Table 3.

Evidence table for use of bupropion and atypical anti-psychotics with hormonal contraception

Author, year, funding source	Design	Study population	Exposure Psychotropic drug	Exposure Contraceptive	Outcomes	Outcomes Results	Strengths	Limitations	Quality
Bupropion
Palovaara, S. 2003  GlaskoSmith Kline provided bupropion	PK Randomized balanced crossover	Healthy women aged 20–25, BMI 18–27 (n=12) No OC use for≤2 months	Bupropion (150 mg) given on day 0 and day 10	EE (30 mcg)/desogestrel (150 mcg) for 10 days	Plasma concentrations of bupropion and metabolites, AUC, Cmax, tmax	COC vs. Non-OC AUC (bup)- ↓ 19% 0.72 vs. 0.89 mcg/ml.h (p<.001) Cmax (bup)- no change 76 vs 80 ng/ml (p=.59) AUC (Hydroxybup) ↓ 31% 16 vs 11 mcg/ml. h (p<.001) Cmax (hydroxybup) ↓ 20% 426 vs 335 ng/ml (p=.009)	Crossover design, single COC given, appropriate PK parameter measured and evaluated known active metabolite	Unable to distinguish if the estrogen or progestin component was associated with the changes seen	Good
Atypical Antipsychotics
Muirhead, G. J. 2000  Pfizer Central Research	PK with some clinical info Double blinded, placebo controlled two way cross-over	Healthy women aged 22–39, non-smokers, within 20% ideal body weight, taking OCPs for ≥3 months (n=19)	COC for 21 days; day 1–7 COC alone and day 8–15 COC + placebo or ziprasidone 7 day washout	EE 30 mcg/LNG 150 mcg	AUC(0,24 h), Cmax and tmax for EE and LNG on cycle day 15 -adverse events, bleeding diaries	EE (no change) Ratio for COC/placebo AUC: 99.3% (93.9, 105.1) Cmax: 93.9 (85.6, 103) tmax (h); difference 0.6 (−0.2, 1.3) LNG Ratio for COC/placebo AUC: 97.8% (92.8, 103) Cmax: 92.7 (84.5, 101.8) tmax (h); difference 0.6 (0.1, 1.3) -Overall COC +ziprasidone did “not produce any clinically significant adverse effects” - shortened menstrual cycle for 1 subject during ziprasidone arm and 1 subject with irregular bleeding during placebo arm	Crossover design, single COC given, appropriate PK parameter measured. Supervised administration of drugs on 13 of 21 days	No ziprasidone levels determined	Good
Haslemo, T. 2011  Funding not s tated	PK Parallel	Women ages 18–45 on olanzapine at one routine therapeutic drug monitoring center n=149 10 Estrogen containing contraceptive (ECC) users 10 Progestogen-based contraceptive (PBC) users 129 non-users	Olanzapine (2.5–30 mg)	Estrogen containing contraceptives or progestin-based contraceptives	Dose-adjusted serum [olanzapine] and [N-desmethylolanzapine] (metabolite) (C:D ratio) one time measurement 10–30 h after last drug dose	C:D ratios (ECC/PBC/non-users) Olanzapine: No change 7.83/7.8/7.67 (p=.99) Metabolite: ECC ↓ 33% PBC No change 1.3/2.2/1.95 (p=.033) Large inter-individual variability for both C:D ratios for olanzapine and metabolite	Separated estrogen containing contraceptives from progestin only ones	Large range of Olanzapine doses however was dose-adjusted Sample size small one time measurement, broad timing for blood draw, Range of doses and formulations for contraceptives. Unclear role of metabolite thus hard to interpret results	Fair
Chiu Y. 2014.  Sunovion Pharmaceuticals inc.	PK Placebo controlled double blind, two-way crossover	Healthy female volunteers, age 18–40 years (n=17)	lurasidone 40 mg or placebo once daily on days 12–21 then crossover	COC 35 mcg ethinyl estradiol and 180–250 mcg norgestimate daily	Cmax and AUC (0–24) of what?	Geometric mean ratio (90% CI) EE-no change AUC: 1.12 (1.06–1.18) Cmax 1.08 (0.97–1.21) Norgestimate no change AUC: 1.03 (0.92–1.15) Cmax 0.98 (0.87–1.10) 1 adverse event (dysmenorrhea)	Crossover design, single COC given, appropriate PK parameter measured	Only 17 completed study out of 23 enrolled (no explanation)	Good

C_max, Maximum concentration; ECC, estrogen containing contraceptive; PBC, progestin based contraceptive; t_1/2, half life; t_max, time to maximum concentration.