Respirology. 2022 Sep 26. doi: 10.1111/resp.14380. Online ahead of print.

NO ABSTRACT

PMID:36156336 | DOI:10.1111/resp.14380

Schizophr Bull. 2022 Sep 26:sbac133. doi: 10.1093/schbul/sbac133. Online ahead of print.

ABSTRACT

BACKGROUND: Several psychotropic drugs can induce weight gain and metabolic alterations. The authors compared metabolic evolutions of patients switching versus continuing psychotropic treatments with different risk profiles.

METHODS: Patients either switched from a high- to a medium- (N = 36) or low-risk drug (N = 27), from a medium- to a low-risk drug (N = 71), or to a same-risk drug (N = 61). Controls were kept using either a high- (N = 35), medium- (N = 155), or low-risk drug (N = 47). The evolution over 2 years of weight and metabolic parameters was analyzed using linear mixed-effect models, also examining the influence of polygenic risk scores for body mass index (BMI) or BMI and psychiatric disorders.

STUDY RESULTS: High-, medium-, or low-risk controls gained on average 1.32%, 0.42%, and 0.36% more weight per month than patients switching from or within these risk categories (P < .001, P < .001, and P = .003, respectively). High-to-high or high-to-medium switches resulted in a greater weight increase than switching to lower-risk categories (+0.77% and + 0.39% respectively, P < .001). No difference was found between switching medium-to-medium and medium-to-low (P ≈ 1). Switching high-to-low resulted in 10% weight loss after 2 years, with the greatest loss occurring the first 6 months after the switch. Compared with high-risk controls, lower total cholesterol (-0.27 mmol/l, P = .043) in the high-to-low group, and lower glucose (-0.44 mmol/l, P = .032) and systolic blood pressure (-5.50 mmHg, P = .034) in the low-to-low group were found. Polygenic scores were not associated with weight changes in controls or after switching.

CONCLUSION: Psychotropic switches to a lower- or same-risk drug can attenuate weight gain, with only switching high to low resulting in weight loss.

PMID:36156101 | DOI:10.1093/schbul/sbac133

J Occup Environ Med. 2022 Sep 22. doi: 10.1097/JOM.0000000000002705. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess adoption of a pharmacogenomic-enriched comprehensive medication management (PGx + CMM) program in a self-insured employer setting and to better understand medication risks that affect employees.

METHODS: Employees were identified to be at high risk of medication mismanagement and were subsequently provided with a program and process to improve their health. DNA testing, a clinical decision support system, and pharmacists were utilized to identify medication safety and effectiveness issues and to recommend appropriate changes.

RESULTS: 10.6% of the invited employees enrolled in the program. Actionable recommendations were suggested by pharmacists for 85.8% of employees who completed the program, averaging 5.2 recommendations per person.

CONCLUSIONS: Implementation of a PGx + CMM program in a self-insured employer setting is feasible, detects risks in prescription regimens, and offers opportunities to improve medication management and reduce the burden of healthcare expenses.

PMID:36155954 | DOI:10.1097/JOM.0000000000002705

Hum Genomics. 2022 Sep 25;16(1):42. doi: 10.1186/s40246-022-00417-9.

ABSTRACT

BACKGROUND: Pharmacogenomic (PGx) testing has proved its utility and cost-effectiveness for some commonly prescribed cardiovascular disease (CVD) medications. In addition, PGx-guided dosing guidelines are now available for multiple CVD drugs, including clopidogrel, warfarin, and statins. The United Arab Emirates (UAE) population is diverse and multiethnic, with over 150 nationalities residing in the country. PGx-testing is not part of the standard of care in most global healthcare settings, including the UAE healthcare system. The first pharmacogenomic implementation clinical study in CVD has been approved recently, but multiple considerations needed evaluation before commencing. The current report appraises the PGx-clinical implementation procedure and the potential benefits of pursuing PGx-implementation initiatives in the UAE with global implications.

METHODS: Patients prescribed one or more of the following drugs: clopidogrel, atorvastatin, rosuvastatin, and warfarin, were recruited. Genotyping selected genetic variants at genes interacting with the study drugs was performed by real-time PCR.

RESULTS: For the current pilot study, 160 patients were recruited. The genotypes and inferred haplotypes, diplotypes, and predicted phenotypes revealed that 11.9% of the participants were poor CYP2C19 metabolizers, 35% intermediate metabolizers, 28.1% normal metabolizers, and 25% rapid or ultrarapid metabolizers. Notably, 46.9% of our cohort should receive a recommendation to avoid using clopidogrel or consider an alternative medication. Regarding warfarin, only 20% of the participants exhibited reference alleles at VKORC1-1639G > A, CYP2C9*2, and CYP2C9*3, leaving 80% with alternative genotypes at any of the two genes that can be integrated into the warfarin dosing algorithms and can be used whenever the patient receives a warfarin prescription. For statins, 31.5% of patients carried at least one allele at the genotyped SLCO1B1 variant (rs4149056), increasing their risk of developing myopathy. 96% of our cohort received at least one PGx-generated clinical recommendation for the studied drugs.

CONCLUSION: The current pilot analysis verified the feasibility of PGx-testing and the unforeseen high frequencies of patients currently treated with suboptimal drug regimens, which may potentially benefit from PGx testing.

PMID:36154845 | DOI:10.1186/s40246-022-00417-9

Eur Heart J Cardiovasc Pharmacother. 2022 Sep 24:pvac038. doi: 10.1093/ehjcvp/pvac038. Online ahead of print.

NO ABSTRACT

PMID:36153632 | DOI:10.1093/ehjcvp/pvac038

Mol Genet Metab. 2022 Sep 17;137(1-2):210-212. doi: 10.1016/j.ymgme.2022.09.003. Online ahead of print.

NO ABSTRACT

PMID:36152474 | DOI:10.1016/j.ymgme.2022.09.003

Clin Transl Sci. 2022 Sep 24. doi: 10.1111/cts.13422. Online ahead of print.

ABSTRACT

Clinical response of clozapine is closely associated with serum concentration. While tobacco smoking is the key environmental factor underlying interindividual variability in clozapine metabolism, recent genome-wide studies suggest that CYP1A and NFIB genetic variants may also be of significant importance, but their quantitative impact is unclear. We investigated the effects of the rs2472297 C>T (CYP1A) and rs28379954 T>C (NFIB) polymorphisms on serum concentrations in smokers and nonsmokers. The study retrospectively included 526 patients with known smoking habits (63.7% smokers) from a therapeutic drug monitoring service in Norway. Clozapine dose-adjusted concentrations (C/D) and patient proportions with subtherapeutic levels (<1070 nmol/L) were compared between CYP1A/NFIB variant allele carriers and homozygous wild-type carriers (noncarriers), in both smokers and nonsmokers. Clozapine C/D was reduced in patients carrying CYP1A-T and NFIB-C variants vs. noncarriers, both among smokers (-48%; p<0.0001) and nonsmokers (-35%; p=0.028). Smoker patients carrying CYP1A-T and NFIB-C variants had a 66% reduction in clozapine C/D vs. nonsmoking noncarriers (p<0.0001). The patient proportion with subtherapeutic levels was 2.9-fold higher in smoker patients carrying NFIB-C and CYP1A-T variants vs. nonsmoking noncarriers (p<0.0001). In conclusion, CYP1A and NFIB variants have significant and additive impact on clozapine dose requirements for reaching target serum concentrations. Smoking patients carrying the studied CYP1A and NFIB variants, comprising 2.5% of the study population, may need 3-fold higher doses to prevent risk of clozapine undertreatment. The results suggest that preemptive genotyping of NFIB and CYP1A may be utilized to guide clozapine dosing and improve clinical outcomes in patients with treatment resistant schizophrenia.

PMID:36152308 | DOI:10.1111/cts.13422

J Bone Miner Res. 2022 Sep 24. doi: 10.1002/jbmr.4708. Online ahead of print.

ABSTRACT

Medication-related osteonecrosis of the jaw (MRONJ) is a rare but severely debilitating drug-induced bone disorder in the jawbone region. The first MRONJ was reported in 2003 after bisphosphonates (BPs) exposure. Recently, other drugs such as receptor activator of nuclear factor kappa-Β ligand (RANKL) inhibitor denosumab and antiangiogenic agents were also associated with MRONJ. The purpose of this study was to evaluate the incidence and risk factors for MRONJ related to BPs and/or denosumab in cancer patients in real-world clinical settings using data from the OneFlorida Clinical Research Consortium. We queried the electronic health records of participants with prescriptions of intravenous (IV) BPs or denosumab between January 1, 2012 and September 1, 2021 in the OneFlorida Consortium. Time to MRONJ diagnosis was evaluated using Kaplan Meier method and Cox regression analysis was performed to estimate the adjusted hazard ratios (HRs) and 95% confidence intervals (CI) for MRONJ. A total of 5,689 participants had one or more prescriptions of IV BP or denosumab within this study period and were included in this study. Among these participants, 52 (0.9%) had a diagnosis of MRONJ. The overall rate of MRONJ was 0.73%, 0.86%, and 3.50% in the cancer patients treated with IV BPs, denosumab, and sequential IV BPs and denosumab, respectively. The risk of MRONJ was similar in participants treated with denosumab alone compared to those treated with IV BPs alone (HR: 1.25, 95% CI: 0.66-2.34, p = 0.49). The patients with sequential prescription of IV BP and denosumab were at much higher risk for MRONJ, with adjusted HR of 4.49, 95% CI of 1.96-10.28, p = 0.0004. In conclusion, in real-world clinical settings, the rates of MRONJ associated with IV BPs and denosumab were similar, while the sequential treatment of these two drug classes was associated with a much higher risk of MRONJ. This article is protected by copyright. All rights reserved.

PMID:36151778 | DOI:10.1002/jbmr.4708

Clin Pharmacol Ther. 2022 Sep 23. doi: 10.1002/cpt.2754. Online ahead of print.

ABSTRACT

The objective of this study was to evaluate the evidence on cost effectiveness of pharmacogenetic (PGx) guided treatment for drugs with Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. A systematic review was conducted using multiple biomedical literature databases from inception to June 2021. Full articles comparing PGx-guided to non-guided treatment were included for data extraction. Quality of Health Economic Studies (QHES) was used to assess robustness of each study (0-100). Data are reported using descriptive statistics. Of 108 studies evaluating 39 drugs, 77 (71%) showed PGx testing was cost effective (CE) (N=48) or cost saving (CS) (N=29); 21 (20%) were not CE; 10 (9%) were uncertain. Clopidogrel had the most articles (N=23), of which 22 demonstrated CE or CS, followed by warfarin (N=16), of which seven demonstrated CE or CS. Of 26 studies evaluating HLA testing for abacavir (N=8), allopurinol (N=10), or carbamazepine/phenytoin (N=8), 15 demonstrated CE or CS. Nine of 11 antidepressant articles demonstrated CE or CS. The median QHES score reflected high quality studies (91; range 48-100). Most studies evaluating cost-effectiveness favored PGx testing. Limited data exist on cost effectiveness of preemptive and multigene testing across disease states.

PMID:36149409 | DOI:10.1002/cpt.2754

Mol Genet Genomic Med. 2022 Sep 23:e2063. doi: 10.1002/mgg3.2063. Online ahead of print.

ABSTRACT

BACKGROUND: ACE1 I/D rs1799752 and ACE2 rs2285666 genetic polymorphisms could play a critical role in altering the clinical outcomes of SARS-CoV-2. The findings of previous studies remained inconclusive. This meta-analysis was performed to evaluate the association and provide a more reliable outcome.

METHODS: This study was completed following the updated recommendations of PRISMA using RevMan 5.4.1 statistical software.

RESULTS: A total of 11 studies with 950 severe cases and 1573 non-severe cases with COVID-19 infection were included. Pooled analysis showed that ACE1 I/D polymorphism was correlated with the severity of SARS-CoV-2 in the DD genotype and D allele for the fixed-effects model (OR:1.27 and OR:1.17). Besides, codominant 3, recessive, and allele models were associated with the severity of the fixed-effects model (OR:1.35, OR:1.37, and OR:1.20) in Caucasian ethnicity. ACE2 rs2285666 was linked with the severity in codominant 3 (OR:2.63, for both random- and fixed effects-models), overdominant (OR:1.97, for random-effects model and OR:1.97, for fixed effects-model), and recessive model (OR:0.41 for fixed- and random-effects model). Allele model of rs2285666 showed a significant association in the fixed-effects model (OR:1.61).

CONCLUSION: Our present meta-analysis suggests that ACE1 I/D rs1799752 and ACE2 rs2285666 variants may enhance the severity in SARS-CoV-2 infected patients. Future studies are warranted to verify our findings.

PMID:36148537 | DOI:10.1002/mgg3.2063

Epilepsia. 2022 Sep 22. doi: 10.1111/epi.17418. Online ahead of print.

NO ABSTRACT

PMID:36148489 | DOI:10.1111/epi.17418

Front Psychiatry. 2022 Sep 6;13:607892. doi: 10.3389/fpsyt.2022.607892. eCollection 2022.

ABSTRACT

INTRODUCTION: Although people who attempted suicide tend to repeat suicide attempts, there is a lack of evidence on the association between psychiatric service factors and suicide reattempt among them.

METHODS: We used a nationwide, population-based medical record database of South Korea to investigate the use of psychiatric services before and after the index suicide attempt and the association between psychiatric service factors after the index suicide attempt with the risk of suicide reattempt.

RESULTS: Among 5,874 people who had attempted suicide, the all-cause mortality within 3 months after the suicide attempt was 11.6%. Among all subjects who attempted suicide, 30.6% of them had used psychiatric services within 6 months before the suicide attempt; 43.7% of them had used psychiatric services within 3 months after the suicide attempt. Among individuals who had visited clinics following attempted suicide, the cumulative incidence of suicide reattempt over a mean follow-up period of 5.1 years was 3.4%. About half of suicide reattempts occurred within 1 year after the index suicide attempt. Referral to psychiatric services within 7 days was associated with a decreased risk of suicide reattempt (adjusted hazard ratio, 0.51; 95% confidence intervals, 0.29-0.89).

CONCLUSION: An early psychiatric referral within 1 week after a suicide attempt was associated with a decreased risk of suicide reattempt.

PMID:36147991 | PMC:PMC9486390 | DOI:10.3389/fpsyt.2022.607892

Pharmaceutics. 2022 Sep 7;14(9):1893. doi: 10.3390/pharmaceutics14091893.

ABSTRACT

Crohn's disease is a consequence of dysregulated inflammatory response to the host's microbiota. Although anti-TNF treatment improves the quality of the patient's life, a large proportion of patients lose response to the treatment. The past decade of research has led to a continuum of studies showcasing the heterogeneity of anti-TNF response; thus, the aim of the present study was to dissect transcriptome-wide findings to transcript isoform specific levels and combine the analyses with refined information of immune cell landscapes in colon tissue, and subsequently select promising candidates using gene ontology and genomic integration. We enrolled Slovenian Crohn's disease patients who were naïve with respect to adalimumab treatment. We performed colon tissue RNA sequencing and peripheral blood mononuclear cell DNA genotyping with a subsequent contemporary integrative approach to combine immune cell deconvoluted isoform transcript specific transcriptome analysis, gene ontology layering and genomic data. We identified nine genes (MACF1, CTSE, HDLBP, HSPA9, HLA-DMB, TAP2, LGMN, ANAPC11, ACP5) with 15 transcripts and 16 variants involved in the adalimumab response. Our study identified loci, some of which were previously shown to contribute to inflammatory bowel disease susceptibility, as novel loci involved in adalimumab response in Crohn's disease patients.

PMID:36145641 | DOI:10.3390/pharmaceutics14091893

Pharmaceutics. 2022 Sep 6;14(9):1882. doi: 10.3390/pharmaceutics14091882.

ABSTRACT

Dalbavancin (DBV) is a lipoglycopeptide approved for the treatment of Gram-positive infections of the skin and skin-associated structures (ABSSSIs). Currently, its off-label use at different dosages for other infections deserves attention. This work aimed to study the clinical effectiveness and tolerability of DBV in outpatients with ABSSSIs, osteoarticular (OA), or other infections, treated with either one or two 1500 mg doses of dalbavancin, for different scheduled periods. A liquid chromatography-tandem mass spectrometry method was used to measure total DBV concentrations. PK/PD parameters and the clinical and microbiological features of this cohort were evaluated in order to investigate the best predictors of treatment success in real-life settings. Of the 76 screened patients, 41 completed the PK study. Long-term PK was comparable to previous studies and showed significant differences between genders and dosing schedules. Few adverse events were observed, and treatment success was achieved in the vast majority of patients. Failure was associated with lower PK parameters, particularly Cmax. Concluding, we were able to describe DBV PK and predictors of treatment success in selected infections in this cohort, finding DBV Cmax as a possible candidate for therapeutic drug-monitoring purposes, as well as highlighting the dual-dose one-week-apart treatment as the optimal choice for OA infections.

PMID:36145630 | DOI:10.3390/pharmaceutics14091882

Pharmaceutics. 2022 Sep 3;14(9):1863. doi: 10.3390/pharmaceutics14091863.

ABSTRACT

Pharmacogenetics (PGx) has the potential to improve opioid medication management. Here, we present patient perception data, pharmacogenetic data and medication management trends in patients with chronic pain (arm 1) and opioid use disorder (arm 2) treated at Cooper University Health Care in Camden City, NJ. Our results demonstrate that the majority of patients in both arms of the study (55% and 65%, respectively) are open to pharmacogenetic testing, and most (66% and 69%, respectively) believe that genetic testing has the potential to improve their medical care. Our results further support the potential for CYP2D6 PGx testing to inform chronic pain medication management for poor metabolizers (PMs) and ultrarapid metabolizers (UMs). Future efforts to implement PGx testing in chronic pain management, however, must address patient concerns about genetic test result access and genetic discrimination.

PMID:36145611 | DOI:10.3390/pharmaceutics14091863

Pharmaceutics. 2022 Sep 1;14(9):1841. doi: 10.3390/pharmaceutics14091841.

ABSTRACT

Despite advances in cancer chemotherapy, gastric cancer (GC) continues to have high recurrence rates and poor prognosis with limited treatment options. Understanding the etiology of GC and developing more effective, less harmful therapeutic approaches are vital and urgent. Therefore, this work describes a novel kinase target in malignant gastric cells as a potential therapeutic strategy. Our results demonstrate that among 147 kinase inhibitors (KI), only three molecules were significantly cytotoxic for the AGP-01 cell line. Hence, these three molecules were further characterized in their cellular mode of action. There was significant cell cycle impairment due to the expression modulation of genes such as TP53, CDKN1A, CDC25A, MYC, and CDK2 with subsequent induction of apoptosis. In fact, the Gene Ontology analysis revealed a significant enrichment of pathways related to cell cycle regulation (GO:1902749 and GO:1903047). Moreover, the three selected KIs significantly reduced cell migration and Vimentin mRNA expression after treatment. Surprisingly, the three KIs share the same target, ALK and INSR, but only the ALK gene was found to have a high expression level in the gastric cancer cell line. Additionally, lower survival rates were observed for patients with high ALK expression in TCGA-STAD analysis. In summary, we hypothesize that ALK gene overexpression can be a promising biomarker for prognosis and therapeutic management of gastric adenocarcinoma.

PMID:36145589 | DOI:10.3390/pharmaceutics14091841

Pharmaceutics. 2022 Aug 25;14(9):1784. doi: 10.3390/pharmaceutics14091784.

ABSTRACT

Multiple myeloma (MM) is a blood cell neoplasm characterized by excessive production of malignant monoclonal plasma cells (activated B lymphocytes) by the bone marrow, which end up synthesizing antibodies or antibody fragments, called M proteins, in excess. The accumulation of this production, both cells themselves and of the immunoglobulins, causes a series of problems for the patient, of a systemic and local nature, such as blood hyperviscosity, renal failure, anemia, bone lesions, and infections due to compromised immunity. MM is the third most common hematological neoplasm, constituting 1% of all cancer cases, and is a disease that is difficult to treat, still being considered an incurable disease. The treatments currently available cannot cure the patient, but only extend their lifespan, and the main and most effective alternative is autologous hematopoietic stem cell transplantation, but not every patient is eligible, often due to age and pre-existing comorbidities. In this context, the search for new therapies that can bring better results to patients is of utmost importance. Protein tyrosine kinases (PTKs) are involved in several biological processes, such as cell growth regulation and proliferation, thus, mutations that affect their functionality can have a great impact on crucial molecular pathways in the cells, leading to tumorigenesis. In the past couple of decades, the use of small-molecule inhibitors, which include tyrosine kinase inhibitors (TKIs), has been a hallmark in the treatment of hematological malignancies, and MM patients may also benefit from TKI-based treatment strategies. In this review, we seek to understand the applicability of TKIs used in MM clinical trials in the last 10 years.

PMID:36145532 | DOI:10.3390/pharmaceutics14091784

Pharmaceutics. 2022 Aug 23;14(9):1755. doi: 10.3390/pharmaceutics14091755.

ABSTRACT

The influence of pharmacogenetics in tacrolimus pharmacokinetics and pharmacodynamics needs further investigation, considering its potential in assisting clinicians to predict the optimal starting dosage and the need for a personalized adjustment of the dose, as well as to identify patients at a high risk of rejection, drug-related adverse effects, or poor outcomes. In the past decade, new pharmacokinetic strategies have been developed to improve personalized tacrolimus treatment. Several studies have shown that patients with tacrolimus doses C0/D &lt; 1 ng/mL/mg may demonstrate a greater incidence of drug-related adverse events and infections. In addition, C0 tacrolimus intrapatient variability (IPV) has been identified as a potential biomarker to predict poor outcomes related to drug over- and under-exposure. With regard to tacrolimus pharmacodynamics, inconsistent genotype-phenotype relationships have been identified. The aim of this review is to provide a concise summary of currently available data regarding the influence of pharmacogenetics on the clinical outcome of patients with high intrapatient variability and/or a fast metabolizer phenotype. Moreover, the role of membrane transporters in the interindividual variability of responses to tacrolimus is critically discussed from a transporter scientist's perspective. Indeed, the relationship between transporter polymorphisms and intracellular tacrolimus concentrations will help to elucidate the interplay between the biological mechanisms underlying genetic variations impacting drug concentrations and clinical effects.

PMID:36145503 | DOI:10.3390/pharmaceutics14091755

Metabolites. 2022 Aug 24;12(9):783. doi: 10.3390/metabo12090783.

ABSTRACT

Patients with higher genetic West African ancestry (GWAA) have hypertension (HTN) that is more difficult to treat and have higher rates of cardiovascular diseases (CVD) and differential responses to antihypertensive drugs than those with lower GWAA. The mechanisms underlying these disparities are poorly understood. Using data from 84 ancestry-informative markers in US participants from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) and PEAR-2 trials, the GWAA proportion was estimated. Using multivariable linear regression, the baseline levels of 886 metabolites were compared between PEAR participants with GWAA &lt; 45% and those with GWAA ≥ 45% to identify differential metabolites and metabolic clusters. Metabolites with a false discovery rate (FDR) &lt; 0.2 were used to create metabolic clusters, and a cluster analysis was conducted. Differential clusters were then tested for replication in PEAR-2 participants. We identified 353 differential metabolites (FDR &lt; 0.2) between PEAR participants with GWAA &lt; 45% (n = 383) and those with GWAA ≥ 45% (n = 250), which were used to create 24 metabolic clusters. Of those, 13 were significantly different between groups (Bonferroni p &lt; 0.002). Four clusters, plasmalogen and lysoplasmalogen, sphingolipid metabolism and ceramide, cofactors and vitamins, and the urea cycle, were replicated in PEAR-2 (Bonferroni p &lt; 0.0038) and have been previously linked to HTN and CVD. Our findings may give insights into the mechanisms underlying HTN racial disparities.

PMID:36144188 | DOI:10.3390/metabo12090783

J Pers Med. 2022 Sep 16;12(9):1524. doi: 10.3390/jpm12091524.

ABSTRACT

The advent of intra-nasal esketamine (ESK), one of the first so called fast-acting antidepressant, promises to revolutionize the management of treatment resistant depression (TRD). This NMDA receptor antagonist has proven to be rapidly effective in the short- and medium-term course of the illness, revealing its potential in targeting response in TRD. Although many TRD ESK responders are able to achieve remission, a considerable portion of them undergo a metamorphosis of their depression into different clinical presentations, characterized by instable responses and high recurrence rates that can be considered closer to the concept of Difficult to Treat Depression (DTD) than to TRD. The management of these DTD patients usually requires a further complex multidisciplinary approach and can benefit from the valuable contribution of new personalized medicine tools such as therapeutic drug monitoring and pharmacogenetics. Despite this, these patients usually come with long and complex previous treatments history and, often, advanced and sophisticated ongoing pharmacological schemes that can make the finding of new alternative options to face the current recurrences extremely challenging. In this paper, we describe two DTD patients-already receiving intranasal ESK but showing an instable course-who were clinically stabilized by the association with minocycline, a semisynthetic second-generation tetracycline with known and promising antidepressant properties.

PMID:36143309 | DOI:10.3390/jpm12091524