The cost-effectiveness of solifenacin vs fesoterodine, oxybutynin immediate-release, propiverine, tolterodine extended-release and tolterodine immediate-release in the treatment of patients with overactive bladder in the UK National Health Service.

OBJECTIVE: To assess the cost-effectiveness of solifenacin vs other antimuscarinic strategies commonly used in UK clinical practice, based on the results of a recent published review. METHODS: Overactive bladder (OAB) syndrome is characterized by symptoms of urgency, frequency, incontinence and nocturia. Pharmacological treatment comprises oral antimuscarinic agents, which are divided into older-generation treatments, including oxybutynin, and new-generation treatments, comprising solifenacin, tolterodine, darifenacin and fesoterodine. The latter have reduced central nervous system penetration and have better selectivity for the M3 subclass of acetylcholine receptors, resulting in improved tolerability. A recent systematic review and meta-analysis of the efficacy and safety of antimuscarinics provided an opportunity for an economic evaluation of these agents using a rigorous assessment of efficacy. A cost-utility analysis was undertaken using a 1-year decision-tree model. Treatment success was defined separately for urgency, frequency and incontinence, with efficacy data taken from the recent review. Treatment persistence rates were taken from the Information Management System database. Utility values for the calculation of quality-adjusted life-years (QALYs) were taken from published sources. The analysis included costs directly associated with treatment for OAB, i.e. antimuscarinic therapy, consultations with general practitioners, and outpatient contacts. Resource use was based on expert opinion. Costs were reported at 2007/2008 prices. Extensive deterministic and probabilistic analyses were conducted to test the robustness of the base-case results. RESULTS: Solifenacin was associated with the highest QALY gains (per 1000 patients) for all three outcomes of interest, i.e. urgency (712.3), frequency (723.1) and incontinence (695.0). Solifenacin was dominant relative to fesoterodine, tolterodine extended-release (ER) and tolterodine immediate-release (IR), and cost-effective relative to propiverine ER for urgency, frequency and incontinence. Solifenacin was not found to be cost-effective relative to oxybutynin IR for the frequency and incontinence outcomes, with an incremental cost-effectiveness ratio of > pound30,000/QALY threshold. CONCLUSIONS: Solifenacin provided the greatest clinical benefit and associated QALYs for all three outcomes of interest across all therapies considered, and to be either dominant or cost-effective relative to all other new-generation agents, but not cost-effective relative to oxybutynin for frequency and incontinence.

Cost-consequence analysis evaluating the use of botulinum neurotoxin-A in patients with detrusor overactivity based on clinical outcomes observed at a single UK centre.

OBJECTIVE(S): This study aimed to assess the resource utilisation, health benefits and cost-effectiveness of intra-detrusor injections of botulinum neurotoxin-A (BoNT/A) in patients with overactive bladder (OAB). METHODS: 101 patients with urodynamically-proven detrusor overactivity of either neurogenic (NDO; n = 63) or idiopathic (IDO; n = 38) origin received intra-detrusor injections of 200-300 units of BoNT/A in 20-30 ml saline as part of a research protocol. Twenty-nine patients received repeat injections after 7-26 months. Symptom severity and urodynamic parameters were assessed at 0, 4 and 16 weeks. The cost of therapy was quantified based on the NHS resources used by typical patients and was used to calculate the cost-effectiveness of BoNT/A compared with standard care from the perspective of the UK NHS. RESULTS: In an intent-to-treat analysis, 82% of patients showed a 25% or greater improvement in at least two out of five parameters (urinary frequency, urgency, urgency incontinence episodes, maximum cystometric capacity and maximum detrusor pressure) four weeks after treatment, reducing to 65% after 16 weeks. A 50% or greater improvement in the frequency of micturition, urgency or urgency incontinence was seen in 73% of patients at four weeks and 54% at 16 weeks. There were no significant differences between IDO and NDO patients in the proportion meeting these endpoints. Therapy cost pounds 826 per patient, with a cost-effectiveness ratio of pounds 617 per patient-year with > or = 25% clinical improvement. CONCLUSION(S): This study demonstrates that intra-detrusor BoNT/A is an effective treatment for OAB that is highly likely to be cost-effective in both idiopathic and neurogenic disease.

Adjunctive topiramate in hospitalized children and adolescents with bipolar disorders.

OBJECTIVE: The aim of this study was to assess topiramate as adjunctive treatment in children and adolescents hospitalized with bipolar disorders. METHODS: Medical records of all children and adolescents with a Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV-TR) (APA, 2000) diagnosis of bipolar disorder, type I, hospitalized for an acute manic, mixed, or depressive episode, were reviewed. The primary outcome measure was the Clinical Global Impression-Severity (CGI-S) score. RESULTS: Twenty-five (25) children and adolescents received topiramate, with a mean final dose of 126 mg/day (range, 25-350 mg). Overall CGI-S scores significantly improved from 5.3+/-1.0 to 3.5+/-0.7, and mania CGI-S scores decreased from 5.4+/-1.0 to 3.3+/-0.9. Sixteen (16) of 25 (64%) bipolar patients were classified as responders (defined by an endpoint overall CGI-I score of less than or equal to 2). No serious adverse events occurred during treatment. Of 25 patients evaluated, 1 (4%) experienced mild sedation while treated with topiramate. CONCLUSIONS: Preliminary results of this retrospective chart review suggest that adjunctive topiramate may be associated with improvements in children and adolescents hospitalized for an acute manic, mixed, or depressive episode. Randomized and controlled trials with adjunctive topiramate in this population are needed to further explore this observation.

Cost-effectiveness of botulinum toxin type a in the treatment of post-stroke spasticity.

OBJECTIVE: Treatment strategies for post-stroke spasticity include oral anti-spastic drugs, surgery, physiotherapy and botulinum toxin type A injection. The objective of this study was to compare the cost-effectiveness and outcomes of oral therapy vs. botulinum toxin type A treatment strategies in patients with flexed wrist/clenched fist spasticity. METHODS: Treatment outcome and resource use data were collected from an expert panel experienced in the treatment of post-stroke spasticity. A decision tree model was developed to analyse the data. RESULTS: Thirty-five percent of patients receiving oral therapy showed an improvement in pre-treatment functional targets which would warrant continuation of therapy, compared with 73% and 68% of patients treated with botulinum toxin type A first- and second-line therapy, respectively. Botulinum toxin type A treatment was also more cost-effective than oral therapy with the "cost-per-successfully-treated month" being 942 pounds, 1387 pounds and 1697 pounds for botulinum toxin type A first-line, botulinum toxin type A second-line and oral therapy, respectively. CONCLUSION: In conclusion, botulinum toxin type A is a cost-effective treatment for post-stroke spasticity.

Parametric neurocognitive task design: a pilot study of sustained attention in adolescents with bipolar disorder.

BACKGROUND: Disruption in attention is one of the core features of bipolar disorder (BP). Therefore, neurocognitive paradigms assessing brain function in response to tasks of increasing attentional difficulty may be useful to clarify the neurophysiology of bipolar disorder. The aim of this study was to obtain pilot performance data using a parametric task of sustained attention that might be useful as an experimental paradigm for future functional neuroimaging studies. We hypothesized that task performance would worsen as task difficulty increased in manic and euthymic bipolar and healthy subjects. Additionally, we hypothesized that the groups would exhibit a similar decline in task performance as level of task difficulty increased and that within each level of task difficulty there would be similar performance among groups. METHODS: A novel parametric Continuous Performance Task-Identical Pairs (CPT-IP) version was administered to manic (N=10) and euthymic (N=10) adolescents with bipolar disorder and healthy controls (N=10). RESULTS: There were no statistically significant group differences in task performance as measured by discriminability, percent correct, false positive hits, and reaction time. However, within each group, performance on all measures worsened with increased attentional difficulty (p<0.0001). There were no statistically significant task difficulty by group interactions. Furthermore, medication exposure and comorbid attention-deficit hyperactivity disorder were not associated with most measures of task performance. However, BP subjects who were treated with medications had slower task performance compared with BP subjects who were unmedicated. LIMITATIONS: Larger studies examining the effects of specific medication classes on task performance are necessary. CONCLUSIONS: The results of this pilot study suggest that manic and euthymic BP patients do not exhibit attentional dysfunction as compared to healthy adolescents using a novel parametric version of the CPT-IP. Furthermore, our parametric CPT-IP version may be useful as a novel parametric neurocognitive paradigm for future functional neuroimaging studies of bipolar adolescents.

Modelling the impact of clozapine on suicide in patients with treatment-resistant schizophrenia in the UK.

BACKGROUND: Schizophrenia is a major cause of suicide, and symptoms characteristic of treatment-resistant disease are strong risk factors. Clozapine reduces symptoms in 60% of such patients and significantly decreases the risk of suicide. AIMS: To model the impact of increased clozapine prescribing on lives saved and resource utilisation. METHOD: A model was built to compare current levels of clozapine prescribing with a scenario in which all suitable patients with treatment-resistant schizophrenia received clozapine. RESULTS: It was estimated that an average of 53 lives could be saved in the UK each year. If clozapine is cost-neutral, the cost per life-year saved is pound 5108. If clozapine achieves a 10% reduction in annual support costs, the net saving is pound 8.7 million per annum. An average of 167 acute beds would be freed each year. CONCLUSIONS: The use of clozapine in treatment-resistant schizophrenia saves lives, frees resources and is cost-effective.

Adjunctive topiramate treatment for pediatric bipolar disorder: a retrospective chart review.

OBJECTIVE: The objective of this study was to evaluate the effectiveness, safety, and tolerability of the anticonvulsant agent, topiramate, as adjunctive treatment for children and adolescents with bipolar disorders. METHODS: The outpatient medical charts of children and adolescents with a Diagnostic and Statistical Manual of Mental Disorders (4th ed.) diagnosis of bipolar disorder, type I or II, and who were treated with topiramate were retrospectively reviewed by two child and adolescent psychiatrists using the Clinical Global Impression (CGI) scale and the Clinical Global Assessment Scale (CGAS). Separate CGI ratings were made for mania and overall bipolar illness. RESULTS: Twenty-six patients (mean age 14 +/- 3.5 years) with bipolar disorder, type I (n = 23) or II (n = 3), who had been treated (mean duration 4.1 +/- 6.1 months) with topiramate (mean dose 104 +/- 77 mg/day) were identified. Response rate (defined by a CGI-Improvement score of < or = 2 at endpoint) was 73% for mania and 62% for overall illness. CGAS scores significantly improved from baseline to endpoint. No serious adverse events were reported. CONCLUSIONS: Although controlled trials are necessary, this retrospective study suggests that topiramate is effective and well tolerated as an adjunctive treatment for children and adolescents with bipolar disorder.