Urinary incontinence and drug use: Data from the Norwegian Prescription Database and the HUNT3 study
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Introduction Urinary incontinence is a common health problem in the female population. The most common drug group used for the treatment of urgency urinary incontinence is anticholinergic drugs, including oxybutynin, tolterodine, solifenacin, darifenacin and fesoterodine. These agents diminish intravesical pressure, increase the volume threshold for micturition, and reduce uninhibited detrusor contractions. Anticholinergic drugs have many potential adverse effects, and these adverse effects can be bothersome. Since the therapeutic effect of these drugs is limited, adherence to anticholinergic drug regimens is low. A known cause of urinary incontinence is the consumption of drugs. For some drug groups, the evidence is relatively strong, whereas for others, the associations are weak or even equivocal and disputed. Therefore, there is a need for novel information about the association between drug use and urinary incontinence. Aim The main objective of this thesis was to study exposure to drugs as a risk factor for urinary incontinence, as well as prescription patterns and the factors associated with the treatment of urinary incontinence using anticholinergic drugs in Norwegian women. The following research aims were addressed: I: This study aimed to investigate associations between the use of specific drugs and drug groups and urinary incontinence in women. II: This study aimed to investigate the factors associated with first-time prescriptions of anticholinergic drugs in women with urinary incontinence. III: This study aimed to investigate adherence, persistence and switch rates for anticholinergic drugs prescribed for urinary incontinence among women. Methods In all three papers, the research was conducted using data from the Norwegian Prescription Database (NorPD). In paper I, data on the drugs dispensed during the 6 months prior to a woman’s participation in HUNT3 were used to study the relation between filled prescriptions and the occurrence of urinary incontinence. The type of urinary incontinence and the severity of urinary incontinence were also evaluated. Prescriptions of the following drugs/drug groups were included in the study: SSRIs, benzodiazepines, zopiclone/zolpidem, antipsychotics, lamotrigine, beta blockers and diuretics. In paper II, data on the drugs dispensed during the 12 months prior to and the 12 months after a woman’s participation in HUNT3 were used to identify current use of anticholinergic drugs and the 12-month incidence of start of treatment, as well as the factors associated with first-time prescriptions. In paper III, all prescriptions registered for anticholinergic drugs from January 1, 2004 to December 31, 2010 were retrieved from the NorPD and analyzed at the individual level. Drug persistence, discontinuation rates and switch rates during a follow-up period of 365 days after the first prescription were calculated. Results An association with urinary incontinence was found for selective serotonin reuptake inhibitors (SSRIs) and lamotrigine. For both SSRIs and lamotrigine, the associations were pronounced for mixed urinary incontinence. The association was strongest in women with the most severe symptoms. No associations were found for benzodiazepines, zopiclone/zolpidem, beta blockers, or diuretics. Only 4.5% of women with urinary incontinence in HUNT3 were prescribed an anticholinergic drug during the 12 months prior to participation, and the 12 month incidence of treatment was 1.8%. Age, urgency or mixed urinary incontinence, severe symptoms, extensive coffee consumption, and visiting a doctor due to urinary incontinence were factors associated with a first-time drug prescription. Overall, the 1-year persistence for new users of anticholinergic drugs was low (38.0%). Users of solifenacin and tolterodine were somewhat more persistent than users of darifenacin and fesoterodine. In total, 31.9% of patients filled only one prescription for an anticholinergic drug. Conclusions The odds of urinary incontinence were found to be about 1.5-fold higher in women using SSRIs and almost 3-fold higher in women using lamotrigine than in non-users. An association with lamotrigine has not been reported previously. Only a small proportion of women with urinary incontinence (4.5%) were prescribed an anticholinergic drug one year prior to participation in HUNT3. The discontinuation rate for anticholinergic drugs was high.