Thorazine

Thorazine (chlorpromazine hydrochloride) is a first-generation typical antipsychotic medication belonging to the phenothiazine class. It represents a cornerstone in psychopharmacology, primarily indicated for the management of manifestations of psychotic disorders, such as schizophrenia. Its efficacy extends beyond psychiatry, serving as a potent antiemetic for severe nausea and vomiting and as an adjunct in the treatment of intractable hiccups. This agent works by blocking postsynaptic mesolimbic dopaminergic D1 and D2 receptors in the brain, alongside antagonizing adrenergic, cholinergic, and histaminergic receptors, which contributes to both its therapeutic effects and its side effect profile. Its introduction marked a revolutionary advancement in the treatment of severe mental illness, transitioning care from largely institutional settings to more manageable outpatient therapies.

Features

• Active Ingredient: Chlorpromazine Hydrochloride
• Drug Class: First-Generation (Typical) Antipsychotic, Phenothiazine Derivative
• Available Formulations: Oral tablets, oral syrup, and injectable solutions (for intramuscular or intravenous administration under strict medical supervision)
• Mechanism of Action: Potent antagonist of dopaminergic (D2), adrenergic (alpha-1), cholinergic (muscarinic M1), and histaminergic (H1) receptors
• Bioavailability: Oral bioavailability is significant but variable and subject to extensive first-pass metabolism
• Half-Life: Approximately 30 hours, allowing for once or twice-daily dosing in maintenance therapy

Benefits

• Effective Reduction of Positive Psychotic Symptoms: Significantly diminishes hallucinations, delusions, and thought disorder in conditions like schizophrenia.
• Rapid Agitation Control: The injectable form provides swift sedation and behavioral control in acute psychotic episodes or severe agitation.
• Powerful Antiemetic Action: Effectively manages severe, refractory nausea and vomiting not responsive to conventional treatments, including that induced by chemotherapy.
• Treatment of Intractable Hiccups: Offers a reliable solution for persistent hiccups that have failed other therapeutic interventions.
• Established Safety Profile: Decades of clinical use have resulted in a well-understood and extensively documented efficacy and adverse reaction profile.
• Cost-Effective Therapy: As a generic medication, it provides a vital, affordable option for long-term management of chronic psychiatric conditions.

Common use

Thorazine is primarily prescribed for the management of schizophrenia and other psychotic disorders to control symptoms such as aggressiveness, impulsivity, and hyperexcitability. It is also widely used off-label for the short-term treatment of severe behavioral problems in children and for the manifestation of manic episodes in bipolar disorder before a mood stabilizer takes full effect. Its second major application is in the field of medicine as a potent antiemetic for severe nausea and vomiting, including that associated with cancer chemotherapy, radiation sickness, and surgery. Furthermore, it is a recognized treatment for intractable hiccups.

Dosage and direction

Dosage is highly individualized based on the patient’s condition, severity of symptoms, age, and response to therapy. For psychotic disorders in adults, the initial oral dose often ranges from 25 mg to 100 mg three times daily. This can be gradually increased over several weeks to a typical maintenance dose of 200 mg to 800 mg daily, though some patients may require higher doses under close supervision. For severe nausea and vomiting in adults, the usual oral dose is 10 mg to 25 mg every 4 to 6 hours as needed. Injectable forms are reserved for acute settings and must be administered by healthcare professionals; doses are typically lower than oral doses due to greater bioavailability. It is crucial to take Thorazine exactly as prescribed by a physician, with or without food, though taking it with food or milk may help minimize gastrointestinal upset. Abrupt discontinuation should be avoided.

Precautions

Patients should be closely monitored for the development of extrapyramidal symptoms (EPS), such as muscle stiffness, tremors, and restlessness, and tardive dyskinesia (involuntary, repetitive body movements), which may be irreversible. Due to its alpha-adrenergic blocking activity, Thorazine can cause orthostatic hypotension (dizziness upon standing); patients should be advised to rise slowly from a sitting or lying position. It can also impair mental and/or physical abilities required for performing hazardous tasks, such as operating machinery or driving. Caution is advised in patients with cardiovascular disease, liver impairment, seizure disorders, or a history of glaucoma. Thorazine can affect body temperature regulation, making patients more susceptible to heat stroke and hypothermia. Regular monitoring of complete blood count, liver function tests, and eye exams is recommended during prolonged therapy.

Contraindications

Thorazine is contraindicated in patients with a known hypersensitivity to chlorpromazine or any phenothiazine. Its use is contraindicated in comatose states or significantly depressed states due to CNS depressants (alcohol, barbiturates, opioids). It should not be used in patients with bone marrow suppression or pre-existing blood dyscrasias. Due to its potent hypotensive effects, it is contraindicated in individuals with severe cardiovascular disease or profound hypotension.

Possible side effect

The side effect profile of Thorazine is extensive due to its action on multiple receptor systems.

• Neurological: Extrapyramidal symptoms (pseudoparkinsonism, akathisia, dystonia), tardive dyskinesia, sedation, drowsiness, dizziness, seizures.
• Anticholinergic: Dry mouth, blurred vision, constipation, urinary retention, reduced sweating.
• Cardiovascular: Orthostatic hypotension, tachycardia, dizziness, fainting, ECG changes (e.g., QT prolongation).
• Endocrine: Galactorrhea (inappropriate milk production), amenorrhea, weight gain, sexual dysfunction.
• Dermatological: Photosensitivity (increased risk of sunburn), skin rashes, pigmentation changes with long-term use.
• Ophthalmic: Deposition of fine particulate matter in the cornea and lens (corneal and lenticular opacities) with prolonged high-dose therapy.
• Other: Neuroleptic malignant syndrome (a rare but life-threatening reaction characterized by fever, muscle rigidity, and autonomic instability), jaundice, agranulocytosis.

Drug interaction

Thorazine has a significant potential for drug interactions.

• CNS Depressants: Concomitant use with alcohol, benzodiazepines, opioids, or other sedatives can result in additive CNS depression, profound sedation, and respiratory depression.
• Antihypertensives: May potentiate the effects of other blood pressure-lowering drugs, leading to severe hypotension.
• Anticholinergics: Concurrent use with other drugs possessing anticholinergic properties (e.g., atropine, antihistamines, tricyclic antidepressants) can intensify side effects like dry mouth, constipation, and urinary retention.
• QT-Prolonging Agents: Concurrent use with other drugs known to prolong the QT interval (e.g., certain antibiotics, antiarrhythmics, other antipsychotics) increases the risk of serious cardiac arrhythmias, including torsades de pointes.
• Levodopa: Thorazine may antagonize the effects of levodopa in Parkinson’s disease.
• Metabolism: It may enhance the effects of certain medications by inhibiting their metabolism.

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, and the regular dosing schedule resumed. Patients should never take a double dose to make up for a missed one, as this increases the risk of adverse effects.

Overdose

Overdose of Thorazine is primarily characterized by profound CNS depression (ranging from sedation to deep coma), hypotension, and extrapyramidal symptoms. Agitation, restlessness, convulsions, fever, and hypothermia may also occur. Anticholinergic effects such as dry mouth, ileus, and blurred vision are common. Cardiac manifestations include QT prolongation and arrhythmias. Overdose is a medical emergency requiring immediate hospitalization. Treatment is supportive and symptomatic, focusing on maintaining airway, breathing, and circulation. There is no specific antidote. Gastric lavage may be considered if presentation is early. Management of hypotension involves IV fluids and vasopressors (avoiding epinephrine). ECG monitoring is essential.

Storage

Thorazine should be stored at room temperature (15°-30°C or 59°-86°F), away from light, moisture, and heat. The oral liquid formulation should be protected from light and freezing. All medications must be kept out of reach of children and pets. Unused or expired medication should be disposed of properly via a take-back program or according to FDA guidelines, not flushed down the toilet or poured into a drain.

Disclaimer

This information is for educational purposes only and 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 before starting any new treatment. Never disregard professional medical advice or delay in seeking it because of something you have read here. The content has not been evaluated by all regulatory agencies and is intended for a professional audience.

Reviews

“Thorazine remains an indispensable tool in our inpatient psychiatric unit for managing acute agitation. While its side effect profile requires vigilant monitoring, its efficacy in rapidly de-escalating crisis situations is unparalleled. It’s a classic for a reason.” – Board-Certified Psychiatrist

“As a medical oncologist, I reserve chlorpromazine for cases of breakthrough CINV (chemotherapy-induced nausea and vomiting) where first-line antiemetics have failed. It is remarkably effective, though its sedative properties mean we use it judiciously, often for overnight control.” – Oncologist

“Managing a patient with decades-long schizophrenia on stable doses of chlorpromazine. The side effects, notably some tardive dyskinesia, are a concern, but the drug has provided him with a stability that newer agents failed to achieve. A complex balance of benefit and risk.” – Psychiatric Nurse Practitioner