Suicidal Thoughts: Latest Risk for Baldness and Prostate Drug Finasteride (PROPECIA, PROSCAR)

In the 1990s, the Food and Drug Administration (FDA) approved two doses of finasteride — an oral prescription drug that belongs to a drug class called 5-alpha reductase inhibitors, which inhibit the formation of a potent form of testosterone — for use in men. The high (5-milligram [mg]) dose, which is sold under the brand name PROSCAR, is approved for use as a stand-alone drug to control symptomatic benign prostatic hyperplasia or enlargement (BPH) and also for joint use with the alpha-blocker doxazosin (CARDURA) to reduce the risk of symptomatic progression of this condition.[1] The low (1-mg) dose, which is sold under the brand name PROPECIA, is approved for male pattern baldness.[2] Both dosage forms are taken once daily.

Public Citizen's Health Research Group classifies both formulations as Do Not Use[3] because their benefits do not outweigh their multiple adverse effects, including high-grade prostate cancer and persistent sexual dysfunction. Yet, with nearly 10 million prescriptions filled in 2016, finasteride continues to be among the top 100 most commonly prescribed drugs in the U.S.[4]

Recent evidence has linked finasteride to suicidal thoughts (ideation), prompting French drug regulators to add this adverse effect to the labeling of finasteride products starting in early 2018.[5] Yet, at press time, the FDA has neither acknowledged this risk nor warned U.S. consumers about it.

Small benefits, multiple risks

The main clinical trials that supported the initial approval of finasteride showed that the drug improves some symptoms of BPH (mainly increased urine output) compared with a placebo. However, a 1993 review by the independent French drug journal Prescrire International characterized these benefits as "slow" and as being of "mild clinical efficacy."[6] It also noted a lack of long-term trials, at that time, comparing finasteride with alpha-blockers (such as doxazosin). Alpha-blockers improve BPH symptoms immediately by relaxing the smooth muscles in the bladder and prostate. In 2010, a review by Cochrane[7] addressed this gap and examined studies that compared finasteride with alpha-blockers for treatment of BPH. This review concluded that the alpha-blocker doxazosin is actually more effective than finasteride and that the long-term effectiveness of finasteride is small.

Likewise, the trials that supported the approval of finasteride for male pattern baldness showed that the drug increased hair growth in half of the male subjects with mild-to-moderate degrees of male pattern baldness after one year of treatment.[8] However, any hair that grew due to finasteride use was shed after the drug was discontinued.

Notably, finasteride is associated with serious adverse effects that were not known until several years after the drug was approved, requiring multiple labeling changes over the years. These adverse events include angioedema (a potentially life-threatening allergic reaction that can cause swelling in the skin, lips, mouth and throat),[9] depression,[10] high-grade prostate cancer,[11] male breast cancer,[12] male breast enlargement,[13] male infertility,[14] and sexual dysfunction that persists after the drug is discontinued.[15] Importantly, finasteride causes abnormalities in the external genitalia of male fetuses of pregnant women who receive the drug.[16]

Suicidal ideation

An analysis of reports submitted to the FDA's Adverse Event Reporting System (FAERS) from 1998 to 2013 identified 39 suicidal ideation reports for low-dose finasteride among men aged 18 to 45.[17] Although the reporting rate for finasteride was disproportionately higher than the rates for other drugs, the difference did not reach statistical significance.

A more specific updated analysis[18] looked at all finasteride reports in the FAERS database submitted from January 2004 to March 2017. It identified numerous reports with suicidal behaviors in which the drug was listed as the "primary suspect": suicidal ideation (341 reports), suicide attempts (50 reports) and completed suicide (49 reports). The researchers who did this analysis concluded that finasteride was positively associated with suicidal ideation and that this association was the highest in reports in which the drug was used for baldness.

Further support for the association between suicidal ideation and finasteride comes from two other studies that used stronger designs.

The first was a 2012 retrospective study of 61 male users of low-dose finasteride who developed chronic sexual adverse effects after they discontinued the drug.[19] These users had no prior history of sexual dysfunction or chronic medical or psychiatric conditions, and they did not use any other oral prescriptions before or during their use of finasteride. Suicidal thoughts occurred in 44 percent of these users, compared with just 3 percent among a similar control group who also had male pattern baldness but did not use finasteride.

The second was a 2017 large, retrospective Canadian study that compared over 93,000 elderly finasteride users with a similar number of carefully matched nonusers.[20] It showed an increased risk of self-harm among finasteride users, although this risk was statistically significant only during the first 18 months of finasteride therapy.

What You Can Do

Do not take finasteride for any purpose. If you are currently using this drug, consult your doctor about switching to a safer alternative treatment. Safer drug options include an alpha-blocker for BPH[21] and the topical over-the-counter drug minoxidil (ROGAINE, THEROXIDIL) for male pattern or female pattern baldness.[22]
 

References

[1] Merck Sharp & Dohme Corp. Label: finasteride (PROSCAR). September 2013. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=7c01f541-1c88-400c-41a9-7cbb9dee50c0&type=display. Accessed February 18, 2019.

[2] Merck Sharp & Dohme Corp. Label: finasteride (PROPECIA). September 2013. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=4e07adb4-7807-47d3-b9a9-2332a3047410&type=display. Accessed February 18, 2019.

[3] Drug profile: finasteride (PROPECIA, PROSCAR). November 2018. /monographs/view/49. Accessed February 18, 2019.

[4] Symphony Health. Top 200 drugs - 2016. https://symphonyhealth.com/wp-content/uploads/2017/04/Top-200-Drug-List-2016.pdf. Accessed February 12, 2019.

[5] Finasteride in alopecia: a disproportionate risk of depression or suicidal thoughts. Prescrire Int. 2018;27(196):214.

[6] Finasteride tablets. Prescrire Int. 1993;2(7):99-101.

[7] Tacklind J, Ha F, Macdonald R, et al. Finasteride for benign prostatic hyperplasia. Cochrane Database Syst Rev. 2010;6(10):CD006015.

[8] Merck Sharp & Dohme Corp. Label: finasteride (PROPECIA). September 2013. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=4e07adb4-7807-47d3-b9a9-2332a3047410&type=display. Accessed February 18, 2019.

[9] Food and Drug Administration. Letter to Merck Sharpe & Dohme Corp. re. supplemental approval NDA 020180/S-044 requiring labeling changes for finasteride (PROSCAR). March 11, 2014. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2014/020180Orig1s044ltr.pdf. Accessed February 12, 2019.

[10] Food and Drug Administration. Letter to Merck Sharp & Dohme Corp. re. supplemental approvals NDA 020180/S-040, NDA 020180/S-041, and NDA 020180/S-042 requiring labeling changes for finasteride (PROSCAR). April 11, 2012. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2012/020180s040,s041,s042ltr.pdf. Accessed February 12, 2019.

[11] FDA Drug Safety Communication: 5-alpha reductase inhibitors (5-ARIs) may increase the risk of a more serious form of prostate cancer. June 9, 2011. https://www.fda.gov/Drugs/DrugSafety/ucm258314.htm. Accessed February 12, 2019.

[12] Food and Drug Administration. Letter to Merck Sharp & Dohme Corp. re. supplemental approval NDA 020180/S-037 requiring labeling changes for finasteride (PROSCAR). October 4, 2010. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2010/020180s037ltr.pdf. Accessed February 12, 2019.

[13] Ramot Y, Czarnowicki T, Zlotogorski A. Finasteride induced gynecomastia: case report and review of the literature. Int J Trichology. 2009;1(1):27-29.

[14] Food and Drug Administration. Letter to Merck Sharp & Dohme Corp. re. supplemental approvals NDA 020180/S-040, NDA 020180/S-041, and NDA 020180/S-042 requiring labeling changes for finasteride (PROSCAR). April 11, 2012. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2012/020180s040,s041,s042ltr.pdf.

[15] Food and Drug Administration. Letter to Merck Sharp & Dohme Corp. re. supplemental approval NDA 020180/S-043 requiring labeling changes for finasteride (PROSCAR). January 16, 2013. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2013/020180Orig1s043ltr.pdf. Accessed February 12, 2019.

[16] Merck Sharp & Dohme Corp. Label: finasteride (PROSCAR). September 2013. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=7c01f541-1c88-400c-41a9-7cbb9dee50c0&type=display. Accessed February 18, 2019.

[17] Ali AK, Heran BS, Etminan M. Persistent sexual dysfunction and suicidal ideation in young men treated with low-dose finasteride: a pharmacovigilance study. Pharmacotherapy. 2015;35(7):687-695.

[18] Gupta MA, Vujcic B, Gupta AK. Suicidal behaviors (suicidal ideation, suicide attempt and completed suicide) in patients treated with finasteride for hair loss: Results from the U.S. FDA Adverse Event Reporting System (FAERS) database. J Am Acad Dermatol. 2018;79(3 Supplement 1):AB274.

[19] Irwig MS. Depressive symptoms and suicidal thoughts among former users of finasteride with persistent sexual side effects. J Clin Psychiatry. 2012;73(9):1220-1223.

[20] Welk B, McArthur E, Ordon M, et al. Association of suicidality and depression with 5α-reductase inhibitors. JAMA Intern Med. 2017;177(5):683-691.

[21] Drug profile: finasteride (PROPECIA, PROSCAR). November 2018. /monographs/view/49. Accessed February 12, 2019.

[22] Medications for hair loss. Worst Pills, Best Pills News. August 2017. /newsletters/view/1145. Accessed February 12, 2019.