Pharmacology of Mood Flashcards
The Monoamine Hypothesis
The players involved are serotonin, norepinephrine, and dopamine.
The theory is that depression results from decreased levels of monoamines, and that by replacing the monoamines we are able to combat depression.
Synthesis of Norepinephrine
Tyrosine —> DOPA —> Dopamine —> Norepinephrine
Important to note that dopamine and norepinephrine exist along the same axis.
Norepinephrine is produced in the locus coeruleus in the brain. It is broken down by monoamine oxidase in the synapse.
Synthesis of Serotonin (5-HT)
Tryptophan —> 5HTP —> Serotonin (5-HT)
Alpha-2 Receptors
Are present in the synapse and are shared by serotonin and norepinephrine.
Norepinephrine can influence serotonergic neurons. The monoamine system has a lot of cross reactivity with each other.
Synaptic Activity in Depression
- Decreased levels of serotonin and norepinephrine in synapse
- Increased in inhibitory autoreceptors leads to inhibition of serotonin and norepinephrine release
- This leads to a decreased number of dendrites
Serotonin Syndrome
Caused by too much serotonin.
This could be due to an overdose of TCAs or by adding any serotonergic agent (SSRI etc.) to MAOI (or within a few weeks if inhibitory).
Symptoms include increased HR, shivering, sweating, dilated pupils, clonus, hyperreflexia, diarrhea. This can lead to death.
SSRIs
Selective serotonin re-uptake inhibitors.
Blocks serotonin re-uptake in the synaptic cleft which leads to increased levels of monoamines in the synapse.
Side effects include extrapyramidal symptoms, decreased libido, anorexia, increased bleeding time, movement disorders, agitation, delayed orgasm (used off-label for premature ejaculation), increase in GI motility.
Note: Paxil is a known teratogen.
SNRIs
Selective norepinephrine re-uptake inhibitors.
Block norepinephrine re-uptake which leads to increased levels of monoamines in the synaptic cleft.
These are good for patients with diabetic neuropathy, neuropathic pain, and migraines prophylaxis where you can potentially kill two birds with one stone.
Examples include venlafaxine, and duloxetine.
NDRIs
Norepinephrine and dopamine re-uptake inhibitors.
Blocks the re-uptake of norepinephrine and dopamine in the synaptic cleft and leads to an increase of monoamines in the synapse.
Buproprion
Adding buproprion to an SSRI may combat the sexual side effects of the SSRI.
TCAs
Tricyclic antidepressants.
“Dirty SNRI”
Blocks norepinephrine and serotonin re-uptake and leads to an increased levels of monoamines in the synaptic cleft.
Very effective for severe depression but rarely used because they are often lethal in an overdose (>2w supply definitely) by causing serotonin syndrome.
Side effects are far worse than SSRIs and include QT prolongation.
Eg. Trazadone
MAOIs
Monoamine oxidase inhibitors.
Can be either reversible, or irreversible and works by blocking the re-uptake of all the monoamines in the synaptic cleft, thereby increasing their level.
Must avoid tyramine in the diet which is typically found in delicious foods like cheese, smoked meat, as well as most processed, cured, or pickled foods. If tyramine is eated, it is stored in the same vesicles as norepinephrine. This displaces the norepinephrine which pours out into the body and causes a hypertensive crisis.
These medications are rarely used.
Alpha-2 Receptor Antagonist
Blocks alpha-2 receptors which leads to an increase in serotonin and norepinephrine in the synaptic cleft.
Mirtazapine (Rameron)
Side effects are weight gain, but decreased nausea.
Electro Convulsive Therapy (ECT)
Electrically induced generalized seizures (with anaesthetic and muscle block). This likely causes receptor down-regulation.
Side effects are short-term memory loss as well as the risk of anaesthetic.
Given 3x/week for 2-3 weeks for patients who are depressed with psychosis, extreme suicidal risk, not eating/drinking, treatment resistant, or if they were previously effective.
Citalopram (Celexa)
SSRI
Pro: few drug interactions and few side effects
Con: mild anti-cholinergic
Fluvoxamine (Luvox)
SSRI
Pro: strong anti-anxiety effect
Con: bad GI side effects, moderate anti-cholinergic
