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Letters to the Editor
Published Online: 1 March 2017

Haloperidol-Associated Uterine Dystonia

To the Editor: Haloperidol is a first-generation antipsychotic recommended for psychosis in pregnancy (1). Up to 60% of patients on first-generation antipsychotics develop an acute dystonia (2). Haloperidol could induce uterine or fetal dystonia (3), although this has not been previously reported. We report the case of a pregnant 27-year-old woman who experienced uterine dystonia associated with haloperidol:
A 27-year-old woman presented during her second pregnancy at 25 weeks’ gestation. She had a history of depressive disorder (unspecified) and anxiety disorder (unspecified) and was admitted for depression. At admission she was taking clonazepam only. Clonazepam was discontinued, and on admission day, she was administered 5 mg of haloperidol as needed for anxiety or agitation. Prior to this hospitalization, the patient was antipsychotic-naive and received nine doses over 3 days. On admission day 4, 2 hours after taking haloperidol, she developed cervical and limb dystonia, uterine contractions lasting 30–45 seconds spaced 10 minutes apart, and increased fetal movements. Uterine tone was moderate. Treatment with 2 mg of benztropine partially improved the cervical and limb dystonia; she continued to report contractions. After receiving 50 mg of diphenhydramine and 1 mg of benztropine, she was sent for emergent obstetric evaluation. Her cervical and limb dystonia resolved, contractions continued at the same rate, and increased fetal movements were noted. Contractions stopped 10 hours later; fetal status was reassuring. She was discharged for continued psychiatric management.
Haloperidol is a D2 antagonist associated with adverse obstetric and neonatal outcomes (4) that may potentiate uterine contractility (5). D2 antagonists increase oxytocin release (6), and haloperidol enhances adenosine receptor function during uterine muscle contraction (7). In addition, haloperidol modulates intracellular calcium pathways associated with myometrial contractility (8). Haloperidol crosses the placenta and is detectable in newborns of mothers taking haloperidol (3). Newborns exposed to antipsychotics in the third trimester are at risk for extrapyramidal symptoms (9); similar symptoms could occur in utero. This case illustrates a potential complication of haloperidol with pregnancy and suggests the need for further research regarding this potential side effect.

References

1.
Chisolm MS, Payne JL: Management of psychotropic drugs during pregnancy. BMJ 2016; 532:h5918
2.
Burkhard PR: Acute and subacute drug-induced movement disorders. Parkinsonism Relat Disord 2014; 20(Suppl 1):S108–S112
3.
Uematsu T, Yamada K, Matsuno H, et al: The measurement of haloperidol and reduced haloperidol in neonatal hair as an index of placental transfer of maternal haloperidol. Ther Drug Monit 1991; 13:183–187
4.
Coughlin CG, Blackwell KA, Bartley C, et al: Obstetric and neonatal outcomes after antipsychotic medication exposure in pregnancy. Obstet Gynecol 2015; 125:1224–1235
5.
Voltolini C, Torricelli M, Conti N, et al: Understanding spontaneous preterm birth: from underlying mechanisms to predictive and preventive interventions. Reprod Sci 2013; 20:1274–1292
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Crowley WR, Parker SL, Armstrong WE, et al: Excitatory and inhibitory dopaminergic regulation of oxytocin secretion in the lactating rat: evidence for respective mediation by D-1 and D-2 dopamine receptor subtypes. Neuroendocrinology 1991; 53:493–502
7.
Trincavelli ML, Cuboni S, Catena Dell’osso M, et al: Receptor crosstalk: haloperidol treatment enhances A(2A) adenosine receptor functioning in a transfected cell model. Purinergic Signal 2010; 6:373–381
8.
Al Otaibi M: The physiological mechanism of uterine contraction with emphasis on calcium ion. Calcium Signal (St Clara) 2014; 1:70–75
9.
US Food and Drug Administration (FDA): FDA Drug Safety Communication: Antipsychotic drug labels updated on use during pregnancy and risk of abnormal muscle movements and withdrawal symptoms in newborns. Silver Spring, Md, FDA, Feb 22, 2011. http://www.fda.gov/Drugs/DrugSafety/ucm243903.htm

Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Pages: 296
PubMed: 28245696

History

Accepted: December 2016
Published online: 1 March 2017
Published in print: March 01, 2017

Keywords

  1. Antipsychotics
  2. Drug Side Effects-Extrapyramidal
  3. Emergency Psychiatry
  4. Women
  5. Dystonia
  6. Pregnancy

Authors

Affiliations

Kathryn K. Ridout, M.D., Ph.D.
From Butler Hospital and the Department of Psychiatry and Human Behavior, Brown University, Providence, R.I.
Samuel J. Ridout, M.D., Ph.D.
From Butler Hospital and the Department of Psychiatry and Human Behavior, Brown University, Providence, R.I.

Funding Information

National Institute of Mental Health10.13039/100000025: R25 MH101076
The authors report no financial relationships with commercial interests.

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