Inter-relationships between isotretinoin treatment and psychiatric disorders: Depression, bipolar disorder, anxiety, psychosis and suicide risks

Abstract

Isotretinoin (Accutane) is a treatment for severe acne that is resistant to other forms of treatment, including antibiotics and topical treatments. The prescription of this drug has been controversial ever since its initial marketing in 1982. It is the only non-psychotropic drug in the Food and Drug Administration top 10 drugs found to be associated with depression. Recently, Bremner et al published an extensive review (until 2010) of the evidence for the association of retinoic acid (RA) with depression and suicide. Some patients who are admitted in psychiatric hospitals report a history of present or past treatment with isotretinoin. Then, the imputability of the molecule in the occurrence of disorders represents necessarily an important question for both professionals and their patients. This paper aims to specify the links between the drug and specific psychiatric disorders. A review of the literature related to isotretinoin, RA, vitamin A, depression, suicide, anxiety, bipolar disorder, psychosis, schizophrenia was performed. Many studies demonstrated an increased risk of depression, attempted suicide and suicide following isotretinoin treatment. However, isotretinoin may have an antidepressant impact, according to some dermatological papers. They consider treating acne with this efficient treatment could improve self-image and make the patient feel better. Several studies showed that patients with bipolar disorder had an increased risk for a clinical exacerbation of symptoms undergoing treatment with isotretinoin. A few studies also seem to suggest a possible link between isotretinoin and psychosis. Nonetheless, studies point out a link between retinoid dysregulation and schizophrenia through modulation of dopamine receptors. From this review, we propose guidelines for isotretinoin prescription to healthcare professionals.

Nuclear Receptors as Regulators of Pituitary Corticotroph Pro-Opiomelanocortin Transcription

“…One potential concern of chronic isotretinoin use is that treatment has been associated with psychiatric disorders, including depression, bipolar disorder, and anxiety [48]. This situation is further complicated by the presence of three distinct RAR isoforms that have redundant but also isotype-specific activities in a context-dependent manner [49,50].…”

Blemish on the Body, Scar on the Mind- Psychiatric Aspects of Acne Vulgaris: An Update.

“…11 The overall frequency of anxiety disorders, generalised anxiety disorders and social phobia in patients with AV was found to be 12%, 6-50% and 2-45.7% respectively. 9,10,15,22,23 The wide differences in the frequency in these various studies could be because of the use of different diagnostic or screening tools. Patients with AV have demonstrated higher performance avoidance and total avoidance scores which caused significant disability in their occupational, social, and familial lives.…”

“…Eating disordered patients may go on restrictive diets in order to control their acne, since levels of androgens (primary stimulants of sebaceous gland activity)are lower in starvation. 27…”

“…He suggested that dysregulation by retinoids may be an important factor in the etiology of schizophrenia. 23 Though isotretinoin was found to worsen obsessive doubting but successful treatment with oral isotretinoin was associated with improvement in depression, anxiety, and obsessive rumination symptoms in acne vulgaris patients. 34…”

Recherche translationnelle sur les troubles cognitifs et comportementaux dans les maladies neurologiques et psychiatriques

“…Citons à titre d'exemple l'isotrétinoïne, (13-cis acide rétinoïque), médicament de l'acné sévère résistant aux autres traitements disponibles, n'appartenant pas à la classe des psychotropes et pourtant associé à des cas de troubles psychiatriques (dépression, troubles de l'humeur, suicides, troubles psychotiques) dans les données de pharmacovigilance [12]. Ces observations de tableaux psychiatriques sont venues ainsi alimenter l'hypothèse neurobiologique de dysrégulation rétinoïde dans certains troubles psychiatriques, dominée par des arguments fondamentaux et biologiques [13][14][15] en y apportant des éléments cliniques. Citons également la kétamine, médicament anesthésique sans effet dépressogène sur la sphère cardiaque et respiratoire, utilisé à la fois en médecine vétérinaire et humaine.…”