What are the risks and alternative treatments for a 32-year-old female with severe anxiety, panic attacks, depression, obsessive-compulsive disorder (OCD), fibromyalgia, migraine, and irritable bowel syndrome (IBS) who is currently taking gabapentin (Neurontin) and wants to become pregnant, considering the potential risks of gabapentin on fetal development and the ineffectiveness of previous selective serotonin reuptake inhibitor (SSRI) trials, including sertraline (Zoloft), duloxetine (Cymbalta), and buspirone (Buspar)?

From the Guidelines

For a 32-year-old female with multiple psychiatric and pain conditions who wishes to become pregnant while on gabapentin, I strongly recommend a careful risk-benefit assessment with consideration of dose reduction rather than complete discontinuation, as the benefits of controlling her symptoms likely outweigh the risks associated with gabapentin use during pregnancy. The patient's history of severe anxiety, depression, and chronic pain, which worsen when untreated, suggests that discontinuing gabapentin could lead to significant functional impairment and potentially harm both the mother and the fetus 1.

Magnitude of Risk with Gabapentin Continued

Gabapentin does carry some pregnancy risks, including a small increased risk of cardiac malformations and potential for preterm birth or small-for-gestational-age infants. However, these risks must be balanced against the significant functional impairment she experiences when her conditions are untreated. It's essential to consider that untreated severe anxiety, depression, and chronic pain also carry their own risks to pregnancy outcomes, which must be factored into treatment decisions.

Pregabalin as an Alternative

Pregabalin is not necessarily safer than gabapentin, as it has similar pregnancy risk concerns. Therefore, switching to pregabalin may not significantly reduce the risks associated with anticonvulsant use during pregnancy.

Alternative Medication Options

Alternative medication options include quetiapine at low doses (25-200mg), which has reasonable pregnancy safety data and can help with anxiety, or mirtazapine (15-45mg), which may address both mood and pain symptoms with relatively acceptable pregnancy risk profiles. For pain management, non-pharmacological approaches should be emphasized, including physical therapy, cognitive behavioral therapy for pain, and mindfulness techniques. If medication changes are implemented, they should be gradual and closely monitored.

Referral to a Reproductive Psychiatrist

A referral to a reproductive psychiatrist in New York would be beneficial, as major academic medical centers like Columbia, NYU, or Cornell have specialized perinatal psychiatry services that could provide comprehensive care. These specialists can help navigate the complex decision-making process regarding medication use during pregnancy and provide guidance on the safest approaches to managing the patient's conditions.

Key Considerations

• The patient's severe anxiety, depression, and chronic pain conditions require effective management to prevent significant functional impairment and potential harm to both the mother and the fetus.
• Gabapentin, while carrying some pregnancy risks, may be necessary for controlling the patient's symptoms, and the benefits may outweigh the risks.
• Alternative medication options and non-pharmacological approaches should be considered and implemented under the guidance of a reproductive psychiatrist.
• Untreated mental health and chronic pain conditions pose significant risks to pregnancy outcomes and must be factored into treatment decisions 1.

From the FDA Drug Label

Use in Specific Populations 8. 1 Pregnancy Pregnancy Category C: There are no adequate and well-controlled studies in pregnant women. In nonclinical studies in mice, rats, and rabbits, gabapentin was developmentally toxic when administered to pregnant animals at doses similar to or lower than those used clinically.

Gabapentin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus

When pregnant mice received oral doses of gabapentin (500 mg, 1000 mg, or 3000 mg/kg/day) during the period of organogenesis, embryo-fetal toxicity (increased incidences of skeletal variations) was observed at the two highest doses

The no-effect dose for embryo-fetal developmental toxicity in mice was 500 mg/kg/day or approximately ½ of the maximum recommended human dose (MRHD) of 3600 mg/kg on a body surface area (mg/m2) basis

In studies in which rats received oral doses of gabapentin (500 to 2000 mg/kg/day), during pregnancy, adverse effect on offspring development (increased incidences of hydroureter and/or hydronephrosis) were observed at all doses.

The lowest effect dose for developmental toxicity in rats is approximately equal to the MRHD on a mg/m2 basis

When pregnant rabbits were treated with gabapentin during the period of organogenesis, an increase in embryo-fetal mortality was observed at all doses tested (60 mg, 300 mg, or 1500 mg/kg).

The lowest effect dose for embryo-fetal developmental toxicity in rabbits is less than the MRHD on a mg/m2 basis

1. Magnitude of risk of gabapentin continued: The FDA drug label indicates that gabapentin is a Pregnancy Category C medication, meaning that it should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. The label also states that gabapentin was developmentally toxic in nonclinical studies in mice, rats, and rabbits at doses similar to or lower than those used clinically.
2. Pregabalin safety: There is no information in the provided drug labels about pregabalin.
3. Alternatives: There is no information in the provided drug labels about quetiapine, mirtazapine, or other alternatives.
4. NY providers for perinatal psych: There is no information in the provided drug labels about NY providers for perinatal psych.

From the Research

Magnitude of Risk with Gabapentin Continued

• The risk of cardiac malformations in the first trimester and pre-term birth/SGA in late pregnancy with gabapentin use is a concern 2.
• However, there is limited research on the specific risks associated with gabapentin use during pregnancy, and more studies are needed to fully understand the potential risks 3.

Pregabalin as a Safer Alternative

• There is no clear evidence to suggest that pregabalin is safer than gabapentin during pregnancy 2.
• Pregabalin is also used off-label for anxiety disorders, but its efficacy and safety in pregnancy are not well established 3.

Alternatives to Gabapentin

• Quetiapine may be considered as an off-label alternative for anxiety, but its use during pregnancy should be carefully evaluated due to potential risks 2.
• Mirtazapine may also be considered, but its efficacy and safety in pregnancy are not well established 3.
• Amitriptyline was not effective in the past, and other alternatives may need to be explored 2.
• Acupuncture therapy may be considered as a non-pharmacologic strategy for pain management, with some evidence suggesting its efficacy in acute pain settings 4.
• A comparison between acupuncture therapy and gabapentin for chronic pain found no significant differences in pain reduction or functionality, but the study had a limited sample size 5.

Specialty Training in Perinatal Psych

• There are no specific studies or references provided that address the availability of NY providers with specialty training in perinatal psych who would be willing to assume care for this patient.
• However, it may be possible to find providers with expertise in perinatal psych through professional organizations or online directories 6.