Thorazine: Effective Management of Severe Psychiatric and Medical Conditions
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Synonyms | |||
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 not a first-line treatment for many conditions due to its significant side effect burden but remains a critical tool in specific clinical scenarios where other agents have failed or are not suitable.
Features
- Active pharmaceutical ingredient: Chlorpromazine Hydrochloride
- Available formulations: Oral tablets (10 mg, 25 mg, 50 mg, 100 mg, 200 mg), Oral concentrate/solution (30 mg/mL, 100 mg/mL), Rectal suppositories (25 mg, 100 mg), Injectable solution for intramuscular or intravenous administration (25 mg/mL)
- Pharmacologic class: Typical (First-Generation) Antipsychotic, Phenothiazine, Aliphatic subgroup
- Comprehensive receptor affinity: Potent antagonist at dopamine D2 receptors, as well as alpha-1 adrenergic, muscarinic (M1), and histamine (H1) receptors
- Extensive clinical history with well-documented efficacy and safety profile established over decades of use
Benefits
- Provides rapid control of acute psychotic agitation and positive symptoms of schizophrenia (e.g., hallucinations, delusions) via central dopamine receptor blockade.
- Offers a non-opioid option for the management of severe, intractable hiccups (singultus) that have not responded to other measures.
- Effective as an antiemetic for severe nausea and vomiting, particularly in scenarios like surgery, cancer chemotherapy, or uremia, by acting on the chemoreceptor trigger zone.
- Can be utilized as a second-line agent for the short-term treatment of severe behavioral problems (e.g., hyperexcitability, combativeness) in children aged 1-12 years.
- Serves as a useful adjunct in the management of acute intermittent porphyria and tetanus due to its sedative and antiadrenergic properties.
- Available in multiple formulations (oral, injectable, rectal) allowing for flexible administration based on patient acuity and compliance.
Common use
Thorazine is commonly prescribed for the management of psychotic disorders, including schizophrenia. It is used to control the positive symptoms such as hallucinations, paranoia, and conceptual disorganization. Outside of psychiatry, it is a recognized treatment for severe, protracted hiccups that are unresponsive to other therapies. It is also employed as an antiemetic to prevent and treat nausea and vomiting associated with surgery, cancer chemotherapy, and other medical conditions. Its use in children is restricted to severe behavioral problems marked by explosive hyperexcitable behavior and for short-term treatment only.
Dosage and direction
Dosage is highly individualized based on diagnosis, severity of condition, patient response, and tolerance to side effects. Treatment should be initiated at the lowest possible dose and titrated gradually.
- Psychotic Disorders (Adults): Oral: Initial dose is typically 25-50 mg administered two to three times daily. For hospitalized patients, dosage may be increased over several days to an average effective range of 400-800 mg daily in divided doses. Some patients may require higher doses. IM: For rapid control of acute agitation, 25-50 mg is administered. Subsequent doses of 25-50 mg may be given in 1-4 hours as needed, gradually converting to oral therapy.
- Nausea and Vomiting (Adults): Oral: 10-25 mg every 4 to 6 hours as needed. IM: 25-50 mg initially, repeated every 3-4 hours as necessary.
- Intractable Hiccups (Adults): Oral/IM: 25-50 mg three to four times daily.
- Behavioral Problems (Children 1-12 years): Oral/IM: 0.25 mg/lb (0.55 mg/kg) every 4-6 hours as needed. IM dose should not exceed 40 mg/day for children up to 5 years or 75 mg/day for children 5-12 years, except in severe cases.
- Administration: Oral concentrate must be diluted in juice or other liquid just prior to administration. Injectable solution is for IM or slow IV administration only; IV administration requires close monitoring of blood pressure due to risk of severe hypotension.
Precautions
- Neurologic Effects: Use with extreme caution due to the risk of tardive dyskinesia (often irreversible) and neuroleptic malignant syndrome (NMS), a potentially fatal condition characterized by hyperpyrexia, muscle rigidity, altered mental status, and autonomic instability.
- Sedation: Causes significant drowsiness and impaired alertness. Patients must be cautioned against operating machinery or driving until their response is known.
- Orthostatic Hypotension: Significant alpha-adrenergic blockade can cause a pronounced drop in blood pressure upon standing. Dose titration should be slow, particularly in the elderly and those with cardiovascular disease.
- Anticholinergic Effects: Can cause dry mouth, blurred vision, urinary retention, and constipation. Use with caution in patients with glaucoma, prostatic hypertrophy, or ileus.
- Seizure Threshold: May lower the seizure threshold. Use with caution in patients with a history of seizure disorders.
- Agranulocytosis: Although rare, potentially fatal agranulocytosis has been reported. Monitor for signs of infection (e.g., fever, sore throat).
- Pregnancy and Lactation: Pregnancy Category C. Should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Appears in breast milk; not recommended for nursing mothers.
- Elderly Patients: Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. They are also more susceptible to postural hypotension, sedation, and anticholinergic effects.
Contraindications
- Known hypersensitivity to chlorpromazine, other phenothiazines, or any component of the formulation.
- Comatose states or significantly depressed states due to CNS depressants (alcohol, barbiturates, opioids).
- Presence of bone marrow suppression (e.g., pre-existing leukopenia, agranulocytosis).
- Should not be used in children under one year of age or under 20 lbs weight.
Possible side effect
Side effects are common and can be severe.
- Common: Marked sedation/drowsiness, orthostatic hypotension, dizziness, blurred vision, dry mouth, nasal congestion, constipation, weight gain.
- Neurologic: Extrapyramidal symptoms (EPS) such as pseudoparkinsonism (tremor, rigidity, bradykinesia), akathisia (motor restlessness), acute dystonic reactions (muscle spasms, torticollis, oculogyric crisis). Tardive dyskinesia (involuntary, repetitive movements of the face, tongue, and limbs).
- Endocrine: Galactorrhea, amenorrhea, gynecomastia, impotence.
- Dermatologic: Photosensitivity, skin rash, pigmentary retinopathy with prolonged high-dose use.
- Cardiovascular: Tachycardia, ECG changes (including prolongation of the QT interval).
- Hematologic: Agranulocytosis, leukopenia, eosinophilia.
- Other: Neuroleptic Malignant Syndrome (NMS), jaundice, hyperprolactinemia.
Drug interaction
Thorazine has a high potential for significant drug interactions.
- CNS Depressants: Concomitant use with alcohol, benzodiazepines, opioids, or other sedating agents can result in additive CNS depression (sedation, respiratory depression).
- Antihypertensives: May potentiate the effects of other antihypertensive drugs, leading to severe hypotension.
- Anticholinergics: Concurrent use with other anticholinergic drugs (e.g., atropine, benztropine, tricyclic antidepressants) can intensify 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 & III antiarrhythmics, certain antibiotics, other antipsychotics) may increase the risk of life-threatening cardiac arrhythmias, including torsades de pointes.
- Levodopa: Thorazine may antagonize the effects of levodopa in Parkinson’s disease.
- Propranolol: May increase the plasma levels of both drugs.
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.
Overdose
Overdose is primarily an extension of its pharmacological actions: profound CNS depression (ranging from drowsiness to coma), hypotension, extrapyramidal symptoms, agitation, restlessness, convulsions, and cardiac arrhythmias. Anticholinergic effects like dry mouth, ileus, and hyperthermia may be present. Treatment is symptomatic and supportive. There is no specific antidote. Emphasis is on maintaining a patent airway and adequate hydration. Gastric lavage may be considered if ingestion was recent. Severe hypotension should be treated with IV fluids and vasopressors like norepinephrine or phenylephrine (epinephrine should be avoided due to paradoxical effects). ECG monitoring is essential. Forced diuresis is not effective.
Storage
Store at controlled room temperature (68°F to 77°F or 20°C to 25°C). Protect from light. The oral concentrate should not be frozen. Keep all medications out of the reach of children and pets. Do not store in bathroom cabinets due to humidity.
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 medication. Never disregard professional medical advice or delay in seeking it because of something you have read here. The information provided may not cover all possible uses, directions, precautions, interactions, or adverse effects.
Reviews
- “As a consulting psychiatrist for over 30 years, chlorpromazine remains a powerful tool in our arsenal for acute agitation in inpatient settings. Its efficacy is undeniable, though its side effect profile mandates vigilant monitoring. It is not a drug for casual use.” – Dr. A., Psychiatry
- “We occasionally use low-dose chlorpromazine for intractable hiccups in the ICU when all else fails. The results can be dramatic and provide immense relief to the patient. The risk of hypotension requires careful hemodynamic monitoring during administration.” – Clinical Pharmacist, ICU
- “The historical significance of this drug is immense, marking the dawn of psychopharmacology. While newer atypical antipsychotics are generally preferred for chronic outpatient management due to a better neurological side effect profile, understanding chlorpromazine’s actions and reactions is fundamental for any practicing clinician.” – Academic Neurologist