Current Psychiatry Reviews - Volume 8, Issue 1, 2012

This issue marks the beginning of the eighth year of Current Psychiatry Reviews and it is hard to believe that the time has passed so quickly! Thinking back to our beginning efforts in 2004-05, our overarching goal was to fill a major void in the psychiatric literature, namely to become the first journal devoted to rapid publication of comprehensive reviews of the most interesting and important topics in psychiatry, psychopathology, and mental health and we hope that you agree that we are accomplishing this mission. In this issue of Current Psychiatry Reviews, for example, there are four papers directly addressing therapeutics, including articles summarizing the state of the science pertaining to sleep and antidepressants, pharmacotherapy of pathological gambling, the safety profiles of second generation antipsychotics, and management of weight gain during treatment with SGAs or mood stabilizers, as well as a paper highlighting the potential therapeutic applications of intranasal oxytocin. With respect to classification, there are papers reviewing the comorbidity of alcoholism and bulimia nervosa and the neurobiological complexity of antisocial personality disorder. As Editor-in-Chief, it is gratifying to see such outstanding papers take form - sometimes beginning with a short abstract outlining the authors' ideas - and reach an increasingly larger audience. This process is depends on the efforts of dozens of peer reviewers, who donate hundreds of hours of time to help our authors sharpen, clarify, and strengthen their contributions. I also wish to thank the editorial staff of Bentham for their tireless efforts to ensure that papers are shepherded through the review process, deadlines get met, and infinitives go unsplit.

Introduction: Depression is a common disorder associated with significant disability and is a substantial burden on the individual, their relatives and friends, and on society as a whole. Sleep disturbances are key features of depressive symptomatology, with more than 80% of depressed patients complaining of poor quality sleep Methods: The range of available antidepressants is here reviewed in relation to mechanisms of action and the evidence of sleep alteration in patients with depression. Results: The available treatments are largely effective but their use is compromised by poor tolerability and low adherence to treatment. It is also clear that currently used antidepressant agents tend to disrupt sleep architecture. Agomelatine, a novel antidepressant, has been found successful in treating depressed patients. Because of its dual mechanism of action on MT1 and MT2 melatonin receptors in the SCN and its 5-HT2c antagonist properties, agomelatine has been effective in improving both quality of sleep and mood in depressed patients. Conclusions: There is clinical and epidemiological evidence that sleep disturbances in depression constitute a risk factor for poor clinical outcomes. Specifically, insomnia complaints precede the onset and recurrence of depression. For this reason antidepressants with a faster onset of action, with less interferences on sleep architecture would be expected to bring larger numbers of depressed patients to full remission.

Antisocial personality disorder (ASPD) is a pervasive condition among youngsters around the globe, which has particular pungency in countries where the socioeconomic context favors delinquency. Several behavioral genetics studies have linked the disorder to the presence of copies of a polymorphic variation of the MAO-A gene that leads to enzymatic hypofunction. An emerging tendency in this literature is to also associate it to the presence of short variations of the 5- HTTLPR polymorphism, which is well-known for its possible role in the vulnerability to major depression of individuals that were exposed to early-life stress. The current paper argues that the association of these findings introduces a theoretical problem that is not trivial (“an apparent paradox”), and further proposes a solution to it.

Pathological gambling (PG) is an impulse control disorder with prevalence estimates in the range of 0.2-2% in the general population. PG can significantly impact one's ability to function as it may negatively influence social, financial, and occupational aspects of life. Historically, PG has received relatively little attention from researchers and clinicians, and few treatments, particularly pharmacological, have been both validated and widely employed. Given the clinical relevance of PG, it is important that researchers examine pharmacological and behavioral treatments for their safety and efficacy and that clinicians use empirically validated therapies. Multiple neurochemicals, including serotonin, dopamine, norepinephrine, and opioids, and related neurocircuitry, particularly ventral cortico-striatal pathways, have been implicated in PG. The neurobiological rationale for therapies, particularly pharmacological ones, is reviewed with a perspective on the generation of improved prevention and treatment strategies for PG.

Pharmacological treatments for serious mental illness (SMI) can cause weight gain and adverse metabolic effects. Many second generation antipsychotics and mood stabilizers appear to be particularly problematic in this regard. Several studies have investigated interventions for antipsychotic-induced, or less commonly mood stabilizer-induced, weight gain. Both lifestyle and pharmacological interventions have demonstrated effectiveness. We systematically review randomized controlled trials of pharmacological interventions for weight gain related to these medications. We conducted a meta-analysis of clinical trials for the most studied agents to estimate mean weight loss: metformin (2.93 kg, 95% C.I. 0.97-4.89, p=0.003), H2 antagonists (1.78 kg (95% C.I. -0.50??4.06, p=0.13), topiramate (3.95 kg 95% C.I. 1.77-6.12, p=0.0004), and norepinephrine reuptake inhibitors (1.30 kg (95% C.I. -0.06-2.66, p=0.06). Among the studied options for antipsychotic-related weight gain, metformin has the strongest evidence base and may improve vascular risk factors beyond obesity. The use of topiramate is also supported by the literature and may improve psychotic symptoms in those refractory to treatment. A marginal benefit is seen with norepinephrine reuptake inhibitors, and any vascular benefits from such weight loss may be counteracted by increases in blood pressure or heart rate. Pharmacological therapies may offer benefits as a means of supplementing the effects of lifestyle changes for weight loss. However, the existing evidence provides little evidence of specificity for pharmacological therapies to antipsychotic-induced weight gain and has not demonstrated any improvement in vascular outcomes.

The hormone oxytocin plays a major role in relationship formation and social functioning in animals and humans. We review theory and research examining the potential for intra-nasal oxytocin as an adjunctive medication for several mental health problems and risks: autism, schizophrenia, developmental precursors of psychopathy, social phobia, anorexia nervosa, obsessive compulsive disorder, depression (especially postnatal) and impaired maternal-infant bonding. Initial findings suggest that oxytocin administration may alleviate symptoms of autism and social phobia, but current evidence is insufficient to recommend oxytocin as a standard treatment. Despite reasonable theoretical indications, there has also been no systematic examination of oxytocin effects with psychopathy, anorexia, depression, or in mothers with problems bonding with their infants. Findings in patients with obsessive compulsive disorder suggest that oxytocin administration may not be beneficial in this group. Overall, there are good reasons to suggest that intra-nasal oxytocin may be a promising adjunctive treatment for specific mental health problems that involve impairments in engaging comfortably with other people; however, research is in its infancy; the specificity and durability of effects remain unknown, and issues of safety and modes of delivery have yet to be addressed.

Early clinical trials had suggested a better safety profile for the second-generation antipsychotics (SGAs; e.g. risperidone, olanzapine, quetiapine, aripiprazole) compared to the older first-generation agents (FGAs; e.g. haloperidol and phenothiazines); however, new long-term studies have determined that important adverse events are associated with the use of the SGAs and that their safety profiles differ significantly. This article reviews the most recent publications (September 2007 to September 2011) of long-term studies of antipsychotic pharmacotherapy with a focus on adverse events and tolerability of second-generation antipsychotic medications. A total of 55 studies were included. Most commonly reported adverse events were weight gain, dyslipidemias, glycemic abnormalities, hyperprolactinemia, movement disorders and cardiovascular events. It would appear that overweight patients and those with dyslipidemia or risk factors for cardiovascular disease are candidates for agents such as aripiprazole or ziprasidone, which have neutral lipid and weight gain profiles. Patients who are not comfortable with the potential risk of developing hyperprolactinemia should not be prescribed risperidone as first line therapy. Those who have arrhythmias should not be treated with clozapine or ziprasidone. More challenging it is to make a straight recommendation for a first-line treatment in patients at risk of movement disorders. Severe SGA-induced adverse events including death have been reported in elderly patients affected by dementia. Adolescents appear to be more susceptible to SGAs adverse events. Potential risks and benefits should always be considered for each individual patient prior to therapy initiation in order to minimize discontinuation rates and treatment failure.

Bulimia nervosa (BN) is a serious eating disorder characterized by recurrent binge eating episodes and dysfunctional compensatory behaviours, with a prevalence rate of up to 3%. Epidemiological studies show that BN and alcohol use disorder (AUD) co-occur very frequently in both clinical and community settings. Considering that eating disorders with comorbid AUD are associated with serious medical complications, poor treatment outcome and the highest lifetime mortality among all psychiatric disorders, there is great need for developing a better understanding of the nature of this comorbid relationship. This review is designed to critically evaluate the literature on BN and AUD and discuss the similarities between these two psychiatric disorders to offer a comprehensive summary of this serious psychiatric comorbidity. We will first analyze the complex and multi-dimensional etiology of these disorders as well as report on shared developmental pathways. We will then review the role of shared neurobiology, focusing on a variety of neurotransmitters including dopamine and serotonin. We will also comment on the role of shared genetic vulnerabilities in the development of BN and AUD. The section on treatment will cover pharmacological and psychological treatments for BN and AUD. Finally, we will discuss the challenges related to gaining a better understanding of comorbid BN and AUD, as well as propose future directions for research.