isotretinoin and Depressive-Disorder--Major

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.

Topics: Adult; Animals; Brain; Corpus Striatum; Depressive Disorder, Major; Disease Models, Animal; Hippocampus; Humans; Isotretinoin; Mice; Mood Disorders; Neurotransmitter Agents; Prefrontal Cortex; Retrospective Studies; Signal Transduction; Suicide; Tretinoin

Isotretinoin-related risk of depression and suicidal behavior is a topic of inconclusiveness. A crucial knowledge gap exists in defining the association of isotretinoin with other psychiatric comorbidities.. To evaluate the risk of psychiatric outcomes among patients with acne treated with isotretinoin versus oral antibiotics.. A global population-based retrospective cohort study enrolled 2 groups of patients with acne managed by isotretinoin (n = 75,708) and oral antibiotics (n = 75,708). Patients were compared regarding the risk of 9 psychiatric outcomes.. Relative to those treated with oral antibiotics, patients prescribed isotretinoin experienced lower risk of depression (hazard ratio [HR], 0.90; 95% confidence interval [CI], 0.87-0.93; P < .001), but comparable risk of major depressive disorder (HR, 0.97; 95% CI, 0.92-1.03; P = .318). Risk of suicidal attempts was comparable between groups (HR, 0.97; 95% CI, 0.85-1.11; P = .663), despite the elevated risk of suicidal ideation in those under isotretinoin (HR, 1.41; 95% CI, 1.32-1.50; P < .001). Patients under isotretinoin had lower risk of post-traumatic stress disorder (HR, 0.75; 95% CI, 0.68-0.82; P < .001), anxiety (HR, 0.84; 95% CI, 0.82-0.87; P < .001), bipolar disorder (HR, 0.65; 95% CI, 0.59-0.72; P < .001), schizophrenia (HR, 0.60; 95% CI, 0.48-0.76; P < .001), and adjustment disorder (HR, 0.82; 95% CI, 0.77-0.87; P < .001).. Retrospective data collection.. Isotretinoin confers lower risk of 6 psychiatric comorbidities and comparable risk of suicidal attempts.

Topics: Acne Vulgaris; Anti-Bacterial Agents; Depression; Depressive Disorder, Major; Dermatologic Agents; Humans; Isotretinoin; Retrospective Studies

Topics: Acne Vulgaris; Adolescent; Depressive Disorder, Major; Dermatologic Agents; Humans; Isotretinoin; Male; Suicide

Depression has been reported in some patients treated with isotretinoin, an effective medication for nodulocystic acne, a serious disorder resulting in permanent scarring. Since major depression, a common disorder associated with multiple health risks including suicide attempts and treatment noncompliance, may occur during the course of treatment with isotretinoin, persons treated with isotretinoin must be screened for depression before starting treatment and monitored for depression regularly during the course of treatment with isotretinoin. Those with evidence of depression must then be referred for prompt treatment to abort serious adverse outcomes, including suicide. Psychologists constitute key members of the treatment team of patients taking isotretinoin.

Topics: Depressive Disorder, Major; Drug Monitoring; Humans; Isotretinoin; Keratolytic Agents; Mass Screening

Topics: Acne Vulgaris; Adolescent; Depressive Disorder, Major; Disorders of Excessive Somnolence; Humans; Isotretinoin; Male