Antipsychotics
Mnemonic
Antipsychotics are thought to work by blocking the D2 receptor.
Psychotic patients sometimes take a DetouR from reality.
- First-generation antipsychotics (also called typical antipsychotics): block D2 receptor → ↑ cAMP
- High-potency antipsychotics have a strong antipsychotic effect even at relatively low doses, but they also more commonly cause neurologic side effects (e.g., extrapyramidal symptoms) than low-potency antipsychotics.
- Haloperidol
- Fluphenazine
- Perphenazine
- Trifluoperazine
- Pimozide
- Low-potency antipsychotics more commonly cause anticholinergic, antihistamine, and sympathetic α1-blockade effects.
- Chlorpromazine
- Thioridazine
- Stored in fat tissue (lipid soluble) and, therefore, only slowly eliminated from the body.
- High-potency antipsychotics have a strong antipsychotic effect even at relatively low doses, but they also more commonly cause neurologic side effects (e.g., extrapyramidal symptoms) than low-potency antipsychotics.
- Second-generation antipsychotics (also called atypical antipsychotics): most are 5-HT2 and D2 antagonists with varying α and H1 receptor effects
- Serotonin antagonism can help modulate dopamine, reducing its EPS side effect.
- Also can improved negative and cognitive symptoms
Tip
Antipsychotics block dopamine receptor, instead of inhibiting dopamine reuptake, as seen in antidepressants.
First-generation antipsychotics (FGAs)
High-potency
Haloperidol
- Brand name: Haldol
- High-potency antipsychotics
- Dopamine-specific antagonism (D2 receptor)
- Extrapyramidal symptoms most common in high-potency FGAs
- HOLD-ol
- HOLD-ol
Adverse effects
- Hyperprolactinemia
- Dopamine inhibits the release of prolactin via the D2 receptor in the tuberoinfundibular pathway. Therefore, dopamine antagonists increase the effects of prolactin.
- Extrapyramidal symptoms most common in high-potency FGAs
- Prolonged QT interval
- Neuroleptic malignant syndrome
Low-potency
Chlorpromazine
- Low-potency antipsychotics
- Dopamine antagonism
- Anticholinergic
- Antihistaminergic
- First discovered, wide range of indications
- Corneal deposits
Mnemonic
氯丙嗪，治精神；阻断多巴Ma不灵。止吐冬眠和降温，就是不治晕动病。不良反应帕金森，张口伸舌坐不能。口干好似阿托品，乳汁分泌羞死人。
Mnemonic
Chlor-neal deposits
Adverse effects
- Anticholinergic effects, sympatholytic effects, metabolic effects, and sedation dominate
- Sedation due to histamine receptor blockade, see Antihistamines
Difference of Adverse Effects
Low-potency antipsychotics require higher doses to achieve the desired effect, which leads to more prominent blockage of other receptors except D2.
Second-generation antipsychotics (SGAs)
Clozapine
- Most effective antipsychotic
- Indications
- Treatment-resistant schizophrenia
- Schizophrenia associated with suicidality
- Clozapine can cause agranulocytosis and lowers the seizure threshold
Mnemonic
You must watch clozapine clozely to monitor for agranulocytosis!
Olanzapine
- Second effective antipsychotic, without risk of agranulocytosis
- Metabolic effects (usually weight gain, hyperglycemia, new-onset diabetes mellitus, dyslipidemia) most prominent
Mnemonic
Olanzapine can make patients gain weight, so it's the pharmacological choice for Anorexia nervosa
Risperidone
- Less sedation, good for elderly patients
Mnemonic
Rise and shine
Quetiapine
- More sedation
Mnemonic
Quietiapine
Adverse effects
Summary
- Extrapyramidal side effects:
- Acute dystonic reaction: sudden-onset, sustained muscle contractions
- Akathisia: subjective restlessness with inability to sit still
- Drug-induced parkinsonism: tremor, rigidity, bradykinesia, masked facies
- Tardive dyskinesia:
- Involuntary movements after chronic use (e.g., lip smacking, choreoathetoid movements)
- Neuroleptic malignant syndrome:
- Fever, rigidity, mental status changes, autonomic instability
- First-generation antipsychotics (FGAs)
- High-potency (eg, haloperidol)
- Extrapyramidal symptoms (acute dystonia, akathisia, parkinsonism), tardive dyskinesia
- Low-potency (eg, chlorpromazine)
- Sedation, cholinergic blockade, orthostatic hypotension, weight gain
- High-potency (eg, haloperidol)
- Second-generation antipsychotics (SGAs)
- Metabolic syndrome, weight gain
- Extrapyramidal symptoms (less common than FGAs)
Hyperprolactinemia
- Elevated prolactin levels: Dopamine inhibits the release of prolactin via the D2 receptor in the tuberoinfundibular pathway. Therefore, dopamine antagonists increase the effects of prolactin.
- ↑ Prolactin → suppression of GnRH → ↓ LH, ↓ FSH → ↓ estrogen, ↓ testosterone → hypogonadotropic hypogonadism
- Most common in risperidone, amisulpride
- In men: gynecomastia, galactorrhea, hypogonadotropic hypogonadism (erectile dysfunction, reduced libido, infertility)
- In women: galactorrhea, oligomenorrhea, hypogonadotropic hypogonadism (amenorrhea, reduced libido, infertility)
Mnemonic
RISE-PAIR-idone gives RISE to a PAIR
Extrapyramidal symptoms (EPS)
- Pathophysiology: Inhibition of the nigrostriatal dopaminergic pathways results in EPS.
- First-generation high-potency antipsychotics: D2 antagonism → EPS
- Second-generation antipsychotics: weaker D2 antagonism → fewer EPS
- Clinical features similar to Parkinson disease: Muscle, rustle, and hustle
- Acute dystonia
- Onset: Hours to days
- Painful and lasting muscle spasms and stiffness predominantly affecting the head, neck, and tongue
- Facial grimacing, torticollis
- Tongue protrusion or twisting
- Oculogyric crisis (upward deviation of the eyes)
- In severe cases: laryngospasm, opisthotonus of the back
- Pseudoparkinsonism
- Onset: ∼ 1–4 weeks
- Akathisia
- 1–8 weeks
- Restlessness/compelling urge to move
- Inability to sit or stand still
- See Restless legs syndrome
- Tardive dyskinesia
- Months to years
- Repetitive chewing and lip smacking
- Choreic movements
- Can be irreversible if drug is not discontinued
- Acute dystonia
- Treatment
- Decrease or discontinue offending medication
- Anticholinergics (trihexyphenidyl, benztropine)
Mnemonic
Chewing Tardive