Chlorpromazine: side effects How Drug Causes Side Effects

• By blocking dopamine 2 receptors in the striatum, it can cause motor side effects

• By blocking dopamine 2 receptors in the pituitary, it can cause elevations in prolactin

• By blocking dopamine 2 receptors excessively in the mesocortical and mesolimbic dopamine pathways, especially at high doses, it can cause worsening of negative and cognitive symptoms (neuroleptic-induced deficit syndrome)

• Anticholinergic actions may cause sedation, blurred vision, constipation, dry mouth

• Antihistaminic actions may cause sedation, weight gain

• By blocking alpha 1 adrenergic receptors, it can cause dizziness, sedation, and hypotension

• Mechanism of weight gain and any possible increased incidence of diabetes or dyslipidemia with conventional antipsychotics is unknown

Notable Side Effects

✽ Neuroleptic-induced deficit syndrome

✽ Akathisia

✽ Priapism

✽ Extrapyramidal symptoms, parkinsonism, tardive dyskinesia

✽ Galactorrhea, amenorrhea

• Dizziness, sedation, impaired memory

• Dry mouth, constipation, urinary retention, blurred vision

• Decreased sweating

• Sexual dysfunction

• Hypotension, tachycardia, syncope

• Weight gain

Life-Threatening or Dangerous Side Effects

• Rare neuroleptic malignant syndrome

• Rare jaundice, agranulocytosis

• Rare seizures

• Increased risk of death and cerebrovascular events in elderly patients with dementia-related psychosis

Weight Gain

• Many experience and/or can be significant in amount

Sedation

• Tolerance to sedation can develop over time

What to Do About Side Effects

• Wait

• Wait

• Wait

• For motor symptoms, add an anticholinergic agent

• Reduce the dose

• For sedation, give at night

• Switch to an atypical antipsychotic

• Weight loss, exercise programs, and medical management for high BMIs, diabetes dyslipidemia

Best Augmenting Agents for Side Effects

• Benztropine or trihexyphenidyl for motor side effects

• Sometimes amantadine can be helpful for motor side effects

• Benzodiazepines may be helpful for akathisia

• Many side effects cannot be improved with an augmenting agent

CHLORPROMAZINE: DOSING AND USE

Usual Dosage Range

• 200–800 mg/day

Dosage Forms

• Tablet 10 mg, 25 mg, 50 mg, 100 mg, 200 mg

• Capsule 30 mg, 75 mg, 150 mg

• Ampul 25 mg/mL; 1 mL, 2 mL

• Vial 25 mg/mL; 10 mL

• Liquid 10 mg/5 mL

• Suppository 25 mg, 100 mg

How to Dose

• Psychosis: increase dose until symptoms are controlled; after 2 weeks reduce to lowest effective dose

• Psychosis (intramuscular): varies by severity of symptoms and inpatient/outpatient status

Dosing Tips

• Low doses may have more sedative actions than antipsychotic actions

• Low doses have been used to provide short-term relief of daytime agitation and anxiety and to enhance sedative hypnotic actions in nonpsychotic patients, but other treatment options such as atypical antipsychotics are now preferred

• Higher doses may induce or worsen negative symptoms of schizophrenia

• Ampuls and vials contain sulfites that may cause allergic reactions, particularly in patients with asthma

• One of the few antipsychotics available as a suppository

• Treatment should be suspended if absolute neutrophil count falls below 1,000/mm³

Overdose

• Extrapyramidal symptoms, sedation, hypotension, coma, respiratory depression

Long-Term Use

• Some side effects may be irreversible (e.g., tardive dyskinesia)

Habit Forming

• No

How to Stop

• Slow down-titration of oral formulation (over 6–8 weeks), especially when simultaneously beginning a new antipsychotic while switching (i.e., cross-titration)

• Rapid oral discontinuation may lead to rebound psychosis and worsening of symptoms

• If antiparkinson agents are being used, they should be continued for a few weeks after chlorpromazine is discontinued

Pharmacokinetics

• Half-life approximately 8–33 hours

Drug Interactions

• May decrease the effects of levodopa, dopamine agonists

• May increase the effects of antihypertensive drugs except for guanethidine, whose antihypertensive actions chlorpromazine may antagonize

• Additive effects may occur if used with CNS depressants

• Some pressor agents (e.g., epinephrine) may interact with chlorpromazine to lower blood pressure

• Alcohol and diuretics may increase the risk of hypotension

• Reduces effects of anticoagulants

• May reduce phenytoin metabolism and increase phenytoin levels

• Plasma levels of chlorpromazine and propranolol may increase if used concomitantly

• Some patients taking a neuroleptic and lithium have developed an encephalopathic syndrome similar to neuroleptic malignant syndrome