reactive Oxygen Species , Mice, Inbred C57BLSubject(s)
Hyponatremia , Mastocytosis, Systemic , Humans , Mirtazapine/therapeutic use , Hyponatremia/chemically induced , Mastocytosis, Systemic/complications , Mastocytosis, Systemic/drug therapy , Anxiety Disorders/drug therapy , Antidepressive Agents, Tricyclic/adverse effects , Mianserin/adverse effectsABSTRACT
OBJECTIVE: Antidepressant-induced pancreatitis is a rare, albeit serious, adverse effect, with a frequency of occurrence that is not equally distributed among antidepressant drugs. The goal of this study was to investigate the association and causal relationship between mirtazapine treatment of patients with depression and pancreatitis. METHODS: The study was designed as a systematic review of the literature, accompanied by the description of a new case of mirtazapine-associated acute pancreatitis. RESULTS: Nine cases of mirtazapine-associated pancreatitis have been reported, involving 7 female patients and 2 male patients with a mean age of 46.4 years (range: 26 to 83 y of age). All of the patients were hospitalized, with an average length of stay of 16.2 days (range: 3 to 34 d). In 6 cases, "de-challenge" followed by improvement was reported. The patients for whom the outcome was reported (7 of 9) recovered completely. CONCLUSION: Although a rare adverse effect, mirtazapine-induced pancreatitis should be considered when patients taking mirtazapine report abdominal discomfort.
Subject(s)
Depression , Pancreatitis , Humans , Male , Female , Middle Aged , Mirtazapine/therapeutic use , Acute Disease , Depression/drug therapy , Pancreatitis/chemically induced , Pancreatitis/drug therapy , Antidepressive Agents/adverse effects , Mianserin/adverse effects , Antidepressive Agents, Tricyclic/adverse effectsABSTRACT
PURPOSE: We aimed to examine the risk of cardiovascular adverse events by tricyclic antidepressant (TCA) dosage among patients with chronic pain. METHODS: A retrospective cohort study was conducted using a nationwide sample cohort. Among patients aged ≥ 18 years with a chronic pain diagnosis and no history of cardiovascular events, we extracted users and non-users of TCAs through 1:1 propensity score matching. TCA users were categorized into three groups according to the mean defined daily dose (DDD): very low doses (< 0.15 DDD), low doses (0.15-0.34 DDD), and traditional doses (≥ 0.34 DDD). A 6-month follow-up was conducted with an intention-to-treat approach. We examined the hazard ratio of cardiovascular adverse events using Cox proportional hazards analysis. RESULTS: In total, 16,660 matched patients were followed up (8330 TCA users and 8330 non-users). TCA use did not significantly increase cardiovascular adverse events (hazard ratio [HR] 1.12, 95% confidence interval [CI] 0.94-1.33). Low-dose (0.15-0.34 DDD) TCAs (HR 1.37, 95% CI 1.08-1.74), particularly low-dose (0.15-0.34 DDD) nortriptyline (HR 2.11, 95% CI 1.44-3.08), was associated with an increased risk of cardiovascular adverse events. Administration of TCAs at the traditional dose (≥ 0.34 DDD) increased the risk of ischemic stroke (HR 2.08, 95% CI 1.11-3.88). CONCLUSION: Close monitoring of patients on long-term, low-dose use of TCAs should be conducted to avoid an increase in the cumulative dose, which increases the risk of cardiovascular adverse events.
Subject(s)
Antidepressive Agents, Tricyclic , Chronic Pain , Humans , Antidepressive Agents, Tricyclic/adverse effects , Retrospective Studies , Chronic Pain/drug therapy , Patients , Nortriptyline/adverse effectsABSTRACT
Tricyclic antidepressants (TCAs) are frequently prescribed for chronic functional pain disorders. Although the mechanism of action targets pain perception, treating patients with TCAs for disorders conceptualized as "functional" can promote stigmatization in these patients because it hints at psychological dimensions of the disorder. The goal of this study was to understand how physicians prescribe TCAs in the face of this challenge. We interviewed eleven gastroenterologists in tertiary care clinics specializing in functional gastrointestinal disorders, such as irritable bowel syndrome. We found that the physicians interviewed (1) were aware of the stigma attached to taking antidepressants for a medical condition, (2) emphasized biological, as opposed to psychological, mechanisms of action, (3) while focusing on biological mechanisms, they nevertheless prescribed TCAs in a way that is highly attentive to the psychology of expectations, making specific efforts to adjust patients' expectations to be realistic and to reframe information that would be discouraging and (4) asked patients to persist in taking TCAs despite common and, at times, uncomfortable side effects. In this context of shared decision making, physicians described nuanced understanding and behaviours necessary for treating the complexity of functional disorders and emphasized the importance of a strong patient-provider relationship.
Subject(s)
Irritable Bowel Syndrome , Physicians , Humans , Irritable Bowel Syndrome/drug therapy , Irritable Bowel Syndrome/chemically induced , Practice Patterns, Physicians' , Antidepressive Agents/therapeutic use , Antidepressive Agents, Tricyclic/adverse effectsABSTRACT
OBJECTIVE: Antidepressants are thought to affect the risk of cardiovascular disease, although the nature of the association is unclear. Men and women have unique cardiovascular risk factors, and sex differences in depression as well as the efficacy of antidepressants are important to consider. We examined whether antidepressant use was associated with risk of having a myocardial infarction (MI) and whether this association was sex-specific. METHODS: Data from The Trøndelag Health Study were used, gathered from a population in Norway ( N = 31,765), collected from 1995 to 2008. These data were combined with the Norwegian Cause of Death Registry and the Norwegian Prescription Database. We performed logistic regression models to examine the association of antidepressant use on risk of having a fatal or nonfatal MI, adjusting for depression, anxiety, diabetes, systolic blood pressure, cholesterol, waist-hip ratio, smoking, age, and sex. Results are presented as odds ratios (ORs) and 95% confidence intervals in parentheses. RESULTS: The results indicated that antidepressant use was associated with a reduced risk of having MI at a later date (OR = 0.49 [0.38-0.64]). Although this association was somewhat stronger for women (OR = 0.46 [0.31-0.68]) compared with men (OR = 0.53 [0.37-0.75]), analysis did not identify a sex-specific association of antidepressant use on MI. Follow-up analyses on different subtypes of antidepressants showed that both selective serotonin reuptake inhibitor and tricyclic antidepressant were associated with a reduced risk of MI. CONCLUSIONS: In this population study, the use of antidepressants was associated with a reduced risk of MI. This association was stronger for women, although we detected no interaction between sex and antidepressant use in terms of reduced risk of MI. Although limitations apply regarding causality, especially concerning a dose-response relationship, the results suggest that antidepressant use might reduce the risk of MI among both men and women.
Subject(s)
Antidepressive Agents , Myocardial Infarction , Female , Humans , Male , Risk Factors , Antidepressive Agents/adverse effects , Selective Serotonin Reuptake Inhibitors , Antidepressive Agents, Tricyclic/adverse effects , Myocardial Infarction/epidemiology , Myocardial Infarction/complicationsABSTRACT
A possible tool to improve the efficacy and safety of managing elderly and senile patients with chronic pain may be the use of adjuvant analgesics, in particular, antidepressants. Available clinical data indicate the possibility of using antidepressants as an alternative to opioid analgesics and non-steroidal anti-inflammatory drugs. The review includes the analysis of the comparative characteristics and peculiarities of prescribing tricyclic antidepressants, selective serotonin and norepinephrine reuptake inhibitors, and selective serotonin reuptake inhibitors as painkillers in elderly patients. Recommendations are given on the use of various representatives of the antidepressant group in elderly patients with various types of pain, aimed at minimizing possible adverse drug reactions and improving the quality of life of this category of patients.
Subject(s)
Chronic Pain , Humans , Aged , Chronic Pain/diagnosis , Chronic Pain/drug therapy , Quality of Life , Antidepressive Agents/adverse effects , Selective Serotonin Reuptake Inhibitors/adverse effects , Antidepressive Agents, Tricyclic/adverse effectsABSTRACT
AIM: This study aims to detect the prevalence of oral manifestations in patients with psychiatric disorders on psychotropic medications. MATERIALS AND METHODS: A total of 46 patients above the age of 18 years who have been diagnosed with psychiatric illness and under psychotropic medications were included in this study. Thorough case history and oral findings were recorded. Patients with already existing systemic illness and other oral manifestations were excluded from this study. RESULTS: Out of 46 patients, 34 patients presented with oral manifestations such as xerostomia, sialorrhea, geographic tongue, candidiasis, and burning mouth syndrome, secondary to the use of psychotropic medications. The oral manifestations were significantly higher in the patients under antipsychotics (80.0%), selective serotonin reuptake inhibitor (66.7%), antiepileptics (55.6%), antidepressants (44.4%), benzodiazepine (44.4%), and tricyclic antidepressants (13.7%). CONCLUSION: The commonly used psychotropic medications to treat patients with psychiatric illnesses such as selective serotonin reuptake inhibitor, tricyclic antidepressants, antidepressants, and benzodiazepines exhibited several oral manifestations. However, long-term use of these medications seems to cause oral changes. CLINICAL SIGNIFICANCE: Awareness among psychiatrists about oral changes associated with the use of psychotropic medication will assist them to make necessary modifications in the prescriptions. Dental practitioners will be able to recognize these changes early in the course of the condition and provide appropriate treatment.
Subject(s)
Antidepressive Agents, Tricyclic , Selective Serotonin Reuptake Inhibitors , Adolescent , Antidepressive Agents/adverse effects , Antidepressive Agents, Tricyclic/adverse effects , Dentists , Humans , Mouth , Professional Role , Psychotropic Drugs/adverse effectsABSTRACT
BACKGROUND: Falls are common in older adults and increase in recent years. This study aimed to examine the risk of falls associated with long-acting benzodiazepines (BZDs) or tricyclic antidepressants (TCAs) use in community-dwelling older adults. METHODS: A nationwide population-based case-crossover design was used. We screened information on 6,370,275 fall or fall fracture cases among community-dwelling elderly patients from the database of the national health insurance data warehouse in South Korea. We extracted the data of elderly patients who visited the hospital for a fall and were diagnosed with the first fall or fall fracture after prescription of long-acting BZDs (n = 1805) or TCAs (n = 554). The study used conditional logistic regression analysis to analyze the associations and stratified analysis by gender and age group to control for their confounding effects. RESULTS: Risk of falls or fall fractures increased by more than two times after taking long-acting BZDs (odds ratio [OR] = 2.16; 95% confidence interval [CI] = 1.85-2.52) or TCAs (OR = 2.13; 95% CI = 1.62-2.83). The longer the prescription period of both, the higher the risk of falls or fall fractures was (≥49 days for long-acting BZDs vs. ≥ 56 days for TCAs). CONCLUSIONS: Long-acting BZDs or TCAs should be avoided or prescribed for a shorter duration based on these adverse effects. Health care providers should focus on fall prevention practices in older adults who take such drugs.
Subject(s)
Accidental Falls , Fractures, Bone , Accidental Falls/prevention & control , Aged , Antidepressive Agents, Tricyclic/adverse effects , Benzodiazepines/adverse effects , Cross-Over Studies , Humans , Independent LivingABSTRACT
BACKGROUND: Animal data suggest that the antidepressant and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor modulator tianeptine is able to prevent opioid-induced respiratory depression. The hypothesis was that oral or intravenous tianeptine can effectively prevent or counteract opioid-induced respiratory depression in humans. METHODS: Healthy male and female volunteers participated in two studies that had a randomized, double blind, placebo-controlled, crossover design. First, oral tianeptine (37.5-, 50-, and 100-mg doses with 8 subjects) pretreatment followed by induction of alfentanil-induced respiratory depression (alfentanil target concentration, 100 ng/ml) was tested. Primary endpoint was ventilation at an extrapolated end-tidal carbon dioxide concentration of 55 mmHg (VÌE55). Next, the ability of four subsequent and increasing infusions of intravenous tianeptine (target tianeptine plasma concentrations 400, 1,000, 1,500, and 2,000 ng/ml, each given over 15 min) to counteract remifentanil-induced respiratory depression was determined in 15 volunteers. Ventilation was measured at isohypercpania (baseline ventilation 20 ± 2 l/min). The primary endpoint was minute ventilation during the 60 min of tianeptine versus placebo infusion. RESULTS: Alfentanil reduced VÌE55 to 13.7 (95% CI, 8.6 to 18.8) l/min after placebo pretreatment and to 17.9 (10.2 to 25.7) l/min after 50-mg tianeptine pretreatment (mean difference between treatments 4.2 (-11.5 to 3.0) l/min, P = 0.070). Intravenous tianeptine in the measured concentration range of 500 to 2,000 ng/ml did not stimulate ventilation but instead worsened remifentanil-induced respiratory depression: tianeptine, 9.6 ± 0.8 l/min versus placebo 15.0 ± 0.9 l/min; mean difference, 5.3 l/min; 95% CI, 2.5 to 8.2 l/min; P = 0.001, after 1 h of treatment. CONCLUSIONS: Neither oral nor intravenous tianeptine were respiratory stimulants. Intravenous tianeptine over the concentration range of 500 to 2000 ng/ml worsened respiratory depression induced by remifentanil.