Long-Acting Injectable (LAI) Aripiprazole Formulations in the Treatment of Schizophrenia and Bipolar Disorder: a Systematic Review.

BACKGROUND: Several second-generation antipsychotics (SGAs) are available in long-acting injectable (LAI) formulations. OBJECTIVE: To systematically review the effects of the two formulations, Monohydrate and Lauroxil, of Aripiprazole LAI in patients with schizophrenia and bipolar disorder during an acute episode or during maintenance treatment. METHODS: On September 18, 2018, we adopted the following search strategy: (aripiprazole OR OPC-14597 OR Abilify) AND (long-acting OR depot OR LAI OR once monthly OR prolonged release OR monohydrate OR lauroxil) on PubMed, Cochrane, Scopus, CINAHL, PsycINFO, and Web of Science to identify randomised controlled trials. Furthermore, we searched the ClinicalTrials.gov site for possible additional studies. RESULTS: We included 28 papers dealing with randomised assignment of aripiprazole LAI formulations in schizophrenia and bipolar disorder in survival studies after stabilisation, in acute studies, and in head-to-head comparisons. Both monohydrate and lauroxil formulations reduced relapses/recurrences with respect to comparators (placebo or 50 mg once-monthly monohydrate) and improved symptomatology in acute schizophrenia. LIMITATIONS: Only a small number of studies were included in our review, with widely overlapping samples. While a high proportion of studies were wholly or partly industry-sponsored, their outcomes do not appear to have been affected. CONCLUSION: Aripiprazole LAI may to be efficacious in reducing relapse of schizophrenia and bipolar disorder in the long term in stabilised patients and in improving symptoms of schizophrenia during its acute phase, with both monohydrate and lauroxil formulations showing efficacy.

Aripiprazole Long-Acting Injection During First Episode Schizophrenia-An Exploratory Analysis.

Background: Long-acting injectable (LAI) aripiprazole was found to be efficacious in schizophrenia. In common clinical practice, the use of LAIs is often restricted to chronic patients with frequent relapses and poor adherence. Recently, some investigators advanced the idea of early LAI use also in young people with schizophrenia at their first psychotic episode (FEP). Objective: Our study aimed to assess the effect of LAI aripiprazole once monthly (AOM) in the treatment of FEP in patients aged 18-26 years. Methods: We included 50 patients with DSM-5 schizophrenia as assessed with SCID, and used the Clinical Global Impressions Scale-Severity of Illness (CGI-S) and the Positive and Negative Syndrome Scale (PANSS) to assess symptom severity and the World Health Organization Quality of Life (WHOQOL), the Short Form Health Survey (SF-36) and the Personal and Social Performance Scale (PSP) to assess quality of life (QoL) and global health perception at baseline and 3, 6, 9, and 12 months after the first AOM injection. Results: AOM was associated with a progressive improvement, compared to baseline, of both positive (p < 0.001) and negative (p < 0.001) symptoms and in general psychopathology (p < 0.001) and decrease in global severity (p < 0.001). We also observed progressive improvement in QoL and social and personal functioning. Treatment adherence was 78% at study endpoint. Our results support that AOM may improve psychotic symptoms, QoL and social functioning in young FEP patients. Further studies should compare AOM to its oral formulation in the treatment of young patients with schizophrenia at the outset of their illness.

Suicide risk in attention-deficit/hyperactivity disorder.

BACKGROUND: ADHD (Attention-deficit/hyperactivity disorder) is a common neurodevelopmental disorder that manifests itself during childhood with various combinations of symptoms, including inattention, hyperactivity and impulsivity. Research has shown that psychiatric comorbidities play an important role in the development of suicidal behavior and, recently, there has been a growing interest in a possible association between ADHD and suicide during both childhood and adulthood. Furthermore, some authors have shown a relationship between pharmacological treatments and suicide in patients affected by ADHD. AIMS: We conducted a selective review of current literature to explore the factors which contribute to suicidal behavior and self-harm in those with ADHD. METHODS: We performed a PubMed/MEDLINE, Scopus, PsycLit, and PsycINFO search to identify all articles and book chapters on the topic up to 2017. RESULTS: Several studies have showed that ADHD may be correlated with an increased suicide ideation and attempts. CONCLUSIONS: Although differences in studies design and samples made the results difficult to compare and interpret, many studies indicate an association between ADHD and suicidal behavior. It remains controversial whether there is a direct relationship or whether the association depends on the increased prevalence of pre-existing comorbid conditions and individual and family dysfunctional factors.

Unmet Needs in Schizophrenia.

BACKGROUND: Schizophrenia is a complex psychiatric disorder that represents a challenge for all clinicians. Although treatment must address both positive and negative symptoms, several authors have reported the importance of managing unmet needs among patients with schizophrenia. Unmet needs in schizophrenia include difficulties at various clinical, psychosocial, relational, economic, and occupational levels. An important unmet need is represented by insight into the illness that is associated with treatment adherence and compliance with medical prescriptions. CONCLUSION: In order to improve our understanding and management of schizophrenia, it is critically important to address the complexity of needs among patients with schizophrenia.

Arsenic: Association of regional concentrations in drinking water with suicide and natural causes of death in Italy.

Arsenic, as a toxin, may be associated with higher mortality rates, although its relationship to suicide is not clear. Given this uncertainty, we evaluated associations between local arsenic concentrations in tapwater and mortality in regions of Italy, to test the hypothesis that both natural-cause and suicide death rates would be higher with greater trace concentrations of arsenic. Arsenic concentrations in drinking-water samples from 145 sites were assayed by mass spectrometry, and correlated with local rates of mortality due to suicide and natural causes between 1980 and 2011, using weighted, least-squares univariate and multivariate regression modeling. Arsenic concentrations averaged 0.969 (CI: 0.543-1.396) µg/L, well below an accepted safe maximum of 10µg/L. Arsenic levels were negatively associated with corresponding suicide rates, consistently among both men and women in all three study-decades, whereas mortality from natural causes increased with arsenic levels. Contrary to an hypothesized greater risk of suicide with higher concentrations of arsenic, we found a negative association, suggesting a possible protective effect, whereas mortality from natural causes was increased, in accord with known toxic effects of arsenic. The unexpected inverse association between arsenic and suicide requires further study.

Suicide in stroke survivors: epidemiology and prevention.

Stroke is a dramatic event and is associated with potentially severe consequences, including disability, mortality, and social costs. Stroke may occur at any age; however, most strokes occur in individuals aged 65 years and older. Previous research has found that stroke increases suicide risk, especially among women and younger patients. The aim of the current review is to investigate the relationship between suicide and stroke in order to determine which stroke patients are at elevated risk for suicide. Moreover, we review the literature in order to provide pharmacological treatment strategies for stroke patients at high risk of suicide. We performed a careful search to identify articles and book chapters focused on this issue, selecting only English-language articles published from 1990 to 2014 that addressed the issue of suicide after stroke and its pharmacological management. We found 12 clinical trials that explored the relationship between stroke and suicidal ideation and/or suicidal plans and 11 investigating suicide as the cause of death after stroke. We identified stroke as a significant risk factor for both suicide and suicidal ideation, especially among younger adult depressed patients in all articles, providing further support for the association between post-stroke and suicidality. Suicide risk is particularly high in the first 5 years following stroke. Depression, previous mood disorder, prior history of stroke, and cognitive impairment were found to be the most important risk factors for suicide. Selective serotonin reuptake inhibitors (SSRIs) represent the treatment of choice for stroke survivors with suicide risk, and studies in rats have suggested that carbolithium is a promising treatment in these patients. Early identification and treatment of post-stroke depression may significantly reduce suicide risk in stroke patients.

Electroconvulsive treatment during pregnancy: a systematic review.

Pharmacological treatment of severe psychiatric disorders during pregnancy is complicated by the potential harmful effects of treatment for the fetus. Electroconvulsive therapy (ECT) has been demonstrated to be effective for the treatment of several mental disorders. The aim of this study was to investigate the safety of ECT in the treatment of psychiatric disorders during pregnancy; to compare its efficacy with medication; and to identify the main indications for use in pregnancy. We performed a careful and systematic review of the literature on ECT and pregnancy was conducted. Almost all patients demonstrated total or at least partial remission of symptoms after ECT treatment. No deaths were reported in ECT-treated pregnant women. We conclude that ECT is probably currently under-used in many psychiatric settings because of its stigmatized perception by patients and by mental health professionals. ECT seems to be effective for treating major psychiatric disorders during pregnancy, and the risks of adverse events are low.

Car accidents as a method of suicide: a comprehensive overview.

The research literature provides evidence on the possible link between single-car accident drivers and suicidal intent, and some scholars have stressed the role of unconscious suicidal motivations in some single-car accidents. This paper review relevant literature on the topic and sheds light on neglected factors that may play a central role in reducing the number of deaths due to car accidents. We performed careful PubMed, and PsycInfo searches to identify all papers and book chapters in English during the period 1955-2011. Our overview of the literature indicates that above 2% of the traffic accidents are suicide behaviors. However, the phenomenon may be underreported, considering that suicides by car accidents may be reported as accidental in the national statistics. On the other hand, the association between accident-pronesses and unconscious self-destructive impulses is an issue that is difficult to solve.

How does subjective experience of pain relate to psychopathology among psychiatric patients?

OBJECTIVE: The study aimed to investigate to what extent general psychopathology is associated with subjective experience of pain in psychiatric outpatients without comorbidity with severe physical diagnosis and whether there are any differences in the experience of pain between genders or diagnoses. METHOD: Participants were 575 consecutive outpatients affected by mood disorder or anxiety disorder. Patients completed the West Haven-Yale Multidimensional Pain Inventory (WHYMPI) and the Symptom Checklist 90-Revised. RESULTS: Women had higher mean scores on the Global Severity Index (1.52±0.76 vs. 1.33±0.79), higher perception of negative responses from others (1.84±1.59 vs. 1.46±1.35) and higher perception of pain severity (3.31±1.73 vs. 2.88±1.63) than men. They also reported higher mean scores on the WHYMPI's General Activity (2.14±0.98 vs. 1.93±0.95) and Household Chores (3.64±1.75 vs. 2.27±1.58) and lower mean scores on the Outdoor Work (1.24±1.26 vs. 1.87±1.51) dimension than men. Higher pain severity, more negative responses from others and higher household chores are predictors of higher psychopathology, while the general level of activity may be considered as a protective factor. CONCLUSIONS: Pain and its subjective experience play a central role in psychiatric disorders, and it is a great burden for patients and caregivers. Clinicians should pay more attention to recognize and adequately treat painful symptoms in patients with anxiety and depressive disorder.

The role of microRNAs in synaptic plasticity, major affective disorders and suicidal behavior.

Major affective disorders are common widespread conditions associated with multiple psychosocial impairments and suicidal risk in the general population. At least 3-4% of all depressive individuals die by suicide. At a molecular level, affective disorders and suicidal behavior are recently associated with disturbances in structural and synaptic plasticity. A recent hypothesis suggested that small non-coding RNAs (ncRNAs), in particular microRNAs (miRNAs), play a critical role in the translational regulation at the synapse. We performed a selective overview of the current literature on miRNAs putative subcellular localization and sites of action in mature neurons analyzing their role in neurogenesis, synaptic plasticity, pathological stress changes, major affective disorders and suicidal behavior. miRNAs have played a fundamental role in the evolution of brain functions. The perturbation of some intracellular mechanisms as well as impaired assembly, localization, and translational regulation of specific RNA binding proteins may affect learning and memory, presumably contributing to the pathogenesis of major affective disorders and perhaps suicidal behavior. Also, miRNA dys-regulation has also been linked to several neuropsychiatric diseases. However, further evidence are needed in order to directly clarify the role of miRNAs in major affective disorders and suicidal behavior.

Unmet treatment needs in schizophrenia patients: is asenapine a potential therapeutic option?

Adverse metabolic events, such as increased adiposity, hyperglycemia, diabetes mellitus and dyslipidemia, have been associated with treatment using atypical antipsychotic medications. However, the complexity of some of the reports on this problem and marketing efforts in this area may make it difficult for psychiatrists to remain fully and accurately informed about the metabolic complications of atypical antipsychotic therapy. Little is currently known about how psychiatrists view what they have read or heard, how they perceive the available information and how this affects their management of patients with schizophrenia. A number of studies have demonstrated that nonadherence to the medication regimen in schizophrenia is associated with poor symptomatic outcome, increased risk of relapse, more frequent use of compulsory treatment and increased risk of suicide and severe self-harm. Suicide is a major cause of death among schizophrenic patients, and their attitude toward medication can make the difference between a proper therapeutic regimen that protects patients from suicide risk versus discontinuation of treatments that are associated with disabling symptoms, some of which are risk factors for suicide. We review the characteristics of a new drug, asenapine, that may improve adherence in patients as a result of a distinctive receptor profile that may be associated with fewer side effects than other second-generation antipsychotic drugs.

Glycosides, depression and suicidal behaviour: the role of glycoside-linked proteins.

Nowadays depression and suicide are two of the most important worldwide public health problems. Although their specific molecular mechanisms are still largely unknown, glycosides can play a fundamental role in their pathogenesis. These molecules act presumably through the up-regulation of plasticity-related proteins: probably they can have a presynaptic facilitatory effect, through the activation of several intracellular signaling pathways that include molecules like protein kinase A, Rap-1, cAMP, cADPR and G proteins. These proteins take part in a myriad of brain functions such as cell survival and synaptic plasticity. In depressed suicide victims, it has been found that their activity is strongly decreased, primarily in hippocampus and prefrontal cortex. These studies suggest that glycosides can regulate neuroprotection through Rap-1 and other molecules, and may play a crucial role in the pathophysiology of depression and suicide.

Antidepressants and Suicide Risk: A Comprehensive Overview.

The annual worldwide suicide rate currently averages approximately 13 per 100,000 individuals per year (0.013% per year), with higher average rates for men than for women in all but a few countries, very low rates in children, and relatively high rates in elderly men. Suicide rates vary markedly between countries, reflecting in part differences in case-identification and reporting procedures. Rates of attempted suicide in the general population average 20-30 times higher than rates of completed suicide, but are probably under-reported. Research on the relationship between pharmacotherapy and suicidal behavior was rare until a decade ago. Most ecological studies and large clinical studies have found that a general reduction in suicide rates is significantly correlated with higher rates of prescribing modern antidepressants. However, ecological, cohort and case-control studies and data from brief, randomized, controlled trials in patients with acute affective disorders have found increases, particularly in young patients and particularly for the risk of suicide attempts, as well as increases in suicidal ideation in young patients. whether antidepressants are associated with specific aspects of suicidality (e.g., higher rates of completed suicide, attempted suicide and suicidal ideation) in younger patients with major affective disorders remains a highly controversial question. In light of this gap this paper analyzes research on the relationship between suicidality and antidepressant treatment.