Early experience with the new DORA daridorexant in patients with insomnia disorder and comorbid mental disturbances: Results of a naturalistic study with 3 months follow-up.

Insomnia disorder may affect mental health, increasing suicidal risk. Targeting insomnia is crucial in the clinical practice. Sixty-six consecutive patients with insomnia disorder according with the DSM-5-TR criteria were treated with the dual orexin receptor antagonist, daridorexant 50 mg. Baseline (T0), 1 month (T1) and 3 month (T2) evaluations were performed. Insomnia severity (Insomnia Severity Index), mood, anxiety symptoms and suicidal risk (Beck Depression Inventory-II, Young Mania Rating Scale, Self-Reported Anxiety Scale, Suicidal Ideation Scale), dysfunctional insomnia-cognitive factors and pre-sleep arousal (Dysfunctional Beliefs About Sleep, Pre-Sleep Arousal Scale) were evaluated. The final sample included 66 patients (n = 36, 54% females, mean age 60 ± 13.6 years). Most of them, 64%, suffered from insomnia disorder comorbid with unipolar/bipolar depression, anxiety disorders and substance use disorders. Repeated ANOVA analyses showed that Insomnia Severity Index, Dysfunctional Beliefs About Sleep and Pre-Sleep Arousal Scale total score decreased across time (F = 68.818, p < 0.001; F = 47.561, p < 0.001; F = 28.142, p < 0.001, respectively). Similarly, Beck Depression Inventory-II, Self-Reported Anxiety Scale, Young Mania Rating Scale, and Suicidal Ideation Scale significantly decreased over time (p < 0.001). Predictors of insomnia remission (Insomnia Severity Index < 8) at T1 were improvement of Insomnia Severity Index at T1 (F = 60.205, p < 0.001), and improvement of Dysfunctional Beliefs About Sleep at T1 (F = 4.432, p = 0.041). Insomnia remission at T2 was best predicted by improvement of Dysfunctional Beliefs About Sleep at T2 (F = 3.993, p = 0.023). Multiple-regression models showed that clinical improvement of Beck Depression Inventory-II was best predicted by improvement in Dysfunctional Beliefs About Sleep at T1 and T2, manic symptoms by Insomnia Severity Index at T2, anxiety symptoms by Dysfunctional Beliefs About Sleep, Insomnia Severity Index and somatic Pre-Sleep Arousal Scale at T1 and T2. With the caution of a naturalistic design, early experience with daridorexant showed that by targeting insomnia it may be possible to improve not only insomnia symptoms but also comorbid symptoms.

Current Trends on Antipsychotics: Focus on Asenapine.

Over the years, both first- (FGAs) and second-generation antipsychotics (SGAs), continue to gain increasing evidence of being effective in the treatment of psychotic symptoms. Currently, they represent the first-line treatment of schizophrenia and bipolar disorder, although they are widely used in psychotic depression and other clinical conditions, such as agitation and/or behavioural disturbances. Despite representing an indispensable tool for the treatment of severe psychotic disorders, they are widely known to have a number of unwanted side effects that the clinician must be aware of, and handle carefully to provide the patient the best available treatment in the short and long-term. However, even with respect to the long-term use of some of the most effective SGAs, it is imperative for clinicians not to overlook the risk linked to the onset of potentially severe metabolic side effects such as weight gain, dyslipidaemia, insulinresistance and type II diabetes. Asenapine is one of the newest SGAs licenced in Europe for the treatment of manic episodes and in the US for schizophrenia. It belongs to the same class of clozapine, olanzapine and quetiapine, sharing with them a rather complex pharmacological binding profile. In fact, asenapine shows a high affinity for the serotonin (5HT) receptor of the type 2A (5HT2A) and to a lesser extent for the dopamine receptor of the type 2 (D2), similar to other SGAs. Asenapine behaves also as an antagonist at the level of 5HT2C, H1 and α2-receptors. Asenapine has been reported to be effective either in monotherapy or in combination with mood stabilers (lithium and valproate) in the treatment of manic or mixed episodes, with a lower propensity to induce, or being followed by, depressive symptoms, when compared to other SGAs. These unique properties may explain the increasing interest towards the use of this drug in mixed states, besides schizophrenia and acute mania. The aim of this paper was at reviewing current data on pharmacological properties and clinical use of asenapine, as well as on possible future indication of this SGA.

Nalmefene: A Novel Drug for an Old Disorder.

Alcoholism is an increasing problem all over the world, and nowadays especially amongst teenagers. Although several drug treatments have been proposed for this condition, only a few have demonstrated a significant efficacy. Nalmefene, a novel compound that combines opioids mu-receptors antagonism and kappa-receptors partial agonism, was recently approved by the European Medicine Agency for the treatment of alcoholism. This drug can be very helpful in reducing the alcohol intake, and, as such, it can be considered one of the first and fundamental steps towards alcohol abstinence. The aim of this review is to discuss and comment on the available literature on nalmefene, as well as on novel treatment strategies of this condition (and perhaps of other addictions) opened by this latest pharmacological approach.

Behavioral addictions: a novel challenge for psychopharmacology.

Although addictive syndromes have been traditionally related to substance-use disorders, during the last few decades a novel addictive group, including the so-called "behavioral or no-drug addictions," has been recognized and has attracted increasing attention for its relevant social impact. This group includes pathological gambling, compulsive shopping, TV/Internet/social network/videogame addictions, workaholism, sex and relationship addictions, orthorexia, and overtraining syndrome. Substance and behavioral addictions show similar phenomenological features, such as craving, dependence, tolerance, and abstinence, and perhaps they share a common possible pathophysiology. It is, however, controversial whether all or at least some of them should be considered real disorders or just normal, albeit extreme, behaviors. The aim of this article is to review current data on pharmacological treatment of behavioral addictions. As no specific and validated treatment algorithms are currently available, only an improved knowledge on their psychopathological, clinical, and neurobiological features may have relevant implications for more focused preventive and therapeutic strategies.

Effectiveness of long-term augmentation with citalopram to clomipramine in treatment-resistant OCD patients.

INTRODUCTION: The high percentage (between 40% and 60%) of resistance to first-line drugs, such as clomipramine or selective serotonin reuptake inhibitors, is a major problem in the pharmacologic management of obsessive-compulsive disorder (OCD). In these cases, different strategies have been employed with controversial outcomes. The meager information available on the association of two serotonergic drugs prompted us to explore the possible effectiveness and tolerability of citalopram+clomipramine in resistant OCD patients. METHODS: Twenty outpatients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of OCD, who had failed to respond to at least two trials with a selective serotonin reuptake inhibitor and were currently taking clomipramine at different doses, were administered citalopram at a maximum dose of 60 mg/day. The clinical assessment was carried out at baseline (t0) and at the 4th (t1), 12th (t2), 24th (t3), 36th (t4), and 48th (t5) week by means of the Yale-Brown Obsessive Compulsive Scale, Hamilton Rating Scale for Depression, Clinical Global Impression scale, and the Dosage Record and Treatment Emergent Symptom Scale. The response was defined as a 35% decrease of the Yale-Brown Obsessive-Compulsive Scale total score. RESULTS: The results showed that approximately 50% of the patients improved significantly after 1 month of this regimen and after 1 year of treatment. CONCLUSION: This study, although carried out in a small sample and in an open fashion, represents one of the few experiences with the association of two serotonergic compounds in resistant OCD and confirms its potential usefulness and good tolerability profile. Controlled research on this association in OCD is recommended.

Pain and psychiatry: a critical analysis and pharmacological review.

Pain is one of the most difficult medical problems to diagnose and treat and can be a common symptom of several psychiatric disorders. Pain-related issues are heterogeneous and often underestimated or misinterpreted, with the result that psychiatric interventions, which might have been beneficial from the outset, are often delayed or requested only as a last measure. Several problems arise from the definition, classification and assessment of pain, when documented according to the different scales which are commonly used, since these attempt to cover a multitude of analytical requirements, without really succeeding. An area of constant debate regards the connection between pain and various psychiatric disorders, and the difficulty in the classification of pain disorders within the currently existing framework. The pharmacological treatment of pain is complex and implies a variety of different compounds, from opioids to psychotropic medications like antidepressants and anticonvulsivants. This paper explores the mutual and reciprocal influence between pain and psychiatric disorders reviewing the latest developments in the definition, assessment and treatment of pain, with special emphasis on the impact of pain on psychiatric disorders (and vice versa), and on the use of psychotropic drugs in the treatment of pain syndromes.

Insight in body dysmorphic disorder with and without comorbid obsessive-compulsive disorder.

INTRODUCTION: The aim of this study was to compare the level of insight in patients with body dysmorphic disorder (BDD) with and without comorbid obsessive-compulsive disorder (OCD), and to measure its possible relationships with clinical features. METHODS: Thirty outpatients affected by BDD, according to Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition criteria, of whom 18 were also suffering from OCD, were included in the study. Clinical assessment was carried out by means of the Yale-Brown Obsessive-Compulsive Scale modified for BDD and a specially designed OCD Questionnaire. The level of insight was measured by means of the score at item 11 of the Yale-Brown Obsessive-Compulsive Scale modified for BDD. RESULTS: The insight resulted to be excellent in four cases, good in four, fair in five, poor in 15 and absent in two. Significant and positive correlations were observed between the level of insight and the following items: resistance to thoughts and to activities as well as to time spent on activities and control on activities related to the defect. The insight was significantly lower in patients affected by both BDD and OCD. CONCLUSION: The findings indicate that the majority of BDD patients in this study, and especially those with comorbid OCD, have a low degree of insight that is significantly correlated to symptoms specific of the disorder.

Augmentation strategy with olanzapine in resistant obsessive compulsive disorder: an Italian long-term open-label study.

The present study reports the results of an open-label trial on the use of the combination of olanzapine (an atypical antipsychotic) serotonin reuptake inhibitors (SRIs) in 26 resistant outpatients affected by resistant obsessive-compulsive disorder (OCD). All patients had been suffering from OCD, according to DSM IV criteria, for at least 2 years and had different comorbid disorders; they had been treated with an SRI at adequate dosages for at least 6 months, or had tried different augmentation strategies with no or poor response. As a result, olanzapine was added and continued for 1 year. After 12 weeks of this regimen, most of the patients (17) had shown a reduction in OC symptoms, as assessed by a decrease in the Yale-Brown Obsessive Compulsive Scale total score, which continued throughout subsequent months. Only mild side-effects were recorded and no patient halted the treatment. The addition of olanzapine would appear to be a useful short- and long-term strategy for augmenting SRI effectiveness in resistant OCD patients, especially in those presenting comorbidity with bipolar disorders.

Kleptomania in impulse control disorders, obsessive-compulsive disorder, and bipolar spectrum disorder: clinical and therapeutic implications.

This paper aims to critically review currently available data on kleptomania and to analyze the possible future evolution of clinical research and therapeutic strategies.

Decreased inhibitory activity of PKC in OCD patients after six months of treatment.

We investigated 5-HT reuptake and protein kinase of type C (PKC) activation in platelets of 14 OCD patients at baseline and after six months of treatment with different serotonin (5-HT) reuptake inhibitors (SRIs). The results showed that all SRIs provoked a significant increase in both the maximal velocity (V(max)) and the Michaelis-Menten constant (K(m)) of 5-HT reuptake, as compared with baseline values. The activation of PKC by means of 4-beta-12-tetradecanoylphorbol 13-acetate provoked a significant decrease in V(max) values, but the effect was not as evident as at baseline. These findings could indicate that, in OCD patients, SRIs increase the rate of reuptake and decrease the inhibitory effect of PKC and that the two phenomena may be linked, the first perhaps depending upon the second.

Kleptomania: clinical features and comorbidity in an Italian sample.

Kleptomania, listed in DSM-IV as an impulse control disorder not elsewhere classified, is a psychiatric condition still poorly understood and subject of only a few systematic studies. The aim of this research was, therefore, to evaluate the clinical features and comorbidity of Italian patients with a DSM-IV diagnosis of kleptomania. Twenty outpatients with a lifetime diagnosis of kleptomania by DSM-IV criteria, were included in the study and underwent a specially designed semistructured interview and the Family History Research Diagnostic Criteria. The majority of patients reported an early and abrupt onset and an episodic course of the disorder, with no gender preponderance. Lifetime comorbidity for other axis I disorders was high, in particular for mood, anxiety, and impulse control disorders. Family history also showed a high prevalence of psychiatric disorders. Our study indicates clear connections between kleptomania and different psychiatric disorders, the exact nature of which has yet to be clarified.

Insight in obsessive-compulsive disorder: a study of an Italian sample.

Insight is a complex phenomenon that can be interpreted according to a dimensional model. Given the controversial data of insight in obsessive-compulsive disorder (OCD), our study aimed to investigate insight in an Italian sample of patients with OCD by means of the specific item on the Yale-Brown obsessive-compulsive scale (Y-BOCS) and to explore the possible correlations between it and clinical features. One hundred and seventeen out-patients with a DSM-IV diagnosis of OCD and different comorbid psychiatric disorders were included in the study and assessed by means of the Y-BOCS, Hamilton rating scale for depression (HRSD) and the global clinical impression. The results showed that almost 50% of the patients had an excellent level of insight and 15% had a little or no insight. No correlation between levels of insight and clinical features was observed, except for a negative trend with the presence of somatic obsessions. In addition, a trend towards a lower level of insight was observed in those bipolar patients with a positive history of repeated manic or hypomanic episodes. Further studies seem to be necessary in order to establish whether or not OCD patients with poor insight represent a distinct sub-group of patients.