Assessment of centanafadine in adults with attention-deficit/hyperactivity disorder: A matching-adjusted indirect comparison vs lisdexamfetamine dimesylate, atomoxetine hydrochloride, and viloxazine extended-release.

BACKGROUND: Head-to-head trials comparing centanafadine, an investigational therapy for adults with attention-deficit/hyperactivity disorder (ADHD), with other treatment options are lacking. OBJECTIVE: To compare safety and efficacy outcomes of centanafadine sustained-release vs lisdexamfetamine dimesylate (lisdexamfetamine), atomoxetine hydrochloride (atomoxetine), and viloxazine extended-release (viloxazine ER), respectively, using matching-adjusted indirect comparison (MAIC). METHODS: This MAIC included patient-level data pooled from 2 centanafadine trials (NCT03605680 and NCT03605836) and published aggregate data from comparable trials of 3 comparators-lisdexamfetamine (NCT00334880), atomoxetine (NCT00190736), and viloxazine ER (NCT04016779)-in adult patients with ADHD. Propensity score weighting was used to match characteristics of individual patients from the centanafadine trials to aggregate baseline characteristics from the respective comparator trials. Safety outcomes were rates of adverse events for which information was available in the centanafadine and respective comparator trials. Efficacy outcome was mean change from baseline in the Adult ADHD Investigator Symptom Rating Scale (AISRS) score (ADHD Rating Scale [ADHD-RS] was used as proxy in the comparison with lisdexamfetamine). Anchored indirect comparisons were conducted across matched populations of the centanafadine and respective comparator trials. RESULTS: After matching, baseline characteristics in the centanafadine trials were the same as those in the respective comparator trials. Compared with lisdexamfetamine, centanafadine was associated with a significantly lower risk of lack of appetite (risk difference [RD] in percentage points: 23.42), dry mouth (19.27), insomnia (15.35), anxiety (5.21), nausea (4.90), feeling jittery (3.70), and diarrhea (3.47) (all P < 0.05) but a smaller reduction in the AISRS/ADHD-RS score (6.58-point difference; P < 0.05). Compared with atomoxetine, centanafadine was associated with a significantly lower risk of nausea (RD in percentage points: 18.64), dry mouth (17.44), fatigue (9.21), erectile dysfunction (6.76), lack of appetite (6.71), and urinary hesitation (5.84) (all P < 0.05) and no statistically significant difference in the change in AISRS score. Compared with viloxazine ER, centanafadine was associated with a significantly lower risk of fatigue (RD in percentage points: 11.07), insomnia (10.67), nausea (7.57), and constipation (4.63) (all P < 0.05) and no statistically significant difference in the change in AISRS score. CONCLUSIONS: In an anchored MAIC, centanafadine showed a significantly better short-term safety profile than lisdexamfetamine, atomoxetine, and viloxazine ER; efficacy was lower than with lisdexamfetamine and comparable (ie, nondifferent) with atomoxetine and viloxazine ER. This MAIC provides important insights on the relative safety and efficacy of common treatment options to help inform treatment decisions in adults with ADHD. Safety assessment was limited to rates of adverse events reported in both trials of a given comparison. STUDY REGISTRATION NUMBERS: NCT03605680, NCT03605836, NCT00334880, NCT00190736, and NCT04016779.

Antimuscarinics in Older People: Dry Mouth and Beyond.

Many common prescription and over-the-counter medications have antimuscarinic effects. Antimuscarinics are a well recognized cause of dry mouth, with potential to cause other physical and cognitive adverse effects. A comprehensive medication review in a patient presenting with dry mouth can lead to overall health improvements. Scoring systems can be helpful in identifying antimuscarinic drugs and their adverse effects. CPD/Clinical Relevance: Antimuscarinic drug use is prevalent and a common cause of dry mouth. Older people are particularly susceptible to antimuscarinic adverse effects.

Correlates of incident bipolar disorder in children and adolescents diagnosed with attention-deficit/hyperactivity disorder.

BACKGROUND: The greater severity and chronicity of illness in youths with co-occurring attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder deserve further investigation as to the risk imparted by comorbid conditions and the pharmacotherapies employed. METHOD: A retrospective cohort design was employed, using South Carolina's Medicaid claims dataset covering outpatient and inpatient medical and psychiatric service claims with International Classification of Diseases, Ninth Revision, Clinical Modification diagnoses and medication prescriptions between January 1996 and December 2006 for patients ≤ 17 years of age. RESULTS: The cohort included 22,797 cases diagnosed with ADHD at a mean age of 7.8 years; 1,604 (7.0%) were diagnosed with bipolar disorder at a mean age of 12.2 years. The bipolar disorder group developed conduct disorder (CD)/oppositional defiant disorder (ODD), anxiety disorder, and a substance use disorder later than the ADHD-only group. The odds of a child with ADHD developing bipolar disorder were significantly and positively associated with a comorbid diagnosis of CD/ODD (adjusted odds ratio [aOR] = 4.01), anxiety disorder (aOR = 2.39), or substance use disorder (aOR = 1.88); longer treatment with methylphenidate, mixed amphetamine salts, or atomoxetine (aOR = 1.01); not being African American (aOR = 1.61); and being treated with certain antidepressant medications, most notably fluoxetine (aOR = 2.00), sertraline (aOR = 2.29), bupropion (aOR = 2.22), trazodone (aOR = 2.15), or venlafaxine (aOR = 2.37) prior to the first diagnosis of mania. CONCLUSIONS: Controlling for pharmacotherapy differences, incident bipolar disorder was more likely in individuals clustering specific patterns of comorbid psychiatric disorders, suggesting that there are different pathways to bipolarity and providing a clinical impetus for prioritizing prevention and preemptive strategies to reduce their hazardous influence.

[Cardiovascular risk assessment for the use of ADHD drugs in children]. / Kardiovaskulær risikovurdering ved bruk av AD/HD-medikamenter hos barn.

BACKGROUND: Drug therapy for ADHD (Attention Deficit Hyperactivity Disorder) has generally been regarded as safe. ECG screening of healthy children and adolescents before initiating this type of treatment appears to be usual in Norway, despite recommendations that ECGs should only be undertaken in individuals who are at risk. The purpose of this article is to clarify relevant guidelines for cardiovascular risk assessment for the use of ADHD drugs in children and adolescents, as well as to propose practical recommendations. METHOD: The article is based on a literature search in PubMed completed on 1 October 2013, and on the author's own clinical experience and discretionary assessments. RESULTS: The use of CNS stimulants and atomoxetine is associated with a slight rise in blood pressure and pulse rate, as well as small changes in QT interval. A small percentage of patients (5-10%) experience a clinically significant rise in blood pressure and pulse rate. Sudden death does not appear to occur more frequently in children and adolescents taking ADHD drugs in therapeutic doses than in children and adolescents who do not use such drugs. There is little knowledge available on the long-term effects of ADHD drugs on the cardiovascular system of otherwise healthy individuals, or on the risk related to the use of ADHD drugs in children and adolescents with cardiac disease. The drugs are thought to increase the risk of sudden cardiac death in some arrhythmia syndromes. INTERPRETATION: Our assessment is that caution should be exercised in the use of ADHD drugs in children with potentially dangerous cardiac arrhythmias. We recommend clinical examination and a thorough medical history review in order to identify individuals at risk before initiating drug therapy, and also suggest that it is not necessary for healthy children to be given an ECG examination before introducing ADHD drugs. In children with known cardiac disease, arrhythmia or risk factors for cardiac disease, ADHD treatment should be undertaken in consultation with a medical specialist with competence in pediatric cardiology.

A review of the abuse potential assessment of atomoxetine: a nonstimulant medication for attention-deficit/hyperactivity disorder.

RATIONALE: Treatment of attention-deficit/hyperactivity disorder (ADHD) has for many years relied on psychostimulants, particularly various formulations of amphetamines and methylphenidate. These are central nervous system stimulants and are scheduled because of their abuse potential. Atomoxetine (atomoxetine hydrochloride; Strattera®) was approved in 2002 for treatment of ADHD, and was the first nonstimulant medication approved for this disorder. It was classified as an unscheduled medication indicating a low potential for abuse. However, the abuse potential of atomoxetine has not been reviewed. OBJECTIVES: In this article, we review the evidence regarding abuse potential of atomoxetine, a selective inhibitor of the presynaptic norepinephrine transporter, which is unscheduled/unrestricted in all countries where it is approved. METHODS: Results from receptor binding, in vitro electrophysiology, in vivo microdialysis, preclinical behavioral, and human laboratory studies have been reviewed. RESULTS: Atomoxetine has no appreciable affinity for, or action at, central receptors through which drugs of abuse typically act, i.e., dopamine transporters, GABA(A) receptors, and opioid µ receptors. In behavioral experiments in rodents, atomoxetine does not increase locomotor activity, and in drug discrimination studies, its profile is similar to that of drugs without abuse potential. Atomoxetine does not serve as a reinforcer in monkey self-administration studies, and human laboratory studies suggest that atomoxetine does not induce subjective effects indicative of abuse. CONCLUSION: Neurochemical, preclinical, and early clinical studies predicted and supported a lack of abuse potential of atomoxetine, which is consistent with the clinical trial and postmarketing spontaneous event data in the past 10 years.

Atomoxetine treatment of attention-deficit/hyperactivity disorder in young adults with assessment of functional outcomes: a randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is associated with significant impairment in multiple functional domains. This trial evaluated efficacy in ADHD symptoms and functional outcomes in young adults treated with atomoxetine. METHODS: Young adults (18-30 years old) with ADHD were randomized to 12 weeks of double-blind treatment with atomoxetine (n = 220) or placebo (n = 225). The primary efficacy measure of ADHD symptom change was Conners' Adult ADHD Rating Scale (CAARS): Investigator-Rated: Screening Version Total ADHD Symptoms score with adult prompts. Secondary outcomes scales included the Adult ADHD Quality of Life-29, Clinical Global Impression-ADHD-Severity, Patient Global Impression-Improvement, CAARS Self-Report, Behavior Rating Inventory of Executive Function-Adult Version Self-Report, and assessments of depression, anxiety, sleepiness, driving behaviors, social adaptation, and substance use. RESULTS: Atomoxetine was superior to placebo on CAARS: Investigator-Rated: Screening Version (atomoxetine [least-squares mean ± SE, -13.6 ± 0.8] vs placebo [-9.3 ± 0.8], 95% confidence interval [-6.35 to -2.37], P < 0.001), Clinical Global Impression-ADHD-Severity (atomoxetine [-1.1 ± 0.1] vs placebo [-0.7 ± 0.1], 95% confidence interval [-0.63 to -0.24], P < 0.001), and CAARS Self-Report (atomoxetine [-11.9 ± 0.8] vs placebo [-7.8 ± 0.7], 95% confidence interval [-5.94 to -2.15], P < 0.001) but not on Patient Global Impression-Improvement. In addition, atomoxetine was superior to placebo on Adult ADHD Quality of Life-29 and Behavior Rating Inventory of Executive Function-Adult Version Self-Report. Additional assessments failed to detect significant differences (P ≥ 0.05) between atomoxetine and placebo. The adverse event profile was similar to that observed in other atomoxetine studies. Nausea, decreased appetite, insomnia, dry mouth, irritability, dizziness, and dyspepsia were reported significantly more often with atomoxetine than with placebo. CONCLUSIONS: Atomoxetine reduced ADHD symptoms and improved quality of life and executive functioning deficits in young adults compared with placebo. Atomoxetine was also generally well tolerated.

An update on the drug treatment of neuropathic pain. Part 1: antidepressants.

Neuropathic pain refers to pain that arises as a direct consequence of a lesion or disease affecting the somatosensory nervous system.(1) Many cases of neuropathic pain run a chronic course, and treatment may be difficult because commonly used analgesics, including NSAIDs and to some extent opioids, are often ineffective. In addition, the use of other pharmacological treatments can be limited by unwanted effects. Management requires a multidisciplinary approach and may involve the use of drug therapy (including antidepressants, anticonvulsants and opioids) with non-pharmacological interventions (including psychological therapies, transcutaneous electrical nerve stimulation and interventional procedures). This month and next month we review the drug treatment of neuropathic pain. In this first part we discuss neuropathic pain and the use of antidepressants.

Use of antidepressant agents and the risk of type 2 diabetes.

PURPOSE: To determine whether there is an association between antidepressant use and the risk of developing type 2 diabetes. METHODS: This study was a retrospective cohort analysis using the Texas Medicaid prescription claims database. Data were extracted for new users of either antidepressant agents (exposed) or benzodiazepines (unexposed) from January 1, 2002 through December 31, 2009. Patients aged 18-64 years without a prior history of diabetes were included. Cox proportional hazards regression was used to examine the association between diabetes incidence among exposed and unexposed groups, while controlling for demographic and clinical covariates. RESULTS: Among the total study population (N = 44,715), the majority were in the exposed (N = 35,552) versus the unexposed (N = 9,163) group. A total of 2,943 patients (6.6%) developed type 2 diabetes during the follow-up period. Antidepressant use was associated with an increase in the risk of diabetes when compared to benzodiazepine use (adjusted hazard ratio [HR] 1.558, 95% confidence interval [CI] 1.401-1.734). The association was observed with tricyclic antidepressants (TCAs; HR 1.759, 95% CI 1.517-2.040), serotonin-norepinephrine reuptake inhibitors (SNRIs; HR 1.566. 95% CI 1.351-1.816), selective serotonin reuptake inhibitors (SSRIs; HR 1.481, 95% CI 1.318-1.665), and "other" antidepressants (HR 1.376; 95% CI 1.198-1.581). CONCLUSIONS: The results of this study suggest that antidepressant use is associated with an increased risk of diabetes. This association was observed with use of TCAs, SNRIs, SSRIs, and "other" antidepressants.

Medication dosing patterns associated with duloxetine and pregabalin among patients with fibromyalgia.

OBJECTIVE: To examine medication dosing patterns of duloxetine and pregabalin among patients with fibromyalgia. METHODS: From a large US administrative claims database, commercially insured fibromyalgia patients aged 18-64 who initiated duloxetine or pregabalin in 2006 were selected. Initiation was defined as a 90-day medication gap, with the dispense date of the first initiation as the index date. All patients selected had continuous enrollment over the 12-month pre- and post-index periods, and were classified into the duloxetine or pregabalin cohorts based on their index agent. Initial daily dose, average daily dose over the 12-month post-index period, mean and median daily doses and daily costs of each of the first 12 prescriptions were examined for both the duloxetine and pregabalin cohorts. RESULTS: Both the duloxetine (n = 3773) and pregabalin (n = 4189) cohorts had a mean age of 50 years (median age: 52 vs. 53). The average initial daily dose was 55.7 mg for duloxetine and 161.5 mg for pregabalin. Over the 12-month post-index period, the average daily dose per patient was 55.6 mg for duloxetine and 195.7 mg for pregabalin. The average daily doses for the first 12 duloxetine prescriptions ranged 55.7-60.3 mg, with the mean daily costs between $3.77 and $4.59. For the first 12 pregabalin prescriptions, the average daily dose increased from 161.5 mg to 282.4 mg, while the average daily costs ranged between $4.30-4.61. CONCLUSIONS: Among patients with fibromyalgia, duloxetine and pregabalin initiators had different dosing patterns. The average daily dose for duloxetine was relatively stable over time, while pregabalin patients had significant dose increase over the 12-month post-index period.

Urinary incontinence: pharmacotherapy options.

The impact of incontinence is felt by millions of people worldwide, with tremendous decrement in quality of life and enormous cost reaching billions of dollars. Urinary incontinence is defined as 'involuntary leakage of urine' and is categorized into two main types: urgency urinary incontinence (UUI) and stress urinary incontinence (SUI). Behavioral modifications and pharmacologic therapies, primarily antimuscarinic agents, are the mainstay of treatment for UUI. These drugs are moderately efficacious but have troublesome side-effects, the combination resulting in poor compliance and persistence with therapy. There are several agents on the market today, each with some variation in pharmacologic properties. Whether these translate into meaningful differences in clinical efficacy and tolerability remains a matter of debate. Treatment of SUI has seen little success with pharmacologic therapy. In Europe, duloxetine is approved for treatment of SUI with marginal success rates; this drug, although available in the United States for treatment of depression, is not approved for SUI. The search for newer and better pharmacologic options and novel therapies is on-going, fueled primarily by the high prevalence of bothersome incontinence and the tremendous number of health care dollars spent on current therapy. This review addresses pharmacologic options for treatment of urinary incontinence.

Tetrabenazine for the treatment of tardive dyskinesia.

OBJECTIVE: To evaluate the safety and effectiveness of tetrabenazine for the treatment of tardive dyskinesia. DATA SOURCES: Literature was accessed through MEDLINE (1966-September 2010) and The Cochrane Library using the terms tetrabenazine, tardive dyskinesia, and movement disorders. In addition, references from publications identified were reviewed. STUDY SELECTION AND DATA EXTRACTION: All English-language articles identified from the data sources were reviewed. DATA SYNTHESIS: Options available for the management of tardive dyskinesia are limited. Tetrabenazine is a central monoamine-depleting agent approved by the Food and Drug Administration for chorea associated with Huntington's disease. Three prospective studies of tetrabenazine in the treatment of tardive dyskinesia were identified, as well as 8 additional trials, 1 case series, and 8 case reports. Tetrabenazine may provide benefit in managing symptoms of tardive dyskinesia unresponsive to other treatment modalities. Treatment of tardive dyskinesia with tetrabenazine may be limited by cost and clinically significant adverse effects such as depression, parkinsonism, and somnolence. CONCLUSIONS: Small trials indicate tetrabenazine may be effective for the treatment of tardive dyskinesia. However, larger, well-conducted trials are needed to confirm these findings. Currently, there is a lack of data coupled with the risk of significant adverse effects to recommend the routine use of tetrabenazine in the management of tardive dyskinesia. Before using tetrabenazine for the management of tardive dyskinesia, all other options should be exhausted and careful monitoring employed.

Duloxetine: a review of its pharmacology and use in chronic pain management.

Duloxetine is a serotonin and norepinephrine reuptake inhibitor that possesses antidepressant and pain-relieving properties. Compared with other antidepressants, it has a high affinity for both norepinephrine and serotonin reuptake transporters, which are relatively balanced. Analgesic onset has been observed within the first week of administration in randomized controlled trials and is likely obtained by enhancing the tone of the descending pain inhibition pathways of the central nervous system. Randomized trials have documented significant analgesic effects for managing chronic pain associated with fibromyalgia and diabetic peripheral neuropathic pain. Studies have also suggested that pain associated with major depressive disorder can be reduced with this medication. Modest effects for headache, osteoarthritic pain, and pain secondary to Parkinson disease have also been documented, but data are obtained from single-blinded or open-label trials that require further corroboration with larger randomized studies. Duloxetine has not yet been directly compared with other antidepressants or anticonvulsants for the treatment of pain syndromes.

Cost effectiveness of escitalopram versus SNRIs in second-step treatment of major depressive disorder in Sweden.

OBJECTIVES: Escitalopram is the S-enantiomer of citalopram and is the most discriminating of the selective serotonin reuptake inhibitors (SSRI). The aim of the current analysis was to assess the cost effectiveness of escitalopram versus the serotonin norepinephrine reuptake inhibitors (SNRI) duloxetine and generic venlafaxine as second-step treatment of major depressive disorder. METHODS: The analysis was based on a decision analytic model. Effectiveness outcomes were quality-adjusted life-years (QALYs) and remission rates; cost outcomes were direct medical costs, including impact of treating adverse events, and indirect costs associated with lost productivity. The analysis was performed from the societal perspective in Sweden over a 6-month timeframe. RESULTS: Estimated remission rates showed an incremental effectiveness in favour of escitalopram of 16.4 percentage points compared with both SNRI comparators. The escitalopram strategy was associated with a 0.025 increase in QALYs. Sensitivity analyses demonstrated that the model is robust and that escitalopram remains a cost-effective option when considering future predicted price reductions of generic venlafaxine. LIMITATIONS: The main limitation in this study was the lack of data available for second-step treatment. The remission rates, which are a key input to the model, were obtained from a relatively small sample of patients on second-step treatment and there are no published relapse rates for second-step treatment. The model also assumed that there was no difference in the adverse event (AE) rates between treatments after the first 8 weeks. CONCLUSIONS: This cost-effectiveness analysis indicates that, at a willingness-to-pay threshold of £30,000, escitalopram is the most cost-effective second-step treatment option for MDD in Sweden in over 85% cases compared with both venlafaxine and with duloxetine. Benefits for escitalopram included both increased effectiveness and reduced overall costs. The major contributing costs were those associated with productivity loss. The model was shown to have internal validity and robustness through the use of stochastic simulations and sensitivity analyses, which were conducted around the key efficacy parameters.

Spotlight on atomoxetine in attention-deficit hyperactivity disorder in children and adolescents.

Atomoxetine (Strattera) is a selective noradrenaline (norepinephrine) reuptake inhibitor that is not classified as a stimulant, and is indicated for use in patients with attention-deficit hyperactivity disorder (ADHD). Atomoxetine is effective and generally well tolerated. It is significantly more effective than placebo and standard current therapy and does not differ significantly from, or is noninferior to, immediate-release methylphenidate; however, it is significantly less effective than the extended-release methylphenidate formulation OROS methylphenidate (hereafter referred to as osmotically released methylphenidate) and extended-release mixed amfetamine salts. Atomoxetine can be administered either as a single daily dose or split into two evenly divided doses, has a negligible risk of abuse or misuse and is not a controlled substance in the US. Atomoxetine is particularly useful for patients at risk of substance abuse, as well as those who have co-morbid anxiety or tics, or who do not wish to take a controlled substance. Thus, atomoxetine is a useful option in the treatment of ADHD in children and adolescents.

Second opinions improve ADHD prescribing in a medicaid-insured community population.

OBJECTIVE: The appropriate use of psychotropic medications in youths is an important public health concern. In this article, we describe a review process developed to monitor the use of stimulants and atomoxetine for attention-deficit/hyperactivity syndrome (ADHD) in youths receiving fee-for-service Medicaid services. METHOD: Washington State Medicaid developed threshold safety parameters for ADHD medications through a process involving the community. A second opinion was mandated when safety thresholds based on dose, combination therapies, or age was exceeded. Use and cost were compared 2 years before and after the program began. RESULTS: From May 2006 to April 2008, 5.35% of ADHD prescriptions exceeded safety thresholds, resulting in 1,046 second-opinion reviews. Of those, 538 (51.4%) resulted in a prescription adjustment. Adjustments were made to primary care physician (52%), psychiatrist (50%), nurse practitioner (54%), and physician assistant-written (51%) prescriptions. When the preperiod and postperiod were compared, second opinions reduced ADHD medication at high doses (53%), in combinations (44%), and for patients 5 years of age and younger (23%). The review process resulted in a savings of $1.2 million, with 538 fewer patients exceeding safety thresholds. This was a 10:1 return over administrative costs; however, the overall Medicaid expenditures for ADHD medication still increased because of higher unit costs and the preferential use by clinicians of newer brands entering the market. CONCLUSIONS: A statewide second-opinion process reduced outlier ADHD medication prescription practices and was cost-effective. Suggestions for process and quality improvements in prescribing to children diagnosed with ADHD are discussed.

Atomoxetine improves patient and family coping in attention deficit/hyperactivity disorder: a randomized, double-blind, placebo-controlled study in Swedish children and adolescents.

This 10-week study assessed the efficacy of atomoxetine in combination with psychoeducation compared to placebo and psychoeducation in the improvement of Quality of Life in Swedish stimulant-naive children and adolescents with attention deficit/hyperactivity disorder. A total of 99 patients were treated with atomoxetine (49 patients) or placebo (50 patients) for 10 weeks and assessed regarding broader areas of functioning using the Quality of Life measures Child Health and Illness Profile-Child Edition (CHIP-CE), Family Strain Index [FSI; equivalent to the Family Burden of Illness Module used in the study], Appraisal of Stress in Child-Rearing (ASCR), Five to fifteen (FTF), "I think I am" ("Jag tycker jag är"), and Children's Depression Rating Scale-Revised (CDRS-R) before and after the active treatment phase. Simultaneously, the patients' parents participated in a 4-session psychoeducation program. A statistically significant difference in favor of atomoxetine was seen in the improvement from baseline to study endpoint for the CHIP-CE domains "Achievement" and "Risk avoidance", for the FSI total score, for the ASCR section (I) domain "Child as a burden", for all FTF domains except for "Language and Speech", and for the CDRS-R total score. No difference between treatment groups was observed in the patient-assessed evaluation of self-esteem using the "I think I am" scale. Atomoxetine combined with psychoeducation had a positive effect on various everyday coping abilities of the patients as well as their families during 10 weeks of treatment, whereas the patients' self-image and the parents' image of the climate in the family were not significantly improved.

Effects of milnacipran and paroxetine on overactive bladder due to neurologic diseases: a urodynamic assessment.

AIMS: To determine the effects of milnacipran hydrochloride, a serotonin-norepinephrine reuptake inhibitor (SNRI), or paroxetine hydrochloride, a selective serotonin reuptake inhibitor, on overactive bladder (OAB) in neurologic diseases, given by objective measures of urodynamic studies. METHODS: This is a prospective open trial, and we enrolled 24 patients (16 men, 8 women; mean age, 63.9 years) with OAB in a neurology clinic. They were randomly allocated into two groups: the milnacipran group (11 patients), and paroxetine group (13 patients). We started with 100 mg/day of milnacipran or 40 mg/day of paroxetine. Before and 3 months after the treatment, we performed a urinary questionnaire and urodynamic studies. RESULTS: Milnacipran reduced daytime urinary frequency (average, from 9.4 to 7.1 times, p < 0.001), improved the quality of life index (p = 0.023), and increased bladder capacity (average, from 289 to 377 ml, p = 0.009) as shown in urodynamic studies. No such changes were noted in the other categories of the lower urinary tract symptoms questionnaire or urodynamic studies, or in the paroxetine group. One male patient complained of mild voiding difficulty. Other adverse effects were not seen during the observation period. CONCLUSION: Milnacipran, an SNRI, increased bladder capacity as shown in urodynamic studies, and thereby ameliorated OAB in patients with neurologic diseases without serious adverse effects.

The effect of pharmacotherapy for attention deficit hyperactivity disorder on risk of seizures in pediatric patients as assessed in an insurance claims database.

PURPOSE: To estimate the rate of new-onset seizure in ADHD patients in relation to ADHD pharmacotherapy. METHODS: A retrospective cohort study of 34,727 patients, ages 6 to 17, with at least two insurance claims bearing ADHD diagnoses during 2003 in the UnitedHealthcare database. Incidence of seizure was calculated for observation time during treatment with atomoxetine and stimulants/bupropion. RESULTS: Seizure incidence among ADHD patients was 4.5/1,000 person-years (p-y; 95% confidence interval 3.7 - 5.5). ADHD patients who received any ADHD medication had an incidence of 3.8/1,000 p-y (3.0 - 4.8) compared to 8.7 (5.8 - 12.4) for patients who did not receive any ADHD medication. The relative risk (RR) for current vs non-use of atomoxetine was 1.1 (0.6 - 2.1). For stimulants and bupropion, the RR for current vs non-use was 0.8 (0.6 - 1.3). Elevated seizure risks were found in association with central nervous system (CNS) disease (OR 3.9, 1.2 - 10.9), CNS medications (OR 2.2, 1.3 - 3.6), metabolic disease (OR 2.9, 1.1 - 6.8), and psychiatric disease risk factors (OR 1.7, 1.1 - 2.6). CONCLUSIONS: In this study, there was no statistically significant association between use of atomoxetine or stimulants and seizure risk in children ages 6 to 17 years with ADHD and without prior seizure disorder.

Emotional expression during attention-deficit/hyperactivity disorders treatment: initial assessment of treatment effects.

OBJECTIVE: The purpose of this research was to provide an initial examination of the effects of atomoxetine and stimulants on emotional expression using a newly developed scale for assessing emotional expression in children with attention-deficit/hyperactivity disorder (ADHD). METHOD: The parent-rated Expression and Emotion Scale for Children (EESC) was collected during two studies. During a cross-sectional validation study, the EESC was completed to assess the child's current treatment and retrospectively for previous medication. In a randomized, placebo-controlled trial of atomoxetine, the EESC was collected at baseline and endpoint. RESULTS: In the validation study, no statistically significant differences in EESC scores were found between groups taking atomoxetine (n = 74) and stimulants (n = 105). Patients who switched from a stimulant to atomoxetine (n = 40) had greater improvement in emotional expression than those switched to another stimulant (n = 21) (p = 0.008). In the clinical trial, no difference in rates of worsening of emotional expression were observed (atomoxetine 8.8%, placebo 12.3%; p = 0.440). CONCLUSION: No treatment differences in emotional expression were observed based on current medications. However, stimulant patients needing to switch medications may have greater improvements in emotional expression by switching to atomoxetine.