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Abstract

The burden of rising health care expenditures has created a demand for information regarding the clinical and economic outcomes associated with complementary and alternative medicines. Meta-analyses of randomized controlled trials have found Hypericum perforatum preparations to be superior to placebo and similarly effective as standard antidepressants in the acute treatment of mild to moderate depression. A clear advantage over antidepressants has been demonstrated in terms of the reduced frequency of adverse effects and lower treatment withdrawal rates, low rates of side effects and good compliance, key variables affecting the cost-effectiveness of a given form of therapy. The most important risk associated with use is potential interactions with other drugs, but this may be mitigated by using extracts with low hyperforin content.

As the indirect costs of depression are greater than five times direct treatment costs, given the rising cost of pharmaceutical antidepressants, the comparatively low cost of Hypericum perforatum extract makes it worthy of consideration in the economic evaluation of mild to moderate depression treatments.

Keywords

economic evaluation depression St John's wort

The annual cost of mental illness in Australia is estimated at $20 billion [1]; mental illnesses account for almost a third of the total disability burden, a figure predicted to increase [2]. The lifetime prevalence for major depression is currently estimated to be 16.6% [3], with a 12-month prevalence of 4.1% for depressive episode [4]. Notwithstanding the availability of drug and psychotherapeutic treatments, much depression remains undiagnosed or inadequately treated [5]. More than 232 million prescriptions were written for antidepressant medications (ADs) in the USA in 2007 alone, more than for any other class of drugs. Optimal treatment for affective disorders has been found to be cost-effective [6], with a cost-effectiveness of $10 475 per year lived with disability (YLD), but current coverage has been estimated at only 60.2%.

In many countries, clinical guidelines for the management of depression recommend medication as first-line treatment in primary care for moderate to severe depression but not for mild depression [7] due to a poor riskbenefit ratio. Although there is insufficient evidence for the cost-effectiveness of ADs in patients with milder forms of depression, general practitioners are known to prescribe ADs to these patients [8]. Given that there is a degree of dissensus regarding the efficacy and effectiveness of ADs, concerns about the value of current depression treatments come at a time when governments universally are facing both increasingly constrained resources and growing demands for more economical health care. Therefore, it is important that healthcare resources are used to maximize health benefits for people with depression. Economic evaluations can contribute pertinent evidence to the discussion and development of policy and practice and can support decisions on resource allocation by providing comparative data to identify which agents deliver the highest value for a given expenditure. Lack of evidence about the cost-effectiveness of complementary and alternative medicine (CAM) therapies is often cited as the main reason for the reluctance of funders to integrate CAM into mainstream service provision [9]. The growth in evidence on clinical effectiveness for CAM treatments such as St John's wort (SJW) for mild to moderate depression is not matched by evidence of cost effectiveness despite clinical evidence. Consequentially, coverage limitations due to the relatively limited amount of high quality outcomes research in CAM has likely reduced access to these medicines by impeding their integration into financial mechanisms commonly found in conventional health care [10]. Thus, the aim of this review is to revise data on the utility of SJW, its low cost and effectiveness relative to current treatment, as the basis for a prospective economic evaluation. Previous cost analyses of drug treatment for depression have highlighted the significance of the cost of ‘treatment resistance’ or ‘treatment failure’ on the expected cost of treatment [11,12]. As drugs with demonstrated clinical efficacy and a better tolerability profile are associated with a lower overall expected cost of treatment, the avoidance of adverse drug effect-related costs and the possibility of treatment failure [13], an economic model of SJW may provide useful information on the costs and consequences of depression treatment and serve as a tool for health-care decision makers.’

Method

An electronic search was conducted to identify studies from 1994 to 2010 in the following databases: MEDLINE, CINAHL, PubMed and Cochrane. The search terms used were antidepressants, St John's wort, Hypericum perforatum, systematic review, randomized controlled trial, depression, mild to moderate depression, and economic evaluation. The search was limited to randomized controlled trials (RCTs) and systematic reviews published in English. Inclusion criteria were RCTs and systematic reviews between the years 1994 and 2010; diagnosis of trial subjects was mild to moderate depression; with comparator antidepressant. Articles were excluded if they were not in English, or included patients with severe depression.

Results

Current CAM use and mental health

Many people opt for CAM, of which herbal medicine is one form of therapy, in an attempt to avoid possible adverse effects [5] as well as a desire to explore all treatment options (often in the face of a lack of success with conventional care) [5]. Previous research has shown that overall CAM use is positively associated with the use of conventional medicine [14–17] with patients often combining prescription medicines with herbal and dietary substances in the belief that the combined use of CAM and conventional medicine will increase the likelihood of improvement [16]. Depression is among the most commonly reported reasons for the use of CAM in community surveys [5,18]. Results from the few previous studies of the use of CAM among psychiatric outpatients reported in the literature are consistent with this in showing high rates of CAM use [19–21]. The combination of CAM and ADs seems to be related to an increase in subjective psychological well-being and thus a decrease in depression symptoms to a greater degree [17]. A study by Knaudt et al. [21] found that more psychiatric patients use CAM than reported in studies of the general population (53% versus 3442%), supporting prior evidence that CAM is frequently used to treat psychiatric symptoms [16,22–24]. This may be a reflection of the chronicity of depression and the high relative risk of relapse. In one population-based survey of 2590 subjects, among users of the 40 most common prescription and over-the-counter drugs, concomitant use of herbals/supplements during a 1-week period ranged from 7% among the AD paroxetine users to 22% for users of the AD fluoxetine [25]. In addition, sufferers of mild to moderate depression are inclined to use more CAM than those with severe depression [16], and this increase has the potential to influence the use of prescribed medication such as ADs.

There has been a paucity of investigations into the true effect of ADs in patients with less severe depression. This is partly the result of the inclusion criteria used for many trials where cut-off scores are imposed at baseline expressly to increase the sensitivity of AD/placebo comparisons [26]. Current trial design and the consequent dissonance between efficacy studies and effectiveness studies has been discussed elsewhere [26,27]. Recent research by Kendrick et al. (2009) showed that treatment with selective serotonin re-uptake inhibitors (SSRIs) is effective for those with mild to moderate depression down to a Hamilton Depression Rating Scale (HAM-D) score of 12, even if the additional benefit is small [28]. With respect to clinical practice findings, research has shown evidence of functional impairment due to very mild depression right down to a level of 7 on the HAM-D [29]. A recent survey of depressed outpatients found that 71% of the 503 patients assessed had HAM-D scores of less than 22 [30]. It is likely that a sizable proportion of depressed individuals who start AD medication in the community present with lower levels of severity [26] for whom SJW might then be a suitable alternative, and that a portion of this subset overlaps with those already self-prescribing SJW. Among patients with HAM-D scores below 23, Cohen d effect sizes for the difference between ADs and placebo are estimated to be less than 0.2 (a standard definition of a small effect), and only become clinically significant with a baseline HAM-D score of 25 [26]. The past selective publication of positive or biased AD studies is likely to have helped contribute to overvaluation of the utility of ADs [12] for the treatment of mild to moderate depression, creating a ‘signal effect’ [8] which consequentially may have affected opinions, motivations and behaviours of patients and physicians in several ways. Patients may have been dissuaded from discussing CAM treatment options such as SJW with their physicians, who may also be less motivated to inform themselves about CAM treatment options [31].

Of course, publication bias is a recognized phenomenon in mainstream medicine and there is some suggestion that it also occurs in CAM [32] along with the related phenomenon of location bias, where the direction of the result may affect the location of a study in terms of language and number of publications and presentations, frequency of citation, and indexing databases, and language bias, where more positive findings are published in non-English-language CAM journals. This applies to SJW, as is documented in the Linde review which found that trials of SJW from German-speaking countries had significantly more positive results than trials from other countries, the results of which were published in German-language journals [33]. This may be because the concept of herbal therapies is well accepted by the general German population, leading to increased rates of compliance, or due to an exaggeration of results of some smaller German trials. The overall net selection pressure in favour of positive clinical trials is as routine for CAM as for orthodox medicine for various reasons including self-censorship of negative findings and editorial and commercial pressures to show positive findings [34]. The exception to this as found in high impact factor medical journals may reflect the reluctance of authors to submit positive trial papers to “flagship” orthodox journals perceived to be hostile to CAM [32].

St John's wort: current use and pharmacodynamics

Of the CAM modalities identified with the treatment of depression, herbal medicine (including SJW) is the most frequently used [16,21]. Drugs based on Hypericum perforatum extract are among the leading ADs in Europe and are increasingly popular in the USA as well [35]. SJW is the most commonly prescribed AD in Germany, outselling the world's most widely used AD, fluoxetine [36], and ranked tenth among the top selling herbal products sold in the USA in 2007, with an estimated 4.4 million adults using a SJW preparation per year [37,38]. Although the exact mechanism has not been defined, its actions include decreased degradation and non-selective re-uptake of serotonin, dopamine and norepinephrine, modulation of neurotransmitter transport systems, and possible neuro-endocrinological effects [39,40].

Evidence for SJW as a treatment for depression

Multiple clinical studies have shown SJW to be effective and safe in the treatment of mild to moderate depression. More than 50 randomized controlled trials and more than 15 larger observational studies have investigated the effectiveness of SJW in the acute treatment of depressive disorders [38], determining SJW to be significantly effective in lowering depression. SJW has been reported to be more effective than placebo and equally as effective as tricyclic antidepressants (TCAs) in the short-term management of mild to moderate depression. The majority of overlapping meta-analyses and systematic reviews published in the last two decades and several more recent, short-term, randomized trials support this conclusion [41–45]. Although the current version of the Cochrane systematic review [33] of Hypericum perforatum extracts for major depression found superiority of SJW over placebo overall (response rate ratio 1.55, 95%CI 1.42 to 1.7), it also found a negative correlation between trial precision and effect size [33], finding that more recent trials had a higher degree of precision and were less likely to demonstrate a larger effect than older trials. In addition, while placebo response rates were found to be broadly similar, analysis of pooled results of trials outside Germany found the difference between SJW and placebo to be non-significant. In the discussion of this finding, the author suggested that this may be due to the acceptability of SJW in a country with an established tradition of usage. It is possible, as argued by Clement [46], that variability in outcomes is due to subtherapeutic levels of ‘active’ ingredients in studies with a wide variability of the same medicinal herb, as studies have shown significant differences in the rate and extent of absorption and the subsequent bioavailability of ‘active’ ingredients in various extract formulations. Although the quality of clinical trials in herbal medicines has improved significantly over the past decade, the grey literature is replete with trials using formulations with unspecified pharmacokinetic profiles. The well-publicized study by Shelton et al. [47] which failed to find effectiveness of SJW over placebo included patients with moderate to severe recurrent depression (an indication for which SJW is not approved in any country) tested a formulation not standardized to hyperforin. Several double-blind trials have compared SJW to fluoxetine, citalopram, paroxetine or sertraline [48–54]. In all of these studies, SJW proved as effective as the AD and caused fewer side effects. In the largest of these trials, SJW proved equally as effective as the drug citalopram and more effective than placebo [48]. The Cochrane systematic review [33] of Hypericum perforatum revealed similar data to the previous review after inclusion of further studies comparing selective serotonin re-uptake inhibitors (SSRIs) to SJW, indicating equivalent efficacy between comparators. The review examined 29 double-blind randomized trials, concluding that SJW is superior to placebo (RR 1.48, CI 1.23 to 1.77) and as effective as standard ADs (RR 1.01, CI 0.93 to 1.12) for the treatment of acute major depression [38], confirming other findings [55], and concluding that there is Level 1 evidence to support the first-line use of SJW as monotherapy in mild to moderate depression. According to National Institute for Health and Clinical Excellence (NICE) guidelines for the treatment of depression, there is a clinically important difference favouring SJW over ADs on increasing the likelihood of achieving a 50% reduction in depression symptoms as measured by the HAM-D [56].

The methodological quality of some studies involving heterogeneous patient populations and inconsistently used standardized symptom rating instruments has been an issue [38]. Some studies have used comparatively large doses of SJW with low doses of standard ADs [57], however, this may reflect the lack of universal consensus on how the effects of ADs should be measured in primary care, as well as dosage levels commonly used in clinical care [58]. Differences in extracts and dosing have also confounded results when examined as a whole [46]. Negative results were published in a large trial that also yielded negative results for the AD sertraline as well as for SJW [59]. However, inclusion criteria of baseline score of 20 on the HAM-D and an average duration of major depression of two years indicates that many subjects had moderate to severe recurrent depression. Long-term data are limited and have yielded inconsistent results, with five positive [54, 60–62,64] and one negative RCT [59]. Safety and tolerability data were consistent in all the studies. Overall, the evidence supporting the efficacy of SJW in mild to moderate depression is cogent.

The main caveat to prescribing SJW is its potential for drug interactions, including a tendency to reduce the serum levels of many pharmaceuticals [65]. Current evidence suggests that this is due to hyperforin (a constituent responsible for pharmacokinetic alterations) increasing the expression of the pregnane X receptor in preparations with a high hyperforin concentration, which increases P-glycoprotein expression. Concurrent use of drugs metabolized by the cytochrome CYP450 liver enzyme system may theoretically result in altered therapeutic levels due to induction or inhibition of enzymes by SJW. A systematic review of 31 clinical studies examining the effect of SJW on drug metabolism concluded that high doses of hyperforin in SJW extracts were most likely responsible, and that preparations with low hyperforin content resulted in fewer drug interactions [66]. The counter side of using low hyperforin extracts is that in vitro and animal models demonstrate that hyperforin exerts greater antidepressant activity than other isolates such as hypericin [67]. Several case reports of serotonin syndrome have been documented by drug surveillance agencies [68]; however, the specificities are based on a theoretical pharmacodynamic antagonism causing serotonin syndrome and/or switching to hypomania or mania [69]. Currently, however, it is not clear whether it is a dose-dependent phenomenon or what its mechanisms may be, and in particular, whether an interaction with ADs causing hyperserotonergism actually occurs [67]. In counterpoint are findings that SJW reduces plasma levels of ADs via P-glycoprotein (PgP) pump up-regulation and CYP450 3A4 induction [70,71]. SJW preparations low in hyperforin are less likely to have this effect on PgP and CYP450 3A4, and consequently may be safer [71]. Prohibitions apply to the use of pharmaceutical ADs with similar metabolic pathways [72]. Newer ADs serve as a substrate or an inhibitor of one or more of the hepatic CYP450 enzymes responsible for the oxidative metabolism of several medications, some with narrow therapeutic indices.

Economic evaluation and CAM

The number of economic evaluations of CAM has increased in recent years [10], with a number of CAM therapies found to be cost-effective compared to usual care. As economic evaluation of CAM logically should include appropriate process and outcome-based measurement of the humanistic outcomes that constitute its philosophical doctrinism in order to account for the full value of CAM therapies, depression is a fitting subject. Maximizing wellness and enhancing well-being are patient-centred outcomes, ones that by definition require the kind of subjective measurement included in trials of depression interventions [99]. The more well-known instruments used to measure health status in these studies include the SF-6D [35] and the EuroQoL (EQ-5D), and health status can be translated into quality of life units using population-based preferences and incorporated into cost-effectiveness studies [27,51]. Sensitivity of these instruments to the changes in quality of life is an important concern for the evaluation of CAM therapies. The collection of economic outcome data is complicated by that fact that many CAM therapies are available over the counter and/or are often paid for out-of-pocket, with a consequent lack of administrative claims data. Additionally, many over-the-counter products, such as SJW, are not standardized and are of inconsistent quality. Standardization and quality will affect both the costs of the therapy and its outcomes, as discussed elsewhere in this paper. Even if the clinical outcomes of a CAM therapy are similar or slightly less beneficial than those of usual care, a lower cost of care can still make these therapies attractive to decision makers.

Cost-effectiveness/economic evaluation and SJW

Several treatment variables have the potential to impact the cost-effectiveness of depression treatment, such as medication cost, likelihood of response, adherence and tolerability, and the cost of treating adverse outcomes. Thus any evidence of clinical advantage and possible superiority of SJW to conventional treatments may translate into demonstrable cost-effectiveness. Current pharmacoeconomic evidence suggests escitalopram is the least expensive and most effective of the second generation AD drugs for the initial treatment of depression, dominating other treatment strategies due to its lower incidence of adverse drug reactions [13,73]. There is also a weak trend to show that SSRIs may be more cost-effective than TCAs [73], again due to decreased professional services utilization. Given the low cost of Hypericum extract, it may have a role in the treatment of patients who are unable to tolerate these drug side effects.

A key issue with respect to cost-effectiveness is the significance of not only the clinical but also the economic impact of non-adherence (non-persistence and non-compliance). Non-adherence is arguably the most important element responsible for the differences that exist between the effectiveness and efficacy of an intervention [74], with tolerability the critical determining factor for patient compliance and treatment outcome [75]. Where a range of non-adherence rates has been considered in economic evaluations, it is clear that not only does the incidence of adverse drug reactions drive the expected cost of treatment, but that subtle changes in non-adherence rates lead to large modification in cost-effectiveness ratios. Agents with a better tolerability profile are associated with a lower overall expected cost of treatment and greater effectiveness because of successful continuation on therapy and avoidance of adverse drug-related costs and treatment failure [13]. Non-adherence most often leads to increased resource utilization and higher total annual medical expenditures [76], as well as higher costs due to absenteeism and disability claims. In addition, even for modest reductions in the incidence of adverse reactions, a therapeutic agent with the lowest rate of adverse reactions can become cost effective, and even cost saving [75]. For example, if escitalopram exhibited an adverse drug rate greater than 6% lower than generic fluoxetine, it becomes cost-effective, and is cost-saving for an adverse drug reaction rate greater than 20% lower than fluoxetine, resulting in greater effectiveness and lower expected costs.

Compliance with AD medication is well-known to be poor, putting patients at risk for worsened clinical and economic outcomes [77]. The strict supervision which forms part of clinical trials is markedly different from the situation occurring in clinical practice, where over 40% of patients discontinue treatment within 3 months [78]. In primary care, discontinuation with TCAs has been reported to be as high as 60% due to adverse events [79] ranging from dry mouth and sedation [80] to weight gain, and sexual dysfunction [81]. There are additional issues of toxicity, in particular with TCAs and also venlafaxine. Compared with more traditional ADs, use of SSRIs is associated with a substantial reduction in adverse reactions [13]. As a result, treatment with SSRIs has been shown to be cost-effective compared with the TCAs when overall healthcare utilization and expenses are considered [13]. However, previous research has shown that SSRI-induced adverse reactions may cause patients to discontinue treatment, require changes in dose or switch to other agents, or require the addition of drugs or other therapies to treat adverse outcomes, having a significant impact on the cost effectiveness of treatment. The results of the cost analysis by Cantrell et al. (2006) verified those of earlier studies in which patients who discontinued therapy early had significantly higher total annual medical expenditures than did patients who continued therapy uninterrupted [76,82]. Being adherent to medication was associated with the lowest total health care resource utilization measured by medical and pharmacy costs [78]. The average percentage of patients developing a treatment-emergent adverse reaction on SSRI therapy requiring a physician visit as determined by Rascati et al. [83] was found to be 41%. A recent systematic review of AD use by Watanabe et al. (2010) found approximately 70% of 4842 patients experienced at least one adverse event.

This contrasts markedly with all current published literature on SJW. In published studies, SJW has been generally well tolerated at recommended doses [41]. Several meta-analyses and a clinical trial [42,43,47,84] have concluded that the rates of adverse events are comparable to those of placebo and less than that of standard AD treatment. A systematic review summarising 16 observational studies of SJW use including a total of 34 804 patients mostly suffering from depression found that the proportion of patients terminating treatment due to side effects varied in the 14 short-term studies from 0 to 2.8% and was 3.4% and 5.7% in the two long-term studies [85]. The proportion of patients reporting side effects was generally low, ranging between 0% and 5.9%. A review of adverse events in patients under treatment with 1.08 mg/day of hypericin from 1991 to 1999, involving approximately 8 million people, documented 95 reports of adverse events [86]. A European drug-monitoring study of 3250 patients receiving 1.08 mg/day of hypericin included an overall rate of adverse reactions of 2.4% [87]. In efficacy trials that undertook laboratory monitoring of subjects (total 386 patients), no changes in complete blood cell count, liver function test results, or serum creatinine levels were found [88–92]. In one of the TCA comparison trials [92], electrocardiograms were performed on study subjects at baseline and again at the end of the study period. Patients who took imipramine had a statistically significant prolongation of conduction intervals and a small increase in the incidence of first-degree atrioventricular block, but no electrocardiographic changes were seen in those taking Hypericum extract. There are few data on the safety of Hypericum extract in overdose, although in one trial, healthy subjects were given single doses up to 3600 mg with no reported adverse effects [93]. In an analysis of 13 trials of SJW, Rahimi et al. found a significant difference in withdrawals due to adverse events between SJW and comparator ADs (RR of 0.53, 95%CI: 0.35 to 0.82, P = 0.004) for withdrawals due to adverse events [55], confirming prior studies [94] and concluding that the lower withdrawal rates conferred an advantage over ADs for depression treatment. According to NICE guidelines, there is strong evidence suggesting a clinically important difference favouring SJW over ADs on reducing the likelihood of patients leaving treatment early due to side-effects and reducing the likelihood of patients reporting adverse effects [56]. On the basis of clinical trial data, post-marketing surveillance and drug monitoring studies, SJW is well tolerated across a range of therapeutic dosages [95].

As relevant factors that may impact adherence include not only adverse events but importantly patient attitude [78], this again may be advantageous given the perception of herbal remedies as effective not only for symptom relief but also to improve general well-being, energy levels and quality of life [16]. Adherent behaviour is governed by the perceived and experienced outcomes rather than by actual outcomes [96], and patient participation exerts a strong influence on clinical outcome via adherence [97]. In some instances, patients may feel less dependent and evaluate themselves more positively when they discontinue AD use and instead use SJW because they no longer violate a (widely held) norm that rejects the use of medication [98], or because of the perception that AD use leads to a worsening of cognitive functioning and loss of self-control [99], self-esteem [98], or is addictive [99]. According to NICE guidelines, given that ADs have largely equal efficacy (although newer ADs are generally preferred on grounds of cost and safety), clinical choice should largely depend on side-effect profile, patient preference and previous experience of treatments (including patient perception of the efficacy and tolerability of any ADs they have previously taken), propensity to cause discontinuation symptoms and safety in overdose [56].

The cost of treating depressive spectrum illness has shown dramatic increases. For the period 2006-2007, 20.7 million prescriptions for mental health-related medications were written by Australian medical practitioners [100] at a cost of $670 million. The number of ADs prescribed in the five year period up until 2006 increased by 4.6% per year [100], accounting for 47.3% of mental health-related PBS expenditure; treatment costs for escitalopram alone in the past financial year amounted to $27 679 506. While many of the listed ADs have already seen price reductions as a result of patent expiry, given the comparatively low cost of SJW, it is worthy of consideration in the economic evaluation of mild-moderate depression treatments. The cost of SJW varies because of the different extracts used and dosages recommended. Comparative daily treatment costs in Germany have been approximated at €1.30 for the older ADs, €2.50 for newer ADs, and €0.90 for SJW [95], thus there are potential savings based on cost price alone. The current lack of regulation and standardization of commercially available preparations and the lack of appropriate control mechanisms for the sale of herbal medicines remains a significant barrier to determining actual costs at this time. Current coverage for depression treatment is approximately 60% [6], with half those diagnosed receiving either medication or CBT. That is, the proportion of the burden of depression averted by current treatment is low. Modelling studies have demonstrated that at optimal treatment levels, the burden of illness averted rises from 15% to 23% at an average of $11 000 per YLD. Thus, treatment is cost-effective. An economic evaluation of SJW has the potential to further augment efficient use of resources.

In standard care, psychological treatments generally tend to be delivered alongside treatment as usual. With respect to clinical efficacy, cognitive behaviour therapy (CBT) has demonstrated equal efficacy to ADs [101], but barriers to implementation have meant alternative methods of delivery of therapy such as computer administered CBT (CCBT) are becoming part of mainstream treatment. In general, the use of self-help programmes for depression has been associated with a low to moderate effect size [102]. Evaluation of programmes in Australia has shown that they can be more effective and much less expensive than standard therapy with medication [103,104]. Other recent research showed low adherence rates and minor improvements in depression and quality of life [105]. Health care costs of CCBT have been shown to be either higher [106] or lower [107] depending on the nature of the intervention. Stepped-care has become an essential feature of most treatment guidelines in psychiatry as a method of enabling patient choice to increase the motivation to comply with treatment. However, not all patients want to start with self-help, whether web-based or not, nor will every patient benefit from it, and consequently it is not generally recommended as a stand-alone therapy [108]. In the highly influential STAR-D trial in the USA, less than 30% of patients were willing to use CBT alone or in combination with medication [109]. SJW may provide a good option within a stepped-care model sequence as a cost-effective way to improve depression management.

Conclusion

There has been little examination of the potential impact of CAM use on the concurrent and separate use of conventional medicine nor of the potential cost savings incurred by the public health care system as a result. The high prevalence of SJW use amongst the general public and the evidence that individuals who use SJW also have a certain level of adherence to their prescribed AD medication regimen supports the need to incorporate the use of CAM into education and practice of both patients and mental health professionals. SJW has proven effectiveness, and a superior profile with respect to adverse events in comparison to synthetic antidepressants. A rigorous economic evaluation of SJW compared to alternatives will provide a synthesis of information currently unavailable that is of direct relevance to the public, clinicians and other stakeholders such as public policy makers and government departments.

Footnotes

Acknowledgements

Declaration of interest: This study has received funding from the University of Queensland, the Complementary Healthcare Council of Australia, Queensland State Government, and Symbion MCP Operations. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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Potential of St John's Wort for the Treatment of Depression: The Economic Perspective

Abstract

Keywords

Method

Results

Current CAM use and mental health

St John's wort: current use and pharmacodynamics

Evidence for SJW as a treatment for depression

Economic evaluation and CAM

Cost-effectiveness/economic evaluation and SJW

Conclusion

Footnotes

Acknowledgements

References