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Retrospective, Prospective and Epidemiology Studies


RETROSPECTIVE STUDY

Millard et al, 1999 - 6/38 patients were identified with major psychiatric symptoms. All patients recovered in 4-6 weeks after stopping medication.

Adverse Mood and Behaviour change in young patients on systemic isotretinoin.British Journal of Dermatology. Millard L.G. 1999

An abstract of paper presented at the BAD conference in 1999. It is a retrospective study of 38 young patients who received isotretinoin with no previous depression identified 6 patients who developed major psychiatric symptoms during treatment. All patients recovered in 4-6 weeks after stopping medication. Two patients were given Prozac. There was no reoccurrence of psychiatric illness on follow up in 18 months. Systemic isotretinoin appears to cause a small but real increase in psychiatric morbidity which needs active identification at clinic review by simple oral questionnaire
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PROSPECTIVE STUDY (QUESTIONAIRRE)

Barak et al, 2005 - describes five adults (5/500 soliders) who devoloped manic psychosis...The present case-series is suggestive of an increase in the likelihood of an association between exposure to isotretinion and manic psychosis.

Affective Psychosis following Accutane (isotretinoin) treatment. Int Clin Psychopharmacology. Barak Y.2005. Isotretinoin (Accutane) ranks in the top 10 of the US Food and Drug Administration's database of drugs associated with reports of depression and suicide attempts. However, this association is still controversial because up to 5.6% of patients with moderate acne may have pre-existing suicidal ideations, improvement of acne often reduces associated depression, and isotretinoin users are reportedly no more likely than those taking antibiotics for acne to have depression or commit suicide. We describe a series of cases of manic psychosis that developed in a 1-year period (2003) in association with isotretinoin treatment and resulted in suicidality and progression to long-standing psychosis. Cases were drawn from 500 soldiers who had been evaluated in a military specialists dermatology clinic for severe acne. Data were summarized from medical records of five severe acne patients treated by isotretinion during their compulsory military service. Data from their draft board examinations and service records, as well as repeated clinical assessments by certified psychiatrists at the Israel Defense Forces (IDF) Mental Health Department clinic, were evaluated. Five young adults developed manic psychosis within a mean of 7.6 months of exposure to isotretinoin. In three cases, this was accompanied by a suicide attempt, and in three cases, psychosis lasted for longer than 6 months. Either a personal history of obsessive-compulsive disorder, neurological insult or family history of a major psychiatric illness were present in all cases. The present case-series is suggestive of an increase in the likelihood of an association between exposure to isotretinion and manic psychosis. Associated risk factors were both family and personal history of psychiatric morbidity. Further studies are needed to establish our findings.


Hull PR et al 2000
- Depression was noted in 4% of patients (124)
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Isotretinoin Use in Acne: Prospective Evaluation of Adverse Events.J. Cutan Med Surg, 4 (2) 66-70. Hull PR, Demkiw-Bartel C. Over the period between January 1991 and July 1996, 124 courses of treatment with isotretinoin for severe acne were followed in Saskatchewan, Canada. The patients were treated for 4 months at a dose of 1mg/Kg/day. A questionnaire was administered monthly, inquiring specifics about side effect. Depression occurred in about 4% of patients and tended to persist throughout the treatment. Only one of these patients had a past history of depression. Unusual tiredness occurred in about a quarter of the patients with a slight drop in the last two months of treatment. Other CNS adverse effects included headaches (7-11%), weight loss (3-10%) and parnoychia (1-0%).

Bruno,N.P et at 1984 Adverse Effects of Isotretinoin Therapy. Depression noted in 10% of patients.

This is a report of the findings of a clinical and laboratory toxic study on ninety-four patients receiving isotretinoin therapy for cystic acne. The patients were divided into two dosage: 0.75 to 1.21 mg/kg a day, and 0.10 to 0.22 mg/kg a day for sixteen weeks. The most common side effects observed were: acne flarnes, cheilitis, facial erythema, xerosis, minor nose bleeds, dry muscous membranes, musculoskeletal symptoms. Central nervous system disorders, including depression, headaches and insomnia and were each seen in approximately 10 percent of the patients in both groups.


EPIDEMIOLOGY STUDIES

The Jick Study found no increased risk of depression in individuals treated with isotretinoin when compared to antibiotics.

Criticisms of Jick Study:

FDA Hearings - Wysowski, 2000 " a large retrospective cohort epidemiological study, referred to as the Jick study for the principal investigator, Susan Jick, that was funded by Hoffmann-LaRoche, found no increased risk of depression in individuals prescribed Accutane compared with those prescribed antibiotics for acne. However, the study had some important limitations. ...Because of these problems and limitations, we believe the results of the Jick study are inclusive.

Wysowski, 2001 -"The industry-sponsored study conducted by Jick et al was intended to help resolve the question of etiology of depression in patients treated with isotretinoin. However, because of the limitations of the study, we believe that the findings are inconclusive and that further studies on the association between isotretinoin and depression should be initiated".

Ng, 2001 (Case Report) -"Despite having the largest data set yet published, the study remains inconclusive because of methodological limitations including the retrospective study design, use of computerised database, inadequate method for case recognition and lack of psychometric measure. Significant variables like severity of acne, treatment compliance, concomitant medications and comorbid conditions were not adequately controlled."

Bremner, 2003 (Review) -"There are several limitations to this study that are worthy of comment." Psychiatric diagnoses were recorded in the database only when patients were hospitalized or were evaluated by a psychiatrist for depression."."The authors also reported relative risks as high as 1.8 for depression with isotretinoin (that is close to a 2-fold increase in risk), which would probably have been statistically significant with a larger sample."

Hull, 2003 (Review)- "[T]here are a number of weaknesses in the study design" "Much of the study was not about depression. Other weaknesses include the failure of the drug data to maximize the identification of the study disease and lack of an attempt at validation".

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