Benzodiazepines

Jul 26, 2018 | Articles

Benzodiazepines

Are benzodiazepines safe during pregnancy?

This is a great question. Unfortunately, there is not a simple answer. Benzodiazepines are not completely risk free, but neither is untreated maternal illness. Women should decide whether or not to take a benzodiazepine during pregnancy after consultation with a perinatal psychiatric specialist. Together, they can evaluate the risks and benefits of taking a benzodiazepine after considering the woman’s personal psychiatric history, preferences, and values.

Untreated maternal mental illness

Anxiety during pregnancy has been linked to bad outcomes. Research has found that prenatal anxiety is linked to a developing baby later having childhood emotional and behavioral problems.[i] Poor sleep in pregnancy also carries risks. Poor sleep has been linked to an increased risk of depression, decreased ability to cope with labor pains, increased risk of long labor duration, increased rates of preterm birth, and increased risks of Caesarean section. Insomnia can also be one of the first signs of mania or postpartum psychosis, which are psychiatric emergencies.[ii]

Mental illness during pregnancy is risky, often—but not always—more risky than the use psychiatric medications.

Benzodiazepines
Benzodiazepines are a type of anti-anxiety medication. They are also called hypnotics. They include alprazolam (Xanax), clonazepam (Klonopin), diazepam (Valium), lorazepam (Ativan), and temazepam (Restoril). Approximately 1 in 40 women take a hypnotic during pregnancy in the United States, and in Utah, at the time of delivery, approximately 1 in 170 women has detectable levels of a hypnotic in her blood.[iii]

Benefits of benzodiazepines in women with anxiety
Benzodiazepines are an effective treatment for anxiety disorders. When benzodiazepines are used in conjunction with psychotherapy, the benefits women experience may be greater than either treatment alone. Benzodiazepines act more quickly than antidepressants, so sometimes they are used to bridge patients until a woman is experiencing the anti-anxiety benefit of an antidepressant. Benzodiazepines can also be prescribed on an “as needed” basis for severe intermittent anxiety.[iv]

Benefits of benzodiazepines in women with insomnia
Benzodiazepines can decrease the time it takes for a woman to fall asleep. They also can help women stay asleep after falling asleep.[v]

Risks of benzodiazepines

Prior to pregnancy

  • Side effects
    It is possible for benzodiazepines to impair memory and make patients feel tired. They can also decrease respiratory drive in certain populations.[vi]
  • Addiction, dependence, withdrawal
    The human body can become dependent on benzodiazepines. With consistent use, perhaps almost a third of patients may develop dependence. Benzodiazepines, if taken regularly, should be tapered (not abruptly stopped), as abrupt discontinuation can lead to withdrawal symptoms, seizures, and, in rare cases, death.[vii]
  • Fertility
    There is no strong evidence that suggests benzodiazepines decrease fertility in women.[viii]

During pregnancy

  • Miscarriage
    There is not sufficient evidence to determine whether or not benzodiazepines are associated with miscarriage. There is evidence on both sides regarding this issue.[ix]
  • Congenital defects
    While individual studies have suggested the possibility of associations between benzodiazepines and certain congenital defects, the scientific literature as a whole does not show a consistent relationship between benzodiazepines and specific malformations. This can be interpreted to mean that any increased risk is either nonexistent or very low. One relatively large study suggested that perhaps alprazolam or diazepam might be associated with abnormalities of the alimentary track (i.e. stomach, intestines) but this study had some methodologic issues and another large study did not come to the same conclusion. Additionally, many of the other studies that suggest an association between benzodiazepines and malformations have serious flaws. The United Kingdom’s National Institute for Health and Care Excellence (excellence) has examined this question closely. It issued an opinion that existing research does not appear to show an association between benzodiazepines and congenital malformations. However, it also recommends that benzodiazepines only be used for short-term treatment of severe symptoms.

    Out of an abundance of caution, sometimes prescribers will attempt to avoid prescribing benzodiazepines to women until after a baby’s organ systems have developed.[x]

  • Preterm birth
    There may be an association between preterm birth and benzodiazepine use. However, this association was stronger for benzodiazepines taken later in pregnancy. The authors recognized that it could be that doctors were prescribing benzodiazepines to women who were anxious because they were already experiencing signs of preterm labor. Whether or not benzodiazepines can cause preterm birth has not been proven.[xi]
  • Low birth weight
    There is not sufficient evidence to suggest an association between benzodiazepines and low birth weight. While some studies examine this question, any conclusion would at this point be an overinterpretation of the data.[xii]

At delivery

  • Floppy infant syndrome
    Floppy infant syndrome has been associated with maternal benzodiazepine use near the time of delivery. This risk can be decreased by using benzodiazepines that remain in the body for shorter periods of time, that are less likely to cross the placenta, and that can be metabolized by the fetus. Again, benzodiazepines are perhaps best used for short-term treatment only.[xiii]
  • Neonatal withdrawal
    The human body can become dependent on benzodiazepines, meaning that after being on these medications for an extended period of time, withdrawal symptoms can develop if the medication is stopped abruptly. Withdrawal has been observed in neonates. Again, benzodiazepines are likely best used for short-term treatment.[xiv]

After delivery

  • Future development of the baby
    The majority of existing evidence suggests that maternal use of benzodiazepines during pregnancy has no effect on a baby’s development later in life.[xv]
  • Breastfeeding
    Breastfeeding is not absolutely contraindicated for women taking a benzodiazepine. While one study found approximately 1 in 60 infants of mothers on benzodiazepines experienced signs of benzodiazepine exposure, such as limpness or sleepiness, the authors of the study concluded that their study overall suggested that even women on benzodiazepines should breastfeed if possible.

    To minimize risks, intermittent maternal use, low doses, and short-acting agents are preferred. Babies are likely to do best when their mothers can tend to their needs. Sometimes this may require the mother to take an anxiolytic. In these cases, the benefits of the medication may very well outweigh the risks.[xvi]

 

Summary

Benzodiazepines during pregnancy are not entirely risk free, but neither is untreated maternal mental illness. Women should decide whether or not to take a benzodiazepine during pregnancy after consultation with a perinatal psychiatric specialist. Together, they can evaluate the risks and benefits of taking a benzodiazepine after considering the woman’s personal psychiatric history, preferences, and values.

[i]

  1. Glover V. Maternal depression, anxiety and stress during pregnancy and child outcome; what needs to be done. Best Pract Res Clin Obstet Gynaecol. 2014 Jan;28(1):25-35.

[ii]

  1. Sharma V, Smith A, Khan M. The relationship between duration of labour, time of delivery, and puerperal psychosis. J Affect Disord. 2004 Dec;83(2-3):215-20.
  2. Reichner CA. Insomnia and sleep deficiency in pregnancy. Obstet Med. 2015 Dec;8(4):168-71.

[iii]

  1. Andrade SE, Gurwitz JH, Davis RL, Chan KA, Finkelstein JA, Fortman K, McPhillips H, Raebel MA, Roblin D, Smith DH, Yood MU, Morse AN, Platt R. Prescription drug use in pregnancy. Am J Obstet Gynecol. 2004 Aug;191(2):398-407.
  2. Buchi KF, Suarez C, Varner MW. The prevalence of prenatal opioid and other drug use in Utah. Am J Perinatol. 2013 Mar;30(3):241-4.

[iv]

  1. Power KG, Simpson RJ, Swanson V, Wallace LA. Controlled comparison of pharmacological and psychological treatment of generalized anxiety disorder in primary care. Br J Gen Pract. 1990 Jul;40(336):289-94.
  2. Pollack MH. Refractory generalized anxiety disorder. J Clin Psychiatry. 2009;70 Suppl 2:32-8.
  3. Offidani E, Guidi J, Tomba E, Fava GA. Efficacy and tolerability of benzodiazepines versus antidepressants in anxiety disorders: a systematic review and meta-analysis. Psychother Psychosom. 2013;82(6):355-62.

[v]

  1. Buscemi N, Vandermeer B, Friesen C, Bialy L, Tubman M, Ospina M, Klassen TP, Witmans M. The efficacy and safety of drug treatments for chronic insomnia in adults: a meta-analysis of RCTs. J Gen Intern Med. 2007 Sep;22(9):1335-50.

[vi]

  1. Chen SJ, Yeh CM, Chao TF, Liu CJ, Wang KL, Chen TJ, Chou P, Wang FD. The Use of Benzodiazepine Receptor Agonists and Risk of Respiratory Failure in Patients with Chronic Obstructive Pulmonary Disease: A Nationwide Population-Based Case-Control Study. Sleep. 2015 Jul 1;38(7):1045-50.iazepines. Psychiatr Danub. 2010 Mar;22(1):90-3.
  2. Uzun S, Kozumplik O, Jakovljević M, Sedić B. Side effects of treatment with benzodiazepines. Psychiatr Danub. 2010 Mar;22(1):90-3

[vii]

  1. Marriott S, Tyrer P. Benzodiazepine dependence. Avoidance and withdrawal. Drug Saf. 1993 Aug;9(2):93-103. Review.

[viii]

  1. Wikner BN, Stiller CO, Källén B, Asker C. Use of benzodiazepines and benzodiazepine receptor agonists during pregnancy: maternal characteristics. Pharmacoepidemiol Drug Saf. 2007 Sep;16(9):988-94.
  2. Mialon O, Delotte J, Lehert P, Donzeau M, Drici M, Isnard V, et al. [Comparison between two analgesic protocols on IVF success rates]. J Gynecol Obstet Biol Reprod (Paris). 2011;40(2):137-43.
  3. Petric D, Peitl MV, Peitl V. High doses alprazolam induced amenorrhoea and galactorrhoea. Psychiatr Danub. 2011;23(1):123-4.

[ix]

  1. Wikner BN, Stiller CO, Bergman U, Asker C, Källén B. Use of benzodiazepines and benzodiazepine receptor agonists during pregnancy: neonatal outcome and congenital malformations. Pharmacoepidemiol Drug Saf. 2007 Nov;16(11):1203-10.
  2. Wikner BN, Stiller CO, Källén B, Asker C. Use of benzodiazepines and benzodiazepine receptor agonists during pregnancy: maternal characteristics. Pharmacoepidemiol Drug Saf. 2007 Sep;16(9):988-94.
  3. Antenatal and Postnatal Mental Health: The NICE Guideline on Clinical Management and Service Guidance. April 2018. https://www.nice.org.uk/guidance/cg192/evidence/full-guideline-pdf-4840896925. Accessed June 25, 2018.

[x]

  1. Wikner BN, Stiller CO, Bergman U, Asker C, Källén B. Use of benzodiazepines and benzodiazepine receptor agonists during pregnancy: neonatal outcome and congenital malformations. Pharmacoepidemiol Drug Saf. 2007 Nov;16(11):1203-10.
  2. Ban L, West J, Gibson JE, Fiaschi L, Sokal R, Doyle P, Hubbard R, Smeeth L, Tata LJ. First trimester exposure to anxiolytic and hypnotic drugs and the risks of major congenital anomalies: a United Kingdom population-based cohort study. PLoS One. 2014 Jun 25;9(6):e100996.
  3. Antenatal and Postnatal Mental Health: The NICE Guideline on Clinical Management and Service Guidance. April 2018. https://www.nice.org.uk/guidance/cg192/evidence/full-guideline-pdf-4840896925. Accessed June 25, 2018.

[xi]

  1. Wikner BN, Stiller CO, Källén B, Asker C. Use of benzodiazepines and benzodiazepine receptor agonists during pregnancy: maternal characteristics. Pharmacoepidemiol Drug Saf. 2007 Sep;16(9):988-94.

[xii]

  1. Wikner BN, Stiller CO, Källén B, Asker C. Use of benzodiazepines and benzodiazepine receptor agonists during pregnancy: maternal characteristics. Pharmacoepidemiol Drug Saf. 2007 Sep;16(9):988-94.
  2. Yonkers KA, Gilstad-Hayden K, Forray A, Lipkind HS. Association of Panic Disorder, Generalized Anxiety Disorder, and Benzodiazepine Treatment During Pregnancy With Risk of Adverse Birth Outcomes. JAMA Psychiatry. 2017 Nov 1;74(11):1145-1152.
  3. Antenatal and Postnatal Mental Health: The NICE Guideline on Clinical Management and Service Guidance. April 2018. https://www.nice.org.uk/guidance/cg192/evidence/full-guideline-pdf-4840896925. Accessed June 25, 2018.

[xiii]

  1. ACOG Committee on Practice Bulletins–Obstetrics. ACOG Practice Bulletin: Clinical management guidelines for obstetrician-gynecologists number 92, April 2008 (replaces practice bulletin number 87, November 2007). Use of psychiatric medications during pregnancy and lactation. Obstet Gynecol. 2008 Apr;111(4):1001-20.
  2. Antenatal and Postnatal Mental Health: The NICE Guideline on Clinical Management and Service Guidance. April 2018. https://www.nice.org.uk/guidance/cg192/evidence/full-guideline-pdf-4840896925. Accessed June 25, 2018.

[xiv]

  1. ACOG Committee on Practice Bulletins–Obstetrics. ACOG Practice Bulletin: Clinical management guidelines for obstetrician-gynecologists number 92, April 2008 (replaces practice bulletin number 87, November 2007). Use of psychiatric medications during pregnancy and lactation. Obstet Gynecol. 2008 Apr;111(4):1001-20.
  2. Antenatal and Postnatal Mental Health: The NICE Guideline on Clinical Management and Service Guidance. April 2018. https://www.nice.org.uk/guidance/cg192/evidence/full-guideline-pdf-4840896925. Accessed June 25, 2018.

[xv]

  1. Gentile S. Neurodevelopmental effects of prenatal exposure to psychotropic medications. Depress Anxiety. 2010 Jul;27(7):675-86.

[xvi]

  1. Maudsley Prescribing Guidelines, 12th 2015. Page 560, 571.
  2. Kelly LE, Poon S, Madadi P, Koren G. Neonatal benzodiazepines exposure during breastfeeding. J Pediatr. 2012 Sep;161(3):448-51.