Postpartum Psychosis Induced by Bromocriptine and Pseudoephedrine

■ brief report Postpartum Psychosis Induced by Bromocriptine and Pseudoephedrine

Roy R. Reeves, DO, PhD, and Harold B. Pinkofsky, MD, PhD Shreveport, Louisiana

Bromocriptine is an ergot-derived dopamine agonist sometimes used for postpartum suppression of lactation. On rare occasions (a total of seven previous reports in the literature), use of the medication has been associated with psychotic symptomatology in postpartum patients. This case report describes a 19-year-old postpartum woman who developed severe psychotic symptoms while taking low doses of bromocriptine and pseudoephedrine. The use of bromocriptine for suppression of lactation is controversial. If prescribed for postpartum patients, bromocrip tine alone or in combination with sympathomimetic drugs should be used only with caution.

KEY WORDS. Bromocriptine; pseudoephedrine; lactation; puerperium; psychotic disorders. (J Fam Pract 1997; 44:164-166)

romocriptine is a semisynthetic ergot dopamine activity. There have been seven reported alkaloid that acts as a dopamine receptor cases o f psychotic symptoms in patients with no his agonist. Its current uses include the treat tory of psychosis for whom bromocriptine was used ment of Parkinson’s disease (optimal for postpartum lactation suppression.3-711 Symptoms dosage 40 to 60 mg daily), prolactinomas described included delusions, hallucinations, and andB acromegaly (usually in dosages o f 7.5 to 30 mg mania. The incidence of postpartum psychosis in per day), and amenorrhea and galactorrhea sec primiparous women is about 1 in 500; after a subse ondary to neuroleptic use.1 The prolactin-producing quent delivery, the risk is about 1 in 3 for previously cells of the anterior pituitary appear to be inhibited affected women.12 Thus, these cases may represent by dopamine. Randomized clinical trials of coincidental occurrence in patients taking bromocriptine vs placebo demonstrating the effica bromocriptine. Postpartum psychosis usually devel cy o f the drug led to the use of bromocriptine at low ops between the 3rd and 14th day postpartum and dosages o f 2.5 mg every 12 hours for 14 days for the may begin with confusion, depersonalization, and inhibition of postpartum lactation.23 Although no insomnia, and then progress rapidly to delirium with drug should be routinely used to prevent postpartum prominent hallucinations and delusions. Rapidly lactation, the texbook Williams Obstetrics, in its changing states o f mania and deep depression may 1993 edition,4 reported that the use o f bromocriptine occur, as well as outbursts o f florid psychosis. for this purpose was “widespread.” As reported in Many sympathomimetic drugs may cause or exac the next edition of the textbook 4 years later,5 the erbate psychotic symptoms, presumably by Physicians’ Desk Reference had subsequently dopaminergic stimulation. This is seen most com removed lactation suppression as an indication for monly with amphetamine and cocaine, but may also using bromocriptine. occur with several less potent drugs, including over- Psychiatric side effects of bromocriptine include the-counter sympathomimetics.13 Psychotic symp hallucinations, delusions, confusion, and mania.6 toms induced by pseudoephedrine have occurred These symptoms are thought to result from excess primarily in patients with an underlying psychiatric disorder or after use o f relatively large doses.1416 Submitted, revised, April 15, 1997. From the Departments o f Psychiatry, Overton Brooks VA Ca s e R e p o r t Medical Center (R.R.R.) and Louisiana State University School of Medicine in Shreveport (H.B.P.), Shreveport, Louisiana. Requests fo r reprints should be addressed to Roy The patient was a 21-year-old white woman, para 8 R. Reeves, DO, PhD, Chief of Psychiatry (116A), Overton gravida 1, who gave birth to a healthy male infant Brooks VA Medical Center, 510 East Stoner, Shreveport, LA without complications. Her prenatal course had 71101-4295.

been uneventful, and her postnatal examinations regimen, 2 days after which her symptoms became were reported unremarkable. She was given marked. Some bromocriptine psychoses, however, bromocriptine, 2.5 mg twice daily, which she took have had their onset as late as 8 to 10 days postpar without any problem for 9 days. On the 9th day she tum. It is conceivable that, since the puerperium is a began taking an over-the-counter preparation of period associated with an increased incidence of pseudoephedrine, 60 mg four times daily. On the psychosis, some such cases may represent postpar next day she was depressed and cried a large part of tum psychosis in patients coincidentally taking the day. She then became hyperactive and delusion bromocriptine. It is clear, however, that bromocrip al, sleeping very little over the next 3 days. She was tine can cause psychosis when given in larger doses brought to the hospital by family members, who felt for pituitary adenoma and Parkinson’s disease. they could not control her. They described her as The above and other such reports suggest that “talking silly” and impossible to “settle down.” bromocriptine may cause psychosis even when Her past psychiatric history was unremarkable, as given in low doses. The mechanism by which this was her medical history. She denied using drugs occurs is probably dopaminergic stimulation. We except for rare use o f marijuana and beer. There was postulate that the psychotic symptoms in this patient no family history o f psychiatric disorder. were secondary to the synergistic effects of both An examination showed her to be alert and hyper bromocriptine and pseudoephedrine on the active. Her mood was elevated and expansive. Her dopaminergic system. It is also likely that the speech was pressured. Her thought processes were increased vulnerability of certain patients to psy tangential with flight of ideas. Her thought content chosis in the puerperium increases the likelihood o f was delusional, including an unfounded belief that their developing psychosis when exposed to she could earn $100,000 per year as a beautician and bromocriptine or other sympathomimetic medica that she had recently bought a new house and a new tions during that period. Wiry certain patients are expensive car. Extremely grandiose ideas about her more vulnerable to psychosis during the postpartum abilities and future plans were stated repeatedly. period remains unknown, but may be related to fluc Results of a physical examination were within tuations in hormonal and neurotransmitter levels. normal limits. Findings from laboratory studies, Because postpartum psychosis is a psychiatric including complete blood count, chemistry survey, emergency that may endanger the mother and her and thyroid function, were also within normal limits. infant, hospitalization and aggressive treatment, A rapid plasma reagin test was nonreactive. A urine sometimes with electroconvulsive therapy, are often drag screening test was negative. necessary. Clinicians should be aware of the poten Bromocriptine and pseudoephedrine were dis tial for medication-induced psychosis so that more continued. She was treated with orally administered conservative treatment, ie, discontinuation of the haloperidol, 5 mg twice daily, and benztropine, 1 mg offending medication, observation, and possibly twice daily. Her symptoms improved slowly and she administration of an antipsychotic agent, may be was discharged 3 days later, still taking these med used before resorting to more aggressive measures. ications. They were discontinued after complete res It should be stressed that bromocriptine is no olution of her symptoms during the following week. longer recommended for routine use in the suppres Subsequently, she had no recurrence of symptoms. sion o f postpartum lactation. In 1994, the Sandoz Twenty months later she gave birth to another Corporation voluntarily withdrew the use of healthy infant. Bromocriptine was not prescribed. bromocriptine (Parlodel) for this purpose because of No psychiatric symptoms occurred during that post concern about reports associating the drug with partum period. strokes, myocardial infarction, seizures, and psychi atric disturbances during the puerperium.1718 While it D is c u s s io n is not totally clear whether these complications were due to bromocriptine or to the increased incidence In this case, the patient appears to have developed of such events during the puerperium, the withdraw psychosis secondary to the combination of low-dose al was undertaken out o f concern that the ablacta bromocriptine and pseudoephedrine. No symptoms tion issue might have a negative impact on the pre were noted until pseudoephedrine was added to the scription of bromocriptine for the treatment of other

The Journal o f Fam ily Practice, Vol. 45, No. 2 (A u g), 1997 1 65 POSTPARTUM PSYCHOSic

medical problems such as Parkinson’s disease, 3. Canterbury RJ, Haskins B, Kahn N, et al. Postpartum psy. hyperprolactinema, infertility, and certain tumors.18 chosis induced by bromocriptine. South Med J 1987; 80:1463- 4. It is also important to be aware that an advisory com 4. Cunningham FG, MacDonald PC, Leveno KJ, Gant NF mittee of the Food and Drug Administration (FDA) Gilstrap LC. Williams obstetrics. 19th ed. Norwalk, Conn' recommended that medications should no longer be Appleton & Lange, 1993:647. 5. Cunningham FG, MacDonald PC, Gant NF, Leveno KJ, used for lactation suppression, but expressed no Gilstrap LC, Hankins GVD, Clark SL. Williams obstetrics. 20th opinion on the safety of bromocriptine for lactation ed. Norwalk, Conn: Appleton & Lange, 1997:563-4. suppression.19 6. Boyd A. Bromocriptine and psychosis: a literature review. Psychiatr Q 1995; 66(l):87-95. The simplest method of lactation suppression 7. Brook NM, Cookson IB. Bromocriptine induced mania? [let consists o f support with a comfortable binder, and ter] BMJ 1978; 1:790. application o f cold packs and mild analgesics for 8. Vlissides DN, Gill D, Castelow J. Bromocriptine induced mania? [letter] BMJ 1978; 1:510. pain. Bromocriptine should be considered only if 9. Iffy L, Lindenthal J, Szodi Z, et al. Puerperal psychosis follow severe mammary engorgement develops in spite of ing ablaction with bromocriptine. Med Law 1989; 8(2):1714. conservative treatment.4,6 If bromocriptine is used, 10. Kemperman CJF, Zwanniken GJ. Psyciatric side effects of bromocriptine therapy for postpartum galactorrhea. J R Soc clinicians should be aware o f potential psychiatric M ed 1987; 80:387-8. complications that may occur even at low doses. The 11. Lake CR, Reid A, Martin C, et al. Cyclothymic disorder and bromocriptine: predisposing factors for postpartum mania? potential medicolegal dangers of using a medication Can J Psychiatry 1987; 32:6934. for a purpose not approved by the FDA should be 12. Parry BL. Postpartum psychiatric syndromes. In: Kaplan HI, seriously considered in the risks-vs-benefits assess Sadock BJ, eds. Comprehensive textbook o f psychiatry/VI. Baltimore, Md: Williams & Wilkins, 1995:1059-66. ment of whether to use bromocriptine for lactation 13. Manshreck TC. Delusional disorder and shared psychotic dis suppression. Clinicians should also be cautious in order. In: Kaplan HI, Sadock BJ, eds. Comprehensive text book of psychiatryA'I. Baltimore Md: Williams & Wilkins, using combinations o f bromocriptine and sympath- 1995:1031-49. omimetics in postpartum cases. Bromocriptine 14. Dalton R. Mixed bipolar disorder precipitated by pseu- alone, or in combination with sympathomimetic doephedrine hydrochloride. South Med J 1990; 83:64-5. 15. Leighton KM. Paranoid psychosis after abuse o f Actifed. BMJ drugs, should be used only with extreme caution in 1982; 284:789-90. patients with a past history of psychosis or mania, as 16. Diaz MA, Wise TN, Semchyshyn GO. Self-medication with such patients would be at a higher risk for psychi pseudoephedrine in a chronically depressed patient. Am J Psychiatry 1979; 136:1217-18. atric complications. 17. Rayburn WF. C linical com m entary: the bromocriptine (Parlodel) controversy and recommendations for lactation REFERENCES suppression. Am J Perinatal 1996; 13:69-71. 1. Barbieri RL, Ryan KJ. Bromocriptine: endocrine pharmacolo 18. Morgans D. Brom ocriptine and postpartum lactation. Br J gy and therapeutic applications. Fertil Steril 1983; 39:727-41. Obstet G ynaecol 1995; 102:851-3. 2. Duchesne C, Leke R. Bromocriptine mesylate for prevention 19. Stehlin D. FDA consumer bulletin 1990. Washington, DC: US o f postpartum lactation. Obstet Gynecol 1981; 37:464-7. Food and Drug Administration, 1990:25-7.

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