By 2030, it is predicted that major depressive disorder (MDD) will overtake cardiovascular disease to become the leading cause of lost DALYs (disability-Adjusted Life Years) linked with ill-health or disease, a burden which reflects the fact that as many as 1 in 2 patients do not respond adequately to antidepressant therapy.

This was one of the stark messages at a satellite symposium entitled “Optimising treatment strategies for patients with MDD who do not respond adequately to antidepressants”, chaired by Professor Michael Thase of the Perelman School of Medicine if the University of Pennsylvannia, USA.

Ripple effects

Patients with MDD are impaired across multiple domains, said Professor Dan Iosifescu of the Icahn School of Medicine at Mount Sinai, New York, USA. He reminded delegates that in addition to the symptom burden posed by MDD, patients often experience cognitive deficits and impairments in social functioning and relationships that have far-reaching ripple effects.

Social relationships, work prospects, marriages and personal relationships, and the family and support systems of a patient with MDD, can all be affected by the condition. Professor Iosifescu highlighted that this burden in part reflects the fact that large numbers of people with MDD do not achieve an adequate clinical response or remission despite ample availability of different classes of antidepressants.

Ever-decreasing circles

Professor Iosifescu went on to cite evidence that shows that for many patients with MDD, a pattern of inadequate response to treatment is then set in motion. He said data from the STAR*D study reveal that as many as 50% of people do not achieve a response to a first-line antidepressant therapy, and response rates become progressively lower with each additional line of treatment, with worsening outcomes for patients.

The vexed question is how best to address inadequate responses to antidepressant therapy.

Professor Iosifescu pointed out that strategies may include increasing the dose of antidepressant, switching treatments or augmenting antidepressant therapy with agents offering complementary pharmacological effects. This latter approach has the potential of retaining and building upon any benefits of initial therapy. He said that in a nutshell, patients with MDD want a full recovery, which according to Professor Iosifescu means good symptom control and functional recovery.

Far-reaching frustrations

This was view echoed by Professor Philip Gorwood of the Sainte-Anne Hospital, Paris, France, who was keen to remind delegates that many of the two-thirds of patients with MDD who fail to achieve full remission are frustrated by what current treatment strategies deliver. He stressed that quality of life is a key goal for patients and he said treatments need to offer the right balance between efficacy and safety.

Professor Gorwood highlighted that one of the signs that patients are seeking better responses to treatment is their willingness to try complementary and alternative medicines (CAMs).

Physicians are also keen to explore ways to support and help MDD patients achieve better response and remission rates. Professor Gorwood flagged a number of unmet needs – including the need for a wider choice of therapies, the need to understand which patients will best benefit from which treatment strategies and the importance of tolerable therapies which patients can comply with. Despite the fact that some of the recent research into the genetics of depression has been disappointing, Professor Gorwood remains hopefully and optimistic that the concept of personalized medicine – fitting the right treatments to the right patients – is a worthwhile and achievable future goal.

He and his presenter-colleagues also shared glimpses into the emerging and increasing evidence-base demonstrating that adjunctive use of atypical antipsychotics may offer a better-tailored strategy for addressing the burden of MDD that does not respond adequately to antidepressant therapy. Interestingly, he reported the results of a survey that showed that the main reasons not to prescribe an antipsychotic were a “wait and see” attitude among physicians and a focus on specific symptoms and tolerability concerns, suggesting that effective adjunctive treatments with an improved tolerability profile would be welcomed into the MDD armamentarium.