Serotonergic Medications Research Articles

526 Characteristics of Augmented RLS Patients on Dopamine Agonists at a Tertiary Referral Center: Where Do We Go From Here?

Abstract Introduction Augmentation is a management dilemma in RLS patients on dopaminergic therapy. Understanding the clinical characteristics of such patients may assist in better management strategies. Methods Consecutive new consultations for RLS from 4/2016-6/2020 were identified from a single tertiary referral center in Boston, USA. Patients were included in this analysis if they had augmentation and current treatment with a dopamine agonist. Clinical information from initial consultation was collected. RLS severity at time of consultation was determined retrospectively with a modified IRLSSG severity score (0–12), assessing RLS symptom frequency (0–4), duration (0–4), and severity (0–4). Results Out of 209 referrals with RLS, 105 patients had augmentation, of whom 88 were on dopamine agonists at initial evaluation. Average age was 67 years (SD 11 years, range 39–88); 62 were female (59%). Mean duration of RLS symptoms was 27 years (SD 20), and 91% had symptoms > 10 years. Mean duration of dopamine agonist therapy was 11 years; 72% had previously been treated with pramipexole, 65% with ropinirole, 73% with rotigotine, and 16% with levodopa; 72% of patients had been treated with alpha-2-delta ligands, and 28% with opioids. Common comorbidities included obstructive sleep apnea (47%), obesity (49%), and depression (44%). Serotonergic medications were currently used by 25%. Of the 88 augmented patients on dopamine agonist therapy, 97% had earlier onset of symptoms and 33% had symptoms in both morning and afternoon; 53% reported anatomical extension. The mean modified IRLSSG score was 8.4 (SD 3.2). 66% of patients had either ferritin <75 mcg/L or transferrin saturation <20%. At the time of initial assessment, 49% were on pramipexole, 47% on rotigotine, 5% on rotigotine and 7% on levodopa: mean daily dopamine agonist dose was 1.23 mg (SD 1.20) of pramipexole equivalent. 37% were on alpha-2-delta ligands: mean daily dose 1014 mg (SD 830, median 700 mg) of gabapentin equivalent. Conclusion Higher than FDA-recommended dopamine agonist dosing and high prevalence of iron deficiency in patients with augmented RLS represent a treatment gap in the care of RLS patients in the community. Controlled studies of guideline-based therapy are indicated to determine optimal management of augmented RLS. Support (if any) Baszucki Brain Research Fund

Attachment styles and propensity for sexual response in adult obsessive-compulsive disorder

An impaired sexual functioning has been found to be more frequent in patients with obsessive-compulsive disorder (OCD) than in the general population and other clinical groups. Less is known about the psychological processes associated with this altered sexual response. The present study was carried out to investigate the association between attachment styles and sexual response (i.e. sexual excitation and inhibition) in a group of patients with OCD, controlling for socio-demographics, OCD severity, psychiatric and personality comorbidity, serotonergic medications, and obsessive cognitions. Seventy-two patients with OCD and 72 matched healthy individuals were recruited. OCD patients self-reported significantly higher levels of sexual excitation and inhibition, obsessive-compulsive symptoms, obsessive cognitions, and attachment styles characterized by discomfort with closeness, need for approval, and preoccupation with relationships. The MANCOVA analysis revealed that patients with more severe symptoms had lower propensity to experience sexual excitation. Patients with stronger confidence and need for approval were less inhibited. Attachment styles may be a feature involved in the propensity for sexual response of OCD patients, and they should be assessed during clinical practice with this clinical population. Interventions aimed to improve sexual life of this type of patients should target attachment.

Priority-Setting to Address the Geriatric Pharmacoparadox for Pain Management: A Nursing Home Stakeholder Delphi Study.

Evidence to guide clinical decision making for pain management in nursing home residents is scant. Our objective was to explore the extent of consensus among expert stakeholders regarding what analgesic issues should be prioritized for comparative-effectiveness studies of beneficial and adverse effects of analgesic regimens in nursing home residents. Two stakeholder panels (nurses only and a mix of clinicians/researchers) were engaged (n = 83). During a three-round online modified Delphi process, participants rated and commented on the need for new evidence on nonopioid analgesic regimens and opioid regimens, short-term adverse effects, long-term adverse effects, comorbid conditions, and other factors in the nursing home setting (9-point scale; 1 = not essential to 9 = very essential to obtain new evidence). The quantitative data were analyzed to determine the existence of consensus using an approach from the RAND/UCLA Appropriateness Method User's Manual. The qualitative data, consisting of participant explanations of their numeric ratings, were thematically analyzed by an experienced qualitative researcher. For nursing home residents, evidence generation was deemed essential for opioids, gabapentin (alone or with serotonin norepinephrine reuptake inhibitors [SNRIs]), and nonsteroid anti-inflammatory drugs with SNRIs. Experts prioritized the following outcomes as essential: long-term adverse effects, including delirium, cognitive decline, and decline in activities of daily living (ADLs). Kidney disease and depression were deemed essential conditions to consider in studies of pain medications. Coprescribing analgesic regimens with benzodiazepines, sedating medications, serotonergic medications, and non-SNRI antidepressants were considered essential areas of study. Experts noted that additional study was essential in residents with moderate/severe cognitive impairment and limitations in ADLs. Stakeholder priorities for more evidence reflect concerns related to treating medically complex residents with complex drug regimens and included long-term adverse effects, coprescribing, and sedating medications. Carefully conducted observational studies are needed to address the vast evidence gap for nursing home residents.

Why the Maternal Medication List Matters: Neonatal Toxicity From Combined Serotonergic Exposures

Serotonergic medications are used for the prevention and treatment of depression during pregnancy. Selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors (SNRIs) can cause poor neonatal adaptation, which has been attributed to withdrawal versus toxicity. Bupropion, a norepinephrine-dopamine reuptake inhibitor, is often used as an adjunctive agent to selective serotonin reuptake inhibitors or SNRIs for refractory depression. Quetiapine, an atypical antipsychotic, may also be used in more complex cases. When combined with serotonergic drugs, bupropion and quetiapine are associated with increased risk of serotonin syndrome in adults. We describe a neonate exposed to venlafaxine (an SNRI), bupropion, and quetiapine in utero who presented nearly immediately after birth with encephalopathy and abnormal movements. The severity and rapidity of symptoms may be attributable to potentiation of venlafaxine's serotonergic effects by bupropion and quetiapine. Neonatal providers should be aware of maternal medications and prepare for possible adverse effects, particularly from common psychotropic exposures.

Harmonizing the Neurobiology and Treatment of Obsessive-Compulsive Disorder

Obsessive-compulsive disorder (OCD) is a common, chronic, and oftentimes disabling disorder. The only established first-line treatments for OCD are exposure and response prevention, and serotonin reuptake inhibitor medications (SRIs). However, a subset of patients fails to respond to either modality, and few experience complete remission. Beyond SRI monotherapy, antipsychotic augmentation is the only medication approach for OCD with substantial empirical support. Our incomplete understanding of the neurobiology of OCD has hampered efforts to develop new treatments or enhance extant interventions. This review focuses on several promising areas of research that may help elucidate the pathophysiology of OCD and advance treatment. Multiple studies support a significant genetic contribution to OCD, but pinpointing the specific genetic determinants requires additional investigation. The preferential efficacy of SRIs in OCD has neither led to discovery of serotonergic abnormalities in OCD nor to development of new serotonergic medications for OCD. Several lines of preclinical and clinical evidence suggest dysfunction of the glutamatergic system in OCD, prompting testing of several promising glutamate modulating agents. Functional imaging studies in OCD show consistent evidence for increased activity in brain regions that form a cortico-striato-thalamo-cortical (CSTC) loop. Neuromodulation treatments with either noninvasive devices (e.g., transcranial magnetic stimulation) or invasive procedures (e.g., deep brain stimulation) provide further support for the CSTC model of OCD. A common substrate for various interventions (whether drug, behavioral, or device) may be modulation (at different nodes or connections) of the CSTC circuit that mediates the symptoms of OCD.

STATUS CATAPLECTICUS INDUCED BY WITHDRAWAL OF DULOXETINE

SESSION TITLE: Fellows Sleep Disorders Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Status cataplecticus is defined as episodes of cataplexy with an increase in duration and severity of the attacks precipitated by minor or no emotional triggers without a refractory period. It’s a poorly understood rare phenomenon only described in case reports. We are presenting a case of status cataplecticus after the withdrawal of duloxetine CASE PRESENTATION: A 77-year-old female with a history of long-standing narcolepsy with cataplexy stable on methylphenidate 50 mg extended-release a day admitted to hospital for multiple brief periods of whole-body weakness. Patient reported progressively increasing episodes of cataplexy in the last few days with more than ten episodes one day before the presentation which would come on even minor or no emotional stimuli. She was able to recall all the episodes and each episode lasted less than one minute and denied having jerking movements of limbs, incontinence, and or tongue biting. She was also taking duloxetine 60 mg a day for chronic pain due to arthritis for the last one year. She was having issues with dry mouth since being started on duloxetine and stopped taking duloxetine one month before the presentation. Vital signs, physical examination, laboratory workup including CT head was unremarkable. She continued to have these episodes while admitted and were observed by the medical staff. She was started on a lower dose of duloxetine 20 mg twice daily and was observed in the hospital until she stopped having these episodes and discharged back to home without any further recurrence. She was counseled about the negative consequences of the abrupt withdrawal of the medications. DISCUSSION: Cataplexy is defined by REM intrusion into wakefulness clinically apparent as transient muscle weakness brought on by emotional triggers. Most triggers are positive emotions such as laughter, joking and affect the muscles of head and neck with knees and if severe enough can cause paralysis culminating in a fall, however, a typical cataplexy episode is followed by a refractory period of at least a few hours to days in which cataplexy is unlikely to happen again. In status cataplecticus these episodes become very frequent and increase in severity without any significant triggers and lack of refractory period and result in significant debilitation. Most of the cases of status cataplecticus have been described in patients withdrawing from serotonergic adrenergic medications such as SSRI, SNRI, and TCA’s. These medications help decrease REM sleep by increasing the levels of serotonin and norepinephrine and improve cataplexy. Withdrawal can lead to worsening cataplexy symptoms by disinhibiting neurons that promote REM sleep. CONCLUSIONS: Patients of Narcolepsy with Cataplexy should be educated about the possible side effect of withdrawal of SSRI, SNRI and TCA's that can lead to this rare often misdiagnosed phenomenon of status cataplecticus. Reference #1: Wang J, Greenberg H. Status cataplecticus precipitated by abrupt withdrawal of venlafaxine. J Clin Sleep Med. 2013;9(7):715-716. Published 2013 Jul 15. doi:10.5664/jcsm.2848 Reference #2: Martínez-Rodríguez JE, Iranzo A, Santamaría J, et al. Estado de mal catapléjico inducido por la retirada brusca de clomipramina [Status cataplecticus induced by abrupt withdrawal of clomipramine]. Neurologia. 2002;17(2):113-116. DISCLOSURES: no disclosure on file for Humberto Battistini; No relevant relationships by Rose Franco, source=Web Response No relevant relationships by Mohsin Hamid, source=Web Response

Multimodal treatment of persistent postural-perceptual dizziness.

BackgroundPersistent postural–perceptual dizziness (PPPD) is a chronic disorder with fluctuating symptoms of dizziness, unsteadiness, or vertigo for at least three months. Its pathophysiological mechanisms give theoretical support for the use of multimodal treatment. However, there are different therapeutic programs and principles available, and their clinical effectiveness remains elusive.MethodsA database of patients who participated in a day care multimodal treatment program was analyzed regarding the therapeutic effects on PPPD. Vertigo Severity Scale (VSS) and Hospital Anxiety and Depression Scale (HADS) were assessed before and 6 months after therapy.ResultsOf a total of 657 patients treated with a tertiary care multimodal treatment program, 46.4% met the criteria for PPPD. PPPD patients were younger than patients with somatic diagnoses and complained more distress due to dizziness. 63.6% completed the follow‐up questionnaire. All patients showed significant changes in VSS and HADS anxiety, but the PPPD patients generally showed a tendency to improve more than the patients with somatic diagnoses. The change in the autonomic–anxiety subscore of VSS only reached statistical significance when comparing PPPD with somatic diagnoses (p = .002).ConclusionsTherapeutic principles comprise cognitive–behavioral therapy, vestibular rehabilitation exercises, and serotonergic medication. However, large‐scale, randomized, controlled trials are still missing. Follow‐up observations after multimodal interdisciplinary therapy reveal an improvement in symptoms in most patients with chronic dizziness. The study was not designed to detect diagnosis‐specific effects, but patients with PPPD and patients with other vestibular disorders benefit from multimodal therapies.

Serotonin toxicity from isolated bupropion overdoses

Background: Bupropion is a synthetic cathinone, which acts therapeutically through norepinephrine and dopamine reuptake inhibition. Recent evidence suggests that serotonin receptor activation occurs with high doses of bupropion and severe serotonin toxicity can occur after isolated bupropion overdoses. Prior observational studies may therefore underestimate the incidence of serotonin toxicity.Methods: A retrospective study of patients with bupropion toxicity at a toxicology referral center from 2015–2017 was performed. Patients who overdosed on other serotonergic medications were excluded. Serotonin toxicity was diagnosed retrospectively using Hunter Criteria.Results: Overall, 96 patients were identified with bupropion toxicity. Of these, 18 patients ingested bupropion in the absence of other serotonergic drugs. The incidence of serotonin toxicity was 33% in this population. Serotonin toxicity was more likely after a suicide attempt than those with an accidental ingestion or after recreational drug use. The median dose of bupropion ingested was 2,250 mg in the cohort diagnosed with serotonin syndrome.Conclusion: The incidence of bupropion induced serotonin toxicity is higher than reported. Clinicians should monitor for serotonergic toxicity when evaluating patients after bupropion overdose.

Fenfluramine acts as a positive modulator of sigma-1 receptors

ObjectiveAdjunctive fenfluramine hydrochloride, classically described as acting pharmacologically through a serotonergic mechanism, has demonstrated a unique and robust clinical response profile with regard to its magnitude, consistency, and durability of effect on seizure activity in patients with pharmacoresistant Dravet syndrome. Recent findings also support long-term improvements in executive functions (behavior, emotion, cognition) in these patients. The observed clinical profile is inconsistent with serotonergic activity alone, as other serotonergic medications have not been demonstrated to have these clinical effects. This study investigated a potential role for σ1 receptor activity in complementing fenfluramine's serotonergic pharmacology. MethodsRadioligand binding assays tested the affinity of fenfluramine for 47 receptors associated with seizures in the literature, including σ receptors. Cellular function assays tested fenfluramine and norfenfluramine (its major metabolite) activity at various receptors, including adrenergic, muscarinic, and serotonergic receptors. The σ1 receptor activity was assessed by the mouse vas deferens isometric twitch and by an assay of dissociation of the σ1 receptor from the endoplasmic reticulum stress protein binding immunoglobulin protein (BiP). In vivo mouse models assessed fenfluramine activity at σ1 receptors in ameliorating dizocilpine-induced learning deficits in spatial and nonspatial memory tasks, alone or in combination with the reference σ1 receptor agonist PRE-084. ResultsFenfluramine and norfenfluramine bound ≥30% to β2-adrenergic, muscarinic M1, serotonergic 5-HT1A, and σ receptors, as well as sodium channels, with a Ki between 266 nM (σ receptors) and 17.5 μM (β-adrenergic receptors). However, only σ1 receptor isometric twitch assays showed a positive functional response, with weak stimulation by fenfluramine and inhibition by norfenfluramine. Fenfluramine, but not the 5-HT2C agonist lorcaserin, showed a positive modulation of the PRE-084-induced dissociation of σ1 protein from BiP. Fenfluramine also showed dose-dependent antiamnesic effects against dizocilpine-induced learning deficits in spontaneous alternation and passive avoidance responses, which are models of σ1 activation. Moreover, low doses of fenfluramine synergistically potentiated the low-dose effect of PRE-084, confirming a positive modulatory effect at the σ1 receptor. Finally, all in vivo effects were blocked by the σ1 receptor antagonist NE-100. SignificanceFenfluramine demonstrated modulatory activity at σ1 receptors in vitro and in vivo in addition to its known serotonergic activity. These studies identify a possible new σ1 receptor mechanism underpinning fenfluramine's central nervous system effects, which may contribute to its antiseizure activity in Dravet syndrome and positive effects observed on executive functions in clinical studies.

Persistent Postural-Perceptual Dizziness.

Persistent postural-perceptual dizziness (PPPD) was defined for the International Classification of Vestibular Disorders in 2017. It is a chronic vestibular disorder that manifests with waxing and waning symptoms of dizziness, unsteadiness, or nonspinning vertigo that last for 3 months or more and are exacerbated by upright posture, active or passive motion of self, and exposure to environments with complex or moving visual stimuli. Triggers of PPPD include a wide variety of conditions that may cause vestibular symptoms or disrupt balance functioning, including neuro-otologic and other medical conditions and psychological distress. The diagnosis is made by identifying key symptoms in patients' histories and conducting physical examinations and diagnostic testing of sufficient detail to establish PPPD as opposed to other illnesses. Ongoing research is providing insights into the pathophysiological mechanisms underlying PPPD and support for multimodality treatment plans incorporating specially adapted vestibular rehabilitation, serotonergic medications, and cognitive-behavior therapy.

Brain Response to Serotonergic Medications in ASD

Brain Response to Serotonergic Medications in ASD

Evaluation of Second Generation Antipsychotics, as Augmentative Plan, in Treatment-Resistant Obsessive-Compulsive Disorder

Introduction: Since around half of the patients with obsessive-compulsive disorder do not respond efficiently to current serotonin- reuptake inhibitors, the objective of the present study was to compare the effectiveness and safety of quetiapine against aripiprazole in patients with obsessive-compulsive disorder, who had not responded successfully to fluvoxamine. Methods: Forty-four patients with obsessive-compulsive disorder, who had not responded efficaciously to fluvoxamine, at maximum dose (300 milligrams per day) and duration (twelve weeks), were allocated randomly in a double-blind assessment to take quetiapine (n=22) or aripiprazole (n=22), plus their serotonin-reuptake inhibitor for twelve weeks. While treatment response was evaluated by the Yale- Brown Obsessive-Compulsive Scale (YBOCS), as the main outcome scale, Clinical Global Impressions-Severity Scale (CGI-S) was also used as an ancillary measure. Results: 54.54% of patients in the quetiapine group and 27.27% of them in the aripiprazole group responded partially to the abovementioned on treatment adds. According to the findings, the YBOCS score dropped from 31.18+/-4.93 to 27.97+/-3.71 (p<0.01), and 33.27 +/- 3.90 to 30.72+/-4.67 (p < 0.06), for quetiapine and aripiprazole, respectively. In this regard, no substantial alteration regarding CGI-S was evident in each of the aforementioned groups. Conclusion: This assessment indicated that patients with treatment-resistant obsessivecompulsive disorder could benefit more from adding quetiapine, in comparison with aripiprazole, to their current serotonergic medication.

Dose-dependent effects of the selective serotonin reuptake inhibitor citalopram: A combined SPECT and phMRI study.

Background:Serotonin transporter blockers, like citalopram, dose-dependently bind to the serotonin transporter. Pharmacological magnetic resonance imaging (phMRI) can be used to non-invasively monitor effects of serotonergic medication. Although previous studies showed that phMRI can measure the effect of a single dose of serotoninergic medication, it is currently unclear whether it can also detect dose-dependent effects.Aims:To investigate the dose-dependent phMRI response to citalopram and compared this with serotonin transporter occupancy, measured with single photon emission computed tomography (SPECT).Methods:Forty-five healthy females were randomized to pre-treatment with placebo, a low (4 mg) or clinically standard (16 mg) oral citalopram dose. Prior to citalopram, and 3 h after, subjects underwent SPECT scanning. Subsequently, a phMRI scan with a citalopram challenge (7.5 mg intravenously) was conducted. Change in cerebral blood flow in response to the citalopram challenge was assessed in the thalamus and occipital cortex (control region).Results:Citalopram dose-dependently affected serotonin transporter occupancy, as measured with SPECT. In addition, citalopram dose-dependently affected the phMRI response to intravenous citalopram in the thalamus (but not occipital cortex), but phMRI was less sensitive in distinguishing between groups than SPECT. Serotonin transporter occupancy showed a trend-significant correlation to thalamic cerebral blood flow change.Conclusion:These results suggest that phMRI likely suffers from higher variation than SPECT, but that these techniques probably also assess different functional aspects of the serotonergic synapse; therefore phMRI could complement positron emission tomography/SPECT for measuring effects of serotonergic medication.

Serotonergic, Dopaminergic, and Noradrenergic Modulation of Erotic Stimulus Processing in the Male Human Brain.

Human sexual behavior is mediated by a complex interplay of cerebral and spinal centers, as well as hormonal, peripheral, and autonomic functions. Neuroimaging studies identified central neural signatures of human sexual responses comprising neural emotional, motivational, autonomic, and cognitive components. However, empirical evidence regarding the neuromodulation of these neural signatures of human sexual responses was scarce for decades. Pharmacological functional magnetic resonance imaging (fMRI) provides a valuable tool to examine the interaction between neuromodulator systems and functional network anatomy relevant for human sexual behavior. In addition, this approach enables the examination of potential neural mechanisms regarding treatment-related sexual dysfunction under psychopharmacological agents. In this article, we introduce common neurobiological concepts regarding cerebral sexual responses based on neuroimaging findings and we discuss challenges and findings regarding investigating the neuromodulation of neural sexual stimulus processing. In particular, we summarize findings from our research program investigating how neural correlates of sexual stimulus processing are modulated by serotonergic, dopaminergic, and noradrenergic antidepressant medication in healthy males.

Evaluation of Flibanserin Safety: Comparison with Other Serotonergic Medications.

Flibanserin, a multifunctional serotonin agonist and antagonist, is approved by the U.S. Food and Drug Administration (FDA) for treatment of acquired, generalized hypoactive sexual desire disorder in premenopausal women. During the FDA's review of flibanserin, concerns were raised about the risks of hypotension, syncope, and sedation-related adverse events, which increase with alcohol use. Based on the results of an alcohol challenge study, the FDA required a boxed warning and alcohol contraindication in the flibanserin prescribing information, as part of a risk evaluation and mitigation strategy program. To evaluate the adverse event profile of flibanserin in the context of that seen with other medications that affect serotonin in the brain and are commonly prescribed for women. This was a review of data provided in the product prescribing information for flibanserin, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, other serotonergic antidepressants, and triptans. The incidence of adverse events was assessed. The incidences of hypotension, syncope, and sedation-related adverse events (eg, dizziness, somnolence, fatigue) in studies of flibanserin were within the ranges observed for serotonergic antidepressants; the rates of these adverse events were generally lower with triptan medications. Other flibanserin-associated adverse events (eg, nausea, insomnia, dry mouth) occurred more commonly in patients taking antidepressant medications. Although medications that affect the serotonin system have varying adverse event profiles (likely mediated by differences in serotonin-related mechanisms of action, specific brain structures affected, and effects on other neurotransmitter systems), the occurrence of central nervous system-related adverse events was not dissimilar between flibanserin and serotonergic antidepressants. Kingsberg SA, McElroy SL, Clayton AH. Evaluation of Flibanserin Safety: Comparison with Other Serotonergic Medications. Sex Med Rev 2019;7:380-392.

Drug-induced Acute Angle-closure Glaucoma: A Review.

ABSTRACTAimOur goal is to review current literature regarding drug-induced acute angle-closure glaucoma (AACG) and provide ophthalmologists and general practitioners with a thorough understanding of inciting medications and treatment pitfalls to be avoided.BackgroundDrug-induced AACG is an ophthalmological emergency that ophthalmologists and general practitioners should be familiar with, given its potentially blinding consequences. Common anatomical risk factors for AACG include a shallow anterior chamber depth, short axial length, plateau iris configuration, thick lens, anteriorly positioned lens, and rarely, intraocular tumor. Demographic risk factors include female sex, Asian ethnicity, family history, and advanced age. In patients with predisposing factors, acute angle closure can be triggered by various classes of medications including adrenergic agonists, anticholinergics, cholinergics, sulfonamides, supplements, and serotonergic medications. Physicians prescribing such inciting medications should be aware of their potentially sight-threatening adverse effects and to inform patients of the warning symptoms. Patients typically present with elevated intraocular pressure (IOP), headache, nausea, blurry vision, and halos around lights.Review resultsThere are two main mechanisms of drug-induced AACG, both with different treatment strategies. The first mechanism of drug-induced AACG is pupillary block and iridocorneal angle closure secondary to thickening of iris base with mydriasis. The second mechanism of drug-induced AACG is anterior displacement of the lens–iris diaphragm due to mass effect (e.g., blood, misdirected aqueous humor, and tumors), uveal effusion, or weakened zonules.ConclusionThis paper reviews drug-induced AACG, high-risk anatomical features, underlying mechanisms, inciting medications, and options for treatment and prevention.Clinical significanceWith proper understanding of the underlying mechanism of drug-induced AACG, physicians can respond promptly to save their patients’ vision by employing the correct treatment strategy.How to cite this articleYang MC, Lin KY. Drug-induced Acute Angle-closure Glaucoma: A Review. J Curr Glaucoma Pract 2019;13(3):104–109.

Challenges in the diagnosis and treatment of pediatric obsessive-compulsive disorder.

Obsessive–compulsive disorder (OCD) affects 1%–3% of children worldwide and has a profound impact on quality of life for patients and families. Although our understanding of the underlying etiology remains limited, data from neuroimaging and genetic studies as well as the efficacy of serotonergic medications suggest the disorder is associated with the fundamental alterations in the function of cortico-striato-thalamocortical circuits. Significant delays to diagnosis are common, ultimately leading to more severe functional impairment with long-term developmental consequences. The clinical assessment requires a detailed history of specific OCD symptoms as well as psychiatric and medical comorbidities. Standardized assessment tools may aid in evaluating and tracking symptom severity and both individual and family functioning. In the majority of children, an interdisciplinary approach that combines cognitive behavioral therapy with a serotonin reuptake inhibitor leads to meaningful symptom improvement, although some patients experience a chronic, episodic course. There are limited data to guide the management of treatment-refractory illness in children, although atypical antipsychotics and glutamate-modulating agents may be used cautiously as augmenting agents. This review outlines a clinical approach to the diagnosis and management of OCD, highlighting associated challenges, and limitations to our current knowledge.

Affect, interpersonal behaviour and interpersonal perception during open-label, uncontrolled paroxetine treatment of people with social anxiety disorder: a pilot study

Laboratory-based research with community samples has suggested changes in affective, behavioural and cognitive processes as possible explanations for the effects of serotonergic medications. Examining the effects of serotonergic medications using an ecological momentary measure (such as event-contingent recording) in the daily lives of people with social anxiety disorder would contribute to establishing the effects of these medications on affect, behaviour and one form of cognition: perception of others’ behaviour. The present study assessed changes in affect, interpersonal behaviour and perception of others’ behaviour in adults with social anxiety disorder using ecological momentary assessment at baseline and over 4 months of a single-arm, uncontrolled, open-label trial of treatment with the selective serotonin reuptake inhibitor paroxetine. Anxiety and concurrent depressive symptoms decreased. Participants also reported increased positive and decreased negative affect; increased agreeable and decreased quarrelsome behaviour; increased dominant and decreased submissive behaviour; and increased perception that others behaved agreeably toward them. Moreover, participants demonstrated reduced intraindividual variability in affect, interpersonal behaviour and perception of others’ behaviour. Limitations included the lack of a placebo group, the inability to identify the temporal order of changes and the restricted assessment of extreme behaviour. The results of the present study demonstrate changes during pharmacotherapy in the manifestation of affect, interpersonal behaviour and interpersonal perception in the daily lives of people with social anxiety disorder. Given the importance of interpersonal processes to social anxiety disorder, these results may guide future research seeking to clarify mechanisms of action for serotonergic medications.

Treatment of anxiety disorders in patients with comorbid bipolar disorder.

Anxiety disorders are the most prevalent comorbid diagnoses in patients with bipolar disorder (BD). A comorbid anxiety diagnosis can significantly impact the severity of bipolar symptoms, increase the risk of suicidality, and decrease psychosocial functioning and quality of life. The Canadian Network for Mood and Anxiety Treatments (CANMAT) task force published recommendations for treatment in 2012 suggesting that specific anticonvulsant mood stabilizers and second-generation antipsychotics are the medications of choice to treat these comorbidities. Serotonergic antidepressant medications are first-line medications for the treatment of most anxiety disorders; however, this can be problematic for a patient with BD. Antidepressant use in BD has been associated with a risk of manic switch as well as potential destabilization of mood. Mood stabilizer therapy should be established for patients with comorbid BD and an anxiety disorder before other medications are added to address the anxiety disorder. While benzodiazepine medications are recommended as third-line therapy in the CANMAT task force recommendations, their use should be avoided in patients with comorbid BD, posttraumatic stress disorder, and substance use disorders. The use of benzodiazepines should in general be avoided for all patients if possible, based upon current clinical research. Interpersonal, cognitive behavioral, and relaxation therapy are effective for the treatment of anxiety symptoms, especially emotional experiences, in patients who are euthymic.

Respiratory-Related Leg Movements of Sleep Are Associated With Serotonergic Antidepressants But Not Bupropion.

Respiratory-related leg movements (RRLMs) may contribute to the cardiovascular risk associated with obstructive sleep apnea (OSA). Selective serotonin reuptake inhibitors (SSRIs), but not bupropion, increase periodic leg movements in sleep. This study examines whether patients with OSA using SSRIs have more RRLMs than those taking bupropion or no antidepressant. Patients with an apnea-hypopnea index (AHI) of at least 10 events/h during a full-night diagnostic study or split-night study, who were taking bupropion (n = 32), an SSRI (n = 31), or no antidepressant (n = 31), were selected from a database of prestudy questionnaires. RRLMs were scored according to World Association of Sleep Medicine 2016 standards. Patients using SSRIs had significantly greater overall RRLM% (defined as the percentage of respiratory events associated with a leg movement, including apneas, hypopneas, and respiratory effort-related arousals), RRLM index, and periodic limb movement index relative to patients using bupropion and control patients. The difference between the RRLM% in the SSRI and bupropion groups was limited to patients undergoing split-night studies, and that of the SSRI and control groups was limited to patients undergoing full-night diagnostic studies. The greater number of RRLMs and PLMs in the SSRI group may contribute to treatment-emergent insomnia often seen with SSRI use. Fragmented sleep and elevated autonomic nervous system activation associated with increased RRLMs in patients with OSA taking SSRIs might also limit the tolerability of antidepressant treatment, as well as increase the risk for cardiovascular disease.