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

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 and 5HT-2 antagonist

• 5HT-2 antagonist blocks negative feedback → increase dopamine → relieve negative sx of schizophrenia

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

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 dose (50mg) → hypnotic (mainly histamine receptors)

• Medium dose (300mg) → antidepressant (mainly serotonin receptors)

• High dose (800mg) → antipsychotic (mainly dopamine receptors)

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: SGA; D2 antagonist and 5HT-2 antagonist

Indication: depression

SE: 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: SSRI (blocks reuptake of serotonin)

Indication: depression, OCD, anorexia, bulimia

SE: fewer autonomic effects than TCAs

Sertraline (Zoloft)

MOA: SSRI (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, withdrawal can be severe/cause brain zaps

Bupropion (Wellbutrin)

MOA:

• MOA in depression: NDRI (Blocks reuptake of NE and dopamine → increase in transmission)

• MOA in smoking cessation: Non-competitive antagonist of nicotinic AChRs at allosteric sites on receptor (changes conformation of receptor to prevent the nicotinic receptor from being fully activated)

Indication: depression; nicotine dependence

SE:

• Lower sexual SEs than SSRI or SNRI d/t minimal or no activity on serotonin receptors

• Increase concentration of drug (ex. nicotine via smoking) → nothing happens d/t change in the conformation of the receptor from non-competitive antagonism

• Can be “activating” and lead to weight loss

Mirtazapine (Remeron)

MOA:

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

• 5HT-2A and 5-HT-3 receptor antagonist

  • Prevents overstimulation of serotonin pathways

  • Blockage of both leaves more serotonin around to bind at 5HT-1 receptors, which act to improve mood

• Antihistamine

• Peripheral a-1 adrenergic receptor antagonist

  • 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

  • Increases noradrenergic and dopaminergic transmissionn in the prefrontal cortex (potentially helping low affect in bipolar depression

Indication: schizophrenia; bipolar disorder

SE: Minimal “HAM” SEs