Isotretinoin and Psychotic Mania

The Editor,

Sir,

Isotretinoin is a synthetic oral retinoid, which is effective against severe, recalcitrant, nodulocystic acne. Since it entered the market, it has been associated with a variety of adverse psychiatric effects, including depression, psychosis, mood swings, violent behaviour, suicide and suicide attempts (1). In a retrospective review of 1743 patients, many side effects were reported. However, only 22 patients had mood swings (2).

Three cases with bipolar disorder, who experienced an untoward psychiatric side effect while receiving isotretinoin treatment, were reported. In that study, psychiatric side effects of isotretinoin were examined in a larger group of patients with bipolar disorder than in previous research (3).

In another review, isotretinoin (Roaccutane) ranks in the top 10 of the US Food and Drug Administration's database of drugs associated with reports of depression and suicidal attempts (4). However, this association is still controversial for the following reasons: (a) up to 5.6% of patients with moderate acne may have pre-existing suicidal ideations, (b) improvement of acne often reduces associated depression and (c) isotretinoin users are not more likely to have depression or commit suicide than those taking antibiotics for acne (4). There are many case reports and reviews about the relationship between depression, suicide and isotretinoin.

We suggest that there is a relationship between isotretinoin and manic psychosis. Further studies are required to strengthen our findings.

TA is a 19-year old female student in law school. She was brought in by her family with complaints of insomnia, nervousness, fear and extreme religious pursuits.

Two weeks previously, she was restless and irritable and had bizarre behaviour. She claimed that she was a special kind of human. Her symptoms increased in the last two days and her family reported that she had totally changed and became religious.

In her mental examination, she was irritable. There were spontaneous increases in her attention. She had paranoid and grandiose delusions and her insight was poor.

When her medical history was examined, it was noted that she had visited a dermatologist two months ago with severe acne complaints. Roaccutane was prescribed to her. During her treatment, her skin complaints had disappeared. Triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone, liver function tests and blood count results were normal.

She was diagnosed with manic episode, and haloperidol (20 mg/day), biperidin (4 mg/day) and olanzapine (20 mg/day) were prescribed to her. Her Roaccutane medication was stopped. No pathologic findings were observed in her magnetic resonance imaging (MRI) and electroencephalography (EEG) results.

She recovered from the acute episode in about 15 days. Haloperidol was reduced and later discontinued. Valproate (1000 mg/day) mercury treatment was maintained with olanzapine (10 mg/day).

According to her Rorschach test results, she had a neurotic structuring, feelings of inadequacy and she was depressive, anxious and narcissistic. She used to cope with difficulties with hypomanic defence mechanisms. No family history of psychiatric illness was determined. Approximately one month later, she asked us to restart Roaccutane medication. Because it might lead to depression, we explained that restarting Roaccutane medication was not a good idea. The patient was closely monitored and controlled while reducing and discontinuing olanzapine. She was able to continue her education. Neither manic nor depressive episodes recurred during two years follow-up, although her grandmother died during the treatment process. After two years, valproate was reduced and later discontinued. During this period, she finished her study and began to work in a corporation. We visited her every three months. Finally, she went to live in another country after not using any drug, and psychiatric control for 1.5 years.