Treatment Resistant Depression: Causes, Consequences and Cures’

During the Biological Psychiatry Congress held in Cape Town, South Africa in September 2022, Dr Allan Young, an invited speaker from the United Kingdom, tackled the important topic of ‘Treatment Resistant Depression: Causes, Consequences and Cures’.

It is widely accepted that after a patient achieves remission from a depressive episode, a wide variety of residual symptoms may persist. This has severe consequences, including increased risks of relapse, a decreased time to the occurrence of a future episode and a profound effect on patient functioning.

Treatment Resistant Depression (TRD) is defined as a failure of two antidepressants from two different classes, that have been trialled at an adequate dose for an adequate length of time. According to the seminal Star*D study, after step 1 (remission achieved by between 27 and 33% of patients) and step 2 (remission achieved by 25% of patients), less than 15% of patients were able to achieve remission in step 3 and 4. As patients move down the steps, their chance of remission decreases and relapse rates and treatment intolerance increase. This is due either to a failure to respond to treatment, or a failure to sustain the response.

As patients move down the steps, their chance of remission decreases and relapse rates and treatment intolerance increase.

Young also took the audience through various staging models for TRD, including the Thase and Rush five level staging method published in 1997. In this model, patients are staged according to the number and classes of antidepressants that have failed to produce a response, moving from more to less common treatments.

 

The more recently published Maudsley Staging Model (MSM) offers increased value over the Thase and Rush model as it is a multidimensional model, which also incorporates the duration and severity of each episode, the number of previous failed treatment trials and also extended to functional impairment.

It was shown that depression was only diagnosed in 50% of patients, the time to treatment was one to eight years after the illness onset and only between 25 – 50% of patients received treatment.

TRD has recently undergone a reconceptualization, and an alternative definition has been proposed, namely Difficult to Treat Depression (DTD). Whilst TRD only focuses on failed treatments, DTD examines acute and long terms outcomes, including chronicity. It allows for the assessment and remediation of any treatment obstacles, as well as a reconfirmation of the primary diagnosis and the identification of any comorbidities identified.

 

A 2022 by Strawbridge R et al[1], examined Care Pathways for people with Major Depressive Disorder. The aim was to elucidate the nature and extent of ‘gaps’ between best practice and current practice care. It was shown that depression was only diagnosed in 50% of patients, the time to treatment was one to eight years after the illness onset and only between 25 – 50% of patients received treatment. Follow up of these patients was poor, and continuity of care was lacking. All of these factors lead to the increasing rate of TRD development which leads to higher comorbidities, suicide risk, service use and functional disabilities and should be as best addressed by the healthcare system as possible.

Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.

References

Strawbridge R, et al European Psychiatry 2022; 65:e36