Review: Persistence and Compliance to Antidepressant Treatment in Patients with Depression

The paper reviewed here is from the open-access journal BMC Psychiatry – and is titled  ‘Persistence and Compliance to Antidepressant Treatment in Patients with Depression: A Chart Review’ by Norifusa Sawada and colleagues and freely available here. In the introduction, the authors characterise adherence to medication as consisting of both persistence in taking treatment and compliance in following the instructions for taking the medication. They set out to investigate these two components and suggest from their examination of the literature that both components have seldom been examined. The study design was very simple and could be relatively easily reproduced by other interested groups. The researchers focused on people with depression who had been referred to a hospital clinician for treatment. There were a few exclusion criteria. For instance the researchers didn’t include people with comorbid mental illnesses as that would complicate the picture. They are primarily interested in adherence to medication in people with depression and as we see in the results section, this pays off. They look back retrospectively through the casenotes. This can be a source of bias particularly if you’ve got a very nice hypothesis that you want to test. I think it’s difficult to comment on this type of bias though just from reading the paper. In order to measure the components of adherence, the researchers have created quantitative proxy markers – medication possession rate (MPR) being one. The MPR is the ratio of number of days of medication divided by duration of treatment prescription is intended for. I was slightly confused by this figure because I thought it was determined primarily by what the doctor had prescribed and the date of the next clinic appointment both of which seem to be features of the medical system rather than the patient. However I assume that the patient has some degree of control over the date of the next appointment.

There were lots of interesting findings. For the primary outcome measures though the reader is referred to Tables 1-4 (Table 2 is reproduced in part below). The persistence rates for medication drop off quite sharply in the first month and are then halved again in some cases by the third month. The stratification according to age and gender also provide interesting results and I wonder if there is a story here to be investigated in further studies. Table 2 shows the persistence levels across antidepressants. What I found really interesting here is that in the Japanese study they most commonly used Sulpiride as a licensed antidepressant. In the table below you can see that they’ve used Sulpiride as a reference point for comparison with the other antidepressants. Sertraline comes out with the highest persistence rates compared to Sulpiride and this result is both clinically and statistically significant and this reminded me of another study which was looking at tolerability and efficacy.

In their conclusions though, the authors do advise caution

‘However, these preliminary results should be interpreted with caution since we did not directly evaluate therapeutic and adverse effects of these medications in this study. In fact, the finding of varying persistence rates across medications could reflect confounding by the provider effect, and sertraline is the newest antidepressant that became available in 2006 in Japan‘

These comments got me thinking. Can we generalise from one culture or medical service to another. There are many factors that vary between cultures including diet, other aspects of lifestyle, role of the doctor and so on and yet many drug trials or research in other areas are included in meta-analyses on which further inferences are drawn. Maybe one useful approach would be to examine local differences in efficacy using this paradigm in order to test the appropriateness of generalisability. It may turn out that there are some interventions where the results are generalisable and others which are not.  Returning to the issue of retrospective bias, I would argue that this approach can be useful in identifying hypotheses for further testing using other approaches (e.g the RCT) so that even if there is bias it will most likely get uncovered when a more rigorous follow-up study methodology is used.

In terms of the compliance rates – the researchers used a cut-off threshold of 0.8 for the MPR for compliance and surprisingly the average score for all antidepressants is below this cut-off point. They respond by stating that even though the average is below this figure, some 55% of subjects scored at or above this level. In conclusion I thought the results were quite profound. The authors refer to schizophrenia and the emphasis that has been placed on ensuring compliance to aid recovery. The message here in this paper though is that the same emphasis needs to be placed on the treatment of depression. In summary, the researchers have produced a very simple study, easily reproduced with important results and a clear message – address adherence in depression. It will be interesting to see the follow-up studies in this area.

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