Introduction

Persistent genital arousal disorder (PGAD) is a condition that affects both people assigned male at birth (AMAB) and people assigned female at birth (AFAB). It is essentially a spontaneous genital arousal without any sexual desire.¹ The most common symptoms include discomfort, stress and sensations in the genital area, which can last from hours to days. This affects individuals psychologically, as unwanted arousal can affect day-to-day life, from relationships to work-life balance. Treating this disorder using antidepressants has been proven to relieve some of the symptoms; however, it can also worsen such symptoms. Selective serotonin reuptake inhibitors (SSRIs) are the commonly prescribed antidepressant type for PGAD, which treats the psychological symptoms of PGAD as well as reduces sexual desire and libido.

Understanding PGAD and its symptoms

There are many symptoms associated with PGAD. Spontaneous genital arousal is one of the most common, where unwanted and persistent arousal can develop without stimulation or sexual desire. Physical discomfort is another symptom which can persist if there is continuous arousal, which can also lead to pain or sensitivity in the genitals.

Nevertheless, individuals with PGAD also experience difficulty with sexual intimacy because there is difficulty experiencing sexual satisfaction.² Emotional stress is also another key symptom that patients experience. Unwanted arousals can lead to anxiety and frustration.

Moreover, psychological distress can develop due to the lack of control over the body, which can be associated with disruptions in social life. This can lead to many problems with social interactions and romantic relationships.

The International Society for the Study of Women's Sexual Health (ISSWSH) suggests that the correct diagnosis of PGAD includes patients who have experienced these symptoms for at least three months.³ Although these symptoms are general, they can vary from patient to patient and may also be triggered by certain factors such as the patient’s mental health.

The possible underlying causes of PGAD involve hormonal, neurological, and psychological aspects. The neurological aspect behind PGAD involves lesions affecting sacral sensory networks, which are networks that transmit sexual arousal.⁴

In particular, AFAB patients with PGAD have been discovered to have Tarlov cysts, which are a type of sacral meningeal cyst that is located in the nerve endings of the spine.⁵ These types of cysts affecting the central nervous system are known to cause sexual dysfunction and bowel problems.

Nevertheless, the underlying psychological factors that cause PGAD are anxiety, depression and stress. Obsessive-compulsive disorder (OCD) and major depressive disorder can be underlying causes of PGAD. ⁶ A psychiatric observation is useful to confirm the PGAD diagnosis.

Additionally, hormonal imbalances are also likely to influence PGAD; high or low oestrogen levels in people AFAB can lead to sensitivity and arousal in the genital area. Also, hormones such as dopamine and serotonin dysregulation can cause PGAD-like symptoms.

How antidepressants work

Antidepressants are widely used for the treatment of PGAD and to relieve the psychological symptoms that are associated with it. The mechanism of action involves altering the balance of neurotransmitters such as serotonin, dopamine, and norepinephrine in the brain, which are dysregulated if you have a mental health illness. This helps treat mood swings and emotional instability, which are symptoms associated with PGAD.

There are a few antidepressants that are widely prescribed for PGAD, depending on the circumstances of the patient:

• SSRIs (selective serotonin reuptake inhibitors)
• SNRIs (serotonin-norepinephrine reuptake inhibitors)
• MAOIs (monoamine oxidase inhibitors)
• TCAs (tricyclic antidepressants)

The impact of antidepressants on PGAD

There are types of SNRIs that are likely to worsen symptoms of PGAD, whereas some show improvement. A recent study of a PGAD patient delineates AFAB, who had taken levomilnacipran to ease anxiety, resulting in worsened PGAD symptoms.⁷

Although this type of SNRI impacted PGAD symptoms negatively, the same patient showed 90% improvement in symptoms by taking pramipexole.⁷ The SNRI mechanism of action involves blocking reuptake of both norepinephrine and serotonin, different from SSRIs. It is also used for treating chronic pain alongside anxiety and depression.

Duloxetine is another SNRI-type antidepressant that is mainly prescribed for mood disorders and chronic pain. A 39-year-old patient AFAB with involuntary genital arousal was observed and prescribed duloxetine 60mg/day to study the effects, whereby observations showed no sign of PGAD symptoms after taking medication.⁸   

The immediate effects of taking certain SSRIs are genital sensory changes, such as numbness in the area and reduced sensitivity. After a while, orgasms and loss of libido are seen as side effects of SSRIs, which are viewed as beneficial for PGAD symptoms, but also used for patients with premature ejaculation.⁹

Nevertheless, tricyclic-type antidepressants’ mechanism of action involves affecting serotonin and norepinephrine neurotransmitters. They may also worsen PGAD symptoms as they have many side effects. Anticholinergic effects are observed, which lead to sexual dysfunction, constipation and dryness, which can in turn intensify genital arousal.

Other types of medication that decrease neuronal activity, such as pregabalin,  calcium channel blockers and drugs like tramadol, could be used to relieve symptoms of pain.

Why antidepressants may worsen PGAD symptoms

As mentioned above, specific antidepressants have been proven to worsen PGAD symptoms, but there are also many side effects associated with these antidepressants that can negatively impact PGAD.

These side effects include, for example, sexual dysfunction,  reduced libido and difficulty performing sexual activities. Approximately 40% of people on antidepressants eventually develop sexual dysfunction side effects, according to research based on the link between sexual function and antidepressants.¹⁰

Individuals AMAB commonly experience erectile dysfunction and delayed ejaculation, whilst those AFAB can experience delayed orgasms and loss of libido. In the short term, antidepressants could potentially help with PGAD symptoms; however, in the long term, this could worsen PGAD symptoms.

The role of serotonin is also important in regulating sexual function and mood. Antidepressants help increase serotonin levels to regulate these functions. However, increasing serotonin levels may lead to increased sexual arousal, potentially worsening PGAD symptoms.

Why antidepressants may relieve PGAD symptoms

PGAD symptoms, such as mood disorders, are common. Anxiety-related panic attacks and depression are often observed in patients. Obsessive-compulsive symptoms, suicidal thoughts and emotional trauma are additional symptoms seen with these patients, and the best way to relieve these symptoms is by taking antidepressants like SSRIs and SNRIs.

Alternative therapy, like cognitive behavioural therapy (CBT), can help manage the symptoms, but it is always better to combine this with antidepressants for successful treatment. Levomilnacipran is a type of SNRI which elevates serotonin levels in the body but also increases dopamine production; however, the downside of this type of SNRI is that it can interact with other medications like varenicline.¹¹ The efficacy of each antidepressant can be affected by co-treatments; therefore, the medical history is important for healthcare professionals to prevent drug interactions.

The right antidepressant is personalised to the patient, taking into consideration factors such as the dosage, medical history and side effects. Although SNRIs relieve PGAD symptoms, the discontinuation of SNRIs could lead to a rebound effect and the development of PGAD symptoms. As you stop using the antidepressant, the brain releases dopamine from chronic inhibition by serotonin, potentially increasing blood flow to the genital area, which can lead to PGAD symptoms.¹²

Other treatment options could also be useful in the event of stopping antidepressant usage. Electroconvulsive therapy (ECT) can be an option for treating severe cases of PGAD, which involves electric pulses sending signals to the brain, relieving symptoms of genital arousal disorder. Alternatively, a new treatment approach involves injecting Botox into the pelvic floor muscles, which helps relax the muscles and relieve symptoms. 

Summary

Persistent genital arousal disorder (PGAD) is a condition characterised by a spontaneous genital arousal without any sexual desire. It affects both people assigned male at birth (AMAB) and people assigned female at birth (AFAB). Antidepressants are useful for treating and improving PGAD and the symptoms associated with it; however, this is not always the case, as some patients can experience worsened PGAD symptoms after a time. A tailored treatment plan for  PGAD patients is the best way to approach relieving symptoms as well as managing the disorder. A combination of taking antidepressants, other types of medication and cognitive behavioural therapy can be useful. Regular checkups with a healthcare professional are also important in managing this disorder, as medication dosage adjustment may be required or stopping a medication entirely, depending on the situation.