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Journal of Alzheimer's Disease Reports 2024Alzheimer's disease (AD) is one of the most debilitating diseases in old age, associated with cognitive decline and behavioral symptoms.
BACKGROUND
Alzheimer's disease (AD) is one of the most debilitating diseases in old age, associated with cognitive decline and behavioral symptoms.
OBJECTIVE
This study aimed to investigate the effect of adding mirtazapine to quetiapine in reducing agitation among patients with AD.
METHODS
Thirty-seven elderly patients (18 cases and 19 controls) with AD, diagnosed according to National Institute on Aging and Alzheimer's Association (NIA-AA) criteria, were enrolled at Nezam-Mafi Clinic. Inclusion criteria comprised a minimum of two years post-diagnosis, a Cohen-Mansfield Agitation and Aggression Questionnaire (CMAI) score above 45, and treatment with 100-150 mg of quetiapine. Patients were randomly assigned to receive mirtazapine (15 mg at night, increased to 30 mg at night after two weeks) or a placebo. Cognitive changes were assessed at weeks 0 and 6 using the Mini-Mental State Examination instrument. Furthermore, symptoms of agitation and aggression were evaluated using the CMAI questionnaire at weeks 4 and 6.
RESULTS
In this study, the mean duration of AD in the control group was 4.68 years, and in the case group, it was 5.05 years. Although the total agitation score showed no significant change at the end of the study compared to the control group, the rate of physical non-aggressive behavior showed a significant decrease ( < 0.05).
CONCLUSIONS
According to this study, adding mirtazapine to the antipsychotic drug regimen may not be an effective treatment for agitation in AD patients.
PubMed: 38312532
DOI: 10.3233/ADR-230123 -
Frontiers in Psychiatry 2023Burning mouth syndrome (BMS) is characterized by persistent oral burning sensations without corresponding organic findings. Dementia with Lewy bodies (DLB) is a common...
Burning mouth syndrome (BMS) is characterized by persistent oral burning sensations without corresponding organic findings. Dementia with Lewy bodies (DLB) is a common type of dementia and generally presents visual hallucination and parkinsonism as motor dysfunction besides cognitive decline. In this case report, we present a case in which DLB emerged during the treatment for BMS, with a relatively positive outcome for BMS. A 74 years-old female complained of burning pain in her mouth and a subsequent decrease in food intake. Following a diagnosis of BMS, pharmacotherapy was initiated. BMS was much improved with mirtazapine 15 mg and aripiprazole 1.0 mg, leading to the restoration of her food intake by day 180. However, BMS flared up again triggered by deteriorating physical condition of herself and that of her husband. With aripiprazole 1.5 mg and amitriptyline 25 mg, her BMS gradually improved by day 482. However, by day 510, an increase in anxiety was noted, accompanied by the occasionally misidentification of her husband on day 566. Her cognitive impairment and disorientation were also reported by her husband on the day 572, she was then immediately referred to a neurologist specialized dementia and diagnosed with DLB on the day 583. Her treatment was adjusted to include the prescription of rivastigmine which was titrated up to 9.0 mg. Considering the potential impact of amitriptyline on cognitive function, it was reduced and switched to mirtazapine; however, her oral sensations slightly got worse. Following the consultation with her neurologist, amitriptyline 10 mg was reintroduced and aripiprazole was discontinued on day 755. Remarkably, BMS gradually improved without deteriorating DLB. This case indicated the reaffirmed necessity of careful interviews for changes in daily life not only with the patients but also with their families through the medical assessments. It highlights the vigilance regarding potential cognitive decline underlying or induced as an adverse event especially when treating elderly patients with BMS. While the interaction between BMS and DLB remains unclear, this case underscores the importance of prudent diagnosis and constructing collaboration with specialists in managing BMS with the early phase of DLB.
PubMed: 38260804
DOI: 10.3389/fpsyt.2023.1329171 -
Biomedicines Dec 2023Fibromyalgia (FM) is a chronic pain condition characterized by widespread musculoskeletal pain and other frequent symptoms such as fatigue, sleep disturbance, cognitive... (Review)
Review
Fibromyalgia (FM) is a chronic pain condition characterized by widespread musculoskeletal pain and other frequent symptoms such as fatigue, sleep disturbance, cognitive impairment, and mood disorder. Based on the view that intermittent stress would be the most probable etiology for FM, intermittent cold- and intermittent psychological stress-induced generalized pain (ICGP and IPGP) models in mice have been developed and validated as FM-like pain models in terms of the patho-physiological and pharmacotherapeutic features that are shared with clinical versions. Both models show long-lasting and generalized pain and female-predominant sex differences after gonadectomy. Like many other neuropathic pain models, ICGP and IPGP were abolished in lysophosphatidic acid receptor 1 (LPAR) knock-out mice or by LPAR antagonist treatments, although deciding the clinical importance of this mechanism depends on waiting for the development of a clinically available LPAR antagonist. On the other hand, the nonsteroidal anti-inflammatory drug diclofenac with morphine did not suppress hyperalgesia in these models, and this is consistent with the clinical findings. Pharmacological studies suggest that the lack of morphine analgesia is associated with opioid tolerance upon the stress-induced release of endorphins and subsequent counterbalance through anti-opioid NMDA receptor mechanisms. Regarding pharmacotherapy, hyperalgesia in both models was suppressed by pregabalin and duloxetine, which have been approved for FM treatment in clinic. Notably, repeated treatments with mirtazapine, an α2 adrenergic receptor antagonist-type antidepressant, and donepezil, a drug for treating Alzheimer's disease, showed potent therapeutic actions in these models. However, the pharmacotherapeutic treatment should be carried out 3 months after stress, which is stated in the FM guideline, and many preclinical studies, such as those analyzing molecular and cellular mechanisms, as well as additional evidence using different animal models, are required. Thus, the ICGP and IPGP models have the potential to help discover and characterize new therapeutic medicines that might be used for the radical treatment of FM, although there are several limitations to be overcome.
PubMed: 38255163
DOI: 10.3390/biomedicines12010056 -
Clinical Psychopharmacology and... Feb 2024: This study aimed to identify serum biomarkers prospectively associated with remission at 12 weeks in out-patients with depressive disorders receiving stepwise...
OBJECTIVE
: This study aimed to identify serum biomarkers prospectively associated with remission at 12 weeks in out-patients with depressive disorders receiving stepwise psychopharmacotherapy, according to the main antidepressant used during the treatment period.
METHODS
: This study included 1,024 depressive outpatients initially treated using antidepressant monotherapy, followed by alternating pharmacological strategies during the acute phase (3-12 weeks; 3-week interval). Fourteen serum biomarkers, sociodemographics, and clinical characteristics were evaluated at baseline. Based on the use frequency and mechanism of action, four main antidepressant types were distinguished: escitalopram, other selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), and mirtazapine. A Hamilton Depression Rating Scale score ≤ 7 was take to indicate remission.
RESULTS
: Lower high-sensitivity C-reactive protein levels were correlated with remission at 12 weeks for all antidepressant types. Lower interleukin (IL)-6 levels and tumor necrosis factor-alpha levels were associated with remission using escitalopram and other SSRIs respectively. Lower IL-1β and leptin levels, predicted remission in association with SSRIs including escitalopram. For SNRIs, remission at 12 weeks was predicted by lower IL-4 and IL-10 levels. For mirtazapine, remission at 12 weeks was associated with lower leptin levels, and higher serotonin and folate levels.
CONCLUSION
: Baseline serum status, as estimated by nine serum markers, may help clinicians determine the most appropriate antidepressant to achieve remission in the acute phase of depression.
PubMed: 38247424
DOI: 10.9758/cpn.23.1071 -
BJPsych Open Jan 2024Despite the availability of effective therapies, many patients with major depressive disorder (MDD) develop treatment-resistant depression (TRD).
BACKGROUND
Despite the availability of effective therapies, many patients with major depressive disorder (MDD) develop treatment-resistant depression (TRD).
AIMS
To evaluate and compare prescribing patterns, contact with specialist services and treatment outcomes in patients with MDD and TRD.
METHOD
This was a retrospective analysis of linked primary and secondary care National Health Service data in the north-west London Discover-NOW data-set. Eligible patients were adults who had diagnostic codes for depression and had been prescribed at least one antidepressant between 2015 and 2020.
RESULTS
A total of 110 406 patients were included, comprising 101 333 (92%) with MDD and 9073 (8%) with TRD. Patients with TRD had significantly higher risks of suicidal behaviour and comorbidities such as anxiety, asthma, and alcohol or substance misuse (all < 0.0001). Citalopram, sertraline, fluoxetine and mirtazapine accounted for 83% of MDD and 71% of TRD prescriptions. Use of antidepressant switching (1% MDD, 7% TRD) and combination therapy (1%, 5%) was rare, whereas augmentation occurred more frequently in the TRD group (4%, 35%). Remission was recorded in 42 348 (42%) patients with MDD and 1188 (13%) with TRD ( < 0.0001), whereas relapse was seen in 20 970 (21%) and 4923 (54%), respectively ( < 0.0001). Mean times from diagnosis to first contact with mental health services were 38.9 (s.d. 33.6) months for MDD and 41.5 (s.d. 32.0) months for TRD ( < 0.0001).
CONCLUSIONS
There appears to be a considerable difference between treatment guidelines for depression and TRD and the reality of clinical practice. Long-term treatment with single antidepressants, poor remission, and high relapse rates among patients in primary care highlight the need to optimise treatment pathways and access to newer therapies.
PubMed: 38240079
DOI: 10.1192/bjo.2023.627 -
Environment International Feb 2024Pharmaceuticals are receiving increasing attention as emerging contaminants in the aquatic environment. Herein, we investigated the occurrence of 11 antidepressants, 6...
Pharmaceuticals are receiving increasing attention as emerging contaminants in the aquatic environment. Herein, we investigated the occurrence of 11 antidepressants, 6 antihistamines and 4 metabolites in treated wastewater effluents, rivers, stormwater, and seawater in Hong Kong, with special focus on chirality. The average levels of ∑pharmaceuticals ranged from 0.525 to 1070 ng/L in all samples and the total annual mass load of target pharmaceuticals in the marine environment of Hong Kong was 756 kg/y. Antihistamines accounted for >80 % of ∑pharmaceuticals, with diphenhydramine and fexofenadine being predominant. The occurrence and enantiomeric profiles of brompheniramine and promethazine sulfoxide were reported in global natural waters for the first time. Among chiral pharmaceuticals, mirtazapine and fexofenadine exhibited R-preference, while others mostly exhibited S-preference, implying that the ecological risks derived from achiral data for chiral pharmaceuticals may be biased. The joint probabilistic risk assessment of fluoxetine revealed that R-fluoxetine and rac-fluoxetine presented different ecological risks from that of S-fluoxetine; Such assessment also revealed that target pharmaceuticals posed only minimal to low risks, except that diphenhydramine posed an intermediate risk. As estimated, 10 % aquatic species will be affected when the environmental level of diphenhydramine exceeds 7.40 ng/L, which was seen in 46.9 % samples. Collectively, this study highlights further investigations on the enantioselectivity of chiral pharmaceuticals, particularly on environmental behavior and ecotoxicity using local aquatic species as target organisms.
Topics: Fluoxetine; Water Pollutants, Chemical; Environmental Monitoring; Antidepressive Agents; Histamine Antagonists; Diphenhydramine; Risk Assessment; Rivers; Pharmaceutical Preparations; Terfenadine
PubMed: 38237506
DOI: 10.1016/j.envint.2024.108434 -
Comparative Medicine Dec 2023Decreased appetite is a common clinical problem in captive rhesus macaques (). Mirtazapine, a tetracyclic antidepressant originally developed for humans, has shown...
Decreased appetite is a common clinical problem in captive rhesus macaques (). Mirtazapine, a tetracyclic antidepressant originally developed for humans, has shown promise as a safe and effective promoter of weight gain and appetite in several veterinary species including rhesus and cynomolgus macaques. Although mirtazapine is available as oral formulations, transdermal delivery in macaques with reduced appetite would allow quick, painless, topical application. Here we describe the pharmacokinetics of a single application of a widely available veterinary transdermal mirtazapine formulation in 6 rhesus macaques. A dose of 0.5 mg/kg of transdermal mirtazapine ointment that has proven to be effective in rhesus was applied to the caudal pinnae of 3 female and 3 male young adult macaques. Serum was collected at 0, 0.5, 1, 3, 6, 8, 12, 24, 36, 48, and 72 h after administration. Our data indicate transdermal mirtazapine is absorbed at a lower level in rhesus as compared with published values in domestic cats (rhesus peak serum concentration: 1.2 ± 0.3 ng/mL), while drug half-life is longer than that reported in cats (rhesus: 33 ± 7 h). Mirtazapine reaches peak plasma concentrations in rhesus at 16 ± 10 h after administration; our model indicates that up to 5 d of serial dosing may be necessary to reach steady state. Our preliminary data also suggest that sex differences may contribute to efficacy and/or indicate sex-based differences, as male macaques reached T more quickly than females (19 ± 2 h in females and 8 ± 3 h in males) and showed higher variation in half-life (33 ± 4 h in females and 34 ± 11 h in males). While previous work indicates clinical efficacy of the 0.5-mg/kg dosage in macaques, further investigation is warranted to determine if rhesus may benefit from higher recommended doses than companion animal species.
Topics: Humans; Animals; Female; Male; Cats; Macaca mulatta; Mirtazapine; Administration, Cutaneous; Macaca fascicularis; Half-Life
PubMed: 38217071
DOI: 10.30802/AALAS-CM-23-000060 -
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 -
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