EDITORIAL: “The Faces of Mania: The Legacy of Athanasios Koukopoulos”

The concept of “Mania” is intimately linked to the evolution of psychiatry itself. The Legacy of Athanasios Koukopoulos

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

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

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

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

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

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

Perinatal Mood and Anxiety Disorders in Women Undergoing Medically Assisted Reproduction

Background: Women taking advantage of medically assisted reproduction (MAR) techniques may differ from spontaneously conceiving women (nonMAR) in risk of depression and/or anxiety. We aimed to investigate possible differences between MAR and nonMAR through the use of the Edinburgh Postnatal Depression Scale in a sample of Italian-speaking women at their third trimester of pregnancy. Methods: We administered the Edinburgh Postnatal Depression Scale (EPDS) to two groups of pregnant women, MAR and nonMAR, at the third trimester of pregnancy (T0), one month after delivery (T1), and three months after delivery (T2) from February 2013 to December 2019. EPDS total scores cutoffs were ≥9 for risk of depression, 9–11 mild depression, ≥12 major depression, and the EPDS-3A cluster ≥4 was a proxy for anxiety. Results: Included were 1303 nonMAR women and 92 MAR, an expected disproportion. NonMAR and MAR women did not differ on depression or anxiety at any assessment timepoint. MAR women were older than nonMAR, consumed more alcohol and medical drugs, and displayed more complications during pregnancy. Scoring over the threshold on depression risk was associated with foreign nationality, unemployment, psychiatric history of the patient, family or partner, psychiatric problems in past pregnancies, hyperemesis, premenstrual syndrome (PMS), and stressful life events in the last year at baseline, and, for some of them, at other timepoints. In contrast, MAR past or current was associated with having suprathreshold depression at the first-month postpartum follow-up. Conclusions: Taken together, our data show that women opting for MAR do not differ from spontaneously conceiving women regarding psychiatric outcomes but do differ on some sociodemographic and clinical variables

A systematic review of manic/hypomanic and depressive switches in patients with bipolar disorder in naturalistic settings: The role of antidepressant and antipsychotic drugs

The present systematic review was aimed at critically summarizing the evidence about treatmentemergent manic/hypomanic and depressive switches during the course of bipolar disorder (BD). A systematic search of the MEDLINE, EMBASE, CINAHL, Web of Science, and PsycInfo electronic databases was conducted until March 24th , 2021, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Observational studies clearly reporting data regarding the prevalence of treatment-emergent mood switches in patients with BD were considered for inclusion. Thirty-two original studies met the inclusion criteria. In the majority of cases, manic switches were analyzed; only 3 papers investigated depressive switches in type I BD. Treatment-emergent mania/hypomania in BD subjects ranged from 17.3% to 48.8% and was more frequent with antidepressant monotherapy compared to combination treatment with mood stabilizers, especially lithium, or second-generation antipsychotics. A higher likelihood of mood switch has been reported with tricyclics and a lower rate with bupropion. Depressive switches were detected in 5-16% of type I BD subjects and were associated with first-generation antipsychotic use, the concomitant use of first- and second-generation antipsychotics, and benzodiazepines. The included studies presented considerable methodological heterogeneity, small sample sizes and comparability flaws. In conclusion, many studies, although heterogeneous and partly discordant, have been conducted on manic/hypomanic switches, whereas depressive switches during treatment with antipsychotics are poorly investigated. In BD subjects, both antidepressant and antipsychotic medications seems to play a role in the occurrence of mood switches, although the effects of different pharmacological compounds have yet to be fully investigated