Giuseppe Di Iorio

The Emerging Role of Melatonin Agonists in the Treatment of Major Depression: Focus on Agomelatine

Major Depressive Disorder (MDD) is an extremely disabling, chronic and recurrent disease. Moreover, subthreshold depressive symptoms often persist during periods of apparent remission. Such symptoms include sleep disturbances, sexual dysfunction, weight gain, fatigue, disinterest, anxiety, and/or emotional blunting, which do not often respond to available antidepressant treatments. Agomelatine is a melatonergic agonist (at both MT1 and MT2 receptors) and serotonin 2C (5-HT2C) receptor antagonist. Agomelatine should be particularly useful in the treatment of MDD because of its unique pharmacological profile, accounting for its effective antidepressant action with a relative lack of serious adverse effects. Several clinical trials confirmed the antidepressant efficacy of agomelatine in patients with MDD, with significant efficacy even in severe manifestations of disease and on residual subtreshold symptoms. This compound showed a relative early onset of action as well as an excellent safety and tolerability profile linked to a low discontinuation rate in MDD patients. Moreover, some data suggest that agomelatine has not only antidepressant effects but also anxiolytic effects, with a potential benefit both on anxiety symptoms associated with MDD and in the treatment of generalised anxiety disorder. This review will summarise the role of the melatonergic system in MDD and will describe the characteristics of agomelatine, focusing on its efficacy and safety in the treatment of MDD.

Alexithymia and Suicide Ideation in a Sample of Patients with Binge Eating Disorder

Objective. The goal of this cross-sectional study was to evaluate the relationships between alexithymia and suicide ideation in 80 adult outpatients with a DSM-IV diagnosis of binge eating disorder (BED). Methods. Alexithymia was measured with the 20-item Toronto Alexithymia Scale (TAS-20); suicide ideation was assessed with the Scale of Suicide Ideation (SSI); severity of BED was assessed with the Binge Eating Scale (BES); and depressive and anxiety symptoms were evaluated, respectively, with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating Scale (Ham-A). Results. Prevalence of current suicide ideation was 27.5% (n=22) in this sample and 10 subjects (12.5%) had attempted suicide at some time in their lives. Subjects with alexithymia had more significant suicide ideation, a higher prevalence of current suicide ideation, and more previous suicide attempts than those without alexithymia. In a linear regression model, higher MADRS scores and higher scores on the Difficulty in Identifying Feelings/Difficulty in Describing Feelings dimensions of the TAS-20 were associated with increased suicide ideation. Discussion. Suicidal behavior is no less common in BED than in other eating disorders. Individuals with BED may show increased suicide ideation, especially in the presence of alexithymia and depressive symptoms, even if these symptoms are subclinical. The authors also discuss limitations of this study and future research needs. (Journal of Psychiatric Practice 2012;18:5–11)

Pharmacological Treatments in Gambling Disorder: A Qualitative Review

Gambling disorder (GD) is a psychiatric condition associated with both social and family costs; DSM-5 currently includes GD among addictive disorders. Despite the high burden of this condition, to date there are no treatment guidelines approved by Food and Drug Administration (FDA). Purpose of this paper is to offer a qualitative overview about the different pharmacologic agents used for the treatment of GD. Our analysis, conducted on a final selection of 75 scientific papers, demonstrates that a variety of pharmaceutical classes have been utilised, with different results. Published data, although limited by brief duration of the studies and small number of enrolled subjects, shows mixed evidence for serotonergic antidepressants, opioid antagonists, and mood stabilizers. Other compounds, such as glutamatergic agents and psychostimulants, deserve further studies.

The Endocannabinoid System: A Putative Role in Neurodegenerative Diseases

Background: Following the characterization of the chemical structure of D9-tetrahydrocannabinol (THC), the main psychoactive constituent of marijuana, researchers have moved on with scientific valuable explorations. Objectives: The aim of this review is to highlight the role of endocannabinoid system in neurodegenerative diseases. Materials and Methods: The article is a critical analysis of the most recent data currently present in scientific literature on the subject; a qualitative synthesis of only the most significant articles has been performed. Results: In central nervous system, endocannabinoids show a neuromodulatory function, often of retrograde type. This way, they play an important role in synaptic plasticity and in cognitive, motor, sensory and affective processes. In addition, in some acute or chronic pathologies of central nervous system, such as neurodegenerative and neuroinflammatory diseases, endocannabinoids can perform a pro-homeostatic and neuroprotective function, through the activation of CB1 and CB2 receptors. Scientific evidence shows that an hypofunction or a dysregulation of the endocannabinoid system may be responsible for some of the symptoms of diseases such as multiple sclerosis, amyotrophic lateral sclerosis, Huntington’s, Parkinson’s and Alzheimer’s diseases. Conclusions: The important role played by endocannabinoid system promises interesting developments, in particular to evaluate the effectiveness of new drugs in both psychiatry and neurology.

Alexithymia, suicide risk and serum lipid levels among adult outpatients with panic disorder

To elucidate the relationships between alexithymia, suicide ideation and serum lipid levels in drug-naïve adult outpatients with a DSM-IV diagnosis of Panic Disorder (PD), 72 patients were evaluated. Measures were the Panic Attack and Anticipatory Anxiety Scale, the Toronto Alexithymia Scale (TAS-20), the Scale of Suicide Ideation (SSI) and the Montgomery Åsberg Depression Rating Scale (MADRS). Alexithymic patients showed higher scores on all rating scales and altered serum lipid levels than non-alexithymics. In the hierarchical regression model, the presence of lower HDL-C and higher VLDL-C levels and Difficulty in Identifying Feelings dimension of TAS-20 were associated with higher suicide ideation. In conclusion, alexithymic individuals with PD may show a cholesterol dysregulation that may be linked to suicide ideation. The authors discuss study limitations and future research needs.

Alexithymia, Suicide Ideation, C-Reactive Protein, and Serum Lipid Levels Among Outpatients with Generalized Anxiety Disorder

The aim of the present study was to investigate the relationships between alexithymia, suicide ideation, C-Reactive Protein (CRP), and serum lipid levels in adult outpatients with a DSM-IV diagnosis of Generalized Anxiety Disorder (GAD). Seventy consecutive patients with GAD were recruited and evaluated. Measures were the Hamilton Anxiety Scale, the Toronto Alexithymia Scale (TAS–20), the Scale of Suicide Ideation (SSI), and the Montgomery Åsberg Depression Rating Scale (MADRS). All patients were assessed for: CRP, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceridaemia (TG), and very-low-density lipoprotein cholesterol (VLDL-C). TC/HDL-C and LDL-C/HDL-C ratios were also evaluated. Alexithymic patients showed higher scores on almost all rating scales and altered serum CRP and lipid levels vs. non-alexithymics. In the hierarchical regression model, the presence of higher MADRS scores together with higher scores at the Difficulty in Identifying Feelings dimension of TAS-20 were associated with higher rates of suicide ideation. Although alexithymic subjects with GAD may show a CRP and cholesterol dysregulation, this latter seems independent on increased suicide ideation, rather to Difficulty in Identifying Feelings, and subthreshold depressive symptoms. Study limitations and future research implications are discussed.

S-Adenosyl-L-Methionine Augmentation in Patients with Stage II Treatment-Resistant Major Depressive Disorder: An Open Label, Fixed Dose, Single-Blind Study

We investigated the efficacy of S-Adenosyl-L-Methionine (SAMe) augmentation in patients with treatment-resistant depressive disorder (TRD). Thirty-three outpatients with major depressive episode who failed to respond to at least 8 weeks of treatment with two adequate and stable doses of antidepressants were treated openly with fixed dose of SAMe (800 mg) for 8 weeks, added to existing medication. The primary outcome measure was the change from baseline in total score on Hamilton Rating Scale for Depression (HAM-D). The Clinical Global Impression of Improvement (CGI-I) was rated at the endpoint. Patients with a reduction of 50% or more on HAM-D total score and a CGI-I score of 1 or 2 at endpoint were considered responders; remission was defined as a HAM-D score ≤7. Secondary outcome measures included the Snaith-Hamilton Pleasure Scale (SHAPS) and the Sheehan Disability Scale (SDS). At 8 weeks, a significant decrease in HAM-D score was observed with response achieved by 60% of the patients and remission by 36%. Also a statistically significant reduction in SHAPS and SDS was observed. Our findings indicate that SAMe augmentation may be effective and well tolerated in stage II TRD. However, limitations of the present study must be considered and further placebo-controlled trials are needed.

Cannabis Use and Psychosis: Theme Introduction

Cannabis is among the most widely used illicit substances. Epidemiological and neuroscientific evidence, though poorly integrated, have established a strong association between cannabis use and increased risk of psychosis. Chronic cannabis use, especially of new synthetic varieties, may trigger psychosis and precipitate schizophrenia in vulnerable individuals. However, the specific pathways by which cannabis affects brain function are unclear. It seems likely that a complex genetic-environmental interaction may underlie the link between cannabis exposure and psychosis onset, with multiple genetic variations and several environmental factors (i.e., trauma or maltreatment during childhood) involved. Also, the possible role of basic symptoms in cannabis users is still not fully acknowledged. Basic symptoms may possibly be a marker for the development of full schizophrenia in cannabis users and their recognition may play a role in prevention strategies. Moreover, the differential impact of different types of cannabis has been generally overlooked and little is known about possible pharmacological treatment approaches (with antipsychotics, cannabis agonists, cannabis antagonists) for cannabis users at risk of psychosis. The aim of the present review is to open this issue with a broad introduction on the clinical and pathophysiological link between cannabis abuse and psychosis onset.

The melatonergic system: effects on sleep and implications for the treatment of psychiatric disorders

Correspondence: Domenico De Berardis National Health Service, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, “G. Mazzini” Hospital, p.zza Aldo Moro 1, 64100 Teramo, italy Tel +39 0861429708 Fax +39 0861429706 email dodebera@aliceposta.it Abstract: The circadian pacemaker or biological clock, located in the hypothalamic suprachiasmatic nucleus, is the generation site of circadian rhythms. The light/dark cycle is the circadian pacemaker’s dominant synchronizing agent, though it is also influenced by neurotransmitters and the phase-shifting effects of various chemical and pharmacological components, of which melatonin (N-acetyl-5-methoxytryptamine) is the most well established. In recent years, melatonin and melatonin analogs have been commercialized in many countries, mainly with hypnotic purposes. A new compound, agomelatine, has been recently synthesized and studied. Among melatonin analogs, this drug possesses unique pharmacological and clinical features; it is an antagonist at 5-HT2B and 5-HT2C receptors and has well established antidepressant and anxiolytic properties. Agomelatine opens new perspectives in the chronobiotic treatment of depression. The purpose of the present review was to elucidate the effects of the melatonergic system on sleep and the implications for the treatment of psychiatric disorders.

A Case of Resistant Schizophrenia Successfully Treated With Clozapine/long-acting Injectable Aripiprazole Combination

BackgroundTreatment-resistant schizophrenia (TRS) is a condition characterized by intense symptom severity and poor response to different antipsychotic agents. The first therapeutic option in TRS is clozapine, but often high/medium doses are not tolerated. Adding an oral antipsychotic to low doses of clozapine is a promising strategy in the management of TRS. On the contrary, there are few data on combined clozapine/long-acting injectable (LAI) medications, and none on clozapine/LAI-aripiprazole. CaseA 21-year-old male schizophrenic patient, resistant to several oral and LAI medications, partially improved after clozapine 300 mg/d treatment. Unfortunately, he also reported excessive sedation and an episode of myoclonus, so clozapine was reduced to 150 mg/d, but no additional benefits were observed. Subsequently, LAI-aripiprazole (first 200 mg/mo, then 400 mg/mo) was added, and the patients conditions dramatically improved over time. After 1 year of observation, symptoms reduction was 50% or greater, without significant adverse events. ConclusionsClozapine use in TRS is often reduced or delayed due to the fear of serious adverse effects. Adding LAI-aripiprazole to low doses of clozapine may be a useful therapeutic option to obtain a good efficacy/tolerability balance.