M. Di Giannantonio

Mono- and polysubstance dependent subjects differ on social factors, childhood trauma, personality, suicidal behaviour, and comorbid Axis I diagnoses

BACKGROUND The study aimed to examine the clinical correlates of polysubstance dependence. SUBJECTS AND METHODS Seven hundred and fifty two substance-dependent subjects were interviewed with the Mini-International Neuropsychiatric Interview, the Brown-Goodwin Assessment for Lifetime History of Aggression (BGLHA), and the Hamilton Depression Rating Scale (HDRS). Subjects completed the Childhood Trauma Questionnaire (CTQ), Eysenck Personality Questionnaire (EPQ), and Barratt Impulsivity Scale (BIS). Subjects found to have polysubstance dependence were compared with subjects with monosubstance dependence. RESULTS Polysubstance dependence was found in 48.3% of the subjects. Subjects with polysubstance dependence were significantly younger, more were separated/divorced and unemployed, and they had significantly higher CTQ scores for childhood emotional and physical neglect, higher EPQ psychoticism scores, higher BGLHA aggression scores, and higher BIS impulsivity scores. Significantly more of the polysubstance dependent subjects had attempted suicide, self-mutilated, and exhibited aggressive behavior. Significantly more monosubstance dependent subjects had an Axis I psychiatric disorder and they had higher HDRS depression scores. CONCLUSIONS Polysubstance dependence is common among the groups studied and may be associated with certain socio-demographic, developmental, and personality factors.

Anhedonia and Substance-Related Symptoms in Detoxified Substance-Dependent Subjects: A Correlation Study

Anhedonia is a condition in which the capacity of experiencing pleasure is totally or partially lost, frequently occurring in mood disorders, as a negative symptom in schizophrenia, and in substance use disorders. In order to test a set of instruments for anhedonia in a population of detoxified opiate, alcohol and multiple substance-dependent subjects, 70 individuals were recruited from three different clinical settings. The following scales were applied: Snaith-Hamilton Pleasure Scale (SHAPS), Bech-Rafaelsen Melancholia Scale (BRMS), Scale for the Assessment of Negative Symptoms (SANS), specific withdrawal scales, and visual analogue scales (VAS) for hedonic capability and substance craving. The scales measuring anhedonia either directly (SHAPS, VAS for hedonic capability) or in some key items (SANS, BRMS) were significantly correlated with each other. The period of time since detoxification was inversely correlated with anhedonia and withdrawal symptomatology. Craving was positively correlated with anhedonia. Out of the total sample, only 18.5% could be defined as psychometrically anhedonic. The same correlations were found in this subsample. The composite instrument employed for assessing anhedonia and hedonic capability was found to be sensitive enough to detect such a dimension in the population considered, with the single scales significantly interrelated. In conclusion, we found interrelations between hedonic capability, craving and protracted withdrawal, particularly in opiate-dependent subjects. The strongest association occurred between hedonic capability and craving.

Quetiapine decreases alcohol consumption, craving, and psychiatric symptoms in dually diagnosed alcoholics

Patients with dual diagnosis are often excluded from clinical trials although more than half of all individuals with Bipolar Disorder have a substance abuse problem at some point in their lifetime, representing a high‐risk clinical population. The purpose of this study was to investigate the safety and efficacy of quetiapine in the treatment of alcohol dependence comorbid with disorders characterized by high levels of mood and behavioral instability.

Aripiprazole in the treatment of patients with alcohol dependence: a double-blind, comparison trial vs. Naltrexone

Abstract Substantial evidence suggests that both partial dopamine agents and mixed 5-HT1A/2A receptor drugs independently show significant efficacy in reducing alcohol use in both animals and humans. Aripiprazole, which acts as a dopamine/5-HT system stabilizer, approaches the optimal characteristics sought in medication to be considered for testing in the treatment of alcohol dependence. In this randomised, double-blind, confrontation trial with naltrexone, we aimed to investigate the efficacy of aripiprazole on alcohol-drinking indices. Craving and psychiatric symptom improvements were the secondary end points. Seventy-five alcohol dependent subjects were detoxified and were subsequently randomised into two groups, receiving 50 mg of naltrexone and 5–15 mg of aripiprazole, respectively. Craving (Visual Analogue Scale; Obsessive and Compulsive Drinking Scale) and withdrawal (Clinical Institute Withdrawal Assessment) rating scales were applied; psychiatric symptoms were evaluated through the Symptom Check List 90–Revised. The number of subjects remained alcohol free for the entire study period (16 weeks) and the number of subjects relapsed were not significantly different in the two groups. The survival function showed that patients treated with aripiprazole remained abstinent from any alcohol amount for a longer time with respect to those treated with naltrexone. As for craving scores, patients treated with naltrexone showed a better outcome. Results from this study globally place aripiprazole at the same range of efficacy of naltrexone, one of the approved drugs used in alcohol relapse prevention. If it could be demonstrated in placebo-controlled trials that aripiprazole is efficacious in decreasing alcohol use, lessening craving, and attenuating psychopathological symptom severity, we will have gained a powerful agent for the treatment of alcohol-dependent subjects.

Agomelatine versus venlafaxine XR in the treatment of anhedonia in major depressive disorder: a pilot study

Abstract The primary aim of the present study was to compare the effects of agomelatine (AGO) and venlafaxine XR (VLX) on anhedonia in patients with major depressive disorder. Secondary end points were to test its antidepressant and anxiolytic efficacy. Sixty patients were enrolled and randomly assigned to two different treatments: AGO (25-50 mg/d; n = 30 subjects) or VLX (75-150 mg/d, n = 30 subjects). Psychopathological assessment was performed at baseline and after 8 weeks of treatment with the Snaith Hamilton Rating Scale (SHAPS), the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, and the Clinical Global Impression for anhedonia, depression, anxiety, and global improvement, respectively. Both groups showed a significant reduction in time for the SHAPS, the Hamilton Depression Rating Scale, and the Hamilton Anxiety Rating Scale. A significant between-group difference was observed for SHAPS scores: patients treated with AGO showed a more relevant reduction compared with that in VLX-treated patients. Moreover, only patients treated with AGO showed a statistically significant improvement in Clinical Global Impression scores. In this study, AGO showed significantly greater efficacy on anhedonia and similar antidepressant efficacy to the serotonin-norepinephrine reuptake inhibitor VLX in patients with major depressive disorder during an 8-week treatment period. Anhedonia has been considered a potential trait marker related to vulnerability for depression. Therefore, the efficacy of AGO on this dimension holds particular importance in the treatment of patients with anhedonic features.

Pregabalin versus naltrexone in alcohol dependence: a randomised, double-blind, comparison trial

Pregabalin (PRE) acts as a presynaptic inhibitor of the release of excessive levels of excitatory neurotransmitters by selectively binding to the α2-δ subunit of voltage-gated calcium channels. In this randomised, double-blind comparison trial with naltrexone (NAL), we aimed to investigate the efficacy of PRE on alcohol drinking indices. Craving reduction and improvement of psychiatric symptoms were the secondary endpoints. Seventy-one alcohol-dependent subjects were detoxified and subsequently randomised into two groups, receiving 50 mg of NAL or 150—450 mg of PRE. Craving (VAS; OCDS), withdrawal (CIWA-Ar) and psychiatric symptoms (SCL-90-R) rating scales were applied. Alcohol drinking indices and craving scores were not significantly different between groups. Compared with NAL, PRE resulted in greater improvement of specific symptoms in the areas of anxiety, hostility and psychoticism, and survival function (duration of abstinence from alcohol). PRE also resulted in better outcome in patients reporting a comorbid psychiatric disorder. Results from this study globally place PRE within the same range of efficacy as that of NAL. The mechanism involved in the efficacy of PRE in relapse prevention could be less related to alcohol craving and more associated with the treatment of the comorbid psychiatric symptomatology.

THE EFFECT OF NEWER SEROTONIN-NORADRENALIN ANTIDEPRESSANTS ON CYTOKINE PRODUCTION: A REVIEW OF THE CURRENT LITERATURE

Cytokines may influence brain activities especially during stressful conditions, and elevated levels of IL-6 and C-reactive protein have been pointed out in subjects with Major Depression. If pro-inflammatory cytokines play a causative role in major depressive disorders, one would expect that antidepressants may down-regulate these cytokines or interfere with their actions, leading to improvement of depressive symptoms. Accumulating evidence has been published that antidepressants modulate cytokine production and this is particularly true for Tricyclics and Selective serotonin reuptake inhibitors (SSRIs), but the influence of newer antidepressants acting on both serotonin (5-HT) and norepinephrine (NE) such as venlafaxine, duloxetine and mirtazapine on cytokine levels has not been extensively studied. However, both pre-clinical and clinical studies examined in this review have demonstrated that newer serotonin-noradrenalin antidepressants can inhibit the production and/or release of pro-inflammatory cytokines and stimulate the production of anti-inflammatory cytokines, suggesting that reductions in inflammation might contribute to treatment response. Moreover, the results of the present review support the notion that the serotonin-noradrenalin antidepressants venlafaxine and mirtazapine may influence cytokine secretion in patients affected by MD, restoring the equilibrium between their physiological and pathological levels and leading to recovery. To date, no studies have evaluated the effect of duloxetine, the newest serotonin-noradrenalin antidepressant, on cytokine levels and therefore this should be evaluated in future studies.

Microstructure of sleep in eating disorders: preliminary results.

Attempts to analyse the sleep structure of patients with eating disorders have so far led to conflicting results. Polygraphic findings suggest that patients with bulimia nervosa are not easily distinguishable from age-matched controls, whereas anorexic patients show some abnormalities in sleep efficiency and sleep architecture. Nevertheless, both bulimic and anorexic patients complain of poor quality sleep. The aim of this study was to evaluate the microstructure of sleep in anorexia and bulimia by analysing arousal (following the rules of the American Sleep Disorders Association) and the cyclic alternating pattern (CAP). The results confirmed the presence of sleep disturbances in eating disordered patients: an increase in arousal length and the CAP rate. They also seem to confirm the findings of previous studies suggesting that altered sleep in eating disordered patients may be related to their body mass index (BMI) and psychopathological status.

Neuropsychological functioning in young subjects with generalized anxiety disorder with and without pharmacotherapy.

The purpose of this study was to investigate the neuropsychological functioning and the effect of antidepressant drug intake on cognitive performance in a group of relatively young generalized anxiety disorder (GAD) patients. Forty patients with a DSM-IV diagnosis of GAD and 31 healthy subjects participated in the study (Control group, CON). None of the selected subjects had comorbid depression. GAD subjects were divided into two different subgroups: 18 were taking antidepressants [GAD-pharmacotherapy (GAD-p group)] and 22 were treatment-naïve (GAD group). Each group was administered with a comprehensive neuropsychological battery to assess attention, memory and executive functions. Performance on executive and non-verbal memory tasks of both GAD groups was largely worse than the CON group. However, these deficits seem to be more marked in patients taking antidepressants, especially in the domains of attention, non-verbal memory and executive functions. The present study indicates that GAD is associated with cognitive impairments among young adults. However, the observed association of neuropsychological deficits and the use of pharmacotherapy suggest a possible effect of antidepressant treatment on attention, executive functioning and non-verbal memory.

Is There a Role for Agomelatine in the Treatment of Anxiety Disorders? A Review of Published Data:

Anxiety disorders (ADs) are the most common type of psychiatric disorders. Pharmacologic options studied for treating ADs may include benzodiazepines, tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRIs), noradrenergic and specific serotonergic antidepressants (NaSSA) and serotonin and noradrenaline reuptake inhibitors (SNRIs). Agomelatine, a new melatonergic antidepressant, has been shown effective in various types of mood disorders. Moreover, some evidence points towards a possible efficacy of such a drug in the treatment of ADs. Therefore, the aim of this review was to elucidate current (facts and views) data on the role of agomelatine in the treatment of ADs. The trials evaluating agomelatine in the treatment of generalized anxiety disorder are few but, overall, encouraging in regards to its efficacy. However, further randomized, placebo-controlled studies on larger samples use are needed. Apart from some interesting case reports, no large studies are, to date, present in literature regarding agomelatine in the treatment of other ADs, such as panic disorder, social anxiety disorder, obsessive-compulsive disorder and post-traumatic stress disorder. Therefore, the clinical efficacy and the relative good tolerability of agomelatine in generalized anxiety (GAD) warrants further investigation in ADs.