This thesis aims to provide policy makers with an evidence base for prioritising interventions for major depressive disorder. Optimal treatment for affective disorders such as depression has been found to be cost-effective but current effective coverage is low. An overview of existing trial data supports a potential role for St. John’s wort for the treatment of mild to moderate depression, with demonstrated efficacy to pharmaceutical antidepressants and a superior tolerability and safety profile. However, the evidence on efficacy for St. John’s wort is not yet matched by any cost effectiveness research. In direct response to this research gap, this research provides a cost-effectiveness analysis of the potential for improved health outcomes and cost savings if SJW were to be approved by policy makers as a treatment for mild to moderate depression.
In order to estimate the cost-effectiveness of treatment with St. John’s wort versus antidepressant therapy, a Markov model was constructed to show how both costs and health outcomes, measured in quality adjusted life years (QALYs), changed from a decision to use St. John’s wort as an alternative to antidepressants for the treatment of mild to moderate depression. Generic venlafaxine and sertraline were chosen as comparators for cost-effectiveness analysis. These two drugs are the most widely prescribed antidepressants in Australia. Evidence from head-to-head trials between St. John’s wort and sertraline have shown no difference in effectiveness; no direct comparisons of St. John’s wort and venlafaxine have been undertaken.
St. John’s wort was found to be cost-effective compared to venlafaxine and sertraline. The total cost savings for the model were $468.79 per individual for the model using venlafaxine as the first line of treatment, and $198.96 per individual for the sertraline model, representing reductions in direct healthcare costs. The use of St. John’s wort also predicted improvements in quality of life compared to pharmaceutical drugs. St. John’s wort was identified by probabilistic sensitivity analysis as the strategy with the highest net monetary benefit.
The strengths of the model are that the findings begin to fill the gap in the available economic evidence for alternative treatments for depression and St. John’s wort in particular, modelled using the most commonly prescribed antidepressants. A powerful aspect of the use of modelling is the ability to quantify the uncertainty surrounding the values of specific parameters - for example, treatment efficacy, adherence to treatment, sensitivity and specificity, and treatment costs - on the estimated outcomes and whether varying parameters alters the optimal decision under a given set of decision rules. The robustness of the results was supported by sensitivity analyses. The cost-effectiveness acceptability curves, summarising the uncertainty of the net benefit estimate, display a clear and understandable summary of the model outcome showing that there is a mean incremental net benefit of $5412 and $7248 per patient compared to venlafaxine and sertraline respectively as a first line of treatment.
The lack of direct comparative clinical trial data comparing St. John’s wort to venlafaxine and limited data with sertraline as a comparator required assumptions to be made based on published literature. Relapse probabilities were not modelled to depend on the disease history including episode length and number of previous episodes as the model incorporated efficacy data from controlled clinical trials and not naturalistic studies. Model parameters for remission rates were derived from only one published study and thus limit the external validity of the results in terms of comparable duration of remission. Current time-frames were based on the average length of clinical trials conducted for drug approval, and this was adapted for the model without allowing for either washout phases, overlapping tapering or dose titrations of medications as are often required in clinical practice.
The model has shown that St. John’s wort is cost-effective relative to pharmaceutical antidepressants based on efficacy data. At the extremes of probabilities tested, St. John’s wort was still associated with lower direct costs and better outcomes than the pharmaceutical comparators. Increased patient demand for alternatives to current treatments for depression and the need for choice are recognised by policymakers and healthcare providers currently reluctant to support its subsidised provision because the value of that provision is as yet unspecified. For a larger proportion of patients, the use of antidepressant drugs may remain the treatment of choice. This research quantified the superiority of St. John’s wort over standard antidepressant therapy in two ways - in benefit to patients in terms of health outcomes, and in cost savings to health service providers. Patients receiving St. John’s wort are more likely to receive antidepressant therapy for a duration consistent with professional guidelines for acute-phase treatment of major depression due to reduced incidence of adverse effects, thus improving mental health outcomes.