RESUMEN
A three-year open-label study of atomoxetine in adults with ADHD followed two multicenter, double-blind trials. In the double-blind trials, female gender and higher levels of emotional symptoms were associated with better outcome. Following a 4-week placebo washout period, 384 (of 536) subjects continued into the open-label study. 61% of subjects entering this open-label study remained after 6 months at an average dose of 100 mg/day. Subjects who had previously responded to double-blind atomoxetine achieved maximum response after 8 weeks of open-label medication, but others continued to improve for 36 weeks. Women improved more (7.7 ± 6.4) than men (6.1 ± 6.4) on the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) (P = .007) and the Conners' Adult ADHD Rating Scale (P = .03). Subjects with emotional dysregulation improved more than others on the WRAADDS (P = .001). Responders ultimately improved approximately 60% in attentional, hyperactive/impulsive, and emotional symptoms. Thirty-nine percent of atomoxetine double-blind non-responders became responders during open-label treatment.
Asunto(s)
Inhibidores de Captación Adrenérgica/uso terapéutico , Síntomas Afectivos/tratamiento farmacológico , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Propilaminas/uso terapéutico , Adulto , Síntomas Afectivos/complicaciones , Síntomas Afectivos/psicología , Clorhidrato de Atomoxetina , Trastorno por Déficit de Atención con Hiperactividad/psicología , Método Doble Ciego , Femenino , Humanos , Masculino , Escalas de Valoración Psiquiátrica/estadística & datos numéricos , Caracteres Sexuales , Factores de TiempoRESUMEN
BACKGROUND: Comorbidity of personality disorder (PD) and attention-deficit/hyperactivity disorder (ADHD) has been suggested in several reports. However, assessment of PD is problematic, and studies have over-relied on baseline evaluations. METHODS: Forty-seven patients entered a double-blind trial of osmotic release oral system (OROS) methylphenidate (MPH). Patients were assessed at baseline with the Wisconsin Personality Inventory IV (WISPI-IV) and the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II). Following the study, all information-including tests, family reports, and extended clinical observations-produced a final PD diagnosis. Three post hoc categories were created: PD-negative (no PD), PD-positive (1 PD), and PD-plus (2 or more PDs). RESULTS: Twenty-one (45%) patients had a PD on the final assessment vs 62% using SCID-II and 33% using WISPI-IV; final PD diagnosis revealed 9% cluster A, 17% cluster B, and 28% cluster C. Twenty-one percent of patients experienced multiple disorders. Using a weighted kappa, the number of PDs on the final assessment correlated with the WISPI-IV (kappa=.53; P > .001) and the SCID-II (kappa =.70; P < .001). However the SCID-II overidentified and the WISPI-IV underidentified PD. CONCLUSION: Almost all PDs were represented in this sample, and past emphasis on cluster B appears unwarranted. Although the SCID-II and WISPI-IV had limited success in identifying specific PDs, they were more successful in identifying the number of PDs present in each patient. The small sample makes these findings preliminary.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Estimulantes del Sistema Nervioso Central/uso terapéutico , Metilfenidato/uso terapéutico , Trastornos de la Personalidad/diagnóstico , Trastornos de la Personalidad/epidemiología , Adulto , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Comorbilidad , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Inhibidores de Captación de Dopamina/uso terapéutico , Humanos , Determinación de la Personalidad , Trastornos de la Personalidad/clasificación , Pruebas Psicológicas , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: This study explored the relationship between personality disorder (PD) and treatment response in a randomized, double-blind, clinical trial of osmotic release oral system (OROS) methylphenidate (MPH). METHODS: Forty-seven patients entered a crossover trial using the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) to assess outcome. A final personality diagnosis was made using staff consensus and information from the Wisconsin Personality Inventory IV (WISPI-IV) and the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II). Three post hoc categories were created: PD-negative (no PD; n = 26), PD-positive (patients with 1 PD; n = 11), and PD-plus (patients with 2 or more PDs; n = 10). Improvement in attention-deficit/hyperactivity disorder (ADHD) symptoms was assessed using a mixed-model analysis with treatment and personality categories as fixed variables. Average z scores on the WISPI-IV and items endorsed on SCID-II provided dimensional measures of PD severity. RESULTS: Different treatment effects were observed for the PD subgroups (P < .001). PD-negative patients improved 40% on OROS MPH vs 7% on placebo, and PD-positive patients improved 66% on OROS MPH vs 9% on placebo. In contrast, PD-plus patients improved 26% on OROS MPH vs 23% on placebo. CONCLUSION: Most patients experienced significantly reduced ADHD symptoms on OROS MPH; however, patients with 2 or more PDs did not. The 2 alternate measures of PD supported this observation in this small exploratory study.
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Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Estimulantes del Sistema Nervioso Central/uso terapéutico , Inhibidores de Captación de Dopamina/uso terapéutico , Metilfenidato/uso terapéutico , Trastornos de la Personalidad/diagnóstico , Trastornos de la Personalidad/epidemiología , Adulto , Comorbilidad , Femenino , Humanos , Masculino , Determinación de la Personalidad , Pruebas Psicológicas , Ensayos Clínicos Controlados Aleatorios como Asunto , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: This study explored the relationship between the dimensions of adult attention-deficit/hyperactivity disorder (ADHD), personality disorder (PD), and adverse social adjustment. METHODS: In a controlled trial of osmotic release oral system methylphenidate, PD was assessed using the Wisconsin Personality Disorders Inventory IV (WISPI-IV), the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II), and a final consensus diagnosis. Participants were categorized 2 ways: (1) ADHD alone, ADHD with emotional dysregulation (ADHD + ED), and ADHD plus emotional dysregulation plus oppositional symptoms (ADHD + ED + ODD); and (2) those with no PD (PD-negative), 1 (PD-positive), and 2 or more (PD-plus) PDs. RESULTS: None of the ADHD-alone patients had a PD compared with 33% of ADHD + ED patients and 68% of ADHD + ED + ODD patients. The level of ADHD-related emotional and oppositional symptoms correlated significantly with the severity of PD dimensions as assessed by WISPI-IV z scores and the number of items endorsed on the SCID-II screening questionnaire. Complex presentations (define by both ADHD and personality categories) were associated with high childhood ADHD ratings and problems in work, extended family, and economic functioning. CONCLUSION: The ADHD symptoms of emotional dysregulation and oppositional symptoms were associated with increased Axis II disorders. Adverse outcomes were concentrated in patients with ADHD combined with emotional and oppositional symptoms, and in those with comorbid PDs.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/psicología , Trastornos de la Personalidad/diagnóstico , Trastornos de la Personalidad/psicología , Ajuste Social , Adulto , Síntomas Afectivos/fisiopatología , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Estimulantes del Sistema Nervioso Central/uso terapéutico , Comorbilidad , Conflicto Psicológico , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Inhibidores de Captación de Dopamina/uso terapéutico , Femenino , Humanos , Masculino , Metilfenidato/uso terapéutico , Determinación de la Personalidad , Trastornos de la Personalidad/epidemiología , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
INTRODUCTION: Stuttering is a speech disorder in which the flow of speech is disrupted by repetitions, prolongation, and blocks of sounds, syllables, or words. No pharmacological treatments are approved for use in stuttering, and the most common form of treatment is speech therapy. This study was designed to assess the safety, tolerability, and effectiveness of pagoclone during 8 weeks of double-blind treatment followed by a 1-year open-label extension in patients who stutter. METHODS: An 8-week, multicenter, parallel-group, 2-arm, randomized (ratio 2:1 pagoclone-placebo), double-blind study with a 1-year open-label extension conducted at 16 US centers, including men and women aged 18 to 65 years who developed stuttering before 8 years of age. Twice-daily dosing with pagoclone (n = 88 patients) or matching placebo (n = 44 patients), with primary and secondary efficacy variables defined a priori, including Stuttering Severity Instrument Version 3 outcomes, clinician global impressions of improvement, and the change in the percentage of syllables stuttered. RESULTS: Pagoclone produced an average 19.4% reduction in percentage of syllables stuttered compared with 5.1% reduction for placebo. During open-label treatment, a 40% reduction in the percent syllables stuttered was observed after 1 year of treatment with pagoclone. The most commonly reported adverse event during double-blind treatment was headache (12.5% pagoclone patients, 6.8% placebo patients). DISCUSSION: Pagoclone was effective in reducing symptoms of stuttering and was well tolerated. In light of its favorable tolerability profile, as well as consistency of effects across multiple efficacy variables, pagoclone may have potential as a pharmacological treatment of stuttering. LIMITATIONS: The main limitation of this study was the adequacy of the number of subjects who participated because this study was conducted as a pilot investigation. Furthermore, as this condition waxes and wanes, the assessment of stuttering within the clinic setting may not be an adequate reflection of the stuttering of the patients within the community.
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Agonistas de Receptores de GABA-A , Isoindoles/uso terapéutico , Naftiridinas/uso terapéutico , Tartamudeo/tratamiento farmacológico , Adolescente , Adulto , Anciano , Método Doble Ciego , Agonismo Parcial de Drogas , Femenino , Humanos , Isoindoles/efectos adversos , Masculino , Persona de Mediana Edad , Naftiridinas/efectos adversos , Proyectos Piloto , Adulto JovenRESUMEN
BACKGROUND: Bright visible-spectrum light therapy has proven effective in the treatment of seasonal affective disorder (SAD) and recent basic research suggests that blue wavelengths approximately 470 nm account for that effectiveness. To more stringently test the importance of these wavelengths, bright red-light was used for the placebo (control) condition. METHODS: Thirty subjects meeting DSM-IV criteria for SAD were randomized to narrow-band light-emitting diode panels emitting blue- or red-light in this 3-week, parallel, double-blind trial. Twenty-five subjects participated in an open-label blue-light follow-up. Subjects were divided in a blinded, post hoc manner into two groups: SAD only and those experiencing depression with seasonal intensification. The outcome was assessed using Hamilton Depression Rating Scale-17 item version (HAMD-17) and the Structured Interview Guide for the Hamilton Depression Rating Scale-SAD version. Responders were defined by Clinical Global Impression-Improvement scale. RESULTS: HAMD-17 scores improved more under the blue-light condition (51%) than under the red-light condition (32%) (P=.05). Further, in the blue arm 60% of subjects responded compared with 13% in the red arm (P=.01). During the open-label phase, subjects from both double-blind arms improved over baseline. SAD alone patients responded numerically better to treatment than those experiencing depression with seasonal intensification during both treatment periods. CONCLUSIONS: Narrow bandwidth blue-light therapy proved superior to red-light therapy. Blue-light therapy produced results similar to both previous 10,000 lux visible-spectrum light studies and many medication studies. The use of bright red panels supported claims that wavelengths of approximately 470 nm account for the documented effectiveness of light therapy.
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Fototerapia/métodos , Trastorno Afectivo Estacional/terapia , Adulto , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Método Doble Ciego , Femenino , Humanos , Masculino , Trastorno Afectivo Estacional/diagnóstico , Trastorno Afectivo Estacional/psicología , Índice de Severidad de la Enfermedad , Encuestas y CuestionariosRESUMEN
BACKGROUND: The realization that attention-deficit/hyperactivity disorder (ADHD) often persists into adulthood has led to increased frequency of diagnosis and treatment in adults. Osmotic release oral system (OROS) methylpheni-date is a long-acting stimulant demonstrated to be effective in the treatment of children and adolescents with ADHD. METHOD: Forty-seven adults entered and 41 completed this double-blind, placebo-controlled, crossover trial of OROS methylphenidate. Each double-blind arm lasted 4 weeks; data were collected from August 2004 through December 2005. Subjects met both DSM-IV-TR and Utah Criteria for ADHD in adults. Outcome measures included the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS), the adult ADHD-Rating Scale (ADHD-RS), and the Clinical Global Impressions-Improvement scale (CGI-I). At baseline, subjects were categorized as having significant emotional symptoms with the WRAADDS and/or significant oppositional-defiant symptoms using a self-report scale assessing the DSM-IV criteria for oppositional defiant disorder. RESULTS: 17% of the sample (N = 8) had ADHD alone, 38% (N = 18) had ADHD plus significant emotional symptoms, and 40% (N = 19) had ADHD with both significant emotional and oppositional symptoms. At a mean +/- SD dose of 64.0 +/- 23.3 (0.75 mg/kg), OROS methylphenidate proved superior to placebo for all clinical measures: total WRAADDS score decrease of 42% versus 13%, respectively, p < .001 and total ADHD-RS score decrease of 41% versus 14%, respectively, p = .003, plus the subscales addressing inattention, hyperactivity/ impulsivity, and emotional dysregulation. CONCLUSIONS: OROS methylphenidate proved effective in treating adult ADHD. ADHD alone was relatively uncommon. Over 80% of our patients had ADHD with a combination of emotional and/or oppositional symptoms.
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Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Trastorno por Déficit de Atención con Hiperactividad/psicología , Estimulantes del Sistema Nervioso Central/administración & dosificación , Estimulantes del Sistema Nervioso Central/uso terapéutico , Metilfenidato/administración & dosificación , Metilfenidato/uso terapéutico , Administración Oral , Adulto , Síntomas Afectivos/psicología , Déficit de la Atención y Trastornos de Conducta Disruptiva/psicología , Estudios Cruzados , Preparaciones de Acción Retardada , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ósmosis , Resultado del TratamientoRESUMEN
BACKGROUND: Before 1980, attention-deficit/hyperactivity disorder (ADHD) was called minimal brain dysfunction and included emotional symptoms now listed as "associated features" in DSM-IV. Data from two multicenter, placebo-controlled studies with 536 patients were reexamined to assess: 1) the pervasiveness of these symptoms in samples of adults with ADHD; 2) the response of these symptoms to atomoxetine; and 3) their association with depressive/anxiety symptoms. METHODS: The Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) was used to assess temper, affective lability, and emotional overreactivity, thus identifying patients exhibiting "emotional dysregulation." Other DSM-IV Axis I diagnoses were exclusionary. Outcome measures were the Conners' Adult ADHD Rating Scale (CAARS) and the WRAADDS. RESULTS: Thirty-two percent of the sample met post hoc criteria for emotional dysregulation and had higher baseline scores on ADHD measures, a lower response to placebo, and greater response to atomoxetine (p = .048). Symptoms of emotional dysregulation had a treatment effect (p < .001) at least as large as the CAARS (p = .002) and the total WRAADDS (p = .001). Emotional dysregulation was present in the absence of anxiety or depressive diagnosis. CONCLUSIONS: Symptoms of emotional dysregulation were present in many patients with ADHD and showed a treatment response similar to other ADHD symptoms.