While a highly effective treatment for acne, isotretinoin has been associated with a variety of potential neuropsychiatric adverse effects, including mood changes.1,2 Here, we present three cases of patients experiencing disturbing, vivid dreams while on isotretinoin.
Case 1:
A female patient in her 20s started isotretinoin 40mg/day (0.45 mg/kg/day) for severe acne. After 2 weeks, she began to experience progressively worsening episodes of nighttime restlessness and vivid nightmares occurring 1–2 times per night. Her partner observed she would wake up in a state of panic, requiring extensive reassurance to fall back asleep. She otherwise experienced no mood changes. Laboratory values found that her vitamin A levels were in the lower half of normal at 43.4 mcg/dL (ref 32.5–78.0 mcg/dL). A trial of low-dose vitamin A supplementation (5000 IU/day) was started, and the patient reported resolution of her symptoms after 2 weeks. A subsequent recurrence of vivid dreams occurred two days after she ran out of vitamin A; however, her symptoms continued after she restarted vitamin A until the completion of her treatment course.
Case 2:
A 15-year-old girl started isotretinoin 20mg/day for severe acne. The dose was subsequently increased to 40mg/day after one month. Three weeks later, she began to experience nearly daily episodes of disturbing, vivid, and lucid dreams. After decreasing her dose to 40mg every other day, symptom resolution was noted without recurrence throughout the rest of her isotretinoin course.
Case 3:
A 12-year-old girl started isotretinoin 20mg/day for severe acne. The dose was increased to 40mg/day, then 60mg/day over the next two months. Incidentally, she developed urticaria during the second month of therapy that resolved with non-sedating antihistamines. Three weeks after starting the 60mg/day dose, she began to experience nearly daily episodes of terrifying dreams in which she was dying. She ultimately continued 3 additional months of treatment at this dose with continued symptoms. Shortly after completing her isotretinoin course, her symptoms resolved.
In all cases, the symptoms were salient enough to be brought up spontaneously by the patient without prompting. None of these patients had any history of psychiatric conditions or psychotropic substance use. The 2nd patient was diagnosed with generalized anxiety disorder 6 months after completing her isotretinoin course.
These cases highlight a potential rare association between isotretinoin and the development of vivid dreams. Although it is possible that these symptoms were coincidental, the severe and dramatic nature of these dreams, as well as the temporal association with isotretinoin initiation and improvement with dose changes or discontinuation, suggest a potential causal relationship.
There are several mechanisms that might explain isotretinoin-associated vivid dreams. Retinoic acid receptor signaling influences the regulation of delta waves, which are associated with deep and rapid eye movement sleep.3 It is possible that isotretinoin could disrupt these deeper sleep stages that are important for dreaming. Additionally, vitamin A promotes neurogenesis and synaptic functioning in the hippocampus, which is involved in memory and dreaming, while isotretinoin has been associated with reduced hippocampal neurogenesis.4,5 Although more data are needed, given their potentially contrasting effects, low-dose vitamin A supplementation might have a role in managing isotretinoin-associated vivid dreams. As low-dose vitamin A (i.e., 5000 IU/day) is substantially less than doses used to treat acne and below the upper limit of recommended daily allowance, it is unlikely to meaningfully increase the risk of vitamin A toxicity.6
Future studies are needed to explore further whether vivid dreams are a potential rare side effect of isotretinoin and to identify optimal management strategies. Gupta et al. describe two cases that improved spontaneously after 4–5 weeks.1 In our series, one patient had possible improvement following low-dose vitamin A supplementation and one following isotretinoin dose reduction. The third continued the same dose and did not have improvement until stopping isotretinoin.
Table 1.
Summary of Cases
| Case 1 | Case 2 | Case 3 | |
|---|---|---|---|
| Age, Sex | 20s, F | 15, F | 12, F |
| Initial Isotretinoin Dose, mg/day (mg/kg/day) | 40 (0.45) | 20 | 20 |
| Isotretinoin Dose with Vivid Dreams, mg/day (mg/kg/day) | 40 (0.45) | 40 | 60 |
| Onset of Symptoms | 2 weeks after starting 40mg/day | 3 weeks after starting 40mg/day | 3 weeks after starting 60mg/day |
| Symptoms | Daily vivid dreams, nightmares, nighttime restlessness | Daily disturbing vivid and lucid dreams | Daily terrifying dreams in which she was dying |
| Outcome | Improved 2 weeks after starting low-dose vitamin A (5000 IU/day). Subsequently recurred two days after stopping vitamin A. However, after restarting vitamin A, her symptoms persisted until the completion of her treatment course. | Decreased Isotretinoin to 40mg every other day | Completed course of Isotretinoin |
Role of the Funder/Sponsor:
The National Institute of Arthritis and Musculoskeletal and Skin Diseases had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Funding source:
Dr Barbieri is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under award No. 1K23AR078930.
Footnotes
Conflict of interest: Dr Barbieri reported personal fees from Dexcel Pharma for consulting outside the submitted work. There are no other conflicts of interest to disclose.
Patient Consent: The authors thank the 3 patients and their families for granting permission to publish their information.
References
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