PSYCH - Anxiety, Depression, Mania

Question 1

What is the monoamine deficiency hypothesis of depression?

Answer 1

depression caused by under-activity or underproduction of monoamines (dopamine, serotonin, and norepinephrine) in the brain

Question 2

What functions do anti-depressant drugs modulate?

Answer 2

initially thought to modulate monoamine neurotransmission, but now speculated to enhance synaptic plasticity, dendritic morphology, and neurogenesis (by modulating transcriptional activity)

Question 3

Where are Serotonin, NE, and Dopamine produced in the brain? Where do these NT-producing cells project to?

Answer 3

Serotonin - raphe nucleus –> projects to amygdala/hippocampus (fear/anxiety, learning/memory)

NE - locus coeruleus –> various sites, but does NOT project to the amygdala/hippocampus

Dopamine - VTA–> projects to frontal lobes (executive functions, decision making)

Question 4

Different classes of antidepressents exert their effects on different neurotransmitters. What NTs do these classes work on:

SSRI
SNRI
MAOi
NDRI
TCA
SARI
NaSSA

Answer 4

SSRI - Serotonin
SNRI - NE
NDRI - dopamine
MAO - ALL
TCA, SARI, NaSSA - Serotonin + NE

Question 5

MAO Inhibitors can cause Serotonin syndrome and/or Hypertensive crisis. How does it do this?

What are the symptoms of each one?

Answer 5

MAO inhibitors blocks MAO from metabolizing serotonin, NE, and dopamine.

Serotonin syndrome and/or Hypertensive crisis occurs when patients are taking a MAOi + another anti-depressant (SSRI, SNRI or tyramine containing products - wine/cheese)

Serotonin Syndrome

• musculoskeletal changes (rigidity, myoclonus)
• autonomic instability (hyperthermia, cardiovascular instability)
• Neuromuscular signs - seizures

Hypertensive Crisis
- NE binds a1 receptors on vascular system, which causes vasoconstriction.

Question 6

Why do patients have to be weaned on/off MAOi?

Answer 6

Long-term use of MAOi can lead to downregulation of beta-receptors; an abrupt stop in MAOi use can result in a rebound effect.

Question 7

Which two antidepressants result in suicidal ideation in patients up to 25 years old?

What is an alternative for these patient populations?

Answer 7

SSRI (Citalopram) and SNRI (Venlafaxine)

Alternative: TCA (Nortriptyline)

Question 8

Citalopram

Class:
Clinical use:
Major side effects:
Contraindications:

Answer 8

Class: SSRI

Clinical use: Depression + OCD

Major side effects: GI DISTURBANCES, QT prolongation, decreased sexual drive, MANIA, weight LOSS, but suicidal ideation in patients up to 25yo

Contraindications: MAOi, TCA, NSAIDs, St. John’s wort, or any drug that inhibits/enhances CYP450, and any drugs that induce QT prolongations (Class IA and Class III anti-arrhythmic drugs)

Question 9

Which three antidepressants decrease sexual drive?

What is an alternative for these patient populations?

Answer 9

SSRI (Citalopram) and SNRI (Venlafaxine), TCAs (Nortriptyline)

Alternative: Bupropion (NDRI)

Question 10

Which antidepressant decrease sexual drive?

What is an alternative for these patient populations?

Answer 10

TCAs

Alternative: Bupropion

Question 11

Why is it that Citalopram causes GI disturbances?

Answer 11

Citalopram = SSRI

most serotonin receptors are present in the gut, so SSRIs tend to increase diarrhea and loose stools, but these tend to resolve quickly

Question 12

Why is that Citalopram can cause mania?

Answer 12

Citalopram = SSRI

most patients with depression also have a comorbidity with bipolar disorder, thus SSRIs can induce mania in these patients, although the onset takes many years

Question 13

Of the SSRIs, which one inhibits cytochrome P450 (thereby enhancing the effect of several drugs metabolized by this enzyme (ie TCAs, haloperidol, anti-arrhythmics)

Answer 13

Fluoxetine

Question 14

Venlafexaine

Class:
Clinical use:
Major side effects:
Contraindications:

Answer 14

Class: SNRI

Clinical use: depression
Major side effects: increase BP, weight gain, sedation, suicidal ideation in patients up to 25yo

Contraindications: Hypertensive patients, MAOi, TCAs, NSAIDs,

Question 15

Nortriptyline

Class:
Clinical use:
Major side effects:
Contraindications:

Answer 15

Class: TCA

Clinical use: depression + enuresis + pain

Major side effects: weight gain, sedation, decreased sexual drive, 3 C’s (coma, convulsions, cardiotoxicity), but NO suicidal ideation

Contraindications: patients in the acute post-MI phase

Question 16

Tertiary TCAs are processed by the body ot produce Secondary TCAs. Give an example of how this changes the function.

Answer 16

Imipramine (3˚) –> desipramine (2˚)
blocks 5HT –> blocks NE

or

amitriptyline –> Nortriptyline

Question 17

Bupropion

Class:
Clinical use:
Major side effects:
Contraindications:

Answer 17

Class: NDRI

Clinical use: depression + ADHD, smoking cessation, SAD

Major side effects: insomnia, tremors, seizures, but NO weight gain or decreased sexual drive

Contraindications: MAOi, TCA, NSAIDs, Levodopa, Tramadol, patients with eating disorders or patients with SEIZURES/EPILEPTIC DISORDERS because it increases the risk of seizures by lowering the seizure threshold.

Question 18

Why is it that patients on MAOi can’t eat cheese, wine, or smoked meats?

Answer 18

MAO metabolizes tyramine, which is found in these products. MAOi prevent the metabolism of tyramine, which results in its accumulation in the gut.

High levels of tyramine stimulates the release of Epi + NE from the nervous tissue, thereby leading to a HTN crisis

Question 19

Phenelizine
Tranylcypromine

Class:
Clinical use:
Major side effects:
Contraindications:

Answer 19

Class: MAOi

Clinical use: Atypical depression, Anxiety (patients with anxiety, phobic features, or hypochondriasis)

Major side effects: Serotonin Syndrome, HTN crisis

Contraindications: anti-depressants, smoked meats, wine, cheese

Question 20

Mirtazapine

Class:
Clinical use:
Major side effects:
Contraindications:

Answer 20

Class: NaSSA

Clinical use: Depression

Major side effects: sedation, weight gain

Contraindications:MAOi or meds that are metabolized by CYP450 because Mirtazapine is a POTENT INHIBITOR of CYP450

Question 21

Nefazodone, Trazodone

Class:
Clinical use:
Major side effects:
Contraindications:

Answer 21

Class: SARI

Clinical use: Depression

Major side effects: sedation, weight gain

Contraindications: meds that are metabolized by CYP450 because Nefazodone, Trazodone are POTENT INHIBITORS of CYP450

Question 22

Diazepam

Class:
Clinical use:
Major side effects:
Contraindications:

Answer 22

Class: Benzodiazepines (binds to GABA receptor with alpha 1, 2, 3, 5 subunits)

Clinical use: anxiety, seizures/status epilepticus, OH withdrawal, anestheisa

Major side effects: sedation, altered mental status, ataxia

Contraindications: patients with liver dz or patients who use OH, barbiturates or other CNS depressants (ie opiates, cimetidine)

Question 23

What is the mechanism of benzodiazepines?

Answer 23

binds to a site on the GABA receptor and enhances its activity (inhibitory effects), thereby leading to hyperpolarization and decreased activity in neurons of the limbic, thalamic, and hypothalamic regions of the CNS

Question 24

Zolpidem

Class:
Clinical use:
Major side effects:
Contraindications:

Answer 24

Class: Benzodiazepines (binds to GABA receptor with alpha 1 subunit only)

Clinical use: insomnia only

Major side effects: anterograde amnesia, hallucinations, sleep walking+eating (esp. with bacon)

Contraindications: patients with liver dz or patients who use OH, barbiturates or other CNS depressants (ie opiates, cimetidine)

Question 25

Buspirone

Class:
Clinical use:
Major side effects:
Contraindications:

Answer 25

Class: 5HT partial agonist

Clinical use: generalized anxiety disorder

Major side effects: dizziness, insomnia, nausea,

Contraindications: MAOi’s or patients with severely compromised liver/renal function

*can use with OH