Thorazine (chlorpromazine hydrochloride) is a first-generation typical antipsychotic medication belonging to the phenothiazine class. It represents a foundational agent in psychopharmacology, primarily indicated for the management of manifestations of psychotic disorders, severe behavioral problems in children, and as an adjunctive treatment for intractable hiccups, severe nausea and vomiting, and acute intermittent porphyria. Its mechanism of action is primarily through antagonism of postsynaptic mesolimbic dopaminergic D1 and D2 receptors in the brain, though it also exhibits significant antagonism at adrenergic, histaminic, and muscarinic receptors, contributing to both its therapeutic effects and its side effect profile. This agent is available in oral (tablet and liquid concentrate) and parenteral (intramuscular and intravenous) formulations, allowing for flexible dosing across various clinical scenarios, from acute agitation to long-term maintenance therapy.

Features

• Active pharmaceutical ingredient: Chlorpromazine Hydrochloride.
• Available formulations: Oral tablets (10 mg, 25 mg, 50 mg, 100 mg, 200 mg), oral concentrate (30 mg/mL, 100 mg/mL), and solution for intramuscular or intravenous injection (25 mg/mL).
• Pharmacologic class: First-generation (typical) antipsychotic; Phenothiazine, aliphatic subgroup.
• Primary mechanism: Potent antagonist of dopaminergic D2 receptors.
• Secondary mechanisms: Antagonism of alpha-1 adrenergic, muscarinic (M1), and histaminic (H1) receptors.
• Prescription status: Available only by prescription (Rx).

Benefits

• Provides rapid control of acute psychotic agitation and aggression through its potent calming (neuroleptic) effect.
• Effectively reduces the positive symptoms of psychosis, including hallucinations, delusions, and thought disorder.
• Serves as a highly effective antiemetic for severe nausea and vomiting not responsive to conventional treatments.
• Offers a therapeutic option for the treatment of intractable hiccups (singultus) via central nervous system modulation.
• Can be utilized as a supportive therapy in the management of acute intermittent porphyria and tetanus.
• Provides a cost-effective foundational treatment option within psychiatric pharmacotherapy.

Common use

Thorazine is commonly prescribed for the management of schizophrenia and other psychotic disorders to control symptoms such as agitation, hostility, and hallucinations. It is used in the treatment of severe behavioral problems in children marked by combativeness and/or explosive hyperexcitable behavior. Beyond psychiatry, it is a recognized treatment for severe nausea and vomiting, particularly in the context of surgery or cancer chemotherapy. It is also indicated for the treatment of intractable hiccups. Furthermore, it finds use as an adjunctive therapy for acute intermittent porphyria and as a supportive treatment for tetanus.

Dosage and direction

Dosage must be highly individualized based on diagnosis, severity of condition, patient response, and emergence of side effects. The smallest effective dosage should always be used.

• Adults (Psychosis): Oral: Initial dosage is typically 10 mg to 25 mg three to four times daily. This may be increased by 20 mg to 50 mg semi-weekly until effective control of symptoms is achieved. Usual maintenance dose is 200 mg to 800 mg daily in divided doses, though some patients may require higher doses. IM: For acute agitation, 25 mg initially. An additional 25 mg to 50 mg may be given in 1 hour if necessary. Subsequent doses can be switched to oral therapy.
• Geriatric or Debilitated Patients: Initiate with one-third to one-half the usual adult dosage, with gradual increases.
• Children (Psychosis or Severe Behavior Problems): Oral: For children over 6 months of age, 0.5 mg/kg per dose every 4 to 6 hours as needed. Alternatively, a starting dose of 10 mg to 25 mg three to four times daily is common, titrating upward as required. IM: 0.5 mg/kg per dose every 6 to 8 hours. Maximum IM dose is 40 mg/day for children up to 5 years or 22.7 kg, and 75 mg/day for children 5 to 12 years.
• Nausea and Vomiting: Oral: 10 mg to 25 mg every 4 to 6 hours as needed. IM: 25 mg initially. If no hypotension occurs, 25 mg to 50 mg every 3 to 4 hours as needed until vomiting stops.
• Intractable Hiccups: Oral: 25 mg to 50 mg three to four times daily. IM: 25 mg to 50 mg for rapid control if oral therapy is not feasible.

Administration Directions: Oral concentrate must be diluted just prior to administration in at least 2 fluid ounces of juice, milk, water, or a semisolid food. Do not mix with caffeinated beverages (coffee, tea) or tannin-containing beverages. Avoid skin contact with the liquid concentrate as it may cause contact dermatitis. IM injection should be administered deeply into a large muscle mass. IV administration is reserved for severe hiccups or nausea/vomiting and must be given as a slow, dilute infusion with close monitoring for hypotension.

Precautions

• Extrapyramidal Symptoms (EPS): Use with caution due to high risk of Parkinsonian symptoms, akathisia, dystonia, and tardive dyskinesia. Assess patients regularly.
• Neuroleptic Malignant Syndrome (NMS): A rare but potentially fatal syndrome characterized by hyperpyrexia, muscle rigidity, altered mental status, and autonomic instability. Discontinue Thorazine immediately and initiate intensive symptomatic treatment if NMS is suspected.
• Tardive Dyskinesia (TD): Risk of developing irreversible, involuntary dyskinetic movements increases with duration of treatment and total cumulative dose. The syndrome can develop after relatively brief treatment periods. Use the smallest effective dose for the shortest duration.
• Sedation: Marked sedation is common, especially during initial therapy. Caution patients against operating hazardous machinery or driving until their response is known.
• Orthostatic Hypotension: Significant alpha-adrenergic blockade can cause dizziness and syncope, particularly with parenteral administration. Monitor blood pressure and advise patients to rise slowly from a sitting or lying position.
• Seizures: May lower the seizure threshold. Use with extreme caution in patients with a history of seizure disorders.
• Agranulocytosis/Leukopenia: Hematologic monitoring is advised, especially during the first few months of therapy, as blood dyscrasias have been reported.
• Hepatic Effects: Transient jaundice and hepatic dysfunction have been observed. Periodic liver function tests are recommended.
• Ocular Changes: Long-term use is associated with irreversible pigmentary retinopathy and corneal and lenticular deposits. Regular eye examinations are recommended.
• Anticholinergic Effects: Can cause dry mouth, blurred vision, urinary retention, and constipation, particularly in the elderly.
• Temperature Regulation: May impair the body’s ability to reduce core body temperature. Caution is advised in patients exposed to extreme heat.

Contraindications

Thorazine is contraindicated in patients with known hypersensitivity to chlorpromazine or any phenothiazine. Its use is contraindicated in patients with significant CNS depression (e.g., comatose states) due to alcohol, barbiturates, opioids, etc. It should not be used in patients with bone marrow suppression or pre-existing blood dyscrasias. It is contraindicated in patients with subcortical brain damage, as it may lower the seizure threshold. Concomitant use with large doses of hypnotics is contraindicated.

Possible side effect

Side effects are common and often dose-related.

• Very Common (>10%): Sedation/somnolence, dizziness, orthostatic hypotension, dry mouth, blurred vision, constipation, nasal congestion.
• Common (1-10%): Extrapyramidal symptoms (akathisia, dystonia, Parkinsonism), weight gain, photosensitivity, skin rash, galactorrhea, amenorrhea, inhibition of ejaculation.
• Uncommon (0.1-1%): Tardive dyskinesia, neuroleptic malignant syndrome, jaundice, leukopenia, agranulocytosis, seizures, pigmentary retinopathy (with long-term, high-dose use).
• Rare (<0.1%): Ventricular arrhythmias, systemic lupus erythematosus (SLE)-like syndrome, ocular changes (corneal and lenticular deposits).

Drug interaction

Thorazine has a significant potential for drug interactions due to its extensive receptor profile and metabolic pathway (primarily CYP2D6).

• CNS Depressants: Concomitant use with alcohol, benzodiazepines, barbiturates, opioids, or other sedating agents can result in additive CNS and respiratory depression.
• Antihypertensives: May potentiate the effects of other antihypertensive drugs, leading to severe hypotension.
• Levodopa and Direct Dopamine Agonists: Direct antagonism; Thorazine may decrease the effectiveness of these Parkinson’s disease medications.
• Anticholinergics: Concurrent use with other anticholinergic drugs (e.g., benztropine, trihexyphenidyl, tricyclic antidepressants) may potentiate anticholinergic side effects (e.g., paralytic ileus, hyperthermia).
• QT-Prolonging Agents: Concomitant use with other drugs known to prolong the QT interval (e.g., Class IA and III antiarrhythmics, certain antibiotics, other antipsychotics) may increase the risk of potentially fatal cardiac arrhythmias, including torsades de pointes.
• CYP2D6 Inhibitors/Inducers: Drugs like fluoxetine, paroxetine, or bupropion (inhibitors) may increase chlorpromazine levels. Drugs like carbamazepine (inducer) may decrease its levels.

Missed dose

If a dose is missed, it should be taken as soon as it is remembered. However, if it is almost time for the next scheduled dose, the missed dose should be skipped. The patient should not double the next dose to make up for the missed one, as this increases the risk of side effects. Patients should be instructed to maintain their regular dosing schedule and contact their physician if multiple doses are missed.

Overdose

Symptoms of overdose are primarily an exaggeration of its known pharmacological effects and can be severe. Manifestations include profound CNS depression (ranging from profound sedation to coma), hypotension, extrapyramidal symptoms, agitation, restlessness, convulsions, hypothermia, hyperthermia, and autonomic reactions (e.g., dry mouth, ileus). Cardiac effects may include QT prolongation, arrhythmias, and tachycardia. Treatment is entirely supportive and symptomatic. There is no specific antidote. Gastric lavage may be considered if ingestion was recent. Aggressive management of hypotension with IV fluids and vasopressors (preferably alpha-adrenergic agonists like norepinephrine, not epinephrine) is critical. ECG monitoring for arrhythmias is essential. Management of seizures and extrapyramidal symptoms with benzodiazepines and anticholinergics, respectively, may be required.

Storage

Store at controlled room temperature, 20°C to 25°C (68°F to 77°F). Protect from light and moisture. Do not freeze the liquid formulations. The oral concentrate should be kept in the original, light-resistant container. Keep all medications out of the reach of children and pets.

Disclaimer

This information is for educational and informational purposes only and does not constitute medical advice. It is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or medication. Never disregard professional medical advice or delay in seeking it because of something you have read here. The author and publisher are not responsible for any specific health or allergy needs that may require medical supervision or for any adverse effects resulting from the use of information contained herein.

Reviews

• Clinical Efficacy (4.5/5): “Thorazine remains a gold-standard for rapid control of acute psychosis and severe agitation in an inpatient setting. Its efficacy is undeniable, though its side effect profile necessitates careful patient selection and monitoring.”
• Side Effect Profile (2/5): “The high incidence of extrapyramidal symptoms and sedation is a significant drawback. It is often a second or third-line choice for long-term management due to the risk of tardive dyskinesia, but its utility in acute crises is unmatched.”
• Formulation Flexibility (5/5): “The availability of oral tablets, concentrate, and IM injection provides unparalleled flexibility for titrating doses and managing patients across different levels of acuity, from the ER to outpatient maintenance.”
• Historical Significance (5/5): “As the first modern antipsychotic, its role in the history of psychiatry is monumental. It revolutionized the treatment of schizophrenia and paved the way for all subsequent antipsychotic development.”