Chlorpromazine (Thorazine)

Saw psychiatrist 2 days ago and he gave me Chlorpromazine 25mg and to take 2 a day. This was in response to a  review of medication and the unsuitablility of Benzo's for Generalised anxiety dosorder.

I gave him the list of all the psych meds I hav'nt been able to tolerate which includes virtually all of the antidepressants. Bipolar disorder was never diagnosed after a few sessions of investigation 3 years ago. Tegretol had little effect even at the highest dose and the atypical antipsychotics (Clozapine, respiridone) gave me terrible side effects even in small doses.

I mentioned that i had taken quarter tablets of Levemopromazine during the end of my taper and had found them sedating without the nasty w/ds but a full strength tablet dose which I cant remember exacty gave me a night of confusion and terror I wont forget in a hurry. I have no idea if this is meant to replace the Diazepam or not..

He just sort of looked at me at the end and asked if there was anything he could prescribe that might help me and Thorazine is well known to be the mother of all tranqs so I thought I would try it. I certainly have no intentin of taking it twice daily and I lnow it is not recommended as a Benzo replacement. I should have asked more questions really!

I took a quarter dose of prob 6mg last night and became very zoned out and didnt take my Nitrazepam meds and slept ok. Its just its side effects profile is horrific and these are just the common ones even at low doses.

Not been on the benzos long this time so far, I think maybe 2-2half months.

any thoughts?

Chlorpromazine

Brand name: Largactil, Thorazine 

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Drug monograph

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Contents

Pharmacology

Indications

Contraindications

Precautions

Adverse Effects

Overdose

Dosage

Research

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Pharmacology

Antipsychotic - Antiemetic

Chlorpromazine is an aliphatic phenothiazine. Phenothiazines are thought to elicit their antipsychotic and antiemetic effects via interference with central dopaminergic pathways in the mesolimbic and medullary chemoreceptor trigger zone areas of the brain, respectively. Extrapyramidal side effects are a result of interaction with dopaminergic pathways in the basal ganglia. Although often termed dopamine blockers, the exact mechanism of dopaminergic interference responsible for the drugs antipsychotic activity has not been determined.

The aliphatic phenothiazines are highly sedating which is often apparent at the start of therapy; with time some tolerance to this effect develops. Chlorpromazine has strong alpha-adrenergic blocking activity and can cause orthostatic hypotension. Infrequently prolongation of the QT interval may occur. Chlorpromazine has moderate anticholinergic activity manifested as occasional dry mouth, blurred vision, urinary retention and constipation.

Chlorpromazine increases prolactin secretion due to its dopamine receptor blocking action in the pituitary and hypothalamus. Galactorrhea and gynecomastia have occurred.

Pharmacokinetics:

Chlorpromazine is readily absorbed from the gastrointestinal tract, however its bioavailability is variable due to considerable first pass metabolism by the liver. Liquid concentrates may have greater bioavailability than tablets. Food does not appear to affect bioavailability consistently. I.M. administration bypasses much of the first pass effect and higher plasma concentrations are achieved. The onset of action after i.m. administration is usually 15 to 30 minutes and after oral administration 30 to 60 minutes. Rectally administered chlorpromazine usually takes longer to act than oral.

Chlorpromazine is highly bound to plasma proteins (>90%), principally albumin. It is not dialysable. It is distributed widely throughout the body; crossing the blood brain barrier, the placenta and is distributed into milk. Volume of distribution is about 20 L/kg.

Chlorpromazine is metabolized extensively and at least 12 different metabolites are known. Less than 1% is excreted unchanged. Most metabolites are excreted in the urine as unconjugated or conjugated forms. The terminal half-life of chlorpromazine is variable at approximately 30 hours.

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Indications

The management of psychotic disorders including manifestations of manic depressive illness, manic phase and severe behavioral problems in children; nausea and vomiting due to stimulation of the chemoreceptor trigger zone.

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Contraindications

Comatose or depressed states due to CNS depressants; blood dyscrasias; bone marrow depression; liver damage. Hypersensitivity to chlorpromazine. Cross allergenicity with other phenothiazines may occur.

Should be avoided in children or adolescents with signs or symptoms suggestive of Reye's Syndrome. Its antiemetic effect may mask the signs and its CNS effect may be confused with the signs of Reye's Syndrome or other encephalopathies.

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Precautions

Phenothiazines should be used with caution in patients with cardiovascular disease. Chlorpromazine is an alpha-adrenergic blocking agent and increased pulse rate and transient hypotension have both been reported in some patients receiving these drugs.

Hypotension, which is typically orthostatic, may occur especially in elderly and in alcoholic patients. This effect may be additive with other agents that cause a lowering of blood pressure. If chlorpromazine should cause severe hypotension, most patients will respond to cautious expansion of the intravascular volume with sodium chloride. If vasopressor drugs are needed, the drugs of choice are alpha-receptor agonists such as phenylephrine or methoxamine.

Chlorpromazine has direct negative inotropic action. It prolongs PR and QT intervals, blunts the T wave and depresses the S-T segment. These changes appear to be reversible and related to disturbance in repolarization. Give phenothiazines cautiously to patients with heart disease.

Most reported cases of agranulocytosis associated with the administration of phenothiazine derivatives have occurred between the fourth and tenth week of treatment. Therefore observe patients on prolonged therapy with particular care during that time for the appearance of such signs as sore throat, fever and weakness. If these symptoms appear, discontinue the drug and perform WBC and differential counts.

Chlorpromazine should be used with caution in patients who have impaired liver function or alcoholic liver disease. CNS depression may be potentiated.

If bilirubinemia, or icterus occur, discontinue the drug and perform liver function tests.

Phenothiazines have been associated with retinopathy. Discontinue chlorpromazine if retinal changes are observed. Regular ophthalmologic exams are recommended.

Use chlorpromazine cautiously in patients with a history of seizures since the drug tends to lower the seizure threshold.

The anticholinergic action of chlorpromazine may be a factor in some cases of intestinal pseudo-obstruction.

Chlorpromazine may mask signs of overdosage of toxic drugs and may obscure conditions such as intestinal obstruction and brain tumor.

Neuroleptic drugs elevate prolactin levels; the elevation persists during chronic administration. Although disturbances such as galactorrhea, amenorrhea, gynecomastia, and impotence have been reported, the clinical significance of elevated serum prolactin levels is unknown for most patients.

Chlorpromazine may impair sensitivity and adaptation to changes of environmental temperature so that fatal hyperthermia and heat stroke are possible complications.

Abrupt Withdrawal:

In general, phenothiazines do not produce psychic dependence; however, gastritis, nausea and vomiting, dizziness, and tremulousness have been reported following abrupt cessation of high dose therapy. Reports suggest that these symptoms can be reduced if concomitant antiparkinsonian agents are continued for several weeks after the phenothiazine is withdrawn.

Occupational Hazards:

Where patients are participating in activities requiring complete mental alertness such as driving an automobile or operating machinery, administer the phenothiazine cautiously, forewarn the patient and increase the dosage gradually.

Photosensitivity may occur. Patients should utilize sunscreens when exposed to sunlight for significant lengths of time.

Drug Interactions:

Anticonvulsants:

Chlorpromazine may lower the seizure threshold. Anticonvulsant therapy should be monitored closely and may require dosage adjustment.

Alcohol:

Additive CNS depressant effects.

Amphetamines:

Amphetamines may cause exacerbation of psychotic symptoms.

Antihistamines, second generation:

Chlorpromazine can prolong the QT interval. Although no case reports exist, patients on chlorpromazine should be administered antihistamine drugs such as astemizole and terfenadine with great caution. The concomitant administration of these agents may have the potential to cause additive effects on the QT interval and increase propensity to ventricular arrhythmia.

Antacids:

May impair the absorption of chlorpromazine. Monitor for decreased effect.

Anticholinergics:

Routine use together is not advisable. If combined use is necessary, monitor carefully for decreased antipsychotic response, adynamic ileus (constipation, abdominal pain and distension). Predisposition to heat stroke may be increased with this combination.

Antidepressants, tricyclic:

May result in increased chlorpromazine concentration, monitor for adverse effects.

CNS Depressants:

Chlorpromazine and other CNS depressants (alcohol, antihistamines, general anesthetics, opiates or other narcotic analgesics, barbiturates, benzodiazepines and other sedative/hypnotic agents) may result in additive CNS depressant effects. Monitor to avoid excessive sedation or respiratory depression.

Epinephrine:

Patients on chlorpromazine who are hypotensive should not be given epinephrine. Chlorpromazine blocks peripheral alpha-adrenergic receptors, thereby inhibiting alpha-agonist effects of epinephrine such as vasoconstriction and increased blood pressure. The beta-agonist effects of epinephrine (vasodilation) may be left unopposed and a further fall in blood pressure may result. Agents such as phenylephrine methoxamine or norepinephrine may be a suitable alternative to raise blood pressure.

Hypotensive Agents:

Chlorpromazine and antihypertensives may result in additive hypotensive effects and increased risk of orthostatic hypotension or syncope (fainting). Chlorpromazine may block the antihypertensive effects of guanethidine by preventing its uptake into sympathetic nerves.

Levodopa:

Phenothiazines may inhibit the antiparkinsonian effects of levodopa due to their dopamine blocking effects in the CNS. Generally, phenothiazines should not be administered to patients who require levodopa.

Lithium:

Patients receiving lithium and chlorpromazine for treatment of acute mania should be monitored closely for signs of adverse neurologic effects, especially if serum concentrations of lithium are in the upper range. Rare cases of severe neurotoxicity have been reported.

Pregnancy:

Safe use of phenothiazines in pregnancy has not been established. Most studies indicate these agents are not teratogenic but there are reports of defects in infants exposed to these drugs during the first trimester. Toxic effects observed after high doses near term include: hypotonia, lethargy, depressed reflexes, paralytic ileus, jaundice, and persistent extrapyramidal syndrome. Therefore, they should be administered cautiously to women of childbearing potential particularly during the first trimester of pregnancy and near term.

Lactation:

Phenothiazines are distributed into milk. Use with caution during lactation because of possible sedative and anticholinergic side effects on the infant.

Geriatrics:

Use reduced dosages. Chlorpromazine may adversely affect many of the conditions commonly occurring in the aged, including cardiovascular problems, parkinsonian extrapyramidal effects and anticholinergic effects (e.g. constipation, blurred vision).

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Adverse Effects

In general members of the aliphatic group of phenothiazines have strong sedative, hypotensive and anticholinergic properties and mild to moderate extrapyramidal effects.

Automatic Nervous System:

Anticholinergic effects including dry mouth, blurred vision, constipation, ileus, nasal stuffiness, photophobia. Syncope and impaired temperature regulation have also occurred.

Cardiovascular:

Chlorpromazine has peripheral alpha-adrenergic blocking activity. Its effects on the heart include: direct negative inotropic and quinidine-like actions. Its effects on the ECG include prolongation of the PR and QT intervals, blunting of the T wave and depression of the S-T segment. Ventricular arrythmia and sudden death have occurred rarely.

Orthostatic hypotension is common after parenteral administration and usually lasts one-half to 2 hours. Patients should be supine when parenteral chlorpromazine is administered. Tachycardia, fainting and dizziness have also occurred. Hypotension can also occur after oral administration. Tolerance to hypotensive effects generally develop over time, however hypotension can persist in some patients, especially the elderly.

CNS:

Extrapyramidal reactions, including pseudoparkinsonism (with motor retardation, rigidity, mask like facies, pill rolling and other tremors, drooling, shuffling gait, etc.); dystonic reactions (including periroral spasms, trismus, tics, torticollis, oculogyric crises, protrusion of the tongue, difficulty swallowing, carpopedal spasm, opisthotonos of the back muscles); and akathisia. In addition, slowing of the EEG rhythm, disturbed body temperature and lowering of the convulsive threshold have occurred. Dizziness has been reported.

Tardive dyskinesia may appear in some patients on long term antipsychotic therapy or may appear after drug therapy has been discontinued. The risk appears to be greater in elderly patients on high-dose therapy, especially females. The symptoms are persistent and in some patients appear to be irreversible. The syndrome is characterized by rhythmical involuntary movements of the tongue, face, mouth or jaw (e.g. protrusion of the tongue, puffing of the cheeks, puckering of the mouth and chewing movements). Sometimes these may be accompanied by involuntary movements of the extremities.

There is no known effective treatment for tardive dyskinesia; antiparkinsonian agents usually do not alleviate the symptoms of this syndrome. All antipsychotic agents should be discontinued if these symptoms appear. Should it be necessary to reinstitute treatment, or increase the dosage of the agent, or switch to a different antipsychotic agent, the syndrome may be masked. The physician may be able to reduce the risk of this syndrome by minimizing the unnecessary use of neuroleptics and reducing the dose or discontinuing the drug, if possible, when manifestations of this syndrome are recognized, particularly in patients over the age of 50. Fine vermicular movements of the tongue may be an early sign of the syndrome. If the medication is stopped at that time, the syndrome may not develop.

Dermatologic:

Itching, rash, hypertrophic papillae of the tongue, angioneurotic edema, erythema, allergic purpura, exfoliative dermatitis, photosensitivity. Contact dermatitis has occurred in personnel handling solutions or injections of chlorpromazine.

Endocrine:

Increased prolactin secretion; gynecomastia, galactorrhea, mastalgia, altered libido, menstrual irregularities, weight gain, alterations in glucose tolerance and false positive pregnancy tests have occurred.

Gastrointestinal:

Nausea, vomiting, increase or decrease in appetite, gastric irritation, constipation, paralytic ileus, rarely diarrhea. Dry mouth.

Genitourinary:

Urinary retention, priapism, inhibition of ejaculation.

Hematologic:

Agranulocytosis, leukopenia, granulocytopenia, eosinophilia, thrombocytopenia, anemia, aplastic anemia, pancytopenia. Agranulocytosis occurs in fewer than 1 in 10000 patients receiving chlorpromazine.

Hepatic:

Cholestatic jaundice can occur infrequently (0.1-4%) and is usually part of a hypersensitivity reaction. Jaundice usually occurs within 2 to 4 weeks of initiation of therapy and chlorpromazine should be discontinued immediately. Rarely progression to chronic jaundice has occurred. Pre-existing liver dysfunction has not yet been proven to be a risk factor for this reaction. Signs and symptoms of cholestatic jaundice include; upper abdominal pain, nausea, flu-like symptoms, yellow skin and conjunctiva, fever, elevated liver enzymes, biliuria.

Hypersensitivity:

Cholestatic jaundice (see under Hepatic), various dermatoses (see under Dermatologic), blood dyscrasias (see under Hematologic), photosensitivity, laryngeal edema, bronchospasm, angioneurotic edema and anaphylactoid reaction.

Ophthalmologic:

A peculiar skin-eye syndrome has been recognized as an adverse effect following long-term treatment with phenothiazines. This reaction is marked by progressive pigmentation of areas of skin or conjunctiva and/or discoloration of the exposed sclera and cornea. Opacities of the anterior lens and cornea described as irregular or stellate in shape have also been reported. Patients receiving higher doses of phenothiazines for prolonged periods should have periodic complete eye examinations.

General Systemic Events:

Sudden death has occasionally been reported in patients who have received phenothiazines. In some cases, the death was apparently due to cardiac arrest; in others, the cause appeared to be asphyxia due to failure of the cough reflex. In some patients, the cause could not be determined nor could it be established that the death was due to the phenothiazine.

Neuroleptic Malignant Syndrome:

As with other neuroleptic drugs, a symptom complex sometimes referred to as neuroleptic malignant syndrome (NMS) has been reported. Cardinal features of NMS are hyperpyrexia, muscle rigidity, altered mental status (including catatonic signs) and evidence of autonomic instability (irregular pulse or unstable blood pressure). Additional signs may include elevated CPK, myoglobinuria (rhabdomyolysis), and acute renal failure. NMS is rare but potentially fatal and therefore requires intensive symptomatic and supportive treatment. Immediate discontinuation of neuroleptic treatment is mandatory. NMS has been successfully managed with various agents e.g. dantrolene and bromocriptine or amantadine. A toxicology reference should be consulted for detailed information.

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Overdose

Symptoms:

Parkinsonism, acute dystonias, somnolence, seizures, dry mouth, blurred vision, urinary retention, tachycardia, cardiac arrhythmias, hypotension, hypothermia or hyperthermia.

Treatment:

Empty stomach using gastric lavage. Administer activated charcoal and a saline cathartic. Repeat activated charcoal and cathartic every 4 to 6 hours to speed elimination. Support respiratory and cardiac functions as needed. Maintain fluid and electrolyte balance. Treat hypotension with i.v. fluids and by placing the patient in shock position. If unresponsive, dopamine may be required. Seizures may be treated with i.v. diazepam. Treat arrhythmias with phenytoin. Acute dystonic reactions may be treated with i.v. diphenydramine, benztropine or trihexyphenidyl. Hemodialysis is ineffective. Hemoperfusion may be effective in severe cases but is usually not necessary.

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Dosage

Adults:

Oral:

In general medicine and psychiatry, average daily oral dose of 25 to 75 mg (mild cases) or 75 to 150 mg (more severe cases) in 2-4 divided doses. It is occasionally necessary to give a higher dosage which, when increased gradually, can reach 900 mg or more per day in some psychiatric patients. Optimum therapeutic response may not occur for weeks or months.

Once the optimum dosage has been reached, it is maintained as long as necessary for the control of symptoms during the critical phase of the illness. Eventually, however, it should be gradually reduced so that the patient can be maintained on the lowest effective dosage.

Elderly and debilitated patients should start with initial doses at the lowest end of the dosage range (e.g. 25 mg daily). Such patients are more susceptible to hypotension and CNS effects and special caution should be exercised when using chlorpromazine in this age group.

During maintenance treatment, if it becomes desirable to reduce the number of daily drug administrations, the dosage may be administered once or twice daily, with the largest dose at bedtime.

Parenteral:

The usual single parenteral dose ranges from 25 to 50 mg and can be repeated 3 or 4 times per day. Elderly or debilitated patients may require lower dosages. The i.m. route is used primarily when rapid action is required to control acute severe symptomatology. Administer by slow deep i.m. injection into upper quadrant of buttock. Oral administration should be substituted as soon as possible. To minimize the occurrence of hypotension keep patient lying down for at least 30 minutes after injection.

Chlorpromazine ampuls should be protected from light. Pink or discolored solutions should be discarded.

Rectal:

100 to 300 mg daily.

Children:

Oral:

Usual single dose is 0.5 mg/kg. This dose may be repeated every 4 to 6 hours as necessary.

Parenteral:

Usual single dose is 0.5 mg/kg i.m. This dose may be repeated every 6 to 8 hours as necessary. Children 6 months to 5 years (up to 23 kg) should receive no more than 40 mg/day. Children 5 to 12 years (23 to 46 kg) should receive no more than 75 mg/day, except in unmanageable cases where dosages can be carefully titrated upward.

Rectal:

The usual rectal dose is 1 mg/kg which can be repeated every 4 to 6 hours as necessary.

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Research

The research information is available separately on Internet Mental Health.

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Note: This information is from a Canadian monograph. There can be differences in indications, dosage forms and warnings for this drug in other countries.

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Internet Mental Health (www.mentalhealth.com) copyright © 1995-2008 by Phillip W. Long, M.D.

This is what I found on this med....

JB

Thanks for that.

I didnt undersand a great but I know it is a serious drug and not to be handed out lightly which is funny as that is exactly what he did. I have taken a quarter 2 nights ago instead of 5 mg of Nitrazepam and was a lot more sedating and felt kind of spaced out. Not a particularly unpleasent experiemce but I feel a bit like I did about LSD all those years ago. Very wary. I dont know if I would be brave enoygh to take a whole one! I do know they are not recommemnded for Benzo withdrawal as can exhasperate w/ds.

Dr Who,

Is there anyway you can get away from all of the chemicals?  You know there's only one true way out of this, don't you?  You're a smart guy, you've been around the block a couple of times.  We know how this works don't we?

Pam