Acute depression from isotretinoin

Scheinman, Pamela L.; Peck, Gary L.; Rubinow, David R.; DiGiovanna, John J.; Abangan, Donita L.; Ravin, Paula D.

doi:10.1016/s0190-9622(08)81018-3

Cited by 82 publications

(78 citation statements)

References 6 publications

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“…Many authors reported the onset of depression at one month after start of treatment (Bigby and Stern 1988;Bravard et al 1993;Bruno et al 1984;Byrne and Hnatko 1995a;Cott and Wisner 1999;Duke and Guenther 1993;Gatti and Serri 1991;Hazen et al 1983; Villalobos et al 1989;Wysowski et al 2001b). Of the case series, Hazen (Hazen et al 1983) reported onset of depression at 2 weeks in the six patients in their paper, while all three of the other case series reported onset at one month (Bruno et al 1984;Hull and Demkiw-Bartel 2000;Scheinman et al 1990). Other authors reported an onset of symptoms at two months after start of treatment (Bigby and Stern 1988;Burket and Storrs 1987;Hepburn 1990;Lindemayr 1986).…”

Section: Temporal Association Between Isotretinoin Treatment and Deprmentioning

confidence: 97%

“…Isotretinoin: A significant number of case reports exist in the literature that describe depression, suicidality, psychosis, violence and aggression developing in conjunction with isotretinoin treatment (Bigby and Stern 1988;Bravard et al 1993;Byrne et al 1998;Byrne and Hnatko 1995a;Duke and Guenther 1993;Gatti and Serri 1991;Hazen et al 1983;Hull and D'Arcy 2003;Hull and D'Arcy 2004;Hull and D'Arcy 2005;Hull and Demkiw-Bartel 2000;La Placa 2005;Meyskens 1982;Middelkoop 1999;Robusto 2002;Scheinman et al 1990;Villalobos et al 1989). Some of the cases used the Hamilton Depression Scale (Ham-D), a clinician administered rating scale that quantitates the severity of depression.…”

Section: Case Reports and Review Of The Literature Related To Suicidementioning

confidence: 99%

“…Eleven percent of patients reported depression. Scheinman et al (Scheinman et al 1990) reported on 7 cases of depression associated with isotretinoin administration. These patients were part of a larger clinical trial of isotretinoin in 700 patients treated for cystic acne and other skin disorders.…”

Section: Data From Case Series and Uncontrolled Clinical Trialsmentioning

confidence: 99%

“…Estimates of the incidence of depression following treatment with isotretinoin in the four largest series range from 1% (Scheinman et al 1990) to 4% (Hull and Demkiw-Bartel 2000) to 6% (Hazen et al 1983) to 11% (Bruno et al 1984). Lower frequencies are probably found when studies are based only on self-reporting since it has been noted that patients report behavioral changes (impulsivity, decreased performance in school or work) less frequently than family members (Meyskens 1982).…”

Section: Data From Case Series and Uncontrolled Clinical Trialsmentioning

confidence: 99%

“…Other authors reported an onset of symptoms at two months after start of treatment (Bigby and Stern 1988;Burket and Storrs 1987;Hepburn 1990;Lindemayr 1986). Most of the other cases developed depression or committed suicide at some point during treatment (2-4 months after onset of treatment) although specific details are not always given (Barak et al 2005;Bravard et al 1993;Byrne and Hnatko 1995a;Cotterill and Cunliff 1997;Ng et al 2002;Scheinman et al 1990;Wysowski et al 2001b). Of course it is always possible (especially in the suicide cases) that symptoms were not reported at the time they actually started, or that patients denied depression.…”

Section: Temporal Association Between Isotretinoin Treatment and Deprmentioning

confidence: 99%

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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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Section: Temporal Association Between Isotretinoin Treatment and Deprmentioning

confidence: 97%

Section: Case Reports and Review Of The Literature Related To Suicidementioning

confidence: 99%

Section: Data From Case Series and Uncontrolled Clinical Trialsmentioning

confidence: 99%

Section: Data From Case Series and Uncontrolled Clinical Trialsmentioning

confidence: 99%

Section: Temporal Association Between Isotretinoin Treatment and Deprmentioning

confidence: 99%

See 3 more Smart Citations

The neurobiology of retinoic acid in affective disorders

Bremner

McCaffery

2008

Progress in Neuro-Psychopharmacology and Biological Psychiatry

147

154

View full text Add to dashboard Cite

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Risk of Suicide and Psychiatric Disorders Among Isotretinoin Users

Tan,

Tang,

MacAlevey

et al. 2024

JAMA Dermatol

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ImportanceIsotretinoin is hypothesized to contribute to the development of psychiatric disorders, but the epidemiological association and risk factors associated with psychiatric disorders among isotretinoin users remain unclear.ObjectiveTo clarify the absolute and relative risk and risk factors associated with suicide and psychiatric disorders among isotretinoin users.Data SourcesPubMed, Embase, Web of Science, and Scopus were searched from inception until January 24, 2023.Study SelectionRandomized trials and observational studies were selected if they reported the absolute risk, relative risk, and risk factors for suicide and psychiatric disorders among isotretinoin users.Data Extraction and SynthesisRelevant data were extracted and risk of bias was evaluated at the study level using the Newcastle-Ottawa Scale. Data were pooled using inverse variance-weighted meta-analyses. Heterogeneity was measured using the I2 statistic, and meta-regression analyses were performed.Main Outcomes and MeasuresAbsolute risk (percentage), relative risks (risk ratios [RR]), and risk factors (RR) of suicide and psychiatric disorders among isotretinoin users.ResultsA total of 25 studies including 1 625 891 participants were included in the review and 24 in the meta-analysis. Among the included studies, participants’ average age ranged from 16 to 38 years, and distribution by sex ranged from 0% to 100% male. The 1-year pooled absolute risk from between 2 and 8 studies of completed suicide, suicide attempt, suicide ideation, and self-harm were each less than 0.5%, while that of depression was 3.83% (95% CI, 2.45-5.93; I2 = 77%) in 11 studies. Isotretinoin users were less likely than nonusers to attempt suicide at 2 years (RR, 0.92; 95% CI, 0.84-1.00; I2 = 0%), 3 years (RR, 0.86; 95% CI, 0.77-0.95; I2 = 0%), and 4 years (RR, 0.85; 95% CI, 0.72-1.00; I2 = 23%) following treatment. Isotretinoin was not associated with the risk of all psychiatric disorders (RR, 1.08; 95% CI, 0.99-1.19; I2 = 0%). Study-level meta-regression found that studies with participants of older age reported lower 1-year absolute risk of depression, while those with a higher percentage of male participants reported a higher 1-year absolute risk of completed suicide.Conclusions and RelevanceThe findings suggest that at a population level, isotretinoin users do not have increased risk of suicide or psychiatric conditions but may instead have a lower risk of suicide attempts at 2 to 4 years following treatment. While these findings are reassuring, clinicians should continue to practice holistic psychodermatologic care and monitor patients for signs of mental distress during isotretinoin treatment.

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Drug Reactions

Breathnach¹

2004

Rook's Textbook of Dermatology

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Acute depression from isotretinoin

Cited by 82 publications

References 6 publications

The neurobiology of retinoic acid in affective disorders

The neurobiology of retinoic acid in affective disorders

Risk of Suicide and Psychiatric Disorders Among Isotretinoin Users

Drug Reactions

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