Does thyroid supplementation accelerate tricyclic antidepressant response? A review and meta-analysis of the literature

OBJECTIVE: The delayed onset of therapeutic response to antidepressants remains a major problem in the treatment of depression. Among the strategies to accelerate response to treatment, the early addition of thyroid hormone to antidepressants has been suggested as a viable method. The authors performed a meta-analysis of the literature on the use of thyroid hormone supplementation to accelerate the treatment of depression to determine whether there is sufficient evidence to support the clinical efficacy of this strategy. METHOD: Both a computer-aided search of the National Library of Medicine MEDLINE and an intensive search by hand were conducted to identify all double-blind, placebo-controlled studies assessing the concomitant administration of thyroid hormone and antidepressant to accelerate clinical response in patients with nonrefractory depression. RESULTS: Six studies were identified. All were conducted with triiodothyronine (T(3)) and a tricyclic antidepressant. Five of the six studies found T(3) to be significantly more effective than placebo in accelerating clinical response. The pooled, weighted effect size index was 0.58, and the average effect was highly significant. Further, the effects of T(3) acceleration were greater as the percentage of women participating in the study increased. CONCLUSIONS: This meta-analysis supports the efficacy of T(3) in accelerating clinical response to tricyclic antidepressants in patients with nonrefractory depression. Furthermore, women may be more likely than men to benefit from this intervention.     

Placebo response in pharmacological trials in patients with functional dyspepsia—A systematic review and meta-analysis

Background

Pharmacological trials in functional dyspepsia (FD) are associated with high placebo response rates. We aimed to identify the magnitude and contributing factors to the placebo response.

Methods

We conducted a systematic review and meta-analysis including randomized controlled trials (RCTs) with a dichotomous outcome in adult patients with FD that compared an active pharmacotherapeutic treatment with placebo. Our main outcome was identification of the magnitude of the pooled placebo response rate for the following endpoints: symptom responder, symptom-free responder, adequate relief responder, and combined endpoint responder (i.e., the primary endpoint of each specific trial regarding treatment response). Several putative moderators (i.e., patient, disease, and trial characteristics) were examined.

Key Results

We included 26 RCTs in our analysis. The pooled placebo response rate was 39.6% (95% CI 30.1–50.0) using the symptom responder definition, 20.5% (12.8–31.0) using the symptom-free responder definition, 38.5% (33.8–43.6) using the adequate relief responder definition, and 35.5% (31.6–39.7) using the combined endpoint responder definition. A lower overall baseline symptom score was significantly associated with a higher placebo response rate. No other moderators were found to significantly impact the placebo response rate. Due to the lack of data, no analyses could be performed according to individual FD subtypes or symptoms.

Conclusions and Inferences

The pooled placebo response rate in pharmacological trials in FD is about 39%, depending on which responder definitions is used. Future trials should consider applying an entry criterion based on minimal level of symptom severity to decrease the placebo response. We also suggest separate reporting of core FD symptoms pending more concrete harmonization efforts in FD trials.     

Does family functioning affect outcome in children with neurological disorders?

Children with neurological disorders are at increased risk of poor psychological and social adjustment. Medical factors are insufficient to explain the individual variation in outcome, so family variables have been considered. This review evaluates studies which have investigated the effect of family functioning on outcome in children with traumatic brain injuries, epilepsy and other neurological disorders. Methodological problems include the cross-sectional nature of many studies and inadequate control for confounding variables. There is good evidence that family functioning influences behavioural adjustment and adaptive functioning after traumatic brain injury. The role of family functioning in epilepsy and other neurological disorders requires further investigation. The development of effective interventions to improve family functioning may lead to important clinical benefits for children and their families.     

Does methylphenidate improve academic performance? A systematic review and meta-analysis

Academic improvement is amongst the most common treatment targets when prescribing stimulants to children with ADHD. Previous reviews on stimulant-related academic improvements are inconclusive and focus on task engagement. Recent literature suggests outcome-domain-specific medication effects that are larger for productivity than for accuracy. The aims of this study are quantifying methylphenidate effects on academic productivity and accuracy for math, reading, spelling; exploring the mediating or moderating effects of symptom improvements, demographic-, design- and disorder-related variables. PubMed, EMBASE, ERIC and PsycINFO were searched for articles reporting methylphenidate effects on academic productivity and accuracy. Thirty-four studies met entry criteria. Methylphenidate improved math productivity (7.8% increase, p < .001); math accuracy (3.0% increase, p = .001); increased reading speed (SMD .47, p < .001) but not reading accuracy. None of the mediators or moderators tested affected methylphenidate efficacy. Academic improvements were small compared to symptom improvements; qualitative changes limited to math. Clinicians should take this discrepancy into account when prescribing medication for ADHD.

     

Does photoparoxysmal response in children represent provoked seizure? Evidence from simultaneous motor task during EEG

Objectives

Acute cognitive changes during epileptiform discharges have been studied using computer assisted cognitive tasks. We aimed to demonstrate acute behavioral change (using a simple motor response task MRT) during photoparoxysmal response (PPR) in children below 18 years.

Methods

Children performed a simple repetitive motor task during intermittent photic stimulation (IPS). All episodes of PPR not associated with obvious clinical change (as observed by the technologist or reported by the patient) were analyzed for this study. The average time interval between two successive motor responses across a PPR (test time) was compared to the average time interval between two successive motor responses during IPS not associated with PPR (control time) using Wilcoxon signed ranks test.

Results

21 children who had PPR successfully completed the MRT. The difference between the mean durations was 0.894 s (p = 0.002). More than 50% increase compared to the control time was considered a delay in MRT during PPR. 10 children showed slowing of MRT during PPR.

Conclusion

By definition, acute behavioral change during generalized epileptiform discharges represent provoked seizures. Detecting subclinical seizures can have important safety implications in children (skiing, skating and driving) with PPR on EEG, but no clinical seizures. We recommend MRT during IPS.     

Can music-based movement therapy improve motor dysfunction in patients with Parkinson’s disease? Systematic review and meta-analysis

Neurological Sciences - This study aimed to quantify whether there is association between music-based movement therapy and motor dysfunction in patients with Parkinson’s disease, and, if so,...     

Clinico – diagnostic and therapeutic relevance of computed tomography scan of brain in children with partial seizures

Background:

Therapeutic relevance of computed tomography (CT) in children with partial seizures is reported to be remarkably low (1-2%). However, in the developing countries where infections involving the nervous system are common, routine CT scan of brain may help in finding treatable causes of seizures.

Objective:

Aim of this study was to evaluate the significance of CT scan of brain in the management of children with partial seizures.

Materials and Methods:

Children with partial epilepsy, whose predominant seizure type was focal motor seizures, were included in the study. CT scan of brain was done in all children aged between 1 month and 12 years with partial seizures of unknown etiology prospectively. The clinical findings of these children were noted along with the CT findings.

Results:

Between August 2001 and July 2002, of the 200 children with seizure disorder 50 children who satisfied the inclusion criteria were included in the study. CT scan of brain was normal in 16 children (32%) and was abnormal in 34 children (68%). Twenty children (~60% of abnormal scan) had potentially correctable lesions: Tuberculoma (n = 13), neurocysticercosis (n = 3), and brain abscess (n = 4). Five children had changes representing static pathology that did not influence patient management. The clinical features correlated with CT findings in 78% children.

Conclusion:

Children with partial motor seizures have high probability of having abnormal findings on CT scan of brain, especially, neuro-infections which are potentially treatable. Therefore, CT scan brain should be carried out in all children with partial motor seizures especially, in developing countries.     

Does regular cannabis use affect neuroanatomy? An updated systematic review and meta-analysis of structural neuroimaging studies

European Archives of Psychiatry and Clinical Neuroscience - Regular cannabis use is associated with adverse cognitive and mental health outcomes that have been ascribed to aberrant neuroanatomy in...     

Can acupuncture improve objective sleep indices in patients with primary insomnia? A systematic review and meta-analysis

BackgroundThe efficacy of acupuncture for treating primary insomnia (PI) has been explored in several meta-analyses where the outcomes measures were based on subjective self-reported sleep rating scales. Sleep state misperception is common in PI and self-reports underestimate sleep duration and quality. No systematic reviews or meta-analyses have investigated the efficacy of acupuncture in improving objective sleep measures in PI.ObjectiveTo perform a systematic review to determine whether objective sleep parameters are improved by acupuncture in patients with PI.MethodsRandomized controlled trials treating PI via verum-acupuncture versus sham-/placebo-acupuncture or waitlist control were searched for in English [MEDLINE (via PubMed), Sciverse ScienceDirect, Cochrane Central Register of Controlled Trials (CENTRAL), AMED, Springer, EMBASE (Elsevier), Ebsco Medline, and PsycINFO (ProQuest)] and Chinese (SinoMed, CNKI, Wanfang and CQVIP) databases, from the dates of the databases' inception to January 2020. The parameters of polysomnography (PSG), actigraphy, or micromovement sensitive mattress/pillow sleep monitoring systems were considered as the primary outcome measures. Revman 5.3 and Stata 16.0 software were used to conduct the meta-analysis. Heterogeneity was examined by using I² statistics and publication bias was assessed via Egger's test.ResultsEleven studies involving 775 patients met the inclusion criteria. The results of meta-analysis suggested that acupuncture can increase total sleep time [MD = 55.29, 95%CI (29.16, 81.42), p < 0.01], increase sleep efficiency [MD = 8.96, 95%CI (3.97, 13.95), p < 0.01], decrease wake after sleep onset [MD = −49.54, 95%CI (−82.98, −16.09), p < 0.01], and reduce number of awakening times [MD = −6.29, 95%CI (−10.75, −1.82), p < 0.01] compared with either sham-/placebo-acupuncture or waitlist control. Subsequent analysis indicated a superior effect for verum-acupuncture in comparison with sham-/placebo-acupuncture or waitlist-control when the recommended lowest threshold dosage (12 sessions) was met. Despite positive outcomes, most studies reviewed were heterogeneous and at risk of bias due to methodological issues.ConclusionsDespite limited evidence, acupuncture was significantly associated with improvements in several objective sleep parameters (increases in total sleep time and sleep efficiency, and reductions in wake after sleep onset and number of awakening times) as well as subjective sleep quantity and quality in patients with PI. A minimum therapeutic threshold dosage (≥12 sessions) is recommended. Well-designed RCTs using PSG are required to clarify the influence of acupuncture on sleep architecture/structure and to promote better application of acupuncture as a treatment for PI.     

Risperidone-induced hepatotoxicity in children and adolescents? A chart review study.

Risperidone is an atypical antipsychotic drug that has been used in the treatment of numerous psychiatric disorders in children and adolescents. The question of whether risperidone-induced weight gain is associated with steatohepatitis has recently been raised. The purpose of this chart review was to ascertain: (1) the rate of liver dysfunction observed during risperidone treatment in children and adolescents; and (2) the clinical factors associated with liver dysfunction. For purposes of this chart review study, abnormal liver function was defined by serum transaminase or bilirubin values falling outside the normal laboratory ranges. Chart reviews were completed on 38 youths with ages ranging from 5-17 years with a variety of psychiatric diagnoses. The mean length of risperidone treatment was 15.2 months at a mean dose of 2.5 mg/day. It was found that 37 of the 38 youths treated with risperidone had no liver enzyme abnormalities at the end of study. One subject had an alanine aminotransferase (ALT) level of 46 U/L which was 7 U/L above the upper limit of normal for this laboratory test. This isolated value was not considered clinically significant. These data were noted in spite of weight gain and the use of numerous concomitant psychotropic medications. These findings suggest that risperidone in short term treatment does not commonly lead to evidence of abnormal liver function at therapeutic doses in children and adolescents. Larger-scale, prospective studies are needed in order to confirm these findings.     

Does prenatal methamphetamine exposure affect seizure susceptibility in adult rats with acute administration of the same drug?

The aim of the present study was to investigate whether sensitivity to flurothyl seizures after an acute methamphetamine (MA) administration is different in prenatally MA-exposed adult rats than in controls without prenatal drug exposure. Adult male and female rats exposed prenatally to MA (5mg/kg), saline or neither (controls) were divided into groups; one group received acute MA (1mg/kg s.c.) injection and the other group received saline. Rats were then challenged with flurothyl at a constant flow rate to induce seizures. The threshold of the first focal clonus, clonic seizures and tonic-clonic seizures were analyzed. EFFECTS OF PRENATAL DRUG EXPOSURE: In animals without acute MA administration prior to seizure testing, prenatal MA exposure decreased threshold of the first clonus relative to control animals. This decrease in threshold was not apparent in groups pretreated with acute MA injection. EFFECTS OF ACUTE MA ADMINISTRATION: There was an increased threshold to both, first focal clonus and clonic seizures in animals with acute MA injection than in animals without it. The increase induced by acute MA pretreatment was higher in prenatally MA-exposed animals relative to controls. Further, clonic seizures were shorter and developed faster into tonic-clonic seizures in these acutely injected animals compared to animals without acute MA injection. EFFECTS OF HORMONES: The threshold of all measured attributes was decreased in males. Estrous cycle influences did not lead to changes between groups of prenatal exposure or acute MA administration. Threshold of tonic-clonic seizures was increased in females in proestrus/estrus stage of the estrous cycle relative to diestrous females. Our study suggests that prenatal MA exposure affects the sensitivity of adult rats to the effect of acute MA treatment prior to flurothyl seizures relative to controls.     

How effective are drug treatments for children with ADHD at improving on-task behaviour and academic achievement in the school classroom? A systematic review and meta-analysis

Attention-deficit hyperactivity disorder (ADHD) has a significant impact on children’s classroom behaviour, daily functioning and experience of school life. However, the effects of drug treatment for ADHD on learning and academic achievement are not fully understood. This review was undertaken to describe the effects of methylphenidate, dexamfetamine, mixed amfetamine salts and atomoxetine on children’s on-task behaviour and their academic performance, and to perform a meta-analysis to quantify these effects. Nine electronic databases were systematically searched for randomized controlled trials comparing drug treatment for ADHD against (i) no drug treatment, (ii) baseline (in crossover trials), or (iii) placebo; reporting outcomes encompassing measures of educational achievement within the classroom environment. Forty-three studies involving a pooled total of 2,110 participants were identified for inclusion. Drug treatment benefited children in the amount of school work that they completed, by up to 15 %, and less consistently improved children’s accuracy in specific types of academic assignments, such as arithmetic. Similar improvements were seen in classroom behaviour, with up to 14 % more of children’s time spent “on task”. Methylphenidate, dexamfetamine and mixed amfetamine formulations all showed beneficial effects on children’s on-task behaviour and academic work completion. Atomoxetine was examined in two studies, and was found to have no significant effect. These review findings suggest that medication for ADHD has the potential to improve children’s learning and academic achievement.     

What influences participation in leisure activities of children and youth with physical disabilities? A systematic review

In 2001 the International Classification of Functioning (ICF) defined participation as ‘someone's involvement in life situations’. Participation in leisure activities contributes to the development of children and their quality of life. Children with physical disabilities are known to be at risk for participation in fewer activities. The group of children with physical disabilities is highly heterogeneous consisting of children with different diagnosis and different ages.This systematic review aims to analyse the literature for the purpose of looking for variables involved in the frequency of participation in leisure activities for children and youth with different diagnoses and ages.Frequency of participation in leisure activities for children and youth with physical disabilities is associated with a variety of variables. Gross motor function, manual ability, cognitive ability, communicative skills, age and gender are the most important variables. The current evidence suggests that similar variables seem to apply to children with different diagnoses. Age is an important variable in participation of children and youth. However evidence about those variables associated with children at different ages is still lacking.     

Is the mirror neuron system involved in imitation? A short review and meta-analysis

It has been suggested that the mirror neuron system provides an important neural substrate for humans’ ability to imitate. Mirror neurons have been found during single-cell recordings in monkeys in area F5 and PF. It is believed that the human equivalent of this mirror system in humans is the pars opercularis of the inferior frontal gyrus (area 44) and the rostral part of the inferior parietal lobule. This article critically reviews published fMRI studies that examined the role of frontal and parietal brain regions in imitation. A meta-analysis using activation likelihood estimation (ALE) revealed that the superior parietal lobule, inferior parietal lobule, and the dorsal premotor cortex but not the inferior frontal gyrus, are all commonly involved in imitation. An additional meta-analysis using a label-based review confirmed that in the frontal lobe, the premotor cortex rather than the inferior frontal gyrus is consistently active in studies investigating imitation. In the parietal region the superior and inferior parietal lobules are equally activated during imitation. Our results suggest that parietal and frontal regions which extend beyond the classical mirror neuron network are crucial for imitation.     

Antidepressants and quality of life in patients with major depressive disorder – Systematic review and meta-analysis of double-blind,placebo-controlled RCTs

Background

Quality of Life (QoL) is an important outcome in mental disorders. We investigated whether antidepressant pharmacotherapy improved QoL vs. placebo among patients with MDD.

Methods

Systematic literature search in CENTRAL, Medline, PubMed Central, and PsycINFO of double-blind, placebo-controlled RCTs. Screening, inclusion, extraction, and risk of bias assessment were conducted independently by two reviewers. We calculated summary standardized mean differences (SMD) with 95%-CIs. We followed Cochrane Collaboration's Handbook of Systematic Reviews and Meta-Analyses and PRISMA guidelines (protocol registration at OSF).

Results

We selected 46 RCTs out of 1807 titles and abstracts screened, including 16.171 patients, 9131 on antidepressants and 7040 on placebo, a mean age of 50.9 years, with 64.8% women. Antidepressant drug treatment resulted in a SMD in QoL of 0.22 ([95%-CI: 0.18; 0.26] I² 39%) vs. placebo. SMDs differed by indication: 0.38 ([0.29; 0.46] I² 0%) in maintenance studies, 0.21 ([0.17; 0.25] I² 11%) in acute treatment studies, and 0.11 ([−0.05; 0.26], I² 51%) in studies focussing on patients with a physical condition and major depression. There was no indication of subtstantial small study effects, but 36 RCTs had a high or uncertain risk of bias, particularly maintenance trials. QoL and antidepressive effect sizes were associated (Spearman's rho 0.73, p < 0.001).

Conclusions

Antidepressants' effects on QoL are small in primary MDD, and doubtful in secondary major depression and maintenance trials. The strong correlation of QoL and antidepressive effects indicates that the current practice of measuring QoL may not provide sufficient additional insights into the well-being of patients.     

Should children with Bell's palsy be treated with corticosteroids? A systematic review

The objective of this study was to evaluate the effect of corticosteroids in the treatment of pediatric Bell's palsy. A systematic review of trials that included pediatric (< 16 years old) cases with Bell's palsy and involved the use of steroids was conducted. Eight trials were identified, five of which were randomized, and prednisone was used in six trials, whereas corticotropin was used in the other two. The methods of randomization and allocation concealment of the treatments used were rarely reported. Only one trial was done exclusively in children; none of the other seven trials analyzed the pediatric cases separately. Four trials reported some benefit from steroids. The pediatric trial did not provide evidence for benefit from corticosteroids. There was substantial heterogeneity in the population and interventions used; hence a meta-analysis was not done. Based on this systematic review, we do not recommend the routine use of steroids in children with Bell's palsy.