Can Accutane (Isotretinoin) Cause Daytime Fatigue?
Yes, isotretinoin can cause daytime fatigue, though it is not among the most common side effects and occurs in a dose-dependent manner.
Frequency and Dose-Dependency
- Fatigue (tiredness) affects approximately 12% of all isotretinoin users across all doses 1
- The occurrence of fatigue is clearly dose-dependent: only 5% of patients on low doses (<0.25 mg/kg/day) experience tiredness, compared to 18% of those on higher doses (>0.75 mg/kg/day) 1
- In the retrospective review of 1,743 patients, tiredness was significant enough to cause 12 patients (0.7%) to discontinue treatment 1
Context Among Other Side Effects
While fatigue does occur, it is far less common than the nearly universal mucocutaneous effects:
- Cheilitis (dry lips) affects up to 78% of users and is the most common side effect 2, 1
- Dry skin and xerosis are very common 2
- Fatigue ranks alongside eczema as the second-tier side effects at 12% incidence 1
Sleep Quality Considerations
Recent evidence suggests a potential mechanism for daytime fatigue:
- A 2025 study found that isotretinoin significantly worsened sleep quality during treatment, with Pittsburgh Sleep Quality Index scores increasing from 9.5-11.5 before treatment to 14.0-18.0 during treatment (p<0.001) 3
- The FDA label notes that hypersomnia has been reported as a side effect 3
- Experimental studies suggest retinoic acids may affect brain pathways that regulate sleep 3
Clinical Management
- If fatigue develops, consider dose reduction rather than immediate discontinuation, as lower doses (<0.25 mg/kg/day) have substantially lower rates of tiredness while maintaining efficacy 1
- Assess for other contributing factors including depression (which can manifest as fatigue), as mood changes should be monitored at each visit per FDA guidelines 4
- Evaluate sleep quality, as isotretinoin-induced sleep disturbances may be contributing to daytime fatigue 3
Important Caveat
Fatigue can also be a symptom of depression, which requires careful monitoring:
- The FDA mandates assessment for depression symptoms at each visit, including fatigue as one potential manifestation 4
- However, most studies show isotretinoin improves mood as acne improves 2
- If fatigue is accompanied by sad mood, loss of interest in activities, or other depressive symptoms, psychiatric evaluation is warranted 4