Antidepressants & Mood Stabilizers Flashcards
MOA of SSRIs
Inhibit the presynaptic reuptake of 5-HT (via SERT)
Indications for SSRIs
1st line for major depression and GAD
Other indications: panic disorder, PTSD, OCD, bulimia, social anxiety disorder
Adverse effects of SSRIs
Hyponatremia (SIADH) QT prolongation Sexual dysfunction Weight gain Drowsiness Suicidality
Clinical features of serotonin syndrome
Hyperthermia
Hypertension
Neuromuscular hyperactivity (e.g., hyperreflexia, clonus)
T/F: Opioids can interact with serotonergic medications and cause serotonin syndrome
True
[risk of serotonin syndrome is increased with any drug that increases serotonin levels]
Treatment for serotonin syndrome and its MOA
Cyproheptadine
Acts as a 5-HT2 blocker
SSRIs may increase suicidality; what age group is at highest risk of this adverse effect?
Children, adolescents, young adults
SSRIs are at high risk of drug-drug interactions due to CYP450 metabolism. What 2 SSRIs are only considered mild inhibitors, and are thus at least risk of causing these drug-interactions?
Citalopram
Sertraline
List antidepressants and mood stabilizers associated with risk for serotonin syndrome
SSRIs SNRIs TCAs MAOIs Trazodone Lithium
List 8 drugs included in SSRI category
Citalopram Fluoxetine Sertraline Escitalopram Paroxetine Fluvoxamine Vilazodone Vortioxetine
Which SSRI is at highest risk for drug-interactions due to its broad and strong inhibition of CYP450?
Fluoxetine
Of the SSRIs, which one is only used for OCD and SAD?
Fluvoxamine
SSRI that is also a partial agonist on 5-HT1A
Vilazodone
SSRI that is also a partial agonist on 5-HT1B, an agonist on 5-HT1A, and an antagonist on 5-HT1D, 5-HT3, and 5-HT7
Vortioxetine
MOA of SNRIs
Inhibit the presynaptic reuptake of NE and 5-HT via actions on NET and SERT
Indications for SNRIs
First line option for major depression and GAD
Panic disorder, PTSD, diabetic neuropathy, chronic pain (e.g., neuropathic pain), fibromyalgia, stress urinary incontinence, vasomotor symptoms of menopause
Adverse effects of SNRIs
Serotonin syndrome
Hypertension
List drugs included in the category of SNRIs
Duloxetine Venlafaxine Desvenlafaxine (metabolite of venlafaxine) Levomilnacipran Milnacipran Amoxapine All TCAs
SNRI commonly utilized for diabetic peripheral neuropathy, fibromyalgia, chronic MSK pain, and stress incontinence
Duloxetine
Levomilnacipran may be used to treat ______
Fibromyalgia
Tetracyclic atypical antidepressant that acts as an SNRI and a dopamine agonist
Amoxapine
TCAs act as SNRIs but also affect what other receptors?
H1 histamine receptors
Alpha-1 adrenergic receptors
Muscarinic (cholinergic) receptors
[also block cardiac fast Na+ channels]
Indications for TCAs
Resistant depression
Diabetic neuropathy
Chronic pain (e.g., neuropathic pain)
Migraine prophylaxis
Enuresis
What is the difference between TCAs that are secondary vs. tertiary amines?
Secondary amines inhibit NE > 5-HT
Tertiary amines inhibit both NE/5-HT relatively equally, except clomipramine and amitriptyline which inhibit 5-HT>NE
Tertiary amine TCAs inhibit both NE/5-HT equally, except clomipramine and amitriptyline which inhibit 5-HT>NE.
Which other TCAs are considered tertiary amines?
Doxepin
Imipramine
Tertiary amine TCA used for OCD
Clomipramine
[remember that SSRIs are first line for this!]
Tertiary amine TCA utilized for enuresis
Imipramine
Secondary amine TCAs inhibit NE > 5-HT. What are the 3 secondary amine TCAs?
Amoxapine
Desipramine
Nortriptyline
Adverse effects of TCAs
Sexual dysfunction
Inhibition of mAChRs —> dry mouth, constipation, blurred vision, urinary retention
Increased appetite and weight gain
Sedation
Orthostatic hypotension
Cardiotoxicity (‘quinidine-like’ effect)
Seizures
Serotonin syndrome
Treatment for cardiotoxicity associated with TCA overdose
Sodium bicarb
TCAs are relatively contraindicated in what pt population due to severe anticholinergic and antihistamine effects?
Elderly
What unicyclic atypical antidepressant is considered an NDRI (noradrenergic-dopamine reuptake inhibitor)?
Buproprion
MOA of Buproprion
Inhibits NET and DAT
Also shown to increase NE/DA presynaptic release
T/F: Buproprion exerts CNS activating effects and is highly likely to induce sexual dysfunction and weight gain
False — it does exert CNS activating effects, but it does NOT cause sexual dysfunction and is among the agents less likely to cause weight gain
Besides being an atypical antidepressant, what else is buproprion indicated for?
Tobacco dependence/nicotine withdrawal
Adverse effects and pt populations in which buproprion is contraindicated
Seizures — makes it a contraindication in anorexia nervosa and bulimia pts
MAO inhibitors act on monoamine oxidase enzymes. What are the normal functions of these enzymes (A and B)?
MAO-A — breaks down serotonin, NE, and dopamine
MAO-B — breaks down dopamine
MAOIs ________ (reversibly/irreversibly) inhibit monoamine oxidase enzymes
Irreversibly
Indications for MAOIs
Depression (not first line!)
May be more useful in atypical and resistant depression
Pts on MAOIs should avoid ______-containing foods like aged wine, cheese, and cured meats
Tyramine
[tyramine is normally broken down by MAO-A in GI tract. On MAOIs, tyramine enters circulation and acts as sympathomimetic agent —> hypertensive crisis]
List 4 MAOIs
Isocarboxazid
Tranylcypromine
Phenelzine
Selegiline
Which of the MAOIs is a selective MAO-B inhibitor making it a useful tx in Parkinsons?
Selegiline
T/F: Maprotiline is an atypical tetracyclic antidepressant
True
Mirtazapine is a tetracyclic atypical antidepressant. What is its MOA?
Blocks alpha-2 receptors —> increases presynaptic release of serotonin and NE
Blocks 5HT2 and 5HT3 receptors
Inhibits H1 histamine receptors
T/F: Mirtazapine is associated with AE of sexual dysfunction
False
Adverse effects of Mirtazapine
Sedation
Weight gain
What are the two 5-HT2 receptor modulators?
Trazodone
Nefazodone
MOA of trazodone
Antagonizes 5HT2 receptors and inhibits 5-HT reuptake (alpha-1 receptors)
Blocks H1 histamine receptors
AEs of trazodone
Priapism
Orthostatic hypotension
Sexual dysfunction
Serotonin syndrome
Weak inhibitor of both SERT and NET; potent antagonist of postsynaptic 5HT2A
Carries black box warning for hepatotoxicity — not commonly prescribed anymore
Nefazodone
Although their MOA for bipolar is undelineated, what are 3 anti-seizure agents prescribed as mood stabilizers?
Carbamazepine
Lamotrigine
Divalproate/valproic acid
Anti-seizure agent used for acute bipolar I (with or without psychotic features)
Divalproate/valproic acid
Anti-seizure agent used for acute and maintenance treatment of acute mania and mixed episodes (bipolar I); major CYP450 inducer
Carbamazepine
Anti-seizure agent used for maintenance therapy in bipolar I and II
Lamotrigine
Indications for lithium therapy
Acute and maintenance tx of mania/bipolar I d/o
Augmentation in unipolar depressive pts with inadequate response to antidepressants
Off label — reduced risk of suicide and all-cause mortality in pts with mood disorders
MOA of lithium therapy
Inhibits Ca-dependent and depolarization-provoked release of NE and DA
Inhibits receptor blockers and substances known to stimulate and inhibit G protein synthesis/actions [may reflect lithium’s ability to interfere with activity of both stimulatory and inhibitory G proteins by keeping them in an inactive state]
AEs of lithium
Polyuria (polydipsia) — clinical picture of nephrogenic diabetes insipidus
Tremor
Mental confusion/dizziness/sedation (take at bedtime)
Thyroid goiter (hypothyroid) — inhibits iodination of thyroid hormone
Leukocytosis (stimulates MCSF — increasing granulocytes)
Seizures and serotonin syndrome
Drug interactions with lithium
Diuretics — esp thiazides (d/t preferential Na+ loss)
ACEIs — esp lisinopril (renally eliminated)
NSAIDs - through alteration of renal perfusion
All antidepressants either are, or can be, associated with a withdrawal syndrome, so slow titration downward is recommended. Symptoms include dizziness, HA, nervousness, nausea, insomnia, and flu-like aches. There is lower risk of this with what agents?
Long-acting agents (e.g., fluoxetine, amitriptyline)
[note that even long acting and XR agents can still cause this withdrawal, just less likely]
