Concurrent Improvement in Both Binge Eating and Depressive Symptoms with Naltrexone/Bupropion Therapy in Overweight or Obese Subjects with Major Depressive Disorder in an Open-Label,Uncontrolled Study

Introduction

Binge eating disorder (BED) is associated with obesity and major depressive disorder (MDD). Naltrexone extended-release (ER)/bupropion ER (NB) is approved as an adjunct to diet and physical activity for chronic weight management. In a prospectively designed 24-week open-label, single-arm, single-site trial of 25 women with MDD and overweight/obesity, NB reduced weight and depressive symptoms.

Methods

This post hoc analysis investigated the relationship between change in self-reported binge eating behavior (evaluated with the Binge Eating Scale [BES]) and changes in weight, control of eating, and depressive symptoms.

Results

At baseline, 91% of subjects had moderate or severe BES scores, suggesting BED. BES scores were significantly improved from week 4, and by week 24, 83% reported “little or no problem.” Improvement in BES scores correlated with improvement in depressive symptoms and control of eating.

Conclusion

NB may be effective in reducing binge eating symptoms associated with MDD and overweight/obesity. Evaluation of NB in BED appears warranted.

Funding

Orexigen Therapeutics, Inc.

     

Comorbidity of Asperger's syndrome and Bipolar disorder

Background and objective

Asperger's Syndrome (AS) is a pervasive developmental disorder that is sometimes unrecognized, especially in the adult psychiatric setting. On the other hand, in patients with an AS diagnosis, comorbid psychiatric disorders may be unrecognized in the juvenile setting. The aim of the paper is to show and discuss some troublesome and complex problems of the management of patients with AS and comorbid Bipolar Disorder (BD).

Methods

The paper describes three patients affected by AS and bipolar spectrum disorders.

Results and conclusion

Mood stabilizers and 2^nd generation antipsychotics were effective in the treatment of these AS patients with comorbid BD, while the use of antidepressants was associated with worsening of the mood disorder.It is of importance to recognize both the psychiatric diagnoses in order to arrange an exhaustive therapeutic program and to define specific and realistic goals of treatment.

     

Earlier Versus Later Augmentation with an Antipsychotic Medication in Patients with Major Depressive Disorder Demonstrating Inadequate Efficacy in Response to Antidepressants: A Retrospective Analysis of US Claims Data

Introduction

There is little evidence regarding the most effective timing of augmentation of antidepressants (AD) with antipsychotics (AP) in patients with major depressive disorder (MDD) who inadequately respond to first-line AD (inadequate responders). The study’s objective was to understand the association between timing of augmentation of AD with AP and overall healthcare costs in inadequate responders.

Methods

Using the Truven Health MarketScan^® Medicaid, Commercial, and Medicare Supplemental databases (7/1/09–12/31/16), we identified adult inadequate responders if they had one of the following indicating incomplete response to initial AD: psychiatric hospitalization or emergency department (ED) visit, initiating psychotherapy, or switching to or adding on a different AD. Two mutually exclusive cohorts were identified on the basis of time from first qualifying event date to first date of augmentation with an AP (index date): 0–6 months (early add-on) and 7–12 months (late add-on). Patients were further required to be continuously enrolled 1 year before (baseline) and 1 year after (follow-up) index date. Patients with schizophrenia or bipolar disorder diagnoses were excluded. General linear regression was used to estimate adjusted healthcare costs in the early versus late add-on cohort, controlling for baseline demographic and clinical characteristics, insurance type, medications, and ED visits or hospitalizations.

Results

Of the 6935 identified inadequate responders, 68.7% started an AP early and 31.3% late. At baseline, before AP augmentation, patients in the early add-on cohort had higher psychiatric comorbid disease burden (47.3% vs. 42.5%; p?<?0.001) and higher inpatient utilization [mean (SD) 0.41 (0.72) vs. 0.27 (0.67); p?<?0.001] than in late add-on cohort. During follow-up, the adjusted total all-cause healthcare cost was significantly lower in the early vs. late add-on cohort ($18,864 vs. $20,452; p?=?0.046).

Conclusion

Findings of this real-world study suggest that, in patients with MDD who inadequately responded to first-line AD treatment, adding an AP earlier reduces overall healthcare costs.

Funding

Otsuka Pharmaceutical Development and Commercialization, Inc. and Lundbeck.

     

The PGRMC1 Protein Level Correlates with the Binding Activity of a Sigma-2 Fluorescent Probe (SW120) in Rat Brain Cells

Purpose

We examined the progesterone receptor membrane component 1 (PGRMC1) protein expression in rat brain cells as the prerequisite step to understand the biology of PGRMC1 in the central nervous system (CNS). We also performed correlation studies between the PGRMC1 protein level and the binding activity of a sigma-2 fluorescent probe, SW120, in order to explore the possibility of using sigma-2 radiotracer of positron emission tomography (PET) to noninvasively image the CNS.

Procedures

Embryonic primary neurons, astrocytes, oligodendrocytes, and microglia cells were cultured. Immunocytochemistry, Western blot, and SW120 staining were performed in these cells.

Results

The protein expression of PGRMC1 determined by immunocytochemistry and SW120 staining is prominent in neurons and relatively low in astrocytes, oligodendrocytes, and microglia cells. The PGRMC1 expression level correlates with the binding activity of SW120 in rat brain cells.

Conclusions

The sigma-2 receptor PET radiotracer can be potentially used to noninvasively image neuron/synapse densities in the CNS.

     

Bipolar disorder in late life: clinical characteristics in a sample of older adults admitted for manic episode

Background

Although manic episodes in older adults are not rare, little published data exist on late-life manic episodes. Resistance to treatment and concomitant neurological lesions are frequent correlates of elderly mania. The aim of this study was to investigate the prevalence of hospitalizations due to mania in patients older than 64 years through a period of 5 years in an Italian public psychiatric ward. Moreover, we aimed at describing clinical presentation of elderly manic episodes.

Methods

A retrospective chart review was conducted in order to describe clinical presentation of 20 elderly patients hospitalized for manic episode; moreover, we compared age at onset, the presence of family history for mood disorders, psychosis and irritability between the elderly group and a matched group of 20 younger manic inpatients.

Results

Seven percent of the whole inpatient elderly people suffered from mania. Half of those patients had a mood disorder age at onset after 50 years and 5 patients were at their first manic episode. Geriatric- and adulthood mania showed similar clinical presentation but younger people had more frequently a mood disorders family history.

Conclusion

Half of our older manic inpatients consisted of "classic" bipolar patients with an extension of clinical manifestations into later life; the other half of our sample was heterogeneous, even though it was not possible to identify clearly which patients may have had vascular lesions related to the onset of mania.

     

Validity of the diagnosis of a single depressive episode in a case register

Objective

To validate the ICD-10 diagnosis of a single depressive episode as used in daily clinical psychiatric practice and as recorded in the Danish Psychiatric Central Research Register.

Methods

Patients discharged with a diagnosis of a single depressive episode were consecutively sampled from the register and diagnosed according to an interview using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN).

Results

A total of 75.4% of 399 patients with a register diagnosis of a single depressive episode also got this diagnosis according to the SCAN interview (82.8% for severe type of a single depression, 76.0% for moderate type of a single depression and 65.2% for mild type of a single depression).

Conclusion

The ICD-10 diagnosis of a single depressive episode can be used in daily clinical practice with sufficient precision. The validity of the diagnosis is highest for severe and moderate type of depression and decreases for mild depression.

     

Sigma-1 Agonist Binding in the Aging Rat Brain: a MicroPET Study with [<Superscript>11</Superscript>C]SA4503

Purpose

Sigma-1 receptor ligands modulate the release of several neurotransmitters and intracellular calcium signaling. We examined the binding of a radiolabeled sigma-1 agonist in the aging rat brain with positron emission tomography (PET).

Procedures

Time-dependent uptake of [¹¹C]SA4503 was measured in the brain of young (1.5 to 3 months) and aged (18 to 32 months) Wistar Hannover rats, and tracer-kinetic models were fitted to this data, using metabolite-corrected plasma radioactivity as input function.

Results

In aged animals, the injected probe was less rapidly metabolized and cleared. Logan graphical analysis and a 2-tissue compartment model (2-TCM) fit indicated changes of total distribution volume (V _T) and binding potential (BP _ND) of the tracer. BP _ND was reduced particularly in the (hypo)thalamus, pons, and medulla.

Conclusions

Some areas showed reductions of ligand binding with aging whereas binding in other areas (cortex) was not significantly affected.

     

Antidepressants and inflammatory bowel disease: a systematic review

Background

A number of studies have suggested a link between the patient's psyche and the course of inflammatory bowel disease (IBD). Although pharmacotherapy with antidepressants has not been widely explored, some investigators have proposed that treating psychological co-morbidities with antidepressants may help to control disease activity. To date a systematic analysis of the available studies assessing the efficacy of antidepressants for the control of somatic symptoms in IBD patients has not been performed.

Methods

We searched electronic databases, without any language restriction. All relevant papers issued after 1990 were examined.

Results

12 relevant publications were identified. All of them referred to non-randomised studies. Antidepressants reported in these publications included paroxetine, bupropion, amitriptyline, phenelzine, and mirtazapine. In 10 articles, paroxetine, bupropion, and phenelzine were suggested to be effective for treating both psychological and somatic symptoms in patients suffering from IBD. Amitriptyline was found ineffective for treating somatic symptoms of IBD. Mirtazapine was not recommended for IBD patients.

Conclusion

Although most of reviewed papers suggest a beneficial effect of treatment with antidepressants in patients with IBD, due to the lack of reliable data, it is impossible to judge the efficacy of antidepressants in IBD. Properly designed trials are justified and needed based upon the available uncontrolled data.

     

Treating bipolar disorder in patients with renal failure having haemodialysis: two case reports

Background

There is little published guideline or evidence on treating bipolar affective disorder in patients with renal failure having haemodialysis.

Case

We present two patients with bipolar affective disorder with renal failure having haemodialysis. We used lorazepam in one patient to manage the immediate risk of non-engagement with dialysis. Risperidone was added in the second patient for managing psychotic symptoms. Valproate was started as a mood stabiliser and titrated upwards for long-term management of the illness.

Conclusion

We discuss the similarities in the two cases and the care plan we used to manage them.

     

The high frequency of manic symptoms in fibromyalgia does influence the choice of treatment?

Background

Mood disorders were found associated with fibromyalgia (FM) and clinical studies have revealed the efficacy of antidepressant drugs in the treatment of FM. However no specific instruments to identify manic symptoms were used.

Objectives

To assess the frequency of anxiety and mood disorders (particularly bipolar disorders and manic symptoms) in a consecutive sample of women affected by FM using standardized diagnostic tools and to compare the prevalence of these disorders with that observed in a sample of healthy controls from the general population.

Methods

Cases: consecutive series of women (N = 37, mean age 50.1 ± 21.0) attending a Rheumatology outpatient Unit at the University of Cagliari. Controls: 148 women, drawn from the data bank of an epidemiological study matched for sex and age with controls according to a randomisation "after blocks" method. The Italian version of the Composite International Diagnostic Interview Simplified were carried out by physicians. Psychiatric diagnosis was formulated according to DSM-IV criteria. The Italian version of the Mood Disorder Questionnaire (MDQ) was administered to identify manic symptoms and bipolar disorders. Diagnosis of FM were carried out by rheumatologist according to the criteria of American College of Rheumatology.

Results

Subjects with FM showed a higher comorbidity with Generalised Anxiety Disorder, Panic Disorder and Major Depressive Disorder than controls. The study showed a high frequency of manic symptoms (MDQ positive) in the sample of fibromyalgic patients (59%), approximately double that found in the control sample (P < 0.001).

Discussion

Clinical studies have shown the efficacy of antidepressants, especially tricyclic antidepressants, in the treatment of FM. The clinical difficulty in identifying hypomanic episodes is well known particularly where previous and not present episodes are concerned as in depressive patients. These data would suggest further studies on the subject are needed and more caution also in prescribing antidepressants in a population apparently at high risk for bipolar disorders.

     

Olanzapine vs haloperidol: treating delirium in a critical care setting

Objective

To compare the safety and estimate the response profile of olanzapine, a second-generation antipsychotic, to haloperidol in the treatment of delirium in the critical care setting.

Design

Prospective randomized trial

Setting

Tertiary care university affiliated critical care unit.

Patients

All admissions to a medical and surgical intensive care unit with a diagnosis of delirium.

Interventions

Patients were randomized to receive either enteral olanzapine or haloperidol.

Measurements

Patient’s delirium severity and benzodiazepine use were monitored over 5 days after the diagnosis of delirium.

Main results

Delirium Index decreased over time in both groups, as did the administered dose of benzodiazepines. Clinical improvement was similar in both treatment arms. No side effects were noted in the olanzapine group, whereas the use of haloperidol was associated with extrapyramidal side effects.

Conclusions

Olanzapine is a safe alternative to haloperidol in delirious critical care patients, and may be of particular interest in patients in whom haloperidol is contraindicated.

     

Low dose quetiapine induced galactorrhoea: a case report

Background

Quetiapine causes less prolactin elevation and/or galactorrhoea than other atypical antipsychotics.

Case Presentation

Ms AB had galactorrhoea and raised prolactin levels at only 100 mg of quetiapine daily.

Conclusion

Low dose quetiapine can also cause galactorrhoea.

     

Aspekte einer liaisonpsychiatrischen Betreuung von Patienten einer universitären Schmerzambulanz

Background

Owing to a rise of psychosomatic comorbidities, the treatment of psychological disorders, which may negatively impact prognosis and therapy, is increasingly becoming a focus of attention for pain outpatient clinics.

Aim

This study investigates and discusses the advantages of liaison psychiatric care in a university pain clinic.

Methods

In this retrospective study, we investigated all patients who presented to an anaesthesiologically led pain clinic between January and June 2014. The psychiatric history was taken by the liaison psychiatrist of the pain clinic.

Results

In the period investigated, 485 patients were treated as outpatients. A psychiatric diagnosis was present 351 patients (72.4%). The distribution of the diagnoses was comparable with that of a consultation service. Adaptation and affective disorders dominated. The patients were preferentially treated with new generation antidepressants.

Conclusion

The constant presence of a liaison psychiatrist allows for timely, specialised care of pain patients in terms of a multimodal therapeutic approach.

     

Affective psychosis,Hashimoto's thyroiditis,and brain perfusion abnormalities: case report

Background

It has recently become evident that circulating thyroid antibodies are found in excess among patients suffering from mood disorders. Moreover, a manic episode associated with Hashimoto's thyroiditis has recently been reported as the first case of bipolar disorder due to Hashimoto's encephalopathy. We report a case in which Hashimoto's thyroiditis was suspected to be involved in the deteriorating course of mood disorder and discuss potential pathogenic mechanisms linking thyroid autoimmunity with psychopathology.

Case presentation

A 43-year-old woman, with a history of recurrent depression since the age of 31, developed manic, psychotic, and soft neurological symptoms across the last three years in concomitance with her first diagnosis of Hashimoto's thyroiditis. The patient underwent a thorough medical and neurological workup. Circulating thyroperoxidase antibodies were highly elevated but thyroid function was adequately maintained with L-thyroxine substitution. EEG was normal and no other signs of current CNS inflammation were evidenced. However, brain magnetic resonance imaging evidenced several non-active lesions in the white matter from both hemispheres, suggestive of a non-specific past vasculitis. Brain single-photon emission computed tomography showed cortical perfusion asymmetry particularly between frontal lobes.

Conclusion

We hypothesize that abnormalities in cortical perfusion might represent a pathogenic link between thyroid autoimmunity and mood disorders, and that the rare cases of severe Hashimoto's encephalopathy presenting with mood disorder might be only the tip of an iceberg.

     

Association of chronic hepatitis C with major depressive disorders: irrespective of interferon-alpha therapy

Background

Mood and anxiety symptoms in chronic hepatitis C (CHC) may be related to the patient awareness of the diagnosis and prognosis, to side effects induced by interferon (IFN)-alpha treatment, as well as to substance abuse. However, the observation of metabolic alterations in patients with CHC has led to hypothesize a direct effect of hepatitis C virus (HCV) on brain function. This study was aimed at elucidating whether CHC is associated with specific anxiety or mood disorders independently of confounding factors.

Methods

Patient cohort: consecutive patients, 135 with CHC and 76 with chronic hepatitis B (CHB). Exclusion criteria: previous treatment with IFN-alpha, co-infection with HCV and hepatitis B virus, infection with human immunodeficiency virus, drug or alcohol abuse, or malignancies. Controls: subjects without evidence of hepatitis randomly extracted from the database of a previous epidemiological study; they were divided into two groups of 540 (332 males) and 304 (220 males) as controls for patients with CHC and CHB, respectively. The psychiatric diagnosis was formulated by means of the Composite International Diagnostic Interview Simplified carried out by a physician according to DSM-IV criteria.

Results

A higher lifetime prevalence of major depressive disorder (MDD) was observed among CHC compared to CHB or controls. The risk of MDD was not statistically different between CHB and controls. Both the CHC and CHB groups showed a significantly higher frequency of panic disorder when compared to controls. No statistical differences were observed in the prevalence of general anxiety disorder and social phobia when CHC or CHB were compared to controls.

Conclusion

The present study provides the first evidence of an association between CHC and MDD, diagnosed on the basis of well-defined international criteria. This association is independent of treatment with IFN-alpha and is not influenced by substance or alcohol abuse. By contrast, anxiety disorders do not appear to be specifically associated with CHC.

     

MAO-B Inhibitors Do Not Block <Emphasis Type="Italic">In Vivo</Emphasis> Flortaucipir([<Superscript>18</Superscript>F]-AV-1451) Binding

Purpose

Recent evidence suggests that the tau radiotracer [¹⁸F]THK-5351 displays high affinity for the monoamine oxidase type B (MAO-B) enzyme. Utilizing another tau-tracer, flortaucipir ([¹⁸F]AV-1451), we previously reported that non-demented Parkinson’s disease patients show off-target binding in subcortical structures, but no appreciable cortical uptake. However, 59 % of these patients were receiving MAO-B inhibitors at the time of their scan. Here, we retrospectively investigated if MAO-B inhibitors in clinical doses affect flortaucipir binding.

Procedures

We compared the standard uptake values of flortaucipir at regional and voxel levels in Parkinson’s disease patients who received MAO-B inhibitors with those who did not.

Results

Sixteen of 27 Parkinson’s disease patients received MAO-B inhibitors at the time of scan. We found no significant flortaucipir uptake differences between the groups at voxel or regional levels.

Conclusion

Use of MAO-B inhibitors at pharmaceutical levels did not significantly affect flortaucipir binding. Thus, MAO-B does not appear to be a significant binding target of flortaucipir.

     

Current and Emerging Treatment Modalities for Leber’s Hereditary Optic Neuropathy: A Review of the Literature

Introduction

The purpose of this review is to present the current and emerging treatment alternatives for Leber’s hereditary optic neuropathy (LHON), emphasizing the most recent use of idebenone and stem cells or gene therapy.

Methods

A comprehensive literature review was performed at the PubMed database regarding the various treatment modalities for LHON.

Results

Treatment modalities for LHON include nutritional supplements, activators of mitochondrial biogenesis, brimonidine, and symptomatic and supportive treatment, but nowadays attention is being paid to idebenone and gene therapy or stem cells.

Conclusion

The treatment of LHON remains challenging, given the nature of the disease and its prognosis.

     

Nalmefene in Alcohol Use Disorder Subjects with Psychiatric Comorbidity: A Naturalistic Study

Introduction

Nalmefene is the first drug to be approved for reducing alcohol consumption in alcohol use disorder (AUD) patients at high drinking risk. In real-world settings, there is a high prevalence of concurrent psychiatric disorders in AUD subjects, with associated increased morbidity and worse prognosis. This study evaluated the use of nalmefene in AUD patients with stabilized psychiatric comorbidity previously treated unsuccessfully for alcohol dependence, and assessed craving reduction and safety.

Methods

Sixty-five AUD outpatients treated with as-needed 18 mg nalmefene for 24 weeks were included. Primary outcome measures were: changes in heavy drinking days (HDDs) and total alcohol consumption (TAC, g/day). Secondary outcome measures were: changes in drinking risk level and craving (obsessive–compulsive drinking scale and visual analogue scale for craving).

Results

Forty-two AUD subjects (64.6%) had one or more stabilized psychiatric comorbidity. There was a significant reduction in HDDs, TAC and craving measures (p < 0.001), with no differences between subjects with and without psychiatric comorbidity. Nalmefene was safe and well tolerated in all patients.

Conclusion

As-needed nalmefene reduced drinking and craving in AUD subjects with and without psychiatric comorbidity. These findings suggest that nalmefene is a valid therapeutic option in real-world clinical settings, where comorbid conditions are common, and has the potential to engage AUD patients who may otherwise not have sought help.

Funding

Lundbeck Italia S.P.A.