Serotonergic Medications Research Articles

Risk for intracranial hemorrhage in individuals after mild traumatic brain injury who are taking serotonergic antidepressants.

Serotonergic antidepressants may predispose to bleeding, but little is known of the risk for traumatic intracranial bleeding. This was a prospective case-control study of 218 patients with mild traumatic brain injuries (TBI) who were treated at a Finnish tertiary trauma hospital. Injury-related information and clinical findings were prospectively collected in the emergency department. Detailed pre-injury health history was collected from electronic medical records. Information on the use of serotonergic antidepressants was attained from the Finnish national prescription registry. All head CT scans were reviewed by a neuroradiologist based on the Common Data Elements. Cases were patients with traumatic intracranial hemorrhage on head CT. Controls were patients from the same cohort, but without traumatic intracranial lesions on CT. The proportion with traumatic intracranial bleeding for patients on serotonergic antidepressant medication was compared to the proportion for patients not on serotonergic medication. The study cohort consisted of 24 cases with traumatic intracranial bleeding and 194 injured controls. The median age of the sample was 70 years (interquartile range = 50-83). One fifth (21.6%) of all the patients were taking a serotonergic antidepressant. Of the patients on an antidepressant, 10.6% (5/47) had an acute hemorrhagic lesion compared to 11.1% (19/171) of those who were not on an antidepressant (p = 0.927). In the regression analysis, traumatic intracranial hemorrhage was not associated with antidepressant use. Serotonergic antidepressant use was not associated with an increased risk of traumatic intracranial hemorrhage after a mild TBI. The patients in this relatively small cohort were mostly middle-aged and older adults. These factors limit the generalizability of the results in younger patients with mild TBI.

Predictors and Interrelationship of Patient-Reported Outcomes in Antiphospholipid Syndrome: A Cross-Sectional Study.

This study assessed patient-reported outcomes (PROs) in individuals with persistently positive antiphospholipid antibodies (aPL) to better understand how living with aPL may affect their quality of life. Patients completed Patient-Reported Outcomes Measurement Information System Physical Function (PF) and Cognitive Function (CF) Short Forms as well as the pain intensity (PI) rating (scale of 1-10). Patients were characterized for demographics, clinical manifestations of antiphospholipid syndrome (APS), cardiovascular risk factors, laboratory test results, and medication usage. Multivariate modeling was done via linear regression. Of 139 patients, 89 had primary APS, 21 had secondary APS, and 29 had persistent aPL without meeting clinical criteria for APS. The average T scores (±SD) for PF and CF were 45.4 ± 9.2 and 48.6 ± 11.6, respectively; the average for PI was 3.0 ± 2.6. Approximately half of the patients (47%) endorsed at least mild impairment in PF (T score < 45). Mean PF, CF, and PI did not differ between diagnostic groups. Individuals who endorsed more impairment on one measure also tended to endorse more impairment on another (Pearson r= 0.43-0.59). In the multivariate models, age, smoking, pain medications, and serotonergic medications were associated with impairment in at least one PRO domain. The Damage Index for APS was significantly correlated with both PF and CF. Individuals living with APS endorsed more impairment in PF (and potentially CF) than expected for the general population. The relationship between certain medications and PROs warrants further study, as does the longitudinal trajectory of these and other PROs.

Alcohol use disorder with comorbid anxiety disorder: a case report and focused literature review

BackgroundAlcohol use disorder (AUD) and anxiety disorders (AnxD) are prevalent health concerns in clinical practice which frequently co-occur (AUD-AnxD) and compound one another. Concurrent AUD-AnxD poses a challenge for clinical management as approaches to treatment of one disorder may be ineffective or potentially counterproductive for the other disorder.Case PresentationWe present the case of a middle-aged man with anxiety disorder, AUD, chronic pain, and gamma-hydroxybutyrate use in context of tapering prescribed benzodiazepines who experienced severe alcohol withdrawal episodes during a complicated course of repeated inpatient withdrawal management. After medical stabilization, the patient found significant improvement in symptoms and no return to alcohol use with a regimen of naltrexone targeting his AUD, gabapentin targeting both his AUD and AnxD, and engagement with integrated psychotherapy, Alcoholics Anonymous, and addictions medicine follow-up.ConclusionProper recognition and interventions for AUD and AnxD, ideally with overlapping efficacy, can benefit individuals with comorbid AUD-AnxD. Gabapentin, tobacco cessation, and integrated psychotherapy have preliminary evidence of synergistic effects in AUD-AnxD. Meta-analysis evidence does not support serotoninergic medications (e.g. selective serotonin reuptake inhibitors) which are commonly prescribed in AnxD and mood disorders as their use has not been associated with improved outcomes for AUD-AnxD. Additionally, several double-blind placebo-controlled randomized trials have suggested that serotonergic medications may worsen alcohol-related outcomes in some individuals with AUD. Areas for future investigation are highlighted.

PAROXETINE OVERDOSE LEADING TO SEROTONIN SYNDROME

PAROXETINE OVERDOSE LEADING TO SEROTONIN SYNDROME

Chronic Serotonin Toxicity in the Older Patient With Polypharmacy.

Clinical pharmacists with experience may identify prescribing patterns resulting in iatrogenic disease, which is commonly encountered in geriatric populations where polypharmacy is common. Serotonin toxicity is one toxidrome clinicians may identify, where specific medications are used in treatment. As a result of their pharmacology training, pharmacists may identify toxidromes caused by medications that other clinicians may overlook. Pharmacogenomic (PGx) testing can provide added insight into a potentially iatrogenic cause for serotonin toxicity, because testing can elucidate how well an individual patient may metabolize serotonergic medications. Using PGx as a resource in addition to clinical experience, pharmacists can better guide therapy in the geriatric, polypharmacy population to avoid serotonin toxicity.

Serotonin Syndrome in an Infant Associated With Linezolid and Opioid Use.

Most reported cases of serotonin syndrome involve either a selective serotonin reuptake inhibitor (SSRI) or monoamine oxidase inhibitors (MAOI) and at least 1 other serotonergic medication or exposure to a single serotonin-augmenting drug. This case report describes serotonin syndrome occurring in association with the concomitant use of the antibiotic linezolid and opioids, specifically methadone, in a pediatric intensive care unit patient. The patient developed hyperpyrexia, muscle rigidity, clonus, and multiorgan dysfunction within 48 hours of receiving linezolid while concurrently on methadone. This drug-drug interaction is a rare cause of serotonin syndrome that has only been described 1 other time in the adult literature. This report raises awareness of this rare but serious and potentially lethal complication of serotonin syndrome associated with concomitant linezolid and opioid use. Timely consideration of the diagnosis in the setting of hyperpyrexia can facilitate prompt initiation of targeted therapies to prevent sequela.

Impact of serotonin transporter (SERT) binding affinity on the risk of libido disorders related to antidepressants

IntroductionSexual dysfunction is a frequent adverse drug reaction (ADR) of antidepressants that considerably affects quality of life and adherence to therapy. We previously investigated the potential underlying neurofunctional mechanisms by neuroimaging methods and revealed a dampening of the dopaminergic mesolimbic-mesocortical reward system along with decreased sexual functioning under serotonergic antidepressants compared to placebo.ObjectivesWithin a combined pharmacoepidemiologic and pharmacodynamic approach, we examined the association between serotonin transporter (SERT) affinity of various antidepressants and corresponding alterations in sexual desire as ADR.MethodsUsing disproportionality analyses, reporting odds ratios (RORs) were calculated for reports indicating decreased sexual desire as ADR under the antidepressants. The data were extracted from the WHO global database of individual case safety reports VigiBase and several MedDRA terms were grouped for “Sexual Desire Disorders”. For the pharmacodynamic assessment, we calculated Pearson correlation coefficients between SERT affinity and corresponding RORsResults16 signals were detected for “Sexual Desire Disorders”. We observed a statistically significant (r (20) =. 65, p = 0.001) association between SERT affinity and decreased sexual desire. Higher SERT affinity was associated with higher risk of sexual desire.ConclusionsWhile sexual dysfunctions under serotonergic medication were previously described, we now elaborated that in particular attenuated sexual desire as ADR is associated with SERT affinity of the antidepressant. These results strengthen our previously described neurofunctional model regarding sexual dysfunction under antidepressant medication and indicate that the specific SERT affinity of the antidepressant drug should be considered in clinical practice to minimize the risk of this ADR.DisclosureNo significant relationships.

0799 Precipitation of Dream Enactment Behavior in the setting of β -Blocker therapy

Abstract Introduction REM sleep behavior disorder (RBD) is defined by dream enactment behavior (DEB) and REM sleep without muscle atonia (RWA). It is proposed that in both isolated and secondary RBD, the loss of REM sleep atonia is related to a failure of spinal motoneuron inhibition in the rostral pons. RBD is most commonly isolated, although it has been attributed to serotonergic antidepressant medication. This is the first report of metoprolol succinate (MS) provoking DEB in patients with RWA which helps shed more light on the mechanism of DEB in RBD. Report of Cases: A 51-year-old male with a new diagnosis of atrial fibrillation (AF) was referred for evaluation of snoring and hypersomnolence. Polysomnography (PSG) revealed obstructive sleep apnea and RWA. DEB was not observed. Compliance with PAP therapy improved his symptoms. Persistent AF required the use of Metoprolol Succinate (MS), which precipitated aggressive DEB. Discontinuation of MS resulted in clinical resolution of DEB. Conclusion The data sheds more light on the potential role of β- blockers, in general, and MS, in particular, in precipitating DEB in susceptible individuals with RWA. While MS is an uncommon cause of visual hallucinations, the data here indicates that it might increase susceptibility to DEB in those who are at risk (RWA). Potential mechanisms include the following: β-blockers bind to serotonin receptors and precipitate DEB in the setting of RWA. β-blockers may also precipitate DEB by suppressing melatonin release via specific inhibition of central beta-adrenoreceptors culminating in sleep instability and DEB as a consequence. This case illustrates a clinically important role of the β-blocker MS, in precipitating DEB, and the need to avoid these agents in the setting of injurious parasomnias. We recommend that clinicians keep a vigilant eye for the exacerbation of DEB in people with RBD who are prescribed β-blockers. Support (If Any)

0806 REM sleep without atonia in the Setting of Duchenne muscular dystrophy: Can it Serve a Protective Role?

Abstract Introduction Duchenne muscular dystrophy (DMD) has well-known associations with sleep-related breathing disorders such as sleep apnea and nocturnal hypoventilation. These disorders naturally follow from the progressive muscle weakness that is the hallmark of DMD. New data is emerging on the prevalence of other polysomnographic features affecting patients with DMD, particularly as they relate to the phenotype of the sleep disorders unique to DMD. We report on a patient with REM sleep without atonia (RWA) in DMD. Report of Cases: A 13-year-old male with DMD was referred for a polysomnogram (PSG) due to new-onset snoring, but there was no history to suggest dream enactment behavior. He was not taking any CNS-acting medication such as serotonergic or sedative-hypnotic medications. Neurologic examination was notable for diffuse symmetric muscle weakness requiring the use of a wheelchair. PSG revealed obstructive sleep apnea syndrome with an apnea-hypopnea index of 3/hr overall and 5/hr during REM sleep, a respiratory disturbance index of 9/hr with minimum O saturation of 84%, and evidence of RWA in three 30-second epochs meeting AASM scoring criteria. Dream-enactment behavior was absent during the PSG and historically. Conclusion We report on a previously unrecognized finding of RWA the setting of DMD. While sleep studies are routinely performed in DMD due to the significant association with sleep-disordered breathing and REM-related hypoventilation, the presence of RWA was unusual. The finding of RWA in the setting of a dystrophinopathy prompts important questions. While it is unlikely that RWA is an emerging sign of an ⍺-synucleinopathy in the setting of DMD, its presence in a young teenager raises the possibility of hypocretin deficiency in the setting of DMD, as is the case with myotonic dystrophy type 1 reflecting impaired hypocretin neurotransmission. However, a more attractive explanation is that RWA may promote a protective effect against sleep apnea in patients with vulnerability to REM-related hypoventilation. Our data suggest a potential protective role conferred by the preservation of muscle tone in the setting of sleep apnea in neuromuscular conditions. Support (If Any) None

Atypical action updating in a dynamic environment associated with adolescent obsessive-compulsive disorder.

Computational research had determined that adults with obsessive-compulsive disorder (OCD) display heightened action updating in response to noise in the environment and neglect metacognitive information (such as confidence) when making decisions. These features are proposed to underlie patients' compulsions despite the knowledge they are irrational. Nonetheless, it is unclear whether this extends to adolescents with OCD as research in this population is lacking. Thus, this study aimed to investigate the interplay between action and confidence in adolescents with OCD. Twenty-seven adolescents with OCD and 46 controls completed a predictive-inference task, designed to probe how subjects' actions and confidence ratings fluctuate in response to unexpected outcomes. We investigated how subjects update actions in response to prediction errors (indexing mismatches between expectations and outcomes) and used parameters from a Bayesian model to predict how confidence and action evolve over time. Confidence-action association strength was assessed using a regression model. We also investigated the effects of serotonergic medication. Adolescents with OCD showed significantly increased learning rates, particularly following small prediction errors. Results were driven primarily by unmedicated patients. Confidence ratings appeared equivalent between groups, although model-based analysis revealed that patients' confidence was less affected by prediction errors compared to controls. Patients and controls did not differ in the extent to which they updated actions and confidence in tandem. Adolescents with OCD showed enhanced action adjustments, especially in the face of small prediction errors, consistent with previous research establishing 'just-right' compulsions, enhanced error-related negativity, and greater decision uncertainty in paediatric-OCD. These tendencies were ameliorated in patients receiving serotonergic medication, emphasising the importance of early intervention in preventing disorder-related cognitive deficits. Confidence ratings were equivalent between young patients and controls, mirroring findings in adult OCD research.

(PO-174) Management of Major Depression Following Vasoconstrictive Stroke due to Serotonergic Medications

(PO-174) Management of Major Depression Following Vasoconstrictive Stroke due to Serotonergic Medications

(PO-130) Serotonergic Toxidrome Following Methylene Blue Administration for Vasoplegia in A Patient on Multiple Serotonergic Medications: The Role of the Proactive Consult-Liaison Psychiatrist in Prevention

(PO-130) Serotonergic Toxidrome Following Methylene Blue Administration for Vasoplegia in A Patient on Multiple Serotonergic Medications: The Role of the Proactive Consult-Liaison Psychiatrist in Prevention

Associations Between Prenatal Exposure to Serotonergic Medications and Biobehavioral Stress Regulation: Protocol for a Systematic Review and Meta-analysis.

BackgroundUp to 20% of mothers experience antenatal depression and approximately 30% of these women are treated with serotonergic psychotropic pharmacological therapy during pregnancy. Serotonergic antidepressants readily cross the placenta and the fetal blood-brain barrier, altering central synaptic serotonin signaling and potentially altering serotonin levels in the developing fetal brain.ObjectiveThe aim of this study is to assess the impact of prenatal exposure to serotonergic antidepressants, accounting for maternal mood disturbances, on markers of stress regulation during childhood.MethodsWe will follow PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and will search MEDLINE, Embase, CINAHL, PsycINFO, and ClinicalTrials.gov for full-length studies that assessed physiological (eg, cortisol level, heart rate variability, salivary amylase, pupillary size, C-reactive protein) indices of stress regulation in children of pregnant people who were treated with a serotonergic antidepressant at any point during pregnancy. We will assess the quality of observational studies using the Newcastle-Ottawa Scale and the quality of experimental studies using the Cochrane risk-of-bias tool. When possible, we will conduct a random-effects meta-analysis. If meta-analysis is not possible, we will conduct a narrative review. If a sufficient number of studies are found, we will perform subgroup analysis and assess outcomes measured by drug class, dose, trimester of exposure, and child’s age and gender.ResultsWe registered our review protocol with PROSPERO (International Prospective Register of Systematic Reviews; CRD42021275750), completed the literature search, and initiated title and abstract review in August 2021. We expect to finalize this review by April 2022.ConclusionsFindings should identify the impact of prenatal antidepressant effects on stress regulation and distinguish it from the impact of prenatal exposure to maternal mood disturbances. This review should inform decisions about serotonergic antidepressant use during pregnancy.Trial RegistrationPROSPERO CRD42021275750; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=275750International Registered Report Identifier (IRRID)PRR1-10.2196/33363

Phenazopyridine-Induced Methaemoglobinaemia The Aftermath of Dysuria Treatment.

IntroductionPhenazopyridine is an over-the-counter urinary analgesic commonly used to alleviate the burning and urgency associated with lower urinary tract infections. Methaemoglobinaemia is an uncommon adverse effect of phenazopyridine use. We report a case of methaemoglobinaemia in a patient prescribed daily phenazopyridine to treat urethral and bladder irritation caused by a chronic indwelling Foley catheter.Case descriptionA 55-year-old female resident of a long-term acute care facility with a chronic Foley, tracheostomy and ventilator-dependent respiratory failure was observed to have generalized dusky skin and hypoxia. Pulse oximetry was reading in the high 80s despite administration of 100% FiO2. ABG revealed paO2 of 451, oxyhaemoglobin level 75% and methaemoglobin level 22%. Medication review indicated that the patient was prescribed phenazopyridine 400 mg TID for the previous 2 months. This medication was discontinued. Considering she was chronically taking mirtazapine, she can increase risk of serotonin syndrome should she be administered first-line treatment with methylene blue. Vitamin C was thus instead administered as a second-line agent. Serial ABGs showed a rapid decline in methaemoglobin levels and an increase in oxyhaemoglobin within 2 days.DiscussionAcquired methaemoglobinaemia is a rare adverse effect of treatment with phenazopyridine. This risk increases when drug dosage and duration exceed manufacturer specifications. Treatment typically includes cessation of the offending drug and administration of methylene blue in severe cases. A thorough medication reconciliation should be performed prior to methylene blue initiation, as patients taking serotonergic medications (for example, MAOIs, SSRIs, SNRIs, TCAs) are at increased risk of serotonin toxicity with co-administration of methylene blue. In these instances, ascorbic acid/vitamin C can be chosen as an alternative treatment agent.ConclusionWork-up of refractory hypoxia should involve a thorough review of medications as even some over-the-counter drugs can cause the fatal side effect of methaemoglobinaemia. Treatment with vitamin C should be considered over methylene blue if serotonergic medications have been recently prescribed in order to avoid risk of serotonin syndrome.LEARNING POINTSMethaemoglobinaemia is an uncommon, life-threatening adverse effect of phenazopyridine use. Presentation depends on the severity of the disorder, ranging from headache, weakness, lightheadedness and dyspnoea, to arrhythmias, confusion, seizures and multiorgan failure.Workup of refractory hypoxia should involve a comprehensive medication review as even some over-the-counter drugs can cause methaemoglobinaemia.Management of methaemoglobinaemia involves cessation of the offending drug, administration of supplemental oxygen and treatment with methylene blue (1–2 mg/kg) if MetHb >30%, or for symptomatic patients with MetHb >20%. Vitamin C can be used as an alternative agent if there is a contraindication to methylene blue (for example, with patients simultaneously receiving serotonergic medications and/or those with G6PD deficiency).

Impact of serotonergic medication on interoception in major depressive disorder

Unmedicated individuals with major depressive disorder (MDD) show abnormal interoception, but it is unclear whether antidepressant treatment via serotonergic medication alters this relationship. The current cross-sectional study examined associations between neural and behavioral indices of interoceptive processing and chronic serotonergic medication administration in MDD. 47 selective serotonin reuptake inhibitor (SSRI)-medicated MDD (MDD-SSRI) individuals were propensity-matched with 48 unmedicated current MDD (MDD-UnMed) and 41 healthy comparison (HC) participants on demographics including age, sex, body mass index, education, as well as on dimensional scales of symptom severity including depression and anxiety. All participants completed an interoceptive attention task during functional magnetic resonance imaging, and a behavioral heartbeat tapping task under three conditions: Guessing, No Guessing, and Breath Hold. Relative to HC, both MDD groups: (1) exhibited lower mid-insula, amygdala, putamen, and caudate activation during interoceptive versus exteroceptive attention; and (2) showed poorer heartbeat tapping performance during the Breath Hold condition. However, the MDD-SSRI group reported higher intensity ratings of heartbeat and stomach sensations than MDD-UnMed and HC during the interoceptive attention task. These findings suggest that the attenuated patterns of neural activation observed in depressed individuals during interoceptive attention are not ameliorated by the chronic administration of serotonergic medications. However, amplified interoceptive sensation ratings suggest a potential impact of chronic serotonergic medication on conscious experiences of internal body states. Future investigations will need to determine the extent to which serotonergic medications acutely influence interoceptive processing, and whether such changes play a role in therapeutic responses during treatment initiation.

Psychiatric management of Patients in intensive care units.

Psychiatric management of Patients in intensive care units.

Association of Environmental Uncertainty With Altered Decision-making and Learning Mechanisms in Youths With Obsessive-Compulsive Disorder

Adults with obsessive-compulsive disorder (OCD) display perseverative behavior in stable environments but exhibit vacillating choice when payoffs are uncertain. These findings may be associated with intolerance of uncertainty and compulsive behaviors; however, little is known about the mechanisms underlying learning and decision-making in youths with OCD because research into this population has been limited. To investigate cognitive mechanisms associated with decision-making in youths with OCD by using executive functioning tasks and computational modeling. In this cross-sectional study, 50 youths with OCD (patients) and 53 healthy participants (controls) completed a probabilistic reversal learning (PRL) task between January 2014 and March 2020. A separate sample of 27 patients and 46 controls completed the Wisconsin Card Sorting Task (WCST) between January 2018 and November 2020. The study took place at the University of Cambridge in the UK. Decision-making mechanisms were studied by fitting hierarchical bayesian reinforcement learning models to the 2 data sets and comparing model parameters between participant groups. Model parameters included reward and punishment learning rates (feedback sensitivity), reinforcement sensitivity and decision consistency (exploitation), and stickiness (perseveration). Associations of receipt of serotonergic medication with performance were assessed. In total, 50 patients (29 female patients [58%]; median age, 16.6 years [IQR, 15.3-18.0 years]) and 53 controls (30 female participants [57%]; median age, 16.4 years [IQR, 14.8-18.0 years]) completed the PRL task. A total of 27 patients (18 female patients [67%]; median age, 16.1 years [IQR, 15.2-17.2 years]) and 46 controls (28 female participants [61%]; median age, 17.2 [IQR, 16.3-17.6 years]) completed the WCST. During the reversal phase of the PRL task, patients made fewer correct responses (mean [SD] proportion: 0.83 [0.16] for controls and 0.61 [0.31] for patients; 95% CI, -1.31 to -0.64) and switched choices more often following false-negative feedback (mean [SD] proportion: 0.09 [0.16] for controls vs 0.27 [0.34] for patients; 95% CI, 0.60-1.26) and true-positive feedback (mean [SD] proportion: 0.93 [0.17] for controls vs 0.73 [0.34] for patients; 95% CI, -2.17 to -1.31). Computational modeling revealed that patients displayed enhanced reward learning rates (mean difference [MD], 0.21; 95% highest density interval [HDI], 0.04-0.38) but decreased punishment learning rates (MD, -0.29; 95% HDI, -0.39 to -0.18), reinforcement sensitivity (MD, -4.91; 95% HDI, -9.38 to -1.12), and stickiness (MD, -0.35; 95% HDI, -0.57 to -0.11) compared with controls. There were no group differences on standard WCST measures and computational model parameters. However, patients who received serotonergic medication showed slower response times (mean [SD], 1420.49 [279.71] milliseconds for controls, 1471.42 [212.81] milliseconds for patients who were unmedicated, and 1738.25 [349.23] milliseconds for patients who were medicated) (control vs medicated MD, -320.26 [95% CI, -547.00 to -88.68]) and increased unique errors (mean [SD] proportion: 0.001 [0.004] for controls, 0.002 [0.004] for patients who were unmedicated, and 0.008 [0.01] for patients who were medicated) (control vs medicated MD, -0.007 [95% CI, -3.14 to -0.36]) on the WCST. The results of this cross-sectional study indicated that youths with OCD showed atypical probabilistic reversal learning but were generally unimpaired on the deterministic WCST, although unexpected results were observed for patients receiving serotonergic medication. These findings have implications for reframing the understanding of early-onset OCD as a disorder in which decision-making is associated with uncertainty in the environment, a potential target for therapeutic treatment. These results provide continuity with findings in adults with OCD.

Glutamatergic medications as adjunctive therapy for moderate to severe obsessive-compulsive disorder in adults: a systematic review and meta-analysis

BackgroundObsessive-compulsive disorder (OCD) is among the most disabling neuropsychiatric conditions characterized by the presence of repetitive intrusive thoughts, impulses, or images (obsessions) and/or ritualized mental or physical acts (compulsions). Serotonergic medications, particularly Selective Serotonin Reuptake Inhibitors (SSRIs), are the first-line treatments for patients with OCD. Recently, dysregulation of glutamatergic system has been proposed to be involved in the etiology of OCD. We designed this systematic review and meta-analysis to evaluate clinical efficacy of glutamatergic medications in patients with OCD, according to the guidelines of Cochrane collaboration.MethodWe searched Medline, Scopus, and Cochrane library without applying any language filter. Two of the authors independently reviewed search results for irrelevant and duplicate studies and extracted data and assessed methodological quality of the studies. We transformed data into a common rubric and calculated a weighted treatment effect across studies using Review Manager.ResultsWe found 476 references in 3 databases, and after exclusion of irrelevant and duplicate studies, 17 studies with total number of 759 patients with OCD were included. In the present review we found evidence for several drugs such as memantine, N-acetylcysteine (NAC), Minocycline, L-carnosine and riluzole. Glutamaterigic drug plus SSRIs were superior to SSRI+ Placebo with regard to Y-BOCS scale [standardized mean difference (SMD = − 3.81 95% CI = − 4.4, − 3.23).ConclusionAugmentation of glutamatergic medications with SSRIs are beneficial in obsessive-compulsive patients, no harmful significant differences in any safety outcome were found between the groups.

Symptom specificity of ayahuasca's effect on depressive symptoms

AbstractBackgroundAyahuasca's effects on symptoms of depression have generated considerable optimism. Clients frequently report more concern about some symptoms than others, and available treatments alter symptoms differentially. Few studies address the symptom specificity of this psychoactive brew.AimsWe examined self-reported effects of ayahuasca on the individual symptoms of depression assessed by the 10-item short-form of Center for Epidemiological Studies of Depression (CESD-10).MethodsWe asked over 120 participants to complete a retrospective assessment of CESD-10 symptoms one month before and one month after using ayahuasca.ResultsParticipants indicated that ayahuasca had a larger influence on affective symptoms like hope, depressed mood, and happiness, than cognitive, interpersonal, and somatic symptoms like restless sleep, loneliness, and difficulty focusing.ConclusionsPotential clients might appreciate identifying if different treatments provide more relief for some depressive symptoms than others. We examined retrospective reports of ayahuasca's potential for differential impact. Those eager to alter hope, happiness, and other affective symptoms will likely find ayahuasca more helpful than those who want an intervention for restless sleep, loneliness, or trouble focusing. This symptom specificity parallels the effects of serotonergic antidepressant medications, suggesting that psychedelic-assisted psychotherapy using ayahuasca might have considerable appeal for those who seek comparable relief but would rather not use prescription serotonergic medications. Jumpstarting psychotherapy with the rapid onset of ayahuasca-induced relief also appears to have potential.

Toxicities of opioid analgesics: respiratory depression, histamine release, hemodynamic changes, hypersensitivity, serotonin toxicity.

Opioid-induced respiratory depression is potentially life-threatening and often regarded as the main hazard of opioid use. Main cause of death is cardiorespiratory arrest with hypoxia and hypercapnia. Respiratory depression is mediated by opioid μ receptors expressed on respiratory neurons in the CNS. Studies on the major sites in the brainstem mediating respiratory rate suppression, the pre-Bӧtzinger complex and parabrachial complex (including the Kӧlliker Fuse nucleus), have yielded conflicting findings and interpretations but recent investigations involving deletion of μ receptors from neurons have led to greater consensus. Some opioid analgesic drugs are histamine releasers. The range of clinical effects of released histamine include increased cardiac output due to an increase in heart rate, increased force of myocardial contraction, and a dilatatory effect on small blood vessels leading to flushing, decreased vascular resistance and hypotension. Resultant hemodynamic changes do not necessarily relate directly to the concentration of histamine in plasma due to a range of variables including functional differences between mast cells and histamine-induced anaphylactoid reactions may occur less often than commonly believed. Opioid-induced histamine release rarely if ever provokes bronchospasm and histamine released by opioids in normal doses does not lead to anaphylactoid reactions or result in IgE-mediated reactions in normal patients. Hypersensitivities to opioids, mainly some skin reactions and occasional type I hypersensitivities, chiefly anaphylaxis and urticaria, are uncommon. Hypersensitivities to morphine, codeine, heroin, methadone, meperidine, fentanyl, remifentanil, buprenorphine, tramadol, and dextromethorphan are summarized. In 2016, the FDA issued a Drug Safety Communication concerning the association of opioids with serotonin syndrome, a toxicity associated with raised intra-synaptic concentrations of serotonin in the CNS, inhibition of serotonin reuptake, and activation of 5-HT receptors. Opioids may provoke serotonin toxicity especially if administered in conjunction with other serotonergic medications. The increasing use of opioid analgesics and widespread prescribing of antidepressants and psychiatric medicines, indicates the likelihood of an increased incidence of serotonin toxicity in opioid-treated patients.