Mirtazapine Improves Locomotor Activity and Attenuates Neuropathic Pain Following Spinal Cord Injury in Rats via Neuroinflammation Modulation.

Neuroinflammation-related locomotor deficits and neuropathic pain are expected outcomes of spinal cord injury (SCI). The atypical antidepressant mirtazapine has exhibited potential neuroprotective and anti-inflammatory effects. This research aims to investigate the impacts of mirtazapine on post-SCI neuropathic pain and locomotor recovery, with a particular focus on neuroinflammation. The study utilized 30 male Wistar rats divided into five groups: Sham, SCI with vehicle treatment, and SCI administered with mirtazapine (3, 10, and 30 mg/kg/day, ip, for one week). Locomotor activity was assessed using the Basso, Beattie, and Bresnahan (BBB) scale. Mechanical, thermal, and cold allodynia were assessed using von-Frey filaments, tail flick latency, and the acetone test, respectively. ELISA was utilized to measure cytokines, while Western blotting was used to determine TRPV1 channel, 5-HT2A receptor, NLRP3, and iNOS expression. Histopathological analyses were also examined, including hematoxylin and eosin (H&E) and Luxol fast blue (LFB) staining. Mirtazapine (10 and 30 mg/kg/day) significantly improved locomotor recovery according to BBB score. It attenuated mechanical, thermal, and cold allodynia post-SCI. Moreover, it decreased pro-inflammatory cytokines TNF-α, IL-1ß, IL-6, and IL-18, while increasing anti-inflammatory cytokine IL-4 and IL-10. Furthermore, it downregulated iNOS, NLRP3, and TRPV1 expression and upregulated the 5-HT2A receptor. H&E and LFB staining further revealed attenuated tissue damage and decreased demyelination. Our findings suggest that mirtazapine can alleviate neuropathic pain and reinforce locomotor recovery post-SCI by modulating neuroinflammatory responses, NLRP3, iNOS, TRPV1 channel, and 5-HT2A receptor expression.

Edema related to treatment with psychotropic drugs.

Edema as an adverse drug reaction is a commonly underestimated yet potentially debilitating condition. This study analyzes the incidence of severe psychotropic drug-induced edema (e.g., edema affecting the face, legs, or multiple body parts and lasting for more than 1 week, or in any case necessitating subsequent diuretic use) among psychiatric inpatients. The cases under examination are derived from an observational pharmacovigilance program conducted in German-speaking countries ("Arzneimittelsicherheit in der Psychiatrie", AMSP) from 1993 to 2016. Among the 462,661 inpatients monitored, severe edema was reported in 231 cases, resulting in an incidence of 0.05%. Edema occurred more frequently in women (80% of all cases) and older patients (mean age 51.8 years). Pregabalin had the highest incidence of severe edema, affecting 1.46‰ of patients treated with pregabalin, followed by mirtazapine (0.8‰). The majority of edema cases showed a positive response to appropriate countermeasures, such as dose reduction and drug discontinuation, and resolved by the end of the observation period. While most instances of drug-induced edema are reversible, they can have a significant impact on patient well-being and potentially result in decreased treatment adherence. It is, therefore, crucial to remain vigilant regarding risk-increasing circumstances during treatment with psychotropic drugs.

Mirtazapine in pregnancy and lactation: A systematic review of adverse outcomes.

INTRODUCTION: Peripartum depression is common and treatment with mirtazapine may be indicated. However, evidence on its safety in pregnancy and lactation is fragmented. The objective of this systematic review was to evaluate the literature on the safety of mirtazapine in pregnancy and lactation. METHODS: PubMed, Embase, Medline, PsycInfo, and clinicaltrials.gov were searched for 'antidepressants' or 'mirtazapine' in combination with 'pregnancy', 'lactation' or 'offspring'. No restrictions on type of study were applied and selection was performed by two independent reviewers using Covidence. Two reviewers extracted data and performed risk of bias assessment and evidence synthesis was performed for each outcome individually. The protocol was registered at PROSPERO (registration number CRD42021275127). RESULTS: The initial search yielded 15,380 articles after removal of duplicates. After screening based on title and abstract, 431 articles remained for full text review. Of these, 41 studies were included (15 cohort studies, one case-control study, 11 case series, and 14 case reports). In most studies, the outcomes in mirtazapine-exposed pregnancies were comparable to controls. However, results on congenital malformations and spontaneous abortion were conflicting. Neonatal adaptation syndrome was reported after mirtazapine exposure in late pregnancy. Data on mirtazapine exposure during lactation were scarce. CONCLUSIONS: We identified no substantial evidence indicating that mirtazapine exposure is associated with adverse outcomes in pregnancy or in offspring, other than neonatal adaptation syndrome. However, overall quality of evidence was low, and results on congenital malformations and spontaneous abortions were conflicting. Data on mirtazapine exposure through breastfeeding were limited and did not allow for conclusions.

Presynaptic Adrenoceptors.

Presynaptic α2-adrenoceptors are localized on axon terminals of many noradrenergic and non-noradrenergic neurons in the peripheral and central nervous systems. Their activation by exogenous agonists leads to inhibition of the exocytotic release of noradrenaline and other transmitters from the neurons. Most often, the α2A-receptor subtype is involved in this inhibition. The chain of molecular events between receptor occupation and inhibition of the exocytotic release of transmitters has been determined. Physiologically released endogenous noradrenaline elicits retrograde autoinhibition of its own release. Some clonidine-like α2-receptor agonists have been used to treat hypertension. Dexmedetomidine is used for prolonged sedation in the intensive care; It also has a strong analgesic effect. The α2-receptor antagonist mirtazapine increases the noradrenaline concentration in the synaptic cleft by interrupting physiological autoinhibion of release. It belongs to the most effective antidepressive drugs. ß2-Adrenoceptors are also localized on axon terminals in the peripheral and central nervous systems. Their activation leads to enhanced transmitter release, however, they are not activated by endogenous adrenaline.

Formulation, optimization and full characterization of mirtazapine loaded aquasomes: a new technique to boost antidepressant effects.

OBJECTIVE: The development of Mirtazapine (MRT)-loaded aquasomes by co-precipitation sonication technique to boost the antidepressant potential of MRT. METHODOLOGY: MRT-loaded aquasomes formulations were prepared using Box-Behnken design to investigate the effect of independent factors including sonication time (X1), sonication temperature (X2), and sugar concentration (X3) on the dependent variables as particle size and drug loading efficiency. The formulation of the optimized formula was verified by Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and X-ray Powder Diffraction (XRPD). Furthermore, the morphology of the formula was evaluated by Transmission Electron Microscopy (TEM). The optimum MRT- loaded aquasomes was assessed for physiochemical properties, in vitro MRT release and in vivo antidepressant effects in mice model. RESULTS: The results revealed that the optimized formula showed a small particle size of 202.7 ± 3.7 nm and a high loading efficiency of 77.65 ± 2.6%. Thermal DSC and XRPD studies demonstrated the amorphous nature of MRT-loaded aquasomes. The in vitro study demonstrated sustained release of F (opt) 88.16% after 8 h, compared with plain MRT release of 63.06% after 1 h. Mice treated with MRT-loaded aquasomes demonstrated reduced immobility time in behavioral analysis to 37% with MRT-loaded aquasomes, while plain MRT reduced it to 55%. CONCLUSION: These results confirmed that the antidepressant effect of MRT was significantly boosted in formulated aquasomes, and thereby they provide a promising carrier nano vesicular system for effective delivery of MRT.

Development of a novel direct compressible co-processed excipient and its application for formulation of Mirtazapine orally disintegrating tablets.

INTRODUCTION: Orally disintegrating tablets (ODTs) are designed to dissolve in the oral cavity within 3 min, providing a convenient option for patients as they can be taken without water. Direct compression is the most common method used for ODTs formulations. However, the availability of single composite excipients with desirable characteristics such as good compressibility, fast disintegration, and a good mouthfeel suitable for direct compression is limited. OBJECTIVE: This research was proposed to develop a co-processed excipient composed of xylitol, mannitol, and microcrystalline cellulose for the formulation of ODTs. METHODS: A total of 11 formulations of co-processed excipients with different ratios of ingredients were prepared, which were then compressed into ODTs, and their characteristics were thoroughly examined. The primary focus was on evaluating the disintegration time and hardness of the tablets, as these factors are important in ensuring the ODTs meet the desired criteria. The model drug, Mirtazapine was then incorporated into the chosen optimized formulation. RESULTS: The results showed that the formulation comprised of 10% xylitol, 10% mannitol and 80% microcrystalline cellulose demonstrated the fastest disintegration time (1.77 ± 0.119 min) and sufficient hardness (3.521 ± 0.143 kg) compared to the other formulations. Furthermore, the drug was uniformly distributed within the tablets and fully released within 15 min. CONCLUSION: Therefore, the developed co-processed excipients show great potential in enhancing the functionalities of ODTs, offering a promising solution to improve the overall performance and usability of ODTs in various therapeutic applications.

Progressive multifocal leukoencephalopathy with a benign prognosis in an immunocompetent patient - A case report.

John Cunningham virus (JCV) is most commonly acquired in childhood and is often asymptomatic throughout life. However, in the case of primary or secondary immunosuppression, it is known to cause progressive multifocal leukoencephalopathy (PML) in the central nervous system. Hereby, we describe a rare case of PML in a patient without known factors of immunosuppression or use of immunomodulation. A 53-year-old female patient was presented with progressive left-side weakness and tremors in the left hand over a period of two months. The patient was diagnosed with PML based on history, examination, cerebrospinal fluid markers, histopathology, and brain magnetic resonance imaging at presentation. Despite detailed examination, nothing was found in the patient to cause an immunosuppressed state. Therapy was started with mirtazapine with significant neurological improvement.To our knowledge, PML in immunocompetent patient with bening prognosis is a very rare condition. There is also no effective treatment. Our case is a complicated example of this condition.

Mirtazapine Therapy for a Patient With Weight Loss and Gastroparesis Associated With Limited Systemic Sclerosis.

Objective: Gastroparesis may be present in individuals with systemic sclerosis. In the United States, metoclopramide is the only medication approved for treating gastroparesis. Our case involves using mirtazapine therapy to help with weight loss and gastroparesis associated with systemic sclerosis. Case: A 70-year-old female with limited systemic sclerosis and sicca syndrome began experiencing weight loss, dysphagia, nausea, and abdominal fullness. Neither an esophageal dilation procedure nor six weeks of metoclopramide therapy alleviated her symptoms. However, 15 mg of mirtazapine once daily provided some symptomatic relief. A gastric emptying scan confirmed gastroparesis. The dose of mirtazapine was later increased to 30 mg once daily. With the mirtazapine therapy, the patient experienced both symptomatic improvement and weight gain benefits. Discussion/Conclusion: Mirtazapine therapy has anti depressive, appetite stimulating, anti-emetic, and prokinetic benefits. Consideration of mirtazapine therapy for patients with weight loss and gastroparesis associated with systemic sclerosis may be beneficial.

Successful treatment of HIV-associated progressive multifocal leukoencephalopathy (PML) with mirtazapine, mefloquine, and IVIG combination therapy: a case report.

Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease of the central nervous system caused by reactivation of the polyomavirus JC (JCV). Human immunodeficiency virus (HIV) infection is one of the leading causes of PML which has high morbidity and mortality due to the lack of a proven standard treatment. We found clinical and radiological improvement with the combination of high-dose methylprednisolone, mirtazapine, mefloquine, and IVIG in our patient who presented with neurological symptoms and had diagnosed concurrent acquired immunodeficiency syndrome (AIDS) and PML. To our knowledge, our case is the first HIV-associated PML which responded to this combination therapy.

Atypical antidepressant mirtazapine inhibits 5-hydroxytryptamine3 receptor currents in NCB-20 cells.

Mirtazapine, an atypical antidepressant, is known to enhance serotonergic transmission by inhibiting the 5-hydroxytryptamine (5-HT)1A, 5-HT2C, and 5-HT3 receptors. However, the mechanism of action on the 5-HT3 receptor remains unclear. We investigated the inhibitory mechanisms of mirtazapine on 5-HT3 receptors of NCB20 neuroblastoma cells using the whole-cell voltage-clamp method. Mirtazapine inhibited the 5-HT3 receptor currents in a concentration-dependent manner, and the inhibitory effect was influenced by the concentration of 5-HT. When mirtazapine was co-applied to 5-HT, the maximal response of the 5-HT3 receptor current was reduced and EC50 was increased, suggesting that mirtazapine might act as a non-competitive inhibitor. Inhibition of 5-HT3 current by mirtazapine was stronger in pre-application than in co-application, which suggests that mirtazapine might act as a closed state inhibitor. This finding was further supported by no use-dependency of the mirtazapine for 5-HT3 receptor inhibition. Finally, mirtazapine accelerated the desensitization and deactivation process in a concentration-dependent manner. The difference in recovery time showed that mirtazapine drastically influences the desensitization process than the deactivation process. These mechanistic characteristics of mirtazapine support the understanding of the relationship between the 5-HT3 receptor and atypical antidepressants.

Usefulness of mirtazapine and SSRIs in late-life depression: post hoc analysis of the GUNDAM study.

OBJECTIVE: Mirtazapine and SSRIs are widely prescribed as first-line agents for late-life depression. However, evidence for these drugs is mostly based on non-elderly patients. Therefore, we reanalyzed a randomized controlled trial of mirtazapine versus SSRIs for depression in a sub-population of late-life patients. METHODS: A randomized controlled trial was conducted with 141 patients, of whom 41 were elderly, and 100 were non-elderly. This study compared SSRIs and mirtazapine in late-life depression, examined late-onset and early adult-onset separately and compared elderly and non-elderly patients for each drug. Treatment effects and adverse events were assessed using the Hamilton Depression Rating Scale and the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale, respectively. RESULTS: In late-life depression, mirtazapine showed faster HAM-D total score improvement (3.3 points difference, p = 0.021) and higher improvement in insomnia (1.7 points difference, p = 0.001) and appetite (1.2 points difference, p = 0.020). Similar findings were observed for late-onset depression with the HAM-D total score (4.3 points difference, p = 0.007) and appetite (0.9 points difference, p = 0.004), favoring mirtazapine. Depressive symptoms were generally less improved in late-life depression than in non-late-life depression. Regarding the effect of mirtazapine on appetite, late-life depression showed greater improvement (0.7 points difference, p = 0.008). Nausea and micturition disturbances were more common with SSRIs in late-life depression than in non-late-life depression. In contrast, somnolence was less common in late-life depression with mirtazapine. CONCLUSION: The potential usefulness of mirtazapine in elderly patients was demonstrated. The results also showed differences in the treatment response to SSRIs and mirtazapine between elderly and non-elderly patients.

Environmentally relevant concentrations of antidepressant mirtazapine impair the neurodevelopment of zebrafish (Danio rerio).

Mirtazapine is a commonly prescribed antidepressant and has been found widespread in aquatic environments. However, its toxicities to aquatic organisms has rarely been explored. Herein, we conducted a comprehensive study on the developmental effects of mirtazapine on early life stages of zebrafish at environmentally relevant concentrations (3.9 ng/L and 43.5 ng/L). Out of the endpoints measured, spontaneous contraction of embryos at 24 h post fertilization (hpf) and hatching rate and heart rate of embryos at 50 hpf and 56 hpf, respectively, were significantly affected. In light-dark transition behavior test, mirtazapine significantly reduced the swimming frequency and swimming speed of embryos at both concentrations of 3.9 ng/L and 43.5 ng/L. Furthermore, the total swimming distances in dark conditions were also significantly reduced. Transcriptomic analysis was further conducted. It demonstrated that the decreased neural activities in embryos may be associated with altered epinephrine and neuregulin signaling. The present results fill a data gap regarding the exposure of fish to mirtazapine at environmentally relevant concentrations and provide new insights into the neurotoxic mechanisms of mirtazapine exposure.

Changes in Multiple microRNA Levels with Antidepressant Treatment Are Associated with Remission and Interact with Key Pathways: A Comprehensive microRNA Analysis.

Individual treatment outcomes to antidepressants varies widely, yet the determinants to this difference remain elusive. MicroRNA (miRNA) gene expression regulation in major depressive disorder (MDD) has attracted interest as a biomarker. This 4-week randomized controlled trial examined changes in the plasma miRNAs that correlated with the treatment outcomes of mirtazapine (MIR) and selective serotonin reuptake inhibitor (SSRI) monotherapy. Pre- and post- treatment, we comprehensively analyzed the miRNA levels in MDD patients, and identified the gene pathways linked to these miRNAs in 46 patients. Overall, 141 miRNA levels significantly demonstrated correlations with treatment remission after 4 weeks of MIR, with miR-1237-5p showing the most robust and significant correlation after Bonferroni correction. These 141 miRNAs displayed a negative correlation with remission, indicating a decreasing trend. These miRNAs were associated with 15 pathways, including TGF-ß and MAPK. Through database searches, the genes targeted by these miRNAs with the identified pathways were compared, and it was found that MAPK1, IGF1, IGF1R, and BRAF matched. Alterations in specific miRNAs levels before and after MIR treatment correlated with remission. The miRNAs mentioned in this study have not been previously reported. No other studies have investigated treatment with MIR. The identified miRNAs also correlated with depression-related genes and pathways.

Treatment-Resistant Depression (TRD): Is the Opioid System Involved?

About 30% of major depression disorder patients fail to achieve remission, hence being diagnosed with treatment-resistant major depression (TRD). Opium had been largely used effectively to treat depression for centuries, but when other medications were introduced, its use was discounted due to addiction and other hazards. In a series of previous studies, we evaluated the antinociceptive effects of eight antidepressant medications and their interaction with the opioid system. Mice were tested with a hotplate or tail-flick after being injected with different doses of mianserin, mirtazapine, trazodone, venlafaxine, reboxetine, moclobemide, fluoxetine, or fluvoxamine to determine the effect of each drug in eliciting antinociception. When naloxone inhibited the antinociceptive effect, we further examined the effect of the specific opioid antagonists of each antidepressant drug. Mianserin and mirtazapine (separately) induced dose-dependent antinociception, each one yielding a biphasic dose-response curve, and they were antagonized by naloxone. Trazodone and venlafaxine (separately) induced a dose-dependent antinociceptive effect, antagonized by naloxone. Reboxetine induced a weak antinociceptive effect with no significant opioid involvement, while moclobemide, fluoxetine, and fluvoxamine had no opioid-involved antinociceptive effects. Controlled clinical studies are needed to establish the efficacy of the augmentation of opiate antidepressants in persons with treatment-resistant depression and the optimal dosage of drugs prescribed.

Mirtazapine attenuated cadmium-induced neuronal intoxication by regulating Nrf2 and NF-κB/TLR4 signals.

Cadmium (Cd) is one of the most hazardous metals to the environment and human health. Neurotoxicity is of the most serious hazards caused by Cd. Mirtazapine (MZP) is a central presynaptic α2 receptor antagonist used effectively in treating several neurological disorders. This study investigated the anti-inflammatory and antioxidant activity of MZP against Cd-induced neurotoxicity. In this study, rats were randomly divided into five groups: control, MZP (30 mg/kg), Cd (6.5 mg/kg/day; i.p), Cd + MZP (15 mg/kg), and Cd + MZP (30 mg/kg). Histopathological examination, oxidative stress biomarkers, inflammatory cytokines, and the impact of Nrf2 and NF-κB/TLR4 signals were assessed in our study. Compared to Cd control rats, MZP attenuated histological abrasions in the cerebral cortex and CA1 and CA3 regions of the hippocampus as well as the dentate gyrus. MZP attenuated oxidative injury by upregulating Nrf2. In addition, MZP suppressed the inflammatory response by decreasing TNF-α, IL-1ß, and IL-6 mediated by downregulating TLR4 and NF-κB. It is noteworthy that MZP's neuroprotective actions were dose-dependent. Collectively, MZP is a promising therapeutic strategy for attenuating Cd-induced neurotoxicity by regulating Nrf2, and NF-κB/TLR4 signals, pending further study in clinical settings.

Sertraline with desvenlafaxine and sertraline with mirtazapine as treatment initiation in MDD patients with moderate to severe depression and effect on inflammatory markers.

BACKGROUND: This study evaluated the effect of sertraline with desvenlafaxine and sertraline with mirtazapine on HAM-D score and inflammatory markers (IL-6 and TNF-α levels) in major depressive disorder. METHODS: Patients (18-60 years) with MDD diagnosed by DSM-V criteria and HAM-D score 18 or more were included (n = 60). Group A patients (n = 30) received sertraline 50 mg/day and desvenlafaxine 50 mg/day. Group B patients (n = 30) received sertraline 50 mg/day and mirtazapine 30 mg/day. All patients were followed up for 8 weeks for the evaluation of clinical efficacy, safety, serum IL-6, and TNF-α levels. RESULTS: Our study showed a comparatively similar and statistically significant (p < 0.05) reduction in HAM-D score in both groups in the 4th and 8th week of the treatment. Both drug combinations significantly (p < 0.05) decreased serum IL-6 and TNF-α after 8 weeks of treatment. CONCLUSION: The present study suggests that the combination therapy (as treatment initiation) with sertraline and desvenlafaxine, and sertraline with mirtazapine is effective and well tolerated in MDD patients with moderate to severe depression, and their therapeutic efficacy is accompanied by decreased inflammatory markers (serum IL-6 and TNF-α).

Recent evidence indicates that combination therapy of antidepressant drugs started as treatment initiation produces superior treatment outcomes in patients of MDD with moderate to severe depression.MDD is associated with increased inflammatory markers.Combination therapy of sertraline with desvenlafaxine and sertraline with mirtazapine as treatment initiation is effective and well tolerated in MDD patients.The therapeutic efficacy of sertraline with desvenlafaxine and sertraline with mirtazapine is associated with a significant decrease in serum levels of IL-6 and TNF-α.

The risk of all-cause and cause-specific mortality in people prescribed mirtazapine: an active comparator cohort study using electronic health records.

BACKGROUND: Studies have reported an increased risk of mortality among people prescribed mirtazapine compared to other antidepressants. The study aimed to compare all-cause and cause-specific mortality between adults prescribed mirtazapine or other second-line antidepressants. METHODS: This cohort study used English primary care electronic medical records, hospital admission records, and mortality data from the Clinical Practice Research Datalink (CPRD), for the period 01 January 2005 to 30 November 2018. It included people aged 18-99 years with depression first prescribed a selective serotonin reuptake inhibitor (SSRI) and then prescribed mirtazapine (5081), a different SSRI (15,032), amitriptyline (3905), or venlafaxine (1580). Follow-up was from starting to stopping the second antidepressant, with a 6-month wash-out window, censoring at the end of CPRD follow-up or 30 November 2018. Age-sex standardised rates of all-cause mortality and death due to circulatory system disease, cancer, or respiratory system disease were calculated. Survival analyses were performed, accounting for baseline characteristics using inverse probability of treatment weighting. RESULTS: The cohort contained 25,598 people (median age 41 years). The mirtazapine group had the highest standardised mortality rate, with an additional 7.8 (95% confidence interval (CI) 5.9-9.7) deaths/1000 person-years compared to the SSRI group. Within 2 years of follow-up, the risk of all-cause mortality was statistically significantly higher in the mirtazapine group than in the SSRI group (weighted hazard ratio (HR) 1.62, 95% CI 1.28-2.06). No significant difference was found between the mirtazapine group and the amitriptyline (HR 1.18, 95% CI 0.85-1.63) or venlafaxine (HR 1.11, 95% CI 0.60-2.05) groups. After 2 years, the risk was significantly higher in the mirtazapine group compared to the SSRI (HR 1.51, 95% CI 1.04-2.19), amitriptyline (HR 2.59, 95% CI 1.38-4.86), and venlafaxine (HR 2.35, 95% CI 1.02-5.44) groups. The risks of death due to cancer (HR 1.74, 95% CI 1.06-2.85) and respiratory system disease (HR 1.72, 95% CI 1.07-2.77) were significantly higher in the mirtazapine than in the SSRI group. CONCLUSIONS: Mortality was higher in people prescribed mirtazapine than people prescribed a second SSRI, possibly reflecting residual differences in other risk factors between the groups. Identifying these potential health risks when prescribing mirtazapine may help reduce the risk of mortality.

Mirtazapine use may increase the risk of hypothyroxinaemia in patients affected by major depressive disorder.

AIMS: Hypothyroxinaemia could be easily neglected if attention is paid only to patients with elevated thyroid-stimulating hormone. We aimed to assess the association between mirtazapine use and hypothyroxinaemia in patients affected by major depressive disorder. METHODS: We conducted a retrospective cohort study in the Second Affiliated Hospital of Xinxiang Medical University between January 2016 and December 2018. Patients affected by major depression disorder and admitted to the hospital for treatment during the study period and who had thyroid tests at admission and after treatment were included. Mirtazapine use during hospitalization was the exposure measure and newly developed hypothyroxinaemia was as the primary outcome and structure parameters of thyroid homeostasis were the secondary outcomes of this study. Log-binomial model was used to estimate the association between mirtazapine use and hypothyroxinaemia, after adjusting for potential confounding factors. RESULTS: A total of 220 eligible patients were included in the final analysis. The incidence of hypothyroxinaemia in patients who used mirtazapine was higher (37.5%) than those patients who did not use (19.7%). The relative risk of developing hypothyroxinaemia was 1.70 (95% confidence interval: 1.21-2.43) for mirtazapine use, after adjusting for confounding factors. The degree of reduction in thyroid feedback quantile-based index in mirtazapine group was significantly greater than that in nonmirtazapine group. CONCLUSION: Mirtazapine use was associated with the increased risk of developing hypothyroxinaemia. The underlying mechanism may be involved the changed central set point of thyroid homeostasis, in which pituitary was in a possibly impaired sensitivity to the lower level of thyroid hormones.

Mirtazapine exposure in pregnancy and fetal safety: A nationwide cohort study.

OBJECTIVE: To investigate the association between mirtazapine exposure in pregnancy and risk of specific adverse pregnancy outcomes. METHODS: A register-based nationwide cohort study was conducted including all registered pregnancies in Denmark from 1997 to 2016. Mirtazapine-exposed pregnancies were compared with mirtazapine unexposed pregnancies in a 1:4 ratio matched according to propensity scores. Outcomes were major congenital malformations analyzed using log binomial models, and spontaneous abortion, stillbirth and neonatal death analyzed using Cox proportional hazard regression. RESULTS: From a source population of 1,650,649 pregnancies, the propensity score-matched cohort included 4475 pregnancies (895 mirtazapine exposed) in the analysis of major congenital malformations. The analyses of spontaneous abortion included 9 500 pregnancies (1900 mirtazapine exposed), and for the analyses of stillbirths and neonatal deaths 9725 (1 945 mirtazapine-exposed) and 4485 pregnancies (897 mirtazapine-exposed) were included, respectively. Thirty-one (3.5%) children were diagnosed with major congenital malformation among the mirtazapine exposed compared with 152 (4.3%) among the unexposed pregnancies (OR=0.81, 95% CI 0.55-1.20). Spontaneous abortion occurred in 237 (12.5%) of the mirtazapine exposed compared with 931 (12.3%) of the unexposed pregnancies (HR = 1.04%, 95% CI 0.91-1.20). The analyses revealed no increased risk of stillbirth (HR = 0.88%, 95% CI 0.34-2.29) or neonatal death (HR = 0.60%, 95% CI 0.18-2.02). CONCLUSIONS: In this nationwide Danish register study, mirtazapine exposure in pregnancy was not associated with major congenital malformations, spontaneous abortion, stillbirth, or neonatal death. Clinicians and patients can be reassured that mirtazapine is safe in pregnancy.

JC virus-induced progressive multifocal leukoencephalopathy in a presumably healthy patient.

BACKGROUND: JC virus (JCV) is common among healthy individuals and remains latent but may be reactivated under immunosuppressive conditions, resulting in progressive multifocal leukoencephalopathy (PML). Here, we present a rare case of PML caused by JC virus infection in a previously healthy and immunocompetent patient. CASE PRESENTATION: A 67-year-old female without any disease history was admitted after presenting with rapidly progressive dementia. The preoperative diagnosis was progressive multifocal leukoencephalopathy, and corticosteroid treatment did not improve the symptoms. Brain lesions were surgically sampled, and JCV infection was confirmed by high-throughput DNA gene detection. This patient received a combined treatment of mirtazapine, mefloquine, and traditional Chinese herbs, and had stabilization of the disease on followed-up. CONCLUSIONS: Although it is a rare, this case demonstrates that JC virus infection within the brain occurs in apparently healthy people. This case may increase our understanding of virus infection when facing the coronavirus epidemic in recent years, considering that similar medications were used.