AssessmentsMajor depressive disorder
Major depressive disorder
USMLE® Step 1 style questions USMLE
USMLE® Step 2 style questions USMLE
A 65-year-old woman comes to the office for evaluation of her depression. She has a history of major depressive disorder that is refractory to SSRIs, buspirone, mirtazapine, and trazodone. She denies homicidal ideations, but when asked about suicide, she states that she has thought of using a rope to hang herself. However, she says she would not do that because it is against her faith. She has family that lives in another state and has been living alone since her husband passed away 7 years ago. She begins a tricyclic antidepressant (TCA) on a limited dosing regimen and comes to the office for regular monitoring of its levels. Which of the following TCAs is most appropriate for this patient?
Content Reviewers:Rishi Desai, MD, MPH
Contributors:Tanner Marshall, MS
Clinical depression, which is sometimes called major depressive disorder or unipolar depression, is a serious mental disorder characterized by by persistent sadness and a loss of interest in the activities of daily life, like working, studying, participating in hobbies, eating, and sleeping.
Clinical depression has a lifetime incidence of up to 20% in women and 12% in men, making it one of the most common reasons people seek out mental health services.
In addition to being relatively common, clinical depression is very serious because it essentially leads to an overall feeling that life isn’t enjoyable.
We don’t exactly know what specifically causes clinical depression, but it’s probably the result of a combination of genetic factors, biological factors, environmental factors, and psychological factors.
It’s been shown that people with family members who have depression are three times more likely to have it themselves, especially if they’re closely related.
Medications that address the biological factors of depression focus specifically on neurotransmitters.
Neurotransmitters are signaling molecules in the brain that are released by one neuron and received by the receptors of another neuron.
Through this process, a message is transmitted from one neuron to the next.
The body’s ability to regulate how many of these neurotransmitters are sent between neurons at any given time is thought to play an important role in the development of depression’s symptoms.
That’s because neurotransmitters are likely involved in regulating a lot of brain functions, including mood, attention, sleep, appetite, and cognition.
The three main neurotransmitters that treatment for depression focuses on are serotonin, norepinephrine, and dopamine.
That’s because medications that increase the amount of these neurotransmitters in the synaptic cleft — this space between the neurons — are shown to be effective antidepressants.
This finding led researchers to develop the monoamine-deficiency theory, which says that the underlying basis of depression is low levels of serotonin, norepinephrine, or dopamine, which are called monoamines because they have one amine group.
Additionally, it’s thought that each of these neurotransmitters might affect a certain set of depression symptoms: norepinephrine may affect anxiety or attention; serotonin may affect obsessions and compulsions; and dopamine may affect attention, motivation, and pleasure.
So, if levels of one of these neurotransmitters are down, a person could experience a specific set of symptoms.
Serotonin, in particular, is thought to be a major player in depression because it’s potentially capable of regulating other neurotransmitter systems; however, evidence supporting this theory is still pretty limited.
There is, however, hard evidence implicating serotonin in depression, and that’s linked to tryptophan depletion.
Tryptophan is an amino acid the body uses to make serotonin, and it’s been shown that tryptophan depletion leads to symptoms of depression.
Overall, though, the reasons that depressed people have decreased serotonin levels — or no serotonin at all — in the first place aren’t well known, and so research is still ongoing.
Research into the causes of depression investigates the relationship between these biological components, genetics, and environmental factors, which could be specific events, like a death or loss, or ongoing trauma, like sexual and physical abuse.
Depression is diagnosed when a person meets certain criteria that are outlined in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders, also known as the DSM-5.
First, a person must be affected by at least five of the following nine symptoms for most of the day, nearly every day: depressed mood; diminished interest or pleasure in activities; significant weight loss or gain; inability to sleep or oversleeping; psychomotor agitation, like pacing or hand-wringing, or psychomotor impairment, which is the overall slowing of thought and movements; fatigue; feelings of worthlessness or guilt; lowered ability to think or concentrate; and, finally, recurrent thoughts of death, which is called suicidality.
This can include suicidal thoughts, with or without a specific plan, as well as suicide attempts.
These symptoms must cause significant distress in the person’s daily life.
Also, a depressive episode cannot be due to a substance or other medical condition, the person’s symptoms cannot be better explained by another mental disorder, like schizoaffective disorder, and the patient cannot have had a manic or hypomanic episode at any point.
Sometimes, depression can be divided into subtypes.
This means that onset happens either during pregnancy or during the four weeks following delivery.