No Clinically Significant Interaction Between SSRIs and Depo-Provera
SSRIs do not interact with depot medroxyprogesterone acetate (Depo-Provera) and can be safely used together without dose adjustments or additional contraceptive precautions. 1
Evidence from Drug Interaction Guidelines
The U.S. Medical Eligibility Criteria for Contraceptive Use comprehensively addresses drug interactions with DMPA and does not list SSRIs or any antidepressants as having interactions with depot medroxyprogesterone acetate. 1 The guideline specifically categorizes drug interactions with DMPA, including:
- Antiretroviral medications (with detailed pharmacokinetic data showing DMPA levels remain stable) 1
- Anticonvulsants (certain ones like phenytoin and carbamazepine) 1
- Antimicrobials (rifampicin, rifabutin) 1
SSRIs are notably absent from this comprehensive list of drug interactions, indicating no clinically relevant interaction exists. 1
Mechanism Supporting Safety
The pharmacokinetic profile of DMPA makes drug interactions unlikely with most medications:
- DMPA is administered as an intramuscular depot injection that releases medroxyprogesterone acetate slowly over 12-13 weeks, achieving plateau serum concentrations around 1.0 ng/mL for approximately three months. 2
- The slow-release mechanism from muscle tissue is independent of hepatic metabolism pathways that typically cause drug-drug interactions with oral contraceptives. 2
- Unlike combined oral contraceptives that undergo first-pass hepatic metabolism, DMPA's depot formulation bypasses many cytochrome P450-mediated interactions that affect other hormonal contraceptives. 2
Clinical Context from SSRI Guidelines
While SSRIs do have documented pharmacokinetic interactions with certain medications metabolized by cytochrome P450 enzymes (such as anticonvulsants, benzodiazepines, tricyclic antidepressants, and warfarin), these interactions do not extend to DMPA. 1 The AUA guideline on SSRIs mentions potential interactions with medications metabolized via the same pathways, but progestin-only injectables like DMPA are not included in this concern. 1
Practical Clinical Recommendations
You can prescribe or continue both medications simultaneously without any modifications:
- No dose adjustment of either SSRI or DMPA is required 1
- No additional backup contraception is needed when starting an SSRI in a patient using DMPA 1
- DMPA maintains its highly effective contraceptive profile (0.2% perfect use failure rate, 6% typical use failure rate) regardless of SSRI co-administration 3
- Continue standard DMPA dosing: 150 mg intramuscularly or 104 mg subcutaneously every 13 weeks, with up to 2 weeks grace period (15 weeks total) 4
Common Pitfall to Avoid
Do not confuse DMPA with combined oral contraceptives when considering drug interactions—the depot injection formulation has a fundamentally different pharmacokinetic profile that makes it largely free of the drug interactions seen with oral contraceptives. 1, 2