Lecture 3-5: Psychotherapeutic Drugs (psychosis, mania, depression)

FGA

first-generation antipsychotic (typical)

SGA

second-generation anti-psychotic (atypical)

EPS

Extrapyramidal symptoms:

• akathisia

• pseudo parkinsonism

• dystonia

TCA

tricyclic antidepressant

“HAM” SEs

Antihistamine: sedation, weight gain, delirium

a-antagonism: hypotension

Anti-muscarinic: dry mouth, blurry vision, urinary retention, delirium

Haloperidol (Haldol)

MOA: FGA; D2 antagonist

• D2 antagonism in the mesolimbic pathway represses positive symptoms of schizophrenia

• D2 antagonism in nigrostriatal pathway responsible for EPS symptoms

Indication: schizophrenia, severely agitated patients

SEs: EPS symptoms, which is managed by

• Benztropine (anti-cholinergic)

• Diphenhydramine (anti-histamine)

• Amantadine (increases dopamine release in basal ganglia)

Clozapine (Clozaril)

MOA: SGA; D2 antagonist and 5HT-2 antagonist

• normally serotonin leads to negative feedback on dopamine release in mesocortical pathway

  • 5HT-2 antagonist effect blocks negative feedback, leading to increase in dopamine (therby relieving negative symptoms of schizophrenia)

Indication: schizophrenia/psychosis

SEs:

• “HAM” SEs

• Risk of agranulocytosis; need frequent WBC monitoring

Olanzapine (Zyprexa)

MOA: SGA; D2 antagonist and 5HT-2 antagonist

Indication: schizophrenia/psychosis

SEs:

• “HAM” SEs

• Fewer autonomic SE than Clozapine

• High risk of weight gain

Quetiapine (Seroquel)

MOA: SGA; D2 antagonist and 5HT-2 antagonist

Indication

• Low doses → used as a hypnotic

• Medium doses → used as an antidepressant

• High doses → used as an antipsychotic

SE: “HAM” SEs

Risperidone (Risperdal)

MOA: SGA; D2 antagonist and 5HT-2 antagonist

Indication: Schizophrenia/psychosis

SE:

• Can increase Prolactin

• Most likely atypical to cause EPS

• Can also be used as injection (Invega)

Aripiprazole (Abilify)

MOA: Dopamine partial agonist

Indication: depression

SE: can cause akathisia; overall not a great antipsychotic

Amitryptyline

MOA: TCA; blocks reuptake of NE and serotonin

Indication: depression

SE: can cause sedation (sometimes used to augment sleep)

Fluoxetine (Prozac)

MOA: blocks reuptake of serotonin

Indication: depression, OCD, anorexia, bulimia

SE: fewer autonomic effects than TCAs

Sertraline (Zoloft)

MOA: blocks reuptake of serotonin

Indication: depression

SE: preferred in elderly patients (elimination not impacted by aging)

Venlafaxine

MOA: SNRI; blocks reuptake of NE and serotonin

Indication: depression

SE: similar to SSRIs

Bupropion (Wellbutrin)

MOA:

• inhibit reuptake of dopamine and NE

  • sometimes labeled as NDRI b/c of effect at blocking NE and dopamine reuptake

• antagonist at nicotinic cholinergic receptors

Indication: depression

SE:

• Can be “activating” and lead to weight loss

• also used for smoking cessation

Mirtazapine (Remeron)

MOA:

• Blocks presynaptic a-2 autoreceptors leading to increase of neuronal release of NE and serotonin

• Antagonist at 5HT-2A receptor

  • prevents overstimulation of serotonin pathways

• Antagonist at 5HT-3 receptors

  • blockage at 5HT-2 and 5HT-3 receptors leaves more serotonin around to bind at 5HT-1 receptors, which act to improve mood

• Antihistamine

• Antagonist at peripheral a-1 adrenergic receptors

  • Can lead to hypotension

Indication: depression/insomnia

SE:

• Orthostatic hypotension

• Antihistamine SEs

Lithium

MOA: Overall reduces neuronal response to serotonin and NE

Indication: bipolar disorder (best tx to control acute mania)

SE: low therapeutic index, need to monitor lithium levels

Vortioxetine (Brintellix)

MOA: Acts as an antagonist, agonist, and partial agonist of multiple serotonin receptors

• Reuptake blockage of serotonin transporter (SERT)

• Partial agonism at 5-HT1A receptor (similar to Buspirone)

• 5-HT7 antagonism

Indication: major depressive disorder

SE: increase risk of serotonin syndrome when used w/ other serotonergic agents

Lurasidone

MOA:

• D2 antagonist

• 5-HT2A antagonist

• 5-HT7 antagonism

• alpha-2c antagonism

Indication: schizophrenia; bipolar disorder

SE:

• Minimal “HAM” SEs

• Antagonism of alpha-2C adrenergic receptors increases noradrenergic and dopaminergic transmission in prefrontal cortex (potentially helping low affect in bipolar depression)