Duloxetine Alternatives: What to Try When It’s Not Working

If duloxetine (Cymbalta) isn’t helping or the side effects are a deal-breaker, you have choices. Duloxetine is an SNRI used for depression, anxiety, neuropathic pain and fibromyalgia. Alternatives fall into two groups: other medications that target mood or nerve pain, and non-drug approaches that can help symptoms on their own or make drugs work better.

Common drug alternatives

Pick an alternative based on why you were taking duloxetine. For depression or anxiety: SSRIs like sertraline (Zoloft) or escitalopram (Lexapro) are often first choices. Bupropion (Wellbutrin) helps mood and energy and usually causes less sexual side effects. Mirtazapine can help if sleep and appetite are also issues.

If you need a drug that treats both mood and pain, venlafaxine (Effexor) is another SNRI some people tolerate better. For neuropathic pain or fibromyalgia specifically, consider tricyclics like amitriptyline or nortriptyline; they can be effective at low doses for nerve pain. Pregabalin (Lyrica) or gabapentin are commonly used for nerve pain and fibromyalgia, and topical lidocaine patches can help localized nerve pain without systemic side effects. Milnacipran is another SNRI approved for fibromyalgia in some places.

Keep in mind side-effect profiles and medical issues: duloxetine can raise blood pressure, cause nausea, dry mouth, or liver problems in rare cases. If you have liver disease, heavy alcohol use, uncontrolled hypertension, or are on MAOIs, discuss these with your doctor before switching.

How to switch and what to ask your doctor

Don’t stop duloxetine suddenly. It can cause withdrawal symptoms like dizziness, irritability, or flu-like feelings. Ask your prescriber whether to taper duloxetine while starting the new drug (cross-taper) or to allow a washout period—this is especially important if switching to or from an MAOI.

Bring a short list to your appointment: 1) why you want to change (side effects, no effect, cost), 2) other medical conditions (blood pressure, liver, pregnancy), 3) current meds and supplements to check interactions, and 4) what outcome you expect (better sleep, less pain, fewer sexual side effects). Ask how long the new treatment should take to show benefit and what side effects to watch for. Also ask about monitoring (blood pressure checks, liver tests) if needed.

Non-drug options matter. Cognitive behavioral therapy (CBT), graded exercise, sleep hygiene, and pain-focused rehab often improve results when combined with medication. For chronic pain, pacing, physical therapy and certain online pain programs can reduce reliance on meds.

Bottom line: there’s no one-size-fits-all swap for duloxetine. Work with your clinician to pick the best option for your symptoms, health history, and lifestyle. If you feel worse after changes or have strong withdrawal effects, contact your provider right away.