Depression Associated with Isotretinoin Therapy

Byrne, Alan; Hnatko, Gary

doi:10.1177/070674379504000915

Cited by 53 publications

(38 citation statements)

References 6 publications

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“…A number of neurological side-effects have been reported including headache and, controversially, depression (Bigby and Stern, 1988;David et al, 1988;Hull and DemkiwBartel, 2000). Numerous anecdotal reports have correlated the use of Accutane with depression (Hazen et al, 1983;Scheinman et al, 1990;Byrne and Hnatko, 1995;Josefson, 1998;Lamberg, 1998); however, at least one epidemiological study has not found evidence for this link (Jick et al, 2000). It has been proposed that shrinkage of the hippocampus (Sheline et al, 1996(Sheline et al, , 2003Sheline, 2000;Vythilingam et al, 2002) or a decline in neurogenesis (Malberg et al, 2000;Vogel, 2000;D'Sa and Duman, 2002;Kempermann, 2002;Duman, 2004) can be contributory factors leading to depression.…”

Section: Neurogenesismentioning

confidence: 94%

Retinoic acid signaling and function in the adult hippocampus

2006

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Retinoic acid (RA) is an essential growth factor, derived from vitamin A, which controls growth by activating specific receptors that are members of the nuclear receptor family of transcriptional regulators. Its function in control of growth and differentiation in the embryonic CNS has been extensively investigated, but a role for RA in the mature brain has only recently become apparent. Although the adult CNS has much less capacity for change compared to the embryonic CNS, a limited amount of flexibility, referred to as neural plasticity, still exists. It is these processes that RA influences in the adult brain, including long-term potentiation and neurogenesis. The hippocampus is a brain region dependent upon neural plasticity for its function in learning and memory, and this review focuses on the roles that RA may play in regulating these processes in the adult.

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Section: Neurogenesismentioning

confidence: 94%

Retinoic acid signaling and function in the adult hippocampus

2006

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“…One of the patients was rechallenged with isotretinoin and experienced a recurrence of symptoms 3 months after re-initiation of treatment. Several other authors have reported individual cases of abatement of symptoms of depression and/or suicidality after discontinuation of isotretinoin (Bigby and Stern 1988;Bravard et al 1993;Burket and Storrs 1987;Byrne and Hnatko 1995b;Duke and Guenther 1993;Ng et al 2002). For instance, Barak reported that 4/5 patients who developed psychosis after receiving isotretinoin had an improvement in symptoms with cessation of isotretinoin and treatment with antipsychotics (Barak et al 2005).…”

Section: Cases Of Challenge/dechallenge Related To Isotretinoin and Dmentioning

confidence: 99%

The neurobiology of retinoic acid in affective disorders

Bremner

McCaffery

2008

Progress in Neuro-Psychopharmacology and Biological Psychiatry

147

154

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Current models of affective disorders implicate alterations in norepinephrine, serotonin, dopamine, and CRF/cortisol; however treatments targeted at these neurotransmitters or hormones have led to imperfect resolution of symptoms, suggesting that the neurobiology of affective disorders is incompletely understood. Until now retinoids have not been considered as possible contributors to affective disorders. Retinoids represent a family of compounds derived from Vitamin A that perform a large number of functions, many via the vitamin A product, retinoic acid. This signaling molecule binds to specific retinoic acid receptors in the brain which, like the glucocorticoid and thyroid hormone receptors, are part of the nuclear receptor superfamily and regulate gene transcription. Research in the field of retinoic acid in the CNS has focused on the developing brain, in part stimulated by the observation that isotretinoin (13-cis retinoic acid), an isomer of retinoic acid used in the treatment of acne, is highly teratogenic for the CNS. More recent work has suggested that retinoic acid may influence the adult brain; animal studies indicated that the administration of isotretinoin is associated with alterations in behavior as well as inhibition of neurogenesis in the hippocampus. Clinical evidence for an association between retinoids and depression includes case reports in the literature, studies of health care databases, and other sources. A preliminary PET study in human subjects showed that isotretinoin was associated with a decrease in orbitofrontal metabolism. Several studies have shown that the molecular components required for retinoic acid signaling are expressed in the adult brain ; the overlap of brain areas implicated in retinoic acid function and stress and depression suggest that retinoids could play a role in affective disorders. This report reviews the evidence in this area and describes several systems that may be targets of retinoic acid and which contribute to the pathophysiology of depression.

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“…Originally intended to treat severe nodular acne that was unresponsive to conventional treatments, the use of 13-cis-RA for milder forms of acne is increasing (Hull and D'Arcy, 2003). Since the mid-1980s, reports in the literature suggest a relationship between 13-cis-RA use and the onset of psychological symptoms including depression, suicidal ideation, and psychosis (Hazen et al, 1983;Bigby and Stern, 1988;Scheinman et al, 1990;Byrne and Hnatko, 1995;Wysowski et al, 2001;Ng and Schweitzer, 2003;O'Connell et al, 2003;Barak et al, 2005). However, there are also studies suggesting that there is no evidence of such a link (Jick et al, 2000;Jacobs et al, 2001;Ferahbas et al, 2004;Chai et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Chronic Administration of 13-Cis-Retinoic Acid Increases Depression-Related Behavior in Mice

O’Reilly

Shumake

González-Lima

et al. 2006

Neuropsychopharmacol

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Retinoid signaling plays a well-established role in neuronal differentiation, neurite outgrowth, and the patterning of the anteroposterior axis of the developing neural tube. However, there is increasing evidence that nutritional vitamin A status and retinoid signaling play an important role in the function of the adult brain. 13-Cis-retinoic acid (13-cis-RA) (isotretinoin or Accutane), a synthetic retinoid that is an effective oral treatment for severe nodular acne, has been linked with depression and suicide in patients. The purpose of this study was to test the hypothesis that chronic administration of 13-cis-RA would lead to depression-related behaviors in mice. Young, adult male mice received 13-cis-RA (1 mg/kg) by daily intraperitoneal injection for 6 weeks. This treatment paradigm produced plasma levels of 13-cis-RA that are comparable to those reported in human patients taking Accutane. In both the forced swim test and the tail suspension test, we found that 13-cis-RA-treated mice spent significantly more time immobile compared to vehicle-treated controls. In the open field test, there was no change in anxiety-related behavior in 13-cis-RA-treated mice. Furthermore, chronic administration of 13-cis-RA did not impair locomotion in either the open field or the rotarod test. Taken together, these results suggest that administration of 13-cis-RA increases depression-related behaviors in mice.

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Depression Associated with Isotretinoin Therapy

Cited by 53 publications

References 6 publications

Retinoic acid signaling and function in the adult hippocampus

Retinoic acid signaling and function in the adult hippocampus

The neurobiology of retinoic acid in affective disorders

Chronic Administration of 13-Cis-Retinoic Acid Increases Depression-Related Behavior in Mice

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