Is a combined oral contraceptive pill appropriate for a woman with bipolar disorder, taking into account her bipolar medication regimen (including possible enzyme‑inducing anticonvulsants) and thrombotic risk factors such as obesity and smoking?

Combined Oral Contraceptives in Women with Bipolar Disorder

Women with bipolar disorder taking enzyme-inducing anticonvulsants (carbamazepine, phenytoin, barbiturates, topiramate, oxcarbazepine) should avoid combined oral contraceptives due to significantly reduced contraceptive efficacy, and those with additional thrombotic risk factors like obesity and smoking face compounded cardiovascular risks that make COCs particularly inappropriate. 1

Primary Contraceptive Considerations

Drug Interactions with Bipolar Medications

Enzyme-inducing anticonvulsants substantially reduce COC effectiveness:

• Carbamazepine, phenytoin, barbiturates, primidone, topiramate, and oxcarbazepine are classified as Category 3 (risks generally outweigh benefits) for COC use due to decreased contraceptive efficacy 1
• These medications increase metabolism of ethinylestradiol and progestogens, leading to contraceptive failure 2, 3
• If a COC must be used with these agents, a minimum of 30 μg ethinyl estradiol is required, though this still provides suboptimal protection 1, 4
• Women should be strongly encouraged to use alternative contraceptive methods rather than attempting dose adjustments 1

Lamotrigine presents a bidirectional interaction:

• COCs significantly decrease lamotrigine levels, potentially triggering breakthrough seizures 1
• This interaction is classified as Category 3, with documented cases of increased seizure activity when both are used together 1
• This interaction only applies to lamotrigine monotherapy; combinations with non-enzyme-inducing agents like valproate do not interact with COCs 1

Non-interacting mood stabilizers:

• Valproic acid (valproate), lithium, and newer agents like gabapentin, levetiracetam do not interact with COCs 2
• Women on these medications can use standard-dose COCs if no other contraindications exist 2

Cardiovascular Risk Assessment

Obesity and smoking create compounded thrombotic risk:

• Women ≥35 years who smoke ≥15 cigarettes daily should not use COCs 4
• Obesity itself represents a relative contraindication for COC use due to increased venous thromboembolism risk 1
• The combination of obesity, smoking, and COC use creates multiplicative rather than additive thrombotic risk 1
• Absolute cardiovascular risk with COC use is approximately 10 per 100,000 person-years for myocardial infarction and 21 per 100,000 person-years for stroke, but this increases substantially with additional risk factors 1, 4

Recommended Contraceptive Alternatives

Long-acting reversible contraception (LARC) should be first-line:

• Levonorgestrel intrauterine devices (LNG-IUD) are Category 1 (no restrictions) for women on anticonvulsants 1
• Copper intrauterine devices (Cu-IUD) are Category 1 and unaffected by any drug interactions 1
• Etonogestrel implants are Category 2 (benefits generally outweigh risks) for enzyme-inducing anticonvulsants, though slightly less preferred than IUDs 1
• These methods are highly effective, acceptable to women, and completely bypass hepatic metabolism concerns 1

Progestin-only options for non-LARC users:

• Depot medroxyprogesterone acetate (DMPA) is Category 1 for enzyme-inducing anticonvulsants 1
• Progestin-only pills are Category 3 with enzyme-inducing anticonvulsants due to reduced efficacy 1, 3
• DMPA injections should be given every 10 weeks instead of 12 weeks when used with enzyme-inducing agents 2

Clinical Decision Algorithm

Step 1: Identify the specific bipolar medication regimen

• Enzyme-inducing anticonvulsants (carbamazepine, phenytoin, barbiturates, topiramate, oxcarbazepine) → COCs contraindicated 1
• Lamotrigine monotherapy → COCs contraindicated 1
• Non-enzyme-inducing mood stabilizers (valproate, lithium) → proceed to Step 2 2

Step 2: Assess cardiovascular risk factors

• Age ≥35 years AND smoking ≥15 cigarettes/day → COCs absolutely contraindicated 4
• Obesity (BMI ≥30) → COCs relatively contraindicated, especially with additional risk factors 1
• Hypertension (BP ≥160/100) → COCs contraindicated 4

Step 3: Recommend appropriate contraception

• If any contraindication exists → Recommend LNG-IUD or Cu-IUD as first-line 1
• If LARC declined → Offer DMPA injections 1
• If no contraindications and non-enzyme-inducing medications → COC with ≤35 μg ethinyl estradiol acceptable 1, 5

Critical Pitfalls to Avoid

Do not attempt to overcome enzyme-inducing effects with higher-dose COCs:

• Even 50 μg ethinyl estradiol formulations provide inadequate protection with strong enzyme inducers 2, 3
• The historical recommendation for 50 μg preparations is outdated and unreliable 1

Do not overlook the lamotrigine interaction:

• This bidirectional interaction can cause both contraceptive failure and seizure breakthrough 1
• Many clinicians focus only on enzyme-inducing anticonvulsants and miss this important interaction 1

Do not underestimate cumulative cardiovascular risk:

• The combination of obesity, smoking, and COC use in women with bipolar disorder (who may have additional metabolic syndrome risk) creates substantial thrombotic danger 1, 4
• Blood pressure measurement is mandatory before COC initiation and at all follow-up visits 4