Bandolera, al igual que muchos lectores se encuentra con asociaciones raras entre una intervención y algunos efectos adversos raros pero importantes y, además interesantes. Intersantes porque porque cualquier evidencia que nos ayude a evitarlos es importante. Además cuando los efectos adversos son raros determinar la relación con una causa puede ser una tarea casi imposible.
Un ejemplo lo constituye la utilizacion de la isotretinoina para el acné y los informes axcerca de suicidios, especialmente en hombres jóvenes. Una búsqueda encuentra tres artículos recientes, dos de ellos revisiones sistemáticas, que pueden ayudar en alguna medida pero dejan insatisfecho a los que quieran encontrar una relacion entre isotretionina y suicidio.
Las dos revisiones sistemáticas [1,2] realizan las búsquedas en tres de cuatro bases de datos relevantes, especialmente para los estudios que relacionen depresión y suicidio con los fármacos. Se podrían tratar de estudio de cohortes o ensayos aleatorizados. Uno informaba de casos [1] y el otro no[2].
De forma sorpendente, dados los criterios similares de inclusión, sólo cuatro estudios fueron comunes a ambos estudios.
The first review included case reports as well as formal studies, mainly from reports to registration authorities. Case reports included depression, psychiatric reactions, and some suicide ideation, suicide attempts, and completed suicides. In 25 cases documented by the FDA, cessation of drug was associated with resolution of mood disturbance, and reinstitution followed by a period of depression.
Many of the studies were small, and only two examined suicidal behaviour and isotretinoin use. One found no events, and the other, looking at attempted and completed suicide together, found 37 such events in 35,000 person-years of isotretinoin exposure. The only predictor was a previous history of depression or psychosis, which had an 8-fold increased risk.
En el año 2003 todos los casos de psicosis asociados a exposicion a isotretinoina entre los miembros de la Fuerza de Defensa Israelí fueron revisados. En este periodo 500 miembros de esta institución visitaron al dermatologo por problemas de acné severo. There were five cases, three female, aged 19 or 20 years, all treated with isotretinoin before developing psychiatric morbidity. All had undergone pre-intake assessment at age 17, including a review of psychiatric history. The lag time was between three and 11 months, with a median of eight months. Three of the five soldiers had attempted suicide.
In all five cases there were predisposing factors, including obsessive-compulsive disorder, family history of schizophrenia or bipolar disorder, pituitary tumour, or intractable headache after head trauma. Three had more than one predisposing condition. One of the cases has a sibling with a manic episode after isotretinoin treatment.
Es imposble afirmar desde la evidencia disponible que existe una relación entre la isotretionina y la conducta suicida. It is impossible to say from the evidence available that there is a link between isotretinoin and suicidal behaviour. Neither is it impossible to say that there is no such link. But there are now two tenuous pieces of evidence to suggest that giving isotretinoin to young people with acne who either themselves have depression or psychiatric history, or who have a family history, may not be the best of ideas.
Young people have higher suicide risk, and acne has itself been associated with increased depression and suicidal behaviour. So is mental illness, and the lifetime risk of suicide is 1 in 20 in schizophrenia [4]. Very high suicide risks can occur on admission to and after discharge from psychiatric hospitals [5].
For a young person with acne and a personal or family history of depression or mental illness, the risk of suicide or suicidal behaviour must be high. Whether treating acne with isotretinoin increases the risk further is an almost impossible question to answer. It may be best avoided in those circumstances by appropriate history-taking.
The issue here, like so many other cases, is not so much whether therapies are effective or harmful, but in whom they are effective or harmful. This is a much under-researched area, where regulation and trials fail practice. It also asks some fundamental questions about our priorities.