Antidepressants and Mood Stabilizers Flashcards
What are some treatment options for depressive disorders?
- Pharmacotherapy
- Biopsychosocial therapies
- Electroconvulsive therapy
- Deep Brain Stimulation
- Transcranial Magnetic Stimulation
- Light therapy
What are some other indications for antidepressants?
- Anxiety
- PTSD
- Panic disorder
- OCD
- SAD
- Premenstrual dysphoric disorder
- Disruptive mood dysregulation disorder
- Nicotine withdrawal
- Enuresis
- Diabetic peripheral neuropathy, fibromyalgia, and chronic musculoskeletal pain
- Stress incontinence
What are the 5 R’s of antidepressant efficacy?
- Response
- Remission
- Relapse
- Recovery
- Recurrence
What is response in antidepressant efficacy?
- > 50% reduction in symptoms form baseline
- Not well, just better
What is remission in antidepressant efficacy?
- Symptom free (very low to no symptoms)
- Not only better, but well; a healthy state of functioning
What is recovery in antidepressant efficacy?
- 6-12 months of ongoing remission
- Not cured
What is relapse in antidepressant efficacy?
- Return of symptoms after Remission but before recovery
What is recurrence in antidepressant efficacy?
- Return of symptoms after recovery
When is the usual time frame for antidepressive agents to demonstrate their clinical benefits?
- 3-8+ weeks
When do most patients see up to 50% of reduction in symptoms?
- Within the first 3-4 weeks
When should you consider switching to another antidepressant in a patient?
- If the patient does not respond after an 8 week trial
What should you do if a partial response is observed?
- Add another drug (like antipsychotics)
What are all antidepressants well know for?
- Cause or be associated with a withdrawal syndrome
- This means that we need to slowly titrate off of medicaton
What is the acronym for the symptoms of the withdrawal syndrome of antidepressants?
- FINISH
What does FINISH stand for?
- Flu-like symptoms
- Insomnia
- Nausea
- Imbalance
- Sensory disturbances
- Hyperarousal
What are the general antidepressants MOA?
- Primarily, agents block 5-HT and/or NE reuptake by presynaptic transporters (SERT, NET, or both)
- Secondary mechanisms of a few agents block or stimulate pre and/or postsynaptic receptors
What are SSRI’s?
- Selectively Inhibit the presynaptic reuptake of serotonin (via SERT)
- Results in enhanced, prolonged serotonergic neurotransmission to postsynaptic receptors
What is seen in SSRI’s when compared to TCA’s?
- Much less impact on histamin, muscarinic, and adrenergic receptors
What are some primary side effects of SSRI’s?
- CNS (sedation or insomnia/agitation/nervousness)
- Sexual dysfunction (change in libido/impotence)
- Weight gain (adults)/Weight loss (mild; adolescents)
- Acute withdrawal reactions (concern with all categories)
What are some rare side effects of SSRI’s?
- QT prolongation
- Hyponatremia
- Serotonin syndrome (sweating, hyperreflexia, akathisia/myoclonus, shivering/tremors)
- Suicidality
What is the risk of drug interactions with SSRI’s?
Variable risk of drug-drug interactions resulting (CYP450):
- Most is fluoxetine
- Least is vortioxetine and escitalopram
- Low/mild include citalopram, sertraline, and vilazodone
What are some drugs that are SSRI’s?
- Citalopram
- Escitalopram
- Fluoxetine
- Paroxetine
- Sertraline
- Vilazodone
- Vortioxetine
What are SNRI’s?
- Selectively inhibit the presynaptic reuptake of serotonin and norepinephrine (via NET)
What is the MOA of tertiary amine TCAs?
- Inhibit both NE/5-HT relatively equally
- Except clomipramine/amitriptyline which impact 5-HT>NE
What is the MOA of secondary amine TCAs?
- Inhibit NE>5-HT
What are some side effects of TCAs?
- Block other receptors like Histamine, Muscarinic, and alpha 1 adrenergic
What are the cardiovascular side effects seen in TCA use?
- Tachycardia
- Orthostatic hypotension
- Dysrhythmias
What are the anticholinergic side effects seen in TCA use?
- Dry mouth
- Urinary retention/constipation
- Blurred vision/Inc. IOP
What are the CNS side effects seen in TCA use?
- Sedation/Fatigue
- Dizziness/Seizures
What are the 3 C’s of toxic ingestion of TCAs?
- Coma
- Cardiotoxicity (conduction abnormalities)
- Convulsions
How are side effects of SNRI’s similar to SSRI’s?
- Relatively similar to SSRI’s with a less risk of sexual dysfunction
What drugs are tertiary amine TCA’s?
- Amitriptyline
- Clomipramine
- Doxepin
- Imipramine
What drugs are secondary amine TCA’s?
- Amoxapine
- Desipramine
- Nortriptyline
What drugs are SNRI’s?
- Desvenlafaxine
- Venlafaxine
- Duloxetine
- Levomilnacipran
What are SARA’s?
- Two agents act like SSRI’s and also selectively block postsynaptic alpha1 receptors on noradrenergic neurons and postsynaptic 5-HT receptors (Trazodone and Nefazodone)
- One agent blocks presynaptic alpha2 receptors on noradrenergic and serotonergic neurons and blocks postsynaptic 5-HT receptors (Mirtazapine)
What are some side effects of SARA’s?
- CNS (sedation) –> most with trazodone/mirtazapine
- Orthostatic hypotension –> most with trazodone
- Weight gain –> mirtazapine
What are NDRI’s?
- Selectively inhibits presynaptic reuptake of norepinephrine (via NET) and dopamine (via DAT)
- Results in enhanced, prolonged NE and DA neurotransmission to postsynaptic receptors
What are some side effects of NDRI’s?
- Agitation/Insomnia (stimulating)
- Hypertension/Tachycardia/Tremors
- Weight loss
- Seizures
What drug is a NDRI?
- Bupropion
What is MAOI’s MOA?
- Inhibition of MAO increases levels of monoamines in neuronal vesicles and increase amounts of NE, 5-HT, and DA released
What are all oral MAOI’s considered?
- Irreversible MAOI’s
What are some side effects of MAOI’s?
- Orthostatic hypotension
- Sexual dysfunction
- Weight gain
- Insomnia/Agitation/Nervousness
What are the drug interactions of MAOI’s?
- Some anti-hypertensives, amphetamines, SSRIs/TCAs/SNRIs
- 2 week wash out period (fluoxetine)
- Risk of serotonin syndrome
- Risk of hypertensive crisis
Why is there a major concern of hypertensive crisis with MAOI’s?
- Non-selective MAOI’s inhibit MAO-A necessary in GI for tyramine metabolism
- Increased tyramine can induce significant catecholamine release and hypertensive crisis
What are the symptoms/signs of hypertensive crisis?
- Severe headache
- Sweating/severe anxiety
- Nosebleeds
- Tachycardia
- Chest pain
- Changes in vision
- Shortness of breath
- Confusion
- Nausea/Vomiting
What are some examples of tyramine containing foods/beverages?
- Aged cheeses
- Fava/broad/soy beans, or snow peas
- Fermented or pickled meats/poultry/fish
- Processed, pickled, or cured meats/sausages (bologna, pepperoni, salami, summer sausage
- Tap beers/beers not pasteurized, or red wine, sherry and liqueurs
- Yeast or protein extracts
- Overripe or spoiled fruits
- Soy/fish/shrimp sauces
What drugs are MAOI’s?
- Isocarboxazid
- Phenelzine
- Selegiline
- Tranylcypromine
What is esketamine?
- An NMDA-receptor antagonist
- Indicated for treatment-resistant depression in conjunction with ongoing antidepressant therapy
How is esketamine given?
- Nasal administration by authorized physician
Why is a patient observed after getting esketamine?
- Look at BP and dissociation/cognitive impairment/sedation
What is brexanolone?
- A GABA-A receptor positive allosteric modulator
- Identical to endogenous allopregnanolone
What is brexanolone indicated for?
- Post-partum depression
How is brexanolone given?
- 60 hour IV administration by authorized physician in healthcare facility
What is observed after giving brexanolone?
- Excessive somnolence
- Loss of consciousness
How long does efficacy last for brexanolone?
- Lasts up to 30 days post dose
What is lithium?
- Monovalent ion
- Handled by kidneys similar to Na+/K+
- Li+ competes with Na+ for kidney reabsorption
What does lithium do in the kidney?
- Li+ enter principal cells of collecting duct via Na+ channels in luminal membrane
- Accumulation of Li+ in these cells interferes with ADH-mediated effects and can lead to resistance to ADH, resulting in polyuring/polydipsia
What is a side effect of lithium?
- Polyuria (polydipsia) –> Clinical picture of nephrogenic diabetes insipidus
- Tremor
- Mental confusion/dizziness/sedation
- Thyroid goiter
- Leukocytosis
- Seizures and serotonin syndrome
What are some drug interactions with lithium?
- Diuretics via preferential Na+ loss and Li+ reabsorption (especially thiazides)
- ACEIs: especially lisinopril
- NSAIDs: through alteration of renal perfusion
What are some indications for lithium?
- Acute and management treatment of mania/bipolar I disorder
- Augmentation in unipolar depressive patients with inadequate response to antidepressant therapy
What is the off label use of lithium?
- Reduced risk of suicide and all cause mortality in patients with mood disorders
What are three mood stabilizers that were initially developed to be anti-seizure agents?
- Valproic acid
- Lamotrigine
- Carbamazepine
What are the uses for mood stabilizers?
- Valproic acid used for acute Bipolar I
- Lamotrigine use for maintenance of bipolar disorder (I and II)
- Carbamazepine used for acute and maintenance treatment of acute mania and mixed episodes (bipolar I)
