Erectile dysfunction and depression: how to choose antidepressants and ED medications safely

Erectile dysfunction (ED) is common, and it is closely linked to mental health. Depression raises the risk of ED, ED raises the risk of depression, and many antidepressants can affect sexual function. As a result, some men avoid antidepressants or stop taking them because they fear sexual side effects. Yet untreated depression can also harm your sex life. This article explains how depression and antidepressants affect erectile function, which treatment options have less impact, and how a pharmacogenetic test can help you and your doctor choose the right medication and dose.

How common is erectile dysfunction?

About half of men aged 40 to 70 have some difficulty with erections, and the problem becomes more common with age. Age was the strongest risk factor, followed by heart disease, high blood pressure, diabetes, the medications used to treat them, and depression. In older men, ED is often an early sign of blood vessel or heart disease. Psychological causes, such as stress, anxiety and depression, are more common in younger men.

If you have ED or reduced sexual desire, it is important to have both your heart health and your mental health checked by a healthcare provider.

How are depression and erectile dysfunction connected?

A meta-analysis of 49 studies found that men with depression were about 40% more likely to have ED, and men with ED were nearly three times as likely to have depression. Depression can reduce sexual desire, arousal and erectile function, and ED can lower self-esteem and strain relationships, which can worsen depression.

This is why depression should be treated, not avoided. The right antidepressant at the right dose can improve mood without making sexual function worse, and doctors should ask about sexual side effects, because many men do not raise the topic themselves.

Which antidepressants affect sexual function?

Sexual side effects, including lower sexual desire, difficulty with erections and delayed orgasm or ejaculation, are among the most common reasons people stop taking antidepressants. A meta-analysis found that, compared with placebo, the following antidepressants had higher rates of sexual side effects, affecting 26% to 80% of people depending on the medication:

• Selective serotonin reuptake inhibitors (SSRIs): sertraline (Zoloft), citalopram (Celexa), paroxetine (Paxil), fluoxetine (Prozac), escitalopram (Cipralex) and fluvoxamine.
• Serotonin and norepinephrine reuptake inhibitors (SNRIs): venlafaxine (Effexor) and duloxetine (Cymbalta).

Antidepressants with sexual side effects no more frequent than with placebo, or with lower rates, include:

• bupropion (Wellbutrin);
• mirtazapine (Remeron);
• moclobemide;
• vortioxetine (Trintellix).

SSRI-related sexual side effects depend on the dose and usually go away when the dose is lowered or the medication is stopped; very rarely, they persist. Never stop or change an antidepressant on your own; talk to your doctor about options such as lowering the dose, switching to an antidepressant with fewer sexual side effects or adding a treatment for ED.

Can ED medications be taken with antidepressants?

Yes. The ED medications sildenafil (Viagra), tadalafil (Cialis) and vardenafil (Levitra) belong to a group called PDE5 inhibitors. A Cochrane review found that adding sildenafil or tadalafil improved erectile function in men with ED caused by antidepressants. Common side effects of these medications include headache, flushing, indigestion, a stuffy nose, back or muscle pain and changes in vision.

PDE5 inhibitors can be taken with most antidepressants, but some combinations are dangerous or need a dose change:

• Nitrates, such as nitroglycerin and isosorbide, used for chest pain: never take them with a PDE5 inhibitor, because the combination can cause a severe drop in blood pressure.
• Alpha-blockers, such as tamsulosin and doxazosin, used for prostate symptoms or high blood pressure: these can also lower blood pressure and require caution.
• Strong blockers of the liver enzyme CYP3A4, such as ritonavir, ketoconazole, itraconazole and clarithromycin: PDE5 inhibitors are broken down mainly by CYP3A4, so these medications can greatly raise their levels and lower doses are needed. Grapefruit juice has a smaller effect.

Your genes can have a similar effect. The CYP3A4 gene has many inherited variants, and some reduce how well the enzyme works. In a laboratory study of 21 CYP3A4 variants, most reduced how fast sildenafil was broken down, some sharply; sildenafil is also broken down to a lesser extent by CYP2C9, which has its own variants. Inherited reduced CYP3A4 function is expected to work like taking a medication that blocks CYP3A4: it raises the levels of ED medications and can cause a stronger response, with more side effects such as headache, flushing, dizziness or low blood pressure. The effect can add up when someone with reduced CYP3A4 function also takes a CYP3A4-blocking medication. There are no genotype-specific dosing guidelines for ED medications yet, so the dose advice that already applies to CYP3A4-blocking medications, such as starting at a lower dose, is a sensible guide for people with reduced CYP3A4 function.

Always tell your doctor and pharmacist about all of your medications before starting an ED medication, including those bought without a prescription.

How do genes affect antidepressant side effects?

Most antidepressants are broken down by the liver enzymes CYP2D6, CYP2C19 and CYP2B6. Inherited differences in these genes can make a standard dose too strong or too weak. People who clear a medication slowly (poor metabolizers) can have higher blood levels and more side effects, including sexual side effects, while people who clear it quickly (ultrarapid metabolizers) may not respond.

Guidelines from the Clinical Pharmacogenetics Implementation Consortium (CPIC) use these genes to guide the choice and dose of many antidepressants. For example, for CYP2C19 poor metabolizers, CPIC recommends considering a lower starting dose and slower dose increases of citalopram, escitalopram or sertraline, or a different antidepressant. For CYP2D6 poor metabolizers, it recommends considering a lower starting dose of paroxetine or vortioxetine, and an alternative to venlafaxine.

How can a Pillcheck test help?

With Pillcheck, a pharmacist reviews your results together with all of your current medications, including any ED medication, accounts for drug-drug-gene interactions and prepares recommendations that you can share with your doctor. For example, the pharmacist can suggest an antidepressant and dose that match your genes, and flag combinations to avoid or medications that may need a dose change. When no genetic guideline exists for a medication, the pharmacist applies what is known about drug-drug interactions to drug-gene interactions: if your genes reduce the activity of an enzyme, your medications are reviewed as if you were taking a medication that blocks that enzyme.

Pillcheck testing is performed in CAP- and COLA-accredited clinical genetic laboratories located in Canada. Pillcheck reports on 24 genes, increasing coverage with new guidelines and drug labels (see the genes tab), and covers 355 medications, which account for over 70% of dispensed prescriptions. The Pillcheck test panel ensures high accuracy for people of non-European and admixed ancestries. Your results last a lifetime, and report updates are free of charge.

Summary

• About half of men aged 40 to 70 have some degree of ED; heart disease, diabetes, high blood pressure and depression all raise the risk.
• Depression and ED are closely linked, and untreated depression can worsen sexual function.
• SSRIs and SNRIs such as venlafaxine and duloxetine commonly cause sexual side effects; bupropion, mirtazapine, moclobemide and vortioxetine cause fewer.
• Sildenafil and tadalafil can improve antidepressant-related ED, but must never be taken with nitrates. Inherited reduced CYP3A4 function works like a CYP3A4-blocking medication and can cause a stronger response to ED medications.
• Genetic testing can help choose an antidepressant and dose that cause fewer side effects.

Frequently asked questions

Should I avoid antidepressants because of sexual side effects?

No. Untreated depression can also cause ED. Talk to your doctor about antidepressants with fewer sexual side effects and about the right dose for you.

Will sexual side effects go away?

Sexual side effects of SSRIs usually go away when the dose is lowered or the medication is stopped. Do not stop an antidepressant suddenly; your doctor can help you make changes safely.

Is it safe to take Viagra or Cialis with my antidepressant?

For most antidepressants, yes. The most important risks come from nitrates, tamsulosin (Flomax) and doxazosin or other alpha-blockers. When combined with an ED medication, they can cause dizziness or fainting from low blood pressure. Ask your pharmacist to check all of your medications.

References

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Liu Q, Zhang Y, Wang J, et al. Erectile dysfunction and depression: a systematic review and meta-analysis. J Sex Med. 2018;15(8):1073-1082.

Serretti A, Chiesa A. Treatment-emergent sexual dysfunction related to antidepressants: a meta-analysis. J Clin Psychopharmacol. 2009;29(3):259-266.

Waldinger MD. Psychiatric disorders and sexual dysfunction. Handb Clin Neurol. 2015;130:469-489.

Jing E, Straw-Wilson K. Sexual dysfunction in selective serotonin reuptake inhibitors (SSRIs) and potential solutions: a narrative literature review. Ment Health Clin. 2016;6(4):191-196.

Taylor MJ, Rudkin L, Bullemor-Day P, Lubin J, Chukwujekwu C, Hawton K. Strategies for managing sexual dysfunction induced by antidepressant medication. Cochrane Database Syst Rev. 2013;(5):CD003382.

Tang PF, Zheng X, Hu XX, et al. Functional measurement of CYP2C9 and CYP3A4 allelic polymorphism on sildenafil metabolism. Drug Des Devel Ther. 2020;14:5129-5141.

Bousman CA, Stevenson JM, Ramsey LB, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6, CYP2C19, CYP2B6, SLC6A4, and HTR2A genotypes and serotonin reuptake inhibitor antidepressants. Clin Pharmacol Ther. 2023;114(1):51-68.