Riccardo Guglielmo

Pregabalin for alcohol dependence: a critical review of the literature

IntroductionAlcohol dependence represents a severe pathological disorder associated with a significant rate of morbidity and mortality. To date, limited pharmacological agents exist to treat this disorder, and there is a growing interest for new therapies. In this context, pregabalin represents a promising strategy. Pregabalin, like gabapentin, selectively binds to the α2δsubunit of voltage-gated calcium channels, inhibiting release of excessive levels of excitatory neurotransmitters. The main focus of this review is the clinical use of pregabalin in alcoholic patients, but the authors also reported some data about chemistry, pharmacology, and pharmacokinetics of this drug.MethodsThe authors conducted a PubMed search of clinical human studies published in English from January 2000 to August 2012 using the following search terms: pregabalin alcohol dependence, pregabalin alcohol withdrawal, pregabalin alcoholism.ResultsThe search revealed a total of five studies: two trials for the treatment of alcohol relapse and three articles for the management of alcohol withdrawal syndrome with pregabalin. The critical review of the literature suggests that pregabalin could be a novel and effective treatment option for the management of alcohol relapse in detoxified patients, whereas until now there have been mixed results for the treatment of alcohol withdrawal syndrome. In particular, pregabalin showed a greater beneficial effect on patients with comorbid conditions such as alcoholism and generalized anxiety disorders. The exact mechanism of action of pregabalin in the management of alcoholism is not well understood but it is thought to be due mainly to the modulation of neurotransmitters such as glutamate and norepinephrine by inhibiting activity-dependent calcium influx in nerve terminals.ConclusionPregabalin, within a dosage of 150–450 mg/day, showed beneficial effects for alcohol relapse prevention and contrasting results for the treatment of the withdrawal syndrome. Its use appears to be safe and well tolerated.

Cognitive markers of psychotic unipolar depression: A meta-analytic study

BACKGROUND The goal of the current meta-analysis was to review and examine in detail the features of cognitive performance in psychotic (MDDP) versus non-psychotic (MDD) major depressive disorder. METHODS An electronic literature search was performed to find studies comparing cognitive performance in MDDP versus MDD. A meta-analysis of broad cognitive domains (processing speed, reasoning/problem solving, verbal learning, visual learning, attention/working memory) and individual cognitive tasks was conducted on all included studies (n=12). Demographic and clinical features were investigated via meta-regression analysis as moderators of cognitive performance. RESULTS No difference in socio-demographic and clinical variables was detected between groups. In general, a poorer cognitive performance was detected in MDDP versus MDD subjects (ES=0.38), with a greater effect size in drug-free patients (ES=0.69). MDDP patients were more impaired in verbal learning (ES=0.67), visual learning (ES=0.62) and processing speed (ES=0.71) tasks. A significantly poorer performance was also detected in MDDP patients for individual tasks as Trail Making Test A, WAIS-R digit span backward and WAIS-R digit symbol. Age resulted to have a negative effect on tasks involved in working memory performance. CONCLUSION In line with previous meta-analyses, our findings seem to support an association between psychosis and cognitive deficits in the context of affective disorders. Psychosis during the course of MDD is associated with poorer cognitive performance in some specific cognitive domains, such as visual and verbal learning and executive functions.

Co-occurrence of alcohol use disorder and behavioral addictions: relevance of impulsivity and craving

PURPOSE The aims of the study were to evaluate the occurrence of behavioral addictions (BAs) in alcohol use disorder (AUD) subjects and to investigate the role of impulsivity, personality dimensions and craving. METHODS 95 AUD outpatients (DSM-5) and 140 homogeneous controls were assessed with diagnostic criteria and specific tests for gambling disorder, compulsive buying, sexual, internet and physical exercise addictions, as well as with the Barratt Impulsiveness Scale (BIS-11) and Temperamental and Character Inventory-Revised (TCI-R). The Obsessive Compulsive Drinking Scale (OCDS) and Visual Analogue Scale for craving (VASc) were also administered to the AUD sample. RESULTS 28.4% (n=27) of AUD subjects had at least one BA, as compared to 15% (n=21) of controls (χ(2)=6.27; p=.014). In AUD subjects, direct correlations between BIS-11 and Compulsive Buying Scale (CBS), Internet Addiction Disorder test (IAD), Exercise Addiction Inventory-Short Form (EAI-SF) scores (p<.01), between OCDS obsessive and CBS and VASc and CBS, IAD scores (p<.003), were found. BIS-11 (t=-2.36; p=.020), OCDS obsessive (Z=-4.13; p<.001), OCDS compulsive (Z=-2.12; p=.034) and VASc (Z=-4.94; p<.001) scores were higher in AUD subjects with co-occurring BAs. The occurrence of BAs was associated with higher impulsivity traits (BIS-11 scores; OR=1.08; p=.012) and higher craving levels (VASc scores; OR=2.48; p<.001). CONCLUSIONS Our findings emphasize a significant rate of co-occurrence of BAs in AUD. High levels of impulsivity and craving for alcohol seem to be associated with other addictive behaviors.

Low-dose topiramate in alcohol dependence: a single-blind, placebo-controlled study.

Introduction Topiramate (TOP) and anticonvulsants in general are considered safe and effective drugs for the treatment of alcohol dependence, even though TOP-induced adverse events are quite common, especially for high initial doses or if titration to 300 mg/d is too rapid. The aim of the present study was to assess the efficacy and tolerability profile of low-dose TOP for relapse prevention. Methods After detoxification, 52 patients were randomized into 2 groups as follows: 26 patients received 100 mg of TOP (oral, twice daily), titrated over 2 weeks, and 26 patients received placebo (PLA). Both groups underwent rehabilitation twice a week. Results After 6 weeks of treatment, compared with the PLA group, patients receiving TOP showed the following: (1) fewer drinking days (P < 0.05); (2) less daily alcohol consumption (P < 0.05); (3) more days of treatment (P < 0.05); (4) reduced levels of craving (Obsessive-Compulsive Drinking Scale) and withdrawal symptoms (Clinical Institute Withdrawal Assessment for Alcohol–Revised); and (5) improvement of anxiety, depression, and obsessive-compulsive symptom severity (Symptom Check List 90 Revised). Conclusions Despite the small sample size and the short follow-up period, the present PLA-controlled study demonstrated the potential usefulness of TOP, even when administered at a dosage of 100 mg/d, for the treatment of detoxified alcohol-dependent subjects, confirming results from previous studies testing higher doses of TOP.

A possible new option for migraine management: agomelatine.

BACKGROUND Migraine is a primary headache disorder characterized by recurrent episodes of headache associated with gastrointestinal, neurologic, and autonomic symptoms. Some evidence in literature suggests that the melatonergic system possibly plays an important role in the pathogenesis of migraine. Few studies have been performed on the use of melatonin as an antimigraine agent. Other than amitriptyline, few antidepressants have been found to be efficacious for migraine prophylaxis. Among antidepressants, agomelatine has a novel neurochemical mechanism. It is an melatonin receptor 1 and melatonin receptor 2 melatonergic receptor agonist and a selective antagonist of the 5-hydroxytryptamine (serotonin) receptor 2C receptors. CASES We report two cases of patients with migraine successfully treated with agomelatine; one patient presented with comorbid depression, whereas the other had no comorbidities. DISCUSSION Given its specific mechanism of action and similarity with melatonin, agomelatine may be a promising new treatment option for migraine prophylaxis. The potential therapeutic action of agomelatine could be due to its synergistic action on both melatonergic and 5-HT2C receptors.

A meta-analysis of cognitive performance in melancholic versus non-melancholic unipolar depression

BACKGROUND Recently there is increasing recognition of cognitive dysfunction as a core feature of Major Depressive Disorder (MDD). The goal of the current meta-analysis was to review and examine in detail the specific features of cognitive dysfunction in Melancholic (MEL) versus Non-Melancholic (NMEL) MDD. METHODS An electronic literature search was performed to find studies comparing cognitive performance in MEL versus NMEL. A meta-analysis of broad cognitive domains (processing speed, reasoning/problem solving, verbal learning, visual learning, attention/working memory) was conducted on all included studies (n=9). Sensitivity and meta-regression analyses were also conducted to detect possible effects of moderator variables (age, gender, education, symptom severity and presence of treatments). RESULTS MEL patients were older and more severly depressed than NMEL subjects. The MEL group was characterized by a worse cognitive performance in attention/working memory (ES=-0.31), visual learning (ES=-0.35) and reasoning/problem solving (ES=-0.46). No difference was detected in drug-free patients by sensitivity analyses. No effect was found for any of our moderators on the cognitive performance in MEL vs NMEL. CONCLUSION Our findings seem to support a moderate but specific effect of melancholic features in affecting the cognitive performance of MDD, in particular as regards visual learning and executive functions.

Pharmacological Treatment of Internet Addiction

The increasing number of Internet users has resulted in an increased population percentage affected by the negative effects of problematic Internet usage. To date, the management of psychopathological Internet use is not supported by extensive empirical research. No standard clinical treatment protocols for pharmacological treatment exist, and as a result, empirical or anecdotal assessments based on case studies are mainly consulted. A relevant problem in performing clinical trials is the evolving nosology, which encompasses ambiguous definitions of Internet addiction and a diversity of diagnostic, prognostic, and therapeutic criteria. The aim of this chapter is to review the current literature, to assess the extent to which specific pharmacological interventions (e.g., using antidepressants, mood stabilizers, opioid receptor antagonists, or antipsychotics) can alleviate the symptomatic burden in patients with “Internet addiction.” We also explore pharmacological interventions that target patterns of comorbidity and underlying psychopathological dimensions (e.g., addiction, impulsivity, obsessive-compulsive spectrum, bipolar spectrum, dissociation, etc.) shared with other behavioral or substance addictions.

Gabapentin as add-on treatment for somatoform disorder: a case report.

Somatoform disorder is a relatively common and severe disorder for which pharmacotherapy has been minimally studied. We report a case of 30-year-old woman with treatment-resistant somatoform disorder that was successfully treated with add-on treatment of gabapentin. Our result showed that gabapentin 1800 mg/day could be tried in case of treatment-resistant somatoform disorder as an add-on strategy. However, controlled trials are needed to investigate the effectiveness of gabapentin in the management of this condition.

PW01-237 - Low-dosage topiramate in alcohol dependence: a randomized, double-blind, placebo-controlled trial

Introduction Topiramate (up to 300 mg per day) is more efficacious than placebo as an adjunct to standardised medication compliance management in treatment of alcohol dependence. However, adverse events can limit its use in different clinical situation. In this randomised, double-blind, placebo controlled trial we aimed to investigate the efficacy of low-dosage topiramate on alcohol drinking indices. Craving and psychiatric symptoms improvements were the secondary endpoints. Methods Forty alcohol dependent subjects where detoxified and subsequently randomised into two groups, respectively receiving topiramate (100mg/die) or Placebo. The level of craving for alcohol was evaluated by a 10-cm Visual Analogue Scale (VAS) and the Italian -version of the Obsessive and Compulsive Drinking Scale (OCDS). Psychiatric symptomatology was evaluated by the Symptom Check List 90 Revised (SCL-90 R). Results The improvement of alcohol drinking indices and craving scores was higher in the topiramate group than placebo. The survival function showed that patients treated with topiramate remained abstinent from any alcohol amount for a longer time with respect to placebo (Z= -2.197; P Discussion To our knowledge, this is the first randomised, parallel group trial to evaluate the efficacy of topiramate at low dosage for alcohol dependence. The use of topiramate at low dosage could increase the number of subjects in treatment, given the reduced possibility of adverse events.

Clinical insights by the presence of bipolar disorder in pseudohypoparathyroidism type 1A

Pseudohypoparathyroidism type 1A and its association with bipolar disorder (BD) have never been reported so far. We report a new case with both clinical entities and discuss the potential pathophysiological mechanisms of this association (protein kinase A hypoactivation, parathyroid hormone, hypocalcemia, protein kinase C activation, vitamin D deficiency). In this patient, the correction of the underlying calcium and vitamin D deficiencies leads to a better BD outcome and lower dosage of psychopharmacological agents. The conclusions might be generalized for a better understanding and management of these conditions.