BACKGROUND:Lithium carbonate has a narrow therapeutic window for the treatment of manic episodes and is mainly excreted via the kidneys. Hypertension may impair lithium clearance, although evidence from relevant studies is insufficient. Based on previous research on the association between hypertension and the lithium concentration-to-dose (C/D) ratio, this study further performed a large-sample stratified analysis to evaluate the independent effects of hypertension on steady-state lithium pharmacokinetics, C/D ratio, rate of achieving therapeutic lithium levels, and risk of lithium toxicity in patients with mania. METHODS:A single-center retrospective cohort study was performed, enrolling 210 patients with mania, who were assigned to a hypertension group (n = 90) or a non-hypertension group (n = 120). The t-test, chi-square test, and multiple linear regression were used to evaluate the relevant parameters. RESULTS:There was no significant difference in the mean daily dose of lithium carbonate between the two groups. However, the hypertension group had significantly higher steady-state serum lithium concentrations and C/D ratios than the non-hypertension group (p < 0.001). The rate of achieving therapeutic lithium levels in the hypertension group was only 42.22%, markedly lower than the 65.83% in the non-hypertension group, while the incidence of lithium toxicity was 11.11% in the hypertension group, significantly higher than the 2.50% in the control group. Multiple regression analysis confirmed that hypertension (β = 0.215), age, and daily dose were independent influencing factors for the C/D ratio, with elderly hypertensive patients showing a more pronounced increase in the C/D ratio. The type of antihypertensive medication did not affect lithium metabolism. CONCLUSION:Hypertension can reduce renal lithium excretion and elevate both the C/D ratio and the risk of toxicity; therefore, in clinical practice, the initial lithium dose should be reduced and therapeutic drug monitoring should be intensified for patients with comorbid hypertension, while elderly patients should receive stratified management with lower serum concentration ranges.
OBJECTIVE:This review critically examines psilocybin, with particular emphasis on its pharmacokinetics and pharmacodynamics, including its serotonergic, neuroplastic, and anti-inflammatory mechanisms. It integrates historical context, preclinical and clinical evidence, and evaluates emerging therapeutic potential, safety, microdosing practices, and pharmacological interactions. METHODS:A literature search was conducted in PubMed and Google Scholar using the keywords "Psilocybin," "Psilocin," "Psychedelic therapy," "Psilocybe cubensis," and "Psychedelic microdosing," supplemented by manual searches of cross-references. All study types were included, from randomized trials to case reports. RESULTS:Psilocybin is metabolized into psilocin, which predominantly interacts with serotonin (5-hydroxytryptamine, 5-HT) receptors. These interactions contribute to enhanced synaptic plasticity, modulation of large-scale brain networks, and regulation of immune responses via microglial activity and suppression of pro-inflammatory cytokines. Preclinical and clinical evidence supports its efficacy in depression, anxiety, substance use disorders, neuropathic pain, epilepsy, and neuroinflammation. Psilocin also inhibits cytochrome P450 enzymes, raising concerns about drug interactions. Microdosing, though popular, remains inconclusive due to methodological limitations. CONCLUSIONS:Current findings suggest psilocybin offers sustained therapeutic effects and a favorable safety profile. However, uncertainties remain regarding long-term safety, individualized responses, and optimal dosing. Ethical and regulatory challenges require rigorous, standardized research for responsible clinical integration.
INTRODUCTION:Citicoline and phosphatidylserine (PS) have been proposed as potential neuroprotective and cognitive-enhancing agents; however, evidence of their therapeutic impact across populations with mental disorders remains limited. This systematic review aimed to evaluate the effects of citicoline and PS, administered as monotherapy or adjunctive treatment, on cognitive performance in children, adolescents, and adults with mental disorders. METHODS:A systematic review of 11 included studies was conducted following PRISMA guidelines. Databases searched were PubMed/MEDLINE, Scopus, Web of Science, and Cochrane CENTRAL through October 2025. Ten studies were randomized controlled trials (RCTs), and one was a non-randomized controlled trial (non-RCT). Methodological quality and risk of bias were evaluated using the RoB 2 and ROBINS-I tools. RESULTS:Five studies focused on children with ADHD, and the remaining studies included adults with mood disorders, alcohol and substance use disorders, and schizophrenia. Regarding ADHD, PS-containing supplementation produced significant improvements in attention and impulsivity in three studies, whereas two studies found no significant differences. A single study in schizophrenia reported significant improvements in verbal free recall but no global cognitive gains. Results for alcohol and substance use disorders, as well as mood disorders were mixed. Two studies revealed selective benefits in cognitive performance, while the others showed none. Overall, findings were heterogeneous and inconsistent across diagnostic groups. CONCLUSION:Given methodological limitations and high risk of bias, current evidence does not support citicoline or PS-containing compounds as effective cognitive enhancers in mental disorders. Consequently, these agents should be positioned as adjunctive or investigational rather than as evidence-based treatments.
OBJECTIVE:Insomnia impairs cognitive and brain function, and its treatment improves outcomes. Eye movements are objective biomarkers of neurocognitive state and are sensitive to sleep loss, but whether treatment improves oculomotor function remains unclear. We examined associations between sleep improvement and eye movement changes after hypnotic intervention. METHODS:In this open-label, single-arm study, 31 Japanese adults aged ≥ 50 years with insomnia and preserved cognition received nightly lemborexant (5-10 mg) and were assessed at baseline, week 4, and week 12. Eye movements were measured using free-viewing, smooth pursuit, and fixation tasks. Objective sleep was assessed with a portable electroencephalogram, and subjective sleep and sleepiness with the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS). Associations were analyzed using linear mixed-effects models. RESULTS:Improvements in ESS and PSQI scores were associated with enhanced visual search performance in the free-viewing task, including increased saccade amplitude, scanpath length, and velocity. ESS improvement correlated with better tracking accuracy during smooth pursuit, reflected by fewer gaze fixations and saccades. Longer total sleep duration was associated with increased saccade duration. CONCLUSION:Selected eye movement metrics were modestly associated with improvements in subjective sleep symptoms following hypnotic treatment in older adults with insomnia.
OBJECTIVE:Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia. However, evidence regarding whether adverse effects are related to the clozapine concentration is insufficient. METHODS:Patients treated with clozapine for at least 6 weeks and maintained on a fixed dose for > 1 week were included (n = 47). Adverse effects were assessed using the self-rated Glasgow Antipsychotic Side-effects Scale for Clozapine (GASS-C). Plasma concentrations of clozapine and norclozapine were measured, and the relationship between the GASS-C score and clozapine concentration was analyzed. RESULTS:Clozapine concentration was significantly associated with both the GASS-C score (rs = 0.435, p = 0.002) and norclozapine concentration (rs = 0.363 p = 0.012). In addition, significant correlations with large effect sizes were found for GASS-C sub-items such as hypersalivation and anticholinergic symptoms. Multiple regression indicated that the GASS-C total score was associated with both clozapine (β = 0.374, p = 0.012) and norclozapine (β = 0.404, p = 0.005) concentrations. CONCLUSIONS:Adverse effects, including subjective ones, of clozapine may be concentration-related and clinically important. However, monitoring clozapine levels may only have a supplementary role in managing its subjective adverse effects because subjective GASS-C scores could be influenced by psychological factors and patient perception, which may not always correlate linearly with pharmacokinetic data.
OBJECTIVES:Etizolam is a short-acting thienodiazepine widely prescribed for anxiety and insomnia despite increasing concerns regarding dependence and guideline recommendations limiting long-term benzodiazepine use. This study examined long-term prescribing trends of etizolam compared with benzodiazepine and non-benzodiazepine hypnotics. METHODS:We conducted a retrospective database study including 16,886,524 prescriptions issued between April 2001 and March 2022 at a tertiary university hospital in Japan. Seventeen hypnotic agents were identified (10 benzodiazepines and 7 non-benzodiazepines). Multivariable logistic regression was used to identify factors associated with prescribing hypnotic etizolam versus non-benzodiazepine hypnotics. RESULTS:Among 124,179 etizolam prescriptions, 83,927 (67.6%) were issued for hypnotic use. Although the absolute number of prescriptions declined over time, the proportion prescribed for hypnotic use remained stable. The ratio of hypnotic etizolam prescriptions to non-benzodiazepine hypnotics was higher in internal medicine than in psychiatry. In multivariable analysis, prescribing hypnotic etizolam was independently associated with internal medicine (adjusted OR 1.57), female sex, outpatient status, younger age, and earlier calendar year. CONCLUSIONS:Despite declining overall use, etizolam continues to be prescribed as a hypnotic, particularly in non-psychiatric settings. These findings highlight the persistence of specialty-specific prescribing patterns and underscore the importance of targeted educational and policy interventions to promote safer hypnotic prescribing practices.
OBJECTIVE:Attention Deficit/Hyperactivity Disorder (ADHD) is increasingly diagnosed in adults, including women of childbearing age. However, limited research exists on how maternal ADHD and psychotropic medication use during pregnancy impact early child development. This study aimed to assess developmental outcomes in children of mothers with ADHD during the first 4 years of life. SETTING:A retrospective cohort study using data from a pilot study, supplemented with data from Isala Hospital Zwolle (a general teaching hospital) and regional child health clinics. PARTICIPANTS:The exposed group comprised mothers diagnosed with ADHD, aged ≥ 18 years at term, with a gestation of ≥ 24 weeks. A subgroup used psychotropic medication during pregnancy (including SSRIs, methylphenidate, benzodiazepines and antipsychotics). The reference group included mothers without psychiatric diagnosis. Relevant somatic and socioeconomic confounders were documented. OUTCOME:Child development was assessed using the Van Wiechen Onderzoek (VWO), a validated Dutch screening tool for early childhood developmental disorders, routinely used in child health clinics. RESULTS:Seventy-two children born to mothers with ADHD were included, of whom 36 were exposed to psychotropic medication in utero. Thirty-two children formed the reference group. Univariate analysis revealed no significant differences in total VWO-scores between children of mothers with and without ADHD, nor between those exposed and unexposed to psychotropic medication. CONCLUSIONS:Maternal ADHD and associated medication use during pregnancy did not appear to adversely affect early childhood development. However, findings are limited by the small sample size and should be interpreted with caution.
OBJECTIVE:Anxiety influences working memory performance, but the effects on clinical neuropsychological assessments of working memory are not well known. METHODS:We examined the effect of anxiety, induced using the 7.5% carbon dioxide model of anxiety on standardized clinical neuropsychological tests of working memory and executive function in a single-blind, placebo-controlled, randomized, crossover within-subjects design. RESULTS:The CO2-challenge reduced spatial working memory performance and verbal working memory performance accuracy when task demands were high. The CO2-challenge increased effort and reduced processing efficiency across all verbal and spatial working memory tasks. CONCLUSIONS:The CO2-challenge resulted in significant reductions in working memory performance and processing efficiency. These results encourage the routine assessment of anxiety when administering and interpreting neuropsychological measures of working memory function in clinical practice.
BACKGROUND:Weight gain and metabolic disturbances are common adverse effects of antipsychotic medications such as clozapine and olanzapine. Beyond their primary role in glycemic control, sodium-glucose cotransporter 2 (SGLT2) inhibitors have been associated with weight loss and improvements in various metabolic parameters. This study compared the efficacy and safety of empagliflozin and metformin in patients with antipsychotic-induced weight gain (AIWG). METHODS:In this 12-week, double-blind, randomized controlled trial, 84 adults with schizophrenia or bipolar disorder and established weight gain from clozapine or olanzapine were assigned to receive either empagliflozin (10 mg daily) or metformin (1000 mg daily). The primary outcome was the percentage change in body weight from baseline to week 12. Secondary outcomes included changes in absolute body weight, body mass index (BMI), waist circumference, waist-hip ratio, and the proportion of patients achieving ≥ 5% weight loss. Exploratory outcomes assessed changes in glycemic and lipid parameters, fasting insulin, and insulin resistance (HOMA-IR). Safety was evaluated by monitoring adverse events, treatment discontinuations, and serious adverse events. RESULTS:Of the 84 randomized participants, 38 (90.5%) in the empagliflozin group and 39 (92.9%) in the metformin group completed the 12-week study. Both treatments produced significant within-group reductions in anthropometric measures (all p < 0.001) and there were no statistically significant differences between groups in the magnitude of change for body weight, BMI, waist circumference, hip circumference, or waist-hip ratio (all p > 0.05). Both groups showed improvements in glycemic and lipid parameters, but empagliflozin resulted in significantly greater reductions in TG (p = 0.004), fasting insulin (p = 0.005), and HOMA-IR (p = 0.012), as well as a greater increase in HDL-C (p < 0.001) compared to metformin. The overall incidence of adverse effects was comparable (33.3% vs. 38.1%; p = 0.650), with no serious adverse events reported. CONCLUSIONS:These findings suggest that empagliflozin is a promising alternative to metformin for managing metabolic complications in patients treated with clozapine or olanzapine. These findings warrant confirmation and further investigation in larger, long-term studies. TRIAL REGISTRATION:The trial was registered prospectively at the Iranian Registry of Clinical Trials (IRCT) with the ID code IRCT20120215009014N538 on November 12, 2024.
Double blind randomized placebo controlled trials (RCTs) have been regarded as the gold standard for evaluation of potential treatments. Nevertheless RCTs for psychiatric illnesses, almost all of which sorely need better medications, have been plagued with high placebo response, practically diluting true drug effects (if any) and potentially discouraging novel drug developments. Various strategies have been considered to tackle this significant issue but none has been particularly successful to date. The author proposes to examine the belief of treatment allocation by the study participants, (at least) twice, during the study period. The results will be interpreted in terms of correctness and consistency, regardless of the actual treatment allocation. Whether response trajectory differs based on these parameters (e.g., robust placebo response stems from those who consistently guessed placebo as active drug) should be tested and analyzed. The concept could be useful regarding functional unblinding, another serious issue in psychiatric RCTs, for drugs with strong clinical effects.
OBJECTIVE:'Ego dissolution' refers to a temporary state characterized by diminished self-referential processing, which leads to a breakdown of personal boundaries and an enhanced sense of unity with the environment. Both psychedelics, such as ayahuasca, and contemplative practices, like meditation, have been proposed as mechanisms for modulating the ego. While ayahuasca induces transient self-perception alterations, meditation promotes more sustained changes through cognitive and emotional regulation. This study examines whether ayahuasca consumption modulates the ego and compares its effects with those of meditation. METHODS:A total of 37 ayahuasca users and 137 meditators participated. We used the "Delusion of Me" (DoM) index, a unidimensional self-report measure comprising three domains: acceptance, decentering, and non-attachment. It could be considered closely related to the concept of self 'as a content' and may potentially serve as a measure of ego. RESULTS:Meditators exhibited significantly higher DoM scores than ayahuasca users. The quadratic regression did not show a cumulative effect, with no significant relationship found between the number of ayahuasca sessions and DoM scores. CONCLUSIONS:Meditation practice correlated with higher DoM scores and cumulative practice showed a significant non-linear association with DoM. Conversely, repeated ayahuasca exposure demonstrated no evidence of a cumulative association in this sample.
OBJECTIVE:To assess the prevalence and severity of vitamin D deficiency in patients with bipolar disorder and examine potential associations with their sociodemographic and clinical characteristics. METHODS:A retrospective study was conducted on 185 inpatients aged 18-65, diagnosed with bipolar disorder and hospitalized at the Clinic for Psychiatry, University Clinical Center of Serbia, between 2022 and 2024. Data were obtained by analyzing medical records using the hospital information system "Heliant". RESULTS:Vitamin D deficiency was observed in 76.8% of patients, with 14.6% having severe deficiency, 36.8% deficiency, and 25.4% insufficiency. Significant associations were found between vitamin D deficiency and the autumn/winter season, as well as lower education levels. Additionally, manic episodes were more frequently observed during spring and summer. No other significant associations were identified. CONCLUSION:A high prevalence of vitamin D deficiency was found among patients with bipolar disorder. Routine screening and early intervention should be considered, including education, supplementation, and lifestyle modifications. Integrating preventive strategies into psychiatric care may improve clinical outcomes and mood stability. Further longitudinal and interventional research is needed to clarify the potential role of vitamin D and to guide evidence-based prevention and treatment in bipolar disorder.
OBJECTIVE:The CYP2D6*10 allele, which is prevalent in the Indian population, is of particular clinical significance. This study aims to investigate the effect of the CYP2D6*10 allele on the pharmacokinetics of risperidone and its metabolites following single-dose administration in healthy South Indian volunteers. METHODS:The study was conducted with twenty healthy volunteers who were administered a single 2 mg dose of risperidone. CYP2D6 genotyping was performed using the PCR-RFLP method. Plasma levels of risperidone (RIS) and its active metabolite 9-hydroxyrisperidone (9-OHRIS) were quantified using a UPLC-DAD system. RESULTS:Significant differences in pharmacokinetic parameters were observed across the CYP2D6*10 genotypes. For intermediate metabolizers, the Cmax, AUC0-t, and T1/2 were approximately 1.2 times higher, and the metabolic ratio was double compared to normal metabolizers. Notably, the Cmax of the active moiety was significantly higher in intermediate metabolizers compared to normal metabolizers (p < 0.05). These findings indicate that CYP2D6 polymorphisms are associated with altered pharmacokinetic profiles of risperidone, with a reduced metabolic activation in individuals carrying the *10 allele. CONCLUSION:The results suggest that CYP2D6 genotyping could help inform personalized dosing strategies for risperidone, though further randomized controlled trials are required to confirm these findings.
INTRODUCTION:Non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol are among the most commonly used medications worldwide. It has been suggested that the misuse of such medications is not uncommon. The objective of the present research was to explore prevalence, reported reasons and psychopathological concomitants related to NSAIDs/paracetamol misuse in a sample of users. METHODS:The sample was made of 346 NSAIDs or paracetamol users (age range: 18-64 years); assessments included the 4-item Perceived Stress Scale (PSS-4), the 10-item version of the Adverse Childhood Experiences International Questionnaire (ACE-IQ-10), the Body Image Concern Inventory (BICI), the Alcohol Use Disorders Identification Test-C (AUDIT-C), and questions related to NSAIDs/paracetamol misuse. RESULTS:Forty-eight individuals (13.9%) were categorized as NSAIDs/paracetamol misusers. A logistic regression model showed that higher scores in AUDIT-C, BICI and ACE-IQ-10, and the use of psychiatric medications, were significantly associated with the likelihood of NSAIDs/paracetamol misuse. Specific reasons related to the misuse are also reported. DISCUSSION:Our findings provide novel insights into the relationship between NSAIDs/paracetamol misuse and psychopathology, with potential clinical implications for prevention and treatment.
OBJECTIVE:Impulsivity is a transdiagnostic risk factor for numerous health morbidities and is strongly associated with early relapse and poor treatment outcomes in addictions and mood-disorders. Lithium carbonate can be helpful in moderating the impulsive behaviors associated with mania, possibly mediated by reduced myo-inositol activity following inhibition of the enzyme inositol monophosphatase (IMPase). We tested the hypothesis that impulsivity-as motor disinhibition, decisions without adequate information, and stronger preferences for small immediate rewards over larger later rewards-can be moderated by the IMPase inhibitor ebselen in healthy adult volunteers. METHODS:One hundred and thirty healthy adults completed a between-subjects, double-blind, placebo-controlled protocol. Over 2 days, participants received a previously validated dose of 1800 mg of ebselen or placebo before completing tests of impulsivity and decision-making. RESULTS:There were no substantive changes in any measure of impulsivity following treatment with ebselen compared with placebo. Neither was there any convincing evidence of stronger treatment effects in high-trait impulsive participants compared with low-trait participants. CONCLUSION:These results fail to replicate findings that ebselen administration moderates validated measures of impulsivity in healthy adults, at least at doses shown to reduce myo-inositol within the medial prefrontal cortex and produce changes in emotional processing and reward-based learning.
INTRODUCTION:Atypical antipsychotics are widely prescribed in child and adolescent psychiatry and are known to affect cardiac repolarization, most commonly reflected by QTc prolongation. However, QTc alone may not fully capture repolarization heterogeneity. The frontal QRS-T angle f(QRS-T) is an electrocardiographic marker reflecting ventricular depolarization-repolarization mismatch. This study aimed to evaluate and compare f(QRS-T) alongside other repolarization parameters in children and adolescents receiving atypical antipsychotics versus healthy controls. METHODS:This retrospective observational study included 45 children and adolescents (6-17 years) receiving atypical antipsychotics for at least six months and 45 age- and sex-matched healthy controls. Standard 12-lead ECG recordings were obtained to measure f(QRS-T), QTc, Tp-e interval, and Tp-e-based ratios. Correlation analyses assessed associations between f(QRS-T), QTc, and duration of antipsychotic use. Hierarchical multiple linear regression was performed to identify independent predictors of f(QRS-T) in the patient group. Receiver operating characteristic (ROC) analysis evaluated the discriminative ability of f(QRS-T) for QTc prolongation (QTc ≥ 440 ms). RESULTS:Children receiving atypical antipsychotics exhibited significantly higher f(QRS-T), QTc interval, Tp-e interval, Tp-e(c), Tp-e(c)/QT, and iCEBc ratios compared with healthy controls (p < 0.05). Frontal QRS-T angle was positively correlated with QTc (r = 0.406, p < 0.001) but not with the duration of antipsychotic treatment. In hierarchical regression analysis, age, sex, QTc and duration of antipsychotic use were not independent predictors of f(QRS-T). ROC analysis demonstrated that f(QRS-T) moderately discriminated patients with QTc prolongation (AUC = 0.735); a cut-off value of 26.5° yielded a sensitivity of 72% and a specificity of 60%. CONCLUSION:f(QRS-T) is significantly increased in children and adolescents receiving atypical antipsychotics and is associated with QTc prolongation, although it is not independently predicted by treatment duration or conventional QT-based indices. These findings suggest that f(QRS-T) may serve as a complementary electrocardiographic marker of repolarization heterogeneity alongside QTc in the cardiac safety monitoring of pediatric patients treated with atypical antipsychotics.
BACKGROUND:Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for metabolic disorders. Howeve, their effects on depressive symptoms and psychological well-being remain uncertain. METHODS:We conducted a systematic review and meta-analysis of randomized controlled trials evaluating the effects of GLP-1RAs on depressive symptoms and psychological well-being. Random-effects models were used to calculate standardized mean differences (SMDs). Subgroup and meta-regression analyses were performed to explore heterogeneity. The protocol was registered with PROSPERO (CRD42024566217). RESULTS:In total, 25 trials (17,751 participants) evaluated psychological well-being and 11 trials (1961 participants) evaluated depressive symptoms. GLP-1RA treatment was associated with a small but significant improvement in psychological well-being compared with control conditions (SMD = 0.374, 95% CI 0.093-0.656), whereas no significant effect was observed for depressive symptoms (SMD = 0.079, 95% CI -0.024-0.182). Improvements in psychological well-being were consistently observed in studies using semaglutide, tirzepatide or liraglutide, subcutaneous administration, and in populations with type 2 diabetes mellitus or obesity. CONCLUSIONS:GLP-1RA treatment was associated with modest improvements in psychological well-being but not depressive symptoms. These findings should be interpreted cautiously and suggest that any observed psychological benefits are likely indirect, potentially reflecting improvements in metabolic status or general health, rather than direct mood-improving effects.
OBJECTIVE:Zolpidem and zopiclone are widely prescribed hypnotics for older adults, yet their comparative safety regarding hip fracture risk remains unclear. This study aimed to compare the risk of hip fracture between zolpidem and zopiclone among adults aged 65-84 years. METHODS:Electronic health records from 166 global healthcare organizations in the TriNetX platform were analyzed. Adults aged 65-84 years who were newly prescribed zolpidem or zopiclone were identified. Propensity score matching was used to balance baseline characteristics. The TriNetX "Compare Outcomes" tool was used to estimate the cumulative incidence of hip fracture, hazard ratio, and 95% confidence interval between zolpidem users and zopiclone users. RESULTS:After propensity score matching, 41,500 adults were included in each group. During the 1-year follow-up period, 100 adults in the zolpidem group and 174 adults in the zopiclone group experienced a hip fracture, corresponding to cumulative incidences of 0.24% and 0.42%, respectively. In the Cox proportional hazards regression model, zolpidem use was associated with a reduced risk of hip fracture (hazard ratio 0.51; 95% confidence interval, 0.40-0.66). CONCLUSION:Zolpidem was associated with a lower risk of hip fracture compared with zopiclone among adults aged 65-84 years. These findings highlight the need for further research to confirm these differences and explore underlying mechanisms.
Treatment-resistant depression (TRD) remains a formidable challenge in psychiatry, with nearly one-third of patients with major depressive disorder (MDD) failing to respond adequately to first-line pharmacological treatments. Pathophysiology in MDD has highlighted the N-methyl-D-aspartate (NMDA) glutamatergic system as a promising therapeutic target. In 2022, the US Food and Drug Administration (FDA) approved the bupropion and dextromethorphan (DXM) combination (BDC), the first oral combination that affects both the NMDA receptor and norepinephrine-dopamine systems. DXM is an uncompetitive NMDA receptor antagonist, and in combination with bupropion, it has been shown to be a rapidly acting oral medication with clinically significant improvement in the first week of treatment. BDC, however, has many inherent limitations such as contraindications in those with eating disorders and a history of seizures. Anxiety is a common comorbidity in MDD, and bupropion has been shown to lack efficacy in treating anxiety. In addition, BDC did not improve cognition. Memantine can treat depression and cognitive impairments concurrently. Fixed-dose combination pills can be less flexible than prescribing each drug separately, as BDC is limited to a 105 mg (bupropion)-45 mg (DXM) combination. The projected 1-month cost of possible combinations of memantine ($5.00) with a selective serotonin reuptake inhibitor (SSRI, $4.00), serotonin-norepinephrine reuptake inhibitor (SNRI, $15.00), and bupropion ($18.00) are cheaper than BDC ($1119.00). Instead of BDC, we propose various alternatives such as a bupropion-memantine combination or SSRI/SNRI and memantine for MDD/TRD.
BACKGROUND AND OBJECTIVE:Isotretinoin is a systemic agent widely used in the treatment of severe acne vulgaris. Previous studies have reported that isotretinoin use may be associated with depression, anxiety, and sleep disorders. The aim of this study was to evaluate changes in sleep quality, anxiety, and depression in patients with acne vulgaris during isotretinoin treatment. MATERIALS AND METHODS:This retrospective analysis of prospectively collected data included 155 patients receiving isotretinoin treatment at a tertiary dermatology outpatient clinic in Turkey between January 2023 and December 2024. The Pittsburgh Sleep Quality Index (PSQI), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and Global Acne Grading System (GAGS) were administered to patients before treatment, at the end of the first month, and at the end of the third month of treatment. Patients with a history of psychiatric disorders, use of psychotropic medications, or systemic diseases affecting sleep or mood were excluded from the study. RESULTS:Isotretinoin treatment was associated with a significant reduction in acne severity over the 3-month follow-up period. A transient increase in depressive and anxiety symptoms was observed during the first month of treatment, followed by a significant improvement by the third month. Overall, isotretinoin treatment was not associated with a significant deterioration in sleep quality throughout the study period. CONCLUSION:Isotretinoin treatment was associated with a significant reduction in acne severity, depression, and anxiety, while no significant overall change in sleep quality was observed. The temporary increase in depression and anxiety observed at the end of the first month may be related to the cutaneous side effects of isotretinoin. Further prospective studies are needed to better clarify the neuropsychiatric effects of isotretinoin.
