Antidepressants and Mood Stabilizers Flashcards
All antidepressant agents are effective, yet may take how long to demonstrate beneficial effects?
This depends on… (2)
3-8+ wks.
Depends on disease severity/duration and dosage of selected agent.
If a patient does not respond to a given antidepressant after an 8-week trial on an adequate dose, what is a reasonable action?
If there is partial response, what can be done?
Another antidepressant with a different MOA.
Adding another drug to the initail agent (including ‘antipsychotics’).
Mono-therapy with antidepressants is only indicated for…
Unipolar depression - not depressive phase of bipolar disorder.
All antidepressants are associated with which side-effects?
What is recommended when prescribing?
Withdrawal syndrome: Flu-like symptoms Insomnia Nausea Imbalance Sensory disturbances Hyperarousal
Slow titration downward (deprescribing).
What are other (non-mental health) indications for antidepressants and which drug is used? (4)
Nicotine withdrawal (Bupropion)
Enuresis/bedwetting (Imipramine)
Diabetic peripheral neuropathy, fibromyalgia and chronic MSK pain (Duloxetine)
Stress incontinence (Duloxetine)
SSRI MOA
Selectively inhibits pre-synaptic reuptake of serotonin (via SERT), which results in enhanced, prolonged serotonergic neurotransmission to post-synaptic receptors.
What are the major side-effects of SSRIs?
Acute withdrawal reactions**
Serotonin syndrome (increased risk when other agents given in addition): sweating, hyperreflexia, akathisia/myoclonus, shivering/tremors
Suicidality (highest risk in younger ages)
Which SSRI is has the greatest risk of drug-drug interaction?
Which one have the least? (2)
Greatest risk = Fluoxetine
Least risk = Vortioxetine and Escitalopram
MOA of SNRIs (including TCAs):
In general for the TCAs, tertiary amine TCAs inhibit:
Secondary amines inhibit:
Selectively inhibit the pre-synaptic reuptake of serotonin (via SERT) and NE (via NET).
3-amine: inhibit both NE/5-HT relatively equally
2-amine: inhibit NE > 5-HT
Which other receptors can TCAs block and which side-effects can ensue? (3)
Histamine (H1): CNS
- sedation, fatigue
- dizziness, seizures
Muscarinic (cholinergic): anti-cholinergic
- dry mouth
- urinary retention, constipation
- blurred vision
alpha-1: CV
- tachycardia
- orthostatic hypotension
- dysrhythmias
What are signs of toxic ingestion of TCAs?
3 Cs
- coma
- cardiotoxicity (conduction abnormalities): ‘quinidine-like’ effect
- convulsions
What are the major side-effects of non-TCA SNRIs?
Relatively similar to SSRIs, but less risk of of sexual dysfunction.
What is the MOA of Trazodone and Nefazodone?
What else can they cause?
(SARA): Acts like SSRIs and also block post-synaptic a1 receptors on NE neurons and post-synaptic 5HT2 receptors.
Cause blockade of H1 - sedation.
What is the MOA of Mirtazapine?
What else can it cause?
(SARA): Blocks pre-synaptic a2 receptors on NE and 5HT neurons and blocks post-synaptic 5HT2/3 receptors.
Causes blockade of H1 - sedation.
*no SERT/NET activity
What is the major side-effect(s) of Trazodone and Mirtazapine?
Trazodone: CNS sedation, orthostatic hypotension
Mirtazapine: CNS sedation, weight gain
What is the MOA of NDRIs?
How do they release effects?
Selectively inhibits pre-synaptic reuptake of NE (via (NET) and DA (via DAT). Results in prolonged stimulation by these NTs.
VMAT2 transporter
What are the side-effects of NDRIs? (3)
Seizures*
Agitation/insomnia (simulating)
-HTN, tachy, tremors
Weight loss
What is the MOA of MAOIs?
All oral agents are considered…
All agents are non-selective, except:
What is unique of Tranylcypromine?
Inhibition of MAO (A/B subtypes) increases levels of monoamines in neuronal vesicles and increase amounts of NE, 5-HT and DA release.
All oral agents are irreversible MAOIs.
All are non-selective (A/B subtypes), except Selegine (B-selective, but non-selective at high doses).
It is a stimulant analog.
What are the major side-effects of MAOIs?
What are the major drug interactions? What must be done?
What are the risks if this does ensue?
Orthostatic hypotension, sexual dysfunction, weight gain, insomnia/agitation/nervousness.
Interactions with 5HT/NE affecting drugs (anti-hypertensives, amphetamines, SSRIs/TCAs/SNRIs).
*2-week washout period! 5-weeks for fluoxetine.
Risk of serotonin syndrome and HTN crisis.
HTN crisis is the major risk for which class?
How does it occur molecularly?
Which drug has a dose-dependent relationship w/ this effect?
MAOIs
Increased tyrmaine can induce significant catecholamine release and HTN crisis.
Selegine.
What is the MOA of Esketamine?
Where is it indicated?
What is the route of administration? What must be done after?
It is an NDMA-receptor (glutamate) antagonist.
Treatment-resistant depression in conjunction w/ ongoing anti-depressant therapy.
Nasal administration and patient observed for 2-hrs. post-dose due to concern of BP and cognitive impairment.
What 2 drugs are considered “miscellaneous anti-depressants”?
Esketamine
Brexanolone
What is the MOA of Brexanolone?
What is the indication?
A GABA-A-receptor positive allosteric modulator (identical to alloprogesterone).
Post-partum depression.
What are the 3 major actions of Lithium?
Brain structure - neuroprotective/neuroproliferative.
NT modulation - inhibits DA neurotransmission, downregulates NMDA receptor, promotes GABAergic neurtransmission.
Intracellular changes - inhibits IPPase and IMPase, inhibits PKC, MARCKS, and GSK-3.
How is Li+ treated by the kidneys?
It competes with…
Similarly to Na+/K+
Na+ for kidney reabsorption
What is the major side-effect of Li+?
Resistance to ADH resulting in polyuria and polydipsia.
-nephrogenic DI
What are 3 other drug classes that may interact with Lithium?
Diuretics (esp. Thiazides)
ACEIs (esp. Lisinopril)
NSAIDs
Which drug is know to be a “narrow therapeutic agent”?
What range should be limited to normally?
In refractory cases?
In the elderly?
Li+
Normally: 0.6-1.2 mEq/L
Refractory cases: up to 1.5 mEq/L
Elderly: 0.4-0.8 mEq/L
What are the indications for Lithium? (2)
What is an off-label use of Li+?
Acute and maintenance treatment of mania/bipolar disorder I.
Augmentation in unipolar depressive in patients w/ inadequate response to anti-depressive therapy.
Reduced risk of suicide.
What is the indication of Valproic acid/Divalproex? Dose?
What is the indication of Lamotrigine?
What is the indication of Carbamazepine?
Valproic acid/Divalproex: Acute bipolar I. 50-125 mcg/mL.
Lamotrigine: Maintenance of bipolar disorder I and II.
Carbamazepine: Acute and maintenance treatment of acute mania and mixed episodes (bipolar I).
What is the major CYP450 inducer?
Carbamazepine (anti-seizure agent)
