Does Cymbalta (duloxetine) cause stomach upset, headache, and tinnitus?

Does Cymbalta (Duloxetine) Cause Stomach Upset, Headache, and Tinnitus?

Yes, Cymbalta commonly causes stomach upset and headache, but tinnitus is rare and primarily occurs during discontinuation rather than during active treatment.

Gastrointestinal Side Effects

Stomach upset is one of the most common adverse effects of duloxetine. The American Academy of Child and Adolescent Psychiatry reports that gastrointestinal effects—including nausea, dry mouth, abdominal discomfort, vomiting, diarrhea, and constipation—are common side effects of Cymbalta 1.

• Nausea is the single most frequent adverse event, occurring most prominently during the first week of treatment and with initial dosing 2, 3.
• In clinical trials, nausea was the only adverse event that resulted in significantly more treatment discontinuations in duloxetine recipients compared to placebo recipients 2.
• Gastrointestinal disturbance typically worsens significantly after the first week of duloxetine treatment, but subsequent dose escalations (from 60 mg to 90 mg to 120 mg daily) produce either no significant worsening or actual improvement in GI symptoms 3.
• Acid reflux has been reported as a rare adverse effect, occurring in only 1.38% of patients 4.

Starting at 30 mg daily for one week before escalating to 60 mg significantly reduces treatment-emergent nausea compared to starting directly at 60 mg 1, 3.

Headache

Headache is a common neurological side effect of duloxetine. The American Academy of Child and Adolescent Psychiatry reports that neurological effects such as dizziness, headache, tremor, insomnia, and somnolence are common side effects 1.

• Headache was among the most frequently reported treatment-emergent adverse events in clinical trials 2, 5.
• Most headaches are mild to moderate in severity and occur during the initial treatment phase 2.
• Headaches should substantially improve or resolve by week 2-3 of continuous duloxetine therapy, as these side effects tend to diminish as the body adjusts to the medication 6.
• Persistent or worsening headaches beyond the initial adaptation period may indicate the need to modify treatment 6.

Tinnitus (Ear Ringing)

Tinnitus is not a common side effect during active duloxetine treatment but is a recognized discontinuation symptom. The FDA label states that tinnitus has been spontaneously reported as an adverse event occurring upon discontinuation of SNRIs, particularly when abrupt 7.

• During active treatment in adult placebo-controlled clinical trials, tinnitus was not listed among the common adverse events occurring at ≥1% 7, 2.
• Tinnitus appears primarily in the context of discontinuation syndrome, along with other symptoms such as dizziness, headache, nausea, paresthesias (electric shock sensations), anxiety, and irritability 7.
• The American Academy of Child and Adolescent Psychiatry notes that discontinuation syndrome may occur when stopping Cymbalta abruptly 1.

Clinical Management Recommendations

To minimize stomach upset and headache:

• Start duloxetine at 30 mg once daily for one week, then increase to the target dose of 60 mg once daily 8, 1.
• Advise patients that nausea and headache are most prominent in the first 1-2 weeks and typically resolve by weeks 2-3 6, 3.
• Assess patient status within 1-2 weeks of initiating therapy to ensure tolerability 6.

To prevent tinnitus and other discontinuation symptoms:

• Never discontinue duloxetine abruptly; taper gradually over at least 2-4 weeks, especially after treatment longer than 3 weeks 1, 7.
• If intolerable symptoms occur following dose reduction, resume the previously prescribed dose and then decrease more gradually 7.

Important Caveats

• The majority of adverse events with duloxetine are mild to moderate in severity and occur during the first week of treatment at 60 mg once daily 3.
• Serious adverse events are uncommon, but patients should be monitored for rare complications including hepatic failure, severe skin reactions, and serotonin syndrome 1, 7.
• Duloxetine can increase blood pressure and heart rate, which should be measured prior to initiating treatment and monitored periodically 7.