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

Periodic Limbic Movement Disorder during Sleep as Diabetes-Related Syndrome? A Polysomnographic Study

Introduction. Periodic limb movements during sleep (PLMs) is common in the elderly. When quality-of-life drops due to sleep disturbances, we speak about periodic limb movement disorder during sleep (PLMD). Another similar disorder, restless legs syndrome (RLS), is considered to be related to diabetes; RLS and PLMDs are genetically related. Our aim was to detect PLMDs in a population of diabetic patients and identify them as possible hallmarks of these autonomic disorders. Material and Methods. We selected 41 type-2 diabetics with no sleep comorbidity, and compared them with 38 healthy matched volunteers. All participants underwent the Epworth Sleepiness Scale (ESS) and polysomnography (PSG). A periodic limb movement (PLM) index >5, that is, the higher number of PLMs/sleep hour for the entire night, was considered as abnormal. Results. Diabetics showed lower sleep efficiency than controls on the ESS, lower proportions of REM and non-REM sleep, and higher arousal and PLM indexes, as assessed through PSG. PLMDs were diagnosed in 13 of 41 diabetic patients (31%); the latter showed lower sleep efficiency, lower non-REM slow-wave sleep, and increased arousal and PLM indexes. Conclusion. The relationship between PLMs-related sleep fragmentation and endocrine carbohydrate metabolism regulation might be casual or genetically determined. This deserves further investigations

Evolution of International Psychiatry

International psychiatry is currently facing serious challenges triggered by the global economic crisis and the COVID-19 pandemic. These global events lead to the need to broaden our nosographic and therapeutic horizons, and to make use of the newest psychological approaches and the latest neuroscience acquisitions. The focus should be on the psychological consequences of the pandemic, not only on people suffering from mental disorders, but also on the general population, for which the risk of developing psychic symptoms appears to be increased. A population that needs special attention is that of health workers involved in the management of the pandemic. In facing these problems, psychiatry today can use numerous new clinical applications and technologies in the fields of precision medicine. These include genomics, neuroimaging, and microbiomics, which can also be integrated with each other through machine learning systems. They can provide new contributions both in treatment personalization and in the evolution of nosographic systems. Besides this, the contribution of psychotherapies and dynamic and clinical psychology appears to be indispensable for a complete understanding of the clinical and personological aspects of patients. This journal aims to include innovative studies deriving from original, clinical, and basic research in the fields of mental health, precision psychiatry, genomics, neuroimaging, neuropsychopharmacology, and dynamic and clinical psychology

Maintenance deep transcranial magnetic stimulation sessions are associated with reduced depressive relapses in patients with unipolar or bipolar depression

Introduction: Deep transcranial magnetic stimulation (dTMS) is a new form of TMS allowing safe stimulation of deep brain regions. The objective of this preliminary study was to assess the role of dTMS maintenance sessions in protecting patients with bipolar disorder (BD) or recurrent major depressive disorder (MDD) from developing depressive or manic relapses in a 12-month follow-up period. Methods: Twenty-four drug-resistant patients with a current depressive episode and a diagnosis of MDD or BD have been enrolled in the study. All the participants underwent daily dTMS sessions for 4 weeks. One group (maintenance - M group) received additional maintenance dTMS sessions weekly or twice a week. Results: After the first dTMS cycle, a significant reduction of Hamilton Depression Rating Scale (HDRS) scores was observed in all participants. Subsequently, the HDRS mean scores did not significantly change over time in the M group, while it significantly increased in the non-M-group after 6 and 12 months. Discussion: This study confirms previous evidence of a positive therapeutic effect of dTMS on depressive symptoms and suggests that, after recovery from acute episodes, maintenance dTMS sessions may be helpful in maintaining euthymia in a 12-month follow-up period

Efficacy of nicotine administration on obsessions and compulsions in OCD. a systematic review

Background: Preliminary studies have tested nicotine as a novel treatment for OCD patients who respond partially/ incompletely or not at all to frst and second-line treatment strategies, with the former represented by SSRIs or clomipramine, and the latter by switching to another SSRI, or augmentation with atypical antipsychotics, and/or combination with/switching to cognitive–behavioural therapy. Some studies found nicotine-induced reduction of obsessive thoughts and/or compulsive behaviour in OCD patients. We aimed to evaluate the efcacy of nicotine administration in OCD patients. Methods: We searched the PubMed, ScienceDirect Scopus, CINHAL, Cochrane, PsycINFO/PsycARTICLES, and EMBASE databases from inception to the present for relevant papers. The ‘Preferred Reporting Items for Systematic Review and Meta-Analyses’ (PRISMA) standards were used. We included all studies focusing on the efects of nicotine administration on OCD patients’ obsessions or compulsions. Studies could be open-label, cross-sectional, randomized controlled trials, case series or case reports. Results: A total of fve studies could be included. Nicotine administration may ameliorate behavioural features and recurrent thoughts of severe, treatment-resistant OCD patients; however, in one study it was not associated with OC symptom improvement or cognitive enhancement across various executive function subdomains. Conclusions: Although encouraging, the initial positive response from the use of nicotine in OCD needs testing in large controlled studies. This, however, raises ethical issues related to nicotine administration, due to its addiction potential, which were not addressed in the limited literature we examined. As an alternative, novel treatments with drugs able to mimic only the positive efects of nicotine could be implemented

Mitochondrial myopathy and comorbid major depressive disorder. effectiveness of dTMS on gait and mood symptoms

Background: Mitochondrial myopathies (MMs) often present with leukoencephalopathy and psychiatric symptoms, which do not respond to or worsen with psychiatric drugs. Case report: A 67-year-old woman with a 10-year history of probable chronic progressive external ophthalmoplegia, an MM, had drug-resistant, anxious-depressive symptoms. Since she had never had seizures, we proposed 20 sessions of deep transcranial magnetic stimulation (dTMS) for her depression. Surprisingly, besides the expected improvement of depression, we observed marked improvement of movement disorder that lasted as long as the patient was undergoing dTMS. She also improved her performance on neuropsychological tests of executive function and cognitive speed. Depressive symptom improvement was persistent, while anxiety symptoms recurred after the end of the sessions. Conclusions: dTMSmay be an alternative antidepressant strategy in patients withMMs, provided that they are free from seizures. The mechanism of improvement of motor disturbance may relate to dorsolateral prefrontal cortex stimulation and improved executive function and needs further investigation

Decisional capacity to consent to treatment and research in patients affected by Mild Cognitive Impairment. A systematic review and meta-analysis.

ABSTRACTObjectives:To perform a meta-analysis of clinical studies on the differences in treatment or research decision-making capacity among patients with Mild Cognitive Impairment (MCI), Alzheimer's disease (AD), and healthy comparisons (HCs).Design:A systematic search was conducted on Medline/Pubmed, CINAHL, PsycINFO, Web of Science, and Scopus. Standardized mean differences and random-effects model were used in all cases.Setting:The United States, France, Japan, and China.Participants:Four hundred and ten patients with MCI, 149 with AD, and 368 HCs were included.Measurements:The studies we included in the analysis assessed decisional capacity to consent by the MacArthur Competence Assessment Tool for Treatment (MAcCAT-T), MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR), Capacity to Consent to Treatment Instrument (CCTI), and University of California Brief Assessment of Capacity to Consent (UBACC).Results:We identified 109 potentially eligible studies from 1672 records, and 7 papers were included in the meta-analysis. The meta-analysis showed that there was significant impairment in a decision-making capacity in MCI patients compared to the HCs group in terms of Understanding (SMD = −1.04, 95% CI: −1.31 to −0.77, P < 0.001; I2 = 52%, P = 0.07), Appreciation (SMD = −0.51, 95% CI: −0.66 to −0.36, P < 0.001; I2 = 0%, P = 0.97), and Reasoning (SMD = −0.62, 95% CI: −0.77, −0.47, P < 0.001; I2=0%, P =0.46). MCI patients scored significantly higher in Understanding (SMD = 1.50, 95% CI: 0.91, 2.09, P = 0.01, I2 = 78%, P = 0.00001) compared to patients affected by AD.Conclusions:Patients affected by MCI are at higher risk of impaired capacity to consent to treatment and research compared to HCs, despite being at lower risk compared to patients affected by AD. Clinicians and researchers need to carefully evaluate decisional capacity in MCI patients providing informed consent

Evaluation of the capacity to consent to treatment among patients with bipolar disorder: Comparison between the acute psychopathological episode and the stable mood phase

Objective: Treatment decision-making capacity (TDMC) is basic to therapeutic processes and can be measured with the MacArthur Competence Assessment Tool for Treatment (MacCAT-T). TDMC may fluctuate in bipolar disorder (BD). We used the MacCAT-T to compare BD inpatients with an acute manic or depressive episode with euthymic BD outpatients on their TDMC. Methods: We used the MacCAT-T to cross-sectionally assessed from May 2018 through October 2019 the TDCM of adult BD patients with a Mini Mental State Examination score ≥ 18, a group of acutely ill hospitalized patients for a manic/hypomanic episode and another of euthymic outpatients during their regular visits at our outpatient clinic. Patients were assessed with other specific psychiatric rating scales. We also tested their TDCM to an alternative treatment. Results: The inpatient group consisted of 53 patients and the outpatient of 47. Inpatients scored worse than out- patients on the MacCAT-T understanding, reasoning and expressing a choice subscale, but not on the appreciating scale. Outpatients were more capable in understanding the characteristics of an alternative advance treatment. MacCAT-T subscales correlated directly with mental state scores, and inversely with mania and psychopathology scores, while only the appreciating subscale correlated inversely with depression scores. Limitations: The limitations include small sample size and cross-sectional design. Conclusions: TDCM is higher in BD patients at their euthymic state, hence this is the right time to obtain consent from a BD patient in view of possibly depositing psychiatric advance directives

The Koukopoulos mixed depression rating scale (KMDRS) and the assessment of mixed symptoms during the perinatal period

Background: Mixed symptoms in depression may underlie bipolar diathesis rather than unipolarity. Uncovering mixed depression (MxD) is crucial for appropriate management, especially in the perinatal period, as it may affect treatment planning and impact future child development. We used a scale specific for identifying MxD and tested its validity in pregnant and postpartum women with depression. Methods: Women developing a major depressive episode (MDE) during their perinatal period extending from pregnancy to one year postpartum from November-2012 through June-2019 were assessed with BPRS-18, EPDS, CGI-S, GAF, HAM-A, HAM-D, Koukopoulos' Mixed Depression Rating Scale (KMDRS), TEMPS, and YMRS. They were classified, based on KMDRS criteria, as with mixed (MxD) or without (nonMxD) mixed symptoms. We conducted ROC analysis and performed factor analysis of the KMDRS. Results: Of 45 included, MxD (N = 19) were biased towards diagnosis of bipolar disorder and nonMxD (N = 26) towards major depressive disorder. Other sociodemographic variables did not differ significantly between MxD and nonMxD. MxD scored higher on total YMRS, BPRS, and KMDRS, and on KMDRS-6 Subjective Feelings of Irritability and KMDRS-12 Suicidal Impulsiveness items. The KMDRS correlated in the entire sample, in MxD and nonMxD, with the YMRS and the BPRS, while correlating with the HAM-D in nonMxD only. The KMDRS showed acceptable AUC distribution, with a 68% sensitivity and 58% specificity. Best-fit was three-factor-structure, explaining 54.66% of cumulative variance. Limitations: Small sample and cross-sectional design. Conclusions: The KMDRS is fit for investigating MxD along with the YMRS and the BPRS in perinatal women with a MDE