Reasons for initiating long-acting antipsychotics in psychiatric practice: findings from the STAR Network Depot Study.

BACKGROUND: Long acting injectable (LAI) antipsychotics have been claimed to ensure treatment adherence and possibly reduce the daily burden of oral formulations. So far, only surveys investigating the theoretical prescribing attitudes of clinicians have been employed. On this basis, we aimed to investigate reasons for prescribing LAIs in a real-world, unselected sample of patients. METHODS: The STAR Network Depot Study is an observational, multicentre study consecutively enrolling adults initiating a LAI over a 12-months period. Clinical severity was assessed with the Brief Psychiatric Rating Scale, and patient's attitude toward medications with the Drug Attitude Inventory 10 items. Psychiatrists recorded reasons for LAI prescribing for each study participant. Responses were grouped into six non-mutually exclusive categories: aggressiveness, patient engagement, ease of drug taking, side-effects, stigma, adherence. RESULTS: Of the 451 patients included, two-thirds suffered from chronic psychoses. Improving patient engagement with the outpatient psychiatric service was the most common reason for prescribing LAIs (almost 80% of participants), followed by increasing treatment adherence (57%), decreasing aggressiveness (54%), and improving ease of drug taking (52%). After adjusting for confounders, logistic regression analyses showed that reasons for LAI use were associated with LAI choice (e.g. first-generation LAIs for reducing aggressiveness). CONCLUSION: Despite the wide availability of novel LAI formulation and the emphasis on their wider use, our data suggest that the main reasons for LAI use have remained substantially unchanged over the years, focusing mostly on improving patient's engagement. Further, clinicians follow implicit prescribing patterns when choosing LAIs, and this may generate hypotheses for future experimental studies.

Molecular Bases of Alzheimer's Disease and Neurodegeneration: The Role of Neuroglia.

Neuroglia is an umbrella term indicating different cellular types that play a pivotal role in the brain, being involved in its development and functional homeostasis. Glial cells are becoming the focus of recent researches pertaining the pathogenesis of neurodegenerative disorders, Alzheimer's Disease (AD) in particular. In fact, activated microglia is the main determinant of neuroinflammation, contributing to neurodegeneration. In addition, the oxidative insult occurring during pathological brain aging can activate glial cells that, in turn, can favor the production of free radicals. Moreover, the recent Glycogen Synthase Kinase 3 (GSK-3) hypothesis of AD suggests that GSK3, involved in the regulation of glial cells functioning, could exert a role in amyloid deposition and tau hyper-phosphorylation. In this review, we briefly describe the main physiological functions of the glial cells and discuss the link between neuroglia and the most studied molecular bases of AD. In addition, we dedicate a section to the glial changes occurring in AD, with particular attention to their role in terms of neurodegeneration. In the light of the literature data, neuroglia could play a fundamental role in AD pathogenesis and progression. Further studies are needed to shed light on this topic.

Gsk3 Signalling and Redox Status in Bipolar Disorder: Evidence from Lithium Efficacy.

Objective. To discuss the link between glycogen synthase kinase-3 (GSK3) and the main biological alterations demonstrated in bipolar disorder (BD), with special attention to the redox status and the evidence supporting the efficacy of lithium (a GSK3 inhibitor) in the treatment of BD. Methods. A literature research on the discussed topics, using Pubmed and Google Scholar, has been conducted. Moreover, a manual selection of interesting references from the identified articles has been performed. Results. The main biological alterations of BD, pertaining to inflammation, oxidative stress, membrane ion channels, and circadian system, seem to be intertwined. The dysfunction of the GSK3 signalling pathway is involved in all the aforementioned "biological causes" of BD. In a complex scenario, it can be seen as the common denominator linking them all. Lithium inhibition of GSK3 could, at least in part, explain its positive effect on these biological dysfunctions and its superiority in terms of clinical efficacy. Conclusions. Deepening the knowledge on the molecular bases of BD is fundamental to identifying the biochemical pathways that must be targeted in order to provide patients with increasingly effective therapeutic tools against an invalidating disorder such as BD.

Psychopathological Variables and Sleep Quality in Psoriatic Patients.

Psoriasis is an inflammatory disease frequently associated with psychiatric disturbances and sleep disorders. The aim of the study was to assess the prevalence of depression, interaction anxiety, audience anxiety, and sleep quality in psoriatic patients. One hundred and two psoriatic patients were enrolled and underwent the following questionnaires: Zung Self-Rating Depression Scale (SDS), Interaction Anxiousness Scale (IAS), Audience Anxiousness Scale (AAS), Pittsburgh Sleep Quality Index (PSQI). The severity of skin lesions was assessed by Psoriasis Area Severity Index (PASI). The presence of a link between clinical variables and with demographic data has been investigated. Psoriasis was linked to depression, interaction and audience anxiety, as well as to poor sleep quality; 37.5% of patients were depressed, 46.1% scored above 37 at the IAS, 47.1% scored above 33 at the AAS. Thirty-nine subjects (38.2%) presented a PSQI ≥ 5. An association between interaction anxiety and lower limbs psoriasis-related erythema as well as between PSQI and head psoriasis-related erythema was found, particularly among male patients. Hence, psoriatic patients should be assessed from a holistic point of view, in order to identify associated disorders that could benefit from targeted treatments.

The Role of Oxidative Damage in the Pathogenesis and Progression of Alzheimer's Disease and Vascular Dementia.

Oxidative stress (OS) has been demonstrated to be involved in the pathogenesis of the two major types of dementia: Alzheimer's disease (AD) and vascular dementia (VaD). Evidence of OS and OS-related damage in AD is largely reported in the literature. Moreover, OS is not only linked to VaD, but also to all its risk factors. Several researches have been conducted in order to investigate whether antioxidant therapy exerts a role in the prevention and treatment of AD and VaD. Another research field is that pertaining to the heat shock proteins (Hsps), that has provided promising findings. However, the role of OS antioxidant defence system and more generally stress responses is very complex. Hence, research on this topic should be improved in order to reach further knowledge and discover new therapeutic strategies to face a disorder with such a high burden which is dementia.

Eating Disorders in Late-life.

Eating disorders are a heterogeneous group of complex psychiatric disorders characterized by abnormal eating behaviours that lead to a high rate of morbidity, or even death, if underestimated and untreated. The main disorders enlisted in the chapter of the Diagnostic and Statistic Manual of Mental Disorders-5 dedicated to "Feeding and Eating Disorders" are: anorexia nervosa, bulimia nervosa and binge eating disorder. Even though these abnormal behaviours are mostly diagnosed during childhood, interesting cases of late-life eating disorders have been reported in literature. In this review, these eating disorders are discussed, with particular attention to the diagnosis and management of those cases occurring in late-life.

Nothing to smile about.

BACKGROUND: Several studies have demonstrated the high incidence of periodontal disorders among patients suffering from mental illnesses, probably because of self-care impairment, the difficult financial conditions, and the lack of motivation. The primary aim of this study was to evaluate the impact of depression and alexithymia on periodontal status. Due to the influence of personality traits on behavior in general, the secondary aim of our study was to investigate the possible impact of personality disorders on dental status. METHODS: Patients with major depression (DP) referred to our psychiatry unit and healthy individuals (controls) were consecutively enrolled during the period April 2012-September 2012. All the participants to the study underwent a psychiatric evaluation (through questionnaires investigating the presence of depression, anxiety, personality disorders, and alexithymia) and a dental examination through the following indexes: plaque index, gingival index, simplified oral hygiene index, periodontal index. RESULTS: Fifty DP (aged 56.7±15.2 years) and 40 controls (aged 56.1±15.9 years) were enrolled in the study. DP showed a worse oral hygiene status. In particular, statistically significant differences were found when comparing DP and controls in terms of plaque index, simplified oral hygiene index, gingival index, periodontal index, and oral health impact profile. In addition, periodontal health was found to be negatively related to the severity of depression and the presence of alexithymia. The strength of association between depression and dental indexes was reduced after adjusting for the other psychiatric variables (alexithymia and personality disorders) and was confirmed only for oral health impact profile. CONCLUSION: Psychiatric variables seem to affect the patients' periodontal status; due to the high frequency of dental problems, patients suffering from mental illnesses should be referred to the oral health services for evaluation.

Effectiveness of lithium in subjects with treatment-resistant depression and suicide risk: results and lessons of an underpowered randomised clinical trial.

BACKGROUND: As lithium treatment might be effective in reducing the risk of deliberate self-harm (DSH) in adult patients with unipolar affective disorders, we designed a pragmatic randomised trial to assess its efficacy in more than 200 patients with treatment-resistant depression. However, we randomised 56 patients only. The aim of this report is therefore twofold: first, to disseminate the results of this underpowered study which may be incorporated into future meta-analytical reviews; second, to analyse some critical aspects of the study which might explain failure to reach the target sample size. METHODS: We carried out a randomised, parallel group, assessor-blinded superiority clinical trial. Adults with a diagnosis of major depression, an episode of DSH in the previous 12 months and inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode were allocated to add lithium to usual care (intervention arm) versus usual care alone (control arm). Suicide completion and acts of DSH during the 12 months of follow-up constituted the composite primary outcome. RESULTS: Of 58 patients screened for inclusion, 29 were allocated to lithium plus usual care and 27 were assigned to usual care without lithium. Six patients in the lithium plus usual care group and seven in the usual care group committed acts of DSH during the follow-up phase. The survival probability did not differ between the two treatment arms (Chi2 = 0.17, p =0.676). With regard to changes in the severity of depressive symptomatology from baseline to endpoint, no significant differences were detected. CONCLUSIONS: The present study failed to achieve the minimum sample size needed to detect a clinically meaningful difference between the two treatment arms. Consequently, the finding that lithium, in addition to usual care, did not exert a positive effect in terms of reduction of DSH after 12 months of follow-up is likely due to the lack of sufficient statistical power to detect a difference, if a difference existed. The dissemination of the results of this underpowered study will inform future meta-analytical reviews on lithium and suicide-related outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00927550.

Prevalence of depression and its relationship with work characteristics in a sample of public workers.

Occupation is a fundamental right, enabling social interaction and financial support for the individual. However, it is an undeniable source of stress, with consequences for physical and mental health. The prevalence of depression and somatic complaints were assessed in 1,013 public workers using the Beck Depression Inventory and a questionnaire investigating for the presence of somatic problems designed by the research team. The results were related to demographic characteristics, history of previous depressive episodes, work schedule (day work, night and day rotating shift work, day rotating shift work), and duration of current work schedule. There were more cases of moderate depression in the day rotating shift workers (84%) than in those working at night (83%). More women had mild or moderate depression than men (22% and 4% versus 10% and 3%, respectively). Severe depression was found only in men. Nearly 10% of depressed individuals reported previous depressive episodes. A link between depression and somatic complaints was also found. In particular, 59% of depressed subjects reported gastrointestinal complaints and 41% did not (P<0.001). In conclusion, the occurrence of depressive symptoms could be facilitated by occupation. A history of depressive symptoms should not be neglected, given the risk of recurrence. Somatic complaints could represent a "wake-up call" regarding depression. Global assessment and effective support are fundamental for promotion of a better quality of life in the at-risk category of workers.

Accelerated aging in major depression: the role of nitro-oxidative stress.

Nitro-oxidative stress (NOS) plays a fundamental role in aging, as well as in the pathogenesis of neurodegenerative disorders, and major depression (MD). The latter is a very frequent psychiatric illness characterized by accelerated aging, neurodegeneration, high comorbidity with age-related disorders, and premature mortality; all of these conditions find an explanation in an altered redox homeostasis. If aging, neurodegeneration, and major depression share a common biological base in their pathophysiology, common therapeutic tools could be investigated for the prevention and treatment of these disorders. As an example, antidepressants have been demonstrated to present neuroprotective and anti-inflammatory properties and to stimulate neurogenesis. In parallel, antioxidants that stimulate the antioxidant defense systems and interact with the monoaminergic system show an antidepressant-like activity. Further research on this topic could lead, in the near future, to the expansion of the therapeutic possibilities for the treatment of NOS-related disorders.

Sleep disorders and depression: brief review of the literature, case report, and nonpharmacologic interventions for depression.

Sleep disorders are so frequently associated with depression that, in the absence of sleep complaints, a diagnosis of depression should be made with caution. Insomnia, in particular, may occur in 60%-80% of depressed patients. Depressive symptoms are important risk factors for insomnia, and depression is considered an important comorbid condition in patients with chronic insomnia of any etiology. In addition, some drugs commonly prescribed for the treatment of depression may worsen insomnia and impair full recovery from the illness. The aim of this paper is to review briefly and discuss the following topics: common sleep disturbances during depression (in particular pavor nocturnus, nightmares, hypersomnia, and insomnia); circadian sleep disturbances; and treatment of depression by manipulation of the sleep-wake rhythm (chronotherapy, light therapy, cycles of sleep, and manipulation of the sleep-wake rhythm itself). Finally, we present a case report of a 65-year-old Caucasian woman suffering from insomnia associated with depression who was successfully treated with sleep deprivation.

Clinical features and imaging findings in a case of Capgras syndrome.

Capgras syndrome consists of the delusional belief that a person or persons have been replaced by doubles or impostors. It can occur in the context of both psychiatric and organic illness, and seems to be related to lesions of the bifrontal and right limbic and temporal regions. Indeed, magnetic resonance imaging has revealed brain lesions in patients suffering from Capgras syndrome. This case study reports the findings of a thorough diagnostic evaluation in a woman suffering from Capgras syndrome and presenting with the following clinical peculiarities: obsessive modality of presentation of the delusional ideation, intrusiveness of such ideation (that even disturbed her sleep), as well as a sense of alienation and utter disgust towards the double. These characteristics bring to mind the typical aspects of obsessive-compulsive disorder. Neuroanatomic investigation, through magnetic resonance imaging, performed on this patient showed alteration of the bilateral semioval centers, which are brain regions associated with the emotion of disgust and often show alterations in subjects suffering from obsessive-compulsive disorder. Hence, neuroimaging allows researchers to put forward the hypothesis of a common neuroanatomic basis for Capgras syndrome and obsessive-compulsive disorder, at least for cases in which the delusional ideation is associated with deep feelings of disgust and presents with a certain pervasiveness.

Effectiveness of lithium in subjects with treatment-resistant depression and suicide risk: a protocol for a randomised, independent, pragmatic, multicentre, parallel-group, superiority clinical trial.

BACKGROUND: Data on therapeutic interventions following deliberate self harm (DSH) in patients with treatment-resistant depression (TRD) are very scant and there is no unanimous consensus on the best pharmacological option for these patients. There is some evidence that lithium treatment might be effective in reducing the risk of completed suicide in adult patients with unipolar affective disorders, however no clear cut results have been found so far. The primary aim of the present study is to assess whether adding lithium to standard therapy is an effective treatment strategy to reduce the risk of suicidal behaviour in long term treatment of people with TRD and previous history of DSH. METHODS/DESIGN: We will carry out a randomised, parallel group, assessor-blinded superiority clinical trial. Adults with a diagnosis of major depression, an episode of DSH in the previous 12 months and inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode will be allocated to add lithium to current therapy (intervention arm) or not (control arm). Following randomisation, treatment is to be taken daily for 1 year unless some clear reason to stop develops. Suicide completion and acts of DSH during the 12 months of follow-up will constitute the composite primary outcome. To preserve outcome assessor blindness, an independent adjudicating committee, blind to treatment allocation, will anonymously review all outcome events. DISCUSSION: The results of this study should indicate whether lithium treatment is associated with lower risk of completed suicide and DSH in adult patients with treatment resistant unipolar depression, who recently attempted suicide. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00927550.

Psychomotor retardation and externally oriented thinking in major depression.

OBJECTIVE: To investigate possible correlations between the tendency towards alexithymia and the depressive state, globally and with regard to the Toronto Alexithymia scale (TAS-20) subscales and the Hamilton rating scale for depression (HAM-D) subscales. METHODS: 75 patients, suffering from Unipolar Depression, were assessed through the HAM-D and the TAS-20 and compared to the control group (n = 63). Both groups were divided into two subgroups (30-60 years old; 61-80 years old). Correlations between the tendency towards alexithymia and depressive symptoms, globally and with regard to the TAS-20 subscales and the HAM-D subscales, were investigated. RESULTS: WITH REGARD TO PATIENTS, A POSITIVE CORRELATION WAS FOUND BETWEEN: the HAM-D total score and the TAS-20 total score; the HAM-D factor V (psychomotor retardation) and the TAS-20 total score; the TAS-20 subscale III (externally oriented thinking) and the HAM-D total score. In addition a positive correlation between the HAM-D factor V and the TAS-20 subscales I and III was found and confirmed among females. In patients aged 30-60 years, the HAM-D factor V was correlated with all the TAS-20 subscales. As to the control group, a positive correlation was found between: the HAM-D factor I (anxiety/somatization) and the TAS-20 total score; the TAS-20 subscale I and the HAM-D total score; the HAM-D factor I and the TAS-20 subscale. The latter was confirmed in the control group aged 30-60 years. CONCLUSION: The link between alexithymia and affective symptoms has been confirmed in the patients and in the control group. An interesting data is the correlation between psychomotor retardation and externally oriented thinking among the patients. According to cognitive theories, psychomotor retardation could be related to feelings of incapacity perceived by an individual. A patient, with an externally oriented thinking, might run into a distorted perception of his own ability to function, thus causing a psychomotor "fattening".

Epidemiology and treatment of mood disorders in a day hospital setting from 1996 to 2007: an Italian study.

BACKGROUND: THE PRESENT STUDY AIMED: to assess prescribing patterns in the treatment of major depression, bipolar disorder type I, cyclothymia, and dysthymia from 1996 to 2007 in a day hospital setting; to evaluate the prevalence of the above-mentioned mood disorders and gender distribution; and to relate familiality, comorbidity, and marital status to each diagnosis. METHODS: Medical records for 777 day hospital patients with a diagnosis of major depression, bipolar disorder type I, cyclothymia, or dysthymia were grouped into two 6-year periods so as to compare the prescribing patterns of tricyclic antidepressants, selective serotonin reuptake inhibitors, noradrenergic reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, noradrenergic and specific serotonergic antidepressants, first-generation antipsychotics, second-generation antipsychotics, and mood stabilizers. Gender, prevalence, familiality, comorbidity, and marital status were related to each diagnosis. RESULTS: The most common mood disorder, with a female preponderance, was major depression, regardless of marital status. High percentages of familiality and comorbidity were found for major depression, while a reduction was found in the utilization of tricyclic antidepressants. There was no statistically significant difference in rates of prescription of selective serotonin reuptake inhibitors and noradrenergic reuptake inhibitors, but some irregularities were found upon evaluating each diagnosis (eg, increased utilization of these agents in dysthymia and major depression, respectively). There was an increase in prescriptions for serotonin and norepinephrine reuptake inhibitors, but no marked differences in utilization of noradrenergic and specific serotonergic antidepressants, which remained basically low. There was no significant difference in prescribing of first-generation antipsychotic agents, although a reduction was found. There was a significant increase in utilization of second-generation antipsychotics and mood stabilizers. CONCLUSION: Our epidemiological findings are consistent with data reported in the literature regarding the high prevalence of major depression among the mood disorders, as well as the impact of familiality and comorbidity. Analysis of prescribing patterns for antidepressants, antipsychotics, and mood stabilizers in the treatment of mood disorders shows a shift from older to newer drugs, and wider use of mood stabilizers.

Haloperidol augmentation of fluvoxamine in skin picking disorder: a case report.

INTRODUCTION: Compulsive skin picking, being part of the broader category of impulse control disorders, is considered a residual diagnosis in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. It is characterized by excessive scratching or picking of normal skin, or skin with minor surface irregularities, and occurs in 2% of patients attending dermatology clinics. Despite the clinical relevance of this disorder, no clear guidelines are available yet; clinical management is, therefore, compromised and the day-to-day clinical practice is burdened by difficulties. Studies on selective serotonin reuptake inhibitors and anti-epileptic drugs have provided limited results. The association between anti-depressants and anti-epileptics has been found to be beneficial in some impulse control disorders, but in skin picking no previous studies have been conducted on this pharmacological approach. There are very few reports on the efficacy of anti-psychotics in skin picking. CASE PRESENTATION: The therapeutic path described in this case report produced good results for a 59-year-old Caucasian woman. The first therapeutic approach, with fluvoxamine and oxcarbazepine was partially effective; then, the suspension of oxcarbazepine and haloperidol augmentation of fluvoxamine were adopted. After 10 weeks, a significant improvement of the disease was observed: the clinical picture and the associated symptoms were nearly solved. CONCLUSIONS: To the best of our knowledge, this is the first article reporting the association of fluvoxamine and haloperidol in skin picking disorder. It might be useful to perform further research regarding the treatment of skin picking disorder: in clinical practice, several variables might limit the choice of certain drugs. Therefore, it would be useful for the clinician to be aware of other therapeutic options.

Bupropion versus sertraline in the treatment of depressive patients with binge eating disorder: retrospective cohort study.

This study sought to compare Bupropion versus Sertraline in the treatment of depressed patients with Binge Eating Disorder (BED) prescribed off-label. Medical records of outpatients with diagnosis of BED and Depression (DSM-IV-TR criteria) were selected: 15 patients were treated with bupropion 150 mg/per day, and 15 with sertraline 200 mg/per day. During the screening and control visits (2°-6°-14°-24° week), the selected patients were first weighed and then evaluated using the following questionnaires: Binge Eating Disorder-Clinical Interview (BEDCI), Beck Depression Inventory (BDI), State-Trait Anxiety Inventory X (STAI-X) and Arizona Sexual Experience Scale (ASEX). Both drugs reduced anxious-depressive symptoms and binge frequency: Bupropion showed a better effectiveness in reducing weight and improving sexual performances; weight loss related to it was proportional to the body mass index. Bupropion may be associated with more weight loss in BED, depressed patients than sertraline.

Borderline personality disorder and depression: an update.

To review the literature related to recent temperamental and biological findings on borderline personality disorder (BPD) and major depression, the close link between the two disorders, and the latest therapeutical findings on BPD, focusing on the conditions of co-morbidity between depression and BPD. The National Institutes of Health's PubMed database was used to identify indexed studies on BPD, depression and the co-morbidity between the two. Only studies published between 2000 and 2011 were assessed. Similar temperamental features have been demonstrated in BPD and depression. The strong link between the two disorders seems to be widely recognized by scientific community. Psychotherapy and new antipsychotics are the topics of current major interest of research. The therapeutic targets in the case of co-morbidity are BPD features associated with depressive symptoms, thus influencing prognosis. A global assessment is, in fact, fundamental for a successful therapy for the treatment of the several aspects of a complex psychopathological phenomenon.

Autonomic nervous system and lipid metabolism: findings in anxious-depressive spectrum and eating disorders.

OBJECTIVE: To correlate lipid metabolism and autonomic dysfunction with anxious-depressive spectrum and eating disorders. To propose the lipid index (LI) as a new possible biomarker. METHODS: 95 patients and 60 controls were enrolled from the University Psychiatry Unit of Catania and from general practitioners (GPs). The patients were divided into four pathological groups: Anxiety, Depression, Anxious-Depressive Disorder and Eating Disorders [Diagnostic and Statistical Manual of Mental Disorders Fourth Edition Text Revision (DSM-IV-TR) official/appendix criteria]. The levels of the cholesterol, triglycerides and apolipoproteins A and B were determined. The LI, for each subject, was obtained through a mathematical operation on the values of the cholesterol and triglycerides levels compared with the maximum cut-off of the general population. The autonomic functioning was tested with Ewing battery tests. Particularly, the correlation between heart rate variability (HRV) and lipid metabolism has been investigated. RESULTS: Pathological and control groups, compared among each other, presented some peculiarities in the lipid metabolism and the autonomic dysfunction scores. In addition, a statistically significant correlation has been found between HRV and lipid metabolism. CONCLUSIONS: Lipid metabolism and autonomic functioning seem to be related to the discussed psychiatric disorders. LI, in addition, could represent a new possible biomarker to be considered.