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The Primary Care Companion For CNS... Jun 2024To review the literature on the neurobiological mechanisms of obsessive-compulsive symptoms (OCS) in people with dementia. MEDLINE/PubMed, CENTRAL, and PsycNet... (Review)
Review
To review the literature on the neurobiological mechanisms of obsessive-compulsive symptoms (OCS) in people with dementia. MEDLINE/PubMed, CENTRAL, and PsycNet databases were searched from inception to March 2023. Original studies of any methodology with newly published data on the neurobiological underpinnings of OCS in patients with dementia, regardless of patient age or comorbidity and publication year, were included. The following search terms were used: (Obses* OR compul* OR OCD) AND (cognitive de* OR cognitive dysfunction OR cognitive disfunction OR dementia). Individual study data were extracted onto a piloted extractions sheet. Patients with dementia and OCS were reported to have atrophy and hypoperfusion of frontal, temporal, striatal, and limbic structures. Serotonergic agents may be efficacious in reducing OCS. One randomized controlled trial of paroxetine in behavioral symptoms of dementia did not show efficacy. Evidence of dopaminergic dysfunction is too sparse to draw conclusions. Microglia dysfunction mediates obsessive-compulsive-like symptoms. Mutations of microtubule-associated protein τ may increase the risk of OCS. Cognitive self-consciousness and obsessive-compulsive-related cognitions may mediate OCS in old age. Dysfunction of the processing of one class of stimuli may increase the salience of other classes of stimuli, leading to OCS. Frontal lobe hypometabolism and temporal lobe atrophy and hypometabolism are unexpected given previous research in obsessive compulsive disorder. Serotonergic agents have encouraging efficacy in case reports but require more specific research. .
Topics: Humans; Obsessive-Compulsive Disorder; Dementia
PubMed: 38905511
DOI: 10.4088/PCC.23r03689 -
MDM Policy & Practice 2024Global climate change is resulting in dramatic increases in wildfires. Individuals exposed to wildfires experience a high burden of posttraumatic stress disorder...
UNLABELLED
Global climate change is resulting in dramatic increases in wildfires. Individuals exposed to wildfires experience a high burden of posttraumatic stress disorder (PTSD), and the cost-effectiveness of the treatment options to address PTSD from wildfires has not been studied. The objective of this study was to conduct a cost-utility analysis comparing screening followed by treatment with paroxetine or trauma-focused cognitive behavioral therapy (TF-CBT) versus no screening in Canadian adult wildfire evacuees. Using a Markov model, quality-adjusted life-years (QALYs) and costs were evaluated over a 5-y time horizon using health care and societal perspectives. All costs and utilities in the model were discounted at 1.5%. Probabilistic and deterministic sensitivity analyses examined the uncertainty in the incremental net monetary benefit (INMB) under a willingness-to-pay threshold of $50,000. From a societal perspective, no screening (NMB = $177,641) was dominated by screening followed by treatment with paroxetine (NMB = $180,733) and TF-CBT (NMB = $181,787), with TF-CBT having the highest likelihood of being cost-effective at a willingness-to-pay threshold of $50,000 per QALY (probability = 0.649). The initial prevalence of PTSD, probability of acceptance of treatment, and costs of productivity had the largest impact on the INMB of both paroxetine or TF-CBT versus no screening. Neither intervention was cost-effective at a willingness-to-pay threshold of $50,000 per QALY from a health care perspective. Screening followed by treatment with paroxetine or TF-CBT compared with no screening was found to be cost-saving while providing additional QALYs in wildfire evacuees. Governments should consider funding screening programs for PTSD followed by treatment with TF-CBT for wildfire evacuees.
HIGHLIGHTS
Two prior studies examined the cost-effectiveness of screening followed by treatment for PTSD among individuals exposed to other disaster-type events (i.e., terrorist attack and Hurricane Sandy) and found screening followed by treatment (i.e., cognitive behavioral therapy [CBT]) to be highly cost-effective.Among wildfire evacuees, screening followed by treatment with paroxetine or trauma-focused (TF)-CBT provides additional quality-adjusted life-years (QALYs) and is cost-saving from a societal perspective. TF-CBT was the treatment option found most likely to be cost-effective.Neither treatment option was cost-effective at a willingness-to-pay threshold of $50,000 per QALY from a health care perspective.Screening programs for PTSD should be considered for wildfire evacuees, and individuals diagnosed with PTSD could be prescribed either TF-CBT or paroxetine depending on their preference and resources availability.
PubMed: 38904072
DOI: 10.1177/23814683241260423 -
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 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 -
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 -
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 -
Cureus Apr 2024Eating disorders (EDs) are among the most dangerous mental illnesses, that are characterized by high mortality rates, multisystem comorbidity, and an often chronic and...
Eating disorders (EDs) are among the most dangerous mental illnesses, that are characterized by high mortality rates, multisystem comorbidity, and an often chronic and relapsing disease course. EDs occur most commonly in the female gender, with a ratio of 10 females to 1 male for anorexia nervosa (AN). We present the case of a 15-year-old Saudi boy who presented with weight loss (BMI 11.6 kg/m) and began to have symptoms of obsessive-compulsive disorder (OCD) in prayer and ablution. His first treatment plan was psychoeducation. He then developed a fear of gaining weight and began to count calories; he was diagnosed with AN and started on olanzapine 2.5 mg. The patient had a history of multiple admissions due to electrolyte imbalance, hypokalemia, hypoglycemia, and anal fissure due to constipation, and was prescribed olanzapine 5 mg, fluoxetine 20. His last admission was the worst, as he became semi-comatose with a Glasgow Coma Scale (GCS) of 13, was diffused and disoriented to time and person, unable to walk or sit, and was uncooperative in answering questions. During admission, we changed the fluoxetine to paroxetine 25 mg and increased the olanzapine to 10 mg, and the patient showed a huge improvement physically and mentally. This case emphasizes the significance of including paroxetine in the treatment of diagnoses for AN to prevent unnecessary wasting of time and effort.
PubMed: 38654963
DOI: 10.7759/cureus.58765