Showing papers in "Pharmacopsychiatry in 2016"
TL;DR: Results from the meta-analyses suggest that oxytocin has no significant effect on social cognition and restricted, repetitive behaviors in individuals with an ASD, while the summary of findings on the effectiveness of Oxytocin on ASD should still be considered tentative.
Abstract: Aim: Oxytocin presents an exciting potential to target the core symptoms of autism spectrum disorder (ASD) pharmacologically in an easily administered, cost-effective form with possibly minimal adverse effects. But, there are still major gaps in this area of research. This paper reviewed randomized controlled trials (RCTs) examining the effects of oxytocin administration on social cognition and restricted, repetitive behaviors in individuals with an ASD. Method: Electronic literature searches were conducted from PsycINFO, PubMed, Web of Knowledge, and EMBASE for RCTs published through June 2015. Results: 12 RCTs were included in this review. 7 out of the 11 studies that examined social cognition reported improvements. Additionally, one out of the 4 studies on restricted, repetitive behaviors, reported improvements following oxytocin administration. However, results from our meta-analyses suggest that oxytocin has no significant effect on these 2 domains. Conclusion: Previous evidence revealed mixed findings about the effects of oxytocin on ASD. Given the limited number of RCTs, our summary of findings on the effectiveness of oxytocin on ASD should still be considered tentative.
80 citations
TL;DR: DBS could be a promising, novel treatment option for severe alcohol addiction, but larger clinical trials are needed to further investigate the efficacy of DBS in addiction.
Abstract: We report on the long-term clinical outcome (up to 8 years) of 5 patients who received deep brain stimulation (DBS) of the nucleus accumbens to treat their long-lasting and treatment-resistant alcohol addiction. All patients reported a complete absence of craving for alcohol; 2 patients remained abstinent for many years and 3 patients showed a marked reduction of alcohol consumption. No severe or long-standing side effects occurred. Therefore, DBS could be a promising, novel treatment option for severe alcohol addiction, but larger clinical trials are needed to further investigate the efficacy of DBS in addiction.
76 citations
TL;DR: PPAR-γ agonists may have antidepressant properties, which need to be assessed in further studies of major depressive episodes, and are associated with changes in biomarkers of metabolism and inflammation.
Abstract: Introduction: Selective agonists of the nuclear transcription factor peroxisome proliferator-activated receptor-gamma (PPAR-γ) are used for the treatment of type 2 diabetes. We reviewed their efficacy and safety for the treatment of major depression and the association of their potential antidepressant effects with changes in biomarkers of metabolism and inflammation. Methods: From 8 studies, 4 open-label trials, and 4 randomized controlled trials (RCT) (3 vs. placebo and 1 vs. metformin), 448 patients with major depression were included, of which 209 patients received PPAR-γ agonists (pioglitazone or rosiglitazone) for 6–12 weeks, either alone or in add-on therapy to conventional treatments. Results: PPAR-γ agonists have antidepressant effects in the 4 open-label studies and in 3 out of 4 RCT. No major adverse event was reported. Improvement in depression scores was associated with improvement in 3 biomarkers of insulin resistance (homeostatic model assessment [HOMA-IR], oral glucose tolerance test, and fasting plasma glucose) and 1 biomarker of inflammation (interleukin-6) among 21 biomarkers studied. Conclusion: PPAR-γ agonists may have antidepressant properties, which need to be assessed in further studies of major depressive episodes.
61 citations
TL;DR: The results of this study may suggest that saffron is a safe alternative medication for improving depressive symptoms of postpartum depression, although it should be mentioned that the trial is not well powered and should be considered a preliminary study.
Abstract: Introduction: Postpartum depression is a common mental health problem that is associated with maternal suffering. The aim of this double-blind clinical trial was to compare safety and efficacy of saffron and fluoxetine in treatment of mild to moderate postpartum depression. Methods: This was a 6-week, double-blind, randomized clinical trial. Subjects were women aged 18–45 years with mild to moderate postpartum depression who had Hamilton Depression Rating Scale (HDRS 17-item) score≤18. Eligible participants were randomized to receive either a capsule of saffron (15 mg capsule) or fluoxetine (20 mg capsule) twice daily for 6 weeks. The primary outcome measure was to evaluate efficacy of saffron compared to fluoxetine in improving depressive symptoms (HDRS score). Results: There was no significant effect for time×treatment interaction on HDRS score [F (4.90, 292.50)=1.04, p=0.37] between the 2 groups. 13 (40.60%) patients in the saffron group experienced complete response (≥50% reduction in HDRS score) compared with 16 (50%) in the fluoxetine group and the difference between the 2 groups was not significant in this regard (p=0.61). Frequency of adverse events was not significantly different between the treatment groups. Discussion: The results of this study may suggest that saffron is a safe alternative medication for improving depressive symptoms of postpartum depression. Nevertheless, it should be mentioned that the trial is not well powered and should be considered a preliminary study. Therefore, large clinical trials with longer treatment periods and comparison with placebo group would be appropriate for future studies.
57 citations
TL;DR: This systematic review extends the established literature by comprehensively reviewing the effects of antidepressants classes on both the innate and adaptive immune system and recommends larger, comparative studies - in clinical and pre-clinical populations.
Abstract: Current reviews exploring for unique immune-modulatory profiles of antidepressant classes are limited by focusing mainly on cytokine modulation only and neglecting other aspects of the innate and adaptive immune system. These reviews also do not include recent comparative clinical trials, immune-genetic studies and therapeutics with unique neurotransmitter profiles (e. g., agomelatine). This systematic review extends the established literature by comprehensively reviewing the effects of antidepressants classes on both the innate and adaptive immune system. Antidepressants appear, in general, to reduce pro-inflammatory factor levels, particularly C-reactive protein (CRP), tumour necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6. We caution against conclusions as to which antidepressant possesses the greater anti-inflammatory effect, given the methodological heterogeneity among studies and the small number of comparative studies. The effects of antidepressant classes on adaptive immune factors are complex and poorly understood, and few studies have been conducted. Methodological heterogeneity is high among these studies (e. g., length of study, cohort characteristics, dosage used and immune marker analysis). We recommend larger, comparative studies - in clinical and pre-clinical populations.
55 citations
TL;DR: The authors of the meta-analysis conclude that due to expectations induced in both the treatment and placebo groups, blinded studies are incapable of distinguishing a difference between groups.
Abstract: As an alcohol-aversive agent, disulfiram occupies an exceptional position in the pharmacological relapse prevention of alcohol dependence. In contrast to anti-craving drugs, disulfiram does not modulate neurobiological mechanisms of addiction, but rather works by producing an aversive reaction when combined with alcohol. Therapeutic and adverse effects are therefore closely related: On the one hand, the aversiveness of the disulfiram ethanol reaction has the potential to support abstinence in a subgroup of alcohol-dependent patients, while on the other hand it becomes a health threat if the patient fails to maintain complete abstinence. The exceptional position of disulfiram is also related to the role that expectations play in the mediation of therapeutic effects. These are not determined by the pharmacological effects or the actual occurrence of a disulfiram-ethanol reaction, but are attributable to patient awareness that the drug was consumed and the corresponding anticipation of an aversive reaction if combined with alcohol. This is in line with the findings of a recent meta-analysis that only showed significant effects for disulfiram in open-label trials. The authors of the meta-analysis conclude that due to expectations induced in both the treatment and placebo groups, blinded studies are incapable of distinguishing a difference between groups. The mediation of therapeutic effects through expectation has a number of consequences for clinical practice and future research on disulfiram.
54 citations
TL;DR: Male gender and prescription of antipsychotics and benzodiazepines were associated with increased risk of use of above the recommended dosage and use of pregabalin above recommended dosages was rare but abuse may occur in susceptible patients.
Abstract: Introduction: Pregabalin is currently approved for the treatment of epilepsy, generalized anxiety disorder and neuropathic pain with a licensed dosage range of 150 mg to 600 mg/day. Growing concern about the abuse potential of pregabalin is partly based on reports of pregabalin being used in dosages that exceed the approved therapeutic range. Methods: To identify predictors of pregabalin use above recommended dosage, we conducted a pharmacoepidemological drug utilization study using the Danish nationwide registers. We deployed 4 measures of abuse: high use (≥600 mg/day) or very high use (≥1 200 mg/day) over a 6- or 12-month period, respectively. Multiple logistic regression was used to identify patient and treatment characteristics that were associated with either abuse marker. Results: Out of 42 520 pregabalin users 4 090 (9.6%) were treated with more than 600 mg/day for 6 months and 2 765 (6.5%) for more than 12 months. Male gender and prescription of antipsychotics and benzodiazepines were associated with increased risk of use of above the recommended dosage. Discussion: Use of pregabalin above recommended dosages was rare but abuse may occur in susceptible patients.
53 citations
TL;DR: This meta-analysis suggests that adjunctive EGb appeared to be an effective and safe option for improving TD in the treatment of schizophrenia patients, however, better RCTs are needed to demonstrate its efficacy and safety especially on cognitive function in TD.
Abstract: Objective: Free radicals may be involved in the pathogenesis of tardive dyskinesia (TD). We conducted this meta-analysis to systematically examine the efficacy of extract of Ginkgo biloba (EGb), a potent antioxidant possessing free radical-scavenging properties, as a treatment for TD in schizophrenia using randomized controlled trial (RCT) data. Method: Drawn from English and Chinese databases, 3 RCTs of EGb augmentation of antipsychotics (APs) vs. AP plus placebo or AP monotherapy were identified. 2 evaluators extracted data. The primary outcome measure was the severity of TD symptoms assessed by the Abnormal Involuntary Movement Scale (AIMS). Weighted mean difference (WMD) and risk ratio (RR) ±95% confidence intervals (CI) were calculated. Statistical analyses were performed using Review Manager (version 5.1.7.0) and STATA (version 12.0). Results: The 3 RCTs (n=299) from China, of 12 weeks duration, involved schizophrenia patients with TD of 55.9±13.4 years old. EGb (240 mg/day) outperformed the control group in reducing the severity of TD and clinical symptoms as measured by the AIMS (trials=3, n=299, WMD: –2.30 (95%CI: − 3.04, −1.55), P Conclusion: This meta-analysis suggests that adjunctive EGb appeared to be an effective and safe option for improving TD in the treatment of schizophrenia patients. However, better RCTs are needed to demonstrate its efficacy and safety especially on cognitive function in TD. Trial registration: PROSPERO: CRD42015024930
30 citations
TL;DR: The findings suggest that NPY may be related to pathophysiology in depression and anxiety, and antidepressants influence NPY levels.
Abstract: Introduction: This study aimed to investigate the neuropeptide Y (NPY) levels in patients with anxiety and depression and also the effects of antidepressants on this neuropeptide. Materials and Methods: The study included 40 outpatients who presented with depressive and anxiety symptoms, and 32 healthy controls. The patients received antidepressant treatment for 6 months. Serum levels of neuropeptide Y were measured before treatment in 40 patients, after 8 weeks of treatment in 32 patients, after 6 months in 10 patients, and once in the controls. Results: Serum NPY levels were lower in the patients than in the controls. NPY levels were increased and normalized by antidepressant treatment. While there was no change in NPY levels in the patients using fluoxetine and sertraline for 8 weeks, an increase was found in patients using escitalopram and venlafaxine. Serum NPY levels were increased by treatment for 8 weeks in the patients with depression, but not in the patients with anxiety. Discussion: The findings suggest that NPY may be related to pathophysiology in depression and anxiety, and antidepressants influence NPY levels.
28 citations
TL;DR: Doxazosin might improve trauma associated nightmares and more general sleep parameters in patients with PTSD and BPD.
Abstract: Objective: Centrally active α-1-adrenergic-receptor antagonists such as prazosin are effective in the treatment of nightmares in patients with posttraumatic stress disorder (PTSD). A pharmacological alternative is doxazosin, which has a longer half-life and fewer side effects. However, doxazosin is currently being used without solid empirical evidence. Furthermore, no study so far has assessed the effects of α-1-antagonists on nightmares in patients with borderline personality disorder (BPD). We retrospectively assessed the effectiveness of doxazosin on nightmares in PTSD and BPD. Method: A retrospective chart review of patients treated with doxazosin for trauma-associated nightmares in our clinic was performed. As in previous prazosin studies, the B2 score of the Clinician-Administered PTSD Scale (CAPS) was used as the primary outcome measure. Furthermore, the Pittsburgh Sleep Quality Index-Addendum for PTSD (PSQI-A) and sleep logs were analyzed. Results: We identified 51 patients with PTSD and/or BPD (mean age 35.7 years, 92.3% women) who received doxazosin for nightmares. Of these, 46 patients continued doxazosin over a 4-week period and 31 patients over a 12-week period. Within the 12-week period, doxazosin treatment significantly reduced nightmares regardless of PTSD/BPD. 25 percent of patients treated for 12 weeks had full remission of nightmares. PSQI-A scores indicated that additional trauma-associated sleep symptoms improved over 12 weeks. Furthermore, recuperation of sleep improved with doxazosin within the first 4 weeks of treatment. Conclusion: Doxazosin might improve trauma associated nightmares and more general sleep parameters in patients with PTSD and BPD. Randomized controlled trials are warranted.
27 citations
TL;DR: An indirect meta-analysis of randomized controlled studies on the treatment of alcohol dependence indicates an advantage of nalmefene over naltrexone, an effective and well-tolerated medication for the reduction of alcohol consumption.
Abstract: Background: The mu-opioid antagonist naltrexone is one of the few approved pharmacotherapies for the treatment of alcohol dependence. Recently, the mu-opioid antagonist and partial kappa agonist nalmefene was approved by the European Medicines Agency for the reduction of alcohol consumption in adult patients with alcohol dependence. To date, no head-to-head studies have compared the efficacy and safety of naltrexone and nalmefene in reducing alcohol consumption. Methods: An indirect meta-analysis of randomized controlled studies on these 2 medications was conducted. A random effects model was used to measure effects and compare the 2 medications. 4 placebo-controlled studies with nalmefene and 13 with naltrexone were included. Results: A statistically significant advantage of nalmefene towards naltrexone in the 2 patient-relevant outcome efficacy criteria, quantity and frequency of drinking, was found. Both drugs had a benign safety profile. Conclusions: This indirect meta-analysis indicates an advantage of nalmefene over naltrexone. Nalmefene is an effective and well-tolerated medication for the reduction of alcohol consumption. Additional data are necessary to demonstrate possible advantages of nalmefene over naltrexone in the treatment of alcohol dependence.
TL;DR: The present study suggests that memantine may have beneficial effects in the treatment of many core symptoms of autism and may be considered as a potential medication in the Treatment of those autistic children who do not respond or cannot tolerate side effects of risperidone.
Abstract: Introduction: This study was aimed to compare the efficacy and side effects of memantine, an antagonist of the NMDA receptor of glutamate, with risperidone given the fact that glutamate has been noted for its possible effects in the pathogenesis of autism. Risperidone, an atypical antipsychotic, has been approved by FDA for the management of irritability associated with autism. Methods: 30 children, aged 4–17 years, entered an 8-week, randomized trial. Patients were randomly assigned to receive either risperidone or memantine. Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), Clinical Global Impressions – Improvement (CGI-I) and Clinical Global Impression-Severity (CGI-S) scales were used to assess behavioral symptoms of the patients. Results: Both risperidone and memantine reduced the scores of 4 subscales of ABC as well as the 10-item and the total score of CARS significantly. However, differences between the 2 drugs in the scores of each evaluating scale were not found to be significant. Relatively, larger number of patients on risperidone showed “very much improvement” when assessed by CGI-I scale when compared with those on memantine. Discussion and conclusion: The present study suggests that memantine may have beneficial effects in the treatment of many core symptoms of autism. Therefore, memantine may be considered as a potential medication in the treatment of those autistic children who do not respond or cannot tolerate side effects of risperidone.
TL;DR: Among psychiatric patients without psychotic symptoms, quetiapine causes an overt decrease in HRV, and the autonomic effects of antidepressants were found not to be significant.
Abstract: Introduction: The autonomic effects of antidepressants and quetiapine on heart rate variability (HRV) are inconsistent based on past studies. The aim of this study was to explore their influence on the HRV of psychiatric patients without psychotic symptoms. Methods: A total of 94 patients with depression, anxiety, or somatic symptoms, were recruited into this study. Based on their medication, 4 groups were identified: the no antidepressant group (n=19), the SSRI group (using sertraline or escitalopram, n=53), the other antidepressants group (using venlafaxine or mirtazapine, n=9), and the augmentation group (AG, using an antidepressant+quetiapine, n=13). The HRV of the 4 groups were compared. The correlations between HRV and the medication(s) used were clarified. Results: Among the 4 groups, the AG had the lowest HRV with its total power (TP), very low frequency power (VLF) and low frequency power (LF) of HRV being significantly different from those of the other groups. Age and using quetiapine were found to be negatively correlated with TP, VLF and LF. With this study group, the autonomic effects of antidepressants were found not to be significant. Discussion: Among psychiatric patients without psychotic symptoms, quetiapine causes an overt decrease in HRV.
TL;DR: The importance of detecting individuals at clinical high-risk for psychosis (schizophrenia) or bipolar disorder, especially in children and adolescents, in order to enable early intervention, and evaluating different intervention strategies during the subsyndromal or "prodromal" stages of these severe and often debilitating disorders is described.
Abstract: This review aims to describe the importance of i) detecting individuals at clinical high-risk for psychosis (schizophrenia) or bipolar disorder, especially in children and adolescents, in order to enable early intervention, and ii) evaluating different intervention strategies, especially pharmacotherapy, during the subsyndromal or “prodromal” stages of these severe and often debilitating disorders. The different approaches regarding the psychotic and bipolar clinical high-risk state are discussed, including reasons and evidence for early (pharmacological) intervention and risks of treatment vs. non-treatment. Only 10 prospective studies of antipsychotics (randomized=4) and 6 prospective studies of non-antipsychotic pharmacologic agents (randomized=3, i. e., omega-3 fatty acids=2, glycine=1) for the psychotic clinical high-risk state and only 4 prospective studies of mood stabilizing medications for the bipolar clinical high-risk state (randomized=2, i. e., lithium=1, valproate=1) were detected. Based on the minimal efficacy data, adverse effect risks, especially in pediatric populations, nonspecific psychopathology, and unknown true risk for the development of either psychosis or bipolar disorder or of chronically disabling symptoms and disability, medication treatment currently remains second choice after psychosocial intervention. Additional research in this area is clearly needed in order to shed more light on the relevance and predictive value of potentially prodromal symptoms, their identification and most appropriate management options.
TL;DR: Genotype information could be used as a valuable tool, in addition to therapeutic drug monitoring, to prevent supratherapeutic drug levels of nortriptyline or venlafaxine in elderly patients with a PM genotype.
Abstract: Objectives: To determine relations between drug concentrations and the cytochrome P450-CYP2D6 genotype or phenotype among elderly patients treated with nortriptyline or venlafaxine. Methods: A post-hoc analysis of a clinical trial was performed. Patients were grouped into phenotypes according to the metabolite/mother compound ratio. Genotypes were assessed by the CYP2D6 *3 and *4 alleles. Results: Data was available from 81 patients (41 nortriptyline, 40 venlafaxine) with a mean age of 72 years. No phenoconversion from poor metabolizers (PM) to extensive metabolizers (EM), or vice versa, was found. However, we did find phenoconversion from PM to intermediate metabolizers (IM), IM to EM, or vice versa in 36% of observations. Among nortriptyline users, patients with a PM or IM genotype had more supra-therapeutic blood levels, although this did not reach statistical significance. In exploratory analyses we found men were more likely (RR: 2.4; 95% CI: 1.14-5.07) to display phenoconversion from an IM genotype to EM phenotype. In addition, compared to non-PMs, PMs were found to have higher risk (RR: 1.56; 95% CI: 1.03-2.37) on non-response, although this was only significant when response was measured on the Hamilton Rating Scale for Depression and not on the Montgomery Asberg Depression Rating Scale. Conclusion: Patients phenoconversed, but we did not observe phenoconversion from PM to EM or vice versa. Genotype information could be used as a valuable tool, in addition to therapeutic drug monitoring, to prevent supratherapeutic drug levels of nortriptyline or venlafaxine in elderly patients with a PM genotype.
TL;DR: Adjunctive aripiprazole may be useful treatment for sexual dysfunction including hyperprolactinemia in schizophrenia, and a significant improvement in total sexual dysfunction as measured by NSFQ at week 8 and later.
Abstract: Introduction: Although adjunctive aripiprazole improves hyperprolactinemia, sufficient evidence for its effects on sexual dysfunction has not been obtained. We assessed the usefulness of adjunctive aripiprazole for schizophrenia with sexual dysfunction. Methods: 22 Japanese schizophrenia patients with antipsychotic-induced hyperprolactinemia and sexual dysfunction were enrolled, and 19 of them completed the study. Aripiprazole was administrated in a flexible titration schedule to participants according to the judgment of each doctor, and patients were followed for 24 weeks. Serum prolactin, Clinical Global Impression Scales-Severity (CGI-S), and Nagoya Sexual Function Questionnaire (NSFQ) were measured at baseline and at 4, 8, 12, and 24 weeks. Results: Prolactin at week 4 and later was significantly lower than that at baseline. Compared to baseline, we observed a significant improvement in total sexual dysfunction as measured by NSFQ at week 8 and later. In males, erectile dysfunction was significantly reduced at week 24. In females, menstrual irregularity and galactorrhea were significantly reduced at week 24. CGI-S did not significantly change. Discussion: Although the small sample size is a limitation in this study, adjunctive aripiprazole may be useful treatment for sexual dysfunction including hyperprolactinemia in schizophrenia.
TL;DR: A need to inform physicians about pharmacovigilance and to modify the required procedure of ADR reporting or to offer other reporting options is suggested.
Abstract: Introduction: Drug safety surveillance strongly depends on the spontaneous reporting of adverse drug reactions (ADRs). A major limiting factor of spontaneous reporting systems is underreporting (UR) which describes incorrectly low reporting rates of ADRs. Factors contributing to UR are numerous and feature country-dependent differences. Understanding causes of and factors associated with UR is necessary to facilitate targeted interventions to improve ADR reporting and pharmacovigilance. Methods: A cross-sectional questionnaire-based telephone survey was performed among physicians in outpatient care in a federal state of Germany. Results: From n=316 eligible physicians n=176 completed the questionnaire (response rate=55.7%). Most of the physicians (n=137/77.8%) stated that they report ADRs which they have observed to the competent authority rarely (n=59/33.5%), very rarely (n=59/33.5%) or never (n=19/10.8%); the majority (n=123/69.9%) had not reported any ADRs in 2014. Frequent subjective reasons for non-reporting of ADR were (specified response options): lack of time (n=52/29.5%), the subjective evaluation that the required process of reporting is complicated (n=47/26.7%) or requires too much time (n=25/14.2%) or the assessment that reporting of an ADR is needless (n=22/12.5%); within open answers the participants frequently stated that they do not report ADRs that are already known (n=72/40.9%) and they only report severe ADRs (n=46/26.1%). Discussion: Our results suggest a need to inform physicians about pharmacovigilance and to modify the required procedure of ADR reporting or to offer other reporting options.
TL;DR: Duloxetine adjuvant to risperidone seems to be a tolerable and efficacious treatment for primary negative symptoms of schizophrenia.
Abstract: Introduction: Although the pathogenesis of symptoms of schizophrenia is largely unknown, a variety of neurotransmitters are implicated, including serotonin and norepinephrine. Here we investigate the effectiveness of duloxetine as a serotonin-norepinephrine inhibitor in the treatment of negative symptoms. Methods: We performed a double-blind clinical trial on 64 patients with stable schizophrenia and no prominent symptoms of depression. Patients received risperidone (up to 6 mg/day) plus either duloxetine (60 mg/day) or placebo. Psychotic symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS) at the onset of the trial, and at 2, 4, 6 and 8 weeks of therapy. Results: Compared to the placebo group, the duloxetine group showed significantly higher improvement in negative symptoms (p Discussion: Duloxetine adjuvant to risperidone seems to be a tolerable and efficacious treatment for primary negative symptoms of schizophrenia.
TL;DR: Patients with schizophrenia are capable of adhering to a diet and fitness program and successfully lose weight, regardless to taking typical or atypical medications.
Abstract: Introduction: Schizophrenia patients, receiving new generation antipsychotics, many times suffer from obesity sometimes leading to metabolic syndrome. Diet and fitness programs which reduce weight should be combined in the treatment plan of these patients. This study evaluated patients’ adherence and the effect of a diet and fitness program in schizophrenia patients treated with typical vs. atypical antipsychotics. Methods: 106 stabilized schizophrenia patients participated in a 9-months diet and fitness program, receiving their own menu and a personal workout plan. Results: 60 patients (57%), 27.8±4.8y age, participated in the program for at least one month, i. e., adherent participants, with 4.0±2 months participation average. Months of participation were correlated with weight loss (r=−0.417; p=0.002). Throughout the study patients lost 3.34±1.2 kg in average: 85.95±14.66 at baseline and 82.61±13.78 at the end of program (t=4.969; p Discussion: Patients with schizophrenia are capable of adhering to a diet and fitness program and successfully lose weight, regardless to taking typical or atypical medications.
TL;DR: Patients with ADHD have an increased risk of injury, significantly more so for those with ADHD and comorbid mental illness, and psychostimulants can lower the risk of Injury among patients with ADHD.
Abstract: Introduction: We identify the risk of selected types of injuries among patients with ADHD or ADHD and comorbid mental illness. We also assess whether selected medications used by patients with ADHD increase the risk of comorbid mental illness or influence the association between ADHD and injury. Methods: A retrospective cohort study design was conducted using medical claims data from the Deseret Mutual Benefit Administrators (DMBA). ADHD diagnosis, injury, medication, and demographic data were extracted from claims files during 2001–2013. Rate ratios were adjusted for age, sex, and calendar year. Results: Patients with ADHD were 7.9 (95% CI 7.6–8.2) times more likely to have psychosis, 5.5 (3.9–7.8) times more likely to have alcohol- or drug-induced psychosis, and 6.0 (5.9–6.2) times more likely to have neurotic or personality disorder. Therapy with amphetamine was positively associated with neurotic or personality disorder (rate ratio=1.08, 1.02–1.15); methylphenidate was negatively associated with neurotic or personality disorder (0.90, 0.84–0.97); and atomoxetine was positively associated with psychosis (1.33, 1.21–1.46), alcohol- or drug-induced psychosis (2.38, 1.04–5.43), and neurotic or personality disorder (2.38, 1.04–5.43). ADHD was associated with an increased risk of injury, with ADHD and comorbid mental illness having a stronger increased risk of injury. Psychostimulants ameliorated the increased risk of injury for patients with ADHD. Conclusion: Patients with ADHD have an increased risk of injury, significantly more so for those with ADHD and comorbid mental illness. Psychostimulants can lower the risk of injury among patients with ADHD.
TL;DR: In this study, clozapine treatment was initiated markedly earlier than in the few existing studies, which may partly be due to the expected poor prognosis of EOS.
Abstract: Introduction: Early-onset schizophrenia (EOS) has a poor prognosis and is difficult to treat, which often leads to the initiation of clozapine treatment. Studies in adults have shown that the initiation of clozapine treatment is often delayed. There is a lack of studies concerning the initiation of clozapine in children and adolescents with EOS. The aim of this study was to investigate the time span from first EOS-related psychiatric hospitalization to clozapine initiation. Methods: We retrospectively studied a consecutive cohort of children and adolescents with EOS and first-time clozapine prescriptions from a tertiary care child and adolescent psychiatric center in Germany. Results: Clinical records with data on clozapine initiation were available for 112 patients (35.7% females, mean age: 15.2±1.6 years). The mean time from first EOS-related hospitalization to clozapine initiation was 1.1 (±1.0) years, with an average of 2.3 (±1.1) prior antipsychotic treatment episodes. Higher age and higher IQ predicted earlier clozapine initiation. At the time of clozapine initiation, 40.2% of patients received antipsychotic polypharmacy. Prior to clozapine, 33.9% of patients had received 3 or more antipsychotic treatment episodes. Discussion: In our study, clozapine treatment was initiated markedly earlier than in the few existing studies, which may partly be due to the expected poor prognosis of EOS. The significant portion of patients undergoing 3 or more antipsychotic trials or antipsychotic polypharmacy prior to clozapine may indicate a need for improved dissemination of knowledge on the effectiveness of clozapine in treatment-resistant schizophrenia in order to promote timely clozapine prescriptions in these cases.
TL;DR: These results challenge the hypotheses that TSPO levels might increase during antidepressant therapy along with a decrease in depressive symptoms and assume that T SPO expression in platelets is not a suitable state marker for MDD.
Abstract: Introduction: A promising candidate in the field of pharmacological treatment options regarding major depressive disorder (MDD) is the mitochondrial translocator protein (18 kDa) (TSPO). TSPO is crucial for neurosteroid synthesis, which is in turn important for the regulation of emotions. It has already been shown that TSPO expression in platelets of depressed patients is reduced compared to healthy subjects. Methods: We measured TSPO levels in platelets of 37 depressed patients before and after 6 weeks of pharmacological treatment to test the hypotheses that i) such treatment would increase TSPO expression and ii) that this increase would be correlated with therapeutic response. Results: Surprisingly, TSPO levels in platelets of all patients were significantly reduced after 6 weeks of treatment (p=0.044). Within the responder group, a non-significant trend towards greater TSPO level reduction could be observed. Discussion: These results challenge our hypotheses that TSPO levels might increase during antidepressant therapy along with a decrease in depressive symptoms. Thus, we assume that TSPO expression in platelets is not a suitable state marker for MDD.
TL;DR: Paliperidone palmitate treatment throughout the gestation period was safe and well tolerated by both mother and foetus, there being no malformations or other perinatal complications in the newborn to date.
Abstract: Introduction: Paliperidone palmitate treatment of schizophrenia or schizoaffective disorder is effective and well tolerated, but there is almost no data on its safety during pregnancy. Case report: An analysis is made of the safety and tolerability of paliperidone palmitate treatment throughout the gestation period in a 34-year-old patient diagnosed with schizoaffective disorder. Discussion: Paliperidone palmitate treatment throughout the gestation period was safe and well tolerated by both mother and foetus, there being no malformations or other perinatal complications in the newborn to date.
TL;DR: The findings suggested the involvement of a GHRL polymorphism in weight gain, which was specifically mediated by appetite change, during antipsychotic treatment in schizophrenia patients.
Abstract: Introduction: This study aimed to investigate the association of multiple candidate genes with weight gain and appetite change during antipsychotic treatment. Methods: A total of 233 single nucleotide polymorphisms (SNPs) within 60 candidate genes were genotyped. BMI changes for up to 8 weeks in 84 schizophrenia patients receiving antipsychotic medication were analyzed using a linear mixed model. In addition, we assessed appetite change during antipsychotic treatment in a different group of 46 schizophrenia patients using the Drug-Related Eating Behavior Questionnaire. Results: No SNP showed a statistically significant association with BMI or appetite change after correction for multiple testing. We observed trends of association (P Discussion: Our findings suggested the involvement of a GHRL polymorphism in weight gain, which was specifically mediated by appetite change, during antipsychotic treatment in schizophrenia patients.
TL;DR: Antipsychotic drugs and polypharmacy may be regarded as predictors of completed suicide.
Abstract: Introduction: Very few studies have explored the adverse effect of psychotropic drugs worldwide. Methods: This study analyzed 1 813 suicide-related drug reports involving 553 patients collected from the Japanese National Adverse Drug Report Database between October 2001 and January 2012 to investigate psychotropic drugs associated with completed suicide vs. other suicide-related behaviors, including ideation and self-injury. The drugs investigated included antidepressants, antipsychotics, benzodiazepines, non-benzodiazepine hypnotic agents, noradrenergic and specific serotonergic antidepressants, selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, and other drugs. Results: These reports referenced 300 (54.2%) individuals who completed suicide. Adjusting for age, sex, and drugs used, the multivariate model revealed that participants who took antipsychotics were 1.70 times (95% CI, 1.11–2.61) more likely to complete suicide compared with those who did not. All other drugs became non-significant. Compared with those who took only one medication, those prescribed more than 4 drugs were more likely to complete suicide (OR 4.44, 95% CI, 2.40–8.20). Discussion: Antipsychotic drugs and polypharmacy may be regarded as predictors of completed suicide.
TL;DR: This selective review aims to provide an overview about current psychopharmacological interventions in child and adolescent psychiatry and indicates either a lower efficacy than other interventions or less beneficial effects compared to possible adverse events in these cases.
Abstract: Pharmacotherapeutic interventions are available for most psychiatric disorders in children. Evidence for these interventions varies, depending on the targeted disorders. For attention-deficit/hyperactivity disorder, a sound database on efficacy and safety of medication exists. For other common disorders or psychopathological phenomena like disruptive behavior, anxiety disorders, depressive disorders, or autism, data on efficacy and safety are much scarcer. This selective review aims to provide an overview about current psychopharmacological interventions in child and adolescent psychiatry. The literature indicates either a lower efficacy than other interventions or less beneficial effects compared to possible adverse events in these cases. Most guidelines recommend psychopharmacotherapy in children to be embedded in a psychosocial or therapeutic intervention plan. Decision for medication depends on the severity of symptoms, chronicity, and, most important, impairment of the child in academic performance, family relationships, and everyday life. The high rates of off-label use in the age group of children are often due to a lack of market authorization studies less indicative of low efficacy. As adverse events need to be monitored closely, pharmacotherapy should mainly be restricted to experienced mental health care providers.
TL;DR: The T allele at position -759 protects against AIWG in female patients with schizophrenia, and this association was not affected by possible confounding factors such as age, baseline BMI, and prior psychopharmacological treatment.
Abstract: Introduction: The HTR2C gene is an important candidate in pharmacogenetic studies of antipsychotic-induced weight gain (AIWG). However, inconsistent results have been obtained. The present study investigated the association between -759C>T, functional polymorphism of the HTR2C receptor, and AIWG. Methods: A prospective cohort of 48 female inpatients with schizophrenia and related illness treated according to normal clinical practice with second generation antipsychotics (SGAs) risperidone, clozapine, quetiapine, and olanzapine were evaluated. Patients were weighted at admission and again at 6 weeks of hospitalization. Weight gain was defined as an increase≥7% of baseline weight. The association between polymorphisms HTR2C and weight gain was evaluated. Multiple logistic regression was run to determine potential confounders. Results: Patients with the T allele at position -759 (TT or CT) gained less weight as compared to patients who did not have the allele. This association was not affected by possible confounding factors such as age, baseline BMI, and prior psychopharmacological treatment. Discussion: The T allele at position -759 protects against AIWG in female patients with schizophrenia.
TL;DR: Abrupt cessation of recreational long-term daily cannabis use was not followed by significant changes in heart rate, blood and pulse pressure, and this merely minor metabolic risk might have contributed to the missing effects of cannabis cessation on the basic cardiovascular functions.
Abstract: Objective: To shed more light on the role of heart rate and blood pressure during cannabis withdrawal. Methods: Post-hoc analysis of data collected during a prospective inpatient monitoring of withdrawal symptoms of 39 (8 female) adult (median 27 year old) treatment-seeking, predominantly white cannabis-dependents (Bonnet et al., Drug Alcohol Depend 2014; 143: 189–97). Beyond tobacco smoking, the body mass index, electrocardiogram and routine laboratory results were considered to estimate the cohort’s risk for cardiovascular disease (CVD). Results: Abrupt cessation of recreational long-term daily cannabis use was not followed by significant changes in heart rate, blood and pulse pressure. Also, these measures were not significantly correlated with the severity of the cannabis withdrawal syndrome. The cohort’s risk for CVD was moderate (all tobacco using, overweight in 9 of 35 patients and elevation of serum C-reactive protein in many patients). Its metabolic risk for CVD was minor considering the mostly normal blood pressure, normal serum lipids and glucose. Discussion: This merely minor metabolic risk might have contributed to the missing effects of cannabis cessation on the basic cardiovascular functions.
TL;DR: Comparisons in response to fluoxetine (FLX) may be influenced by certain genes that are involved in FLX transportation (ABCB1), and a significant association was observed between the G2677T ABCB1 polymorphism and suicide attempts.
Abstract: Introduction: Differences in response to fluoxetine (FLX) may be influenced by certain genes that are involved in FLX transportation (ABCB1). We examined remission and recovery from the index episode in a cohort of patients treated with FLX, and also investigated associations between genetic variants in ABCB1 and remission, recovery, and suicide risk. Methods: This was a naturalistic 1-year follow-up study of 46 adolescents diagnosed with major depressive disorder (MDD). At 12 months they underwent a diagnostic interview with the K-SADS-PL. Results: It was found that remission was around 69.5% and recovery 56.5%. Remission and recovery were associated with lower scores on the CDI at baseline, with fewer readmissions and suicide attempts, and with lower scores on the CGI and higher scores on the GAF scale. No relationship was found between ABCB1 and remission or recovery. However, a significant association was observed between the G2677T ABCB1 polymorphism and suicide attempts. Conclusion: Other factors such as stressful events, family support, and other genetic factors are likely to be involved in MDD outcome.
TL;DR: It is corroborate that there are neither cytogenetic effects of chronic stress nor of chronic MPH intake even after several years of treatment, and whether chronic psychosocial stress leads to mutagenic effects by itself.
Abstract: Introduction: Methylphenidate (MPH) is widely used to treat childhood and adult attention-deficit/hyperactivity disorder (ADHD). However, there are still safety concerns about side effects in long-term treatment. The aim of this study was to assess cytogenetic effects of chronic MPH treatment in adult ADHD and to find out if chronic social stress is attenuated by medication and to investigate whether chronic psychosocial stress leads to mutagenic effects by itself. Methods: Lymphocytes for micronucleus assay and saliva samples for cortisol measurement were collected from adult ADHD patients and healthy controls. Stress exposure of the last 3 months was assessed by TICS (Trier Inventory for Chronic Stress). Results: We could not detect an influence of MPH treatment on cytogenetic markers. ADHD patients displayed significantly higher chronic stress levels measured by TICS compared to healthy controls which were influenced by duration of MPH treatment. ADHD patients also showed significantly lower basal cortisol levels. Discussion: We could corroborate that there are neither cytogenetic effects of chronic stress nor of chronic MPH intake even after several years of treatment.