Published: December 1998


Acute Depression and Isotretinoin

Information on this subject has been updated. Read the most recent information.

Prescriber Update 17: 17-19
December 1998

Dr Marius Rademaker, Specialist Dermatologist, Health Waikato, Hamilton

Isotretinoin (Roaccutane) is an extremely effective anti-acne preparation.  However, in a small number of patients (less than 1%) it may be associated with symptoms of a major depressive episode.  Symptoms resolve rapidly (within 2-7 days) on discontinuation of the medicine.  After a period off medication, it is worthwhile recommencing therapy at a lower dose.

Mild depression common but often masked by musculoskeletal effects

A spectrum of central nervous system side effects, similar to that observed with hypervitaminosis A syndrome,1 can be induced with synthetic retinoids such as isotretinoin (Roaccutane) and neotigason (Acitretin).

At July 1998, the Centre for Adverse Reactions Monitoring (CARM) database held 9 reports of depression or symptoms of depression with isotretinoin (5 severe, 4 mild), although one case was considered unlikely to be associated with the drug.  The symptoms were somnolence, aggressiveness, dizziness, depersonalisation, abnormal behaviour, fatigue, and personality disorder. Recurrence occurred in the 2 cases that were rechallenged.

Early studies suggest that up to 10% of patients with nodulocystic acne treated with isotretinoin will develop symptoms of mild depression.2,3  However, it is often difficult to separate such symptoms from the musculoskeletal adverse effects of the retinoids, namely fatigue, muscle aches and pains.  The depression subsides with discontinuation of isotretinoin, but may recur with reinstitution of therapy.4

Acute severe depression rare (<1%)

Acute, severe depression, on the other hand, is more obvious although fortunately much less common.  Scheinman et al reported 7 cases of major depressive symptoms occurring amongst a group of 700 patients (1%) involved in various trials of oral isotretinoin used for cystic acne, psoriasis, basal cell carcinoma or cutaneous disorders of keratinisation.5

Two of the seven patients had a prior history of depression.  The symptoms of depression occurred during the first course of isotretinoin in five patients, and in the second or third course in the remaining two patients.  The seven patients voluntarily reported the following characteristic symptoms of a major depressive episode: fatigue (5), irritability (4), decreased concentration (4), sadness (4), crying spells (3), loss of motivation (3), forgetfulness (2), suicidal ideation (1), anhedonia (1) abnormal dreams (1) and fear of going insane (1).  All symptoms resolved within 2 to 7 days of discontinuing the medicine.  One patient was rechallenged several months later, with recurrence of the depressive symptoms during the third month of his second course of therapy.

Stop drug, consider rechallenging later at lower dose

Isotretinoin should be discontinued in patients who develop symptoms of a major depressive episode.  After a period of time, it may be worthwhile rechallenging the patient with a smaller dose.  If symptoms recur, either the medicine should be discontinued or the patient treated with a selective serotonin reuptake inhibitor.

Effective treatment with isotretinoin reduces anxiety & depression

This adverse effect of isotretinoin needs, however, to be placed into context.  Many patients with acne demonstrate symptoms of anxiety and depression which can range from psychological distress to psychiatric morbidity.  Isotretinoin is an extremely effective anti-acne treatment, and it is therefore not surprising that in most cases there is a significant reduction in both anxiety and depressive symptoms following successful treatment with isotretinoin.5

Class effect likely but depression not reported with topical retinoids

The side effects of isotretinoin are likely to be a class effect, so one would expect to see similar problems with other retinoids used for non-dermatological indications.  There have been no reports of depression following use of topical retinoids.

Correspondence to Dr Marius Rademaker, Specialist Dermatologist, Health Waikato, Hamilton. phone 07 839 8944, fax 07 839 8787, e-mail

  1. Peck GL, DiGiovanna JJ. The retinoids. In: Fitzpatrick TB, et al, eds. Dermatology in general medicine. 4th ed. New York: McGraw-Hill, 1993;2883-908.
  2. Bruno NP, Beacham BE, Burnett JW. Adverse effects of isotretinoin therapy. Cutis 1984;33:484-9.
  3. Hazen PG, Carney JF, Walker AE, et al. Depression - a side effect of 13-cis-retinoic acid therapy. J Am Acad Dermatol 1983;9:278-9.
  4. Scheinman PL, Peck GL, Rubinow DR, DiGiovanna JJ, et al. Acute depression from isotretinoin. J Am Acad Dermatol 1990;22:1112-4.
  5. Rubinow DR, Peck GL, Squillace KM, Gantt GG. Reduced anxiety and depression in cystic acne patients after successful treatment with oral isotretinoin. J Am Acad Dermatol 1987;17:25-32.


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