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PCN Reports : Psychiatry and Clinical... Sep 2023Nocturnal eating behavior in patients with sleep-related eating disorder (SRED) is difficult to control and can become chronic, causing weight gain and psychological...
BACKGROUND
Nocturnal eating behavior in patients with sleep-related eating disorder (SRED) is difficult to control and can become chronic, causing weight gain and psychological distress. Here, we report a case of SRED comorbid with major depressive disorder successfully treated by switching from brotizolam to suvorexant, that is, from a benzodiazepine to an orexin receptor antagonist.
CASE PRESENTATION
A 25-year-old woman complained of night snacking with partial/complete amnesia and sleepwalking for 1 year. She had a diagnosis of major depressive disorder at age 20 and was on paroxetine and brotizolam for depression and insomnia. At 24 years of age, she experienced her second depressive episode, then her amnestic nocturnal eating became prominent. Even after improvement in depressive symptoms, she experienced uncontrollable nocturnal eating episodes every 2 days, resulting in weight gain of over 10 kg. After a partial amnestic eating episode following an awakening from stage N2 sleep was confirmed through video polysomnography, she was diagnosed with SRED. Considering her strong desire to resolve involuntary eating, we instructed her to discontinue brotizolam and start suvorexant. Subsequently, her nocturnal eating completely disappeared. She experienced rebound insomnia, which improved within 1 month. She was then continued on 10 mg of suvorexant and has not experienced nocturnal eating for 2 years.
CONCLUSION
This case highlights the importance of discontinuing benzodiazepines in the treatment of SRED, but also suggests the potential benefit of orexin receptor antagonists in the treatment of SRED. The efficacy of orexin receptor antagonists in idiopathic SRED should be tested in future studies.
PubMed: 38867814
DOI: 10.1002/pcn5.123 -
The Journal of Pharmacy and Pharmacology Jun 2024This study aimed to assess the erectogenic properties of isoliquiritigenin taking sildenafil (SDF) as the standard.
OBJECTIVE
This study aimed to assess the erectogenic properties of isoliquiritigenin taking sildenafil (SDF) as the standard.
METHODS
The binding affinity of isoliquiritigenin (ISL) with the erectile marker proteins (endothelial nitric oxide synthase [eNOS] and enzyme phosphodiesterase type 5 [PDE5]) was investigated using Autodock Vina, which was validated using molecular dynamics simulation. Furthermore, the effect of ISL on the eNOS and PDE5 messenger ribonucleic acid (mRNA) expression and the sexual behavior of mice was investigated, along with the assessment of the pharmacokinetics of ISL.
KEY FINDINGS
The results revealed that the binding affinity of ISL-eNOS/PDE5 and SDF-eNOS/PDE5 was in the range of -7.5 to -8.6 kcal/mol. The ISL-eNOS/PDE5 complexes remained stable throughout the 100 ns simulation period. Root mean square deviation, Rg, SASA, hydrogen, and hydrophobic interactions were similar between ISL-eNOS/PDE5 and SDF-eNOS/PDE5. Analysis of mRNA expressions in paroxetine (PRX)-induced ED mice showed that the co-administration of PRX with ISL reduced PDE5 and increased eNOS mRNA expression, similar to the co-administered group (PRX+SDF). The sexual behavior study revealed that the results of PRX+ISL were better than those of the PRX+SDF group. Pharmacokinetic evaluation further demonstrated that ISL possesses drug-like properties.
CONCLUSIONS
The results showed that ISL is equally potent as SDF in terms of binding affinity, specific pharmacological properties, and modulating sexual behavior.
PubMed: 38865360
DOI: 10.1093/jpp/rgae054 -
The Lancet. Psychiatry Jul 2024Antidepressant discontinuation symptoms are becoming an increasingly important part of clinical practice, but the incidence of antidepressant discontinuation symptoms... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Antidepressant discontinuation symptoms are becoming an increasingly important part of clinical practice, but the incidence of antidepressant discontinuation symptoms has not been quantified. An estimate of antidepressant discontinuation symptoms incidence could inform patients and clinicians in the discontinuation of treatment, and provide useful information to researchers in antidepressant treatments. We aimed to assess the incidence of antidepressant discontinuation symptoms in patients discontinuing both antidepressants and placebo in the published literature.
METHODS
We systematically searched Medline, EMBASE, and CENTRAL from database inception until Oct 13, 2022 for randomised controlled trials (RCTs), other controlled trials, and observational studies assessing the incidence of antidepressant discontinuation symptoms. To be included, studies must have investigated cessation or tapering of an established antidepressant drug (excluding antipsychotics, lithium, or thyroxine) or placebo in participants with any mental, behavioural, or neurodevelopmental disorder. We excluded studies in neonates, and those using antidepressants for physical conditions such as pain syndromes due to organic disease. After study selection, summary data extraction, and risk of bias evaluation, data were pooled in random-effects meta-analyses. The main outcome was the incidence of antidepressant discontinuation symptoms after discontinuation of antidepressants or placebo. We also analysed the incidence of severe discontinuation symptoms. Sensitivity and meta-regression analyses tested a selection of methodological variables.
FINDINGS
From 6095 articles screened, 79 studies (44 RCTs and 35 observational studies) covering 21 002 patients were selected (72% female, 28% male, mean age 45 years [range 19·6-64·5]). Data on ethnicity were not consistently reported. 16 532 patients discontinued from an antidepressant, and 4470 patients discontinued from placebo. Incidence of at least one antidepressant discontinuation symptom was 0·31 (95% CI 0·27-0·35) in 62 study groups after discontinuation of antidepressants, and 0·17 (0·14-0·21) in 22 study groups after discontinuation of placebo. Between antidepressant and placebo groups of included RCTs, the summary difference in incidence was 0·08 [0·04-0·12]. The incidence of severe antidepressant discontinuation symptoms after discontinuation of an antidepressant was 0·028 (0·014-0·057) compared with 0·006 (0·002-0·013) after discontinuation of placebo. Desvenlafaxine, venlafaxine, imipramine, and escitalopram were associated with higher frequencies of discontinuation symptoms, and imipramine, paroxetine, and either desvenlafaxine or venlafaxine were associated with a higher severity of symptoms. Heterogeneity of results was substantial.
INTERPRETATION
Considering non-specific effects, as evidenced in placebo groups, the incidence of antidepressant discontinuation symptoms is approximately 15%, affecting one in six to seven patients who discontinue their medication. Subgroup analyses and heterogeneity figures point to factors not accounted for by diagnosis, medication, or trial-related characteristics, and might indicate subjective factors on the part of investigators, patients, or both. Residual or re-emerging psychopathology needs to be considered when interpreting the results, but our findings can inform clinicians and patients about the probable extent of antidepressant discontinuation symptoms without causing undue alarm.
FUNDING
None.
Topics: Humans; Antidepressive Agents; Incidence; Substance Withdrawal Syndrome; Randomized Controlled Trials as Topic
PubMed: 38851198
DOI: 10.1016/S2215-0366(24)00133-0 -
International Journal of Pharmaceutics Jun 2024Depression is one of the most common psychiatric disorders. Nanotechnology has emerged to optimize the pharmacological response. Therefore, the aim of this work was to...
Depression is one of the most common psychiatric disorders. Nanotechnology has emerged to optimize the pharmacological response. Therefore, the aim of this work was to develop and characterize liposomes and nanocapsules containing paroxetine hydrochloride and evaluate their antidepressant-like effect using the open field and tail suspension tests in mice. Liposomes and nanocapsules were prepared using the reverse-phase evaporation and nanoprecipitation methods, respectively. The particle size of the formulation ranged from 121.81 to 310.73 nm, the polydispersity index from 0.096 to 0.303, the zeta potential from -11.94 to -34.50 mV, the pH from 5.31 to 7.38, the drug content from 80.82 to 94.36 %, and the association efficiency was 98 %. Paroxetine hydrochloride showed slower release when associated with liposomes (43.82 %) compared to nanocapsules (95.59 %) after 10 h. In Vero cells, in vitro toxicity showed a concentration-dependent effect for paroxetine hydrochloride nanostructures. Both nanostructures decreased the immobility time in the TST at 2.5 mg/kg without affecting the number of crossings in the open field test, suggesting the antidepressant-like effect of paroxetine. In addition, the nanocapsules decreased the number of groomings, reinforcing the anxiolytic effect of this drug. These results suggest that the nanostructures were effective in preserving the antidepressant-like effect of paroxetine hydrochloride even at low doses.
PubMed: 38848799
DOI: 10.1016/j.ijpharm.2024.124304 -
Frontiers in Pharmacology 2024This study aimed to investigate the plasma and breastmilk concentrations for sertraline, citalopram and paroxetine for assessment of the Milk/Plasma (M/P) ratio and...
OBJECTIVES
This study aimed to investigate the plasma and breastmilk concentrations for sertraline, citalopram and paroxetine for assessment of the Milk/Plasma (M/P) ratio and Absolute Infant Dose (AID), and to determine actual infant drug exposure through breastfeeding. Subsequently, informed recommendations will be formulated regarding the advisability of breastfeeding in women undergoing treatment with the three most widely used antidepressants.
METHODS
A pharmacokinetic study in lactating women and their infants using sertraline, citalopram or paroxetine was performed. Paired breastmilk and plasma samples and single point infant plasma samples were collected to determine antidepressant concentrations. An Area Under the Curve (AUC) based approach with the trapezoidal rule was used to calculate M/P ratios and AID for all three antidepressants by combining all measured concentrations for the same dose.
RESULTS
Thirty-seven lactating women and their infants participated in this study. 111 paired breastmilk and plasma samples and 37 single point infant plasma samples were collected. Detectable concentrations of sertraline, citalopram and paroxetine were present in all breastmilk samples. For sertraline and citalopram M/P ratio is above one, indicating higher breastmilk than plasma concentrations, however, drug exposure by breastmilk did not lead to detectable plasma drug levels in any of the 15 infants for sertraline, for nine (out of 13) infants for citalopram and for eight (out of nine) infants for paroxetine.
CONCLUSION
Given the well-known benefits of breastfeeding, our findings support breastfeeding of infants by mothers who are taking sertraline, citalopram or paroxetine is safe. Sertraline and paroxetine are the preferred antidepressants during breastfeeding, reaching mostly undetectable infant drug levels.
PubMed: 38841362
DOI: 10.3389/fphar.2024.1414677 -
Expert Review of Neurotherapeutics Jul 2024Despite its milder severity, the chronic nature of dysthymia leads to significant impairments and functional limitations. The treatment of dysthymia has received... (Review)
Review
INTRODUCTION
Despite its milder severity, the chronic nature of dysthymia leads to significant impairments and functional limitations. The treatment of dysthymia has received considerably less research attention compared to major depressive disorder (MDD).
AREAS COVERED
The authors have conducted a comprehensive review on the treatment of dysthymia. Their primary objective was to identify therapeutic options that have demonstrated genuine efficacy. To do this, they searched the PubMed database, without any time restrictions, to retrieve original studies. The samples were exclusively comprised individuals diagnosed with dysthymia according to the diagnostic criteria outlined in DSM-III, DSM-III-R, DSM-IV, or DSM-IV-TR.
EXPERT OPINION
Within the realm of dysthymia treatment, several antidepressants, including imipramine, sertraline, paroxetine, minaprine, moclobemide, and amineptine, in addition to the antipsychotic agent amisulpride, have demonstrated superiority over placebo. In certain studies, psychotherapeutic interventions did not distinguish themselves significantly from pharmacological treatments and failed to exhibit greater efficacy than a placebo. However, these findings remain inconclusive due to the limited number of studies and substantial methodological limitations prevalent in a significant proportion of them. Limitations include factors like small sample sizes, the absence of placebo comparisons, and a lack of study blinding.
Topics: Humans; Dysthymic Disorder; Antidepressive Agents; Antipsychotic Agents; Psychotherapy
PubMed: 38805342
DOI: 10.1080/14737175.2024.2360671 -
Sleep Medicine Jul 2024Sleep disturbances are an important symptom dimension of post-traumatic-stress-disorder (PTSD). There is no meta-analytic evidence examining the effects of all types of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Sleep disturbances are an important symptom dimension of post-traumatic-stress-disorder (PTSD). There is no meta-analytic evidence examining the effects of all types of pharmacotherapy on sleep outcomes among patients with PTSD.
METHODS
Medline/Embase/PsychInfo/CENTRAL/clinicaltrials.gov/ICTRP, reference lists of published reviews and all included studies were searched for Randomised Controlled Trials (RCTs) examining any pharmacotherapy vs. placebo or any other drug among patients with PTSD.
PRIMARY OUTCOMES
total sleep time, nightmares, sleep quality.
SECONDARY OUTCOMES
sleep onset latency, number of nocturnal awakenings, time spent awake following sleep onset, dropouts due to sleep-related adverse-effects, insomnia/somnolence/vivid-dreams as adverse-effects. Pairwise and network meta-analyses were performed.
RESULTS
99 RCTs with 10,481 participants were included. Prazosin may be the most effective treatment for insomnia (SMD = -0.88, 95%CI = [-1.22;-0.54], nightmares (SMD = -0.44, 95%CI = [-0.84;-0.04]) and poor sleep quality (SMD = -0.55, 95%CI = [-1.01;-0.10]). Evidence is scarce and indicates lack of efficacy for SSRIs, Mirtazapine, z-drugs and benzodiazepines, which are widely used in daily practice. Risperidone and Quetiapine carry a high risk of causing somnolence without having a clear therapeutic benefit. Hydroxyzine, Trazodone, Nabilone, Paroxetine and MDMA-assisted psychotherapy may be promising options, but more research is needed.
CONCLUSIONS
Underpowered individual comparisons and very-low to moderate confidence in effect estimates hinder the generalisability of the results. More RCTs, specifically reporting on sleep-related outcomes, are urgently needed.
Topics: Humans; Stress Disorders, Post-Traumatic; Network Meta-Analysis; Sleep Wake Disorders; Prazosin; Randomized Controlled Trials as Topic; Dreams; Sleep Initiation and Maintenance Disorders
PubMed: 38795401
DOI: 10.1016/j.sleep.2024.05.032 -
EBioMedicine Jun 2024Understanding the impact of CYP2D6 metabolism on paroxetine, a widely used antidepressant, is essential for precision dosing. (Meta-Analysis)
Meta-Analysis
Dose adjustment of paroxetine based on CYP2D6 activity score inferred metabolizer status in Chinese Han patients with depressive or anxiety disorders: a prospective study and cross-ethnic meta-analysis.
BACKGROUND
Understanding the impact of CYP2D6 metabolism on paroxetine, a widely used antidepressant, is essential for precision dosing.
METHODS
We conducted an 8-week, multi-center, single-drug, 2-week wash period prospective cohort study in 921 Chinese Han patients with depressive or anxiety disorders (ChiCTR2000038462). We performed CYP2D6 genotyping (single nucleotide variant and copy number variant) to derive the CYP2D6 activity score and evaluated paroxetine treatment outcomes including steady-state concentration, treatment efficacy, and adverse reaction. CYP2D6 metabolizer status was categorized into poor metabolizers (PMs), intermediate metabolizers (IMs), extensive metabolizers (EMs), and ultrarapid metabolizers (UMs). The influence of CYP2D6 metabolic phenotype on paroxetine treatment outcomes was examined using multiple regression analysis and cross-ethnic meta-analysis. The therapeutic reference range of paroxetine was estimated by receiver operating characteristic (ROC) analyses.
FINDINGS
After adjusting for demographic factors, the steady-state concentrations of paroxetine in PMs, IMs, and UMs were 2.50, 1.12, and 0.39 times that of EMs, with PM and UM effects being statistically significant (multiple linear regression, P = 0.03 and P = 0.04). Sex and ethnicity influenced the comparison between IMs and EMs. Moreover, poor efficacy of paroxetine was associated with UM, and a higher risk of developing adverse reactions was associated with lower CYP2D6 activity score. Lastly, cross-ethnic meta-analysis suggested dose adjustments for PMs, IMs, EMs, and UMs in the East Asian population to be 35%, 40%, 143%, and 241% of the manufacturer's recommended dose, and 62%, 68%, 131%, and 159% in the non-East Asian population.
INTERPRETATION
Our findings advocate for precision dosing based on the CYP2D6 metabolic phenotype, with sex and ethnicity being crucial considerations in this approach.
FUNDING
National Natural Science Foundation of China; Academy of Medical Sciences Research Unit.
Topics: Adult; Female; Humans; Male; Middle Aged; Anxiety Disorders; China; Cytochrome P-450 CYP2D6; Depressive Disorder; East Asian People; Genotype; Paroxetine; Polymorphism, Single Nucleotide; Prospective Studies; Treatment Outcome
PubMed: 38776596
DOI: 10.1016/j.ebiom.2024.105165 -
Heliyon May 2024To investigate whether SJF functions in similar manner as the key substance in the inflammatory process, soluble epoxide hydrolase (sEH) inhibitor, to inhibit the...
AIM
To investigate whether SJF functions in similar manner as the key substance in the inflammatory process, soluble epoxide hydrolase (sEH) inhibitor, to inhibit the arachidonic acid metabolic pathway and nuclear factor kappa-B(NF-κB) signal path in the hippocampi of postpartum depression rats.
METHODS
The rats were subcutaneous injected estradiol benzoate and progesterone to build PPD rat model. SJF, paroxetine hydrochloride and sEH inhibitor (AUDA) were used to treat PPD rats for 3 weeks. Then the morphological changes of hippocampi and various proteins were observed after that behavioral test were conducted in all 36 SD rats in six group: SJF, paroxetine, AUDA, PPD, sham and normal group.
RESULTS
Weight, results of sucrose preference, upright times, total and center squares crossing decreased significantly (P < 0.01), whereas immobility time increased (P < 0.01). Results above were reversed in animals that in the SJF, paroxetine and AUDA groups. Hippocampal neurons in PPD rats partially degenerated with narrowed nuclei, increased autophagy and mitochondria bound to lysosomes were visible while the autophagy of hippocampal neurons in the paroxetine and AUDA group decreased, with a small amount of lysosomes. sEH, COX-2, 5-LOX, TNF-α, IL-1, IL-6, NF-κB p65, and Cor increased in hippocampi of PPD rats while EETs and 5-HT decreased. Protein expressions of Ibal, GFAP, p-IκBα, p65, and p-p65(S536)increased in PPD animals. Those changes were reversed by SJF, paroxetine and AUDA. Gene expressions of TNF-α, IL-1β, IL-6, 5-LOX, COX-2 and p65 increased in PPD rats and the changes of expression in these genes were reversed by paroxetine and AUDA. SJF reversed the gene expression changes of COX-2, TNF-α, and IL-1β.
CONCLUSION
SJF may have an analogous effect as sEH inhibitor to relieve depressive symptoms by suppressing inflammatory signaling pathways in hippocampi of PPD rats, which involves AA metabolic pathway and NF-κB signal pathway.
PubMed: 38726147
DOI: 10.1016/j.heliyon.2024.e29978 -
Cureus Mar 2024Neuroleptic malignant syndrome (NMS) is a severe reaction to antipsychotic medications characterized by fever, muscle rigidity, altered mental status, and autonomic...
Neuroleptic malignant syndrome (NMS) is a severe reaction to antipsychotic medications characterized by fever, muscle rigidity, altered mental status, and autonomic dysfunction. Here, we describe the case of a 58-year-old female who presented with altered mental status two days after open reduction and internal fixation of the hip. A rapid response team was called when the patient appeared agitated with increased respiratory demand. After being intubated and moved to the ICU, she became febrile and rigid. A preliminary diagnosis of metabolic encephalopathy of unknown origin was made. Before being transported to the ICU, the patient was given multiple haloperidol doses in addition to her continued at-home medication, paroxetine, for major depressive disorder. The differential diagnosis included a workup for NMS, serotonin syndrome, and infectious processes. Once NMS was determined as the most likely etiology, all antipsychotic and serotonergic medications were discontinued. Then dantrolene and amantadine were administered, which resulted in clinically significant improvement. This case report demonstrates the importance of early identification of and intervention for NMS.
PubMed: 38686249
DOI: 10.7759/cureus.57276