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Medical research on strattera
Psychopharmacology (Berl). 2008 Jun 22;
Newman LA, Darling J, McGaughy J
BACKGROUND: The majority of studies assessing executive function in attention deficit disorder (ADD) have shown deficits in attentional set shifting using either the Wisconsin card sorting task or the intra-dimensional/extra-dimensional set-shifting task (ID/ED). Damage to the prefrontal cortex in humans, primates, and rodents impairs extra-dimensional (ED) shifts. Noradrenergic depletion of the medial prefrontal cortex in rats is sufficient to impair attentional set shifting. Atomoxetine, a selective norepinephrine (NE) re-uptake inhibitor, is hypothesized to produce beneficial effects in patient with ADD by augmenting NE release in prefrontal cortex. MATERIALS AND METHODS: We assessed the effects of systemic administration of atomoxetine (0.0, 0.1, 0.3, and 0.9 mg/kg/ml) in normal and noradrenergically lesioned (NE-LX) rats on attentional-set shifts. We replicated findings showing NE-LX rats are selectively impaired on the ED shifts but not reversals or other discriminations. RESULTS: Atomoxetine remediated the attentional set-shifting impairments in NE-LX rats but impaired ED performance of non-lesioned rats. DISCUSSION: Though atomoxetine is neurochemically selective, it is not wholly specific at doses >0.3 mg/kg. All doses of the drug were similar in their efficacy in reversing the ED deficit, but the effectiveness of the 0.1 mg/kg dose supports the hypothesis that increases in prefrontal NE alone are sufficient to improve attention in NE-LX rats. Moreover, the detrimental effects of the drug in non-lesioned rats support the hypothesis that optimal levels of NE in prefrontal cortex are critical to attentional set shifting with both supra- and sub-optimal levels producing attentional impairments.
Pharmacotherapy of ADHD in adults.
CNS Spectr. 2008 May; 13(5 Suppl 8): 11-3
Wilens TE
Risperidone-induced sexual dysfunction in a prepubertal child - a case report.
J Psychopharmacol. 2008 Jun 18;
Wadoo O, Chalhoub N
Abstract We report on a child with attention deficit hyperactivity disorder and motor tics, who developed frequent penile erections during treatment with risperidone and atomoxetine. On discontinuation of risperidone, he recovered fully. Clinicians should be alert to the adverse effects of atypical antipsychotics, which are used to treat a wide variety of paediatric psychiatric disorders.
Evolution of the treatment of attention-deficit/hyperactivity disorder in children: A review.
Clin Ther. 2008 May; 30(5): 942-57
Findling RL
Background: Efficacious and well-tolerated medications are available for the treatment of attention-deficit/hyperactivity disorder (ADHD). Stimulants such as methylphenidate (MPH) and amphetamines are the most widely used medications approved by the US Food and Drug Administration for the treatment of ADHDin children. Objective: This article reviews the literature on the development and use of medications for the treatment of ADHD in children. Methods: A search of MEDLINE was conducted toidentify relevant studies and critical reviews on the treatment of ADHD in children.The main criteria for inclusion of a study were that it have a controlled design, enroll >100 subjects if a clinical trial and >20 subjects if a classroom study, assess symptoms with the most widely used scales and tests,and be published from 2000 to 2008.A few older pivotal studies were also included. Results: Many studies have reported the long-term efficacy and tolerability of immediate-release formulations of MPH. The disadvantages of such formulations include the need for multiple daily dosing and a potential for abuse. Various extended-release formulations of MPH have been found effective in controlled studies enrolling large numbers of children with ADHD. The efficacy and tolerability of dexmethylphenidate, the active D-isomer of MPH, in an extended-release formulation have also been reported. An extended-release formulation of mixed amphetamine salts (MMAS-XR) that is dosed once daily has been found to be efficacious and well tolerated. The non-stimulant atomoxetine has been reported to be well tolerated and efficacious, although it may not be as effective as stimulants; this formulation is, however, less likely than stimulants to be associated with abuse and diversion. A recently approved prodrug stimulant, lisdexamfetamine dimesylate (LDX), was developed to provide a long duration of effect that is consistent throughout the day, with a reduced potential for abuse. In a placebo-controlled study in children with ADHD, less intersubject variability in T(max), C(max), and AUC from time zero to the last quantifiable concentration was seen in the 8 subjects who received LDX (percent coefficient of variation, 15.3, 20.3, and 21.6, respectively) compared with the 9 subjects who received MAS-XR (52.8, 44.0, and 42.8).In 2 clinical trials, significantly greater improvements in teacher and parent ratings of ADHD symptoms were seen with LDX compared with placebo (P
[Multimodal treatment of attention-deficit hyperactivity disorder in children.]
Nervenarzt. 2008 Jun 12;
Jans T, Kreiker S, Warnke A
Evidence-based treatments for attention-deficit hyperactivity disorder (ADHD) in children include primarily medication (stimulants and atomoxetine) and psychosocial interventions (parent training and behavioural classroom interventions). Results of treatment studies suggest that ADHD without significant coexisting disorders can be treated effectively by pharmacotherapy and expert counselling, while additional behaviour therapy demonstrates no significant improvement. Incremental benefits of combined pharmacological and behavioural interventions emerge if a comorbid condition is present. Behaviour therapy alone may be useful for treating less pronounced ADHD symptoms. Therapeutic strategies also account for the specific treatment of comorbid disorders and the need for support by youth welfare services.
[Multimodal treatment of adult attention-deficit hyperactivity disorder.]
Nervenarzt. 2008 Jun 11;
Jacob CP, Philipsen A, Ebert D, Deckert J
The indication for treatment of adult attention-deficit hyperactivity disorder (adult ADHD) is derived not from the diagnosis itself but results from the severity of symptoms, comorbidities, psychosocial consequences, and a lack of defined resources for ADHD. The basis of therapy is psychoeducation that includes teaching about symptoms, models of the disorder, and options for treatment. The combination of pharmacotherapy and psychotherapy is recommended. Methylphenidate is considered the first-line therapy, because of its strong effect and modest side effects, but is not authorized in Germany ("off-label use"). Atomoxetine, which is authorized for continuing treatment into adulthood, is indicated if methylphenidate is insufficient or has unacceptable side effects and in case of comorbid substance use. Various psychotherapeutic interventions using available ADHD-typical resources have demonstrated positive effects. Psychosocial support and self-help groups complete the treatment concept. Persistence of the treatment indication has to be reevaluated at regular intervals. Disorder-specific multimodal therapy of adult ADHD conforms to the complex, primarily neurobiologic etiology and the psychosocial consequences.
Psychopharmacology (Berl). 2008 Jun 6;
Jentsch JD, Aarde SM, Seu E
RATIONALE: The ability to detect unpredictable cues can involve stimulus-elicited orienting of attention (bottom-up processing); however, in many settings, target onset is partially predictable, meaning that subjects can benefit from the rule-guided, endogenous control of attention (top-down processing). Noradrenaline has been implicated in attention per se, but it is not clear whether it differentially participates in these two dimensions of attentional function. OBJECTIVES: We sought to examine the effects of selective or nonselective inhibitors of noradrenaline reuptake on different modes of attentional performance in rats. MATERIALS AND METHODS: Adult male Long-Evans rats were trained to perform a lateralized reaction time task where a variable-duration preparatory period preceded delivery of a visual target stimulus. Atomoxetine (1 mg/kg, i.p.) or methylphenidate (0.32 mg/kg, i.p.) were administered before sessions in which the preparatory period was systematically varied. RESULTS: When the preparatory time was brief (0.2 s), response times were significantly longer than when the preparatory time was long (1.0 s), suggesting that rats were able to orient their attention before target onset when the longer period was imposed. Atomoxetine differentially modulated performance in these two conditions, improving response accuracy when a long preparatory period was imposed but impairing accuracy when the preparatory time was made brief. Methylphenidate did not differentially affect responding under the two conditions. CONCLUSIONS: These data suggest that selective inhibition of the noradrenaline transporter may specifically benefit attentional performance of tasks that permit the controlled recruitment of attention, rather than during tests of pure stimulus-driven attention.
Effects of atomoxetine on subjective and neurocognitive symptoms of nicotine abstinence.
J Psychopharmacol. 2008 May 30;
Ray R, Rukstalis M, Jepson C, Strasser AA, Patterson F, Lynch K, Lerman C
Abstract Nicotine dependence has been linked to attention-deficit hyperactivity disorder (ADHD) symptoms in both clinical and general populations. This behavioural pharmacology study used a within-subject, double-blind, crossover design to test the effects of atomoxetine, a medication for ADHD, on nicotine abstinence symptoms. Fifty non treatment-seeking smokers (>/=15 cigarettes/day) completed a baseline session when they were smoking as usual and then two laboratory testing sessions after overnight abstinence and treatment with 7 days of either atomoxetine (1.2 mg/kg) or placebo. During each laboratory session, participants completed subjective measures of abstinence symptoms and performed neurocognitive tasks. In mixed effects models, atomoxetine, compared with placebo, was found to be associated with a reduction in abstinence-induced subjective withdrawal symptoms. Atomoxetine was also associated with significant reductions in self-reported smoking urges amongst smokers who scored high on a baseline measure of smoking for stimulation. However, atomoxetine had no effect on any of the cognitive tasks employed in the study. Thus, atomoxetine may reduce cravings to smoke among smokers who use nicotine to increase arousal.
Child Adolesc Psychiatry Ment Health. 2008; 2(1): 11
Wehmeier PM, Schacht A, Lehmann M, Dittmann RW, Silva SG, March JS
ABSTRACT: BACKGROUND: The objective of this analysis was to measure changes in items on the Pediatric Adverse Event Rating Scale (PAERS) that relate to emotional well-being of children and adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD) during treatment with atomoxetine for up to 24 weeks from the perspective of the patient, the parent, and the physician. METHODS: Patients aged 6-17 years with ADHD were treated with atomoxetine (target dose 1.2 mg/kg/day). In the two studies on which this secondary analysis is based the PAERS was used to assess the tolerability of atomoxetine in children and adolescents. This scale has a total of 48 items. The ten items that reflect emotional well-being were selected to measure changes over time from a patient, parent, and physician perspective. RESULTS: 421 patients were treated with atomoxetine. 355 patients completed the 8-week treatment period, and 260 patients completed the 24-week treatment period. The ten items that reflect emotional well-being were grouped in five dimensions: depressed mood, self-harm, irritability/agitation, drowsiness, and euphoria. The scores of these dimensions decreased over time, both from a patient as well as from a parent and physician perspective. Only the dimension self-harm was extremely low at baseline and stayed low over time. The mean scores for the ten items depended on the rater perspective. CONCLUSION: The emotional well-being of children and adolescents with ADHD improved in terms of depressed mood, irritability/agitation, drowsiness, and euphoria during treatment with atomoxetine for up to 24 weeks.
Child Adolesc Psychiatry Ment Health. 2008; 2(1): 10
Wehmeier PM, Schacht A, Dittmann RW, Döpfner M
ABSTRACT: BACKGROUND: The objective of this analysis was to evaluate the psychometric properties of a brief scale developed to assess the degree of difficulties in children with Attention-Deficit/Hyperactivity Disorder (ADHD). The Global Impression of Perceived Difficulties (GIPD) scale reflects overall impairment, psychosocial functioning and Quality of Life (QoL) as rated by patient, parents and physician at various times of the day. METHODS: In two open-label studies, ADHD-patients aged 6-17 years were treated with atomoxetine (target-dose 0.5-1.2 mg/kg/day). ADHD-related difficulties were assessed up to week 24 using the GIPD. Data from both studies were combined to validate the scale. RESULTS: Overall, 421 patients received atomoxetine. GIPD scores improved over time. All three GIPD-versions (patient, parent, physician) were internally consistent; all items showed at least moderate item-total correlation. The scale showed good test-retest reliability over a two-week period from all three perspectives. Good convergent and discriminant validity was shown. CONCLUSION: GIPD is an internally consistent, reliable and valid measure to assess difficulties in children with ADHD at various times of the day and can be used as indicator for psychosocial impairment and QoL. The scale is sensitive to treatment-related change.