isotretinoin and Mental-Disorders

Despite many years of clinical use of isotretinoin, a comprehensive review of evidence for isotretinoin therapy in patients with acne is lacking. We searched MEDLINE, Embase, Cochrane Central, relevant web pages and bibliographies for randomized controlled trials in acne evaluating isotretinoin vs. control (placebo or other therapy). Data were extracted and summarized descriptively. Eleven trials were identified (total 760 patients randomized), containing mostly men. Mean treatment ages ranged from 18 to 47·9 years and participants generally had moderate-to-severe acne. Across all trials, isotretinoin therapy reduced acne lesion counts by a clinically relevant amount, and always by a greater amount than control, which was either placebo (two studies), oral antibiotics (seven studies) or other control (two studies). Across trials with an overall low risk of bias, two of three demonstrated statistically significant differences between isotretinoin and control. The frequency of adverse events was twice as high with isotretinoin (751 events) than with control (388 events). More than half of all adverse events were dermatological and related to dryness. Adverse events from isotretinoin causing participant withdrawal from trials (12 patients) included Stevens-Johnson syndrome, cheilitis, xerosis, acne flare, photophobia, elevated liver enzymes, decreased appetite, headaches and depressed mood. This review suggests that isotretinoin is effective in reducing acne lesion counts, but adverse events are common. This study was registered with PROSPERO number CRD42015025080.

Topics: Acne Vulgaris; Administration, Oral; Adolescent; Adult; Anti-Bacterial Agents; Dermatologic Agents; Drug Eruptions; Eye Diseases; Female; Gastrointestinal Diseases; Humans; Isotretinoin; Male; Mental Disorders; Middle Aged; Otorhinolaryngologic Diseases; Treatment Outcome; Young Adult

Acne is a common condition among adolescents and has the potential to negatively impact on the psychological well-being of those who suffer from it. In particular, depression and suicidal ideation are more common in adolescents with acne. Successful treatment of acne can improve the quality of life and reduce levels of anxiety and depression in these individuals. The current treatment of choice for severe or refractive acne is isotretinoin, a retinoid. While the possible causal association between isotretinoin and mental illness remains a controversial topic, a recent systematic review has presented evidence to support this relationship. In light of this evidence, a group of dermatologists and psychiatrists have collaborated to develop these recommendations to aid the safe prescribing of isotretinoin in adolescents. These clinical suggestions are aimed at practitioners in both disciplines to increase awareness of the current evidence in support of the association between isotretinoin and adolescent depression.

Topics: Acne Vulgaris; Australia; Dermatologic Agents; Humans; Isotretinoin; Mental Disorders; Patient Selection; Quality of Life

Acne vulgaris (AV) is a chronic inflammatory skin disease that affects millions of people. Psychologic disorders such as depression, anxiety, and body dysmorphic disorder are common in patients with AV and the reported prevalence of suicidal ideation and suicide completion in acne patients also is remarkable. Part 1 of this series provided an overview of the prevalence of psychologic disorders in patients with AV Part 2 reviews depression, anxiety, body dysmorphic disorder, and suicidal ideation and completion seen in AV patients. Treatments available for acne patients with coexisting psychiatric illness also are discussed, along with the relationship between oral isotretinoin and depression and suicide.

Topics: Acne Vulgaris; Anxiety Disorders; Body Dysmorphic Disorders; Depression; Dermatologic Agents; Humans; Isotretinoin; Mental Disorders; Risk; Suicidal Ideation; Suicide

Isotretinoin is a synthetic oral retinoid that has great efficacy against severe, recalcitrant, nodulocystic acne. Since its introduction to the market, it has been associated with a variety of adverse psychiatric effects, including depression, psychosis, mood swings, violent behavior, suicide, and suicide attempts. A MEDLINE review was performed to compile all case reports, case series, adverse drug event reportings, and prospective and retrospective studies relating psychiatric adverse events to isotretinoin. In addition, literature linking a biological mechanism for psychiatric adverse events to retinoid signaling pathways was also reviewed. Although a variety of anecdotal and epidemiologic studies are available, the overall lack of concrete scientific data limits any conclusion that can be drawn about a causal relationship between istotretinoin and psychiatric adverse events. Several lines of evidence link retinoid signaling to theorized psychiatric pathogenesis, but are limited in their applicability to adult neurophysiology.

Topics: Acne Vulgaris; Brain; Dermatologic Agents; Humans; Isotretinoin; Mental Disorders; Receptors, Retinoic Acid

Isotretinoin (Accutane, Roche Laboratories Inc, Nutley, NJ) is an important drug, not only for the treatment of severe acne, but also for other diagnoses and in chemoprevention settings. Because the use of isotretinoin is increasing, it is important for physicians to be aware of the adverse events, toxicities, and management issues related to its use. The most important issue is that of congenital defects, which has resulted in new pregnancy prevention policies and programs implemented by the manufacturer. A relatively new concern is that of depression associated with isotretinoin use, also resulting in new policies placed by the manufacturer and the FDA. The most common adverse effects observed during treatment are mucocutaneous and ocular in nature, but laboratory abnormalities and effects in the nervous, musculoskeletal, gastrointestinal, pulmonary, hematologic, and other systems are also described. Additionally, potential drug interactions, follow-up, and toxicity prevention measures are discussed.

Topics: Abnormalities, Drug-Induced; Acne Vulgaris; Cheilitis; Dermatologic Agents; Drug Interactions; Eye Diseases; Humans; Isotretinoin; Liver Function Tests; Mental Disorders; Mouth Mucosa; Musculoskeletal Diseases

Patients with severe recalcitrant nodular acne that is unresponsive to conventional therapy (including topical and systemic antibiotics) have few alternative effective treatment modalities other than the use of oral isotretinoin (Accutane). The cause of acne vulgaris is multifactorial, but the pathogenesis of this disorder of the pilosebaceous follicles arises mainly from endogenous factors. It is usually, but not always, associated with the onset of puberty. Severe acne, defined by the prevalence of facial and truncal inflammatory lesions, is a disfiguring disease that can often result in significant permanent scarring after the healing of deep inflammatory lesions and other disorders, such as systemic bacterial infections. Topical treatments are considered as the first line of therapy for less severe forms of acne, although systemic treatments such as antibiotics or antiandrogen agents are effective for either mild or moderate forms and sometimes effective for severe acne. However, in many patients with large numbers of nodules, longer treatment periods with these agents are required to reduce the count of inflammatory lesions. It has become increasingly evident that (because topical agents and antibiotic or antiandrogenic therapy have a slow onset of action) even mild or moderate acne that is treated in this way can result in scarring. In addition, the excessive use of systemic antibiotics has led to the detection of increasing numbers of antibiotic-resistant bacteria on the skin of patients with acne.(1) Therefore, because of its relatively rapid onset of action and its high efficacy with reducing more than 90% of the most severe inflammatory lesions, Accutane has a role as an effective treatment in patients with severe acne that is recalcitrant to other therapies.

Topics: Acne Vulgaris; Adolescent; Adult; Chemical and Drug Induced Liver Injury; Clinical Trials as Topic; Female; Humans; Hypertriglyceridemia; Isotretinoin; Male; Mental Disorders; Mucous Membrane; Patient Education as Topic; Product Labeling; Stomatitis; Vision Disorders

The connection between P. ovale and seborrhoeic dermatitis has been clearly demonstrated in a number of treatment studies but we still do not know how P. ovale induces skin lesions. An enhanced growth of P. ovale cannot be the cause, because a number of studies with quantitative determinations of P. ovale have not been able to show any difference in the number of yeast cells between patients and healthy controls. The number of P. ovale is probably only important for the individuals who are susceptible to seborrhoeic dermatitis. An abnormal immune response to P. ovale could be another explanation. Sohnle et al. have shown that P. ovale can activate complement by both the classical and the alternative pathway. A defective cell-mediated immunity to P. ovale in patients with seborrhoeic dermatitis has been demonstrated by Wikler et al. In patients with AIDS, who are known to have a diminished T-cell function, a high incidence of seborrhoeic dermatitis has been found. Activation of the alternative complement pathway by P. ovale, which does not require T-cell function, could be an explanation for the inflammatory response. I also believe that the skin lipids are important in the pathogenesis. An improvement of seborrhoeic dermatitis has been demonstrated after treatment with drugs that reduce the sebum excretion. Pityrosporum has lipase activity and may generate free fatty acids, which could also contribute to the inflammatory response. There are a number of factors which are probably important in the pathogenesis of seborrhoeic dermatitis, that is, the number of P. ovale, P. ovale lipase activity, skin lipids, immune function, heredity, atmospheric humidity and emotional state. A reduction in the number of P. ovale in patients suffering from seborrhoeic dermatitis and being treated with antimycotic treatment is, at the present state of knowledge, the best way to treat the disease.

Topics: Acquired Immunodeficiency Syndrome; Adrenal Cortex Hormones; Dermatitis, Seborrheic; HIV Infections; Humans; Imidazoles; Incidence; Isotretinoin; Malassezia; Mental Disorders; Occupational Diseases; Organometallic Compounds; Prevalence; Propylene Glycol; Propylene Glycols; Pyridines; Selenium Compounds; Succinates; Ultraviolet Therapy

Since isotretinoin marketing, reports of psychiatric events have been noted. Howeverto date, a relation between these events and acne or isotretinoin treatment has not been clearly established. Our objective was to analyze the incidence of psychiatric events in women receiving isotretinoin.. Self-controlled study including women treated with isotretinoin from July 2014 to December 2018. Data source was SIDIAP, a primary health care-based database from Catalonia, Spain. Risk of psychiatric events was analyzed during the isotretinoin exposure and during the previous and posterior periods of non-exposure.. We included 4,738 women in the study, 25.3% of them had history psychiatric disorders prior to receiving isotretinoin. During the follow-up, 782 (16.5%) patients were diagnosed with new mental disorders and 925 (19.5%) received new psychotropic drug prescriptions. We found a trend to an increase of new events when the previous non-exposure and the isotretinoin exposure periods were compared, with no significant differences. Incident psychiatric events during isotretinoin exposure was significantly higher in those patients with previous psychiatric history.. We cannot conclude any causality between acne and isotretinoin and the appearance of new psychiatric events. However, we contribute to the evidence with a more robust methodological approach, which minimizes the effect of confounding variables.

Topics: Acne Vulgaris; Databases, Factual; Female; Humans; Isotretinoin; Mental Disorders; Spain

After isotretinoin's approval to treat patients with recalcitrant acne, there have been continued debates around its psychiatric safety profile. This study aimed to assess the risk of psychiatric disorders in patients with acne who are taking isotretinoin.. We used de-identified information from Taiwan's National Health Insurance Research Database from 2000 to 2015 to examine the risk for psychiatric disorders among patients with acne who were taking isotretinoin. We performed subgroup analyses based on the dosage and duration of isotretinoin administration.. This study included 29,943 participants during a 16-year follow-up period. We found no significantly increased risk for psychiatric disorders among patients taking isotretinoin compared with patients who did not receive isotretinoin treatment (adjusted hazard ratio [aHR]: 1.009, 95% confidence interval [CI]: 0.422-1.696). Subgroup analyses showed no significantly increased risk for psychiatric disorders in patients taking different doses of isotretinoin (≤ 20 mg per day, aHR: 0.892, 95% CI: 0.371-1.501; > 20 mg per day, aHR: 1.068, 95% CI: 0.446-1.798). There was also no significant increase in risk for patients undergoing isotretinoin treatment over different periods (≤ 6 months, aHR: 0.924, 95% CI: 0.392-1.612; > 6 months, aHR: 1.196, 95% CI: 0.488-2.004).. We did not analyze the risk of suicidal ideation, and it could be underestimated in medical claims databases.. We found no increased risk of psychiatric disorders among Taiwanese patients with acne who were taking isotretinoin. Higher dosage or longer duration of isotretinoin treatment did not increase the risk for developing a psychiatric disorder.

Topics: Acne Vulgaris; Cohort Studies; Humans; Isotretinoin; Mental Disorders; Taiwan

Biological, genetic and psychosocial factors may play a role in the aetiology of bipolar mood disorder (BPD). BPD episodes might be triggered by isotretinoin, a retinoid derivative of vitamin A with a role in cellular proliferation and differentiation. Due to its association with depression, suicidal ideation and suicide attempts, American Food and Drug Administration (FDA) issued a placement of a label warning for isotretionin. Personal or family history of psychiatric disorders was emphasized in the literature for the risk of mood episodes following isotretionin treatment. Here we aim to present the case of an 18- year old young male adult, without personal or family history of a psychiatric disorder, who developed psychotic mania within the first week of isoretinoin which was prescribed for acne vulgaris. Psychotic mania symptoms receded within one week after starting olanzapine (10 mg/day). We believe this case is significant in demonstrating the occurence of a manic episode after isoretinoin in individuals lacking a personal or family history of psychiatric diagnoses.

Topics: Acne Vulgaris; Adolescent; Adult; Bipolar Disorder; Humans; Isotretinoin; Male; Mania; Mental Disorders

Biological, genetic and psychosocial factors may play a role in the aetiology of bipolar mood disorder (BPD). BPD episodes might be triggered by isotretinoin, a retinoid derivative of vitamin A with a role in cellular proliferation and differentiation. Due to its association with depression, suicidal ideation and suicide attempts, American Food and Drug Administration (FDA) issued a placement of a label warning for isotretionin. Personal or family history of psychiatric disorders was emphasized in the literature for the risk of mood episodes following isotretionin treatment. Here we aim to present the case of an 18- year old young male adult, without personal or family history of a psychiatric disorder, who developed psychotic mania within the first week of isoretinoin which was prescribed for acne vulgaris. Psychotic mania symptoms receded within one week after starting olanzapine (10 mg/day). We believe this case is significant in demonstrating the occurence of a manic episode after isoretinoin in individuals lacking a personal or family history of psychiatric diagnoses.

Topics: Acne Vulgaris; Adolescent; Adult; Bipolar Disorder; Humans; Isotretinoin; Male; Mania; Mental Disorders

The association between isotretinoin and psychiatric disturbance, including depression and suicidal behavior, is controversial.. To investigate whether acne patients prescribed isotretinoin or antibiotics were more likely to have psychiatric disorders and/or engage in suicidal behavior.. Retrospective cohort study using the IBM MarketScan Research Databases, which contain commercial insurance claims in the United States, to identify acne patients who were prescribed isotretinoin or oral antibiotics between 2011 and 2017 and who were diagnosed with psychiatric disorders or suicidal behavior.. A total of 72,555 patients were included in the study. Patients in the general population were 1.47 times more likely to be diagnosed with suicidal ideation or attempt compared to acne patients prescribed isotretinoin (adjusted odds ratio [OR] 1.47; confidence interval [95% CI], 1.27, 1.70; P < .0001). The general population (adjusted OR 0.87; 95% CI, 0.84, 0.89; P < .0001) and acne patients prescribed antibiotics (adjusted OR 0.88; 95% CI, 0.85, 0.91; P < .0001) were less likely to have a psychiatric diagnosis compared to acne patients prescribed isotretinoin. The prevalence of suicidal behavior during isotretinoin treatment was lower (0.10%; P = .082) than in the year prior to isotretinoin treatment (0.22%) and in the year following treatment (0.34%; P = .004).. The study excluded individuals with public insurance and those who were uninsured, and the data in the study relied on the accuracy of the medical coding.. Compared to the general population, acne patients prescribed isotretinoin were less likely to engage in suicidal behavior. Further exploration into the slight increase in suicidal behavior seen in isotretinoin patients 1 year after therapy is warranted.

Topics: Acne Vulgaris; Anti-Bacterial Agents; Dermatologic Agents; Humans; Insurance; Isotretinoin; Mental Disorders; Retrospective Studies; Suicidal Ideation; United States

Although the causal role of isotretinoin in suicidal behaviour is controversial, suicide attempts (SA) do occur among patients taking isotretinoin.. To describe patient profiles and the management of isotretinoin among patients who committed or attempted suicide under treatment. To assess the risk factors for SA under isotretinoin.. We performed a comprehensive case series of suicides and SAs under isotretinoin, and a case-control study, using Nationwide French Health Insurance database. The main analysis compared cases (subjects with a SA during a course of isotretinoin) to controls, individually matched for age, gender and rank of the current course; controls were to be exposed to isotretinoin at the index date (date of SA for the corresponding cases). The patients' psychiatric history at isotretinoin initiation was studied. In a secondary analysis, patients who continued their isotretinoin treatment after their SA were compared to patients who discontinued it.. In all, 328 018 subjects started a course of isotretinoin between 1 January 2010 and 31 December 2014 and 184 patients were hospitalized for a SA; half of them had a psychiatric history at initiation. In the multivariate analysis, psychiatric history and history of anxiety alone were risk factors for SA [Odds ratio (OR), 18.21; 95% confidence interval (CI), 9.96-33.30 and 4.78; 95% CI, 2.44-9.33, respectively]. Among 176 cases of SA with sufficient follow-up, 103 (58.5%) carried on with their treatment after their SA. Treatment initiation by a dermatologist was inversely associated with the continuation of the treatment after a SA (OR, 0.38; 95% CI, 0.18-0.80).. Suicide attempts under isotretinoin are rare events, and our results suggest that most of the patients concerned have a risk-prone profile detectable at the time of treatment initiation. The risk-benefit ratio of continuing isotretinoin after a SA warrants further careful evaluation.

Topics: Acne Vulgaris; Administrative Claims, Healthcare; Adolescent; Adult; Anxiety; Case-Control Studies; Databases, Factual; Dermatologic Agents; Female; France; Humans; Isotretinoin; Male; Mental Disorders; Patient Acceptance of Health Care; Risk Factors; Suicide, Attempted; Young Adult

The link between isotretinoin, treatment of a severe form of acne, and psychiatric disorders remains controversial, as acne itself could explain the occurrence of psychiatric disorders. This study aims at assessing the disproportionality of psychiatric adverse events reported with isotretinoin in the French National PharmacoVigilance Database, compared with other systemic acne treatments and systemic retinoids.. Data were extracted from the French National PharmacoVigilance Database for systemic acne treatments, systemic retinoids and drugs used as comparators. Each report was subjected to double-blind analysis by two psychiatric experts. A disproportionality analysis was performed, calculating the number of psychiatric ADRs divided by the total number of notifications for each drug of interest.. Concerning acne systemic treatments: all 71 reports of severe psychiatric disorders involved isotretinoin, the highest proportion of mild/moderate psychiatric adverse events was reported with isotretinoin (14.1%). Among systemic retinoids, the highest proportion of severe and mild/moderate psychiatric events occurred with isotretinoin and alitretinoin.. Our study raises the hypothesis that psychiatric disorders associated with isotretinoin are related to a class effect of retinoids, as a signal emerges for alitretinoin. Complementary studies are necessary to estimate the risk and further determine at-risk populations.

Topics: Acne Vulgaris; Adverse Drug Reaction Reporting Systems; Alitretinoin; Databases, Factual; Dermatologic Agents; Female; France; Humans; Isotretinoin; Male; Mental Disorders; Pharmacovigilance; Retinoids; Risk; Severity of Illness Index; Tretinoin; Young Adult

Systemic isotretinoin effectively treats all forms of acne vulgaris. However, it has many side-effects, some potentially serious, that warrant limiting its use to serious cases of acne. Inappropriate use in large numbers of patients puts prescribers at risk of malpractice litigation should serious side-effects occur where safer alternative treatments were available. Doctors also risk losing access to the drug should authorities limit its use to reduce the occurrence of side-effects.

Topics: Acne Vulgaris; Administration, Oral; Attitude of Health Personnel; Chemical and Drug Induced Liver Injury; Dermatologic Agents; Humans; Hypertriglyceridemia; Isotretinoin; Mental Disorders; Practice Guidelines as Topic; Professional-Patient Relations; South Africa; Stomatitis; Vision Disorders

Topics: Dermatologic Agents; Humans; Hyperhomocysteinemia; Isotretinoin; Mental Disorders

Topics: Adolescent; Adult; Depressive Disorder; Dermatologic Agents; Female; Genetic Predisposition to Disease; Hallucinations; Humans; Isotretinoin; Male; Mental Disorders; Young Adult

Oral isotretinoin is a highly effective agent for the treatment of moderate to severe acne, but ever since oral isotretinoin was introduced as a modality for acne, the relationship between oral isotretinoin therapy and psychiatric problems, especially depression, has been controversial. The purposes of this study were to know the acute effects of oral isotretinoin therapy on psychiatric symptoms and to investigate the relationships among them, which have not been reported in the published work. This cohort study included 38 acne patients who started oral isotretinoin therapy. Individual patients were examined before administering oral isotretinoin and 2 and 8 weeks after commencement. Acne severity was graded using the Leeds revised acne grading system. Acute psychiatric effects of oral isotretinoin were assessed using a questionnaire authorized by two psychiatrists. This questionnaire included assessments of acne-related quality of life (Assessment of the Psychological and Social Effects of Acne [APSEA]), depression (Beck's depression inventory [BDI]), anxiety (Beck's anxiety inventory [BAI]) and psychopathology (Symptomchecklist-90-revised [SCL-90-R]). Acne grading and APSEA showed similar change patterns. Both improved after 8 weeks of oral isotretinoin treatment. On the other hand, the severity of depression decreased after 2 weeks of treatment. A significant correlation was found between BDI and APSEA, but no correlation was found between BDI and acne grade. These results indicate that oral isotretinoin therapy alleviates depressive symptoms. Improvements in depression are directly related to acne-related life quality improvements rather than to improvement in acne grade.

Topics: Acne Vulgaris; Adolescent; Adult; Dermatologic Agents; Female; Humans; Isotretinoin; Male; Mental Disorders; Quality of Life; Young Adult

Disturbing reports of suicides have been collected in several countries. The role of isotretinoin should be considered when mental disorders occur in patients taking the drug.

Topics: Acne Vulgaris; France; Humans; Isotretinoin; Mental Disorders; Suicide

The association between exposure to Isotretinoin, the development of depression and suicide attempts is controversial.. To retrospectively assess pattern of utilization of mental health services in the Israeli Defense Forces (IDF) during a 5-year period for all subjects exposed to Isotretinoin in comparison to a control group consisting of army conscripts suffering from psoriasis. All subjects were young adults (18 to 21 years old) in compulsory military service.. Exposure to Isotretinoin mandates reporting and marking as a coded medical profile in the IDFs' computerized medical record of each conscript and soldier. Medical data, tracked by military medical profiles, were summarized from medical records of all subjects treated by Isotretinion during the years 1999-2003 and for the control group for the same period. Use of mental health services was the a-priori defined primary outcome measure.. During the study period 1419 subjects were exposed to Isotretinoin and 1102 suffered from psoriasis. Utilization of mental health services was highest for the index group wherein 17.2% (245/1419) of subjects were evaluated or treated compared to 12.5% in the control group (psoriasis). The inter-group differences were statistically significant; Chi-square=15.9 (df=2), p=0.0003.. We suggest that psychiatric evaluation be regularly undertaken prior to initiation of Isotretinion treatment in young adults at risk, as well as providing follow-up visits during and at completion of treatment.

Topics: Acne Vulgaris; Adolescent; Adult; Female; Health Services; Humans; Isotretinoin; Israel; Male; Mental Disorders; Mental Health Services; Military Personnel; Psoriasis; Retrospective Studies

Topics: Adolescent; Animals; Child; Dietary Supplements; Drug Labeling; Humans; Isotretinoin; Meat; Mental Disorders; Mice; Night Blindness; Rats; Retinal Rod Photoreceptor Cells; Vegetables; Vitamin A; Vitamin A Deficiency

Although knowledge concerning the dermatological treatment of chronic acne has grown considerably in recent years, relatively few studies have assessed the impact of effective physical intervention upon the psychoemotional functioning of patients. Hypotheses regarding the psychological impact of acne were developed using concepts drawn from evolutionary psychology. A sample of 34 patients (19 men and 15 women) with chronic acne were assessed for psychological, emotional and dermatological symptomatology using a variety of self-report questionnaires over four time-points during 16 weeks treatment with isotretinoin. Thirty-four patients completed the first assessment, 21 the second, 20 the third and 15 the fourth and final assessment. At the first assessment, prior to isotretinoin treatment, 15 patients (44%) reported clinically significant levels of anxiety, while six patients (18%) reported clinically significant depression. Women with acne were significantly more embarrassed than their male counterparts about their skin disease. Treatment with isotretinoin produced significant improvements across a wide variety of psychological functions, although the emotional status of patients appeared to be more resistant to change. Acne appears to be a condition which has the potential to damage, perhaps even in the long term, the emotional functioning of some patients.

Topics: Acne Vulgaris; Adolescent; Adult; Anxiety Disorders; Chronic Disease; Depressive Disorder; Emotions; Female; Follow-Up Studies; Humans; Isotretinoin; Keratolytic Agents; Male; Mental Disorders; Psychiatric Status Rating Scales; Psychometrics