bluuebunny/crossref_metadata_2025 huggingface dataset:
Confronting Trauma's Early Aftermath and the Risk for Posttraumatic Stress Disorder
Authors: Klein Ehud
Published: August 2016

Posttraumatic stress disorder (PTSD) is a well-defined clinical syndrome that develops in individuals who have witnessed or been exposed to an event that involves a direct threat to life or physical and/or psychological integrity.

While numerous studies indicate that PTSD will develop in 15% to 25% of trauma victims, time-limited responses develop in a larger portion of victims during the first 48–72 hours (acute stress reaction) and to a lesser extent over the first 4 weeks (acute stress disorder). Many of those who suffer from acute posttraumatic symptoms eventually recover and overcome the consequences of the traumatic event. However, ∼30% to 50% of those with acute stress disorder will eventually develop PTSD. It is obvious that some individuals are vulnerable to the adverse effects of trauma while others have neurobiological and psychological resources that make them resilient to the long-term impact of traumatic exposure. The identification of risk factors and early predictors for PTSD is thus of major importance for identifying those at risk and for initiating therapeutic interventions aimed to reduce long-term morbidity and suffering.
The Future of Depression Psychopharmacology
Authors: Belmaker Robert H.
Published: August 2016

Along with the development of selective sertonin reuptake inhibitors there has been a tremendous widening of the definition of depression and an impressive decrease in the placebodrug difference in controlled studies. In the early 1960s, about one third of depressed patients improved with placebo and two thirds with active compounds. Current controlled studies suggest that the situation has certainly not improved. The Sequenced Treatment Alternatives to Relieve Depression Study found that response rates to new compounds after the failure of the first antidepressant are low. The monoamine hypothesis of depression was formulated in the mid 1960s based on the antidepressant efficacy of the monoamine reuptake inhibitors, monoamine oxidase inhibitors, and the depressogenic effects of reserpine as a monoamine depleter. However, no monoamine-related finding has been found that is diagnostic for depression. A second major hypothesis regarding depression has been the stress cortisol hypothesis. However, blood cortisol levels are not diagnostic of depression. Psychiatric clinicians are convinced that there are patients for whom antidepressants have made the difference between life and death. However, physicians may generalize unjustifiably based on single dramatic cases to a much larger diagnostic group. Perhaps there are many causes of different types of human sadness, and perhaps only some of these involve mechanisms related to monoamines. Thus, perhaps only some kinds of depression are responsive to monoamine affecting antidepressants.
Factors Associated With Rapid Cycling in Bipolar I Manic Patients:Findings From a French National Study
Authors: Azorin Jean-Michel , Kaladjian Arthur , Adida Marc , Hantouche Elie G. , Hameg Ahcene , Lancrenon Sylvie , Akiskal Hagop S.
Published: August 2016

Introduction: Despite numerous explanatory hypotheses, few studies have involved a large national clinical sample examining risk factors in the occurrence of rapid cycling during the course of bipolar illness.

Methods: From 1,090 manic bipolar I disorder inpatients included in a multicenter national study in France, 958 could be classified as rapid or non-rapid cyclers and assessed for demographic, illness course, clinical, psychometric, temperament, comorbidity, and treatment characteristics.

Results: Rapid cycling bipolar disorder occurred in 9% (n=86) of the study group. Compared to nonrapid cyclers (n=872), patients with rapid cycling experienced the onset of their illness at a younger age, a higher number of prior episodes, more depression during the first episode, and more suicide attempts. At study entry, they also experienced manic episodes with more depressive and anxious symptoms, but less psychotic features. The following independent variables were associated with rapid cycling: longer duration of illness, antidepressant treatment, episodes with no free intervals, cyclothymic temperament, lower scores on the Scale for Assessment of Positive Symptoms and presence of thyroid disorder. Retrospective study limited to bipolar I disorder inpatients; several factors previously associated with rapid cycling were not assessed.

Conclusion: Our findings may confirm previous descriptions, according to which rapid-cycling develops later in the course of illness following a sensitization process triggered by antidepressant use or thyroid dysfunction, in patients with a depression-mania-free interval course, and cyclothymic temperament.
Pregnancy Exposure to Serotonin Reuptake Inhibitors and the Risk of Spontaneous Abortions
Authors: Gentile Salvatore
Published: August 2016

Introduction:A growing number of studies have suggested that maternal exposure to post-tricyclic antidepressants during pregnancy might be associated with an increased risk of poor birth, obstetrical, and neonatal outcomes. Among these complications, the occurrence of spontaneous abortions represents one of the most dramatic events for the pregnant woman.

Methods:The purpose of this study was to review all studies reporting primary data investigating the rate of spontaneous abortions in women treated with selective serotonin reuptake inhibitors during pregnancy. Medical literature information published in English since 1980 was identified usingMEDLINE/PubMed, TOXNET, EMBASE, and The Cochrane Library. Searches were performed using various combination of search terms and were last updated May 2008. No other limitations were imposed. Twelve articles reporting primary data on the rate of spontaneous abortions in women treated with selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors during early pregnancy outcome of pregnancies exposed to antipsychotics were selected for the review. The author was the only reviewer who performed selection and data extraction.

Results:Information from reviewed studies are scarce and methodologically inadequate to draw definitive conclusions about the hypothesized risk of spontaneous abortions associated with serotoninergic antidepressant exposure during early pregnancy.
Effectiveness of Long-Term Augmentation with Citalopram to Clomipramine in Treatment-Resistant OCD Patients
Authors: Marazziti Donatella , Golia Francesco , Consoli Giorgio , Presta Silvio , Pfanner Chiara , Carlini Marina , Mungai Francesco , Dell'Osso Mario Catena
Published: August 2016

Introduction: The high percentage (between 40% and 60%) of resistance to first-line drugs, such as clomipramine or selective serotonin reuptake inhibitors, is a major problem in the pharmacologic management of obsessive-compulsive disorder (OCD). In these cases, different strategies have been employed with controversial outcomes. The meager information available on the association of two serotonergic drugs prompted us to explore the possible effectiveness and tolerability of citalopram+clomipramine in resistant OCD patients.

Methods: Twenty outpatients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of OCD, who had failed to respond to at least two trials with a selective serotonin reuptake inhibitor and were currently taking clomipramine at different doses, were administered citalopram at a maximum dose of 60 mg/day. The clinical assessment was carried out at baseline (t0) and at the 4th (t1), 12th (t2), 24th (t3), 36th (t4), and 48th (t5) week by means of the Yale-Brown Obsessive Compulsive Scale, Hamilton Rating Scale for Depression, Clinical Global Impression scale, and the Dosage Record and Treatment Emergent Symptom Scale. The response was defined as a 35% decrease of the Yale-Brown Obsessive Compulsive Scale total score.

Results: The results showed that ∼50% of the patients improved significantly after 1 month of this regimen and after 1 year of treatment.

Conclusion: This study, although carried out in a small sample and in an open fashion, represents one of the few experiences with the association of two serotonergic compounds in resistant OCD and confirms its potential usefulness and good tolerability profile. Controlled research on this association in OCD is recommended.
Short-Term Cardiovascular Effects of Mixed Amphetamine Salts Extended Release in Children and Adolescents With Oppositional Defiant Disorder
Authors: Connor Daniel F. , Spencer Thomas J.
Published: August 2016

Objective

Assess cardiovascular effects of mixed amphetamine salts extended release (MAS XR) in children and adolescents (6–17 years of age) with oppositional defiant disorder (ODD).

Methods

A 4-week, double-blind, randomized, placebo-controlled, forced dose-titration study of once-daily 10-, 20-, 30-, or 40-mg MAS XR (n=308). Resting/sitting systolic blood pressure (SBP) and diastolic blood pressure (DBP) and pulse were measured at baseline and weekly thereafter. Electrocardiograms (ECGs) were obtained at screening and study end point.

Findings

At study end point, mean changes in SBP and DBP were minimal with MAS XR (SBP: -0.2 to 1.1 mm Hg; DBP: -1.0 to 2.1 mm Hg) and comparable to placebo (SBP: -0.6 mm Hg; DBP: -0.4 mm Hg). Mean end point pulse was similar with MAS XR (80.6–84.7 bpm) and placebo (81.8 bpm). No dose-related trends in blood pressure and pulse changes were observed. No clinically significant changes in ECG parameters were seen with MAS XR. Changes in QTcB (Bazett's formula) interval with MAS XR were small (0.5 to 3.9 msec). No patient discontinued due to a cardiovascular adverse event.

Conclusion

Cardiovascular effects of MAS XR (10–40 mg) were minimal and comparable to those with placebo in children and adolescents with ODD.
Transdermal Selegiline:The New Generation of Monoamine Oxidase Inhibitors
Authors: Patkar Ashwin A. , Pae Chi-Un , Masand Prakash S.
Published: August 2016

The clinical use of monoamine oxidase inhibitors (MAOIs) has declined due to concerns about food and drug interactions and waning physician experience. Evidence indicates that MAOIs are effective in depressive disorders, in particular depression with atypical features. Efforts to address safety issues have led to the development of more selective and reversible MAOIs, such as moclobemide. Selegiline, a selective monoamine oxidase B inhibitor, has been approved for the adjunctive treatment of Parkinson's disease at low doses. At higher doses, oral selegiline is also effective in major depressive disorder (MDD) but loses its selectivity and has the potential for tyramine interactions.To overcome these problems, a transdermal formulation of selegiline, the selegiline transdermal system (STS), was developed with novel pharmacokinetic and pharmacodynamic properties. Compared with oral administration, transdermal selegiline leads to sustained plasma concentrations of the parent compound, increasing the amount of drug delivered to the brain and decreasing metabolite production. In addition, STS allows targeted inhibition of central nervous system monoamine A (MAO-A) and monoamine B isoenzymes with minimal effects on MAO-A in the gastrointestinal and hepatic systems, thereby reducing the risk of interactions with tyramine-rich foods (the “cheese-reaction”). Clinical trials have found 6 mg/24 hours of STS to be effective in MDD without the need for dietary restrictions. The efficacy and safety profile of STS supports its use in MDD. It is possible that STS may demonstrate benefit in MDD with atypical features or MDD resistant to other antidepressants. However, more research is needed. Clinicians should familiarize themselves with the properties and indications for the new generation of MAOIs.
Aripiprazole-Related Tardive Dyskinesia
Authors: Maytal Guy , Ostacher Michael , Stern Theodore A.
Published: August 2016

The low prevalence of extrapyramidal symptoms associated with atypical antipsychotics has led to their widespread use during the past decade. Aripiprazole, the newest medication in this class, has been associated with extrapyramidal symptoms (eg, akathisia) and with improvement of tardive dyskinesia (TD), but to date it has not been associated with the development of TD. We report a case of TD associated with the use of aripiprazole 15 mg/day for 18 months for refractory depression. Symptoms of TD resolved within several weeks of discontinuation of aripiprazole.
Anorexia Nervosa and Brain Tumor in a 14-Year-Old Girl
Authors: Sokol Mae S. , Fujimoto Chrystie K. , Jackson Tammy K. , Silberberg Phillip J.
Published: August 2016

A 14-year-old girl with anorexia nervosa (AN) was found to have an intracranial neoplasm. Atypical psychological symptoms prompted further evaluation, including electroencephalogram and neuroimaging, which revealed a sellar and suprasellar mass.This patient had an eating disorder and a brain tumor, which appear to be two unrelated conditions. However, it remains unclear how each affected the other. The diagnosis of AN, like all other psychiatric disorders, requires that possible medical etiologies and coexisting medical problems be excluded. AN and other eating disorders are particularly difficult to diagnose in children and adolescents because they often do not present in the manner typical of adults. Perceptual and cognitive disturbances associated with AN are difficult to evaluate because children and adolescents normally change over time as they progress through different stages of development. Therefore, It is particularly important to evaluate for the presence of medical conditions when a diagnosis of an eating disorder is made in a child or adolescent.
Adjunctive Treatment for Mood Stabilization of Patients with Bipolar I Disorder Treated with Lamotrigine
Authors: Spaulding Theodore , Westlund Ronald , Thomason Christine , White Robin , Dann Rebekkah , Thompson Thomas
Published: August 2016

Objective:

To describe the effect of supplemental psychotropic medications, specifically anxiolytics with sedative/hypnotics (ASH) combined with lamotrigine (LTG) on stabilization of symptoms in patients with bipolar I disorder.

Method:

Symptomatic patients participating in two LTG maintenance trials were classified post-hoc as those initiating LTG as monotherapy (n=313) or as adjunctive therapy (n=814) and further characterized by supplemental add-on therapies received during an open-label treatment phase. Patients were considered stabilized if they reached a stable dose of LTG monotherapy (100–200 mg/day) and had a Clinical Global Impressions-Severity scale score ≤3 for at least 4 weeks. Stabilization rates were compared across initial- and supplemental-treatment groups.

Results:

Patients who initiated and were maintained on LTG monotherapy were stabilized at a slightly higher rate compared with those taking LTG adjunctive therapy (55% vs 48%; P=.080). Stabilization rates were numerically higher for LTG monotherapy patients who later received only ASH as supplemental medication compared with LTG monotherapy throughout, but this difference was not significant (66% vs 55%; P=.271). Stabilization rates were significantly higher for monotherapy patients who later received ASH alone versus other psychotropic medications (66% vs 28%; P=.001). For patients initiating LTG as adjunctive therapy, adding ASH alone resulted in significantly higher stabilization rates than adding another psychotropic medication (62% vs 33%; P<.001).

Conclusion:

LTG and adjunctive treatment with ASH may be useful in the treatment of acute mood symptoms in patients with bipolar I disorder.
The Application of Mindfulness-Based Cognitive Interventions in the Treatment of Co-occurring Addictive and Mood Disorders
Authors: Hoppes Kimberly
Published: August 2016

This article reviews the theory, clinical application, and empirical findings on mindfulness–based cognitive therapy (MBCT) for mental health and addictive disorders. Expanding upon the research demonstrating the efficacy of cognitive-behavioral therapy (CBT) for addiction, this article develops and explores the rationale for combining mindfulness-based interventions with evidence-based CBTs in treating addictive disorders, with an emphasis on substance use disorders with co-occurring mood disorders.This article proposes that deficits in affect regulation — related to the behavioral and emotional effects of neurobiological changes that occur with longterm substance abuse — pose a unique set of challenges in early recovery. Prolonged use of addictive substances impairs the brain pathways to detach or maintain perspective in response to strong emotional states. In treating this affective dysregulation, which can contribute to the vulnerability to relapse in the early stages of recovery, the affect–regulation-specific focus of MBCT adds a valuable element to augment CBT for addiction. Summarizing magnetic resonance imaging and positron emission tomography findings on the effects of MBCT and the neurobiology of drug addiction, this article out-lines directions for further research on potential benefits of MBCT for the recovering individual. Finally, this article describes a structured protocol, developed at the Mount Sinai School of Medicine in New York City, which combines CBT with mindfulness-based intervention, for the treatment of affect-regulation issues specific to co-occurring addictive and mood disorders.
From Impulse-Control Disorders Toward Behavioral Addictions
Authors: Pallanti Stefano
Published: August 2016

In the last 20 years, research on substance addictions has changed its focus from the social foundations to the neurobiological foundations. Hence, some behaviors have begun to be considered as equivalent to addiction based on proposed criteria: salience, withdrawal symptoms, tolerance, conflicts, relapse, and mood modifications.

New knowledge about the brain's reward system suggests that “as far as the brain is concerned a reward is a reward, regardless of whether it comes from a chemical stimulus or an experience.”

Pathological gambling was the prototypical addiction disorder, sharing some hallmarks with substance addictions: a high rate of comorbidity and treatment response to pharmacotherapies, such as opioid antagonist. However, compulsive sexual behavior, compulsive exercise, food starving, binge eating, and, most recently, Internet addiction have been gradually conceptualized as non-substance addictions with overlapping features with substance dependence. Several definitions” have been adopted regarding these behaviors: natural addiction, non-chemical addiction, and negative dependence are only some examples. This issue of CNS Spectrums focuses on behavioral addictions.
New Paradigm for Treating Recurrent Depression: From Symptom Control to Managing Enduring Vulnerabilities
Authors: Schatzberg Alan F.
Published: August 2016

Optimal management of depression remains a long-term challenge. Long-term maintenance treatment with antidepressants has been shown to be effective for preventing or delaying recurrence for many patients with a history of previous multiple episodes. However, aside from a history of multiple recurrences, it remains difficult to identify patients who are most likely to experience recurrence and when. Thus we do not really know who might particularly benefit from maintenance therapy and what type may be efficacious. In patients with depression, research has shown there are structural and functional alterations in the brain, particularly in patients with recurrent or chronic depression. These changes have been generally viewed to be consequences of the disease, which are seen to worsen with a longer duration of untreated illness and with a greater number of depressive episodes. However, these neurobiological characteristics may also represent risk factors or vulnerabilities that predispose some patients to chronic or recurrent depression. Additional research has demonstrated that antidepressant treatment may reduce or modulate these functional and structural changes, suggesting that long-term treatment may, in fact, benefit patients not only by controlling symptoms but also by managing these underlying vulnerabilities. A new treatment paradigm, which focuses on identifying patients with risk factors and managing the disease process rather than suppression of symptoms, is needed for recurrent depression.
Beyond Remission: Rationale and Design of the

P

revention of

R

ecurrent

E

pisodes of Depression with

Ven

lafaxine for

T

wo Years (PREVENT) Study
Authors: Kornstein Susan G.
Published: August 2016

Recurrent major depressive disorder (MDD) is a common and disabling illness, but few studies have addressed long-term antidepressant treatment of recurrent MDD (ie, beyond 1 year of maintenance therapy) or compared the efficacy and safety of different antidepressant classes in this population. This article describes the rationale and design of a unique multi-phase trial in patients with recurrent MDD. The Prevention of Recurrent Episodes of Depression with Venlafaxine for Two Years (PREVENT) study is a large double-blind, randomized, multi-center trial designed to assess the long-term efficacy of venlafaxine extended release (ER) in the prevention of depressive recurrence. Approximately 1,100 adult outpatients with MDD and a history of ≥3 lifetime episodes (with at least two occurring in the past 5 years) were randomized to 10 weeks of acute-phase treatment with either venlafaxine ER 75–300 mg/day or fluoxetine 20–60 mg/day, followed by 6 months of continuation-phase treatment for patients experiencing a satisfactory therapeutic response or remission during the acute phase. Responders and remitters to continuation phase treatment were then entered into a 2-year maintenance phase study, in which those receiving venlafaxine ER were re-randomized to either venlafaxine ER or placebo at the start of two 12-month maintenance periods. Those taking fluoxetine during the acute and continuation phases continued to receive double-blind treatment with fluoxetine. This study will address several unanswered questions about the long-term treatment of recurrent MDD, such as whether extended maintenance treatment (ie, up to 2 years) lessens the risk for developing future depressive episodes; whether fluoxetine and venlafaxine ER are effective for both short- and long-term treatment of MDD; whether rates of tachyphylaxis differ between anti- depressant classes; and whether the likelihood of depressive recurrence differs according to the time point when treatment is discontinued.
A Case of Resolution of an Acute Psychotic Episode After High Fever
Authors: Sani Gabriele , Manfredi Giovanni , Pacchiarotti Isabella , Caltagirone Saverio Simone , Mancinelli Iginia , Koukopoulos Alexia E. , Tatarelli Caterina , Kotzalidis Giorgio D. , Tatarelli Roberto , Girardi Paolo
Published: August 2016

Fever (pyretotherapy) was used for psychosis during the turn of the 19th century, but pyretotherapy (ie, the treatment of a disorder by inducing fever) fell out of use after the introduction of convulsive methods. Here, we report on a case of schizoaffective disorder and review classical and recent literature on fever and psychosis. The patient developed auditory hallucinations, persecutory delusional ideas, and was terrified soon upon his arrival in a foreign country. After being treated for 12 days with olanzapine and haloperidol, he developed a fever due to urinary infection; his creatine phosphokinase levels were high, prompting the suspension of antipsychotics. Psychotic symptom resolution followed immediately fever abatement. Antipsychotics were reintroduced at lower dosages. He was discharged asymptomatic with a prescription of olanzapine 15 mg/day and haloperidol 3 mg/day. The time course of symptom resolution in this patient suggests that fever had a beneficial role in this case. The associations between body temperature changes and psychotic symptoms need to be further studied.
Prevalence and Associated Factors for Suicidal Ideation and Behaviors in Obsessive-Compulsive Disorder
Authors: Torres Albina Rodrigues , Ramos-Cerqueira Ana Teresa de Abreu , Torresan Ricardo Cezar , Domingues Mariana de Souza , Hercos Ana Carolina R. , Guimarães Aron Barbosa C.
Published: August 2016

Introduction

Patients with obsessive-compulsive disorder (OCD) have historically been considered at low risk for suicide, but recent studies are controversial.

Objective

To study the prevalence of suicidal thoughts and attempts in OCD patients and to compare those with and without suicidality according to demographic and clinical variables.

Methods

Fifty outpatients with primary OCD (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) from a Brazilian public university were evaluated. The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was used to assess OCD severity, the Beck Depression Inventory to evaluate depressive symptoms and the Alcohol Use Disorders Identification Test to assess alcohol problems.

Results

All patients had obsessions and compulsions, 64% a chronic fluctuating course and 62% a minimum Y-BOCS score of 16. Half of the patients presented relevant depressive symptoms, but only three had a history of alcohol problems. Seventy percent reported having already thought that life was not worth living, 56% had wished to be dead, 46% had suicidal ideation, 20% had made suicidal plans, and 10% had already attempted suicide. Current suicidal ideation occurred in 14% of the sample and was significantly associated with a Y-BOCS score ≥16. Previous suicidal thoughts were associated with a Beck Depression Inventory score ≥19.

Conclusion

Suicidality has been underestimated in OCD and should be investigated in every patient, so that appropriate preventive measures can be taken.
Drug-Drug Interactions with Antipsychotics
Authors: Meyer Jonathan
Published: August 2016

Recognizing drug-drug interactions (DDIs) has become increasingly important as the country's demographics have aged, resulting in more complex medication regimens. Budnitz and colleagues highlighted the frequency of adverse drug reactions (ADRs) and the substantial morbidity that results. Their study estimated >700,000 cases of ADRs in emergency rooms (ER) in the United States between 2004 and 2005, and that ADRs accounted for 6.7% of ER visits for unintentional injuries that led to hospitalization. Moreover, medications that require monitoring accounted for 41.5% of all the ADR-related hospitalizations.

These data have tremendous implications for the field of psychiatry because many psychiatric drugs require therapeutic monitoring. The importance of DDIs is particularly relevant for the psychiatric population, where adverse effects not only cause short-term morbidity, but may lead to long-term treatment noncompliance. For many patients taking antipsychotics, adherence is the key to a successful outcome. Minimizing DDIs maximizes the chance that people will avoid unnecessary ADRs while achieving therapeutic drug levels.
Impact of Medical Comorbidity on Medication Management of Schizophrenia
Authors: Haupt Dan W.
Published: August 2016

Schizophrenia is associated with increased medical comorbidity likely caused by interactions between life-style, environment, and the disease itself. High rates of medical comorbidity exist among all forms of serious mental illness. Affective disorders such as bipolar disorder and unipolar depression are associated with 1.5–2 times the mortality rate observed in the general population, and high rates of HIV and hepatitis A, B, and C exist among patients with severe mental illness. However, schizophrenia is particularly affected by medical comorbidities, and is associated with a 20% shorter-than-normal lifespan. This discussion focuses on rates of medical comorbidity in people with schizophrenia and the effects of medication on cardiometabolic risk factors. It is also important to recognize that lifestyle and environmental factors associated with serious mental illness, as well as poor access to healthcare, contribute to the elevated rates of medical illnesses observed in these populations as well.

Studies of the association between schizophrenia and medical comorbidities have suggested that the introduction of second-generation antipsychotics (SGAs) may be responsible for the increases observed in cardiovascular disease rates in this patient population, and that cardiovascular disease mortality may be shifting to an earlier stage of life. Ösby and colleagues observed that while overall cardiovascular mortality in schizophrenia patients in Sweden increased from 1976–1995, an even greater increase occurred in men from 1991–1995. This latter increase corresponded temporally to an increased use of SGAs.

Osborne and colleagues recently confirmed the observation made by Osby and colleagues. They compared 46,000 people with serious mental illness and a general population sample of ∼300,000 people from 1987–2002.
Panic Disorder: The Psychobiology of External Treat and Introceptive Distress
Authors: Stein Dan J.
Published: August 2016

Panic disorder seems to be mediated by the neuronal circuitry and neurochemical systems that have evolved to respond to external threatening stimuli. Distant threats activate prefrontal cortex (involved in complex planning of avoidance strategies), while immediate threats activate midbrain structures (involved in fast reflexive behaviors). Panic disorder may, however, also involve more specific interoceptive mechanisms. For example, the association between respiratory dysfunction and panic disorder has bolstered a false suffocation alarm hypothesis. Genetic and environmental contributors to panic disorder are beginning to be delineated. Effective pharmacotherapy and psychotherapy are able to normalize the relevant psychobiology.
Systematic Reviews of Clinical of Acupuncture as Treatment for Depression:How Systematic and Accurate Are They?
Authors: Halbreich Uriel
Published: August 2016

Complementary and alternative medicine (CAM) is very popular in the United States, Canada and other Western societies, and the number of patients seeking treatment by CAM practitioners is increasing. This trend also affects treatment-seeking patients with affective disorders. Many patients and mental health providers update their information and formulate opinions and decisions based on second-hand digested summaries and scientific reviews of the literature. This results in the proliferation of review articles and journals that are exclusively dedicated to reviews. Since most medical schools do not teach CAM and most continuing medical education programs still ignore these subjects, it is of interest to examine the reliability of reviews that claim to be “systematic” and not to take their procedures and conclusions for granted.
Delayed Sleep Phase in Severe Obsessive-Compulsive Disorder: A Systematic Case-Report Survey
Authors: Mukhopadhyay Suman , Fineberg Naomi A. , Drummond Lynne M. , Turner Joanne , White Sarah , Wulff Katharina , Ghodse Hamid
Published: August 2016

Introduction:

To study the prevalence of delayed sleep phase (DSP) in a cohort of inpatients with severe obsessive-compulsive disorder (OCD) and to identify clinical and demographic correlates.

Methods:

A systematic retrospective case-report study of consecutive OCD admissions to a specialist inpatient unit from January 1995 to December 2003. Nursing and medical records of sleep, demographic, clinical, and other relevant details were recorded.

Results:

Of 194 eligible consecutive case reports, 187 were located, and nursing and medical reports of sleep were identified in all 187 (100%). Thirty-three patients (17.6%) fulfilled operationally defined criteria for DSP after exclusion of possible confounding factors. All the patients with DSP were unemployed. Phase-shifted patients were significantly younger than non-shifted patients (P=.019) and reported an earlier age of onset of their OCD (P=.005). There was a non-significant trend toward more severe OCD in the phase-shifted group, but they were not more depressed than their non-shifted counterparts.

Conclusion:

A substantial number of patients with severe, enduring OCD also suffer with DSP, which seems to be specifically linked to OCD as opposed to comorbid depression. Clarification of the etiology within DSP and its interaction with core OCD symptoms on clinical function and disability may identify new treatment targets. To this end, further studies of sleep in OCD using actigraphy and biological measures are indicated.
Long-Term Effectiveness and Safety of Lisdexamfetamine Dimesylate in School-Aged Children with Attention-Deficit/Hyperactivity Disorder
Authors: Findling Robert L. , Childress Ann C. , Krishnan Suma , McGough James J.
Published: August 2016

Introduction:

Lisdexamfetamine dimesylate (LDX), a prodrug stimulant, is indicated for attention-deficit/hyperactivity disorder (ADHD) in children 6–12 years of age and in adults. In shortterm studies, once-daily LDX provided efficacy throughout the day. This study presented here was conducted to assess the long-term safety, tolerability, and effectiveness of LDX in 6- to 12-year-olds with ADHD.

Methods:

This open-label, multicenter, singlearm study enrolled children with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision criteria for ADHD. Following 1-week screening and washout periods, subjects were titrated to LDX 30, 50, or 70 mg/day over 4 weeks and placed on maintenance treatment for 11 months. The ADHD Rating Scale and Clinical Global Impression-Improvement scale measured effectiveness.

Results:

Of 272 subjects receiving LDX, 147 completed the study. Most adverse events were mild to moderate and occurred during the first 4 weeks. There were no clinically meaningful changes in blood pressure or electrocardiographic parameters. From baseline to endpoint, mean ADHD Rating Scale scores improved by 27.2 points (P<.0001). Improvements occurred during each of the first 4 weeks, and were maintained throughout. Based on Clinical Global Impression-Improvement scale scores, >80% of subjects at endpoint and >95% of completers at 12 months were rated “improved.”

Conclusion:

Long-term 30, 50, and 70 mg/day LDX was generally well tolerated and effective in children with ADHD.
Improving the Prediction of Treatment Response in Depression:Integration of Clinical, Cognitive, Psychophysiological, Neuroimaging, and Genetic Measures
Authors: Kemp Andrew H. , Gordon Evian , Rush A. John , Williams Leanne M.
Published: August 2016

Antidepressants are important in the treatment of depression, and selective serotonin reuptake inhibitors are first-line pharmacologic options. However, only 50% to 70% of patients respond to first treatment and <40% remit. Since depression is associated with substantial morbidity, mortality, and family burden, it is unfortunate and demanding on health resources that patients must remain on their prescribed medications for at least 4 weeks without knowing whether the particular antidepressant will be effective. Studies have suggested a number of predictors of treatment response, including clinical, psychophysiological, neuroimaging, and genetics, each with varying degrees of success and nearly all with poor prognostic sensitivity and specificity. Studies are yet to be conducted that use multiple measures from these different domains to determine whether sensitivity and specificity can be improved to predict individual treatment response. It is proposed that a focus on standardized testing methodologies across multiple testing modalities and their integration will be crucial for translation of research findings into clinical practice.
Early Identification of Alzheimer's Disease: What Have we Learned from Mild Cognitive Impairment?
Authors: Feldman Howard H. , Kandiah Nagaendran
Published: August 2016

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline, functional disability, and neuropsychiatric symptoms. Initial diagnosis is often delayed to a point when there is significant neurodegenerative pathology and secondary downstream pathogenic sequelae. The disease should be diagnosed during its earliest stage, as this would likely represent an ideal therapeutic window for disease-modifying therapies. Despite recent research that has focused on defining the clinically identifiable at-risk phase that precedes AD, reliable criteria for identifying patients in the prodromal to incipient stages of AD remain elusive.

In addressing the prodrome of AD, it has been clearly recognized that there are age-inappropriate cognitive declines that fall short of meeting the criteria for dementia. Most broadly, patients in this category have been classified as cognitively impaired not demented (CIND). In epidemiological studies, it has been estimated that 19% to 37% of patients ≥65 years of age are CIND. Conditions within the taxonomy of CIND include age-associated memory impairment (AAMI), age-associated cognitive decline (AACD), and mild cognitive impairment (MCI) (Slide 1).

AAMI is defined psychometrically by memory test scores that are ≥1 standard deviation below scores of young healthy control patients. AACD is characterized by scores in any cognitive domain that are ≥1 standard deviation below age- and education-adjusted normal measures. MCI is identified by memory function at a level ≥1.5 standard deviations below age- and education-adjusted means. Of these three conditions, MCI has been investigated most thoroughly and is defined by a clinical phenotype.
Sleep Disorders Associated with Parkinson's Disease:Role of Dopamine, Epidemiology, and Clinical Scales of Assessment
Authors: Mehta Shyamal H. , Morgan John C. , Sethi Kapil D.
Published: August 2016

Sleep dysfunction is common among patients with Parkinson's disease and occurs in approximately two thirds of patients. The problems range from nocturnal issues such as difficulty with sleep initiation, sleep fragmentation, disturbance of circadian rhythm, and rapid eye movement sleep behavior disorder, to daytime problems such as excessive daytime sleepiness. Frequent nighttime awakening and sleep disruption are the most common sleep problems in Parkinson's disease. Dopamine plays an important role in maintaining wakefulness. To improve sleep in Parkinson's disease, it is important to achieve the critical balance of adequate dopaminergic therapy and control of symptoms. Increased dopaminergic agents can cause dyskinesias and painful dystonia, and undertreatment can cause nighttime akinesia, rigidity, and worse quality of sleep. Other nondopaminergic drugs commonly used in Parkinson's disease can also affect sleep. In patients with advanced Parkinson's disease, deep brain stimulation of the subthalamic nucleus has a favorable impact on sleep quality and sleep architecture.
Sleep Disturbances and Parkinson's Disease
Authors: Friedman Joseph H. , Millman Richard P.
Published: August 2016

Although Parkinson's disease is defined by its motor symptoms, the symptoms that are most devastating to patients and caregivers are dementia and psychosis. In addition, sleep has a tremendous impact on patient well being and quality of life. Eighty percent to 90% of Parkinson's disease patients have a sleep disorder affecting their ability to fall asleep, ability to stay asleep, dreams, motor activity during sleep, post-sleep behavior, or day-time somnolence. Treatment plans for patients with Parkinson's disease who experience sleep disorders aim to improve nighttime sleep or daytime wakefulness, and treatment options vary by sleep disorder.
Introduction: The Impact of Continuous Levodopa Infusion in the Treatment of Parkinson's Disease
Authors: Wolters Erik
Published: August 2016

Parkinson's disease was first described in 1817 by James Parkinson. Based on his observation of only six individuals, Parkinson accurately described the resting tremor and festinate gait, bradykinesia, and postural instability associated with the disease today. Parkinson's disease primarily affects people >50 years of age and causes progressive neurological degeneration, physical disability, and worsening quality of life.

Consequently, most currently available drugs aim to restore striatal dopamine signaling. This can be best reached by increasing the supply of dopamine with oral levodopa (L-dopa), but also by stimulating dopamine receptors directly using dopamine agonists, or by inhibiting the reuptake of endogenous dopamine. Unfortunately, mainly due to the short half-life of L-dopa and the erratic absorption of oral L-dopa (causing pulsatile dopaminergic stimulation) these treatment strategies become increasingly ineffective in the course of this disease, and motor complications may further reduce the quality of life in these patients.
Continuous Drug Delivery with Levodopa/Carbidopa Infusion: Review and First Data of a Dutch Cohort
Authors: van Laar Teus , Hovestadt Ad
Published: August 2016

A duodenal levodopa (L-dopa) and carbidopa infusion has been developed to stabilize plasma levels of L-dopa, in order to reduce existing motor response fluctuations. Stable plasma levels have been shown to reduce these fluctuations significantly. A constant duodenal infusion with an L-dopa solution can improve response fluctuations, however L-dopa has very poor solubility. Only in an acidic environment can L-dopa be dissolved in large volumes. To supply 1 day of infusion with the conventional L-dopa solution, ∼4–5 liters are necessary, an inconvenience to most patients. With L-dopa/carbidopa infusion, L-dopa and carbidopa are concentrated in a water-based gel-like suspension to 20 mg/mL, which has reduced the infusion volumes to <100 mL/day.
Psychological Status and Levels of Sleepiness-Alertness Among Patients With Insomnia
Authors: Rosenthal Leon D. , Meixner Renata M.
Published: August 2016

Are symptoms of daytime sleepiness relevant among patients with insomnia? Patients with insomnia frequently report daytime consequences secondary to their difficulty initiating and maintaining sleep. The purpose of this study was to determine the frequency of daytime sleepiness as defined by a self-reported measure of daytime sleepiness (the Epworth Sleepiness Scale). In addition, the study characterized the patients' psychological status using the Symptom Checklist-90-Revised. The study corroborated a relatively high frequency of excessive daytime sleepiness and psychiatric conditions among patients with insomnia. Furthermore, the results of the study suggest variation in psychological distress levels, according to the different levels of sleepiness/alertness.
Medication Treatment for Depression in Children and Adolescents
Authors: Ryan Neal D.
Published: August 2016

Depression in children and adolescents is relatively common and associated with significant morbidity and mortality—thus, it is strongly deserving of treatment. To date, there have been a number of randomized, controlled trials of both tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) in the acute treatment of depression in youths. Surprisingly, the available data do not demonstrate TCA superiority over placebo for this disorder in this age group. There is, however, evidence of SSRI superiority to placebo, and longer-term treatment with SSRIs may help prevent recurrence. There is almost no data on other pharmacologic approaches. Effective use of the efficacious treatments also depends on effective case-finding and providing treatment, which families and youths will take in adequate quantity and duration. The right approaches to these aspects of effective treatment are greatly understudied.
Cognitive-Behavioral Therapy for Generalized Anxiety Disorder With Integrations From Interpersonal and Experiential Therapies
Authors: Borkovec Thomas D. , Newman Michelle G. , Castonguay Louis G.
Published: August 2016

After providing background information on the definition and nature of generalized anxiety disorder, this article describes cognitive-behavioral therapy (CBT) methods that have been empirically supported in the treatment of this disorder. Subsequent to this description, relevant outcome literature is briefly reviewed, along with evidence that the addition of other techniques beyond traditional CBT methods may be necessary to maximize clinical outcome. A description is then provided of an integrated interpersonal/emotional processing therapy that the authors have recently added to their CBT protocol. CBT with and without this integrated treatment is currently being evaluated in an experimental trial.
Beyond the Treatment of Epilepsy: New Applications of Vagus Nerve Stimulation in Psychiatry
Authors: Kosel Markus , Schlaepfer Thomas E.
Published: August 2016

Vagus nerve stimulation (VNS) in humans generally refers to stimulation of the left vagus nerve at the cervical level. VNS is an established treatment largely devoid of severe side effects for medically refractory partial-onset seizures and has been used in more than 16,000 patients. Over the past 5 years, applications in other neuropsychiatric disorders have been investigated, with a special emphasis on depression. Recent data from an open-label, multi-center pilot study involving 60 patients suggest a potential clinical usefulness in the acute and maintenance treatment of drug-resistant depressive disorder. The perspective of VNS as a long-term treatment with the advantage of assured compliance makes it an interesting technique to potentially treat drug-resistant depression. However, definite therapeutic effects of clinical significance remain to be confirmed in large placebo-controlled trials. Results of clinical pilot studies involving patients suffering from obesity and Alzheimer's disease indicate that VNS might induce weight loss and improve cognition. Besides its clinical usefulness, VNS can be used as a research tool, allowing neuro-physiologic investigations of the parasympathetic system and its interactions with other parts of the central nervous system.