Pharmacolocy-Antidepressants and Mood Stabilizers

Question 1

How long does a clinician usually need to wait to see if an anti-depressant is working for their patient?

Answer 1

2 to 6 weeks

Question 2

How many of your patients will not respond to multiple trials of anti-depressant therapy?

Answer 2

1/3. Some of your unipolar patients may also be bipolar

Question 3

What is the monoamine hypothesis of depression? What are the limitations of this hypothesis?

Answer 3

Depression is due to an imbalance of serotonin, dopamine or epinephrine in the brain. Limitations: antidepressants increase monamine levels instantly, but mood takes 2-6 weeks to improve, some drugs increase neurotransmitter levels and are poor antidepressants, depletion of monamines does not induce depression.

Question 4

What is the neurogeneis hypothesis of depression?

Answer 4

Depression is due to impaired hippocampal neurogenesis. Monamines increase BDNF (brain derived neurogenic factor) and increase hippocampal neurogenesis

Question 5

A patient comes to see you in clinic because he is depressed. You try to help him out by increasing his serotonin (5HT) levels at the synaptic cleft. What is the mechanism of action of the drug you prescribed him?

Answer 5

Blockage of 5HT reuptake by the SERT (serotonin transporter). SSRIs, SNRIs, tricyclics and cocaine all do this.

Question 6

Why do many patients like SSRIs as opposed to other drugs that block SERT?

Answer 6

It is highly specific for SERT, minimally affecting NET and DAT. They have fewer side-effects.

Question 7

You have a new patient come to see you complaining of depression. You give him an SSRI to treat his depression. He comes back to the clinic a few days after taking the medication with lots of side effects. History reveals that he is also on a MAO inhibitor and tricyclic antidepressant from his previous doctor. What symptoms would you expect him to present with?

Answer 7

This patient has Serotonin syndrome, this occurs when you take any combination of SSRIs, MAOIs or tricyclic antidepressants. He would present with “HARM”: hyperthermia, autonomic instability, rigidity and myoclonus. THIS CAN BE LIFE THREATENING

Question 8

What drug do you not want to give a patient who is currently receiving treatment to limit the recurrence of breast cancer?

Answer 8

Fluoxetine. It inhibits metabolism of Tamoxifen by CYP2D6 and can increase recurrence of breast cancer.

Question 9

A patient comes to see you in clinic because he is depressed. You try to help him out by increasing his serotonin (5HT) and NE levels at the synaptic cleft. What drugs have the ability to make this happen?

Answer 9

Cocoaine, TCAs, SNRIs and buprion

Question 10

What is mirtazapine’s mechanism of action?

Answer 10

Inhibition of the alpha-2 receptor inhibits its ability to inhibit NE release, so you get more NE release.

Question 11

What kind of side-effects are often seen when enhancing serotonin function?

Answer 11

Agitation, apathy, decreased libido, diarrhea, ED, insomnia, nausea, weight gain

Question 12

What kind of side-effects are often seen when enhanging NE function?

Answer 12

Agitation, dry mouth, hypertension

Question 13

What kind of side-effects are often seen when enhancing DA function?

Answer 13

Agitation, constipation, insomnia

Question 14

What kind of side-effects are often seen when inhibiting H1 receptors?

Answer 14

Drowsiness, sedation, weight gain

Question 15

What kind of side-effects are often seen when blocking muscarinic receptors?

Answer 15

Blurred vision, cognitive impairment, constipation, decreased sweating, dry mouth, memory impairment, urinary retention

Question 16

What side effects are seen when blocking dopamine receptors?

Answer 16

Decreased attention, sedation

Question 17

Why would you prescribe imipramine and amitriptyline over desipramine and nortriptyline?

Answer 17

Imipramine and amitriptyline have increased affinity to block SERT > NET. They are then broken down to desipramine and nortriptyline that have increased affinity to block NET > SERT.

Question 18

What is a major concern of giving a depressed, suicidal patient two weeks worth of TCAs?

Answer 18

They have a narrow therapeutic window with lots of serious side effects and could kill the patient (coma, seizures, arrhythmias)

Question 19

How are monoamine oxidase inhibitors effective drugs in increasing NE and 5HT at the synaptic cleft?

Answer 19

Inhibiting MAO increases the amount of monoamines in the neuron terminal that can be secreted.

Question 20

Why are MAOIs not the 1st line drug used to treat depression?

Answer 20

Foods containing Tyramine cannot be eaten. Tyramine displaces NE from the vesicles and pushes lots of NE out into the synaptic cleft and causes mass vasoconstriction and hypertensive crisis.

Question 21

What level of anti-cholinergic, sedative, agitative, insomniac, hypotensive, cardiac, GI, and appetite side effects exist with the following drugs:

Answer 21

*

Question 22

You are treating a patient for depression with SSRIs. She is seeing some effect, but there is still room for improvement. What drugs could you prescribe to augment the antidepressant efficacy?

Answer 22

Lithium, thyroid hormones, aripiprazole, olanzapine, quetiapine, buspirone.

Question 23

What SSRI has a risk of causing heart defects in a growing fetus if taken during pregnancy? When should SSRIs be stopped during pregnancy?

Answer 23

Paroxetine. Other SSRIs should be stopped during the third trimester because they are associated with withdraw symptoms and persistent pulmonary hypertension.

Question 24

Why should you think about taking an SSRI if you are depressed while pregnant? What about after birth?

Answer 24

Untreated depression can cause pre-term labor, low birth weight and problems with bonding. After birth, the mother needs to know that anti-depressants and lithium are secreted in the breast milk and their safety is unknown.

Question 25

What are the only antidepressants that have clinical trial evidence for use in children?

Answer 25

SSRIs (fluoxetine and sertraline)

Question 26

What is the difference between a manic episode and hypomania?

Answer 26

Manic episode: lasts at least a week. Hypomania: lasts at least 4 days.

Question 27

What symptoms are characteristic of mania?

Answer 27

“DIG FAST” Distractibility, Indescretion, Gradiosity, Flight of ideas, Activities increased, Sleep decreased, Talkativeness.

Question 28

What are the stages of bipolar disorder that you need to consider when considering drug therapy for the patient?

Answer 28

Acute mania (antipsychotic + mood stabilizer), maintenance (mood stabilizer) and bipolar depression (mood stabilizer + SSRI or buprion)

Question 29

What side effect of lithium makes you want to monitor kidney function closely in a patient who is taking it?

Answer 29

It inhibits the ADH response causing polyuria and eventually nephrogenic diabetes insidpidus

Question 30

A patient comes to see you in the ED complaining of nausea, vomiting, abdominal pain, diarrhea, sedation and a fine tremor. You decide that he has the stomach flu and send him home. A day later he comes in with vomiting, profuse diarrhea, coarse tremor, ataxia, convulsions and confusion. History reveals that he has bipolar disorder and a recent torn ACL. How will you treat this patient?

Answer 30

This patient was originally presenting with mild lithium toxicity symptoms that have now progressed to acute toxicity. This is because he probably took NSAIDs with his torn ACL while he was on lithium. This decreased the GFR and increased blood lithium levels. You treat him with haemodialysis.

Question 31

Why do you need to constantly monitor patients serum lithium levels?

Answer 31

Therapeutic window is very low.

Question 32

Why is it important to take a very careful history when a patient first comes in with depression?

Answer 32

50% of bipolar I patients first present with depression. Prescribing an antidepressant can push them into a manic episode.