Combined NMDA Inhibitor Use in a Patient With Multisubstance-induced Psychotic Disorder

This document is an Accepted Manuscript reprinted from Journal of Addiction Medicine, Vol. 12 (3): 247-251, May 2018, with permission of Kluwer Law International. Under embargo until 1 May 2019. The Version of Record is available online at DOI: https://doi.org/10.1097/ADM.0000000000000390: Novel psychoactive substance use is a major social concern. Their use may elicit or uncover unpredictably as yet undescribed clinical pictures. We aimed to illustrate a multisubstance use case indistinguishable from paranoid schizophrenia, so to alert clinicians on possibly misdiagnosing substance-induced psychotic disorders. CASE REPORT: We describe a case of a 32-year-old man who started at 18 years with cannabinoids and ketamine, and is currently using N-methyl-D-aspartate (NMDA) antagonists. At age 23, he developed social withdrawal after being assaulted by a stranger, but did not consult psychiatrists until age 26; during this period, he was using internet-purchased methoxetamine and ketamine, and was persecutory, irritable, suspicious, and insomniac and discontinued all received medical prescriptions. He added dextromethorphan to his list of used substances. At age 31, while using phencyclidine, and, for the first time, methoxphenidine, he developed a religious delusion, involving God calling him to reach Him, and the near-death experiences ensured by NMDA antagonists backed his purpose. He received Diagnostic and Statistical Manual of Mental Disorders, 5th Edition diagnosis of multisubstance-induced psychotic disorder and was hospitalized 8 times, 6 of which after visiting the emergency room due to the development of extreme anguish, verbal and physical aggression, and paranoia. He reportedly used methoxphenidine, methoxyphencyclidine, ethylnorketamine, norketamine, and deschlorketamine, to achieve near-death experiences, and eventually to reach God in heavens. CONCLUSIONS: This case points to the need for better control of drugs sold on the internet. It also illustrates that people using NMDA antagonists may present clinical pictures indistinguishable from those of major psychoses and are likely to be misdiagnosed.Peer reviewe

Use of benzylglycinamide by a HIV-seropositive polysubstance user: : the changing pattern of novel psychoactive substance use among youths

This document is the Accepted Manuscript of the following article: Matteo Caloro, et al, ‘Use of benzylglycinamide by a HIV-seropositive polysubstance user: The changing pattern of novel psychoactive substance use among youths’, Addictive Behaviors, Vol. 60, pp. 53-57, September 2016. The Version of Record is available online at doi: https://doi.org/10.1016/j.addbeh.2016.03.032. © 2016 Elsevier Ltd. All rights reserved.A 24-year old woman with multisubstance use since the age of 13, including opioids and cocaine, and long-standing HIV/HCV seropositivity status, presented with psychosis, agitation, and insomnia at the emergency department of a university hospital. She had been abusive and physically aggressive frequently without specific reasons and was involved in criminal legal cases. She was hospitalized twice. During her first hospital stay she experienced a brief episode of detachment from her environment, similar to episodes reportedly suffered at home. Psychosis had developed following heavy polysubstance abuse. Her mother provided sachets containing benzylglycinamide, a substance with no known psychotropic effects, which were also present in the patient's urine. She was occasionally positive for cannabinoids. She used to buy various novel psychoactive substances (NPSs) from the internet and used experimentally various substances freely made available to her by drug suppliers/dealers. She was unable to explain clearly why she was taking any of the identified NPS. She stated she was taking benzylglycinamide to calm her when smoking synthetic cannabinoids. While it appears that benzylglycinamide is not likely to constitute a novel drug of abuse, her polysubstance use exemplifies trends in NPS use patterns among the youths in the Western world and should alert mental health workers as to the possible dangers of such behavior and its reflection on social behavior and psychopathology.Peer reviewedFinal Accepted Versio

Hiccup with aripiprazole plus benzodiazepines resolving with pregabalin and/or benzodiazepine switch/discontinuation. four case reports

Hiccup lasting for more than 2 days is termed protracted and hiccup lasting for more than 2 months is termed intracta- ble; hiccup is associated with high mortal- ity.1 The neurochemistry associated with hiccup is unknown. However, it is believed that dopamine facilitates the hiccup, whereas γ-aminobutyric acid (GABA) reduces it through GABAB receptors but may2 in- crease it through GABAA receptors. In fact, antiparkinsonian medication induces it,3 whereas dopamine receptor blockers and the GABAB agonist baclofen are used in its treatment.4,5 Alternative proposed treatments include the dihydropyridine L-type calcium channel blocker, nimodipine,6 and the α2δ subunit of voltage-gated calcium channels ligands gabapentin7 and pregaba- lin.8,9 Gabapentin and pregabalin are active on L-, N-, P-, and R-type calcium channels. Summarizing the previous data, D2 dopa- mine and GABAA receptor facilitation acti- vates the hiccup reflex in combination with voltage-gated calcium ions, whereas GABAB receptor activation, dopamine D2 inhibi- tion, and voltage-gated calcium channel blockade inhibit the reflex. Calcium ion channel inhibition is able to block hiccup; however, the mechanism is currently un- known. Interestingly, dopaminergic firing of ventral tegmental area dopamine neu- rons is supported by N-type channels,10 and both N- and P-type channel–mediated calcium ion influx facilitate somatodendri- tic and terminal dopamine release.11 In addi- tion, GABAB receptors directly inhibit voltage-gated calcium ion channels,12 whereas GABAA receptor activation in- creases intracytosol calcium in astrocytes through L- and T-type voltage-gated cal- cium channels.13 D2 dopamine receptor–blocking anti- psychotics should theoretically decrease the risk for hiccup, but aripiprazole is a par- tial D2 receptor agonist at lower doses; thus, it may be expected to increase it. Adding a benzodiazepine to aripiprazole might fur- ther increase the risk for hiccup. We describe 4 cases of patients who developed hiccup after taking aripiprazole and benzodiazepines; the symptom improved after discontinuation of one of the drugs or after adding a voltage-gated calcium ion blocker

Does the efficacy of asenapine in bipolar disorder increase in the presence of comorbidity with a substance use disorder? A naturalistic study

Background: Asenapine is a second-generation antipsychotic approved in Europe for treating moderate-to-severe manic episodes in adults affected by type I bipolar disorder (BD-I). We aimed to compare its efficacy in psychiatric inpatients with BD-I, with or without substance use disorder (SUD). Methods: We administered flexible asenapine doses ranging from 5–20 mg/day to 119 voluntarily hospitalized patients with Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) BD-I diagnosis, with or without SUD. Patients were assessed with clinician-rated questionnaires [i.e. Brief Psychiatric Rating Scale (BPRS), Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale (HARS), and Global Assessment of Functioning (GAF)]. Assessments were carried out at baseline (T0, prior to treatment), and 3 (T1), 7 (T2), 15 (T3), and 30 days (T4) after starting treatment for all clinical scales and at T0 and T4 for the GAF. Results: Patients improved on all scales (p < 0.001) across all timepoints, as shown both by paired-sample comparisons and by applying a repeated-measures, generalized linear model (GLM). Patients without comorbid SUD showed greater reductions in BPRS scores at T2 and T3, greater reduction in YMRS scores at T3, and lower HARS scores at all timepoints. HDRS scores did not differ between the two groups at any timepoint. However, the reduction in HARS scores in the comorbid group was stronger than in the BD-I only group, albeit not significantly. Side effects were few and mild-to-moderate. Conclusions: The open-label design and the relatively short observation period may expose to both type I and type II statistical errors (false positive and false negatives). Asenapine showed effectiveness and safety in hospitalized BD-I patients. Its effect was stronger in patients without comorbid SUD

[Functional neuroimaging of the amygdala: the response to threatening and phobogenic stimuli]

Recent functional neuroimaging studies show that the amygdala has a central role in threat evaluation, in response to conditioned and unconditioned stimuli, in fear learning and fear extinction. The amygdala is involved in the pathophysiology of phobias and anxiety. In this review we critically examine the main findings of functional neuroimaging studies reporting data on the amygdala. Findings suggest that the response of the amygdala to threatening stimuli is mainly modulated by the infralimbic and prefrontal cortices, which inhibit activation of the amygdala (top-down inhibition), and by the hippocampus, the function of which is related to stimulus learning. The activity of the amygdala is modulated by various factors, like stimulus type and origin, emotion triggered by stimulus perception, and attention. The neural network comprising the amygdala and the frontal cortex is involved not only in top-down inhibition, but also in the emotional perception of facial expressions. This network also includes the thalamic pulvinar, which is densely interconnected with the amygdala, directly or indirectly, and which is activated by emotional face recognition of scary fear. Both top-down inhibition mechanisms and emotional face recognition are altered in anxiety disorders, particularly in specific and social phobia, resulting in reduced amygdalar activity inhibition after anxiety - or fear - inducing stimulus perception. Future functional neuroimaging studies will be able to provide new insights of normal and altered neurophysiology of the amygdala.I recenti studi di neuroimaging funzionale dimostrano che l’amigdala ha una funzione fondamentale nella va- lutazione dei pericoli, nella risposta a stimoli condizionati e non condizionati, così come in altre forme associative di appren- dimento di stimoli potenzialmente pericolosi come l’apprendimento e l’estinzione della paura. Essa è implicata nella fisiopa- tologia delle fobie e dell’ansia. In questa rassegna sono raccolti i principali dati riguardanti l’amigdala ottenuti attraverso gli studi di neuroimaging funzionale. Secondo tali dati, la risposta dell’amigdala agli stimoli minacciosi è modulata principalmen- te dalla corteccia infralimbica e prefrontale, che ne inibisce l’attivazione (top-down inhibition), e dall’ippocampo, la cui fun- zione è legata all’apprendimento degli stimoli. L’attività dell’amigdala è modulata da diversi fattori, tra cui la tipologia dello stimolo, la sua provenienza, l’emotività scatenata dalla percezione e i livelli di attenzione. Il network neuronale tra amigdala e corteccia frontale è implicato non solo nella top-down inhibition, ma anche nella percezione delle espressioni facciali. In ta- le rete rientra anche il pulvinar del talamo, attraverso le sue numerose connessioni dirette e indirette con l’amigdala, attivo nel riconoscimento delle espressioni facciali di spavento. Sia i meccanismi di top-down inhibition sia il riconoscimento delle espressioni facciali sono alterati nei disturbi d’ansia, in particolar modo nella fobia specifica e nella fobia sociale, il che com- porta una ridotta inibizione dell’attività dell’amigdala dopo la percezione di uno stimolo ansiogeno o inducente spavento. I futuri studi di neuroimaging funzionale potranno fornire nuove conoscenze sull’attività fisiologica e sulle alterazioni neuro- fisiopatologiche dell’amigdala

Quetiapine Abuse Fourteen Years Later: Where Are We Now? A Systematic Review

Background: Quetiapine, an atypical antipsychotic endowed with weak dopamine antagonist, potent 5-HT2A-blocking, partial 5-HT1A-agonist, anti-H-1 histamine, adrenolytic, and sigma(1) receptor agonist activities, since an original 2004 report is increasingly misused. Although some of its pharmacodynamics might explain some motives for voluptuary use, most of its actions are directed at setting-off those motives. Hence, it is possible that its popularity in special populations is due to the fact that the unpleasant or unwanted effects of addiction substances are somehow soothed by quetiapine. Currently, quetiapine is tested in substance use disorders, showing some promise, but it is likely to be misused in certain contexts. Objectives: To review the evidence for the use of quetiapine as addiction substance and investigate the characteristics of populations involved in such addiction. Methods: A systematic review of literature on various databases retrieved on September 7, 2018 87 records to comment. Results. We reviewed the evidence for quetiapine?s addictive potential in the light of its pharmacodynamics properties and presented two cases of recreational quetiapine use, by a 35-year old male patient with past addictive behavior and by a 50-year-old woman with major depressive disorder and conversion disorder. We found quetiapine to be abused mainly by addict populations and people with law involvement. Conclusions/Importance: There is no reason to include quetiapine among regulated substances, but monitoring of its use in selected populations is warranted. Psychiatrists and physicians working in the penitentiary system should be aware of the addictive potential of quetiapine and adopt measures restricting its use

Stenosi aortica severa inoperabile trattata con successo mediante impianto di valvola aortica per via percutanea

Patients with severe calcific aortic stenosis are occasionally not amenable to surgery because of advanced age or severe co-morbidities. Percutaneous aortic valve dilation is used but has only limited time relief. While preclinical evidence on percutaneous aortic valve replacement seems promising, only very limited clinical data are available worldwide. We hereby present the first case of percutaneous aortic valve replacement successfully performed in Italy in a 74-year-old high-risk female. This case emphasizes the technical challenges inherent to this procedure and its promising role in selected very high-risk patients with severe aortic stenosis, notwithstanding the early and long-term risk of adverse events. © 2005 CEPI Srl

Aumento dei livelli sierici di Dickkopf-1 nei pazienti psicotici che abusano di droghe.

Serum DKK1 levels examination as an indicator of ongoing neurodegeneration in psychotic patients, with or without a recent or current history of drug abuse

Increased serum Dickkopf-1 levels in drug-abusing psychotic patients

Background: Dickkopf-1 (DKK1) is an inhibitor of the canonical Wnt pathway, which is known to be impaired in both psychotic and neurodegenerative disorders. Here, we examined serum DKK1 levels as an indicator of ongoing neurodegeneration in psychotic patients, with or without a recent or current history of drug abuse. Methods: We measured serum DKK1 levels by ELISA in 22 inpatients with psychosis and no history of drug abuse, 22 with psychosis and drug abuse, and 16 controls. We rated psychopathology using the following rating scales: the Positive and Negative Syndrome Scale (PANSS); the Clinical Global Impressions (CGI) severity scale; and the Global Assessment of Functioning (GAF) scale. Extrapyramidal motor symptoms were assessed by the Simpson-Angus Neurological Rating Scale (NRS). Results: Inpatients with psychosis and comorbid substance abuse showed significantly higher serum DKK1 levels than inpatients with psychosis and no comorbid substance abuse or controls. Comorbid patients had earlier onset, longer duration of psychosis, and more severe extrapyramidal motor symptoms. However, we did not find any significant correlation between DKK1 levels and rating scale scores. Conclusion: Psychosis led to elevated serum DKK1 levels, and substance abuse led to a further increase. Knowing that there is a correlation between brain and blood levels of DKK1, we speculate that the observed increase in DKK1 levels reflects drug-induced neurotoxicity in our patients. (C) 2011 Elsevier Inc. All rights reserved