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JAMA Oncology Mar 2024Currently there is no standard therapy to improve cancer-related anorexia, hampering survival. Mirtazapine has been suggested as a feasible option in this context. (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Currently there is no standard therapy to improve cancer-related anorexia, hampering survival. Mirtazapine has been suggested as a feasible option in this context.
OBJECTIVES
To assess the effect of mirtazapine on appetite and energy consumption in patients with advanced non-small cell lung cancer (NSCLC).
DESIGN, SETTING, AND PARTICIPANTS
This randomized, double-blind, placebo-controlled clinical trial including adults was performed in a tertiary cancer care center from August 2018 to May 2022 with a follow-up of 8 weeks. Overall, 134 patients were screened; 114 were assessed for eligibility and 28 were excluded.
INTERVENTIONS
Patients were randomized in a 1:1 ratio to receive mirtazapine, 15 mg, or placebo for 2 weeks followed by a dose escalation to 30 mg until week 8 or placebo. Both groups received nutritional assessment and dietary advice.
MAIN OUTCOMES AND MEASURES
Appetite was assessed by the Anorexia Cachexia Scale and energy intake. Dietary parameters were evaluated at baseline, 4 weeks, and 8 weeks, with a 24-hour dietary recall, and energy quantification based on the Mexican system of nutritional equivalents.
RESULTS
A total of 86 patients met the inclusion criteria and were randomized to the placebo (n = 43) or the mirtazapine group (n = 43). The mean (SD) age was 63.5 (11.2) years, 41 were women (57.7%) and had adenocarcinoma, Eastern Cooperative Oncology Group performance status scale score of 1, stage IV NSCLC, and were receiving first-line treatment. Baseline characteristics were similar between groups. There was no difference in appetite scores in patients who received mirtazapine or placebo after 4 and 8 weeks. After 4 weeks, mirtazapine significantly increased energy intake (379.3 kcal; 95% CI, 1382.6-576.1; P < .001) including proteins (22.5 g; 95% CI, 11.5-33.4; P = .001), carbohydrates (43.4 g; 95% CI, 13.1-73.8; P = .006), and fats (13.2 g; 95% CI, 6.0-20.4; P = .006). Fats intake was significantly higher in patients in the mirtazapine group (14.5 g vs 0.7 g; P = .02) after 8 weeks. The mirtazapine group significantly decreased the proportion of patients with sarcopenia (82.8% vs 57.1%, P = .03) at 8 weeks. Patients on mirtazapine tolerated the treatment well, but reported a higher perception of nightmares at 2 weeks based on a 10 cm VAS score (0 [25th-75th percentile, 0-1] vs 0 [25th-75th percentile, 0-0] in the control group; P = .009) but this finding was nonsignificant after 4 and 8 weeks.
CONCLUSION AND RELEVANCE
In this randomized clinical trial of patients with advanced NSCLC, there was no difference in appetite scores in all patients who received mirtazapine or placebo, but the mirtazapine group had a significant increase in energy intake through the 4- and 8-week follow-up, mainly in fat intake, which is a better and crucial source of energy. The addition of mirtazapine in the treatment of patients with advanced NSCLC and anorexia may help these patients achieve their energy requirements and improve health-related quality of life, specifically emotional and cognitive functioning.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04748523.
Topics: Aged; Female; Humans; Male; Middle Aged; Anorexia; Appetite Stimulants; Carcinoma, Non-Small-Cell Lung; Double-Blind Method; Lung Neoplasms; Mirtazapine; Quality of Life; Adult
PubMed: 38206631
DOI: 10.1001/jamaoncol.2023.5232 -
European Journal of Clinical... Mar 2024The aim of this study was to examine the age of onset for increased dose-adjusted serum concentrations (C/D ratio) of common antidepressant drugs and to explore the... (Observational Study)
Observational Study
PURPOSE
The aim of this study was to examine the age of onset for increased dose-adjusted serum concentrations (C/D ratio) of common antidepressant drugs and to explore the potential association with sex and CYP2C19/CYP2D6 genotype.
METHODS
Serum concentrations and prescribed daily doses for citalopram, escitalopram, sertraline, venlafaxine and mirtazapine, and CYP genotypes, were obtained from a therapeutic drug monitoring (TDM) service. Segmented linear regression analysis was used to examine the relationship between age and antidepressant log C/D ratio in (i) all individuals, (ii) men and women, and (iii) CYP2D6/CYP2C19 normal metabolizers (NMs) and CYP2D6/CYP2C19 intermediate or poor metabolizers (IMs/PMs).
RESULTS
A total of 34,777 individuals were included in the study; CYP genotype was available for 21.3%. An increase in C/D ratio started at 44‒55 years of age. Thereafter, the increase progressed more rapidly for citalopram and escitalopram than for venlafaxine and mirtazapine. A doubled C/D ratio was estimated to occur at 79 (citalopram), 81 (escitalopram), 86 (venlafaxine), and 90 years (mirtazapine). For sertraline, only modest changes in C/D ratio were observed. For escitalopram and venlafaxine, the observed increase in C/D ratio started earlier in women than in men. The results regarding CYP genotype were inconclusive.
CONCLUSION
The age-related increase in C/D ratio starts in middle-aged adults and progresses up to more than twofold higher C/D ratio in the oldest old. Sertraline seems to be less prone to age-related changes in C/D ratio than the other antidepressants.
Topics: Adult; Male; Middle Aged; Aged, 80 and over; Female; Humans; Citalopram; Sertraline; Venlafaxine Hydrochloride; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2D6; Mirtazapine; Escitalopram; Age of Onset; Antidepressive Agents; Genotype
PubMed: 38197945
DOI: 10.1007/s00228-023-03611-3 -
Drug Development and Industrial Pharmacy Jan 2024Orally 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...
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.
Topics: Humans; Excipients; Mirtazapine; Drug Compounding; Solubility; Xylitol; Administration, Oral; Tablets; Mannitol
PubMed: 38149637
DOI: 10.1080/03639045.2023.2294095 -
Canadian Journal of Ophthalmology.... Jun 2024
Review
Topics: Humans; Mirtazapine; Intracranial Hypertension; Female; Antidepressive Agents, Tricyclic; Intracranial Pressure; Adult
PubMed: 38145627
DOI: 10.1016/j.jcjo.2023.11.014 -
The Medical Letter on Drugs and... Dec 2023
Topics: Humans; Antidepressive Agents; Selective Serotonin Reuptake Inhibitors
PubMed: 38133585
DOI: 10.58347/tml.2023.1691a -
Journal of Pharmaceutical Policy and... Dec 2023The COVID-19 pandemic globally impacted healthcare provision. Prescribing changes in common medications can be used as a marker for new diagnoses. We describe how the...
INTRODUCTION
The COVID-19 pandemic globally impacted healthcare provision. Prescribing changes in common medications can be used as a marker for new diagnoses. We describe how the prescribing of specific psychotropics was impacted by the pandemic.
METHODS
Primary Care Prescribing data for different classes of drugs from March 2017 to February 2022 were considered. To capture the impact during periods of restricted access to health services for new diagnoses/existing conditions, repeat prescriptions/episodic prescribing were included with account taken of historical trends. The pre-pandemic prescriptions issued each month from March 2018 to February 2020 were linearly extrapolated forward to give an expected annual growth (EAG). The monthly average expected prescriptions for the pandemic period (March 2020-February 2022) were compared.
RESULTS
Physical health medications had lower monthly prescriptions during the pandemic, most markedly for antibiotics - 12.5% (EAG - 1.3%). Bronchodilator prescribing showed a marked increase in the early pandemic months from March 2020 of 5% (EAG 0.1%). Mental health medication prescribing increased above trend for hypnotics/anxiolytics by 0.2% (EAG - 2.3%), while antidepressants fell by - 0.2% (EAG 5.0%), with no net change for antipsychotics (EAG 2.8%), but a temporary increase in antipsychotic prescribing in the early pandemic period. For all the main antidepressants prescribed in England (Sertraline, Mirtazapine, Venlafaxine, Fluoxetine and Citalopram), prescribing actually decreased in the main pandemic period vs historical trend.
CONCLUSIONS
The increase in anxiolytic/hypnotic prescribing above trend links to pandemic effects on anxiety/worry. If anything, there was a slight fall in prescribing of the main antidepressants prescribed, which given prevailing circumstances at the time, suggests that access to services may have restricted access to timely assessment.
PubMed: 38124123
DOI: 10.1186/s40545-023-00655-9 -
Journal of Eating Disorders Dec 2023Appetite suppression and weight loss are established potential side effects of most medications for attention deficit/hyperactivity disorder (ADHD). These side effects...
Pharmacotherapy for attention deficit/hyperactivity disorder in youth with avoidant restrictive food intake disorder: a case series of patients prescribed stimulant medication in a partial hospitalization program for eating disorders.
BACKGROUND
Appetite suppression and weight loss are established potential side effects of most medications for attention deficit/hyperactivity disorder (ADHD). These side effects may be especially problematic when using stimulants to treat ADHD in the context of a restrictive eating disorder, such as avoidant restrictive food intake disorder (ARFID), although these diagnoses are often comorbid in children. This paper presents a combined approach to treating ADHD comorbid with ARFID using stimulant medication and behavior management within a partial hospitalization program (PHP) and intensive outpatient program (IOP)for eating disorders. The aim of this paper is to determine if the continued or new use of stimulant medication allows for adequate weight restoration by reviewing a series of cases receiving the combined treatment.
CASE PRESENTATIONS
Consecutive patients with a historical or new diagnosis of ADHD when presenting for treatment for ARFID were included in this case series. This series included 10 patients (8 male, 2 female) who received pharmacotherapy using stimulants and behavior management interventions involving structured mealtimes and contingency management. All treatment occurred within the context of a PHP/IOP for childhood eating disorders. All youth were able to effectively continue on stimulant medication, show clinical benefit in core ADHD symptoms, and able to gradually restore weight. In all cases, stimulant medications were not discontinued, but in some cases, doses were optimized (increased or decreased), switched to a different stimulant, or augmented with non-ADHD medication, such as mirtazapine, to support the management of ADHD while concurrently assisting in weight gain as necessary for the treatment of ARFID. Only one patient was newly started on a stimulant medication; as this was near the end of her treatment stay, limited conclusions can be drawn from this case.
CONCLUSIONS
These findings support the use of pharmacotherapy, including continuing stimulant medication, when combined with behavior management strategies as a potentially effective treatment approach for ADHD in youth with ARFID in the PHP/IOP setting. Future studies using more rigorous methodology, longer follow-up times, and within other treatment settings are needed.
PubMed: 38111067
DOI: 10.1186/s40337-023-00954-1 -
The Veterinary Record Apr 2024Canine behaviour problems seen by speciality behavioural medicine services often involve chronic anxiety disorders that have resulted in maladaptation of the individual...
BACKGROUND
Canine behaviour problems seen by speciality behavioural medicine services often involve chronic anxiety disorders that have resulted in maladaptation of the individual to its environment. Common stressors include the presence of other individuals (other dogs or people), noise and being alone. The treatment of these behavioural problems usually includes a combination of behaviour modification, environmental modification and biological therapies. Within the latter, anxiolytic drugs such as clomipramine or fluoxetine have proven useful.
METHODS
Here, we present a retrospectively analysed series of 32 cases that were treated with the anxiolytic drug mirtazapine, which is widely used in human medicine but has not previously been reported for the treatment of behavioural problems in dogs (although it is marketed as an appetite stimulant in cats). Cases included dogs with a range of anxiety-related behavioural problems.
RESULTS
Eighty-one percent of dogs that presented with a behavioural problem showed improvement and suspected adverse effects were mild and tolerable.
LIMITATIONS
Further studies are required to isolate this result from the other therapeutic measures and to compare its efficacy with other drugs.
CONCLUSION
Mirtazapine appears to be a suitable and safe option for the treatment of anxiety-related behavioural problems in dogs.
Topics: Animals; Dogs; Anti-Anxiety Agents; Anxiety; Anxiety Disorders; Mirtazapine; Retrospective Studies; Dog Diseases
PubMed: 38083822
DOI: 10.1002/vetr.3670 -
Alternative Therapies in Health and... Dec 2023To observe the effects of traditional Chinese medicine (TCM) five-element music therapy combined with mirtazapine on depression and limb function recovery after ischemic...
OBJECTIVE
To observe the effects of traditional Chinese medicine (TCM) five-element music therapy combined with mirtazapine on depression and limb function recovery after ischemic stroke.
METHODS
A total of 110 patients treated in the Departments of Geriatrics, Cardiology, and Psychology of three hospitals in Qinhuangdao City, Hebei Province, China from October 2022 to August 2023 were selected. Based on the scores of 24-item Hamilton Depression Scale (HAMD-24), Barthel (BL) index, and National Institute of Health Stroke Scale (NIHSS) before enrollment, the patients were randomly divided into control group (n = 58) and experimental group (n = 52). The patients in control group were treated with limb rehabilitation, while those in experimental group underwent limb rehabilitation combined with five-element music therapy and mirtazapine.
RESULTS
After 12 weeks of treatment and observation, 11 patients in control group and 9 patients in experimental group withdrew from this trail. As for the proportions of score changes, experimental group had higher decline proportions of HAMD-24 score and NIHSS score as well as an increased proportion of BL index score than control group, which were 43.97%, 69.32%, and 44.12%, respectively.
CONCLUSION
TCM five-element music therapy combined with mirtazapine significantly improves depression and limb function recovery after ischemic stroke.
PubMed: 38064630
DOI: No ID Found -
Clinical Journal of the American... Dec 2023Depression is prevalent in patients with CKD and is related to poor prognosis. Despite the widespread use of antidepressants in the CKD population, their safety remains...
BACKGROUND
Depression is prevalent in patients with CKD and is related to poor prognosis. Despite the widespread use of antidepressants in the CKD population, their safety remains unclear.
METHODS
We identified adults with CKD stages G3-5 (eGFR <60 ml/min per 1.73 m2 not treated with dialysis) and incident depression diagnosis during 2007-2019 from the Stockholm Creatinine Measurements project. Using the target trial emulation framework, we compared the following treatment strategies: (1) initiating versus not initiating antidepressants, (2) initiating mirtazapine versus selective serotonin reuptake inhibitors (SSRIs), and (3) initiating SSRIs with a lower dose versus a standard dose.
RESULTS
Of 7798 eligible individuals, 5743 (74%) initiated antidepressant treatment. Compared with noninitiation, initiation of antidepressants was associated with higher hazards of short-term outcomes, including hip fracture (hazard ratio [HR], 1.23; 95% confidence interval [CI], 0.88 to 1.74) and upper gastrointestinal bleeding (HR, 1.38; 95% CI, 0.82 to 2.31), although not statistically significant. Initiation of antidepressants was not associated with long-term outcomes, including all-cause mortality, major adverse cardiovascular event, CKD progression, and suicidal behavior. Compared with SSRIs, initiation of mirtazapine was associated with a lower hazard of upper gastrointestinal bleeding (HR, 0.52; 95% CI, 0.29 to 0.96), but a higher hazard of mortality (HR, 1.11; 95% CI, 1.00 to 1.22). Compared with the standard dose, initiation of SSRIs with a lower dose was associated with nonstatistically significantly lower hazards of upper gastrointestinal bleeding (HR, 0.68; 95% CI, 0.35 to 1.34) and CKD progression (HR, 0.80; 95% CI, 0.63 to 1.02), but a higher hazard of cardiac arrest (HR, 2.34; 95% CI, 1.02 to 5.40).
CONCLUSIONS
Antidepressant treatment was associated with short-term adverse outcomes but not long-term outcomes in people with CKD and depression.
PubMed: 38032000
DOI: 10.2215/CJN.0000000000000348