To our knowledge, this is the first study to assess the prevalence and patterns of strategies applied after an IAD changed because of a suboptimal response in patients with MDD in Qatar and the Middle East.
In this retrospective study, we found that the IAD was an SSRIs in 80% of the cases. Almost half of the patients (49% [44% − 53%]) had their IAD changed within less than one month, whereas the proportions of patients whose IAD changed in 31 to 90 days, 91 to 180 days, or more than 180 days were lower (20%, 19%, and 11% respectively). The most common IAD change strategy used was switching, mostly to an SSRI or to an atypical AD (40% and 37% respectively), followed by combination strategy (21%), then augmentation with antipsychotics (11%). The median time to IAD change was 43 days [33.2–52.7]. The factors which were associated with a higher hazard to change in IAD were younger age, un-optimization of the IAD dose before any change, and comorbid anxiety.
ADs are indicated for the treatment of depression, generalized anxiety disorders, obsessive-compulsive disorder, and post-traumatic stress disorder. There are 13 ADs in HMC formulary representing the different AD classes. ADs take considerable time to induce either response or remission and for many patients, the response is considered suboptimal . This lag in the AD response may lead to negative MDD outcomes including increased risk of suicidal behavior and other deliberate self-harm, psychological distress, occupational and functional limitations, and lack of adherence to medications. The results of this study showed that almost half of the patients underwent a change in their IAD treatment due to a perceived lack of response in the first 30 days of the treatment. The International guidelines such as National Institute for Health and Care Excellence (NICE-2018) and the Canadian Network for Mood and Anxiety Treatments (CANMAT-2016) generally specify a timeframe of 2–4 weeks to switch from the IAD at an adequate dose if no response was observed . The rate of switching considerably varied throughout different studies ranging from 8–40% [20, 21].
We found that a quicker change in the IAD strategy was associated with younger age. There has been some evidence that older patients might exhibit a slightly slower response to AD medication even though other studies did not show any link between age and speed of response [21, 22]. The possibly slower response in older patients might explain why the time to change IAD in our study was longer in older individuals. In addition, since polypharmacy is much more common in older patients, it is understandable that clinicians could be more reluctant to prescribe yet another drug, and it seems wise to wait longer before having to combine ADs or augment the AD medication with an antipsychotic drug [23, 24]. This goes in line with international guidelines recommending monotherapy in older patients with MDD .
Patients with unoptimized IAD doses also had a higher hazard to undergo a change in their IAD. This might be due to some clinicians resorted to switch, combine, or augment IAD without optimizing the IAD dose first. Since we basically relied on documentation of the physicians to report the reasons behind IAD change, we found some patients’ files with unclear justifications whether those patients underwent a change to their IAD due to side effects or suboptimal response. To reduce bias or imprecision, we decided to perform adjustment for “bothersome side effects” variable in the list of independent factors included in the regression models. However, the final MI multivariate model showed statistically insignificant association with the likelihood of IAD change.
Even though the conventional approach remains to optimize the dose of the AD medication before switching or adding another psychotropic medication, there has been some evidence that “early switching strategies” might actually yield better MDD outcomes [16, 26, 27]. A meta-analysis showed that the lack of early improvement (often defined by less than 20% reduction in a depression scale score) at two weeks may indicate that changes in depression management should be considered earlier than conventionally thought. . Meanwhile, a double-blind, randomized study showed that the time to regaining normal functionality might be shorter when adopting the early compared to the conventional switching strategy . Another recent meta-analysis of nine studies showed significant associations between early improvement, response, and remission. Nevertheless, the treatment scenario associated with the best remission rate was switching at four weeks rather than at two or six weeks .
Change in the IAD strategy was slower in patients with comorbid anxiety. This was consistent with previous studies showing that patients with a comorbid anxiety disorder or with anxiety symptoms concurrently with the depressive episode might have a slower onset of action of AD medication . In level one of STAR*D, MDD patients with anxiety symptoms exhibited significantly lower rates of remission as well a significantly slower remission than in patients with MDD without anxiety . Hence, it seems reasonable to wait longer in patients with comorbid anxiety before changing the IAD strategy.
The findings of this study can have direct clinical guidance for health care professionals since an optimized, evidence-based use of AD medication can improve the clinical outcomes of patients with MDD; and to identify high-risk factors that could worsen the survival time on IAD such as young age and comorbid anxiety . We included most of the presently available AD medications commonly used in a clinical practice setting, and we compared median IAD change time and percentages in an actual clinical situation in both inpatient and outpatient settings.
Despite the merits, several limitations in our study need to be acknowledged: the retrospective design and the reliance on medical records led to missing data. Nevertheless, most evidence comes from retrospective studies (with their inherent limitations), or from trials where “the most complex” patients are excluded (including patients with multiple comorbidities, with a neurocognitive disorder, or with acute suicidality). This may partly explain the gap that exists between the data of the literature and the clinical practice. In addition, we did not include the “IAD pharmacological group” variable in the Cox regression model because of the number of patients who had their IAD as SSRIs were incomparable to non-SSRIs users. Our sample was also recruited from the main psychiatric hospital in the state; however, patients with MDD treated in primary healthcare centers or in the private sector might have different severity of illness; hence, our findings can probably be extrapolated to the entire population of patients treated with AD medications with caution. Furthermore, the use of psychometric scales to assess the efficacy of the AD medication could have provided a much more objective and quantifiable assessment of the response; however, in this setting, measurement-based care (MBC) is not being routinely used. Finally, adherence was not assessed, and it was possible that adherence problems could have resulted from other residual confounders.