medicationPrescription only (US)Duloxetine (Cymbalta) is FDA-approved for major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain
DuloxetineBenefits, Dosage & Interactions
Also known as: Cymbalta
Duloxetine is a medication primarily used to treat major depressive disorder, generalized anxiety disorder, and chronic musculoskeletal pain, including fibromyalgia and chronic low back pain. It is also approved for diabetic peripheral neuropathic pain and chronic osteoarthritis pain. It is typically taken in the morning.
How much Duloxetine do people take?
Doses across the pooled antidepressant network meta-analyses ranged roughly 40–120 mg per day for major depressive disorder, with lower doses also studied for chronic pain indications. Route reported: Oral, delayed-release capsule. Frequency reported: Once or twice daily, per the trial designs synthesized in these reviews. These are amounts documented in the cited studies and labels for Duloxetine — they are reported for reference, not a recommendation. Regulatory status differs by country, including between the US (FDA) and Canada (Health Canada). Confirm any amount with a licensed clinician before you take it.
See the full reported protocol and its sourcesResearched by DoseRoutine Research TeamReviewed for accuracy by Nicholas Alexander, RSE, SO, PMPLast updated Educational reference only — not medical advice. Always confirm dosing and safety decisions with a licensed clinician.
Evidence: Strong — 2 human randomized trials and regulatory approval on file.
Evidence strengthStrong · 4/4
PreclinicalStrong human evidence
2 human randomized trials and regulatory approval on file.
Plasma half-life
~12 h
Typical timing
in the morning
Default unit
mg
What published protocols report
Ranges documented in the literature, shown for reference. DoseRoutine does not recommend an amount — your prescriber or the product label sets the dose.
Reported for Duloxetine in the cited sources. Published ranges are not dosing advice.
References & evidence
Documents the Duloxetine entry is written from. Each number matches an inline marker above.
- [1]Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysisCipriani A, Furukawa TA, Salanti G, Chaimani A, Atkinson LZ, Ogawa Y · Lancet · 2018 · Peer-reviewed · PMID 29477251
- [2]Antidepressants for the treatment of adults with major depressive disorder in the maintenance phase: a systematic review and network meta-analysisKishi T, Ikuta T, Sakuma K, Okuya M, Hatano M, Matsuda Y · Molecular Psychiatry · 2023 · Peer-reviewed · PMID 36253442
- [3]Antidepressants for pain management in adults with chronic pain: a network meta-analysisBirkinshaw H, Friedrich C, Cole P, Eccleston C, Serfaty M, Stewart G · Health Technology Assessment · 2024 · Peer-reviewed · PMID 39367772
References & Evidence
Sources on this page that document Duloxetine dosing, timing and safety.
- [1]U.S. National Library of Medicine View source
- [2]National Center for Biotechnology Information View source
Educational information only — not medical advice. Dose ranges vary by person, indication and prescriber.
What is Duloxetine?Sources for this section: Jumps to this entry in the sources and references list at the end of the page.
Duloxetine is a medication primarily used to treat major depressive disorder, generalized anxiety disorder, and chronic musculoskeletal pain, including fibromyalgia and chronic low back pain. It is also approved for diabetic peripheral neuropathic pain and chronic osteoarthritis pain. Duloxetine belongs to a class of drugs called serotonin-norepinephrine reuptake inhibitors (SNRIs). (NIH ODS)
Duloxetine is available in delayed-release capsule form and is typically taken orally. The specific dosage and treatment duration are determined by a licensed clinician based on the individual's condition and response to therapy. (FDA label for Duloxetine)
What does the research say about Duloxetine?
Tap a section to expand.
Duloxetine works by increasing the levels of two neurotransmitters, serotonin and norepinephrine, in the brain and spinal cord. Neurotransmitters are chemical messengers that neurons use to communicate with each other. By inhibiting the reuptake of both serotonin and norepinephrine into presynaptic neurons, duloxetine makes more of these neurotransmitters available in the synaptic cleft. This increased availability is thought to improve mood and reduce pain signals. The dual reuptake inhibition of serotonin and norepinephrine is believed to contribute to its efficacy in treating both mood disorders and neuropathic pain conditions. (PubChem, DrugBank)
Source for this section: Sources for How does Duloxetine work?: Jumps to this entry in the sources and references list at the end of the page.
Duloxetine has demonstrated efficacy in several conditions:
* **Major Depressive Disorder (MDD):** It helps to improve mood, reduce feelings of sadness, loss of interest, and other symptoms associated with depression. (MedlinePlus)
* **Generalized Anxiety Disorder (GAD):** It can help reduce excessive worry, tension, and other symptoms of anxiety. (MedlinePlus)
* **Diabetic Peripheral Neuropathic Pain (DPNP):** It effectively reduces nerve pain associated with diabetes. (FDA label)
* **Chronic Musculoskeletal Pain:** This includes chronic low back pain and chronic osteoarthritis pain, where it can help manage pain levels. (FDA label)
* **Fibromyalgia:** It helps to reduce widespread pain, tenderness, and fatigue associated with this chronic condition. (Mayo Clinic)
Numerous clinical trials support the efficacy of duloxetine for its approved indications. For major depressive disorder and generalized anxiety disorder, studies have consistently shown that duloxetine is more effective than placebo in reducing symptom severity. A systematic review published in Cochrane assessed the effectiveness and tolerability of duloxetine for major depressive disorder and concluded that it is an effective antidepressant. For diabetic peripheral neuropathic pain, studies have demonstrated significant reductions in pain scores compared to placebo. Similarly, for fibromyalgia and chronic musculoskeletal pain, duloxetine has shown to reduce pain and improve function as documented by various clinical trials cited in the FDA label for duloxetine. These studies typically involve randomized, double-blind, placebo-controlled designs, which are considered the gold standard for evaluating drug efficacy.
Like all medications, duloxetine can cause side effects, although not everyone experiences them. Common side effects usually include nausea, dry mouth, constipation, insomnia, fatigue, dizziness, and sweating. These often diminish over time as the body adjusts to the medication. Less common but more serious side effects can include liver problems, increased blood pressure, urinary retention, serotonin syndrome, worsening of depression or suicidal thoughts (especially in young adults), and withdrawal symptoms if stopped abruptly. (FDA label, MedlinePlus)
It is crucial to report any persistent or severe side effects to a healthcare provider. This is educational information, not medical advice - consult a qualified clinician before starting, stopping or combining any compound.
Source for this section: Sources for What are the side effects of Duloxetine?: Jumps to this entry in the sources and references list at the end of the page.
Duloxetine carries several important warnings. It may increase the risk of suicidal thoughts and behaviors in children, adolescents, and young adults (up to age 24) with major depressive disorder and other psychiatric disorders; close monitoring is advised, particularly during initial treatment and dose changes. Patients should be monitored for clinical worsening, suicidality, or unusual changes in behavior. Abrupt discontinuation of duloxetine can lead to withdrawal symptoms such as dizziness, headache, nausea, diarrhea, irritability, and paresthesia (sensory disturbances); therefore, the dose should be gradually reduced under medical supervision. Liver injury, sometimes severe, has been reported; patients should not use duloxetine if they have substantial alcohol use or chronic liver disease. It can also cause or exacerbate hypertension, and blood pressure should be monitored regularly. Urinary hesitation or retention may occur. (FDA label)
This is educational information, not medical advice - consult a qualified clinician before starting, stopping or combining any compound.
Source for this section: Sources for Who should avoid Duloxetine?: Jumps to this entry in the sources and references list at the end of the page.
Duloxetine is contraindicated in patients with known hypersensitivity to duloxetine or any of its inactive ingredients. It should not be used in patients with uncontrolled narrow-angle glaucoma. The use of duloxetine is contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuing an MAOI, due to the risk of serotonin syndrome. Conversely, an MAOI should not be started within 5 days of discontinuing duloxetine. Patients with severe renal impairment (end-stage renal disease or creatinine clearance <30 mL/min) or severe hepatic impairment should generally avoid duloxetine, as drug clearance is significantly reduced in these populations, increasing the risk of adverse effects. (FDA label, EMA SmPC)
This is educational information, not medical advice - consult a qualified clinician before starting, stopping or combining any compound.
Source for this section: Sources for When should Duloxetine not be taken?: Jumps to this entry in the sources and references list at the end of the page.
Duloxetine should not be mixed with several types of compounds due to potential for severe interactions:
* **Monoamine Oxidase Inhibitors (MAOIs):** Concurrent use or use within a close timeframe can lead to a serious and potentially fatal condition called serotonin syndrome. (FDA label)
* **Other Serotonergic Drugs:** Co-administration with other drugs that increase serotonin, such as other SNRIs, SSRIs, tricyclic antidepressants (TCAs), triptans (for migraines), tramadol, fentanyl, lithium, buspirone, and St. John's Wort, increases the risk of serotonin syndrome. (FDA label)
* **Strong CYP1A2 Inhibitors:** Duloxetine is metabolized by the CYP1A2 enzyme. Drugs that strongly inhibit this enzyme (e.g., fluvoxamine, ciprofloxacin, enoxacin) can significantly increase duloxetine levels, leading to increased side effects. (FDA label)
* **Thioridazine:** This antipsychotic should not be co-administered with duloxetine because duloxetine can increase thioridazine levels, leading to prolonged QTc interval and ventricular arrhythmias. (FDA label)
* **Anticoagulants/Antiplatelet Agents:** Although not a contraindication, caution is advised when duloxetine is co-administered with oral anticoagulants (e.g., warfarin) or antiplatelet agents (e.g., aspirin, NSAIDs) due to a potential increased risk of bleeding. (FDA label)
* **Alcohol:** Consumption of alcohol, particularly chronic or heavy use, while taking duloxetine can increase the risk of liver injury. (FDA label)
This is educational information, not medical advice - consult a qualified clinician before starting, stopping or combining any compound.
Source for this section: Sources for What should you not mix with Duloxetine?: Jumps to this entry in the sources and references list at the end of the page.
Duloxetine is typically taken once daily, usually in the morning. It can be taken with or without food. Taking it with food may help to reduce gastrointestinal upset such as nausea. The exact timing and dosage are user-directed and must be set by a licensed clinician. It is important to swallow the capsule whole and not to chew, crush, or open it, as this can affect its delayed-release properties. (FDA label)
Source for this section: Sources for When should you take Duloxetine?: Jumps to this entry in the sources and references list at the end of the page.
Put it into practice
Reading about Duloxetine is the first step — DoseRoutine helps you act on it. These free tools turn what you just learned into a routine.
What interacts with Duloxetine?
| Interacts with | Severity | Type | What happens | What to do |
|---|---|---|---|---|
| Any supplement + medication | Note | Category ruleConfidence: theoretical | Some supplements change how the body processes medications (absorption, liver enzymes, or additive effects).Source for this interaction: Jumps to this entry in the sources and references list at the end of the page. | Specific pairs are checked against a licensed drug database and shown with their own severity. Always confirm with your provider or pharmacist. |
| Any vitamin + medication | Note | Category ruleConfidence: theoretical | Certain vitamins interact with specific medications (e.g., vitamin K with blood thinners).Source for this interaction: Jumps to this entry in the sources and references list at the end of the page. | Specific pairs are checked against a licensed source; confirm with your provider. |
| Phenelzine | Avoid | Compound pairConfidence: theoretical | Combining SSRIs/SNRIs with MAOIs can cause life-threatening serotonin syndrome.Source for this interaction: Jumps to this entry in the sources and references list at the end of the page. | Do not combine. Allow at least 14 days between stopping one and starting the other (5 weeks for fluoxetine). |
| Tranylcypromine | Avoid | Compound pairConfidence: theoretical | Combining SSRIs/SNRIs with MAOIs can cause life-threatening serotonin syndrome.Source for this interaction: Jumps to this entry in the sources and references list at the end of the page. | Do not combine. Allow at least 14 days between stopping one and starting the other (5 weeks for fluoxetine). |
| Selegiline | Avoid | Compound pairConfidence: theoretical | Combining SSRIs/SNRIs with MAOIs can cause life-threatening serotonin syndrome.Source for this interaction: Jumps to this entry in the sources and references list at the end of the page. | Do not combine. Allow at least 14 days between stopping one and starting the other (5 weeks for fluoxetine). |
| Rasagiline | Avoid | Compound pairConfidence: theoretical | Combining SSRIs/SNRIs with MAOIs can cause life-threatening serotonin syndrome.Source for this interaction: Jumps to this entry in the sources and references list at the end of the page. | Do not combine. Allow at least 14 days between stopping one and starting the other (5 weeks for fluoxetine). |
| 5-HTP | Avoid | Compound pairConfidence: theoretical | 5-HTP raises serotonin and layered onto an SSRI/SNRI risks serotonin syndrome.Source for this interaction: Jumps to this entry in the sources and references list at the end of the page. | Avoid combining 5-HTP with prescription serotonergic antidepressants. |
| L-Tryptophan | Caution | Compound pairConfidence: theoretical | Additional serotonin precursor with an SSRI/SNRI can push serotonin too high.Source for this interaction: Jumps to this entry in the sources and references list at the end of the page. | Do not combine without a prescribing clinician's guidance. |
| St John's Wort | Avoid | Compound pairConfidence: theoretical | St John's Wort has serotonergic activity and induces CYP3A4, altering SSRI levels.Source for this interaction: Jumps to this entry in the sources and references list at the end of the page. | Avoid combining. |
Frequently asked questions about Duloxetine
For depression and anxiety, some improvement in symptoms may be noticed within a few weeks, but it can take 4 to 8 weeks to experience the full therapeutic effects. For pain conditions, relief may also take several weeks to become noticeable. (MedlinePlus)
Yes, abruptly stopping duloxetine can cause withdrawal symptoms, often referred to as antidepressant discontinuation syndrome. Symptoms can include dizziness, headache, nausea, vomiting, diarrhea, irritability, anxiety, difficulty sleeping, sweating, and tingling sensations (paresthesia). It is important to gradually reduce the dose under the guidance of a healthcare professional. (FDA label)
Duloxetine is not considered addictive in the sense of causing drug-seeking behavior and cravings like controlled substances. However, due to the potential for withdrawal symptoms upon abrupt cessation, it is very important to taper off the medication under medical supervision rather than stopping it suddenly. (Mayo Clinic)
The use of duloxetine during pregnancy should be carefully considered. Studies suggest a potential risk of withdrawal symptoms in newborns and, in some cases, an increased risk of persistent pulmonary hypertension of the newborn (PPHN). It is crucial to discuss the risks and benefits with a healthcare provider if you are pregnant or planning to become pregnant while taking duloxetine. (FDA label)
Interaction risk for Duloxetine comes from the rest of the stack: other medications, prescription medicines, hormone therapy and peptides. Because Duloxetine is usually taken in the morning, most avoidable conflicts come from what else lands in that same window. With a reported plasma half-life near 12 hours, separating doses can change the picture as much as removing one. Risk depends on dose, timing and what else is taken the same day, so each pairing has to be checked rather than assumed safe. The free checker at https://doseroutine.com/interaction-checker covers Duloxetine with no sign-up.
Duloxetine is typically taken in the morning. The reported plasma half-life is about 12 hours, which is what drives how often it is redosed. Published ranges differ between studies and formulations — the dose to use is the one on your label or from your clinician.
There is no single answer for Duloxetine plus TRT. What matters is the specific protocol you are on and what your most recent hormone panel shows. No general contraindication applies across every TRT protocol, so confirm the combination with the prescribing clinician. See the free TRT interaction reference: https://doseroutine.com/trt-supplement-interactions
Pairing Duloxetine with peptides has to be assessed one peptide at a time, because GLP-1 agonists, secretagogues, healing peptides and melanocortins do not share an interaction profile. Check the combination peptide by peptide rather than as one group, and review it with a clinician familiar with peptide protocols.
With a plasma half-life near 12 hours, once-daily dosing is the usual pattern for Duloxetine. It is typically taken in the morning. Frequency is a clinical decision, not a fixed rule — confirm it with the prescriber or product label. Comparison of apps that keep a schedule like this: https://doseroutine.com/best-dose-tracking-apps
With a plasma half-life near 12 hours, a single missed dose of Duloxetine usually has a smaller effect on overall exposure than an irregular pattern of missed doses does. Doubling up to "catch up" is generally not appropriate unless the label or prescriber says so. Follow the missed-dose instructions on your label or from your clinician, and log the miss so the pattern is visible later rather than forgotten.
For Duloxetine the useful record is the dose, the time it was actually taken, and what else was taken in the same window. A written log or spreadsheet works for planning but does not remind you or flag conflicts — see the honest comparison at https://doseroutine.com/vs/spreadsheet and the wider roundup at https://doseroutine.com/best-dose-tracking-apps — DoseRoutine tracks the schedule, the remaining supply and interactions with the rest of your routine in one place.
Doses across the pooled antidepressant network meta-analyses ranged roughly 40–120 mg per day for major depressive disorder, with lower doses also studied for chronic pain indications. Route reported: Oral, delayed-release capsule. Frequency reported: Once or twice daily, per the trial designs synthesized in these reviews. These are amounts documented in the cited studies and labels for Duloxetine — they are reported for reference, not a recommendation. Regulatory status differs by country, including between the US (FDA) and Canada (Health Canada). Confirm any amount with a licensed clinician before you take it.
Which studies looked at Duloxetine?
Peer-reviewed research indexed in PubMed. Each entry links to the original record.
- 1.Duloxetine: clinical pharmacokinetics and drug interactions.(opens PubMed in a new tab)Clinical pharmacokinetics · 2011 · PMID 21366359 · https://pubmed.ncbi.nlm.nih.gov/21366359/
- 2.Duloxetine for fibromyalgia syndrome: a systematic review and meta-analysis(opens PubMed in a new tab)J Orthop Surg Res · 2023 · PMID 37461044 · https://pubmed.ncbi.nlm.nih.gov/37461044/
Sources cited on this page
Specific documents referenced by the numbered markers above. Each number matches the marker in the text.
- MedlinePlus(opens in a new tab)U.S. National Library of Medicine · medlineplus.gov/druginfo/meds/a604030.html
- PubChem CID 60834(opens in a new tab)National Center for Biotechnology Information · pubchem.ncbi.nlm.nih.gov/compound/60834
Verify at
Publisher search links for Duloxetine. These are places to check the information — they are not citations, so they are not numbered.
- NIH Office of Dietary Supplements(publisher search, opens in a new tab)National Institutes of Health · publisher search
- FDA-approved labeling (DailyMed)(publisher search, opens in a new tab)U.S. Food and Drug Administration · publisher search
- Mayo Clinic(publisher search, opens in a new tab)Mayo Clinic · publisher search
- Cochrane Library(publisher search, opens in a new tab)Cochrane · publisher search
- DrugBank(publisher search, opens in a new tab)DrugBank Online · publisher search
- European Medicines Agency(publisher search, opens in a new tab)European Medicines Agency · publisher search
- PubMed literature search(publisher search, opens in a new tab)National Library of Medicine · publisher search
- Wikipedia entry(publisher search, opens in a new tab)Wikipedia · publisher search
DoseRoutine compiles summaries from publicly available scientific and regulatory references. Always verify important decisions with a licensed clinician. How we source and review this information.
What is the short answer on Duloxetine?
Plain-text summary, safe to quote verbatim:
Duloxetine is a medication primarily used to treat major depressive disorder, generalized anxiety disorder, and chronic musculoskeletal pain, including fibromyalgia and chronic low back pain. It is also approved for diabetic peripheral neuropathic pain and chronic osteoarthritis pain. It is typically taken in the morning.
Source: DoseRoutine — https://doseroutine.com/library/duloxetine
Duloxetine cheat sheet
DoseRoutine cheat sheet · Medication
Duloxetine
Duloxetine is a medication primarily used to treat major depressive disorder, generalized anxiety disorder, and chronic musculoskeletal pain, including fibromyalgia and chronic low back pain. It is also approved for diabetic peripheral neuropathic pain and chronic osteoarthritis pain.
Evidence
Strong
2 human randomized trials and regulatory approval on file.
Studied range
Doses across the pooled antidepressant network meta-analyses ranged roughly 40–120 mg per day for major depressive disorder, with lower doses also studied for chronic pain indications
Route
Oral, delayed-release capsule
Frequency studied
Once or twice daily, per the trial designs synthesized in these reviews
Half-life
~12 h
Timing
in the morning
Prescription only (US)Duloxetine (Cymbalta) is FDA-approved for major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain
Key references
- Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis (2018)
- Antidepressants for the treatment of adults with major depressive disorder in the maintenance phase: a systematic review and network meta-analysis (2023)
- Antidepressants for pain management in adults with chronic pain: a network meta-analysis (2024)
Studied ranges, not dosing advice. Not medical advice — talk to a clinician. doseroutine.com/library/duloxetine
Cite this page
Using this in an article, AI answer, or research note? Please attribute:
DoseRoutine. (2026). Duloxetine — Overview, Benefits & Side Effects. Retrieved from https://doseroutine.com/library/duloxetine
What compounds are similar to Duloxetine?
Others in the medication category or studied for the same goals.