ISSUE:A striking and unexpected pharmacologic synergy has been shown between antagonist actions at serotonergic 5HT2C receptors, and agonist actions at melatonergic receptors by agomelatine, a drug that has both of these properties.

A major challenge in the treatment of major depressive episodes associated with bipolar disorder is differentiating this illness from major depressive episodes associated with major depressive disorder. Mistaking the former for the latter will lead to incorrect treatment and poor outcomes. None of the classic antidepressants, serotonin specific reuptake inhibitors, or serotonin-norepinephrine reuptake inhibitors have ever received regulatory approval as monotherapies for the treatment of bipolar depression. At present, there are only 3 approved medication treatments for bipolar depression: olanzapine/fluoxetine combination, quetiapine (immediate or extended release), and lurasidone (monotherapy or adjunctive to lithium or valproate). All 3 have similar efficacy profiles, but they differ in terms of tolerability. Number needed to treat (NNT) and number needed to harm (NNH) can be used to quantify these similarities and differences. The NNTs for response and remission for each of these interventions vs placebo range from 4 to 7, and 5 to 7, respectively, with overlap in terms of their 95% confidence intervals. NNH values less than 10 (vs placebo) were observed for the spontaneously reported adverse events of weight gain and diarrhea for olanzapine/fluoxetine combination (7 and 9, respectively) and somnolence and dry mouth for quetiapine (3 and 4, respectively). There were no NNH values less than 10 (vs placebo) observed with lurasidone treatment. NNH values vs placebo for weight gain of at least 7% from baseline were 6, 16, 58, and 36, for olanzapine/fluoxetine combination, quetiapine, lurasidone monotherapy, and lurasidone combined with lithium or valproate, respectively. Individualizing treatment decisions will require consideration of the different potential adverse events that are more likely to occur with each medication. The metric of the likelihood to be helped or harmed (LHH) is the ratio of NNH to NNT and can illustrate the tradeoffs inherent in selecting medications. A more favorable LHH was noted for treatment with lurasidone. However, OFC and quetiapine monotherapy may still have utility in high urgency situations, particularly in persons who have demonstrated good outcomes with these interventions in the past, and where a pressing clinical need for efficacy mitigates their potential tolerability shortcomings. In terms of maintenance therapy, adjunctive quetiapine is the only agent where the NNT vs lithium or valproate alone is less than 10 for both the prevention of mania and the prevention of depression.

ISSUE:Many individuals with total blindness can develop a circadian rhythm disorder—called non-24 sleep wake syndrome—because they cannot detect light to resynchronize their sleep–wake cycles. A new melatonin 1 and melatonin 2 agonist tasimelteon improves sleep in these patients, resetting their circadian sleep–wake clocks.

ISSUE:Vilazodone is an antidepressant with a novel mechanism of pharmacologic action: serotonin partial agonist reuptake inhibitor (SPARI).

ISSUE:Although many patients with schizophrenia fail to respond adequately to trials of 2 or more antipsychotics, utilization of clozapine for these patients remains low, despite recommendations for its use by accepted treatment guidelines. Some experts estimate that 5–10 times more patients could benefit from clozapine than who are now receiving it. Learning how to manage the unique side effect profile of clozapine can potentially remove barriers to prescribing this agent and thus unlock its unique therapeutic efficacy for more patients.

ISSUE:Violence is a major management issue for forensic mental health systems. Violence can be approached as a medical syndrome and deconstructed into psychotic, impulsive, and predatory subtypes, which are hypothetically mapped onto corresponding malfunctioning brain circuits. Rational management of violence balances treatment with security, while targeting each subtype of violence with approaches unique to the psychotic, impulsive, and predatory forms of violence.

This article reviews the literature regarding the impact of cosmetic surgery on health-related quality of life (QOL). Studies were identified through PubMed/Medline and PsycINFO searches from January 1960 to December 2011. Twenty-eight studies were included in this review, according to specific selection criteria.

The procedures and tools employed in cosmetic surgery research studies were remarkably diverse, thus yielding difficulties with data analysis. However, data indicate that individuals undergoing cosmetic surgery began with lower values on aspects of QOL than control subjects, and experienced significant QOL improvement post-procedurally, an effect that appeared to plateau with time.

Despite the complexity of measuring QOL in cosmetic surgery patients, most studies showed an improvement in QOL after cosmetic surgery procedures. However, this finding was clouded by measurement precision as well as heterogeneity of procedures and study populations. Future research needs to focus on refining measurement techniques, including developing cosmetic surgery–specific QOL measures.

Treatment resistance, along with its sibling partial response, remains a common phenomenon in schizophrenia, complicating the disability burden inherent in the disease. Antipsychotic medications are the mainstay of treatment, and treatment resistance has mainly been defined in terms of poor response to antipsychotic medication. At the same time, clozapine, the most effective antipsychotic, remains underutilized at the expense of exposing patients to polypharmacy. We review known causes of disability in schizophrenia, how they impact various areas of everyday functioning, and discuss potential treatment options including but not limited to pharmacological approaches aimed at maximizing treatment response and reducing treatment resistance.

Telepsychiatry, thanks to the continuous advance of technologies, is an area with excellent prospects to become an effective tool for assistance in psychiatry. Many studies evaluated the effectiveness of telepsychiatry in different psychiatric disorders like anxiety disorders, psychotic disorders and depression. Results showed that telepsychiatry seems to be promising in anxiety and depressive disorders, especially in the maintenance phase, and also for psychotic disorders, especially for these cases with a poor compliance. We reviewed the literature to evaluate the feasibility of telepsychiatry in Italy in terms of satisfaction, costs and cultural acceptability and considering ethical and legal aspects. In Italy the development of telemedicine still presents a high level of fragmentation. A potential integration of these new types of services with the health care system is a very challenging task and poses many legal and ethical challenges. Therefore the creation of legal instruments and formal professional ethical guidelines are needed.

ISSUE:A paradigm shift is afoot in which the “last shall be first,” namely, use of long-acting injectable (LAI) antipsychotics, rather than being reserved for use only at the last stages of schizophrenia, may be shifting to first-line treatment of early episodes of this illness.

In this editorial, it is strongly advocated that a change of policy is warranted in order to prevent neuroscience from becoming a waste of time and money in the 21st century. Repeating the same trick in different patient populations and perusing the scientific literature seems to currently be the backbone of medical science. However, this approach does not provide knowledge on how the brain works or how specific dysfunctions result in specific diseases. Therefore, earlier findings should, first, be combined to develop new theories on the mechanics of the mind, and, second, these new ideas should be tested in well-designed experiments.

Major depression is associated with a 4-fold increased risk for premature death, largely accounted by cardiovascular disease (CVD). The relationship between depression and CVD is thought to be mediated by the so-called metabolic syndrome (MeS). Epidemiological studies have consistently demonstrated a co-occurrence of depression with MeS components, ie, visceral obesity, dyslipidemia, insulin resistance, and hypertension. Although the exact mechanisms linking MeS to depression are unclear, different hypotheses have been put forward. On the one hand, MeS could be the hallmark of the unhealthy lifestyle habits of depressed patients. On the other, MeS and depression might share common alterations of the stress system, including the hypothalamus–pituitary–adrenal (HPA) axis, the autonomic nervous system, the immune system, and platelet and endothelial function. Both the conditions induce a low grade chronic inflammatory state that, in turn, leads to increased oxidative and nitrosative (O&NS) damage of neurons, pancreatic cells, and endothelium. Recently, neurobiological research revealed that peripheral hormones, such as leptin and ghrelin, which are classically involved in homeostatic energy balance, may play a role in mood regulation. Metabolic risk should be routinely assessed in depressed patients and taken into account in therapeutic decisions. Alternative targets should be considered for innovative antidepressant agents, including cytokines and their receptors, intracellular inflammatory mediators, glucocorticoids receptors, O&NS pathways, and peripheral mediators.

When a person has a goal of drinking alcohol or using another addictive substance, the person appears to be automatically distracted by stimuli related to the goal. Because the attentional bias might propel the person to use the substance, an intervention might help modify it. In this article, we discuss techniques that have been developed to help people overcome their attentional bias for alcohol, smoking-related stimuli, drugs, or unhealthy food. We also discuss how these techniques are being adapted for use on mobile devices. The latter would allow people with an addictive behavior to use the attentional training in privacy and as frequently as needed. The attentional training techniques discussed here appear to have several advantages. They are inexpensive, can be fun to use, and have flexibility in when, where, and how often they are used. The evidence so far also suggests that they are effective.

The medications used to treat narcolepsy are targeted toward alleviating symptoms such as excessive sleepiness and cataplexy. The cause of this neurological sleep disorder is still not completely clear, though a destruction of hypocretin/orexin neurons has been implicated. The destruction of these neurons is linked to inactivity of neurotransmitters including histamine, norepinephrine, acetylcholine, and serotonin, causing a disturbance in the sleep/wake cycles of narcoleptic patients. Stimulants and MAOIs have traditionally been used to counteract excessive daytime sleepiness and sleep attacks by inhibiting the breakdown of catecholamines. Newer drugs, called wake-promoting agents, have recently become first-line agents due to their better side-effect profile, efficacy, and lesser potential for abuse. These agents similarly inhibit reuptake of dopamine, but have a novel mechanism of action, as they have been found to increase neuronal activity in the tuberomamillary nucleus and in orexin neurons. Sodium oxybate, a sodium salt of gamma-hydroxybutyrate (GHB), is another class that is used to treat many symptoms of narcolepsy, and is the only U.S. Food and Drug Administration (FDA)-approved medication for cataplexy. It has a different mechanism of action than either stimulants or wake-promoting agents, as it binds to its own unique receptor. Antidepressants, like selective serotonin re-uptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs), have also been used, as similar to stimulants, they inhibit reuptake of specific catecholamines. In this article, we seek to review the mechanisms behind these classes of drugs in relation to the proposed pathophysiology of narcolepsy. Appropriate clinical strategies will be discussed, including specific combinations of medications that have been shown to be effective.

The association between violence and mental illness is well-studied, yet remains highly controversial. Currently, there appears to be a trend of increasing violence in state hospital settings, including both civilly and forensically committed populations. In fact, physical aggression is the primary reason for admission to many state hospitals. Given that violence is now often both a reason for admission and a barrier to discharge, there is a case to be made for psychiatric violence to be re-conceptualized dimensionally, as a primary syndrome, not as the byproduct of one. Furthermore, treatment settings need to be enhanced to address the new types of violence exhibited in inpatient environments, and this modification needs to be geared toward balancing safety with treatment.

This issue of CNS Spectrums contains a unique collection of manuscripts that examine compulsivity and impulsivity from a broad range of perspectives and helps to shape our evolving understanding of compulsivity and impulsivity as orthogonal symptom dimensions arising from parallel tightly regulated brain circuits giving rise to a spectrum of overlapping diagnostic categories.