Antidepressant Agents Flashcards
What is it called when depression and mania occur simultaneously? What is it called when you have rapid switching between these two different states?
Mixed mood state
Called rapid cycling, often from hypomania to depression
What is dysthymia?
A less severe but long-lasting form of depression
What are the diagnostic criteria for depression?
AD to SIGECAPS for two week period
At least 1 of two major criteria (AD)
Anhedonia and Dysphoria - inability to feel pleasure and depressed mood
At least 5 of the minor criteria (SIGECAPS) Sleep - increased or decreased Interest - decreased Guilt - increased Energy - decreased Concentration - decreased Appetite - increased or decreased Psychomotor depression Suicide ideation
How long is a typical major depressive episode, and what is the greatest predictor of them?
6 to 24 months, number of prior episodes predicts likelihood of developing subsequent ones
What is the monoamine receptor hypothesis of depression and how does this correlate with treatment?
Decreased levels of NE / 5-HT leads to upregulation of receptors as a compensatory mechanism.
Treatment is effective after long-term increase in 5-HT and/or NE levels leads to downregulation of receptors once more, and a return to equilibrium
What treatment is recommended in patients with MDD and a high suicide risk / treatment resistant depression or depression in pregnancy? Side effects?
Electroconvulsive therapy
Amnesia around time of ECT, confusion, muscle aches
What is the mechanism of action of St. John’s wort and its drug interaction of concern?
It has some mild MAO-inhibiting properties as herbal treatment for mild / moderate depression.
Induces CYP3A4
What is the difference between MAO-A and MAO-B?
MAO-A - present in GI tract and liver, preferentially metabolizes 5-HT and NE, linked to depression
MAO-B - present in platelets and lymphocytes, preferentially metabolizes DA
Both will metabolize tyramine, but MAO-A inhibitors most important in GI tract (restrict diet here)
What are the two clinically important MAO inhibitors? What is their mechanism of action?
- Tranylcypromine - try a sip of wine
- Phenelzine - funnel leading into bottle of wine
They nonselectively bind and irreversibly inhibit MAO-A and MAO-B
What is the clinical indication for MAO inhibitors and who is it most useful in?
Second-line treatment for MDD which is treatment-resistant. Most useful in those with other complications like significant anxieties, phobias, or hypochondriasis
What serious syndromes can happen from food / drug interactions with MAO? Why?
Hypertensive crisis and serotonin syndrome
Hypertensive crisis because tyramines are normally metabolized by MAO-A, and work similar to amphetamines by inhibiting / reversing VMAT and causing catecholamine overload
Serotonin syndrome is due to buildup of 5-HT in the synapse, especially with other SSRI’s / SNRI’s
What is one strange cardiovascular side effect of MAOI’s which has not been explained? What are the other general side effects beside this?
Orthostatic hypotension -> strange because it causes NE buildup.
Other side effects are otherwise the same as SSRI’s
What are the important tricyclic antidepressants?
Imipramine
Desipramine
Clomipramine
Think of “imprint” from dodgeball
What is the mechanism of action of TCA’s? What other receptors do they inactivate?
Primary:
Blockage of NE and 5-HT reuptake, and blockade of 5-HT2 subtypes
Secondary: "Dirty drugs" - blockade of: H1 receptor - swatting bee dodgeball alpha1 receptor - alpha1 cupcake candle M1 receptor - anticholinergic tea party Na channels - peanut stand, heart effects
What are the clinical indications of TCA’s?
Major depressive disorder - second line due to toxicity
Chronic pain syndromes - i.e. migraine bell, diabetic neuropathy diasweeties
OCD - kid compulsively sorting marbles
What TCA is given for OCD?
Clomipramine
What are the contraindications of TCA’s and why?
Prostatism / narrow angle glaucoma - anticholinergic effects
Post-MI and heart block - anticholinergic effects
Bipolar disorder -> can lead to a switch syndrome (mania after depressive episode)
What are the adverse effects of TCA’s not in overdose?
- Weight gain
- Anticholinergic effects
- Cardiovascular effects - tachycardia (M1), orthostatic hypotension (alpha 1), conduction delay and arrhythmias (Na channel)
- CNS - drowsiness / lethargy (H1), lowers seizure threshold - shaking kid
What are the features of TCA overdose?
Other than craziness from anticholinergic effect:
3 C’s
Coma
Convulsions - seizures, agonist to GABA-A receptor?
Cardiotoxicity - Na channel interference can cause prolonged QRS and QT -> leads to TdP arrhythmia
How should TCA overdose be managed?
IV diazepam to control seizures, and gastric lavage if possible to flush out TCA’s. Otherwise, treatment is supportive.
Why are SSRI’s the first line treatment for depression?
They have no receptor blocking properties, lack cardiotoxic effects, and are safe in overdose
Which SSRI is most selective but has dose-dependent cardiac effects and what is the effect?
Citalopram / escitalopram
QT prolongation
List the major SSRIs?
- Fluoxetine - Fly Out
- Citalopram / Escitalopram -The City
- Fluvoxamine
- Paroxetine - Parrot Air
- Sertraline - DeSERT
Which SSRI is most associated with weight gain?
Paroxetine
What are the other indications for SSRI’s other than depression?
Bipolar depression OCD - dwight with his stapler PTSD - dogtags Anxiety disorders - guy hiding behind desk + anxious worker, + the scream screensaver Bulimia - woman at desk PMDD (premenstrual dysphoric disorder)
What are the CNS, GI, and sexual side effects of SSRI’s?
CNS - stimulant effect - can cause insomnia, anxiety, agitation, and restlessness
GI - NVD
Sexual dysfunction - big one, delayed orgasm, decreased libido, decreased arousal anorgasmia
What are the dosing strategies used to manage SSRI-induced sexual dysfunction?
Reduce the dosage or permitting “drug holidays” -> skip doses on the weekends
What major medication is considered an NDRI?
Bupropion -> NET DAT ball pro
Norepinephrine dopamine reuptake inhibitor
What are the clinical indications for bupropion?
Firstline treatment in depressed patients not responsive to SSRI
Augmentation therapy for SSRI/SNRI
Antidote to SSRI-induced sexual dysfunction
Why might bupropion be superior to SSRI’s / SNRI’s in some cases?
Not associated with sexual dysfunction or weight gain
What are the adverse effects of bupropion? How does this relate to contraindication?
Can cause insomnia, nightmares, anxiety, and seizures
Contraindicated (seizure risk) for patients with history of CNS tumor, seizures, head trauma, or eating disorders - think of girls having a seizure with their eating disorders on the basketball court in sketchy
What are the two major SNRI’s?
Duloxetine (dual copier / scanner) and venlafaxine (fax machine)
Other than depression, what are SNRI’s good for treating?
Neuropathic pain (diasweeties machine with broken cord) as well as fibromyalgia (fiber bars)
What is duloxetine also particularly good for?
Diabetic neuropathy and chronic musculoskeletal pain (back pain or knee pain)
Other than the typical SSRI side effects, what are two extra side effects which can be troublesome in SNRI’s?
- Nausea
2. Hypertension (due to increased NE, think of the guy working on the fax machine with steam coming from his ears)
What drug is a SPARI and what does that mean? What is its mechanism?
Serotonin 1A Partial Agonist / Reuptake Inhibitor
Vilazodone
What is Vilazodone used for?
Augmentation therapy for increasing tolerability of SSRIs / SNRI’s
Lacks the sexual dysfunction and weight gain
What drug class is trazodone in? Mechanism of action?
Trazodone trombone
In the SARI class - Seratonin antagonist / Reuptake Inhibitor
Antagonizes the 5-HT-2 receptors in specific (basketball number 52), also the alpha 1 receptor (burnt out alpha1 lighter) and H1 receptor (bee being swatted on head of player)
What does trazodone do at low and high doses?
Low doses - hypnotic - antagonizes the receptors without enough serotonin to cause stimulation
High doses - antidepressant
What are the main clinical indications of trazodone?
- Augmentation therapy for SSRI/SNRI to reduce insomnia, allowing better sleep
- Treatment of insomnia alone
Rarely used as monotherapy
What are the side effects for trazodone / one good non-side effect?
Orthostatic hypotension (alpha 1 antagonist), priapism (drug is sometimes called trazabone)
It lacks sexual side effects!
What does NaSSA stand for and what drug falls in this class?
Noradrenergic and Specific Serotonin Antagonist
Mirtazapine
What serotonin receptors are responsible for anxiety, anorexia, insomnia, sexual dysfunction, nausea, and GI problems?
5-HT-2: Anxiety, insomnia, sexual dysfunction, anorexia
5-HT-3: Nausea, GI problems
What is the mechanism of action of Mirtazapine?
Alpha-2 antagonist -> increases NE and serotonin in the synapse
H1 antagonist: insomnia at night but possible daytime sleepiness
Antagonizes 5-HT-2 and 5-HT-3: Less nausea, GI, insomnia, and anxiety
Net effect is boosted 5-HT to 5-HT-1 receptor: decreased depression
What are some side effects of mirtazapine?
Blocks 5-HT-2: may cause weight gain (fat guy watching the game)
Histamine blockage can cause sedation (fat guy sleeping)
What are the major clinical indications of mirtazapine?
Depression in elderly patients with insomnia + weight loss - can cause sedation + weight gain
Also augmentation for SSRI / SNRI due to lack off sexual dysfunction (people kissing on megatron)
What class of drugs is Nefazodone in and what does it share all its characteristics with?
SPARI - like trazodone
What are the side effect differences between TCAs and newer SSRIs/SNRI’s?
TCAs: Sedation, anticholinergic, orthostatic hypotension, and weight gain
SSRIs: Agitation/insomnia, GI effects, and sexual dysfunction
What antidepressants have the shortest half lives and why? What is their elimination?
SNRI’s, because they are the only antidepressants which are not highly protein bound to act as a reservoir
All are renally eliminated after hepatic metabolism
What antidepressant has the longest halflife, why, and what must be done before switching to a MAOI? What period is sufficient for others?
Fluoxetine
- has active metabolites
- need to wait 5 weeks for plasma concentration to drop to guarantee no serotonin syndrome
- 2 weeks is enough for others (5 drug half lives minimum)
What are bupropion, nefazodone, duloxetine, and all SSRI’s known for?
Inhibition of CYP450 enzymes and increased plasma concentrations, which could lead to hypertensive crisis or serotonin syndrome
What is the treatment for MAO-induced hypertensive crisis and a few symptoms?
Phentolamine - alpha1/alpha2 antagonist
high BP, headache, nausea / vomiting / sweating, dilated pupils, chest pain
What types of cold medications are contraindicated with MAOs?
Sympathomimetics like pseudoephedrine and phenylephrine
What are the clinical features of serotonin syndrome? When does this most often occur?
Hyperpyrexia (high temp), hyperreflexia, hypertension, agitation, tremor, tachycardia, and myoclonus
Any serotonin reuptake blocking agent (including drugs of abuse like cocaine, and dextromethorphan / linezolid) + a MAO-Inhibitor
What should be done to treat serotonin syndrome?
Muscle relaxants, antiseizure drugs, and the 5-HT antagonist called cyproheptadine (silly pranks prohibited in sketchy)
How long should trial therapy for an antidepressant last to see if it works? Why?
8-12 weeks
Takes 2-4 weeks to see improvement at all, and 6-8 weeks to see full effect
What are the three phases of MDD and their approximate lengths?
- Acute treatment phase - 3 months
- Continuation treatment phase - 4-9 months
- Maintenance phase - variable
Through what phases of MDE (major depressive episode) should you be treated and why?
Acute and continuation phase -> dropping of treatment during continuation phase could result in a relapse depression (most MDE’s last 6 months or longer). For this reason, most patients should take antidepressants for at least a year
Give three scenarios in which life treatment for MDD during the maintenance phase is warranted?
- Three or more previous MDE’s - 3 strikes and you’re on
- Two or more MDE’s and greater than age 50
- One or more MDE and greater than age 60
What are two reasons why we taper SSRI’s / SNRI’s with short half lives (other than fluoxetine)?
- Withdrawal syndrome is decreased, which includes - insomnia, anxiety, fatigue, mood changes, and GI disturbances
- If gradual tapering shows early signs of depression, dose can be restored without risk of having to start over on 8-12 week clock
What is the general treatment algorithm for antidepressants if they arent working?
first line SSRI/SNRI/NDRI monotherapy -> augmentation therapy i.e. SSRI + NDRI -> second line monotherapy -> ECT / Vagus nerve stimulation
What SSRI’s are safest and most dangerous in pregnancy?
Safest - Fluoxetine and citalopram
Dangerous - Paroxetine, particularly ASDs and VSDs of the heart
What antidepressants are approved in children under 18?
Fluoxetine and escitalopram
Are all antidepressants currently out equally effective in treating depression?
Yes, actually. Just need to worry about side effects
For patients with psychotic depression, what should they be on?
An antipsychotic medication combined with antidepressant
