In this pharmacoeconomic analysis we compared the use of pregabalin and venlafaxine XR in the treatment of generalized anxiety disorder in Portugal. The clinical side of this economic evaluation relies on a single clinical trial, in which a direct comparison between the alternatives considered was performed. In most cases, there are no direct comparisons between active treatments, so while the reliance on a single clinical study could be a weakness of this analysis, the strength derived from the direct comparison should also be acknowledged. Furthermore, the trial considered is the only one comparing flexible doses of pregabalin and venlafaxine XR, which is a more appropriate approach than assuming fixed doses. The placebo-adjusted effect size of pregabalin in this trial is similar to the effect estimated in other trials [28–32].
Concerning economic inputs, this analysis do not rely on collected data but rather on the consensus elicited via an expert panel. This is a common feature on Portuguese economic evaluations that evaluate treatments provided on an ambulatory setting, as there are no national databases of resource consumption. However, both the sensitivity analysis on costs and the small difference between the incremental cost-utility ratios with or without the cost savings due to the better health states of those patients taking pregabalin show that the expert panel findings do not influence the results. It should also be stressed that we assumed the mean dose used during the clinical trial, while it could be argued that after the first 8 weeks of modelling the mean final dose should be used. However, this was a conservative assumption as the incremental cost of pregabalin compared to venlafaxine XR is higher for the mean doses than for the final doses.
The assumption of no discontinuation could also be discussed, as it may be unrealistic, but it makes it possible to differentiate the consequences attributable to the initial treatments from the options that patients could change to. The sensitivity analysis also showed that this assumption does not impact the results significantly. Moreover, if those who discontinued treatment were included assuming that they had consumed one of the comparators without achieving any clinical gain, the ICER would decline below 23,000€.
Waxing and waning effects are not explicitly included in the model. This limitation implies that real absolute effectiveness of both drugs may differ from the estimated effectiveness. However, it should not impact incremental results, as those effects should impact results of both drugs to the same extent.
An aspect that should also be discussed is the perspective under which this analysis was conducted. In fact, we assumed a payers perspective, implying that the full cost of all resources must be included. However, as pregabalin is an anticonvulsant agent, patients only pay 10% of its price, while the nominal copayment rate for venlafaxine XR is 63%. So, under the patients perspective, pregabalin is a dominant option, i.e., it is both cheaper and more efficacious.
To our knowledge, there are only three economic studies comparing pregabalin to venlafaxine XR [8, 9, 33]. NICE  performed an economic evaluation based on a network meta-analysis in which the probability of discontinuation due to serious adverse events and the probability of response in patients without those adverse events were estimated. Pregabalin was associated with less adverse events (8.6% vs. 14.2%) and a lower conditional response probability (59.0% vs. 61.6%). Therefore, concerning response, the results of this network meta-analysis are in conflict with the conclusions of the only clinical trial directly comparing flexible doses of both drugs .
Either in NICE evaluation or in the first application of the model used in this study  it is concluded that pregabalin is associated to more QALYs. However, given the divergences in clinical inputs, the magnitude of the gains is different.
In a recent work , the authors also concluded for the cost-effectiveness of pregabalin vs. SSRIs/SNRIs in benzodiazepine-refractory outpatients with GAD.
In this study, assuming a threshold of 30,000€ per QALY, it is concluded that pregabalin is cost-effective in comparison with venlafaxine XR in the treatment of patients with generalized anxiety disorder in the Portuguese context.