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Isotretinoin and Psychopathology
October 1, 2010
Acne is a skin disorder that can lead to both physical and emotional scarring. With 85% of teenagers suffering from acne, it doesn’t come as a surprise when doctors and patients alike try anything to get rid of pimples, whiteheads, and other embarrassing marks (http://www.acne-resource.org/understanding-acne/acne-statistics.html). But, what happens when a drug designed to clear skin and improve self-esteem becomes associated with depression and suicide? Is it still worth the risk to get rid of zits? This paper will look deeper into the anti-acne drug Accutane in order to understand how it works, its effectiveness in treating acne, and its psychological effects on patients.
What is Accutane and what is it used for?
Accutane, scientifically called isotretinoin, is a synthetic oral retinoid (Kontaxakis, 2009). Retinoids are a type of alcohol containing Vitamin A that are fat soluble and unsaturated (Strahan, 2006). The average person only needs about one milligram of retinol per day, but the drug isotretinoin significantly increases the amount of retinol in the bloodstream (Strahan, 2006). However, isotretinoin is a modified version of retinoic acid, which makes it less toxic to the human body (Strahan, 2006). Retinoids in general can have innumerable effects on cell processes, including cell division, RNA and protein synthesis, and glycosylation (Strahan, 2006). The effects that isotretinoin can have on the cell membranes and biosynthesis are the properties that make isotretinoin effective in treating severe acne (Strahan, 2006). Accutane works primarily by inhibiting the function of the sebaceous gland, limiting sebum secretion to less than one-tenth of what it was before treatment started (Strahan, 2006). Sebum is an agent secreted from hair follicles that causes acne by clogging pores. Although isotretinoin is primarily used in treating patients with severe acne, it has also been used to treat other skin disorders and even some types of leukemia (Strahan, 2006).
Accutane: A Brief History
Accutane was introduced to the public in July, 1982 (Kontaxakis, 2009). Since then, it has been the subject of tremendous debate. The movement against Accutane started to grow exponentially in 2000, when the son of a member of the House of Representatives killed himself (Strahan, 2006). The member, Representative Bart Stupak attributed his son’s depression to the drug Accutane (Strahan, 2006). Kontaxakis points out that the American Academy of Dermatology met in 2002 to discuss the drug that was evoking so much controversy (2009). During their conference, entitiled “Depression, Suicide, and Isotretinoin,” it was determined that although isotretinoin had not been proven to cause depression, doctors should still be wary when prescribing such a potent drug to adolescents (Kontaxakis, 2009).
Unintended Physiological Effects of Accutane
Although acne reduction is the desired physiological effect of Accutane, it is not the only effect. Accutane also has effects in the brain, inducing projections from neurons to go into various parts of the brain, and therefore changing behavior and/or emotions (Strahan, 2006). The parts of the brain that could be affected are the hypothalamus, which has been associated with appetite changes; the basal ganglia, which have been associated with Obsessive Compulsive Disorder; and the frontal cortex, associated with changes in mood (Strahan, 2006). These neuron projections can also reach into the limbic system, which could lead to anxiety, fatigue, and agitation (Strahan, 2006).
Side Effects and Case Studies
Some side effects associated with Accutane use are depression, psychosis, violent behavior, suicide, suicide attempts, anti-inflammatory effects, euphoria, and irritability (Strahan, 2006). These have been observed in the following studies:
Meyskens used isotretenoin at a dosage of 3 mg/kg/day to treat cancer (Meyskens, 1982). One-fourth of his patients experienced psychological changes that improved with the termination of isotretenoin usage (Meyskens, 1982).
Hazen found depression in six of the 110 patients he was treating with isotretinoin (Hazen, 1983). Out of the six patients with depression, five of them were being treated with isotretinoin for the purpose of eliminating acne (Hazen, 1983). Other side effects witnessed by Hazen were crying spells, malaise, and forgetfulness (Hazen, 1983).
Bruno’s experimental group consisted of 94 patients being treated with different dosages of isotretenoin solely for acne (Bruno, 1984). Twenty-two of these patients experienced depression and insomnia (Bruno, 1984).
Seven out of 700 patients receiving isotretinoin were diagnosed with depression. These 700 patients were receiving an average of .7 mg/kg/day (Scheinman, 1990). Five of the seven diagnosed with depression were being treated for acne (Scheinman, 1990).
Hull and Demkiw-Bartel
Four percent of 124 patients receiving 1 mg/kg/day of isotretenoin for acne experienced depression (Hull, 2000). However, all of the patients continued with the treatment (Hull, 2000).
Wysowski looked at the Adverse Event Reporting System of the Food and Drug Administration in the 18 years following the release of isotretenoin (Wysowski, 2001). They noticed that although depression occurred in 431 patients, 69% of them had preexisting histories of psychiatric problems and 29% of them continued to be depressed after use of isotretinoin was terminated (Wysoski, 2001).
The Case for Isotretinoin
From analyzing the case studies above, it can be seen that although some of the same patients taking isotretinoin are the same patients experiencing depression, there could also be other variables that are causing this besides the isotretinoin. Strahan points out that there hasn’t been an association established between isotretinoin and depression or suicide because acne alone is a risk factor for depression (2006). This is shown in the Hazen case because in this case, a relatively small percentage of the sample population receiving isotretinoin experienced depression. However, out of the few that did experience depression, only one of them was not taking isotretinoin for acne. This shows that perhaps the link between isotretinoin and depression could actually be a link between acne and depression. This same pattern repeats itself in the Scheinman case.
In addition, the Wysowski case shows that a lot of the depression patients could have premorbid states of depression, family histories of depression, or could be on other medications that are causing the depression. In these cases, isotretinoin cannot be solely blamed for depression. There is a lack of strong reproducible scientific data to prove absolutely that isotretenoin is causing depression (Strahan, 2006).
Some of these studies show that depression may or may not continue after the use of isotretinoin is discontinued. Either way, isotretenoin cannot be blamed for the depression. If the depression does end when medication ends, it could be for a variety of other reasons, like an enhanced self-esteem due to reduced acne. If the depression doesn’t stop when medication stops, then the isotretinoin cannot be blamed for the depression anyways.
Another problem with these studies is that the same people who are usually depressed in the general population are the same people who usually suffer from acne: adolescents (Strahan, 2006).
Finally, there is controversy over the drug because other studies suggest the opposite effect of isotretinoin on patients. Peck’s study found patients to be less depressed and more confident with isotretinoin use (Strahan, 2006).
The point is, when studying the effects of isotretinoin on depression and other psychopathic disorders, there are so many external variables that it is hard to isolate isotretinoin as the cause of depression.
Heer states, “Out of more than 500,000 drugs on the market, Accutane is only one of three that carries the words suicide, suicide attempts, and suicide ideation as a warning” (2006). This statistic cannot be taken lightly. However, Accutane is a widely-used drug and in many cases, the benefits outweigh the costs. For example, the patients in the Hull and Demkiw-Bartel study realized the medicine could be causing their depression, but continued to take the medicince because of the tremendous effects of Accutane on their acne. Heer also emphasizes these effects, stating that many dermatologists deem Accutane an “essential tool of practice” (2002). He also indicates that the rate of suicide among the Accutane-taking population is actually lower than the rate of suicide among the general population (Heer, 2002). Finally, there are insufficient studies to prove that isotretinoin has a causal relationship with suicide or depression.
Bruno, N.P., Beacham, B. E., Burnett J. W. (1984). Adverse effects of isotretinoin therapy. Cutis, 33, 484-489.
Hazen, P. G., Carney, J. F., Walker, A. E., et al. (1983). Depression - a side effect of 13-cis-retinoic acid therapy. Journal of the American Academy of Dermatology, 9, 278- 279.
Heer, J. (2002). Good drug/bad drug: Critics of Accutane say the popular acne medication is getting out of control. National Post.
Hull, P. R., Demkiw-Bartel, C. (2000). Isotretinoin use in acne: prospective evaluation of adverse events. Journal of Cutaneous Medicine and Surgery, 4, 66-70.
Kontaxakis, V. P. et al. (2009). Isotretinoin and psychopatology: a review. Annals of General Psychiatry, 8.
Meyskens, F. L. (1982). Short clinical reports. Journal of the American Academy of Dermatology, 6, 732.
Scheinman, P. L., Peck, G. L., Rubinow, D.R., et al. (1990). Acute depression from isotretinoin. Journal of the American Academy of Dermatology, 22, 1112-1113.
Strahan, J. E., Raimer, S. (2006). Isotretinoin and the controversy of psychiatric adverse effects. International Journal of Dermatology, 45, 789-799.
Wysowski, D. K., Pitts, M., Beitz, J. (2001). An analysis of reports of depression and suicide in patients treated with isotretinoin. Journal of the American Academy of Dermatology, 45, 515-519.
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