Chlorpromazine

Mental Health and Behavioral Conditions

Chlorpromazine is primarily used to manage symptoms of schizophrenia and other psychotic disorders. It is also used to treat the manic phase of bipolar disorder (manic-depressive illness). In children aged 3 to 12 years, it may be prescribed to manage severe behavioral problems, such as explosive hyperexcitability or combativeness.

Nausea, Vomiting, and Hiccups

This medication is effective in controlling severe nausea and vomiting. It is also used to treat intractable hiccups, which are hiccups that have lasted for a long time and have not responded to other treatments.

Other Medical Uses

Chlorpromazine has several other specific applications, including:

• Relieving restlessness and apprehension before surgery.
• Treating acute intermittent porphyria, a rare genetic blood disorder.
• Acting as an additional treatment for tetanus.

Mechanism of Action

Chlorpromazine belongs to a group of drugs called phenothiazines. It is classified as a conventional or first-generation antipsychotic. The medication works by changing the activity of natural substances in the brain and other parts of the body.

Dopamine Regulation

The primary function of chlorpromazine is to block dopamine receptors in the brain. Dopamine is a neurotransmitter involved in regulating mood, thinking, and behavior. In people with certain psychiatric conditions, dopamine activity may be overactive. By blocking these receptors, chlorpromazine helps to reduce symptoms such as hallucinations, delusions, and disorganized thinking.

Other Effects

Chlorpromazine also affects several other neurotransmitters, including serotonin, histamine, and acetylcholine. These interactions contribute to the medication's various effects:

• Sedation: Its impact on histamine and other receptors can cause a calming or sedative effect.
• Nausea Control: It acts on the chemoreceptor trigger zone, a specific area of the brain that triggers vomiting, which helps control severe nausea and vomiting.
• Hiccup Relief: While the exact mechanism for stopping hiccups is not fully understood, it is believed to involve the medication's effect on the nerves that control the diaphragm.

Common Side Effects

• Drowsiness or dizziness
• Dry mouth or stuffy nose
• Blurred vision
• Constipation
• Weight gain
• Breast swelling or discharge
• Changes in menstrual periods
• Difficulty having an orgasm or impotence

Serious Side Effects

• Uncontrolled muscle movements in the face, tongue, or limbs (tardive dyskinesia)
• High fever, stiff muscles, confusion, and sweating (neuroleptic malignant syndrome)
• Yellowing of the skin or eyes (jaundice)
• Difficulty urinating
• Vision changes or decreased night vision
• Signs of infection, such as fever, chills, or sore throat
• Seizures
• Slow heart rate or fainting

Boxed Warning: Dementia-Related Psychosis

Elderly patients with dementia-related psychosis who are treated with antipsychotic drugs face an increased risk of death. Chlorpromazine is not approved for the treatment of patients with dementia-related psychosis.

Neuroleptic Malignant Syndrome (NMS)

A potentially fatal condition called Neuroleptic Malignant Syndrome has been reported with the use of antipsychotic drugs. Clinical manifestations include high fever, muscle rigidity, altered mental status, and autonomic instability, such as irregular pulse or blood pressure, tachycardia, and sweating.

Tardive Dyskinesia

Tardive dyskinesia is a syndrome consisting of potentially irreversible, involuntary movements that may develop in patients treated with antipsychotic drugs. Although the prevalence appears to be highest among the elderly, especially elderly women, it is impossible to predict which patients are likely to develop the syndrome. The risk increases with the duration of treatment and the total cumulative dose.

Contraindications

Chlorpromazine should not be used in individuals with the following conditions:

• Comatose states.
• Presence of large amounts of central nervous system depressants, such as alcohol, barbiturates, or narcotics.
• Known hypersensitivity to phenothiazines.
• Bone marrow depression.

Major Precautions

• Hypotension: Severe low blood pressure may occur, particularly in patients with cardiovascular disease or those receiving the drug by injection.
• Seizure Threshold: Chlorpromazine may lower the seizure threshold. It should be used with caution in patients with a history of seizures or those receiving anticonvulsant medications.
• Blood Disorders: Serious blood conditions, including agranulocytosis, have been reported. Regular monitoring of blood counts may be required if signs of infection appear.
• Liver Injury: Jaundice may occur, typically between the second and fourth weeks of therapy. Treatment should generally be discontinued if jaundice is observed.
• Visual Changes: Long-term use of high doses may lead to ocular changes, including deposits in the lens and cornea or pigmentary retinopathy.
• Temperature Regulation: Antipsychotic drugs can interfere with the body's ability to reduce core temperature. Caution is advised for those exposed to extreme heat, strenuous exercise, or dehydration.

Pregnancy

Newborns exposed to antipsychotic medications like chlorpromazine during the third trimester of pregnancy may be at risk for symptoms after delivery. These symptoms, which vary in severity, may include:

• Muscle stiffness or weakness
• Tremors
• Agitation
• Sleepiness
• Breathing problems
• Difficulty feeding

Some infants may recover quickly, while others may require specialized medical care or longer hospital stays. Chlorpromazine should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the developing fetus.

Breastfeeding

Chlorpromazine passes into breast milk. Because of the potential for serious adverse reactions in a nursing infant, healthcare providers typically recommend a decision between discontinuing breastfeeding or discontinuing the medication. This decision is based on the importance of the drug to the mother's health.

If you are pregnant, planning to become pregnant, or breastfeeding, it is important to discuss the risks and benefits of chlorpromazine with your healthcare provider. Do not start or stop this medication without medical guidance.

Oral Forms

Chlorpromazine is available in several oral formulations to allow for flexible dosing:

• Tablets: These are the most common form and are available in multiple strengths.
• Oral Liquid: This includes oral concentrates and syrups, which are often used for individuals who have difficulty swallowing solid tablets.

Injectable Forms

Chlorpromazine is available as a solution for injection, which is typically administered by a healthcare provider. It can be given as:

• Intramuscular Injection: Injected into a muscle.
• Intravenous Infusion: Delivered directly into a vein, usually in a clinical setting for specific conditions.

Rectal Forms

For patients who cannot take medication by mouth, chlorpromazine is available as a rectal suppository.

FDA Approval and Indications

Chlorpromazine is a conventional antipsychotic medication that received FDA approval for the treatment of several psychiatric and medical conditions. Its approved uses include the management of schizophrenia, the manic phase of bipolar disorder, and severe behavioral problems in children. Beyond psychiatric care, it is also indicated for the treatment of nausea and vomiting, restlessness before surgery, acute intermittent porphyria, and as an adjunct in the treatment of tetanus. It is also one of the few medications approved for the treatment of intractable hiccups.

Boxed Warning

Increased Mortality in Elderly Patients with Dementia-Related Psychosis: The FDA has issued a boxed warning for chlorpromazine. Elderly patients with dementia-related psychosis who are treated with antipsychotic drugs are at an increased risk of death. Chlorpromazine is not approved for the treatment of patients with dementia-related psychosis.

Regulatory Classification

Chlorpromazine is a prescription-only medication. It is not a controlled substance. While it was the first drug in the phenothiazine class, its clinical use is monitored due to the potential for serious side effects, such as tardive dyskinesia and neuroleptic malignant syndrome, which are documented in its regulatory labeling.

Withdrawal Symptoms

If you stop taking chlorpromazine abruptly, especially after long-term use or high doses, you may experience withdrawal symptoms. These symptoms are generally physical reactions and do not necessarily mean the medication is addictive.

Common withdrawal symptoms include:

• Nausea and vomiting
• Stomach pain
• Dizziness
• Shakiness or tremors

To avoid these symptoms, do not stop taking this medication without consulting your healthcare provider. They will typically provide a schedule to gradually reduce your dose before stopping the medication entirely.