Isotretinoin (Roaccutane®, Roche), a retinoid, has been available in Singapore since 1984 and is used for the treatment of severe nodular cystic acne and acne which has failed to respond to other therapies.

To-date, the causal linkage between isotretinoin treatment and psychiatric events has not been established from the observations in post-marketing reports due to under-reporting, the high incidence of psychiatric illness in the population and the incomplete nature of spontaneous reports. Nonetheless these observations serve as important signals of a potential drug safety problem.

Based on the post-marketing surveillance reports received by Roche, as of April 2000, there has been 5,665 serious adverse event reports reported with Accutane® (brand name of isotretinoin in the US). Psychiatric disorders constitute 18.8% of these reports.

The US Food and Drug Administration (FDA) has performed an analysis on the reports of suicides and hospitalised cases of depression, suicidal ideation and suicide attempts in US patients on isotretinoin for the period 1982 to May 2000. In total, there were 147 cases reported of suicide and hospitalised depression. Among these, 38% had a previous psychiatric history, 33% had none, and information was unknown for 29%.

Thirty-seven of these persons committed suicide during or after isotretinoin use. The median age was 17 years and 84% of the 37 reports were male. The median time from starting use of isotretinoin to suicide was about three months. Eighty-five persons were hospitalised for depression, suicidal ideation, and/or suicide attempt during or shortly after isotretinoin use, and 25 persons reported being hospitalised for these conditions after stopping isotretinoin. Of these reports, 56% of the patients were female. The median time for onset of the adverse effects from use of isotretinoin to hospitalisation was about one month, and 18% experienced persistent problems after isotretinoin was stopped.

In Singapore, the Pharmacovigilance (PV) Unit has received one report of depression in a young Chinese male who was prescribed Roaccutane®. However, the patient did not experience any suicidal ideation.

Physicians are advised to be alert for any adverse mood changes in their patients taking isotretinoin and to withdraw the drug if these occur or refer patients to a psychiatric specialist. The warnings on psychiatric and behavioural disorders have been included in the local package insert.