Psychopharmacology (Antidepressants)

Antidepressants/ TCAs List the major AE and TOXICITIES of the TCAs. What is the recommendation for serum blood monitoring?

-CARDIAC: prolongation of the QT interval, orthostasis similar effects of Class 1A antiarrhythmics, decrease conduction (monitor) -Neuro: lower seizure threshold -Antimuscarinic effects (dry, eyes, constipation, urinary retention_) -Antihistamineregic effects (sedation, weight gain) -Sexual dysfunction -tremor -weight gain **Generally monitor serum levels (trough) )

Antidepressants - TCAs Toxicity and Overdose How to recognize and treat?

Cardiac: prolongation of the QT interval, leading to arrhythmia Prolongation of the QRS >100 msec Abnormal morphology of the QRS widening of the QRS interval. Sedation--> agitation Anticholinergic effects Treatment: ABCs, IV saline Bolus, NaHCO3 IV, Lorazapem, activated charcoal

Atypical Antidepressants MIRTAZAPINE MOA and indications

MOA: Antagonizes presynaptic alpha-2 adrenergic receptors and postsynaptic serotonin 5-HT2 and serotonin 5-HT3 receptors (enhances 5HT and NE neurotransmission) Affects other receptors as well antihistamine esp. Indications major depression, generalized anxiety disorder (not first line)

Atypical Antidepressants Names

●Bupropion ●Mirtazapine

Atypical Antidepressants ●Bupropion What are the AE? What are the contraindications?

AE: dry mouth, nausea, and insomnia Lowers seizure threshold Contraindications: Seizure disorders (or any condition increases risk for seizures) bulimia nervosa, anorexia nervosa Use of monoamine oxidase inhibitors in the past two weeks

Atypical Antidepressants MIRTAZAPINE AE:

AE: sedation most common increases appetite and weight gain common dry mouth

MAO inhibitors (MAOIs) MOA Names

Drugs inhibiting monoamine oxidases that metabolize norepinephrine and serotonin (MAO type A) and dopamine (MAO type B)--> increases 5HT, NE and DA Irreversible effects last 2 weeks ** NAMES: Tranylcypromine, Phenelzine

Antidepressants Atypical Antidepressants Names Selective Norepinephrine / Serotonin reuptake inhibitors Besides MDD what are other indications?

INDICATIONS: Depressive disorders and anxiety disorders (eg, generalized anxiety disorder, panic disorder, or social anxiety disorder SNRIs: chronic pain syndromes, including diabetic peripheral neuropathy, fibromyalgia, and chronic musculoskeletal pain.

ANTIDEPRESSANTS Serotonin Modulators Trazodone (BID or qhs) Indications and AE:

Indications: Major Depression and insomnia related to depression AE: Sedation - 61 percent of patients who received trazodone ●Dizziness - 36 percent ●Dry mouth - 27 percent ●Nausea - 19 percent RARE: penile priapism

Antidepressants Selective Norepinephrine / Serotonin reuptake inhibitors Adverse Effects

M/C AE are **Nausea ●Dizziness ●Diaphoresis Others: sexual dysfunction, headache Possible increase in BP (monitor)

Antidepressants MAO inhibitors (MAOIs) AE and Toxicity

MAO Inhibitors AE: orthostasis edema weight gain sedation sexual dysfunction CANNOT eat tyramine containing foods why? can get hypertensive crisis Cannot use other meds that affect serotonin 2 week effect after last dose !! https://medmadeez.com/test-question-maoi/

Antidepressants Selective Norepinephrine / Serotonin reuptake inhibitors What is the primary MOA: Who are we / names?

MOA: Blocking presynaptic serotonin and norepinephrine transporter proteins This inhibits reuptake of these neurotransmitters, Increases stimulation of postsynaptic receptors NAMES: Desvenlafaxine ●Duloxetine ●Levomilnacipran ●Milnacipran ●Venlafaxine

Atypical Antidepressants ●Bupropion What is the MOA? What are the indications?

MOA: Inhibits presynaptic reuptake of dopamine and norepinephrine (with a greater effect upon dopamine) Indications: major depression seasonal affective disorder Attention deficit hyperactivity disorder Tobacco dependence Hypoactive sexual disorder, and obesity

ANTIDEPRESSANTS- Tricyclic Antidepressants (TCAs) List the mechanism of action of the tricyclic antidepressants Which receptors do the TCAs affect?

MOA: inhibits reuptake of both serotonin and norepinephrine (transporters in synaptic cleft) Other receptors: antimuscarinic M1, antihistamine H1, and alpha-adrenergic receptors, and commonly cause cardiac effects, anticholinergic effects, antihistaminic effects three-ring central structure plus a side chain

Antidepressants Selective Serotonin Reuptake Inhibitors (SSRIs) What are the indications?

Major Depressive Disorder panic disorder obsessive-compulsive disorder Generalized anxiety disorder social anxiety disorder Posttraumatic stress disorder Body dysmorphic disorder Bulimia nervosa, binge eating disorder Premenstrual dysphoric disorder (premenstrual syndrome), and somatoform disorders

Classes of Antidepressants List the major classes of Antidepressants

Monoamine Oxidase (MAO) Inhibitors Tricyclic and Tetracyclic Antidepressants Selective Serotonin Reuptake Inhibitors (SSRIs) Selective Norepinephrine / Serotonin reuptake inhibitors Atypical Antidepressants Serotonin Modulators

ANTIDEPRESSANTS- Tricyclic Antidepressants (TCAs) Name the 2 sub-classes of TCAs List some names of TCAs in each class

Secondary and tertiary amine agents TCAs Secondary amines: nortriptyline, desipramine, and are selective inhibitors of norepinephrine more than serotonin Tertiary amines: amitriptyline, imipramine, and clomipramine block the reuptake of both serotonin and norepinephrine and affect other receptors medscape.org

Antidepressants Selective Serotonin Reuptake Inhibitors (SSRIs) What is the MOA and the names of the SSRIs?

Selectively inhibits serotonin reuptake and results in potentiation of serotonergic neurotransmission ●Citalopram (prolongs QT) ●Escitalopram ●Fluoxetine (may be more activating) ●Fluvoxamine (more Nausea) ●Paroxetine (sedating) ●Sertraline

ANTIDEPRESSANTS Serotonin Modulators Names: MOA:

Serotonin Modulators ●Nefazodone (not used) ●Trazodone ●Vilazodone ●Vortioxetine MOA: Serotonin modulators act as antagonists and agonists at postsynaptic serotonin receptors and inhibits reuptake of postsynaptic serotonin

What is serotonin syndrome?

Serotonin syndrome: present within 24 hours, and most within six hours of increased heart rate, sweating, dilated pupils, tremors, twitching, hyperthermia, agitation, confusion, disorientation, hallucinations Rare and life-threatening event Occurs in drugs which increase serotonin (abruptly) especially SSRIS

Antidepressants Selective Serotonin Reuptake Inhibitors (SSRIs) Adverse Effects Drug Interactions

Sexual dysfunction Drowsiness > insomnia or anxiety daytime sedation associated with malaise, diminished mental energy Nausea Discontinuation effects (taper off) ----------------------------------------------------------- Some SSRIs are moderate to potent inhibitors of hepatic cytochrome P450 drug metabolism Most potent inhibitors are : PAROXetine, FLUOXetine, FLUVOXamine

ANTIDEPRESSANTS- TCAs What are major differences in adverse effect profile of the 2 categories of TCAs? List the primary AE, precautions and toxicities associated with the TCAs?

Tricyclics block muscarinic M1, histamine H1, and alpha-adrenergic receptors, and commonly cause cardiac effects, anticholinergic effects, antihistaminic effects Tertiary amine TCAs have more AE because they are less selective and block above receptors AE: cardiac effects, orthostatic hypotension, antimuscarinic effects, antihistaminic effects, decreased seizure threshold, sexual dysfunction, diaphoresis, and tremor.

ANTIDEPRESSANTS Serotonin Modulators 1. Vortioxetine (AE) ---------------------------------------------- 2. Vilazodone

Vortioxetine is used to treat major depression and may help with associated cognitive issues AE: Nausea is most common plus usual serotonergic effects --------------------------------------------------------- Vilazodone is used to treat major depression. AE: Nausea, Diarrhea