Patients often perceive symptoms and treatment outcomes differently than healthcare providers. A recent survey revealed disparities between patient-reported experiences of MDD and healthcare provider assessments, highlighting the need for a deeper understanding of patient expectations for anti-depressant therapy.¹

Despite the growing emphasis on the early optimisation of MDD therapy, there is currently no consensus on what constitutes ‘fast’ relief from a patient's viewpoint or whether certain symptom improvements are more valued than others.¹

Commonly reported symptoms among patients living with MDD include fatigue, low motivation or loss of interest, anxiety or panic, and cognitive symptoms such as a ‘foggy’ mind. All these symptoms can lead to a sense of loss of control over their lives, social isolation, and complications in patients' daily functioning, which significantly impact daily life.

Treatment priorities

Treatment outcomes that MDD patients prioritise include relief from feelings of sadness, hopelessness, anxiety, and fear, as well as increased motivation, improved coping abilities, reduced nightmares, reduced cognitive ‘fogginess’, and enhanced social engagement.¹

Patients often find that anti-depressant medication alleviates anxiety, enhances their ability to cope, and fosters optimism. While some experience improvements in motivation, productivity, and concentration, others do not find relief from fatigue and sadness.¹

Despite these potential benefits, some patients express dissatisfaction with anti-depressant treatment, primarily due to adverse effects, including weight gain and concerns about habit-forming properties. The speed of symptom resolution is a crucial aspect of treatment for patients living with MDD.¹

While responses vary, many consider fast relief to occur within a week to two months, depending on the specific symptom. Anxiety or panic attacks demand immediate relief, while improvements in fatigue and mood are perceived as fast within one to two weeks.¹ 

What are some of the consequences of uncontrolled MDD?

Uncontrolled or untreated MDD can result in depressive episodes that persist for six to 12 months. Tragically, about 66% of patients living with MDD contemplate suicide, with 10% to 15% committing suicide.²

MDD typically follows a chronic and recurrent course, with recurrence rates of 50% after the first episode, 70% after the second, and 90% after the third. Furthermore, 5% to 10% of patients living with MDD are at risk of developing bipolar mood disorder.²

The prognosis of patients living with MDD varies. Patients with mild episodes, no psychotic symptoms, good treatment compliance, robust support systems, and strong premorbid functioning tend to have a favourable prognosis. Conversely, a poor prognosis is associated with comorbid psychiatric or personality disorders, multiple hospitalisations, and an older age of onset.²

As mentioned, psychiatric complications associated with MDD are significant. Additionally, it can exacerbate medical conditions like diabetes, hypertension, chronic obstructive pulmonary disease, and coronary artery disease. Uncontrolled MDD can drive self-destructive behaviours as a coping mechanism, rendering it profoundly debilitating.²

First-line therapies for MDD

Selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) are recommended as first-line treatment. Psychotherapy, including cognitive-behavioural therapy (CBT) and interpersonal therapy, also plays a crucial role in MDD management. For severe cases, electroconvulsive therapy, transcranial magnetic stimulation, vagus nerve stimulation, and ketamine can be considered, especially for treatment-resistant depression or specific conditions like acute suicidality or severe psychosis.^2,3

What to do if anti-depressants are not effective

About 30% of patients living with MDD do not achieve adequate response or remission with first-line anti-depressant therapy. In the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, the cumulative remission rate after four trials of anti-depressant treatment (within 14 months) was 67%. Even after sequential treatments, 10% to 20% of patients living with MDD remained significantly symptomatic for two years or longer.^3,4

Several studies have examined the use of psychotropic augmentation, anti-depressant switches, and combination therapy to manage treatment-resistant MDD.³

The use of atypical anti-psychotic agents, particularly second-generation anti-psychotics (SGAs), has been extensively studied for the management of treatment-resistant MDD, following risperidone's successful augmentation with SSRIs in 1991.⁴

Subsequently, the American Food and Drug Administration approved three SGAs (olanzapine in 2007, quetiapine XR in 2007, and aripiprazole in 2009) as augmentation therapies for MDD alongside anti-depressants.³

Several randomised controlled trials have explored the effectiveness of quetiapine as an augmentation therapy for MDD alongside anti-depressants. Monotherapy studies indicated that quetiapine XR effectively reduced depressive symptoms within one week. Flexible-dose and long-term studies showed its superiority over placebo. As an augmentation therapy, quetiapine demonstrated efficacy in most trials.⁴

Additionally, when combined with CBT, quetiapine showed significant symptom reduction. Despite some metabolic side effects, quetiapine XR is a well-tolerated option for MDD treatment across various disease severities.⁴

Conclusion

MDD presents a significant challenge for patients and society, impacting various aspects of patients' lives. Uncontrolled or untreated MDD can lead to severe consequences, including prolonged depressive episodes and a heightened risk of suicide. First-line treatments for MDD primarily involve SSRIs, SNRIs, and psychotherapy. However, a significant portion of patients do not achieve an adequate response to these therapies. For treatment-resistant MDD, SGAs like quetiapine have emerged as valuable augmentation options. Quetiapine has demonstrated efficacy in both monotherapy and augmentation therapy.

References

1. Baune BT, et al. Patient Expectations and Experiences of Antidepressant Therapy for Major Depressive Disorder: A Qualitative Study. Neuropsychiatr Dis Treat, 2021.
2. Bains N, Abdijadid S. Major Depressive Disorder. [Updated 2023 Apr 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK559078/
3. Tran K, Argáez C. Quetiapine for Major Depressive Disorder: A Review of Clinical Effectiveness, Cost-Effectiveness, and Guidelines [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health, 2020 Jan 30. Available from: https://www.ncbi.nlm.nih.gov/books/NBK562922/
4. Wang SM, et al. Second Generation Antipsychotics in the Treatment of Major Depressive Disorder: An Update. Chonnam Med J, 2016.