Use of antidepressant medication has increased substantially nowadays. Investigations of their photostability in aqueous environment are therefore needed both for shelf life assessment of liquid pharmaceutical formulations and for development of wastewater remediation technologies. In this work, the comparative kinetics of photodegradation of five tricyclic antidepressants (TCAs) in aqueous solution was studied under direct photolysis using UVA, UVB, and UVC sources, respectively. A gas chromatography-mass spectrometry (GC-MS) method was developed and validated intra-laboratory for accurate quantification of the five TCAs (amitriptyline hydrochloride AMI, doxepin hydrochloride DOX, imipramine hydrochloride IMI, clomipramine hydrochloride CLO, trimipramine maleate TRI) in the course of photodegradation. UVC photolysis yielded the highest rates of photodegradation, followed by UVB and then UVA. The molecular structure and UV absorption characteristics of individual TCAs were shown to influence photodegradation rates as well. Specifically, heteroatoms (N, O, Cl) present in the molecule and redshifted UV absorption bands increased photosensitivity typically in the order: AMI < IMI < TRI < CLO < DOX. The effect that some mono- and polycarboxylic acids dissolved in the aqueous solutions had on TCA photodegradation kinetics under UVC was also investigated and, for most TCAs, rates were faster and durations required for their complete photodegradation decreased generally in the order: citric > oxalic > maleic > benzoic acid. Furthermore, citric acid was reused for a second round of TCA photodegradation and showed rate enhancement effects very close to those exhibited in the first round.

The present study describes the development and validation of a simple, rapid, and reliable RP-HPLC method for the simultaneous estimation of acyclovir and doxepin hydrochloride in bulk and topical cream formulation using an Analytical Quality by Design (AQbD) approach. The combination of acyclovir, an antiviral agent, and doxepin, an antipruritic and anti-inflammatory drug, offers a combined topical approach for the management of herpes-associated skin conditions. The method development was guided by a predefined Analytical Target Profile (ATP), followed by systematic risk assessment to identify critical quality attributes (CQAs) and critical method parameters (CMPs). The central composite design (CCD) was employed to optimize key chromatographic variables, including mobile phase composition and flow rate. The chromatographic separation was achieved on a C18 column using an isocratic mobile phase of acetonitrile and water (40:60 v/v) at a flow rate of 1.0 mL/min, with UV detection at 240 nm. The retention times were found to be 2.58 min for acyclovir and 4.64 min for doxepin hydrochloride, indicating efficient separation with good peak symmetry. The method was validated according to ICH Q2(R2) guidelines and demonstrated excellent linearity over the concentration ranges of 2-10 µg/mL (acyclovir) and 12-28 µg/mL (doxepin hydrochloride), with correlation coefficients greater than 0.997. The method exhibited high precision (%RSD < 2%), accuracy (recovery within 99-101%), and good sensitivity with low LOD and LOQ values. The robustness studies confirmed the reliability of the method under small, deliberate variations in chromatographic conditions. The developed cream formulation showed uniform drug content and satisfactory in vitro drug release, with a sustained release profile reaching approximately 96% over 24 h. In conclusion, the proposed AQbD-based RP-HPLC method is suitable for routine quantitative analysis and quality control of acyclovir and doxepin hydrochloride in combined topical formulations.

Insomnia is a highly prevalent sleep disorder among Veterans and frequently co-occurs with post-traumatic stress disorder (PTSD), depression, chronic pain, and substance use disorders.

Insomnia symptoms in major depressive disorder (MDD) are clinically heterogeneous, ranging from presleep rumination and prolonged sleep latency to repeated nocturnal awakenings and early-morning awakening. Their clinical significance and treatment implications may also differ between active MDD and residual insomnia symptoms during partial remission. This narrative review examines how these presentations may inform the use of sedating antidepressants and dual orexin receptor antagonists (DORAs). Sedating antidepressants, including mirtazapine, trazodone, doxepin, and other tricyclic antidepressants, differ in dose-dependent antidepressant activity, receptor profile, and adverse-effect burden. DORAs directly target orexin-mediated wake drive and have the strongest evidence for insomnia disorder, particularly sleep-maintenance outcomes, although evidence in active MDD remains limited. Because clinical presentations neither establish an underlying mechanism nor reliably predict treatment response, the proposed framework should be used as a hypothesis-generating aid rather than a validated treatment algorithm. Pharmacological selection should also consider suicide risk, substance-use history, comorbid sleep disorders, concomitant central nervous system depressants, and next-day functioning.

We report a case of a 62-year-old woman presenting with a 6-year history of purpuric patches and macules on the lower extremities, initially misdiagnosed as allergic purpura and treated with prednisone. Skin biopsy revealed dilated dermal vessels with perivascular collagen deposition, positive for collagen IV and diastase-periodic acid-Schiff (D-PAS) staining, consistent with cutaneous collagenous vasculopathy (CCV). Treatment included hydroxychloroquine, vitamin C, doxepin, and topical mucopolysaccharide polysulfate cream. Prednisone was tapered by one tablet every 3 days. After 4 weeks, the rash improved significantly with no new lesions. We would like to present a case of CCV.

Objective: To establish a rapid method for the determination of doxepin and its metabolite nordoxepin residues in plasma samples by PRiME mixed cation-exchange solid-phase extraction coupled with ultra-performance liquid chromatography-high resolution mass spectrometry (PRiME MCX-UPLC-HRMS) . Methods: Plasma samples were extracted with 2% (V/V) aqueous phosphoric acid and purified by a PRiME MCX SPE cartridge. The target compounds were separated on an aurorasil MMP-G column (100 mm×2.1 mm, 3 μm) and gradient elution was performed with the mobile phases 5.0 mmol/L ammonium formate -0.1% (V/V) aqueous formic acid and methanol, and were determined in electrospray positive ionization mode (ESI(+)) and full mass scan-data dependent ms(2) scan (Full mass-ddMS(2)) mode, and the internal standard method was used for quantification. The limits of detection (LODs) and limits of quantification (LOQs) were calculated at signal-to-noise ratios of 3 and 10, respectively. Results: The linear ranges of doxepin and its metabolite nordoxepin were 1.0-100.0 ng/ml with correlation coefficients of 0.9988-0.9999. The LODs and LOQs for doxepin and its metabolite nordoxepin were determined to be 0.18-0.22 ng/ml and 0.54-0.66 ng/ml, respectively. The spiked recoveries of doxepin and its metabolite nordoxepin in plasma at the four concentration levels of 1.0 ng/ml, 10.0 ng/ml, 50.0 ng/ml and 80 ng/ml ranged from 90.8% to 105%, with relative standard deviations (RSDs) of 1.31%-4.59%. Conclusion: The method was rapid, sensitive and accurate and was suitable for the monitoring and analysis of doxepin and its metabolite nordoxepin in plasma samples from clinical patients.

Candida species are associated with invasive infections characterized by causing high rates of mortality and morbidity, particularly when linked to biofilm formation. The present study investigated the in vitro antifungal activity of doxepin (DOX) against fluconazole-resistant strains of Candida spp., including 10 clinical isolates, 2 ATCC strains and 1 CDC strain. Antifungal susceptibility assays were performed on planktonic cells and biofilms, followed by cytometric analyses, including reactive oxygen species (ROS) production, mitochondrial depolarization, phosphatidylserine externalization, and cell viability. Molecular analyses involved docking and gene expression by qRT-PCR. DOX exhibited fungicidal activity against all strains, with MIC50 values ranging from 64 to 256 μg/mL, as well as significant reduction of biofilm formation. In combination with amphotericin B, a predominantly synergistic effect was observed, with increased efficacy at lower concentrations. Mechanistically, DOX induced oxidative stress, mitochondrial dysfunction, and apoptosis, reducing fungal viability. The in silico ADME profile showed high gastrointestinal absorption, indicating potential for oral bioavailability, compatible with systemic use. Furthermore, it established stable interactions with the Als3 and Sap5 proteins, also promoting changes in the expression of virulence-related genes, such as als3, sap5, ece1, and hwp1. These findings indicate that DOX exhibits promising antifungal activity for the treatment of Candida infections, particularly highlighting its potential against biofilms.

Insomnia is a common reason for patients to seek medical care. A careful history should be obtained to identify predisposing, precipitating, and perpetuating factors contributing to sleep disturbance. Cognitive behavioral therapy for insomnia is the first-line treatment for chronic insomnia, offering effectiveness with minimal risk, though access may be limited by availability. Pharmacologic therapy should ideally be reserved for short-term use and initiated only after setting clear expectations and considering potential risks. Evidence-based medication options include low-dose doxepin, melatonin receptor agonists, dual orexin receptor antagonists, and nonbenzodiazepine benzodiazepine receptor agonists. Ongoing follow-up is essential to monitor treatment response.