What is the best oral contraceptive (OC) for a patient with mood swings that has the least risk of thrombosis (blood clots)?

Best Oral Contraceptive for Mood Swings with Lowest Thrombosis Risk

For a patient with mood swings seeking the lowest thrombosis risk, a progestin-only pill (POP) or levonorgestrel IUD is the safest choice, as these methods do not increase venous thromboembolism risk (RR 0.90 and 0.61 respectively) and avoid the mood-destabilizing effects of ethinyl estradiol. 1

Thrombosis Risk Hierarchy

Lowest Risk Options (Recommended)

• Levonorgestrel IUD: No increase in VTE risk (RR 0.61,95% CI 0.24-1.53) 1
• Progestin-only pills: No increase in VTE risk (RR 0.90,95% CI 0.57-1.45) 1
• Copper IUD: Non-hormonal option with no thrombosis risk 1

Moderate Risk Options (Use with Caution)

• Combined oral contraceptives with levonorgestrel: Lower VTE risk than newer progestins, but still 3-9 per 10,000 woman-years 1
• Low-dose ethinyl estradiol (≤20 mcg) with levonorgestrel: Second-generation progestins show safer coagulation profile 1

High Risk Options (Avoid)

• Injectable medroxyprogesterone (DMPA): Significantly elevated VTE risk (RR 2.67,95% CI 1.29-5.53) and should be avoided 2
• Drospirenone-containing pills: 50-80% higher VTE risk than levonorgestrel formulations, approximately 10 per 10,000 woman-years 1, 3
• Third-generation progestins (gestodene, desogestrel): Higher VTE risk than levonorgestrel 1

Mood Considerations

Formulations That May Improve Mood

• Drospirenone-containing pills: Despite higher thrombosis risk, these reduce depressive symptoms and premenstrual tension through anti-mineralocorticoid effects 4, 5
• Natural estrogens (17β-estradiol): Newer pills with physiological estrogens may be better tolerated for mood than ethinyl estradiol 6

Formulations That May Worsen Mood

• Ethinyl estradiol-containing pills: Older formulations linked to severe mood problems 6
• Higher progestogen doses: The amount and type of progestogen correlates with mood disturbances 6

Clinical Algorithm

Step 1: Assess thrombosis risk factors

• High-risk conditions: cyanosis, Fontan physiology, mechanical valves, prior thrombotic events, pulmonary arterial hypertension, antiphospholipid antibodies 1
• If ANY high-risk factor present → Levonorgestrel IUD or progestin-only pill ONLY 1

Step 2: For standard-risk patients with mood swings

• First choice: Levonorgestrel IUD (addresses both concerns optimally) 1
• Second choice: Progestin-only pill (no VTE risk, though may have breakthrough bleeding) 1
• Third choice: If combined pill preferred, use ≤20 mcg ethinyl estradiol with levonorgestrel (lowest VTE risk among combined pills) 1

Step 3: If drospirenone considered for mood benefits

• Only in patients WITHOUT thrombosis risk factors 1
• Counsel on 50-80% higher VTE risk versus levonorgestrel 1
• Monitor for leg pain/swelling, chest pain, shortness of breath 2

Critical Contraindications

Absolutely avoid estrogen-containing contraceptives in:

• Antiphospholipid antibody-positive patients (estrogen increases thromboembolism risk) 1
• Cyanotic congenital heart disease 1
• Prior thrombotic events 1
• Fontan physiology 1
• Pulmonary arterial hypertension 1

Avoid DMPA in:

• Any patient with thrombosis risk factors (RR 2.67 for VTE) 2
• Antiphospholipid antibody-positive patients 1, 2
• Chronic coronary disease or previous stroke 2

Common Pitfalls

• Assuming all progestins have equal thrombosis risk: Levonorgestrel has significantly lower VTE risk than drospirenone, desogestrel, or gestodene 1
• Overlooking non-oral routes: Transdermal patches result in greater estrogen exposure and higher thrombosis risk than oral formulations 1
• Prescribing drospirenone for mood without considering VTE risk: While effective for mood, the 50-80% increased VTE risk may outweigh benefits 1, 3
• Using DMPA in high-risk patients: This formulation has the highest thrombosis risk among progestin-only methods 2