Eradicating Suicide at Its Roots: Preclinical Bases and Clinical Evidence of the Efficacy of Ketamine in the Treatment of Suicidal Behaviors.

Despite the continuous advancement in neurosciences as well as in the knowledge of human behaviors pathophysiology, currently suicide represents a puzzling challenge. The World Health Organization (WHO) has established that one million people die by suicide every year, with the impressive daily rate of a suicide every 40 s. The weightiest concern about suicidal behavior is how difficult it is for healthcare professionals to predict. However, recent evidence in genomic studies has pointed out the essential role that genetics could play in influencing person's suicide risk. Combining genomic and clinical risk assessment approaches, some studies have identified a number of biomarkers for suicidal ideation, which are involved in neural connectivity, neural activity, mood, as well as in immune and inflammatory response, such as the mammalian target of rapamycin (mTOR) signaling. This interesting discovery provides the neurobiological bases for the use of drugs that impact these specific signaling pathways in the treatment of suicidality, such as ketamine. Ketamine, an N-methyl-d-aspartate glutamate (NMDA) antagonist agent, has recently hit the headlines because of its rapid antidepressant and concurrent anti-suicidal action. Here we review the preclinical and clinical evidence that lay the foundations of the efficacy of ketamine in the treatment of suicidal ideation in mood disorders, thereby also approaching the essential question of the understanding of neurobiological processes of suicide and the potential therapeutics.

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.

Treatment of antipsychotic-induced hyperprolactinemia: an update on the role of the dopaminergic receptors D2 partial agonist aripiprazole.

Hyperprolactinemia is an unwanted adverse effect present in several typical and atypical antipsychotics. Aripiprazole is a drug with partial agonist activity at the level of dopamine receptors D2, which may be effective for antipsychotic- induced hyperprolactinemia. Therefore, we analyzed the literature concerning the treatment of antipsychoticinduced hyperprolactinemia with aripiprazole by updating a previous paper written on the same topic. More recent studies were reviewed. They showed that there are two options for the treatment of antipsychotic-induced hyperprolactinemia with aripiprazole. The safest strategy may require the addition of aripiprazole to ongoing treatments, in the case patients had previously responded to antipsychotic drugs and then developed hyperprolactinemia. However, it is advisable to monitor the patients in case relapses and/or side effect, although rare, might occur. Switching drugs should be considered when a patient does not appear to be responding to the previous antipsychotic, thus developing hyperprolactinemia. A cross-taper switch should always be considered, but the risk of a relapse in the disorder may occur more frequently and the patients should be closely monitored. However, limitations must be considered and further studies are needed to definitely elucidate this important issue. Some relevant patents are also described in this review.

The role of intranasal oxytocin in the treatment of patients with schizophrenia: a systematic review.

Oxytocin is a nonapeptide mammalian hormone, best known for its role in childbirth, parturition and lactation. It has been implicated in the control of social behaviors and relationships, such as monogamy or promiscuous behaviors. The putative involvement of oxytocin in schizophrenia was first postulated following several pioneer reports of oxytocin use in schizophrenia and observations of increased oxytocin levels in the cerebrospinal fluid of schizophrenic patients, although this latter finding has subsequently been challenged. More recently, oxytocin plasma levels have been found to be decreased in schizophrenic individuals, particularly in those exhibiting hyponatremic polydipsia and emotional dysregulation. Some authors report that intranasal oxytocin administration to schizophrenic patients may reduce symptomatology. The aim of the present paper was to review studies investigating symptomatology, social cognition and emotion recognition changes in DSM-IV-TR schizophrenic patients, after administration of intranasal oxytocin at different doses. Literature search was conducted in March, 2012. PubMed and Scopus databases were used to find studies for inclusion in the systematic review. Oxytocin may represent an important novel adjunctive treatment for patients with schizophrenia. However, some limitations of current studies cannot be overlooked and further investigations are certainly needed.

Efficacy and safety of long acting injectable atypical antipsychotics: a review.

Schizophrenia is a chronic, severe and recurrent brain disorder that requires continuous, long-term treatment with antipsychotic medication to minimize relapse and provide clinical benefit to patients. For patients with schizophrenia, non-adherence to medication is a major risk factor for relapse and re-hospitalization. Long-acting injectable formulations of second-generation antipsychotics (SGAs-LAIs) provide constant medication delivery and the potential for improved adherence. Currently, three drugs are available for the treatment of schizophrenia, risperidone longacting injectable, olanzapine pamoate and paliperidone palmitate. Several studies have also demonstrated efficacy and safety of such drugs in patients with acute schizophrenia. In the present paper the literature on LAI atypical antipsychotics will be reviewed and practical advice will be given concerning the use of these drugs in the clinical practice.

The potential of pregabalin in neurology, psychiatry and addiction: a qualitative overview.

Pregabalin is an anticonvulsant drug that binds to the α2δ (alpha2delta) subunit of the voltage-dependent calcium channel in central nervous system (CNS). Pregabalin decreases the release of neurotransmitters, including glutamate, norepinephrine, substance P and calcitonin gene-related peptide. Purpose of this paper is to offer a qualitative overview of the studies currently available in literature about this drug, examining the effectiveness of pregabalin in its various fields of application. Our analysis, conducted on a final selection of 349 scientific papers, shows that pregabalin may help to reduce pain in diabetic neuropathy, in post-herpetic neuralgia and in some patients affected by fibromyalgia. It is also effective for the treatment of diverse types of seizures and has similar efficacy to benzodiazepines and venlafaxine in anxiety disorder. Moreover, pregabalin may be a therapeutic agent for the treatment of alcohol abuse, in both withdrawal phase and relapse prevention. Possible implications in the treatment of benzodiazepines dependence are emerging, but a potential abuse or misuse of the drug has also been reported. Range of dosage may fluctuate considerably, from 75 mg to 600 mg per day. Further studies are needed to completely understand pregabalin mechanism of action in the different diseases.

Update on the adverse effects of clozapine: focus on myocarditis.

Clozapine, an atypical antipsychotic, is a dibenzodiazepine derivative and its therapeutic effects are probably mediated by dopaminergic and serotonergic activity. In accordance to several studies, it appears to be the most effective antipsychotic drug for treatment-resistant schizophrenia. Moreover, clozapine appears to be particularly beneficial in patients with schizophrenia who are suicidal and in those with comorbid substance use disorder. However, despite its efficacy, the general use of clozapine in clinical practice is somewhat limited because of the risk of several serious adverse effects such as agranulocytosis and thromboembolism. Clozapine may be associated with fatal myocarditis and cardiomyopathy in physically healthy young adults. Consequently, the FDA and the drug's manufacturer have strengthened warnings to include that a potentially fatal myocarditis may occur when taking clozapine. In the present paper the literature on clozapine-related myocardis will be reviewed and practical advice will be given concerning the diagnosis and management of such potentially fatal adverse effect.

The Relationships between Cholesterol and Suicide: An Update.

Cholesterol is a core component of the central nervous system, essential for the cell membrane stability and the correct functioning of neurotransmission. It has been observed that cholesterol may be somewhat associated with suicidal behaviours. Therefore, the aim of this paper was to elucidate current facts and views about the role of cholesterol levels in mood disorders. The majority of the studies reviewed in the present paper suggest an interesting relationship between cholesterol (especially lower levels) and suicidality. On the other hand, particularly during the last years, relationships between serum cholesterol and suicidality were doubted on the basis of some recent studies that have not found any correlation. However, the debate on relationships between cholesterol and suicide is open and longitudinal studies on a larger sample of patients are needed to further clarify this important issue.

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 its relationships with dissociative experiences and Internet addiction in a nonclinical sample.

The aim of the present study was to evaluate alexithymia, dissociative experiences, and Internet addiction (IA) in a nonclinical sample of 312 undergraduate students, identifying predictive factors associated with the possible risk of developing IA. We found that alexithymics had more consistent dissociative experiences, lower self-esteem, and higher obsessive-compulsive symptoms than nonalexithymics. In addition, alexithymics reported a higher potential risk for IA when compared to nonalexithymics. Difficulty in identifying feelings, higher dissociative experiences, lower self-esteem, and higher impulse dysregulation were associated with higher IA. Thus, a combination of alexithymia, dissociative experiences, low self-esteem, and impulse dysregulation may be a risk factor for IA, at least in a nonclinical sample.