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1.
J Child Adolesc Psychopharmacol ; 30(1): 32-37, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31800306

RESUMO

Background: Many children and adults with Obsessive-Compulsive Disorder (OCD) fail to respond to first-line pharmacological and behavioral treatments. Glutamate dysfunction may contribute to the development of OCD. N-acetylcysteine (NAC), a glutamate modulating drug, has shown to be a promising agent in adults with OCD. Methods: We conducted a double-blind, placebo-controlled clinical trial from July 2012 to January 2017. Children ages 8 to 17 years with OCD were assigned to receive NAC (up to 2700 mg/day) or the matching placebo for a period of 12 weeks. Children were required to be on stable psychiatric treatment (both medication and therapy) but were not required to be treatment-refractory. The primary outcome was OCD symptom severity as measured by the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). We used linear mixed models to analyze the effect of NAC compared to placebo. Results: Due to poor recruitment and eventual expiration of the study medication, enrollment was stopped at 11 children out of a planned sample size of 40. Nonetheless, NAC was associated with significant reduction in CY-BOCS total score compared to placebo (Satterthwaite's test: t (37) = 2.36, p = 0.024) with effects separating from placebo beginning at week 8. Mean CY-BOCS total score decreased in the NAC group from 21.4 ± 4.65 at baseline to 14.4 ± 5.55 at week 12. In the placebo group, mean CY-BOCS total score remained unchanged (21.3 ± 4.65). In the NAC group, 1 out of 5 participants achieved >35% improvement in CY-BOCS total score, while none of the six patients in placebo group reached this improvement level. NAC and placebo were well tolerated. One mild adverse event was reported in each group. Conclusions: Our trial suggests that there may be some initial improvement in OCD symptom severity with NAC treatment. NAC was well tolerated in the study population. Future trials should employ multiple sites and have a larger study population to further confirm any benefits of NAC.

2.
Eur Child Adolesc Psychiatry ; 28(8): 1129-1135, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30661132

RESUMO

Although the DSM-5 chronic motor tic disorder (CMTD) and Tourette syndrome (TS) are distinct diagnostic categories, there is no genetic or phenotypic evidence that supports this diagnostic categorization. The aim of this study was to compare patients with both diagnoses along a number of clinical characteristics to provide further diagnostic clarity. Our sample consisted of 1018 patients (including adult and child patients) suffering from chronic tic disorders. Tic severity was assessed via Shapiro Tourette-Syndrome Severity Scale (STSS). Lifetime prevalence of other comorbid conditions was assessed in a semi-structured clinical interview. The data were gained through retrospective chart analysis. The two groups did not differ significantly in any of the clinical or demographic variables. Patients only differed in tic severity, with CMTD patients (n = 40) having lower mean tic severity (STSS = 2.0 vs. 2.8; p < 0.001), prevalence of complex motor tics (27.5% vs. 55.9%; p < 0.01), copropraxia (0% vs. 16.2%; p < 0.01) and echopraxia (10.0% vs. 23.8%; p < 0.05), and a markedly lower comorbidity score (1.9 vs. 2.7; p < 0.001) as compared to TS patients (n = 978). Our results suggest that both disorders exist along a symptom severity continuum of which TS constitutes a more severe and CMTD a less severe form. We therefore suggest the introduction of the term "tic spectrum disorders", instead of using different diagnostic categories.


Assuntos
Manual Diagnóstico e Estatístico de Transtornos Mentais , Transtorno Obsessivo-Compulsivo/epidemiologia , Transtornos de Tique/diagnóstico , Síndrome de Tourette/diagnóstico , Criança , Feminino , Humanos , Masculino , Estudos Retrospectivos , Índice de Gravidade de Doença
3.
Depress Anxiety ; 36(3): 198-212, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30479005

RESUMO

BACKGROUND: We aimed to examine the efficacy of selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) for anxiety disorders examining overall symptom improvement, likelihood of treatment response, time course of treatment response, individual pharmacological agent, diagnostic indication dose, and tolerability. METHODS: We searched PubMed and Cochrane Central Register of Controlled Trials. We included randomized placebo-controlled clinical trials of SSRIs/SNRIs in adult patients with anxiety disorders that provided data at three or more time points. Extracted data included trial duration, weekly/biweekly anxiety scores for 12 weeks. RESULTS: Meta-analysis included 57 trials (N = 16,056). A linear mixed model analysis based on weekly outcome data suggested that for SNRI a logarithmic model offered the best fit compared to placebo (indicating the greatest incremental improvement from baseline occurred early in treatment); whereas for SSRI a linear model provided the best fit (indicating a similar improvement over the duration of the acute treatment phase). There were no significant differences in efficacy between pharmacological agents within each class or when comparing SSRIs to SNRIs. The greatest treatment benefits were observed for social anxiety disorder for both medication classes. Higher doses of SSRIs, but not SNRIs, were associated with significantly greater symptom improvement and likelihood of treatment response. For both medical classes, higher doses were associated with an increased likelihood of dropout due to side effects. CONCLUSIONS: SSRIs and SNRIs are effective in treating anxiety disorders. Higher doses of SSRIs within the therapeutic range are associated with greater treatment benefit, whereas higher doses of SNRIs are not.


Assuntos
Transtornos de Ansiedade/tratamento farmacológico , Inibidores de Captação de Serotonina/administração & dosagem , Inibidores de Captação de Serotonina/uso terapêutico , Inibidores da Recaptação de Serotonina e Norepinefrina/administração & dosagem , Inibidores da Recaptação de Serotonina e Norepinefrina/uso terapêutico , Transtornos de Ansiedade/metabolismo , Humanos , Norepinefrina/metabolismo , Fobia Social/tratamento farmacológico , Fobia Social/metabolismo , Serotonina/metabolismo , Inibidores de Captação de Serotonina/farmacologia , Inibidores da Recaptação de Serotonina e Norepinefrina/farmacologia
4.
J Child Adolesc Psychopharmacol ; 28(7): 474-484, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29920116

RESUMO

BACKGROUND: Antipsychotic-related weight gain is a common clinically relevant side effect when treating psychotic disorders in pediatric populations, yet few predictors and no moderators of antipsychotic-related weight gain are known. METHODS: The Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS) study randomized 119 youths (age 8-19 years) with schizophrenia or schizoaffective disorder to 8 weeks of antipsychotic treatment with molindone, risperidone, or olanzapine and assessed treatment response and side effects. In this secondary analysis, we used multivariable linear regression and receiver operating characteristic analysis to investigate predictors and moderators of weight change and percent weight change from baseline to week 8. RESULTS: Treatment assignment was the most discriminant predictor of weight change [F(2, 66) = 17.00, p < 0.001] and percent weight change [F(2, 66) = 16.85, p < 0.001]. Mean weight gain was 0.74 (standard deviation ±3.51) kg for molindone, 4.13 ± 3.79 kg for risperidone, and 7.29 ± 3.44 kg for olanzapine. After adjusting for treatment assignment, lower pretreatment hemoglobin A1C (HgbA1C) predicted more weight gain [F(1, 55) = 4.71, p = 0.03]. Diagnosis (schizoaffective vs. schizophrenia) moderated weight change [F(2, 63) = 6.02, p = 0.004] and percent weight change [F(2, 63) = 5.26, p = 0.008] such that schizoaffective diagnosis predicted larger weight gain for youths in the risperidone treatment arm. Age, sex, family income, baseline weight, and symptoms neither predicted nor moderated weight change or percent weight change. CONCLUSION: We identified prognostic subgroups and novel risk factors for antipsychotic-related weight gain. We confirmed that antipsychotic choice is extremely important for predicting future weight gain. We also found that younger age did not predict greater weight gain, in contrast to prior studies. Our findings require replication in an independent sample because we did not adjust for multiple comparisons to minimize false negatives. ClinicalTrials.gov Identifier: NCT00053703.


Assuntos
Antipsicóticos/uso terapêutico , Olanzapina/uso terapêutico , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico , Adolescente , Feminino , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Fatores de Risco , Ganho de Peso
5.
Dis Markers ; 2018: 2358451, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29545905

RESUMO

Background: Electroconvulsive therapy (ECT) is one of the most effective treatment options for refractory depressed patients. To date, there are only a few predictors of response. Aim: The aim was to identify predictive biomarkers of remission to ECT on a molecular level. Methods: 11 patients suffering from a major depressive episode-according to the Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)-underwent 10 ECT sessions. Blood samples were taken, and the depression severity was assessed before, one hour and 24 hours after sessions 1, 4, 7, and 10 using the Montgomery Asberg Depression Rating Scale (MADRS). A MADRS total score < 12 was interpreted as remission. Results: Patients remitting under ECT had significantly higher homocysteine (p < 0.001), S100B (p < 0.001), and procalcitonin (PCT) (p = 0.027) serum levels. On the contrary, serum levels of vitamin B12 (p < 0.001) and folic acid (p = 0.007) were significantly lower in remitters compared to those in nonremitters. Levels remained unchanged throughout the whole ECT course. Conclusions: Our findings indicate that lower levels of vitamin B12 and folic acid associated with higher levels of homocysteine, S100B, and PCT point to a subgroup of depressed patients sensitive to ECT. Due to the limited sample size, further studies are required to replicate our findings.


Assuntos
Calcitonina/sangue , Transtorno Depressivo Maior/sangue , Eletroconvulsoterapia/métodos , Ácido Fólico/sangue , Homocisteína/sangue , Subunidade beta da Proteína Ligante de Cálcio S100/sangue , Vitamina B 12/sangue , Adulto , Idoso , Biomarcadores/sangue , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Indução de Remissão , Índice de Gravidade de Doença , Resultado do Tratamento
6.
Eur Arch Psychiatry Clin Neurosci ; 268(3): 301-316, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28555406

RESUMO

Genetic studies in Tourette syndrome (TS) are characterized by scattered and poorly replicated findings. We aimed to replicate findings from candidate gene and genome-wide association studies (GWAS). Our cohort included 465 probands with chronic tic disorder (93% TS) and both parents from 412 families (some probands were siblings). We assessed 75 single nucleotide polymorphisms (SNPs) in 465 parent-child trios; 117 additional SNPs in 211 trios; and 4 additional SNPs in 254 trios. We performed SNP and gene-based transmission disequilibrium tests and compared nominally significant SNP results with those from a large independent case-control cohort. After quality control 71 SNPs were available in 371 trios; 112 SNPs in 179 trios; and 3 SNPs in 192 trios. 17 were candidate SNPs implicated in TS and 2 were implicated in obsessive-compulsive disorder (OCD) or autism spectrum disorder (ASD); 142 were tagging SNPs from eight monoamine neurotransmitter-related genes (including dopamine and serotonin); 10 were top SNPs from TS GWAS; and 13 top SNPs from attention-deficit/hyperactivity disorder, OCD, or ASD GWAS. None of the SNPs or genes reached significance after adjustment for multiple testing. We observed nominal significance for the candidate SNPs rs3744161 (TBCD) and rs4565946 (TPH2) and for five tagging SNPs; none of these showed significance in the independent cohort. Also, SLC1A1 in our gene-based analysis and two TS GWAS SNPs showed nominal significance, rs11603305 (intergenic) and rs621942 (PICALM). We found no convincing support for previously implicated genetic polymorphisms. Targeted re-sequencing should fully appreciate the relevance of candidate genes.


Assuntos
Saúde da Família , Polimorfismo de Nucleotídeo Único/genética , Transtornos de Tique/genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Desequilíbrio de Ligação , Masculino , Proteínas Associadas aos Microtúbulos/genética , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Triptofano Hidroxilase/genética , Adulto Jovem
7.
J Clin Child Adolesc Psychol ; 47(2): 266-281, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28956620

RESUMO

This secondary analysis of the Child/Adolescent Anxiety Multimodal Study (CAMS) used baseline patient characteristics to identify prognostic subgroups of children based on likelihood of remission. We also investigated predictors and moderators of outcome. CAMS randomized 488 youths with generalized, social, and separation anxiety disorders to cognitive behavioral therapy (CBT), sertraline, both, or pill placebo. Outcomes were Week 12 child, parent, and independent evaluator (IE) ratings of child anxiety. We used receiver operating characteristics analysis and stepwise regression to identify predictors and moderators of outcome. Severe anxiety, lower socioeconomic status, and comorbid obsessive-compulsive disorder predicted higher IE-rated anxiety posttreatment; child-rated social anxiety predicted poorer outcomes reported by all informants. Regarding moderators, Hispanic ethnicity predicted higher IE-rated anxiety after CBT and higher parent-rated anxiety after sertraline. In youths with severe anxiety (Pediatric Anxiety Rating Scale ≥ 20, <italic>n</italic> = 220), combination treatment increased remission (relative risk [RR] = 2.85, <italic>p</italic> < .001), 95% confidence interval (CI) [1.51, 5.39], whereas CBT (RR = 1.55, <italic>p</italic> = .20), 95% CI [0.77, 3.10], and sertraline (RR = 1.27, <italic>p</italic> = .53), 95% CI [0.59, 2.73], did not significantly increase remission relative to placebo. These are the first findings demonstrating that a combination of CBT and a selective serotonin reuptake inhibitor, not monotherapy, is likely key for achieving remission in severe anxiety. CAMS was not powered to detect treatment efficacy after stratification by anxiety severity, so further research is needed regarding effective treatments in severe anxiety. Our main effect findings suggest youth with severe anxiety (especially social phobia), low socioeconomic status and obsessive-compulsive disorder benefit less from current first-line treatments relative to other anxious youth. ClinicalTrials.gov: NCT00052078.


Assuntos
Transtornos de Ansiedade/tratamento farmacológico , Adolescente , Transtornos de Ansiedade/psicologia , Criança , Feminino , Humanos , Masculino , Prognóstico
8.
Neuropsychopharmacology ; 43(2): 325-333, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28849779

RESUMO

Many patients with social anxiety disorder (SAD) experience inadequate symptom relief from available treatments. Ketamine is a potent N-methyl-D-aspartate receptor antagonist with a potentially novel mechanism of action for the treatment of anxiety disorders. Therefore, we conducted a double-blind, randomized, placebo-controlled crossover trial in 18 adults with DSM-5 SAD and compared the effects between intravenous ketamine (0.5 mg/kg over 40 min) and placebo (normal saline) on social phobia symptoms. Ketamine and placebo infusions were administered in a random order with a 28-day washout period between infusions. Ratings of anxiety were assessed 3-h post-infusion and followed for 14 days. We used linear mixed models to assess the impact of ketamine and placebo on anxiety symptoms. Outcomes were blinded ratings on the Liebowitz Social Anxiety Scale (LSAS) and self-reported anxiety on a visual analog scale (VAS-Anxiety). We also used the Wilcoxon signed-rank test to compare the proportion of treatment responders. Based on prior studies, we defined response as a greater than 35% LSAS reduction and 50% VAS-Anxiety reduction. We found ketamine resulted in a significantly greater reduction in anxiety relative to placebo on the LSAS (Time × Treatment: F9,115=2.6, p=0.01) but not the VAS-Anxiety (Time × Treatment: F10,141=0.4, p=0.95). Participants were significantly more likely to exhibit a treatment response after ketamine infusion relative to placebo in the first 2 weeks following infusion measured on the LSAS (33.33% response ketamine vs 0% response placebo, Wilcoxon signed-rank test z=2.24, p=0.025) and VAS (88.89% response ketamine vs 52.94% response placebo, Wilcoxon signed-rank test z=2.12, p=0.034). In conclusion, this proof-of-concept trial provides initial evidence that ketamine may be effective in reducing anxiety.


Assuntos
Ansiolíticos/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Ketamina/farmacologia , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Adulto , Ansiolíticos/administração & dosagem , Estudos Cross-Over , Método Duplo-Cego , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Feminino , Humanos , Ketamina/administração & dosagem , Masculino , Fobia Social , Escalas de Graduação Psiquiátrica , Adulto Jovem
9.
J Child Adolesc Psychopharmacol ; 27(8): 747-754, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28771386

RESUMO

OBJECTIVE: This study examines predictors of later risky driving behavior in children with attention-deficit/hyperactivity disorder (ADHD). METHODS: Stepwise logistic regression and receiver operating characteristic (ROC) analysis were used to explore baseline predictors of risky driving behavior for adolescents who completed the 8-year follow-up assessment in the Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder (MTA). RESULTS: Stepwise logistic regression analysis explained 19% of the total variance in risky driving behavior. Increased likelihood of risky driving behavior was associated with parental history of conduct disorder, low parental monitoring and supervision, and increased age. ROC analysis identified discriminative predictors for adolescents older and younger than 16 years of age at follow-up. The most discriminative predictors of later risky driving behavior were parental stress at baseline (for children 16 years or older) and increased child-rated parental protectiveness (for children less than 16 years old). CONCLUSION: Risky driving behavior was significantly predicted by baseline characteristics for the MTA cohort. Aspects of parenting behavior (or the child's perception of them), including parental stress levels, parental protectiveness, and parental levels of monitoring and supervision, were most informative in predicting these outcomes. Our results suggest that interventions to reduce high-risk behaviors in these high-risk children with ADHD might involve targeted parenting interventions.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Condução de Veículo/estatística & dados numéricos , Poder Familiar , Assunção de Riscos , Adolescente , Criança , Feminino , Seguimentos , Humanos , Modelos Logísticos , Masculino , Relações Pais-Filho , Pais/psicologia , Curva ROC , Fatores de Risco , Estresse Psicológico/epidemiologia
10.
Int J Mol Sci ; 18(8)2017 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-28796166

RESUMO

We report the cases of two young German male patients with treatment-resistant Tourette syndrome (TS), who suffer from incapacitating stuttering-like speech disfluencies caused by vocal blocking tics and palilalia. Case 1: a 19-year old patient received medical cannabis at a dose of 1 × 0.1 g cannabis daily. Case 2: a 16-year old patient initially received dronabinol at a maximum dose of 22.4-33.6 mg daily. Both treatments provided significant symptom improvement of vocal blocking tics as well as of comorbid conditions and were well tolerated. Thus, cannabis-based medicine appears to be effective in treatment-resistant TS patients with vocal blocking tics.


Assuntos
Agonistas de Receptores de Canabinoides/uso terapêutico , Dronabinol/uso terapêutico , Maconha Medicinal/uso terapêutico , Tiques/tratamento farmacológico , Síndrome de Tourette/tratamento farmacológico , Adolescente , Adulto , Agonistas de Receptores de Canabinoides/administração & dosagem , Dronabinol/administração & dosagem , Humanos , Masculino , Maconha Medicinal/administração & dosagem , Índice de Gravidade de Doença , Tiques/complicações , Tiques/patologia , Síndrome de Tourette/complicações , Síndrome de Tourette/patologia , Adulto Jovem
11.
Psychother Psychosom Med Psychol ; 67(6): 252-268, 2017 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-28722101

RESUMO

Gilles de la Tourette syndrome is a chronic neuropsychiatric movement disease with combined motor tics and at least one vocal tic for a minimum period of 1 year. It typically begins in the childhood (under 18 years of age).Most of the patients with Tourette syndrome have comorbidities, which often impair their quality of life more than the tics themselves.There are reported abnormalities in the cortico-striato-thalamo-cortical regions as well as in the neurotransmission of dopamine and other neurotransmission systems. Genetic and non genetic factors are discussed.In each patient psychoeducation is the basis of treatment. Specific treatment is only needed in more severe tic disorders which cause evident psychosocial impairment.Behavior therapy should be tried before drug treatment. For very severely affected adults, deep brain stimulation is a further treatment option.


Assuntos
Síndrome de Tourette/psicologia , Síndrome de Tourette/terapia , Adulto , Criança , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Tiques/etiologia , Tiques/psicologia , Tiques/terapia , Síndrome de Tourette/complicações , Síndrome de Tourette/etiologia
12.
Psychiatry Res ; 255: 248-255, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28595147

RESUMO

The Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS) compared the efficacy of risperidone, olanzapine, and molindone over 8 weeks in 119 youths age 8-19 years with early-onset schizophrenia or schizoaffective disorder. From this large dataset, we examined predictors of treatment response and drop out using stepwise regression and receiver operating characteristics curve (ROC) analysis. Treatment response was defined as having both a ≥ 20% improvement in Positive and Negative Syndrome Scale (PANSS) score and a Clinical Global Impression-Improvement (CGI-I) score < 3. More severe baseline symptoms, having a history of being in an early education program, and previous prescription of a mood stabilizer increased the likelihood of responding to treatment. Anhedonia and poor community functioning predicted a reduction in symptom severity on the PANSS. Random assignment to different antipsychotic treatment was not predictive of outcome. Parental report of aggressive behaviors at baseline and being African American were associated with a greater likelihood of drop out. Our results suggest youth with more severe psychotic symptoms are most likely to benefit from treatment with antipsychotics and that aggressive youth may require additional support to improve treatment adherence. Further investigation is needed to understand potentially modifiable predictors of response like early education programs.


Assuntos
Pacientes Desistentes do Tratamento/psicologia , Esquizofrenia/diagnóstico , Esquizofrenia/tratamento farmacológico , Psicologia do Esquizofrênico , Adolescente , Adulto , Antipsicóticos/uso terapêutico , Benzodiazepinas/uso terapêutico , Método Duplo-Cego , Diagnóstico Precoce , Feminino , Humanos , Olanzapina , Valor Preditivo dos Testes , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/psicologia , Risperidona/uso terapêutico , Resultado do Tratamento
13.
Brain Sci ; 7(5)2017 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-28445405

RESUMO

Early anecdotal reports and preliminary studies suggested that cannabinoid-based medicines such as delta-9-tetrahydrocannabinol (THC) are effective in the treatment of Gilles de la Tourette syndrome (TS). We report a single case study of a patient with otherwise treatment-resistant TS successfully treated with nabiximols. Our patient was a 22-year-old male suffering from severe and complex TS. Treatment with nabiximols was commenced at a dose of 1 puff/day (= 100 µL containing 2.7 mg THC and 2.5 mg cannabidiol (CBD)) and slowly increased up to a dosage of 3 × 3 puffs/day (= 24.3 mg THC and 22.5 mg CBD). Several clinical measures for tics, premonitory urges, and global impairment were acquired before and after two weeks of treatment. Treatment with nabiximols resulted in major improvements of both tics and premonitory urges, but also global impairment and health-related quality of life according to all used measurements without causing relevant adverse effects. Our results provide further evidence that treatment with nabiximols may be effective in the treatment of patients with TS. Given the positive response exhibited by the patient highlighted in this report, further investigation of the effects of nabiximols is proposed on a larger group of patients in a clinical trial setting.

14.
J Child Adolesc Psychopharmacol ; 27(4): 296-309, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28253029

RESUMO

OBJECTIVE: To explore predictors of 8-year school-based behavioral outcomes in attention-deficit/hyperactivity disorder (ADHD). METHODS: We examined potential baseline predictors of school-based behavioral outcomes in children who completed the 8-year follow-up in the multimodal treatment study of children with ADHD. Stepwise logistic regression and receiver operating characteristic (ROC) analysis identified baseline predictors that were associated with a higher risk of truancy, school discipline, and in-school fights. RESULTS: Stepwise regression analysis explained between 8.1% (in-school fights) and 12.0% (school discipline) of the total variance in school-based behavioral outcomes. Logistic regression identified several baseline characteristics that were associated with school-based behavioral difficulties 8 years later, including being male (associated with truancy and school discipline), African American (school discipline, in-school fights), increased conduct disorder (CD) symptoms (truancy), decreased affection from parents (school discipline), ADHD severity (in-school fights), and study site (truancy and school discipline). ROC analyses identified the most discriminative predictors of truancy, school discipline, and in-school fights, which were Aggression and Conduct Problem Scale Total score, family income, and race, respectively. CONCLUSIONS: A modest, but nontrivial portion of school-based behavioral outcomes, was predicted by baseline childhood characteristics. Exploratory analyses identified modifiable (lack of paternal involvement, lower parental knowledge of behavioral principles, and parental use of physical punishment), somewhat modifiable (income and having comorbid CD), and nonmodifiable (African American and male) factors that were associated with school-based behavioral difficulties. Future research should confirm that the associations between earlier specific parenting behaviors and poor subsequent school-based behavioral outcomes are, indeed, causally related and independent cooccurring childhood psychopathology. Future research might target increasing paternal involvement and parental knowledge of behavioral principles and reducing use of physical punishment to improve school-based behavioral outcomes in children with ADHD.


Assuntos
Agressão/psicologia , Transtorno do Deficit de Atenção com Hiperatividade/terapia , Comportamento Problema/psicologia , Adolescente , Afro-Americanos , Criança , Terapia Combinada , Transtorno da Conduta , Feminino , Humanos , Estudos Longitudinais , Masculino , Relações Pais-Filho , Poder Familiar/psicologia , Instituições Acadêmicas , Fatores Sexuais
15.
Front Neurosci ; 10: 415, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27672357

RESUMO

BACKGROUND: Gilles de la Tourette syndrome (TS) is a complex neuropsychiatric disorder defined by the presence of motor and phonic tics, but often associated with psychiatric comorbidities. The main objective of this study was to explore the clinical presentation and comorbidities of TS. METHOD: We analyzed clinical data obtained from a large sample (n = 1032; 529 children and 503 adults) of patients with tic disorders from one single German TS center assessed by one investigator. Data was collected with the help of an expert-reviewed semi-structured interview, designed to assess tic severity and certain comorbidities. Group comparisons were carried out via independent sample t-tests and chi-square tests. RESULTS: The main findings of the study are: (1) tic severity is associated with the presence of premonitory urges (PU), copro-, echo-, and paliphenomena and the number of comorbidities, but not age at tic onset; it is higher in patients with comorbid obsessive-compulsive disorder (OCD) than in patients with comorbid attention deficit/hyperactivity disorder (ADHD). (2) PU were found to be highly associated with "not just right experiences" and to emerge much earlier than previously thought alongside with the ability to suppress tics (PU in >60% and suppressibility in >75% at age 8-10 years). (3) Self-injurious behavior (SIB) is highly associated with complex motor tics and coprophenomena, but not with OCD/obsessive-compulsive behavior (OCB). While comorbid ADHD is associated with a lower ability to suppress tics, comorbid depression is associated with sleeping problems. DISCUSSION: Our results demonstrate that tic severity is not influenced by age at onset. From our data, it is suggested that PU represent a specific type of "not just right experience" that is not a prerequisite for tic suppression. Comorbid ADHD reduces patients' ability of successful tic suppression. Our data suggest that SIB belongs to the coprophenomena spectrum and hence should be conceptualized as a complex tic rather than a compulsion. Finally, this study strongly supports the hypothesis that TS+OCD is a more severe form of TS and that comorbid OCD/OCB, depression, and anxiety belong to the TS spectrum, while ADHD should be better conceptualized as a separate problem.

16.
Front Neurosci ; 10: 416, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27672358

RESUMO

Gilles de la Tourette Syndrome (GTS) is characterized by motor and vocal tics, as well as associated comorbid conditions including obsessive-compulsive disorder (OCD), attention deficit/hyperactivity disorder (ADHD), depression, and anxiety which are present in a substantial number of patients. Although randomized controlled trials including a large number of patients are still missing, aripiprazole is currently considered as a first choice drug for the treatment of tics. The aim of this study was to further investigate efficacy and safety of aripiprazole in a group of drug-free, adult patients. Specifically, we investigated the influence of aripiprazole on tic severity, comorbidities, premonitory urge (PU), and quality of life (QoL). Moreover, we were interested in the factors that influence a patient's decision in electing for-or against- pharmacological treatment. In this prospective uncontrolled open-label study, we included 44 patients and used a number of rating scales to assess tic severity, PU, comorbidities, and QoL at baseline and during treatment with aripiprazole. Eighteen out of fortyfour patients decided for undergoing treatment for their tics with aripiprazole and completed follow-up assessments after 4-6 weeks. Our major findings were (1) aripiprazole resulted in significant reduction of tics, but did not affect PU; (2) aripiprazole significantly improved OCD and showed a trend toward improvement of other comorbidities including depression, anxiety, and ADHD; (3) neither severity of tics, nor PU or QoL influenced patients' decisions for or against treatment of tics with aripiprazole; instead patients with comorbid OCD tended to decide in favor of, while patients with comorbid ADHD tended to decide against tic treatment; (4) most frequently reported adverse effects were sleeping problems; (5) patients' QoL was mostly impaired by comorbid depression. Our results suggest that aripiprazole may improve associated comorbid conditions in addition to tics in patients with GTS. It can be hypothesized that these beneficial effects are related to aripiprazole's adaptive pharmacological profile, which exhibits an influence on the dopaminergic as well as a number of other neurotransmitter systems. For the first time, our data provide evidence that patients' decision making process for or against medical treatment is influenced by other factors than tic severity and QoL.

17.
J Clin Psychiatry ; 77(10): e1262-e1269, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27631142

RESUMO

OBJECTIVE: Selective serotonin reuptake inhibitors are first-line treatment for major depressive disorder (MDD), but their impact on suicidal ideation is equivocal. Our goal is to examine the time course and clinical predictors of citalopram-induced suicidal ideation during phase 1 of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. METHODS: Of the 4,041 subjects with DSM-IV nonpsychotic MDD in the STAR*D trial phase 1 (2001-2006), we included in our analysis 3,577 subjects who reported side-effect data and had received citalopram (20-60 mg/d) for 8-14 weeks. Suicidal ideation was reported on item 12 of the Quick Inventory of Depressive Symptomatology, Self-Report. Survival analysis and receiver operating characteristic analysis were used to assess baseline characteristics associated with emergence and worsening of suicidal ideation. RESULTS: Suicidal ideation was more likely to occur early in citalopram treatment, with few subjects showing emergence or worsening occurring after 6 weeks of treatment. Clinical variables explained very little of the variance in worsening or emergence of suicidal ideation with citalopram treatment (generalized R² ≤ 2% in survival analysis). Being Hispanic, taking sedative medications, increased depression severity, absence of hypersomnia, and cardiac comorbidity were significantly (P ≤ .04) associated with greater likelihood of emergence of suicidal ideation in patients without suicidal ideation at baseline. Being widowed, better work performance, weight loss at baseline, and the presence of vascular or neurologic comorbidities were associated with a greater likelihood of worsening of suicidal ideation. CONCLUSIONS: Baseline clinical variables were poor predictors of emergence or worsening of suicidal ideation. As such, increased research focusing on clinical correlates rather than clinical predictors of suicidal ideation may be useful, as intervening events may be crucial in bringing about increased suicidality. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00021528.


Assuntos
Citalopram/efeitos adversos , Citalopram/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Ideação Suicida , Adulto , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Inventário de Personalidade/estatística & dados numéricos , Psicometria/estatística & dados numéricos , Fatores de Risco , Fatores de Tempo
18.
J Am Acad Child Adolesc Psychiatry ; 55(10): 851-859.e2, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27663940

RESUMO

OBJECTIVE: We conducted a meta-analysis to examine the following: the time course of response to selective serotonin reuptake inhibitors (SSRIs) and clomipramine in pediatric obsessive-compulsive disorder (OCD); whether higher doses of SSRIs are associated with an improved response in pediatric OCD; differences in efficacy among SSRI agents; differences in efficacy between SSRIs and clomipramine; and whether the time course and magnitude of response to SSRIs are different in pediatric and adult patients with OCD. METHOD: We searched PubMed and CENTRAL for randomized controlled trials comparing SSRIs (or clomipramine) to placebo for the treatment of pediatric OCD and using the Children's Yale-Brown Obsessive-Compulsive Scale as an outcome. We extracted weekly symptom data from trials to characterize the trajectory of pharmacological response to SSRIs. Pooled estimates of treatment effect were calculated based on weighted mean differences between the treatment and placebo groups. RESULTS: Nine trials involving 801 children with OCD were included in this meta-analysis. A logarithmic model indicating that the greatest benefits occurred early in treatment best fit the longitudinal data for both clomipramine and SSRIs. Clomipramine was associated with a greater measured benefit compared to placebo than SSRIs. There was no evidence for a relationship between SSRI dosing and treatment effect, although data were limited. Adults and children with OCD demonstrated a similar degree and time course of response to SSRIs in OCD. CONCLUSION: These results suggest that the greatest incremental treatment gains in pediatric OCD occur early in SSRI treatment (similar to adults with OCD and children and adults with major depression).


Assuntos
Clomipramina/uso terapêutico , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Inibidores de Captação de Serotonina/uso terapêutico , Criança , Humanos , Transtorno Obsessivo-Compulsivo/psicologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
20.
Front Psychiatry ; 7: 119, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27445874

RESUMO

BACKGROUND: In recent years, behavioral therapy with comprehensive behavioral intervention for tics (CBIT) has been recognized as an effective and safe treatment in patients with Gilles de la Tourette syndrome. In Germany, however, dissemination of CBIT is restricted due to a considerable lack of well-trained therapists. The aim of this study is to overcome this deficiency by creating a new and sophisticated Internet-delivered CBIT (iCBIT) program. With this study, we want to demonstrate that iCBIT is superior to Internet-delivered psychoeducation and comparable to face-to-face CBIT. METHOD AND ANALYSIS: This is a multicenter, prospective, randomized, controlled, observer-blind clinical trial, which will be conducted at five sites in Germany (ONLINE-TICS). Over the course of 2 years, 160 adult patients with chronic tic disorders will be assigned to one of three treatment arms: iCBIT (n = 72), online psychoeducation (n = 72), or face-to-face CBIT (n = 16). All treatments will consist of eighty therapy sessions over a period of 10 weeks and will follow the well-established CBIT manual by Woods and colleagues. The primary outcome measure will be the change in Yale Global Tic Severity Scale (YGTSS) at 1-week posttreatment. Secondary outcome measures include YGTSS change at 3 and 6 months, video- and self-ratings of tics as well as scales for psychiatric comorbidities assessed at each visit. The primary analysis will compare iCBIT to online psychoeducation using a mixed linear model with the YGTSS change as dependent variable. Secondary analyses will look at the comparison between iCBIT and face-to-face CBIT in a non-inferiority analysis. DISCUSSION: If iCBIT proves to be effective, it would be a considerable contribution to close the wide gap in treatment providers for tic disorders not only in Germany but also in several other countries, since this Internet-delivered therapy does not require the supervision of a therapist. In addition, iCBIT would be a cost-effective and readily available treatment alternative that guarantees high quality standard of CBIT. ETHICS AND DISSEMINATION: All institutional review boards approve the protocol. All participants will provide informed consent. There are no conflicts of interest. After study completion, the results will be published. STUDY REGISTRATION: ClinicalTrials.gov Identifier: NCT02413216.

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