Quinestrol and Amitriptyline: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Amitriptyline
Quinestrol
No brand names on record
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
You're taking amitriptyline (an antidepressant) along with quinestrol (an estrogen). When these are used together, the estrogen may change how your body handles the antidepressant. This can create a tricky mix: your depression symptoms might not be as well controlled, while at the same time you could notice more side effects from the amitriptyline, like drowsiness, dizziness when standing up (low blood pressure), or restlessness.
The good news is this is considered a minor, theoretical concern, and it mostly matters if you were already doing well on amitriptyline and then start the estrogen. Just let your pharmacist or doctor know how you're feeling. They can adjust your doses if needed to keep things working smoothly.
Effect: Estrogen (quinestrol) may alter tricyclic (amitriptyline) response, with the paradoxical combination of reduced antidepressant efficacy and simultaneous TCA toxicity (sedation, orthostatic hypotension, akathisia).
Mechanism: Proposed estrogen-enhanced hepatic metabolism of the tricyclic; effect appears estrogen dose-related. Neither agent is a prodrug requiring activation.
- Onset: delayed
- Evidence: theoretical, isolated case reports
- Severity: minor
- At risk: patients stabilized on TCA who then initiate estrogen
Management: Monitor for altered antidepressant response and anticholinergic/orthostatic effects. Dose of either component may be individualized downward; occasionally withdrawal is required.
What happens
Attenuation of antidepressant effectiveness; tricyclic toxicity (drowsiness, hypotension, akathisia)
Interaction Deep Dive
Estrogens have, in a small number of cases, been reported to either heighten or diminish the pharmacologic activity of tricyclic antidepressants3. A paradoxical presentation has been observed in which the antidepressant benefit is lost while signs of tricyclic toxicity emerge at the same time 1. This interaction seems to depend on the estrogen dose 2, and its clinical relevance is most likely to be seen in patients who had already been stabilized on tricyclic treatment and are subsequently beginning estrogen therapy 6.
Why it happens (mechanism)
Possible estrogen-enhanced hepatic metabolism of the tricyclic
How to manage this interaction
This is a low-level, theoretical interaction, so the plan is mostly about paying attention and communicating.
- Keep taking both medications as prescribed unless your care team tells you otherwise.
- Watch for signs your depression is not as well managed, or new side effects like drowsiness, feeling faint when standing, or restlessness.
- This matters most if you were already stable on amitriptyline and are just starting quinestrol.
If you notice any of these changes, tell your pharmacist or prescriber. The dose of either the estrogen or the amitriptyline may be adjusted and individualized by your care team, and they may monitor you more closely to keep everything working well.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
7 reports — tap to read
a) An investigation looked at the qualitative outcomes of giving estrogen together with TCAs. In one trial, 30 depressed female prisoners were randomly allocated to four treatment groups. Ten patients received placebo, 10 received imipramine (150 mg daily) plus placebo, five patients received imipramine (150 mg daily) plus ethinyl estradiol (50 mcg daily), and five patients received imipramine (150 mg daily) plus ethinyl estradiol (25 mcg daily). The 10 patients on placebo showed no improvement across the six weeks of the study. The 10 patients taking estrogen and imipramine showed a significantly greater symptom improvement than the 10 patients on imipramine alone. However, after two weeks, the five patients on imipramine and high-dose estrogen had not improved as much as those on imipramine and low-dose estrogen. The only reported adverse effect was drowsiness, which occurred only in patients taking imipramine. After ethinyl estradiol was stopped, the high-dose estrogen group needed two weeks to reach the same level as the low-dose group. This effect was ascribed to residual estrogen remaining in the high-dose group. In a separate group, five women given imipramine 150 mg and ethinyl estradiol 50 mcg daily did not improve as much as 10 patients receiving imipramine only. Furthermore, the patients on the combination experienced severe adverse effects, including lethargy, coarse tremor, and systolic hypotension 1.
b) A case described by 2 showed an interaction in a 32-year-old woman taking conjugated estrogens 2.5 mg and imipramine 100 mg. She developed lethargy, tremors, and signs of depersonalization. After two years of treatment, she raised her estrogen dose to 5 mg and then 7.5 mg daily. She became nauseated, had persistent headaches, and had low normal blood pressure. All laboratory results were normal. When the estrogen was stopped, the adverse effects subsided. Some researchers have suggested that the adverse effects arose from increased TCA effects caused by estrogen inhibition of hepatic microsomal enzymes 3.
c) A study assessed women who received clomipramine with oral contraceptives or clomipramine alone. At the study outset there were 30 women on the combination, but 12 later dropped out. The 18 patients on the combination were matched with 18 patients on clomipramine alone. No significant difference was seen in the patients' responses to clomipramine. It was suggested that there was no significant difference in adverse effects between the groups; however, the groups were matched after patients had withdrawn from the study. Had the patients been matched before the study, different conclusions might have been reached 4.
d) A study examined the effects of oral contraceptives on clomipramine in 42 women aged 18 to 40 years. Twenty-three women took clomipramine 25 mg at bedtime, while 19 took clomipramine 25 mg at bedtime along with oral contraceptives. During the four-week study, three control patients (two due to adverse effects) and five in the experimental group (two due to adverse effects) dropped out. Venous blood samples were collected weekly to measure serum clomipramine concentrations. No difference in serum concentrations was found between the groups. However, this result may be partly attributable to the low dose of clomipramine administered 5.
e) Three patients who received conjugated estrogens and tricyclic antidepressants at the same time developed akathisia. A 24-year-old patient receiving clomipramine 120 mg daily for anorexia nervosa and conjugated estrogens 1.25 mg daily for amenorrhea developed restless legs and a persistent urge to move continuously. Estrogen was discontinued and benztropine 2 mg was given, producing marked reduction and resolution within 48 hours. Akathisia and disorientation appeared in a 55-year-old patient on conjugated estrogens 1.25 mg daily who was prescribed amitriptyline 50 mg daily for depression. Within hours of the amitriptyline, the patient became confused, restless, and had an inner urge to move continuously. Symptoms resolved after amitriptyline was stopped. A third case of akathisia was reported in a 35-year-old patient who received conjugated estrogens 1.25 mg daily and amitriptyline 50 mg daily. Akathisia developed within a few hours after the first dose of amitriptyline and resolved within 48 hours after the antidepressant was discontinued 6.
f) The absolute bioavailability of imipramine rose in women who received low-dose oral contraceptives (50 mcg or less of ethinyl estradiol) from 27% to 44% (p less than 0.05), as shown by an increase in the area under the plasma concentration time curve 7.
g) Estrogens may inhibit the oxidation of TCAs by affecting hepatic microsomal enzymes 8. Many TCAs are metabolized through oxidation and conjugation pathways. Inhibiting the oxidation of TCAs could lead to accumulation and toxicity because of reduced clearance. Estrogens are suspected of having other effects on the central nervous system that produce an antidepressant effect 9.
Common questions
Can I take Quinestrol and Amitriptyline together?
Estrogen may change how amitriptyline works, possibly lowering its antidepressant effect while increasing side effects like drowsiness or dizziness. Keep taking both as prescribed and report any changes so your team can adjust the dose if needed. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Quinestrol and Amitriptyline interaction?
It is rated minor. Usually limited clinical impact.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How is the Quinestrol and Amitriptyline interaction managed?
This is a low-level, theoretical interaction, so the plan is mostly about paying attention and communicating. Keep taking both medications as prescribed unless your care team tells you otherwise. Watch for signs your depression is not as well managed, or new side effects like drowsiness, feeling faint when standing, or restlessness. This matters most if you were already stable on amitriptyline and… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Quinestrol or Amitriptyline need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there anything you'd monitor while I'm on both?
References (9)
- Prange AJ Jr: Estrogens may well affect response to antidepressants. JAMA 1972; 219:143-144.
- Khurana RC: Estrogen-imipramine interaction (letter). JAMA 1972; 222:702-703. PubMed
- Somani SM & Khurana RC: Mechanism of estrogen-imipramine interaction (letter). JAMA 1973; 223:560. DOI
- Beaumont G: Drug interactions with clomipramine. J Int Med Res 1973; 1:480-484.
- Luscombe DK & John V: Influences of age, cigarette smoking and the oral contraceptive on plasma concentrations of clomipramine. Postgrad Med J 1980; 56(suppl 1):99-102.
- Krishnan KR, France RD, & Ellinwood EH: Tricyclic-induced akathisia in patients taking conjugated estrogens. Am J Psychiatry 1984; 141:696-697. PubMed
- Abernethy DR, Greenblatt DJ, & Shader RI: Imipramine disposition in users of oral contraceptive steroids. Clin Pharmacol Ther 1984; 35:792-797. PubMed
- John VA, Luscombe DK, & Kemp H: Effects of age, cigarette smoking and the oral contraceptive on the pharmacokinetics of clomipramine and its desmethyl metabolite during chronic dosing. J Int Med Res 1980; 8(suppl 3):88-95.
- Oppenheim G: Estrogens in the treatment of depression: neuropharmacological mechanisms. Biol Psychiatry 1983; 18:721-725.
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