Methylphenidate for attention-deficit/hyperactivity disorder in adults: a narrative review.

RATIONALE: Psychostimulants, including methylphenidate (MPH), are the mainstay of pharmacotherapy for attention-deficit/hyperactivity disorder (ADHD) in adults. Even though MPH is the most commonly used medication for ADHD these days, there are relatively few resources available that provide comprehensive insight into the pharmacological and clinical features of the compound. OBJECTIVE: The aim of this paper is to provide an up-to-date outline of the pharmacology and clinical utility of MPH for ADHD in adult patients. METHODS: While conducting the narrative review, we applied structured search strategies covering the two major online databases (MEDLINE and Cochrane Central Register of Controlled Trials). In addition, we performed handsearching of reference lists of relevant papers. RESULTS: Methylphenidate exhibits multimodal mechanism of action, working primarily as a dopamine and noradrenaline reuptake inhibitor. It also protects the dopaminergic system against the ongoing 'wearing off' (by securing a substantial reserve pool of the neurotransmitter, stored in the presynaptic vesicles). In placebo-controlled trials, MPH was shown to be moderately effective both against the core ADHD symptoms (standardized mean difference [SMD], 0.49; 95% confidence interval [CI], 0.35-0.64), and the accompanying emotion regulation deficits (SMD, 0.34; 95% CI, 0.23-0.45). The most common adverse events related to long-term treatment with MPH are decreased appetite (~ 20%), dry mouth (15%), heart palpitations (13%), gastrointestinal infections (~ 10%), and agitation/feeling restless (~ 10%). CONCLUSIONS: There is substantial body of evidence to suggest that MPH is an effective and safe treatment option for adults with ADHD.

A systematic review of how patients value COPD outcomes.

Our objective was to summarise systematically all research evidence related to how patients value outcomes in chronic obstructive pulmonary disease (COPD).We conducted a systematic review (systematic review registration number CRD42015015206) by searching PubMed, Embase, PsycInfo and CINAHL, and included reports that assessed the relative importance of outcomes from COPD patients' perspective. Two authors independently determined the eligibility of studies, abstracted the eligible studies and assessed risk of bias. We narratively summarised eligible studies, meta-analysed utilities for individual outcomes and assessed the certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluations approach.We included 217 quantitative studies. Investigators most commonly used utility measurements of outcomes (n=136), discrete choice exercises (n=13), probability trade-off (n=4) and forced choice techniques (n=46). Patients rated adverse events as important but on average, less so than symptom relief. Exacerbation and hospitalisation due to exacerbation are the outcomes that COPD patients rate as most important. This systematic review provides a comprehensive registry of related studies.

Risk and surrogate benefit for pediatric Phase I trials in oncology: A systematic review with meta-analysis.

BACKGROUND: Pediatric Phase I cancer trials are critical for establishing the safety and dosing of anti-cancer treatments in children. Their implementation, however, must contend with the rarity of many pediatric cancers and limits on allowable risk in minors. The aim of this study is to describe the risk and benefit for pediatric cancer Phase I trials. METHODS AND FINDINGS: Our protocol was prospectively registered in PROSPERO (CRD42015015961). We systematically searched Embase and PubMed for solid and hematological malignancy Phase I pediatric trials published between 1 January 2004 and 1 March 2015. We included pediatric cancer Phase I studies, defined as "small sample size, non­randomized, dose escalation studies that defined the recommended dose for subsequent study of a new drug in each schedule tested." We measured risk using grade 3, 4, and 5 (fatal) drug-related adverse events (AEs) and benefit using objective response rates. When possible, data were meta-analyzed. We identified 170 studies meeting our eligibility criteria, accounting for 4,604 patients. The pooled overall objective response rate was 10.29% (95% CI 8.33% to 12.25%), and was lower in solid tumors, 3.17% (95% CI 2.62% to 3.72%), compared with hematological malignancies, 27.90% (95% CI 20.53% to 35.27%); p < 0.001. The overall fatal (grade 5) AE rate was 2.09% (95% CI 1.45% to 2.72%). Across the 4,604 evaluated patients, there were 4,675 grade 3 and 4 drug-related AEs, with an average grade 3/4 AE rate per person equal to 1.32. Our study had the following limitations: trials included in our review were heterogeneous (to minimize heterogeneity, we separated types of therapy and cancer types), and we relied on published data only and encountered challenges with the quality of reporting. CONCLUSIONS: Our meta-analysis suggests that, on the whole, AE and response rates in pediatric Phase I trials are similar to those in adult Phase I trials. Our findings provide an empirical basis for the refinement and review of pediatric Phase I trials, and for communication about their risk and benefit.

Vortioxetine: A review of the pharmacology and clinical profile of the novel antidepressant.

The aim of this paper was to review the up-to-date evidence base on pharmacology and clinical properties of vortioxetine. Vortioxetine is a novel antidepressant, approved by the US Food and Drug Administration (FDA) for the treatment of major depressive disorder (MDD). Because vortioxetine exhibits both an antidepressant and anxiolytic effect, it may be effective in treating both depressive and anxiety disorders, such as generalized anxiety disorder (GAD). Based on its pharmacodynamics profile and preclinical studies, it is believe that the drug's clinical action is mediated mainly by selective blockade of serotonin reuptake (by inhibiting the serotonin transporter [SERT]) and direct modulation of 5-HT receptors activity (such as 5-HT3, 5-HT7, 5-HT1D and 5-HT1B). In patients with MDD the recommended doses range is 5-20mg/day. Vortioxetine was shown to be more effective than placebo both in MDD and GAD. In terms of side effects, nausea, vomiting, diarrhea, and dry mouth were most commonly observed in individuals receiving vortioxetine. In direct comparison to duloxetine, vortioxetine is found to have a smaller efficacy but had a lower risk of developing the common antidepressant-induced adverse effects.

Postpartum depression: bipolar or unipolar? Analysis of 434 Polish postpartum women.

Objective: To assess the prevalence of soft bipolar features in a sample of women with postpartum depressive symptoms, as well as to compare the sociodemographic and obstetric characteristics of subjects with bipolar or unipolar postpartum depressive symptomatology. Methods: Four hundred and thirty-four participants were enrolled in this cross-sectional study. Postpartum depression (PPD) symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS), while the Mood Disorder Questionnaire (MDQ) was used to screen for bipolarity features. Results: Of the 434 participants, 66 (15.2%) scored ≥ 13 points on the EPDS, thus fulfilling the screening criteria, and 103 scored ≥ 7 points on the MDQ. In comparison with non-depressed subjects, the women who scored positively on the EPDS were significantly more likely to exhibit symptoms of bipolar spectrum disorders (38 vs. 21%; chi-square test, p = 0.015). Women with bipolar PPD symptomatology were significantly younger than those exhibiting unipolar PPD symptoms (31.0±4.8 years vs. 28.5±4.1 years; t-test, p = 0.03). The groups did not differ in terms of obstetric characteristics. Conclusion: Our findings suggest that patients with PPD symptomatology may be more likely to exhibit soft bipolarity features as compared with non-depressed women.

Lurasidone: The 2016 update on the pharmacology, efficacy and safety profile.

The aim of this paper was to review the up-to-date evidence base on pharmacology and clinical properties of lurasidone. Lurasidone is an atypical antipsychotic, approved by the US Food and Drug Administration (FDA) for the treatment of schizophrenia and bipolar depression. Lurasidone exhibits both an antipsychotic and antidepressant action. Based on its pharmacodynamics profile, it is believed that the drug's clinical action is mediated mainly through the D2, 5-HT2A and 5-HT7 receptors inhibition. In patients with schizophrenia the recommended dose range is 40-80mg/day. In bipolar depression broader dosage ranges (20-120mg/day) were found to be effective. In terms of side effects, higher rates of akathisia, parkinsonism and hyperprolactinemia were observed in individuals receiving lurasidone (as compared to patients treated with other atypical antipsychotics). On the other hand, treatment with lurasidone yields relatively lower risk for developing sedation or overweight/obesity.

A web-based study of bipolarity and impulsivity in athletes engaging in extreme and high-risk sports.

BACKGROUND: We hypothesised that men and women who engage in extreme or high-risk sports would score higher on standardised measures of bipolarity and impulsivity compared to age and gender matched controls. METHODS: Four-hundred and eighty extreme or high-risk athletes (255 males and 225 females) and 235 age-matched control persons (107 males and 128 females) were enrolled into the web-based case-control study. The Mood Disorder Questionnaire (MDQ) and Barratt Impulsiveness Scale (BIS-11) were administered to screen for bipolarity and impulsive behaviours, respectively. RESULTS: Results indicated that extreme or high-risk athletes had significantly higher scores of bipolarity and impulsivity, and lower scores on cognitive complexity of the BIS-11, compared to controls. Further, there were positive correlations between the MDQ and BIS-11 scores. CONCLUSION: These results showed greater rates of bipolarity and impulsivity, in the extreme or high-risk athletes, suggesting these measures are sensitive to high-risk behaviours.

Bipolar spectrum features in obese individuals.

UNLABELLED: AIM : The relationships between obesity and bipolar spectrum disorders (BSD) are unclear. Thus, the aim of our study were to approximate the prevalence of soft bipolar features in patients seeking treatment for obesity. METHODS: We performed a nested case-control study (cases: 90 patients with the mean BMI=38.1±7.0 [range: 30.1-62.5]; controls: 70 healthy volunteers with the mean BMI=21.6±2.1 [range: 18.5-24.9]). The participants were screened for the BSD symptoms with the Mood Disorder Questionnaire. RESULTS: Patients with obesity were significantly more likely to score ≥7 pts. on the MDQ 25.6% vs. 8.6%; p=0.01). In comparison to non-obese individuals, the obese patients scored significantly higher in MDQ section I and on the MDQ items referring to the 'irritability-racing thoughts' dimension of hypomania. The multiple logistic regression analysis revealed that obesity had been significantly related to the odds of obtaining ≥7 pts. on the MDQ section 1 (odds ratio [OR] = 2.07; 95% confidence interval [CI]: 1.17-3.63), and marginally significantly related to experiencing periods of 'ups' and 'downs'(OR = 1.67; 95% CI: 1.00-2.81). CONCLUSIONS: Our study adds to previous suggestions that obesity may be significantly related to the BSD. However, the clinical implications of this finding need to be determined in further studies, performed in accordance with the paradigm of evidence based medicine (EBM).

[The place of quetiapine extended release in the treatment of mental disorders]. / Miejsce kwetiapiny o przedluzonym uwalnianiu w terapii osób z zaburzeniami psychicznymi.

This article presents a summary of available data on the use of quetiapine extended release (QUE-XR). QUE-XR is an example of an atypical antipsychotic drug that can be used in a single dose, thereby simplifying the treatment regimen. From the therapeutic standpoint, this issue is of paramount importance, since approximately 50% of patients have adherence issues. Therefore, availability of the drug which is comfortable in administration can significantly improve treatment outcomes. Due to its antipsychotic, antidepressive, mood stabilizing and anxiolytic efficacy, QUE-XR seems to be a promising drug with potentially broad spectrum of indications (in patients with schizophrenia, bipolar disorder, major depression and some anxiety disorders - both in the acute phase of treatment, and the maintenance treatment). Notably, QUE-XR seems to ameliorate sleep disturbances, and it may also improve patients' quality of life (as suggested by some studies). Due to the simple dosing regimen of QUE-XR, conducting therapy with this drug may contribute to the improvement of compliance. Yet, the primary clinical criterion for selection of the type of formulation of quetiapine should be the individual preferences of the patient, and the knowledge and experience of the treating physician.

Temperamental dimensions of the TEMPS-A in male and female subjects engaging in extreme or/and high risk sports.

OBJECTIVES: We investigated temperamental dimensions of the Temperament Evaluation of Memphis, Pisa and San Diego Autoquestionnaire (TEMPS-A) as well as bipolarity features in male and female subjects engaging in extreme or/and high risk sports. METHODS: The web-based case-control study was performed in 480 subjects engaging in extreme or/and high risk sports (255 male, 225 female) aged 26 ± 6 years and in 235 age- and sex-matched healthy controls subjects (107 male, 128 female), aged 28 + 9 years. The TEMPS-A questionnaire, 110 questions version, has been used, evaluating five temperament domains: depressive, cyclothymic, hyperthymic, irritable and anxious. The Mood Disorder Questionnaire (MDQ) was employed for the assessment of bipolarity. RESULTS: Both male and female athletes had significantly higher scores of hyperthymic temperaments compared with control male and female subjects who had declared themselves as not involved into the activities of extreme or/and high risk sports. In addition, compared with controls, male sportsmen had lower scores of depressive and anxious temperaments, and female athletes had higher scores of cyclothymic and irritable temperaments. Both male and female athletes obtained significantly higher scores of bipolarity as measured by the MDQ, than control men and women. LIMITATIONS: Web-based study involving a risk of selection and recall bias, problematic homogeneity of the experimental group. CONCLUSIONS: Subjects engaged into extreme or/and high risk sports have significantly higher scores of hyperthymic temperament, measured by the TEMPS-A and present sex-specific features of other temperaments. Such subjects obtain also greater bipolarity scores as measured by the MDQ.

[Spousal burden in partners of patients with major depressive disorder and bipolar disorder]. / Brzemie malzonków osób chorujacych na depresje nawracajaca lub chorobe afektywna dwubiegunowaq.

OBJECTIVE: The objective of this study was to investigate the relationship between the burden level of spouses of patients in the symptomatic remission state of the major depressive disorder (MDD; 60 patients) or bipolar disorder (BD; 65 patients) and coping styles. METHODS: The Involvement Evaluation Questionnaire was used to assess the burden magnitude. Coping styles were evaluated by the Coping Inventory for Stressful Situation. Information concerning patients' clinical histories, a marriages characteristics and sociodemographic data were obtained from a structured clinical interview. RESULTS: There were significant levels of the perceived burden in spouses of patients with either BD or MDD. In both groups the burden level was significantly higher for spouses with worse appraisal of the marital adjustment and functioning. A positive correlation between higher perceived level of burden and emotion-focused coping style was found in both groups. For the problem-oriented coping style a negative correlation with the perceived burden level was found in the BD group only. The quality of'current sexual satisfaction' was significantly lower among the spouses of BD patients. The sense of illness-driven deterioration of the quality of their sexual lives implied higher level of total and objective burden of spouses in the MDD sample. This was not the case among the spouses of patients diagnosed with BD. CONCLUSIONS: Spouses of patients with affective disorders should be offered with opportunities of training in more effective methods of coping (including problem-solving methods) with an illness of a family member, in order to decrease the level of burden.

Postpartum depression: identifying associations with bipolarity and personality traits. Preliminary results from a cross-sectional study in Poland.

The goals of this study have been to determine the prevalence of the bipolar spectrum features in the population of women with postpartum depression (PPD) symptoms, as well as to analyze the personality differences between putative 'unipolar' and 'bipolar' PPD subjects. The sample enrolled into the cross-sectional study consisted of 344 women at 6-12 weeks postpartum. The authors used the Edinburgh Postnatal Depression Scale (EPDS; cut-off score: 13 pts.) for the assessment of the PPD symptoms, the Mood Disorder Questionnaire (MDQ; cut-off scores: 7 or 8 pts.) for diagnosing the bipolar features, and the NEO-Five Factor Inventory (NEO-FFI) for the assessment of personality traits. The EPDS-positive subjects were more likely to score positively on the MDQ, as compared to the EPDS-negative ones. The EPDS-positive subjects who also scored ≥8 pts. on the MDQ were characterized by higher index of neuroticism, as compared to those who scored positively on the EPDS only. The results suggest that the presence of PPD symptoms is related to significantly higher scores of bipolarity and neuroticism. The more robust trait of neuroticism might be a marker of the 'bipolar' PPD, as compared to the 'unipolar' form of the disorder.

Diagnostic conversions from major depressive disorder into bipolar disorder in an outpatient setting: results of a retrospective chart review.

BACKGROUND: The aim of the study was to check the stability of a diagnosis of major depressive disorder (MDD) in an outpatient setting, as well as to assess the scope of diagnostic conversions into bipolar disorder (BD). METHODS: Retrospective chart review of 122 patients with a primary diagnosis of MDD. RESULTS: Diagnostic conversion from MDD into BD was noticed in 40 subjects (32.8%), 25 patients (20.5%) were treatment-resistant. Mean time to the conversion was 9.27±8.64 years. A negative correlation between the age of illness onset and time to diagnostic conversion was observed (-0.41; p<0.05). Earlier onset of MDD was associated with higher risk of diagnostic conversion (<30vs≥30 years of age at onset: 69% vs 28%, p=0.0001; <35vs≥35 years of age: 50% vs 25%, p=0.0065). Treatment-resistance was more prevalent in the BD conversion group (40% vs 11%; p=0.0002). Diagnostic conversion into BD was also related longer duration of treatment received, higher number of illness episodes, and higher number of hospitalizations. LIMITATIONS: Retrospective design of the study. CONCLUSIONS: The problem of diagnosis evolution from MDD to BD was observed in about 1/3 of patients, and was associated with treatment-resistance of depression, earlier onset of depression, longer time of treatment, higher number of depressive episodes and hospitalizations. The variables above may be a useful predictor of bipolar diathesis.

[The affective disorder-related burden imposed on the family environment--an overview]. / Brzemie rodziny chorych z zaburzeniami afektywnymi--zarys problemu.

The family burden (FB) has been defined as a multidimensional impact imposed by an illness on caregivers. FB can be divided into objective (i.e. related to measurable problems) and subjective one (i.e. related to caregivers' emotions arising in response to objective difficulties). FB is known to be related to disturbances in the functioning of the family system, higher level of stress, and the presence of financial problems. Some gender-dependent differences in the characteristics of FB have been found. Since family member's illness can be not only a ballast, but also a potential source of satisfaction, it has been found that the level of caregiving-related satisfaction is a significant predictor of FB severity. FB dynamics does not seem to be parallel to the course of illness. Problem-focused and task-focused coping strategies are known to be related to lower values of FB. There is evidence suggesting that in families of patients with BD depressive episodes trigger substantially higher severity of FB, as compared to manic episodes. Data on FB related to major depressive disorder (MDD) are scarce. Assertive community treatment strategies are the main option of reducing FB in the context of affective disorders, yet data on their effectiveness are inconclusive.

[Randomized controlled trials in psychiatry]. / Badania z randomizacja w psychiatrii.

In the past twenty years, evidence based medicine (EBM) has become a dominant paradigm of the contemporary medical practice. Since the emergence of the significant article by Geddes and Harrison in 1997, this doctrine has become part of psychiatry too. According to the rules of EBM, the most valuable clinical data comes from randomized-controlled trials (RCT). Nevertheless there are numerous researchers who point out at some limitations making RCT less valid in psychiatry than in other medical disciplines. The authors of this paper reviewed the available literature on the place of RCT in psychiatry and subsequently presented current opinions about the reliability of those trials, as well as highlighted the possible solutions of potential controversies. We suggest that in spite of the limitations mentioned above, RCT remains the most valuable research strategy in psychiatry. Most of the obstacles do not differ significantly from the problems seen in other medical fields. There are also known methods of improving methodology of RCT (such as recruiting larger groups of patients or performing expertise-based RCT).

[Schizophrenia-like psychotic symptoms in a patient with confirmed Huntington's disease: a case report]. / Objawy psychotyczne sugerujace schizofrenie u pacjenta z potwierdzonym rozpoznaniem choroby Huntingtona--opis przypadku.

AIM: The aim of this study is to discuss diagnostic and therapeutic challenges in a patient with a mutation in the gene responsible for the development of Huntington's disease (HD) who presented schizophrenia-like psychotic symptoms. METHOD: A case report. RESULTS: A 35-year old man with genetically-confirmed HD who developed significant behavioural changes that occurred many years prior to the outbreak of choreic movements. There was a close temporal relationship between an onset of discrete involuntary movements and schizophrenia-like psychotic symptoms (delusions of persecution, reference and bodily change, as well as auditory pseudohallucinations of threatening and commanding voices). At admission (subsequently to a suicidal attempt) he was ambivalent, ambitendent and--periodically--agitated. Pharmacotherapeutic regime of olanzapine (20 mg qd) and amisulpride (400 mg qd) led to a gradual improvement of the patient's mental status. CONCLUSIONS: HD should always be included in the differential diagnosis of psychotic disorders. Patients with HD can exhibit various psychopathological symptoms (including psychotic ones) prior to the outbreak of movement symptoms. Both neurologists and psychiatrists should take part in the therapeutic process. Atypical antipsychotics seem to be effective in the discussed group of patients (although the evidence body consists mainly of scarce, low-quality data).

[Neurobiology of suicidal behaviour]. / Neurobiologia zachowan samobójczych.

The authors of this paper present a review of actual data on the neurobiological background of suicidal behaviour. The results of epidemiological studies suggest that suicidal behaviours have certain genetic background which do not depend on the presence of concomitant mental disorders. The estimated heritability rate of suicide is about 21-50%, while the heritability rate of suicidal ideation and behaviour is about 30-55%. The genes of serotonergic and noradrenergic systems, as well as the HPA axis genes, have been scrutinised in context of suicidal behaviour. Epigenetic factors are also believed to be involved in the pathogenesis of suicide. Serotonergic, noradrenergic, glutamatergic and GABAergic systems, as well as the HPA axis, are the main neural networks involved in the pathophysiology of suicide. Disorders of opioid and endocannabinoid systems can also be found in suicide victims. Pathogenesis of suicidal behaviour also contains abnormalities of cell signalising and pathology ofglial cells. Neurobiological background of akathisia and impulsivity (clinical issues closely related to the pathogenesis of suicidal behaviour) have also been presented. Most of the available trials on neurobiological background of suicidal behaviour have significant methodological weaknesses, making the results difficult to interpret. Usually they contain small samples and only single biological variables (without adjustment on environmental factors) are being analysed.