Obsessive-Compulsive Disorder as an Epiphenomenon of Comorbid Bipolar Disorder? An Updated Systematic Review.

BACKGROUND: Bipolar disorder (BD) and obsessive-compulsive disorder (OCD) comorbidity is an emerging condition in psychiatry, with relevant nosological, clinical, and therapeutic implications. METHODS: We updated our previous systematic review on epidemiology and standard diagnostic validators (including phenomenology, course of illness, heredity, biological markers, and treatment response) of BD-OCD. Relevant papers published until (and including) 15 October 2023 were identified by searching the electronic databases MEDLINE, Embase, PsychINFO, and Cochrane Library, according to the PRISMA statement (PROSPERO registration number, CRD42021267685). RESULTS: We identified 38 new articles, which added to the previous 64 and raised the total to 102. The lifetime comorbidity prevalence ranged from 0.26 to 27.8% for BD and from 0.3 to 53.3% for OCD. The onset of the two disorders appears to be often overlapping, although the appearance of the primary disorder may influence the outcome. Compared to a single diagnosis, BD-OCD exhibited a distinct pattern of OC symptoms typically following an episodic course, occurring in up to 75% of cases (vs. 3%). Notably, these OC symptoms tended to worsen during depressive episodes (78%) and improve during manic or hypomanic episodes (64%). Similarly, a BD course appears to be chronic in individuals with BD-OCD in comparison to patients without. Additionally, individuals with BD-OCD comorbidity experienced more depressive episodes (mean of 8.9 ± 4.2) compared to those without comorbidity (mean of 4.1 ± 2.7). CONCLUSIONS: We found a greater likelihood of antidepressant-induced manic/hypomanic episodes (60% vs. 4.1%), and mood stabilizers with antipsychotic add-ons emerging as a preferred treatment. In line with our previous work, BD-OCD comorbidity encompasses a condition of greater nosological and clinical complexity than individual disorders.

Keep in mind sex differences when prescribing psychotropic drugs.

Women represent the majority of patients with psychiatric diagnoses and also the largest users of psychotropic drugs. There are inevitable differences in efficacy, side effects and long-term treatment response between men and women. Psychopharmacological research needs to develop adequately powered animal and human trials aimed to consider pharmacokinetics and pharmacodynamics of central nervous system drugs in both male and female subjects. Healthcare professionals have the responsibility to prescribe sex-specific psychopharmacotherapies with a priority to differentiate between men and women in order to minimize adverse drugs reactions, to maximize therapeutic effectiveness and to provide personalized management of care.

Third-Generation Antipsychotics and Lurasidone in the Treatment of Substance-Induced Psychoses: A Narrative Review.

This narrative review explores the efficacy and tolerability of third-generation antipsychotics (TGAs)-aripiprazole, cariprazine, brexpiprazole, and lurasidone-for the management of substance-induced psychosis (SIP). SIP is a psychiatric condition triggered by substance misuse or withdrawal, characterized by unique features distinct from those of primary psychotic disorders. These distinctive features include a heightened prevalence of positive symptoms, such as hallucinations and delusions, in addition to a spectrum of mood and cognitive disturbances. This review comprehensively investigates various substances, such as cannabinoids, cocaine, amphetamines, and LSD, which exhibit a greater propensity for inducing psychosis. TGAs exhibit substantial promise in addressing both psychotic symptoms and issues related to substance misuse. This review elucidates the distinctive pharmacological properties of each TGA, their intricate interactions with neurotransmitters, and their potential utility in the treatment of SIP. We advocate for further research to delineate the long-term effects of TGAs in this context and underscore the necessity for adopting an integrated approach that combines pharmacological and psychological interventions. Our findings underscore the intricate and multifaceted nature of treating SIP, highlighting the potential role of TGAs within therapeutic strategies.

Non-binary gender, vulnerable populations and mental health during the COVID-19 pandemic: Data from the COVID-19 MEntal health inTernational for the general population (COMET-G) study.

BACKGROUND: The COVID-19 pandemic has brought significant mental health challenges, particularly for vulnerable populations, including non-binary gender individuals. The COMET international study aimed to investigate specific risk factors for clinical depression or distress during the pandemic, also in these special populations. METHODS: Chi-square tests were used for initial screening to select only those variables which would show an initial significance. Risk Ratios (RR) were calculated, and a Multiple Backward Stepwise Linear Regression Analysis (MBSLRA) was followed with those variables given significant results at screening and with the presence of distress or depression or the lack of both of them. RESULTS: The most important risk factors for depression were female (RR = 1.59-5.49) and non-binary gender (RR = 1.56-7.41), unemployment (RR = 1.41-6.57), not working during lockdowns (RR = 1.43-5.79), bad general health (RR = 2.74-9.98), chronic somatic disorder (RR = 1.22-5.57), history of mental disorders (depression RR = 2.31-9.47; suicide attempt RR = 2.33-9.75; psychosis RR = 2.14-10.08; Bipolar disorder RR = 2.75-12.86), smoking status (RR = 1.15-5.31) and substance use (RR = 1.77-8.01). The risk factors for distress or depression that survived MBSLRA were younger age, being widowed, living alone, bad general health, being a carer, chronic somatic disorder, not working during lockdowns, being single, self-reported history of depression, bipolar disorder, self-harm, suicide attempts and of other mental disorders, smoking, alcohol, and substance use. CONCLUSIONS: Targeted preventive interventions are crucial to safeguard the mental health of vulnerable groups, emphasizing the importance of diverse samples in future research. LIMITATIONS: Online data collection may have resulted in the underrepresentation of certain population groups.

Cariprazine Augmentation in Treatment-Resistant Bipolar Depression: Data from a Retrospective Observational Study.

BACKGROUND: Treatment-resistant bipolar depression is one of the leading problems in psychiatry with serious consequences on patients functioning, quality of life and resource utilization. Despite this, there is a lack of consensus on diagnostic criteria and treatment algorithms. OBJECTIVE: The objective of the present study is to assess the acute effectiveness and tolerability of cariprazine in the management of treatment resistant bipolar depression. METHODS: This is a four weeks retrospective multicentric observational study on patients with treatment resistant bipolar depression receiving cariprazine in augmentation to the current treatment. Cariprazine dosage changed during the follow-up period according to clinical judgment. Since data followed a non-normal distribution, non-parametric tests were used to pursue the analysis. The effectiveness of cariprazine was assessed through the mean change in Hamilton Depression rating scale (HAM-D) scores from baseline to endpoint. For missing values, a "Last Observation Carried Forward" approach was applied. RESULTS: Fifty-one patients were enrolled. Four patients (7.8%) discontinued cariprazine mainly due to adverse events. Mean cariprazine dose was 1.7 mg/day. The mean HAM-D score decreased significantly from baseline (T0) to week 4 (T4) at each evaluation point. Fourty-five.one per cent of the patients benefited of cariprazine add-on strategy: 23.5% achieved a clinical response and 21.6% were remitters. Among the completers, 70.6% experienced at least one adverse event. All side effects were mild to moderate. CONCLUSION: Cariprazine seems to be an effective and well tolerated option in the management of patients with treatment resistant bipolar depression.

Bipolar Disorder: Identity, Social Support, Religiosity and Spirituality. Can Religiosity/Spirituality be a Mood Balancing Factor? An Italian Case Report.

This paper presents a case study to support the hypothesis that religiosity and spirituality (R/S), as mood balancing factors, could facilitate the recovery process for patients suffering from bipolar disorder (BD) once they have been stabilized and are receiving appropriate support (e.g., in a residential rehabilitative center). After a succinct review of BD and R/S, the patient's medical history and rehabilitation pathway are described, with a particular focus on the role played by R/S. The authors found that in this case, once the patient was stabilized, R/S helped to consolidate her feelings of well-being, increasing her positive perception of social support services and ultimately her self-confidence.

Somatic multicomorbidity and disability in patients with psychiatric disorders in comparison to the general population: a quasi-epidemiological investigation in 54,826 subjects from 40 countries (COMET-G study).

BACKGROUND: The prevalence of medical illnesses is high among patients with psychiatric disorders. The current study aimed to investigate multi-comorbidity in patients with psychiatric disorders in comparison to the general population. Secondary aims were to investigate factors associated with metabolic syndrome and treatment appropriateness of mental disorders. METHODS: The sample included 54,826 subjects (64.73% females; 34.15% males; 1.11% nonbinary gender) from 40 countries (COMET-G study). The analysis was based on the registration of previous history that could serve as a fair approximation for the lifetime prevalence of various medical conditions. RESULTS: About 24.5% reported a history of somatic and 26.14% of mental disorders. Mental disorders were by far the most prevalent group of medical conditions. Comorbidity of any somatic with any mental disorder was reported by 8.21%. One-third to almost two-thirds of somatic patients were also suffering from a mental disorder depending on the severity and multicomorbidity. Bipolar and psychotic patients and to a lesser extent depressives, manifested an earlier (15-20 years) manifestation of somatic multicomorbidity, severe disability, and probably earlier death. The overwhelming majority of patients with mental disorders were not receiving treatment or were being treated in a way that was not recommended. Antipsychotics and antidepressants were not related to the development of metabolic syndrome. CONCLUSIONS: The finding that one-third to almost two-thirds of somatic patients also suffered from a mental disorder strongly suggests that psychiatry is the field with the most trans-specialty and interdisciplinary value and application points to the importance of teaching psychiatry and mental health in medical schools and also to the need for more technocratically oriented training of psychiatric residents.

Lorcaserin: Worthy of Further Insights? Results from Recent Research.

Lorcaserin is a 3-benzazepine that binds 5-HT2C serotonin receptors in the hypothalamus, where it mediates lack of hunger and/or satiety, and in the ventral tegmental area, the site of origin of the mesolimbic and mesocortical dopaminergic projections, which mediate pleasure and reward. The drug has been first developed for the treatment of obesity, where it has shown efficacy, and subsequently trialed to counter substance use (mostly cocaine, cannabis, opioids, and nicotine) and craving, but showed inconsistent effects. Since 2020, the US Food and Drug Administration obtained that the drug was voluntarily withdrawn from the US market on the grounds that its long-term use was found to be associated with a greater incidence of some types of cancer. Provided it can show to be free from cancerogenic effects, ongoing research suggests that lorcaserin may have therapeutic potential for a variety of disorders and conditions beyond obesity. Since 5-HT2C receptors are involved in many diversified physiological functions (mood, feeding, reproductive behavior, neuronal processes related to impulsiveness, and modulating reward-related mechanisms) this drug has the potential to treat different central nervous system conditions, such as depression and schizophrenia.

Alexithymia, Burnout, and Hopelessness in a Large Sample of Healthcare Workers during the Third Wave of COVID-19 in Italy.

In the present study, we aimed to assess the frequency of and the relationships between alexithymia, burnout, and hopelessness in a large sample of healthcare workers (HCWs) during the third wave of COVID-19 in Italy. Alexithymia was evaluated by the Italian version of the 20-item Toronto Alexithymia Scale (TAS-20) and its subscales Difficulty in Identifying Feelings (DIF), Difficulty in Describing Feelings (DDF), and Externally Oriented Thinking (EOT), burnout was measured with the scales emotional exhaustion (EE), depersonalisation (DP), and personal accomplishment (PA) of the Maslach Burnout Test (MBI), hopelessness was measured using the Beck Hopelessness Scale (BHS), and irritability (IRR), depression (DEP), and anxiety (ANX) were evaluated with the Italian version of the Irritability' Depression' Anxiety Scale (IDA). This cross-sectional study recruited a sample of 1445 HCWs from a large urban healthcare facility in Italy from 1 May to 31 June 2021. The comparison between individuals that were positive (n = 214, 14.8%) or not for alexithymia (n = 1231, 85.2%), controlling for age, gender, and working seniority, revealed that positive subjects showed higher scores on BHS, EE, DP IRR, DEP, ANX, DIF, DDF, and EOT and lower on PA than the not positive ones (p < 0.001). In the linear regression model, higher working seniority as well as higher EE, IRR, DEP, ANX, and DDF scores and lower PA were associated with higher hopelessness. In conclusion, increased hopelessness was associated with higher burnout and alexithymia. Comprehensive strategies should be implemented to support HCWs' mental health and mitigate the negative consequences of alexithymia, burnout, and hopelessness.

Nationwide consensus on the clinical management of treatment-resistant depression in Italy: a Delphi panel.

BACKGROUND: Treatment-resistant depression (TRD) is defined by the European Medicines Agency as a lack of clinically meaningful improvement after treatment, with at least two different antidepressants. Individual, familiar, and socio-economic burden of TRD is huge. Given the lack of clear guidelines, the large variability of TRD approaches across different countries and the availability of new medications to meet the need of effective and rapid acting therapeutic strategies, it is important to understand the consensus regarding the clinical characteristics and treatment pathways of patients with TRD in Italian routine clinical practice, particularly in view of the recent availability of esketamine nasal spray. METHODS: A Delphi questionnaire with 17 statements (with a 7 points Likert scale for agreement) was administered via a customized web-based platform to Italian psychiatrists with at least 5 years of experience and specific expertise in the field of depression. In the second-round physicians were asked to answer the same statements considering the interquartile range of each question as an index of their colleagues' responses. Stata 16.1 software was used for the analyses. RESULTS: Sixty panellists, representative of the Italian territory, answered the questionnaire at the first round. For 8/17 statements more than 75% of panellists reached agreement and a high consensus as they assigned similar scores; for 4 statements the panellists assigned similar scores but in the middle of the Likert scale showing a moderate agreement with the statement, while for 5 statements there was indecision in the agreement and low consensus with the statement. CONCLUSIONS: This Delphi Panel showed that there is a wide heterogeneity in Italy in the management of TRD patients, and a compelling need of standardised strategies and treatments specifically approved for TRD. A high level of consensus and agreement was obtained about the importance of adding lithium and/or antipsychotics as augmentation therapies and in the meantime about the need for long-term maintenance therapy. A high level of consensus and agreement was equally reached for the identification of esketamine nasal spray as the best option for TRD patients and for the possibility to administrate without difficulties esketamine in a community outpatient setting, highlighting the benefit of an appropriate educational support for patients.

MDMA-Based Psychotherapy in Treatment-Resistant Post-Traumatic Stress Disorder (PTSD): A Brief Narrative Overview of Current Evidence.

Post-traumatic stress disorder (PTSD) is a debilitating mental health disorder that causes significant dysfunction in individuals. Currently, there are many approved pharmacotherapy and psychotherapy treatment options for PTSD, but unfortunately, half of the patients do not respond to traditional therapies. In this article, we review clinical trials and research on 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy in PTSD patients, its pharmacokinetics, and current treatment guidelines for PTSD. Our findings are based on the results of the efficacy of MDMA-assisted psychotherapy from six phase II randomized controlled trials. MDMA-assisted psychotherapy for PTSD has received the "breakthrough therapy" designation from the FDA. MDMA can reduce PTSD symptoms even in treatment-resistant cases by increasing certain neurohormones, i.e., dopamine, serotonin, norepinephrine, and oxytocin. It also modulates activities in the brain regions involved in fear and anxiety. Future research is needed to show whether the advantages outweigh the disadvantages and whether its use can be integrated into available treatment options for PTSD.

Immunomodulatory Effects of Clozapine: More Than Just a Side Effect in Schizophrenia.

Recent evidence suggests a possible relationship between the immune system and schizophrenia spectrum disorders (SSDs), as neuroinflammation appears to play a role in major psychiatric conditions. Neuroinflammation is as a broad concept representing a physiological protective response to infection or injury, but in some cases, especially if chronic, it may represent an expression of maladaptive processes, potentially driving to clinical dysfunction and neurodegeneration. Several studies are concurrently highlighting the importance of microglia, the resident immune cells of the central nervous system, in a huge number of neurodegenerative diseases, including multiple sclerosis, Alzheimer's and Parkinson's diseases, as well as SSDs. A more fundamental phenomenon of maladaptive coupling of microglia may contribute to the genesis of dysfunctional brain inflammation involved in SSDs, from the onset of their neurophenomenological evolution. Clozapine and other antipsychotic drugs seem to express a provable immunomodulant effect and a more specific action on microglia, while neuroactive steroids and nonsteroidal anti-inflammatory drugs may reduce some SSDs symptoms in add-on therapy. Given these theoretical premises, this article aims to summarize and interpret the available scientific evidence about psychotropic and anti-inflammatory drugs that could express an immunomodulant activity on microglia.

CANNABIS USE AND SUICIDE IN NON-AFFECTIVE PSYCHOSIS: A MINI-REVIEW OF RECENT LITERATURE.

Proof of correlation between psychotic spectrum disorders and suicide are found in literature, as well as between cannabis use disorder (CUD) and suicide and between CUD and schizophrenia. The study population of the selected papers consists of subjects diagnosed with schizophrenia spectrum or cannabis or SCs induced psychosis. Our objective is to assess how suicide risk (defined as suicidal ideation/attempt or death by suicide) in this population may vary with exposure to cannabis or one of its main active compounds. We searched PubMed, Scopus and Psycinfo database from January 2010 to February 2022. Study designs of the included articles are distributed as follows: 6 cross-sectional studies, 3 cohort studies, 1 case-control studies, 1 randomized double-blind study, 1 case report. Selected cohort studies seem to agree in identifying an increased suicide risk in patients with schizophrenia spectrum disorders when exposed to cannabis use. The case-control study and selected cross-sectionals provide contradictory data. However, qualitative analysis seem to point toward a positive correlation between cannabis use and increased suicidal risk in patients with schizophrenia spectrum disorders. In conclusion, emerging data on the correlation between cannabis use and suicide risk in patients with schizophrenia or other schizophrenic spectrum disorders are insufficient to draw firm conclusions. Nonetheless these studies seem to suggest a positive correlation of cannabis use with increased suicide risk, particularly regarding first episode psychosis (FEP) and male gender. Clinicians should be aware of the possibility of a higher risk of suicidal behavior associated specifically with cannabis use for men and patients during FEP.

Neurotrophic Factors In Cannabis-Induced Psychosis: An Update.

BACKGROUND: Cannabis is the most widely used illicit substance. Numerous scientific evidence confirm the strong association between cannabis and psychosis. Exposure to cannabis can induce the development of psychosis and schizophrenia in vulnerable individuals. However, the neurobiological processes underlying this relationship are unknown. Neurotrophins are a class of proteins that serve as survival factors for central nervous system (CNS) neurons. In particular, nerve growth factor (NGF) plays an important role in the survival and function of cholinergic neurons while brain-derived neurotrophic factor (BDNF) is involved in synaptic plasticity and the maintenance of midbrain dopaminergic and cholinergic neurons. Glial Cell Derived Neurotrophic Factor (GDNF) promotes the survival of midbrain dopaminergic neurons and Neuregulin 1 (NrG-1) contributes to glutamatergic signals regulating the N-methyl-D-aspartate (NMDA). They have a remarkable influence on the neurons involved in the Δ-9-THC (tethra-hydro-cannabinol) action, such as dopaminergic and glutamatergic neurons, and can play dual roles: first, in neuronal survival and death, and, second, in activity-dependent plasticity. METHODS: In this brief update, reviewing in a narrative way the relevant literature, we will focus on the effects of cannabis on this class of proteins, which may be implicated, at least in part, in the mechanism of the psychostimulant-induced neurotoxicity and psychosis. CONCLUSION: Since altered levels of neurotrophins may participate in the pathogenesis of psychotic disorders which are common in drug users, one possible hypothesis is that repeated cannabis exposure can cause psychosis by interfering with neurotrophins synthesis and utilization by CNS neurons.

Therapeutic Appropriateness of Cariprazine in the Management of Schizophrenia: Experts' Opinion using a Delphi Approach.

BACKGROUND: Schizophrenia is a psychiatric disorder whose therapeutic objectives are aimed at reducing symptoms and improving patient's quality of life. First- and second-generation antipsychotics present numerous side effects. Recently introduced in the treatment of schizophrenia, cariprazine has shown to improve positive and negative symptoms as well as cognitive impairment, with good tolerability. OBJECTIVE: To assess the level of consensus among Italian psychiatrists in relation to the use of cariprazine in the treatment of schizophrenia by using the Delphi technique. METHOD: A Delphi study was undertaken between January and July 2022. Two questionnaires were consecutively sent to a panel of 97 psychiatrists from all over Italy, of which 81 actively participated, anonymously, in at least one of the two consultations with a sufficiently high response rate (83%). RESULTS: Broad consensus in terms of the efficacy and safety of cariprazine in the treatment of schizophrenia during all phases of the disorder. The young first-episode schizophrenia patient with or without substance abuse seems to be an excellent candidate for cariprazine therapy. In addition, the lack of side effects makes cariprazine a suitable drug for adult and elderly patients with schizophrenia. However, there is still limited experience with the use of cariprazine, along with little knowledge of the most recent real-life data. CONCLUSION: These results could encourage wider dissemination of evidence-based practices with the final aim of optimizing the clinical use of cariprazine in patients with schizophrenia.

Resilience and Attachment in Patients with Major Depressive Disorder and Bipolar Disorder.

BACKGROUND: Resilience represents one of the fundamental elements of attachment and has often been investigated in mood disorders. This study aims to investigate possible correlations between attachment and resilience in patients with major depressive disorder (MDD) and bipolar disorder (BD). METHODS: 106 patients (51 MDD, 55 BD) and 60 healthy controls (HCs) were administered the 21-item Hamilton Depression Rating Scale (HAM-D-21), the Hamilton Anxiety Rating Scale (HAM-A), the Young Mania Rating Scale (YMRS), the Snaith-Hamilton Pleasure Scale (SHAPS), the Barratt Impulsiveness Scale-11 (BIS-11), the Toronto Alexithymia Scale (TAS), the Connor-Davidson Resilience Scale (CD-RISC), and Experiences in Close Relationship (ECR). RESULTS: MDD and BD patients did not significantly differ from each other according to the HAM-D-21, HAM-A, YMRS, SHAPS, and TAS, while they scored higher than HCs on all these scales. Patients in the clinical group scored significantly lower on CD-RISC resilience than HCs (p < 0.01). A lower proportion of secure attachment was found among patients with MDD (27.4%) and BD (18.2%) compared to HCs (90%). In both clinical groups, fearful attachment prevailed (39.2% patients with MDD; 60% BD). CONCLUSIONS: Our results highlight the central role played by early life experiences and attachment in participants with mood disorders. Our study confirms the data from previous research showing a significant positive correlation between the quality of attachment and the development of resilience capacity, and supports the hypothesis that attachment constitutes a fundamental aspect of resilience capacity.