Antidepressants and sexual health - How pharmacogenetics can help find the right medication for you

Antidepressants, low libido and sexual health

Stress, anxiety, and depression can have a negative impact on sexual health, causing low libido, premature ejaculation, and erectile dysfunction. However, many men and women are hesitant to seek or continue treatment for these mental health conditions due to the well-known negative effects of commonly prescribed SSRIs on sexual health. It's important to remember that sexual health is a vital aspect of overall mental and physical well-being. Antidepressant medications come in many different types, and depending on the individual drug, they can have unique impacts on an individual’s sexual health and well-being. Additionally, not every individual will respond to a specific drug in the same way. Using pharmacogenetics, DNA testing can help identify which medications are the best fit for you personally.

Stopping medication too early

According to a recent study, women tend to discontinue their antidepressant therapy within 1.9 years, while men continue it for an average of 2.6 years. The risk of relapse and worsening symptoms increases when therapy is stopped prematurely. The most common reasons for discontinuation are sexual dysfunction and strained spousal relationships, which may lead to misguided decisions to stop the medications too early.

Genes, drugs and sexual health

Most antidepressant medication side effects, such as low libido, depend on the dosage. The majority of antidepressants are metabolized by liver enzymes. Variations in the genes that control the production of these enzymes can affect the drug's blood levels via the speed and efficiency with which your body is able to process the drug, dictating its relative effectiveness, and the likelihood of side effects. If your body can't sufficiently process an antidepressant, it will accumulate in the body and cause unwanted side effects, which are the most common reason for discontinuing treatment or switching to another medication. Conversely, overly rapid elimination can lead to inadequate dosing and worsening depression. Genetically-guided drug therapy can help you and your doctor determine the optimal drug dose to improve your mental health and minimize sexual side effects.

Medications that have a lower impact on sexual health

More details on selected medications

Clomipramine (Anafranil) is a tricyclic antidepressant (TCA) that is commonly prescribed for obsessive–compulsive disorder, panic disorder, major depressive disorder, and chronic pain. TCAs, including clomipramine, are also used for Irritable Bowel Disease (IBD), depression, sleep paralysis, and trichotillomania. It shares similar side effects with many antidepressants in this class. However, clomipramine is uniquely associated with a rare side effect of spontaneous orgasms in women when sneezing or yawning (yawngasms). It is also effective for men on the drug who develop sexual dysfunction and can be used for the treatment of premature ejaculation. Men taking clomipramine were more likely to continue therapy due to the benefits on sexual health.

Dapoxetine is a fast-acting selective serotonin reuptake inhibitor (SSRI) used for the treatment of premature ejaculation that goes by the brand names Westoxetin and Priligy. It is quickly absorbed by the body and eliminated from the system. The medication is most effective when taken one to three hours before anticipated sexual activity. Dapoxetine is metabolized by two enzymes, CYP2D6 and CYP3A4. The effectiveness and safety of the medication can be impacted by genetic variations in these enzymes or other medications that affect their function. Special caution is needed when using dapoxetine and other erectile dysfunction (ED) drugs like tadalafil (Cialis) or sildenafil (Viagra), as well as other antidepressants. Some medications that induce CYP3A4 can decrease the effectiveness of ED drugs and dapoxetine. Conversely, some antiviral and antifungal medications can drastically increase the risk of severe side effects when taken with ED drugs and dapoxetine. Dapoxetine may also pose a risk of serotonin syndrome when taken together with antidepressants, opioid painkillers (tramadol), lithium and even herbal medicines (St John’s wort). Talk to your pharmacist before taking dapoxetine or changing any other medications you are taking.

Antidepressants that don't affect serotonin levels

Most antidepressants aim to increase serotonin levels in the brain, but some mental health conditions are caused by the disruption of other neurotransmitters. For people with bipolar disorders, the use of SSRIs can worsen anxiety symptoms. If you experience negative side effects such as worsened sleep, anxiety, and significantly reduced libido while taking the first-line SSRIs (escitalopram and sertraline), it's recommended that you and your doctor consider switching to antidepressants that have a lower impact on serotonin. Antidepressants such as agomelatine, bupropion, and trazodone have a lesser impact on serotonin levels and can potentially improve treatment tolerability. SNRIs, including desvenlafaxine and vortioxetine, could also be tried.

Pharmacogenetics, diet, lifestyle and cognitive therapy

When it comes to selecting a drug and determining the right dose, it's important to consider your metabolic profile for key liver enzymes, your specific symptoms, any other medications you're taking, age, and lifestyle. In addition to optimizing medications, a healthy diet, active lifestyle, adequate sleep, cognitive behavioral therapy, and even some supplements can help to support good mental and sexual health. For personalized advice on how to optimize your health, consult with your doctor, pharmacist, or nutritionist.

Selected references

Kosaski DL et al., Impact of sex on antidepressant discontinuation in groups of similar cytochrome P450 phenotypes Mental Health Clinician (2023) 13 (6): 303–310.