Laura Orsolini

Novel psychoactive substances of interest for psychiatry

Novel psychoactive substances include synthetic cannabinoids, cathinone derivatives, psychedelic phenethylamines, novel stimulants, synthetic opioids, tryptamine derivatives, phencyclidine‐like dissociatives, piperazines, GABA‐A/B receptor agonists, a range of prescribed medications, psychoactive plants/herbs, and a large series of performance and image enhancing drugs. Users are typically attracted by these substances due to their intense psychoactive effects and likely lack of detection in routine drug screenings. This paper aims at providing psychiatrists with updated knowledge of the clinical pharmacology and psychopathological consequences of the use of these substances. Indeed, these drugs act on a range of neurotransmitter pathways/receptors whose imbalance has been associated with psychopathological conditions, including dopamine, cannabinoid CB1, GABA‐A/B, 5‐HT2A, glutamate, and k opioid receptors. An overall approach in terms of clinical management is briefly discussed.

Profiling online recreational/prescription drugs' customers and overview of drug vending virtual marketplaces

Internet and social networking sites play a significant role in the marketing and distribution of recreational/prescription drugs without restrictions. We aimed here at reviewing data relating to the profile of the online drug customer and at describing drug vending websites.

Novel psychoactive substances: the pharmacology of stimulants and hallucinogens

ABSTRACT There are increasing levels of concern relating to the rapidly evolving novel psychoactive substances/NPS and web markets’ scenarios. The paper aims at providing an overview of the clinical pharmacological issues related to some of the most popular NPS categories, e.g. stimulants and hallucinogens. NPS intake is typically associated with the imbalance of a complex range of neurotransmitter pathways/receptors, namely: dopamine; cannabinoid/CB1; and 5-HT2A. The intake is almost invariably undetectable with standard screening tests. Hence, it may frequently occur that the acute management of NPS misusers will need to focus on decreasing levels of both self/outward-directed aggression and agitation. Benzodiazepines may be considered as first line treatment. Alternatively, propofol and/or antipsychotics can be administered. Focus will be as well on treatment of possible rhabdomyolysis and hyperthermia. Indeed, future studies should inform better tailored management/treatment strategies.

An update of safety of clinically used atypical antipsychotics

ABSTRACT Introduction: The atypical antipsychotic (APs) drugs have become the most widely used agents to treat a variety of psychoses because of their superiority with regard to safety and tolerability profile compared to conventional/‘typical’ APs. Areas covered: We aimed at providing a synthesis of most current evidence about the safety and tolerability profile of the most clinically used atypical APs so far marketed. Qualitative synthesis followed an electronic search made inquiring of the following databases: MEDLINE, Embase, PsycINFO and the Cochrane Library from inception until January 2016, combining free terms and MESH headings for the topics of psychiatric disorders and all atypical APs as following: ((safety OR adverse events OR side effects) AND (aripiprazole OR asenapine OR quetiapine OR olanzapine OR risperidone OR paliperidone OR ziprasidone OR lurasidone OR clozapine OR amisulpride OR iloperidone)). Expert opinion: A critical issue in the treatment with atypical APs is represented by their metabolic side effect profile (e.g. weight gain, lipid and glycaemic imbalance, risk of diabetes mellitus and diabetic ketoacidosis) which may limit their use in particular clinical samples. Electrolyte imbalance, ECG abnormalities and cardiovascular adverse effects may recommend a careful baseline and periodic assessments.

“Noids” in a nutshell: everything you (don’t) want to know about synthetic cannabimimetics

Purpose – “Spice” products are synthetic cannabimimetics (SC; also called “synthetic cannabinoids”)-based designer drugs used as a legal alternative to cannabis for their very strong tetrahydrocannabinol (THC)-like effects. The purpose of this paper is to provide an analysis of more recent clinical and pharmacology/toxicology findings relating to SC and describe how they could impact on health, with a particular focus on mental health. Design/methodology/approach – A systematic search and descriptive analysis of the available evidence on psychopathological issues related to misuse was performed here, whilst taking into account the Pubmed/Medline databases, a range of conference proceedings and national/international agencies’ reports. Findings – While THC is a partial agonist, SC are full agonists on the cannabinoid receptors (CB-rs) and the administration of multiple SC can produce additive and/or synergistic agonistic interaction effects on the endocannabinoid system. These levels of strong CB-rs’ activ...

The prevalence and predictors of bipolar and borderline personality disorders comorbidity: Systematic review and meta-analysis

INTRODUCTION Data about the prevalence of borderline personality (BPD) and bipolar (BD) disorders comorbidity are scarce and the boundaries remain controversial. We conducted a systematic review and meta-analysis investigating the prevalence of BPD in BD and BD in people with BPD. METHODS Two independent authors searched MEDLINE, Embase, PsycINFO and the Cochrane Library from inception till November 4, 2015. Articles reporting the prevalence of BPD and BD were included. A random effects meta-analysis and meta-regression were conducted. RESULTS Overall, 42 papers were included: 28 considering BPD in BD and 14 considering BD in BPD. The trim and fill adjusted analysis demonstrated the prevalence of BPD among 5273 people with BD (39.94 ± 11.78 years, 44% males) was 21.6% (95% CI 17.0-27.1). Higher comorbid BPD in BD were noted in BD II participants (37.7%, 95% CI 21.9-56.6, studies=6) and North American studies (26.2%, 95% CI 18.7-35.3, studies=11). Meta regression established that a higher percentage of males and higher mean age significantly (p<0.05) predicted a lower prevalence of comorbid BPD in BD participants. The trim and fill adjusted prevalence of BD among 1814 people with BPD (32.22 ± 7.35 years, 21.5% male) was 18.5% (95% CI 12.7-26.1). LIMITATIONS Paucity of longitudinal/control group studies and accurate treatment records. CONCLUSIONS BPD-BD comorbidity is common, with approximately one in five people experiencing a comorbid diagnosis. Based on current diagnostic constructs, and a critical interpretation of results, both qualitative and quantitative syntheses of the evidence prompt out the relevance of differences rather similarities between BD and BPD.

Suicide during Perinatal Period: Epidemiology, Risk Factors, and Clinical Correlates

Perinatal period may pose a great challenge for the clinical management and treatment of psychiatric disorders in women. In fact, several mental illnesses can arise during pregnancy and/or following childbirth. Suicide has been considered a relatively rare event during the perinatal period. However, in some mental disorders (i.e., postpartum depression, bipolar disorder, postpartum psychosis, etc.) have been reported a higher risk of suicidal ideation, suicide attempt, or suicide. Therefore, a complete screening of mothers’ mental health should also take into account thoughts of suicide and thoughts about harming infants as well. Clinicians should carefully monitor and early identify related clinical manifestations, potential risk factors, and alarm symptoms related to suicide. The present paper aims at providing a focused review about epidemiological data, risk factors, and an overview about the main clinical correlates associated with the suicidal behavior during the pregnancy and postpartum period. Practical recommendations have been provided as well.

Treating the Synapse in Major Psychiatric Disorders: The Role of Postsynaptic Density Network in Dopamine-Glutamate Interplay and Psychopharmacologic Drugs Molecular Actions

Dopamine-glutamate interplay dysfunctions have been suggested as pathophysiological key determinants of major psychotic disorders, above all schizophrenia and mood disorders. For the most part, synaptic interactions between dopamine and glutamate signaling pathways take part in the postsynaptic density, a specialized ultrastructure localized under the membrane of glutamatergic excitatory synapses. Multiple proteins, with the role of adaptors, regulators, effectors, and scaffolds compose the postsynaptic density network. They form structural and functional crossroads where multiple signals, starting at membrane receptors, are received, elaborated, integrated, and routed to appropriate nuclear targets. Moreover, transductional pathways belonging to different receptors may be functionally interconnected through postsynaptic density molecules. Several studies have demonstrated that psychopharmacologic drugs may differentially affect the expression and function of postsynaptic genes and proteins, depending upon the peculiar receptor profile of each compound. Thus, through postsynaptic network modulation, these drugs may induce dopamine-glutamate synaptic remodeling, which is at the basis of their long-term physiologic effects. In this review, we will discuss the role of postsynaptic proteins in dopamine-glutamate signals integration, as well as the peculiar impact of different psychotropic drugs used in clinical practice on postsynaptic remodeling, thereby trying to point out the possible future molecular targets of “synapse-based” psychiatric therapeutic strategies.

A comprehensive review on the efficacy of S-Adenosyl-L-methionine in Major Depressive Disorder.

OBJECTIVE To review the antidepressant efficacy of S-Adenosyl-L-Methionine (SAMe) both in monotherapy and/or in augmentation with antidepressants to better understand its potential role in the treatment of patients with Major Depressive Disorder (MDD) and Treatment-Resistant Depression (TRD). DATA SOURCES A MEDLINE/PubMed search was carried out by using the following set of keywords: ((SAMe OR SAdenosyl- L-Methionine) AND (major depressive disorder OR depression)). Data Selection and Data Extraction: No language or time restrictions were placed on the electronic searches. Randomized controlled trials and open trials involving humans were here included and analyzed. The references of published articles identified in the initial search process were also examined for any additional studies appropriate for the review. DATA SYNTHESIS SAMe is an important physiologic compound, playing a central role as precursor molecule in several biochemical reactions. Numerous studies have shown that SAMe may affect the regulation of various critical components of monoaminergic neurotransmission involved in the pathophysiology of MDD. Some findings have suggested its antidepressant efficacy in treating MDD. Several randomized controlled trials have supported that the antidepressant efficacy of SAMe in monotherapy is superior to placebo and tricyclic antidepressants. Recent findings have also demonstrated its efficacy in patients nonresponsive to selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. CONCLUSION Overall, SAMe is a well-tolerated medication, which may offer considerable advantages as an alternative to antidepressant drugs or as an add-on therapy in the treatment of MDD and TRD. More large-scale controlled trials are needed to gain a better understanding of the relative efficacy of this drug.

Aripiprazole for relapse prevention and craving in alcohol use disorder: current evidence and future perspectives

ABSTRACT Introduction: Among other approaches, the modulation of the dopaminergic pathway has been advocated in the therapeutic management of Alcohol Use Disorders (AUD). A potential avenue toward the modulation of the dopaminergic pathway across varying substance disorders seems to be provided by aripiprazole, a second-generation antipsychotic characterized by a peculiar pharmacodynamics signature. Areas covered: In this review, the authors provided a qualitative synthesis and a critical perspective on the efficacy of aripiprazole in relapse prevention and craving in AUD. A systematic search was carried out through MEDLINE/Embase/PsycINFO/Cochrane Library from inception until September 2015, combining free terms and MESH headings for the topics of AUD and aripiprazole as following: (((Alcohol use Disorder) OR (Alcohol use)) AND aripiprazole). Expert opinion: Based both on a qualitative synthesis and a critical interpretation of the evidence, the authors submit that aripiprazole would promote alcohol abstinence and reduce the alcohol seeking behaviour possibly via dopaminergic and serotoninergic modulations at the fronto-subcortical circuits underpinning alcohol reward and craving, impulsive behaviour as well as reduce alcohol-related anxiety/low mood and anhedonia. However, due to the lack of published studies, a conclusive statement about any direct effect of aripiprazole in the prevention of craving and/or alcohol consumption is not possible.