isotretinoin and Mood-Disorders

The psychological consequences of acne have been the subject of many studies. As a particularly visible skin disorder, acne complicates the daily lives of adolescents who are undergoing multiple transformations: physical, intellectual and emotional. While it is well established that acne can be responsible for depression and low self-esteem, it is likely that this impact is aggravated by the sociological evolution of adolescents in the 21st century. Understanding the codes of adolescents today (who can be characterized as being more concerned by their appearance than previous generations at the same age) allows us to optimize our medical approach to acne and facilitates treatment compliance and adherence.

Topics: Acne Vulgaris; Adolescent; Adult; Anxiety Disorders; Attitude to Health; Depressive Disorder; Dermatologic Agents; Emotions; Female; Humans; Isotretinoin; Male; Mental Health; Mood Disorders; Physician-Patient Relations; Psychiatric Status Rating Scales; Surveys and Questionnaires; Young Adult

Isotretinoin (13-cis-retinoic acid), approved by the US Food and Drug Administration for the treatment of acne, carries a black box warning related to the risk of depression, suicide, and psychosis. Retinoic acid, the active form of vitamin A, regulates gene expression in the brain, and isotretinoin is its 13-cis isomer. Retinoids represent a group of compounds derived from vitamin A that perform a large variety of functions in many systems, in particular the central nervous system, and abnormal retinoid levels can have neurologic effects. Although infrequent, proper recognition and treatment of psychiatric side effects in acne patients is critical given the risk of death and disability. This article reviews the evidence for isotretinoin's relationships with depression and suicidality.. The PsycINFO, MEDLINE, and PubMed searchable database indexes were searched for articles published in the English language from 1960 to June 2010 using the key words isotretinoin, retinoids, retinoic acid, depression, depressive disorders, and vitamin A. Evidence examined includes (1) case reports; (2) temporal association between onset of depression and exposure to the drug; (3) challenge-rechallenge cases; (4) class effect (other compounds in the same class, like vitamin A, having similar neuropsychiatric effects); (5) dose response; and (6) biologically plausible mechanisms.. All articles in the literature related to isotretinoin, depression, and suicide were reviewed, as well as articles related to class effect, dose response, and biologic plausibility.. Information from individual articles in the literature was extracted, including number of episodes of depression, suicidality, suicide, psychosis, violence and aggression, past psychiatric history, time of onset in relation to isotretinoin usage, medication dosage, duration of treatment, and dechallenge and challenge history.. The literature reviewed is consistent with associations of isotretinoin administration with depression and with suicide in a subgroup of vulnerable individuals.. The relationship between isotretinoin and depression may have implications for a greater understanding of the neurobiology of affective disorders.

Topics: Acne Vulgaris; Brain; Dose-Response Relationship, Drug; Humans; Isotretinoin; Models, Biological; Mood Disorders; Retinoids; Self Concept; Suicide

The potential relationship between systemic retinoids used in dermatology and affective disorders is controversial. Acitretin, which is widely used in the treatment of psoriasis is part of this controversy secondary to its chemical relation to isotretinoin, a drug which has been associated with a large number of anecdotal case reports of depression and suicidal ideation. Moreover, an FDA package insert precaution regarding acitretin's association with depression and suicide has elevated the level of concern for patient safety. The objective of this article is to review the evidence in the literature regarding acitretin's association with affective disorders. After 12 years of worldwide use only two cases involving acitretin have been reported in the literature. In addition, despite many anecdotal cases involving isotretinoin, there have been no clinical studies that have proven a causal relationship between isotretinoin and depression or suicidal ideation. For acitretin there have been no systematic clinical studies that examine such a relationship. Moreover, it is notable that the FDA precaution regarding depression and suicide on the package insert of acitretin predates the publication of the aforementioned two cases. This suggests that a relationship between acitretin and affective disorders is a class labeling rather than a scientifically proven association.

Topics: Acitretin; Depression; Dermatologic Agents; Drug Labeling; Humans; Isotretinoin; Mood Disorders; Psoriasis; Suicidal Ideation; Suicide; United States; United States Food and Drug Administration

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

Depression and mood changes appear as potentional side effects of isotretinoin in the Summary of Product Characteristics. There have been many studies treating this topic but in most cases not identifying any significant depression or suicide risk. To further investigate this issue, we conducted a prospective, uncontrolled study to evaluate mood changes and suicidal ideations in patients receiving isotretinoin therapy.. One-hundred patients were included in our single center, no-blind, and no controlled prospective study. All patients completed the Beck's Depression Inventory, Version II (BDI-II) before the treatment, following the first month of the treatment and then every third month until finishing the isotretinoin therapy. All questionnaires were checked by a psychiatrist. Suicidal ideations were monitored. Statistical analysis of BDI-II scores was performed.. All patients completed the study. Before the treatment, six percent of the patients had suffered from depressive symptoms. During the isotretinoin treatment, we did not find any deterioration of depression problems in any of these patients. On the contrary, in most patients the depressive symptoms disappeared. Symptoms of depression occurred in two patients, in which case coexisting situational factors were found to be the cause. No occurrence of suicidal ideations was found.. We did not find any depressive symptoms or suicide risk caused by isotretinoin. On the contrary, a statistically significant improvement of BDI-II scores was found. In our opinion, patients have to be informed about the risk of depression but emphasizing the fact that it is very rare.

Topics: Acne Vulgaris; Adolescent; Adult; Affective Symptoms; Child; Depressive Disorder; Dermatologic Agents; Female; Follow-Up Studies; Humans; Isotretinoin; Male; Middle Aged; Mood Disorders; Prospective Studies; Psychological Tests; Risk Factors; Suicidal Ideation; Surveys and Questionnaires; Young Adult

Topics: Acne Vulgaris; Depression; Dermatologic Agents; Dermatologists; Dermatology; Humans; Isotretinoin; Mental Health; Mood Disorders; Prevalence; Risk Factors; Scotland; Suicide, Completed; Surveys and Questionnaires

To analyse cases of 9 patients (18-27 yo) who were consequently admitted to our department and treated with affective disorders (AD) while undergoing isotretinoin (INN) therapy.. A semi-structured questionnaire designed by the authors was used to analyse many variables related to demographic characteristics, dermatologic and psychiatrics symptoms, AD course and treatment, family history of mental disorders, building on medical histories of patients and their families, and available medical records.. Patients were diagnosed (DSM-IV-TR) with: a major depressive episode (4 patients), a recurrent major depressive episode (3), a bipolar mixed episode (1), and rapid cycling bipolar I disorder (1). The mean time from the first use of INN to: I. the onset of mental disorders was approximately 2 months (1-6 months), II. a visit with a psychiatrist was about 12 months (1-38 months). The predictors of occurrence of AD included a family history of AD and a prior episode of mental disorders. The onset of AD was in most cases preceded by prodromal symptoms such as headaches, sleep disorders, fatigue, drowsiness, or general weakness. Five patients reported suicidal ideation, four patients showed suicidal tendencies, and two persons attempted to commit suicide during the treatment.. Psychiatrists should pay special attention to isotretinoin as a drug that may trigger episodes of AD, particularly in patients with a family history of AD or prior episodes of mental disorders. Isotretinoin therapy of patients with acne and a family history of AD or prior episodes of mental disorders requires special care and, if symptoms of depression develop or worsen during the INN treatment, collaboration between a dermatologist and a psychiatrist is needed.

Topics: Acne Vulgaris; Adolescent; Adult; Dermatologic Agents; Female; Humans; Isotretinoin; Male; Mood Disorders; Risk Factors; Surveys and Questionnaires; Young Adult

Topics: Acne Vulgaris; Dermatologic Agents; History, 20th Century; Humans; Isotretinoin; Mood Disorders; Time Factors

Isotretinoin has revolutionized the management of acne vulgaris. However, concerns continue regarding the adverse effect profile of isotretinoin. This study aims to review the adverse effects experienced by patients started on isotretinoin by a single dermatologist.. Retrospective chart review of 1743 patients started on isotretinoin for various dermatological conditions over a 6-year period. Details of the dose of isotretinoin used, concomitant medications, adverse effects and outcome were recorded.. One-fifth (18.5%) of patients reported no adverse effects during the study period. Cheilitis was the most commonly reported adverse effect, affecting 78% of users, followed by eczema and tiredness, seen in 12% each. However, these were clearly dose-dependent, as the group treated with doses of isotretinoin under 0.25 mg/kg/day only reported cheilitis in 47%, eczema in 7% and tiredness in 5%, compared with 96%, 16% and 18%, respectively, in those treated with more than 0.75 mg/gm/day. Twenty-four patients (1.4%) stopped isotretinoin because of adverse effects; a further three patients complained of severe adverse effects on at least one occasion, but continued taking the medication. The adverse effect(s) that led to patients stopping isotretinoin were cheilitis (22 patients), mood change (13), tiredness (12), eczema (6) and pregnancy (2). There were no reported instances of suicidal ideation or attempted suicide.. Other than the two oral contraceptive failures, there were no serious adverse events recorded during this review period. Isotretinoin is a very effective medication with a low adverse-effect profile when used at lower doses.

Topics: Acne Vulgaris; Adolescent; Adult; Aged; Aged, 80 and over; Cheilitis; Child; Dermatologic Agents; Dose-Response Relationship, Drug; Eczema; Fatigue; Female; Humans; Isotretinoin; Male; Middle Aged; Mood Disorders; Pregnancy, Unplanned; Retrospective Studies; Young Adult

Topics: Abnormalities, Drug-Induced; Acne Vulgaris; Dermatologic Agents; Female; Humans; Isotretinoin; Male; Mood Disorders; Practice Guidelines as Topic; Pregnancy; United Kingdom