March 27 - Depression

Question 1

How common is major depressive disorder?

Answer 1

Lifetime prevalence of approximately 16% (almost 1 in 6)

Question 2

Describe a major depressive episode?

Answer 2

Causes significant distress/dysfunction. It is not due to medication, medical illness or drug abuse. It is not associated with bereavement, i.e., symptoms persists for more than 2 months or features marked functional impairment, preoccupation with worthlessness, suicidal intent, psychosis, psychomotor retardation. Must include depressed mood or anhedonia (unable to enjoy things) and five or more of the follwoing through a 2 week period: depressed most of the day, anhedonia, weight loss, sleep disturbance, psychomotor changes, fatigue, feelings of worthlessness or guilt, inability to concentrate or make decisions, thoughts of death or suicidal intent

Question 3

Describe the neuropathophysiology and neuroimaging associated with MDD

Answer 3

A small reduction in hippocampal size
Increased activation of the amygdala by negative stimuli
Reduced activation of the nucleus accumbens by rewarding stimuli
Deep brain stimulation (DBS) of either the nucleus accumbens or subgenual area 25 elevates mood in normal and depressed individuals

Question 4

What needs to be considered before MDD can be diagnosed?

Answer 4

Medical causes (low thyroid activity, anemia, chronic pain, infections, electrolytes, liver, cardiovascular, epilepsy, parkinson’s, alzheimer’s, malignancy
Substance-related causes (alcohol, THC, nicotine, opiate, stimulant)
Drugs/hormones
Stresses/losses

Question 5

What is used to diagnose MDD?

Answer 5

Validated “questionnaires” or scales to screen for and measure depression/anxiety. Also requires medical/pharmacological work up, and must include thyroid function

Question 6

Why would we want to use benzodiazepines for depression?

Answer 6

Help the patient sleep, relax. It also tends to reinforce the notion of trust between patient and the pharmacist

Question 7

What are the potential upsides to benzodiazepines?

Answer 7

It will probably work, to at least help the patient sleep or relax

Question 8

What are the potential downsides to benzodiazepines?

Answer 8

If it works and seems to solve the problem in the moment, it might be harder to convince the patient that they need long term plan (also there is a potential for abuse)

Question 9

What do antidepressants target?

Answer 9

Neurotransmitters that we think are involved in the pathophys of depression

Question 10

Why take antidepressants when thing are going better?

Answer 10

Most people don’t like taking medications long term. But there’s evidence that the longer they take them, the better they get and the less likely they are to relapse

Question 11

Can people become addicted to antidepressants?

Answer 11

No (in the same way that someone with diabetes doesn’t become addicted to insulin)

Question 12

What is St. John’s Wort?

Answer 12

The leading antidepressant in Germany. It has multiple active components which impacts many neurotransmittes/targerts. It is effective for mild to moderate depression. But there is poor evidence for moderate to severe depression. Also, there is potential for interacting with medications

Question 13

What are the potential sites for drug action?

Answer 13

1. Action potential in the presynaptic fibre
2. Synthesis of transmitter in presynaptic fibre
3. Storage of transmitter in the presynaptic fibre
4. Metabolism of transmitter in presynaptic fibre
5. Release of transmitter into synaptic cleft
6. Reuptake of transmitter into the nerve ending (presynaptic fibre) or uptake into a glial cell
7. Degradation of transmitter within synaptic cleft
8. Receptor for the transmitter on postsynaptic fibre
9. Receptor-induced increase or decrease in ionic conductance
10. Retrograde signaling (postsynaptic to presynaptic)

Question 14

Which potential site of action is most used?

Answer 14

The majority of drugs we use affect reuptake. A few drugs affect degradation

Question 15

What is the mechanism of action of antidepressants?

Answer 15

Enhance the “impact” of neurotransmitter in the synpase (especially serotonin, norepinephrine, and likely dopamine)
It effects depression by sustaining signaling normalizes downstream processes, which appears to include gene expression, which increase brain derived neurotropic factor (BDNF; and other neurotropic factors)
They do not cause addiction or dependency
Long-term administration is needed for full and optimal benefits
Neurotransmission changes induces a cascade of adaptations in the brain that underlie their clinical effects

Question 16

Why is BDNF important in depression?

Answer 16

It is a complex chemical that works to help repair nerve cells, establishing new ones
We also know that when someone with depression gets better, BDNF goes up (good outcome measure in basic research)

Question 17

Describe the prognosis associated with depression?

Answer 17

The more severe the presentation, the longer time left undertreated, the number of episodes, the frequency of relapse are all markers of poor outcomes.
Access to supports, adherence to treatment, a history of “quick” responses to treatment, lower life stressors are all consistent with better outcomes. We try to boost thses things (ex. encourage patient to spend time with family and/or friends) and ease life stressors

Question 18

What is the role of a pharmacist in the treatement of depression?

Answer 18

Educating patients on the importance of adherence (not compliance - making it their plan), educating the patient about what depression is (make sure they know it’s not their fault), educate the patient about reducing adverse effects