Chlorpromazine

 Risk Factor: C
 Class: CENTRAL NERVOUS SYSTEM DRUGS / Tranquilizers

Contents of this page:

Fetal Risk Summary
Breast Feeding Summary
References
Questions and Answers

Fetal Risk Summary

Chlorpromazine is a propylamino phenothiazine. The drug readily crosses the placenta (1,2,3 and 4). Reproductive studies in rodents have shown a potential for embryotoxicity, increased neonatal mortality, and decreased offspring performance (5). In animals, selective accumulation and retention occur in the fetal pigment epithelium (6). Although delayed ocular damage from high prolonged doses in pregnancy has not been reported in humans, concern has been expressed for this potential toxicity (6,7).

Chlorpromazine has been used for the treatment of nausea and vomiting of pregnancy during all stages of gestation, including labor, since the mid-1950s (8,9 and 10). The drug seems to be safe and effective for this indication. Its use in labor to promote analgesia and amnesia is usually safe, but some patients, up to 18% in one series, have a marked unpredictable fall in blood pressure that could be dangerous to the mother and the fetus (11,12,13,14 and 15). Use of chlorpromazine during labor should be discouraged because of this adverse effect.

One psychiatric patient, who consumed 8000 mg of chlorpromazine in the last 10 days of pregnancy, delivered a hypotonic, lethargic infant with depressed reflexes and jaundice (4). The adverse effects resolved within 3 weeks.

An extrapyramidal syndrome, which may persist for months, has been observed in some infants whose mothers received chlorpromazine near term (16,17,18,19 and 20). This reaction is characterized by tremors, increased muscle tone with spasticity, and hyperactive deep tendon reflexes. Hypotonicity has been observed in one newborn and paralytic ileus in two after exposure at term to chlorpromazine (4,21). However, most reports describing the use of chlorpromazine in pregnancy have concluded that it does not adversely affect the fetus or newborn (22,23,24,25,26 and 27).

The Collaborative Perinatal Project monitored 50,282 mother-child pairs, 142 of whom had 1st trimester exposure to chlorpromazine (28). For use anytime during pregnancy, 284 exposures were recorded. No evidence was found in either group to suggest a relationship to malformations or an effect on perinatal mortality rate, birth weight, or intelligence quotient scores at 4 years of age. Opposite results were found in a prospective French study that compared 315 mothers exposed to phenothiazines during the 1st trimester with 11,099 nonexposed controls (29). Malformations were observed in 11 exposed infants (3.5%) and in 178 controls (1.6%) (p<0.01). In the phenothiazine group, chlorpromazine was taken by 57 women who produced four infants with malformations: Syndactyly Microcephaly, clubfoot/hand, muscular abdominal aplasia (also exposed to acetylpromazine) Endocardial fibroelastosis, brachymesophalangy, clinodactyly also exposed to pipamazine) Microcephaly (also exposed to promethazine) The case of microcephaly, although listed as a possible drug-induced malformation, was considered by the authors to be more likely a genetic defect since the mother had already delivered two previous children with microcephaly (29). However, even after exclusion of this case, the association between phenothiazines and malformations remained significant (29). In another report, a stillborn fetus delivered at 28 weeks with ectromelia and omphalocele was attributed to the combined use of chlorpromazine and meclizine in the 1st trimester (30).

In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 36 newborns had been exposed to chlorpromazine during the 1st trimester (F. Rosa, personal communication, FDA, 1993). No major birth defects were observed (two expected).

In an in vitro study, chlorpromazine was shown to be a potent inhibitor of sperm motility (31). A concentration of 53 mmol/L produced a 50% reduction in motility.

Using data from the CPP, researchers discovered that offspring of psychotic/neurotic mothers who had consumed chlorpromazine or other neuroleptics for more than 2 months during gestation, whether or not they were breast fed, were significantly taller than nonexposed controls at 4 months, 1 year, and 7 years of age (32). At 7 years of age, the difference between the exposed and nonexposed groups was approximately 3 cm. The mechanisms behind these effects were not clear, but may have been related to the dopamine receptor-blocking action of the drugs.

In summary, although one survey found an increased incidence of defects and a report of ectromelia exists, most studies have found chlorpromazine to be safe for both mother and fetus if used occasionally in low doses. Other reviewers have also concluded that the phenothiazines are not teratogenic (26, 33). Another review concluded that because of its extensive clinical experience, chlorpromazine should be included among the treatments of choice if antipsychotic therapy was required during pregnancy (34). However, use near term should be avoided due to the danger of maternal hypotension and adverse effects in the newborn.

Breast Feeding Summary

Chlorpromazine is excreted into breast milk in very small concentrations. Following a 1200 mg oral dose (20 mg/kg), peak milk levels of 0.29 mg/mL were measured at 2 hours (35). This represented a milk:plasma ratio of less than 0.5. The drug could not be detected following a 600 mg oral dose. In a study of four lactating mothers consuming unspecified amounts of the neuroleptic, milk concentrations of chlorpromazine ranged from 798 ng/mL with maternal serum levels ranging from 1652 ng/mL (36). In two mothers, more of the drug was found in the milk than in the plasma. Only two of the mothers breast-fed their infants. One infant, consuming milk with a level of 7 ng/mL, showed no ill effects, but the second took milk containing 92 ng/mL and became drowsy and lethargic.

With the one exception described above, there has been a lack of reported adverse effects in breast-fed babies whose mothers were ingesting chlorpromazine (26). Based on this report, however, nursing infants exposed to the agent in milk should be observed for sedation. The American Academy of Pediatrics classifies chlorpromazine as an agent whose effect on the nursing infant is unknown but may be of concern because of the drowsiness and lethargy observed in the infant described above, and because of the galactorrhea induced in adults (37).

References

1. Franchi G, Gianni AM. Chlorpromazine distribution in maternal and fetal tissues and biological fluids. Acta Anaesthesiol (Padava)1957;8:197207.
2. Moya F, Thorndike V. Passage of drugs across the placenta. Am J Obstet Gynecol 1962;84:177898.
3. O'Donoghue SEF. Distribution of pethidine and chlorpromazine in maternal, foetal and neonatal biological fluids. Nature 1971;229:1245.
4. Hammond JE, Toseland PA. Placental transfer of chlorpromazine. Arch Dis Child 1970;45:13940.
5. Product information. Thorazine. SmithKline Beecham Pharmaceuticals, 2000.
6. Ullberg S, Lindquist NG, Sjostrand SE. Accumulation of chorio-retinotoxic drugs in the foetal eye. Nature 1970;227:12578.
7. Anonymous. Drugs and the fetal eye. Lancet 1971;1:122.
8. Karp M, Lamb VE, Benaron HBW. The use of chlorpromazine in the obstetric patient: a preliminary report. Am J Obstet Gynecol 1955;69:7805.
9. Benaron HBW, Dorr EM, Roddick WJ, et al. Use of chlorpromazine in the obstetric patient: a preliminary report I. In the treatment of nausea and vomiting of pregnancy. Am J Obstet Gynecol 1955;69:7769.
10. Sullivan CL. Treatment of nausea and vomiting of pregnancy with chlorpromazine. A report of 100 cases. Postgrad Med 1957;22:42932.
11. Harer WB. Chlorpromazine in normal labor. Obstet Gynecol 1956;8:19.
12. Lindley JE, Rogers SF, Moyer JH.Analgesic-potentiation effect of chlorpromazine during labor; a study of 2093 patients. Obstet Gynecol 1957;10:5826.
13. Bryans CI Jr, Mulherin CM. The use of chlorpromazine in obstetrical analgesia. Am J Obstet Gynecol 1959;77:40611.
14. Christhilf SM Jr, Monias MB, Riley RA Jr, Sheehan JC. Chlorpromazine in obstetric analgesia. Obstet Gynecol 1960;15:6259.
15. Rodgers CD, Wickard CP, McCaskill MR. Labor and delivery without terminal anesthesia. A report of the use of chlorpromazine. Obstet Gynecol 1961;17:925.
16. Hill RM, Desmond MM, Kay JL. Extrapyramidal dysfunction in an infant of a schizophrenic mother. J Pediatr 1966;69:58995.
17. Ayd FJ Jr, ed. Phenothiazine therapy during pregnancy-effects on the newborn infant. Int Drug Ther Newslett 1968;3:3940.
18. Tamer A, McKay R, Arias D, Worley L, Fogel BJ. Phenothiazine-induced extrapyramidal dysfunction in the neonate. J Pediatr 1969;75:47980.
19. Levy W, Wisniewski K. Chlorpromazine causing extrapyramidal dysfunction in newborn infant of psychotic mother. NY State J Med 1974;74:6845.
20. O'Connor M, Johnson GH, James DI. Intrauterine effect of phenothiazines. Med J Aust 1981;1:4167.
21. Falterman CG, Richardson J. Small left colon syndrome associated with maternal ingestion of psychotropic drugs. J Pediatr 1980;97:30810.
22. Kris EB, Carmichael DM. Chlorpromazine maintenance therapy during pregnancy and confinement. Psychiatr Q 1957;31:6905.
23. Kris EB. Children born to mothers maintained on pharmacotherapy during pregnancy and postpartum. Recent Adv Biol Psychiatry 1962;4:1807.
24. Kris EB. Children of mothers maintained on pharmacotherapy during pregnancy and postpartum. Curr Ther Res 1965;7:7859.
25. Sobel DE. Fetal damage due to ECT, insulin coma, chlorpromazine, or reserpine. Arch Gen Psychiatry 1960;2:60611.
26. Ayd FJ Jr. Children born of mothers treated with chlorpromazine during pregnancy. Clin Med 1964;71:175863.
27. Loke KH, Salleh R. Electroconvulsive therapy for the acutely psychotic pregnant patient: a review of 3 cases. Med J Malaysia 1983;38:1313.
28. Slone D, Siskind V, Heinonen OP, Monson RR, Kaufman DW, Shapiro S. Antenatal exposure to the pheothiazines in relation to congenital malformations, perinatal mortality rate, birth weight, and intelligence quotient score. Am J Obstet Gynecol 1977;128:4868.
29. Rumeau-Rouquette C, Goujard J, Huel G. Possible teratogenic effect of phenothiazines in human beings. Teratology 1976;15:5764.
30. O'Leary JL, O'Leary JA. Nonthalidomide ectromelia; report of a case. Obstet Gynecol 1964;23:1720.
31. Levin RM, Amsterdam JD, Winokur A, Wein AJ. Effects of psychotropic drugs on human sperm motility. Fertil Steril 1981;36:5036.
32. Platt JE, Friedhoff AJ, Broman SH, Bond RN, Laska E, Lin SP. Effects of prenatal exposure to neuroleptic drugs on children's growth. Neuropsychopharmacology 1988;1:20512.
33. Ananth J. Congenital malformations with psychopharmacologic agents. Compr Psychiatry 1975;16:43745.
34. Elia J, Katz IR, Simpson GM. Teratogenicity of psychotherapeutic medications. Psychopharmacol Bull 1987;23:53186.
35. Blacker KH, Weinstein BJ, Ellman GL. Mothers milk and chlorpromazine. Am J Psychol 1962;114:1789.
36. Wiles DH, Orr MW, Kolakowska T. Chlorpromazine levels in plasma and milk of nursing mothers. Br J Clin Pharmacol 1978;5:2723.
37. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:13750.
    
    

Questions and Answers

What is usual dosage of chlorpromazine for someone suffering from agitation and anxiety?, I have been prescribed 25mg 3 times daily. Is this normal? Should I feel as tired and zoned out as I do.

Chlorpromazine is a very old major tranquiliser which is not used very often at all now(in the UK anyway) due to nasty side effects.If you are taking this i would advise you to see your doc and get this reviewed, there a re loads of more suitable drugs on the market now which would be more beneficial and with less side effects.

What's the difference between poikilothermic effect of chlorpromazine and the antipyretic effect of aspirin., pharmacology...

Chlorpromazine is used for people with schizophrenia. Schizophrenics need more dopamine receptors active. The effect of chlorpromazine is to raise the level of a neurotransmitter. The effect of aspirin is to thin the blood.

Is mellaril ok to use for my awful anxiety instead of chlorpromazine?, Switching to mellaril want to make sure its ok

I am not a medical doctor but have taken both Mellaril and Chlorpromazine for psychosis. They are extremely old medications. If you have anxiety there are much more current medications for this. You might look up "Medications for anxiety disorders" under Yahoo! search to find out what is available and discuss them with your doctor. There is also a natural medication for anxiety, Melatonin, which is available without prescription.

Both Mellaril and chlorpromazine have bad side effects, chlorpromazine being the worst. Tardive diskonesia sometimes develops which is a parkinsonism like tremor due to nerve damage. I developed it after years of taking the medication trifluoperazine, which is a related drug.

Good health, good luck, peace and love!

I am on chlorpromazine for anxiety/to help me sleep. I know it is an old-fashioned drug-anyone else on it?,

im not sure if its the same or similar but i was on promazine to help me get off an antidepressant withdrawal.i found it better than diazepam.i also found it easy to stop.it is an old drug but it is used to treat alot of things even travel sickness.its an antipsychotic which freaked me out at first.it can cause involuntary movements of the limbs though so try to keep the dose as though as possible.i got a bit of twitching in my fingers but it stopped soon after i stopped them.

LSD with Chlorpromazine?, if you are tripping on LSD and took Chlorpromazine would your trip instantly go away?

I remember way back in the day that citrus would make you come down. My friend used to keep a bottle of lemon juice in the refrigerator. That strong lemon juice in the green bottle- like the kind in the plastic lemons from the store.
The use of chlorpromazine has been largely replaced by newer generation of atypical antipsychotics which are generally better tolerated. Chlorpromazine is classified as a low-potency antipsychotic and in the past was used in the treatment of both acute and chronic psychoses, including schizophrenia and the manic phase of manic depression as well as amphetamine-induced psychoses.

Chlorpromazine formerly was the drug of choice to treat LSD (and other psychedelic/hallucinogen) intoxication in a hospital setting, resulting in it gaining an erroneous reputation as the LSD antidote. Now haloperidol is more commonly used in such situations

Is Chlorpromazine a tranquilizer?,

It is a "major tranquiliser" which is basically an anti-psychotic but can be used for a variety of reasons in mental health. There are newer drugs with less side effects that do the same job though! Could be prescribed for a variety of reasons.

How can I get the drug I want? (Chlorpromazine)?, Okay. My mom has had a BAD case chronic hiccups for around 4 days now. They're stopping her from sleeping, eating, or even BREATHING. She's been to 2 GPs and the hospital (CGH), but the drugs they prescribed aren't helping much.

I finally did some research online and found out that the drugs she's on DON'T HELP. They're mostly for nausea, or anti-depressants. One of them even exacerbates hiccups (Valium).

Anyway, I read on http://www.emedicine.com/emerg/topic252.... that Chlorpromazine and Metoclopramide are the most common drug used to cure hiccups. Since the doctors we've been to didn't prescribe them, my question is, how do we go about obtaining them? Can we maybe call up a clinic and ask if they have the drug available? Or the hospital pharmacy?

Thanks in advance!

I suggest going back to your dr. and telling him that you've done your research and what you have learned the meds they are prescribing arent what she needs and that she needs one of the other two. It might work, it does when i take my 3 yr old to the nuerologists. They will usually listen to you because you are her advocate right now you know whats goin on and see it first hand all day they dont. try it

Why do i keep getting a terrible feeeling of fear?, Hi there I have been to a psychiatrist and they say I dont have a mental llness. I am on chlorpromazine and cipramil but they dont seem to help. But all the time I seem to be scared of everything including myself. I fear my own existence. I am on nervous disability. I just wish someone could take this fear away please as its ruining my life. Doe anyone have any ideas about what I could do. I would really apprciate it. Also I have tried relaxation therapy but nothing takes this fear away. Please help

First you need to find a new doctor ! What you are feeling of course is not normal. And if you are taking such meds. they had to be prescribed for a reason. If they are not helping there are a million other meds. out there for what you are describing and therapy would need to be included. So please seek help from another doctor.

Where can I find a list of Caveolae and Clathrin pathway inhibitors?, I need info on the endocytosis pathway inhibitor drugs such as Ginestein, Nystatin, Fillipn, Chlorpromazine.

I need a list of them. Is there any list of these inhibitors.

Thanks.

1.Here is an medical journal article that has some inhibitors mainly dependent on clathrin
http://www.pubmedcentral.nih.gov/article...
HAVE A LOOK AT THE REFERENCE PAGE at the bottom and you have a plenty of publication with information
Here is one of them
http://www.ncbi.nlm.nih.gov/pubmed/16051...

2. This artile may be useful for you. here the endocytosis pathway is blocked by an inhibitor called nimodipin
http://www.nature.com/cgi-taf/DynaPage.t...
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3. Some more links related with the subject matter......
http://jcs.biologists.org/cgi/content/fu...
http://iai.asm.org/cgi/content/abstract/...

People's experiences with Chlorpromazine (Thorazine) ?, Just would like to know opinions of anyone who has been using this drug, as even taking 100-125mg at once doesn't affect me?

Before you jump to conclusions (Like my last question which was removed for the amount of abuse i got) i am not a junkie, i am on prescribed medications for severe anxiety and a personality disorder.

I have used Diazepam in the past, which worked, but i came off it as i know there's a risk of addiction with Valiums.

I would love to hear others experiences with this drug, and/or any others that you could recommend trying?

Thank you in advance.

Hi,

I have been perscribed Chlorpromazine on a 'take when needed basis' due to having extreme depression/ anxiety/ BPD and self harming problems. Each tablet I have is only 25mgs and I have only taken two at a time before. I don't take it often but I find if i take one 25mg tablet it doesn't do much, it may take teh tiniest edge off my problems. 50mgs helps more however after an hour after taking it I am so drowsy that I have to go to sleep before I just collapse and I usually have avery high tolerance level of taking tablets that induce drowsiness. I couldn't imagine taking 100-125mgs however I know some people,like yourself do.

I think your best bet is to go to see your GP or make an appointment with your psychiatrist and explain chlorpromazine isn't working for you, even at high doses and your concerns about being on diazepam- perhaps they can put your mind at ease about it and at least it did work for you..but definately ask one of them whats best

best of luck
x