Efficacy and safety of methylphenidate and behavioural parent training for children aged 3-5 years with attention-deficit hyperactivity disorder: a randomised, double-blind, placebo-controlled, and sham behavioural parent training-controlled trial.

BACKGROUND: There is insufficient evidence to support treatment recommendations for preschool children aged 3-5 years with attention-deficit hyperactivity disorder (ADHD). We aimed to investigate the efficacy and safety of methylphenidate and behavioural parent training in reducing the frequency and severity of symptoms and improving global functioning in preschool children with ADHD. METHODS: We did an 8-week, randomised, double-blind, placebo-controlled and sham behavioural parent training-controlled clinical trial (the MAPPA Study) in children aged 3-5 years with moderate-to-severe ADHD. The trial was conducted at the Institute of Psychiatry, Hospital das Clinicas, University of São Paulo Medical School, São Paulo, Brazil. Participants were randomly assigned (1:1:1) to receive immediate-release methylphenidate plus educational intervention (sham behavioural parent training), placebo medication plus behavioural parent training, or placebo medication plus educational intervention. Randomisation was done by an independent research manager by use of a permuted block randomisation procedure. Parents, teachers, study staff, and evaluators remained masked to group allocation. Methylphenidate and placebo were titrated to a maximum dose of 1·25 mg/kg per day administered orally twice daily, and behavioural parent training and the educational intervention were delivered weekly through 90 min sessions with both the child and parent, conducted by two psychologists or learning therapists. The primary outcomes were parents' and teachers' composite scores of the Swanson, Nolan, and Pelham-IV scale (SNAP-IV-P/T), the Clinical Global Impressions Severity (CGI-S) scale, and the Children's Global Assessment Scale (CGAS). This trial is registered with ClinicalTrials.gov, NCT02807870, and is now complete. All participants were invited to participate in an open observational follow-up, which is ongoing. FINDINGS: Between Aug 21, 2016, and Oct 21, 2019, 153 children were randomly assigned to receive methylphenidate plus the educational intervention (n=51), placebo plus behavioural parent training (n=51), or placebo plus the educational intervention (n=51). Nine (6%) children discontinued treatment. All participants were included in the intention-to-treat analysis. Children in the methylphenidate plus educational intervention group showed greater reductions in the SNAP-IV-P/T (endpoint mean difference -3·93 [95% CI -7·14 to -0·73], p=0·049; effect size -0·55 [95% CI -0·99 to -0·10]) and CGI-S scores (endpoint mean difference -0·49 [-0·82 to -0·17], p=0·0088; effect size -0·70 [-1·16 to -0·24]) and a greater increase in CGAS scores (endpoint mean difference 5·25 [95% CI 2·09 to 8·40], p=0·0036; effect size 0·80 [95% CI 0·32 to 1·28]) than children in the placebo plus educational intervention group. Children in the placebo plus behavioural parent training group did not have significantly different SNAP-IV-P/T scores (endpoint mean difference -3·18 [95% CI -6·38 to 0·02], p=0·077; effect size -0·44 [95% CI -0·89 to 0·003]) or CGI-S scores (endpoint mean difference -0·35 [-0·68 to -0·03], p=0·052; effect size -0·50 [-0·96 to -0·04]) compared to children in the placebo plus educational intervention group, but they had a greater increase in CGAS scores compared to the placebo plus educational intervention group (endpoint mean difference 3·69 [0·53 to 6·85], p=0·033; effect size 0·56 [0·08 to 1·04]). Children in the methylphenidate plus educational intervention versus placebo plus behavioural parent training group did not have statistically or clinically significant differences in primary outcomes. Children in the methylphenidate plus educational intervention group had more mild adverse events than the other two groups, and there were no between-group differences for moderate or severe adverse events. INTERPRETATION: Methylphenidate was effective in reducing ADHD symptoms and improving functionality, and behavioural parent training was effective in improving functionality for preschool children with ADHD after 8 weeks of treatment. FUNDING: São Paulo Research Foundation and Brazilian National Council for Scientific and Technological Development.

Measuring racing thoughts in healthy individuals: The Racing and Crowded Thoughts Questionnaire (RCTQ).

Racing thoughts refer to an acceleration and overproduction of thoughts, which have been associated with manic and mixed episodes. Phenomenology distinguishes 'crowded' from 'racing' thoughts, associated with mixed depression and mania, respectively. Recent data suggest racing thoughts might also be present in healthy individuals with sub-affective traits and symptoms. We investigated this assumption, with a 34-item self-rating scale, the Racing and Crowded Thoughts Questionnaire (RCTQ), and evaluated its reliability, factor structure, and concurrent validity. 197 healthy individuals completed the RCTQ, the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego - autoquestionnaire (TEMPS-A), the Beck Depression Inventory (BDI), the Altman Self-Rating Mania scale (ASRM), and the Ruminative Response Scale (RRS). Exploratory factor analysis yielded a three-factor solution, labeled 'thought overactivation', 'burden of thought overactivation', and 'thought overexcitability'. Internal consistency of each of the three subscales of the RCTQ was excellent. The TEMPS-A cyclothymia score was associated with the three factors, suggesting good concurrent validity. The 'thought activation' subscale was selectively associated with current elated mood and included items conveying both the notion of increased amount and velocity of thoughts, whereas the 'burden of thought overactivation' subscale was associated with current low mood. The 'thought overexcitability' subscale included items conveying the notion of distractibility, and was associated with both elated and low mood. Rumination was not a significant predictor of RCTQ subscores. These results suggest that the RCTQ has good psychometric properties. Racing and crowded thoughts, as measured by the RCTQ, are a multi-faceted phenomenon, distinct from rumination, and particularly associated with mood instability even in its milder forms.

Hyperthyroid rage: when bipolar disorder hides the real disorder.

Long-term lithium therapy has been associated with euthyroid goiter, hypothyroidism, and less commonly, hyperthyroidism. We report a case of a 19-year-old male patient with schizoaffective disorder who was hospitalized after trying to suffocate his mother. Severe psychomotor agitation persisted despite the high dose of antipsychotics. Initial laboratory tests showed elevated creatine kinase and free thyroxine. Lithium was replaced by sodium valproate, and new laboratory tests were obtained. After lithium discontinuation, the patient had a rapid improvement in agitation and tremors. Antithyroid drugs were not necessary, suggesting the diagnosis of lithium-associated thyrotoxicosis that progressed to spontaneous remission. There are only 2 other reports of lithium-associated thyrotoxicosis successfully treated with lithium withdrawal. Even patients on long-term use of lithium are not free from having acute thyroid dysfunction and may present with treatment-resistant symptoms.

Prevalence of bipolar disorder in a HIV-infected outpatient population.

This study assesses the prevalence of bipolar disorder (BD) among 196 HIV-infected adult outpatients attending in a specialized unit in Fortaleza, Brazil. Patients were interviewed with the Mood Disorder Questionnaire (MDQ), the Mini International Neuropsychiatric Interview (MINI), the Alcohol Use Disorders Identification Test (AUDIT), and a socio-demographic questionnaire based on WHO's behavioral surveillance surveys. Positive MDQ screening was found in 13.2% (N=26) and the BD diagnosis was confirmed in 8.1% (N=16) of the sample. There is an almost four times higher prevalence of BD among the HIV-infected patients of the sample (8.1%) than in the general population from the USA (2.1%). The prevalence of BD type I in the HIV patients was 5.6% (N=11) which is almost six times higher than the US general population (1%). The odds ratios of sexual behaviors and substance abuse variables correlated with BD were calculated. The variables associated with the diagnoses of BD were sex with commercial partners, sex outside the primary relationship, alcohol use disorders, and illicit drug abuse. The most common psychiatric comorbidity in the BD group was substance abuse (61.5%). A better understanding of psychiatric comorbidities and behavioral aspects of HIV-positive patients may help in improving long-term outcome of these patients.

Brazilian Portuguese validation of Mood Disorder Questionnaire.

BACKGROUND: The Mood Disorder Questionnaire (MDQ) is a screening instrument for bipolar spectrum disorders already validated in many languages. METHODS: Patients from 2 psychiatric outpatient facilities were diagnosed with bipolar disorder (BD) type I and II and major depression according to the mood module of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (SCID), Axis I Disorders--Clinician Version. In addition, a control group of healthy subjects was selected. The diagnostic interviews were used as the gold standard against which to investigate the performance of the MDQ. The MDQ was administered to 153 subjects, distributed among 4 groups. We analyzed the test reliability and discriminative capacity of the MDQ for the detection of patients with BD. RESULTS: Based on the SCID, Axis I Disorders--Clinician Version, 52 subjects (33.3%) presented a bipolar spectrum disorder (type I, II, or not otherwise specified), 48 (32.4%) were diagnosed as having unipolar depressive disorder, whereas 54 (35.3%) were unaffected by any type of psychiatric disorder (had no psychiatric disorder according to SCID results). The sensitivity for bipolar disorder was 0.72 (bipolar I disorder, 0.81; bipolar II disorder, 0.58; and bipolar disorder not otherwise specified, 0.69), with specificity of 0.95. The Brazilian Portuguese MDQ demonstrated adequate internal consistency (Cronbach α = .87). LIMITATIONS: Recruiting patients attending tertiary services may inflate the performance of the MDQ. CONCLUSIONS: The performance of the Brazilian Portuguese MDQ is comparable with other language validations. In a psychiatric outpatient sample, the Brazilian Portuguese MDQ proves to be a feasible and reliable screening instrument.