8.3 Concepts Antidepressants Portage Pharm Psych

Antidepressants MOA (General)

Increase neurotransmitter concentration in the CNS

Target Serotonin, Dopamine, and Norepinephrine

Antidepressant TX approach

Acute phase where the goal is to see an improvement in the patient’s symptoms in the first 6-8 weeks.

Continue treatment for an additional 8-14 months after the remission of depressive symptoms.

Selection of drug therapy factors

Psychotropic drug history, family history, and side effect profile of the drugs all into account

Nonresponse to antidepressant

Failure to respond after at least 6 weeks at adequate dose

1st vs 2nd gen of antidepressants

The First generation (Tricyclic Antidepressants, Monoamine Oxidase Inhibitors) have almost been completely replaced by the newer second generation due to better side effect profiles and less interactions.

Tricyclic Antidepressants MOA

Block the reuptake of serotonin and norepinephrine

Correct imbalance of neurotransmitters — make available to transmit nerve impulses

Tricyclic Antidepressants uses

Depression (have been replaced by SSRIs and SNRIs)

Neuropathic pain

OCD in childhood

Tricyclic Antidepressants Adverse Events

Blockade of Anticholinergic effects — urinary retention and constipation (Blockin them UP)

Blockade of adrenergic and dopaminergic receptors — cardiac effects

Histamine blockade — sedation

Serotonergic blockade — lower seizure threshold, sexual dysfunction

Tricyclic Antidepressants Drug Interactions

MAOIs: Increased serotonergic effects → Serotonin Syndrome

MAOIs MOA

Inhibit monoamine oxidase

(Enzyme system that breaks down neurotransmitters)

Serotonin Syndrome

Excessive Serotonin!

Confusion, agitation, rapid HR, sweating, headache, muscle rigidity, fever

In severe cases: seizures, irregular heartbeat, and unconsciousness.

Since MAOIs don’t treat depression as often, what do they treat?

Parkinson’s disease

MAOIs Adverse Events

Dry mouth, urinary retention, constipation, blurred vision, hypotension, weight gain, sexual dysfunction, CNS disturbances such as restlessness, dizziness, insomnia, tremors, and seizures.

Fatal Liver damage!!!

HTN crisis!

MAOIs Drug interactions

HTN crisis with stimulants

Why did 2nd gen antidepressants replace MAOIs and TCAs?

Superior side effect profiles, less anticholinergic and cardiac probs

How long does it take to see full clinical effect of 2nd gen antidepressants?

~4-6 weeks

SSRIs MOA

Block reuptake of serotonin

SNRIs MOA

Block reuptake of serotonin and norepinephrine

SSRI/SNRI Use

Depression

But also bipolar disorder, obesity, eating disorders, OCD, panic attacks, social anxiety, and PTSD

SSRI/SNRI Adverse Events

insomnia, weight gain, and sexual dysfunction

SSRI/SNRI can cause ____ when combined w/ other drugs that increase serotonin levels

Serotonin Syndrome

SSRI Drug interactions

Serotonin syndrome risk: MAOIs, lithium, and buspirone

Toxicity: Benzos'

Increase levels of other drugs: Warfarin, phenytoin

SNRI Drug interactions

Serotonin Syndrome: SSRIs, Triptans

Increase risk of bleeding: Warfarin, NSAIDS

Bupropion Uses

Depression (and add-on therapy)

Smoking cessation

What condition can Bupropion not be used for? Why?

Seizures — lowers seizure threshold

Drug interaction for Bupropion

MAOIs

Bupropion Adverse Effects

Dizziness, confusion, tachycardia, agitation, tremor, and dry mouth

Trazodone MOA and bonus

The first of the second-generation antidepressants that could selectively inhibit serotonin reuptake without affecting norepinephrine.

T/F: Trazodone has minimal cardiac side effects

TRUE

Uses of Trazodone

Depression, insomnia

Vilazodone (Viibryd) MOA

similar to trazodone although it acts both on serotonin and 5-HT_1A receptors.

Psychosis

a type of serious mental illness associated with being out of touch with reality. The individual is unable to distinguish the imaginary from real circumstances and events.

Schizophrenia - define and symptoms

a major form of psychosis where behavior is inappropriate

Symptoms of this include bizarre behavior, auditory and visual hallucinations, lack of motivation and emotional expression, and diminished speech and thought processes.

Dopamine Hypothesis of Psychosis

Asserts patients have excessive dopaminergic activity in the brain.

Conventional Antipsychotics vs Atypical Antipsychotics

Conventional - can help positive symptoms of schizo but not the negative symptoms

Atypical - can treat both (+) and (-) symptoms of schizo

Antipsychotics MOA

Block dopamine receptors in the brain →

Decrease concentration of dopamine in CNS

Phenothiazine antipsychotics MOA

Block receptors in areas of the brain, i.e. limbic system and basal ganglia, which are areas associated with cognitive, motor, and emotional function

The _____ are more selective in the dopamine blockade targeting a specific dopamine receptor, dopamine 2 (D₂) in addition to some serotonin (5-HT₂) receptors.

Atypical antipsychotics

Antipsychotics 3 Adverse Effects

(1) extrapyramidal symptoms

(2) tardive dyskinesia

(3) neuroleptic malignant syndrome.

Extrapyramidal symptoms for antipsychotics

Akathisia (motor restlessness)

Dystonia (muscle spasms)

[Think, Parkinson’s]

Tardive Dyskinesia for antipsychotics

Drug-induced involuntary movements of the lips, jaw, tongue, and extremities.

Neuroleptic Malignant Syndrome in antipsychotics

Fever, cardiovascular instability, and muscle breakdown.

Alpha receptor adverse events

Hypotension, lightheadedness, increased heart rate

Endocrine receptor adverse effect

Gynecomastia, menstrual changes, sexual dysfunction

Histamine receptor adverse event

Sedation, drowsiness, hypotension, weight gain

Cholinergic Receptor Adverse Effect

Blurred vision, dry mouth, increased heart rate, constipation, urinary retention, decreased sweating

Metabolic Syndrome

Insulin resistance, weight gain, changes in lipids

Antipsychotics Drug Interactions

CNS drugs

Anti-HTN drugs