Dr Melane Van Zyl

About 33% of patients with depression are still depressed after two different types of treatment. These are the patients that should be treated by psychiatrists.

The psychotherapist in me wants to validate and reassure patients with depression that one out of three is a lot, so this means if you struggle to get better it does not say anything about you as a person, it is just a scientific fact. Try not to go into the “downward spiral” thinking that goes with depression e.g., I do not deserve to get better, others are better off without me, I am a burden, etc. There is hope, and novel treatments are becoming accessible (more about that later).

Firstly, TRD is not mild or moderate depression. So, what is mild to moderate depression?

Mild to moderate major depression is characterized by the following clinical features:

●No suicidal or homicidal ideation or behaviour, or ideation that does not pose an imminent risk. Ideation that does not pose an imminent risk includes the wish or hope that death will overtake oneself (e.g., “Life is not worth living” or “I would be better off dead”); or fleeting thoughts of killing oneself, with non-existent or vague plans to commit suicide and no intent.
●No psychotic features (e.g., delusions or hallucinations).
●Little to no aggressiveness.
●Intact judgment such that the patient or others are not at imminent risk of being harmed.
●Impaired functioning is not obvious.

In addition, mild to moderate major depression is indicated by a score of <20 points on the Patient Health Questionnaire – Nine Item (PHQ-9).

I have been doing PHQ-9’s on all my patients since the beginning of the year, so we have a clearer idea of how patients are improving (or not).

And then there are different types of “difficult to treat” depression:


•Unipolar major depression – Unipolar major depression (major depressive disorder) is diagnosed in patients who have suffered at least one major depressive episode and have no history of mania or hypomania
•Treatment-resistant depression – Treatment-resistant depression typically refers to a major depressive episode that does not respond satisfactorily after two trials of antidepressant monotherapy; however, the definition has not been standardized.
•Treatment-refractory depression – Treatment-refractory depression typically refers to unipolar major depressive episodes that do not respond satisfactorily to many sequential standard regimens, including multiple antidepressants and adjunctive drugs, as well as at least one trial each of adjunctive psychotherapy, repetitive transcranial magnetic stimulation, and electroconvulsive therapy. However, the definition has not been standardized, and there is no clear demarcation between treatment-resistant and treatment-refractory depression.

Among patients with unipolar major depression who receive initial treatment, the estimated incidence of treatment resistance ranges from approximately 45 to 65 percent. Risk factors include general medical and psychiatric comorbidity, severe intensity of depressive symptoms, and adverse life events.

Treatment resistant unipolar major depression eventually remits after one or more next step treatment trials in approximately 67 percent of patients.

This means that 33 percent of patients remain depressed after trying two different treatments.

Risk factors — Treatment resistant, unipolar major depression has been associated with many factors, including:

●Comorbid general medical disorders (e.g., coronary heart disease and hypothyroidism
●Chronic pain
●Medications (e.g., glucocorticoids and interferons)
●Comorbid psychiatric disorders (e.g., anxiety, personality, and substance use disorders)
●Severe intensity of depressive symptoms
●Suicidal thoughts and behaviour
●Adverse life events (e.g., childhood trauma or marital discord)
●Personality traits (e.g., low reward-dependence, low extraversion, and high neuroticism)
●Early age of onset of major depression (e.g., age <18 years)
●Recurrent depressive episodes
●Loss of employment and low socioeconomic status

In the next article, we will begin to look at the treatment options for TRD.

Reference: UptoDate, 2022




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