Overview 

Antidepressants are a class of drugs used for the treatment of depression. They are among the most widely prescribed medications worldwide.¹

In addition to depression, they are also used in managing several other mental health conditions, including social phobia, panic disorder, obsessive-compulsive disorder, generalised anxiety disorder and post-traumatic stress disorder.²

These drugs function by making more neurotransmitters, which are chemicals in the brain that control mood and behaviour. Antidepressants help maintain emotional health by keeping these substances in balance.³

Like most medications, antidepressants can cause side effects. Common ones include problems with sexual function, sleepiness, trouble sleeping, anxious feelings, dry mouth, weight gain, blurry vision, nausea, skin rashes and shaking or tremors.²

Types of antidepressants

Selective serotonin reuptake inhibitors (SSRIs)

SSRIs increase the amount of serotonin in the brain, a chemical that helps regulate mood. They work by preventing the reabsorption (reuptake) of serotonin, allowing it to remain active in the brain for a longer period.²

Examples: fluoxetine, sertraline, citalopram, escitalopram, paroxetine

Selective serotonin noradrenaline reuptake inhibitors (SNRIs)

SNRIs prevent the reabsorption of serotonin and norepinephrine, two neurotransmitters that play a role in regulating mood and emotions.

Examples: venlafaxine, duloxetine, and desvenlafaxine.

MAOIs (Monoamine Oxidase Inhibitors) 

MAOIs function by stopping the action of monoamine oxidase, an enzyme responsible for breaking down neurotransmitters like serotonin, norepinephrine, and dopamine. Blocking this enzyme leads to higher levels of these chemicals in the brain.

Examples: phenelzine, tranylcypromine, isocarboxazid

Tricyclic antidepressants (TCAs)

TCAs raise serotonin and norepinephrine levels by blocking their reabsorption into nerve cells. They are prescribed less often due to a higher risk of side effects compared to newer antidepressants.

Examples: amitriptyline, nortriptyline, imipramine, clomipramine

Atypical antidepressants

They affect various neurotransmitters in unique ways. Atypical antidepressants are often prescribed when other treatments are ineffective or cause side effects.

Examples: bupropion, mirtazapine, trazodone

Sexual desire

Sexual desire is a fundamental aspect of human life, both for satisfaction and reproduction. 

Libido, or sexual desire, refers to a person’s interest in sex or sexual activities.⁴

The normal sexual response cycle has four stages: desire, arousal, orgasm, and resolution. These phases are regulated by the activities of neurotransmitters, hormones, and other physiological factors.⁵

While more research is needed, existing studies generally suggest that antidepressants can negatively affect sexual desire.⁵

Many individuals report experiencing a reduced interest in sex, difficulty becoming aroused, trouble reaching orgasm, erectile dysfunction, or delayed ejaculation.⁵ There are also case reports describing unusual sexual side effects, such as prolonged and painful erections (priapism), ejaculation-related pain, penile numbness, or reduced sensation in the vagina or nipples.⁵

Sexual desires and antidepressants

Antidepressants can affect sexual desire by acting on the neurotransmitters, hormones, and brain regions that regulate sexual motivation and arousal.

These effects can influence various phases of the sexual response cycle to varying degrees, depending on the specific mechanism of action of the antidepressant.⁵

Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs are the classes most commonly associated with sexual side effects, and these effects tend to occur more frequently in men than in women.^4,5

Neurotransmitters and antidepressants 

Neurotransmitters are chemical messengers in your brain that facilitate communication between nerve cells. They play a crucial role in regulating thoughts, emotions, and behaviours.

The main neurotransmitters involved in sexual desire are serotonin, dopamine, and noradrenaline

Serotonin

Serotonin is primarily responsible for regulating mood, anxiety, and overall emotional well-being. 

In sexual function, increased serotonin levels are associated with reduced libido and diminished sexual desire.

Antidepressants that increase serotonin levels by inhibiting its reuptake, such as selective serotonin reuptake inhibitors (SSRIs), are most commonly linked to these effects.

These medications often result in decreased sexual desire, anorgasmia, and erectile dysfunction.

Serotonin-norepinephrine reuptake inhibitors (SNRIs) can produce similar sexual side effects, although to a reduced extent than SSRIs.

Monoamine oxidase inhibitors (MAOIs) increase serotonin levels by preventing its breakdown, which may similarly lead to reduced libido.

In contrast, atypical antidepressants generally have minimal effects on serotonin levels and are therefore less likely to cause sexual side effects.

High serotonin levels can also inhibit dopamine, a neurotransmitter crucial for sexual motivation and reward, further contributing to reduced libido and difficulty achieving orgasm.

Additionally, serotonin may lower the production of nitric oxide, a molecule that helps blood vessels relax and enhance blood flow to sexual organs. Reduced nitric oxide means reduced blood flow to the sexual organs, which subsequently affects sexual arousal and function.⁶

Dopamine

Dopamine increases libido by enhancing arousal and the anticipation of sexual pleasure.

Antidepressants like SSRIs increase serotonin, which decreases dopamine, leading to decreased arousal.

Norepinephrine 

Norepinephrine is very much involved in the body's "fight or flight" response. 

In sexual activity, norepinephrine contributes to physical arousal and readiness, especially through the sympathetic nervous system.

However, excessive norepinephrine activity can lead to anxiety and vasoconstriction, affecting sexual function.

Hormones and antidepressants

Hormones are chemical messengers produced by glands in the body and are sent into the blood, where they tell other parts of the body what to do.

Hormones are involved in sexual function, and they can be affected by antidepressants.

Testosterone

Testosterone is the primary male sex hormone and plays a crucial role in regulating sexual desire and function.⁶

Antidepressants may influence testosterone levels, which can, in turn, affect sexual desire.

For example, some studies suggest that Selective Serotonin Reuptake Inhibitors (SSRIs) may reduce testosterone levels, although further research is needed to fully understand this effect.⁷

Oestrogen 

Oestrogen plays a vital role in female sexual desire, arousal, and overall sexual function. 

Some antidepressants, particularly SSRIs, may affect oestrogen levels; however, findings in this area remain mixed.⁷

Brain regions associated with libido and antidepressants

Sexual desire is also controlled by a complex network of brain regions and activities primarily in the limbic system.⁴

The most important areas involved include:⁴

Hypothalamus

The hypothalamus primarily controls sexual behaviours. It plays a central role in regulating sexual behaviour and the release of sex hormones such as testosterone and estrogen from the pituitary gland.⁴ Also, it controls autonomic processes involved in sexual activity.⁴

A study examining the effects of antidepressant treatment on sexual arousal in women with depression found that mirtazapine administration was associated with increased hypothalamic activation during sexual stimulation.⁸

This suggests that certain antidepressants may help restore or enhance hypothalamic function related to sexual arousal.

Amygdala 

It processes emotional responses and sexual arousal, playing a key role in sexual attraction.⁹ Antidepressants may reduce hyperactivity in these neural circuits, leading to improved regulation of emotional responses and sexual desire.⁹

Nucleus accumbens

This is the brain's reward system, which controls pleasure, motivation, and reinforcement, and plays a central role in the rewarding aspects of sex.⁴

Dopamine release in the nucleus accumbens is closely linked to sexual arousal and reward.¹⁰

Studies also show that increased dopamine levels enhance nucleus accumbens activation in response to sexual stimuli, whereas dopamine antagonists reduce this response.¹⁰

SSRIs can indirectly suppress dopaminergic activity in the nucleus accumbens by increasing serotonin levels. This suppression may reduce sexual desire and pleasure, contributing to sexual dysfunction.

Prefrontal cortex

It regulates sexual behaviour in socially appropriate ways.⁴ The prefrontal cortex integrates cognitive and emotional aspects of sexual behaviour, influencing sexual desire and decision-making related to sexual activity.

Coping strategies 

Some of the ways to handle the side effects of antidepressants on sexual desires include:

• Switching to a different class of antidepressant with fewer sexual side effects, such as bupropion 
• Sexual side effects can be both biological and psychological. Working with a sex therapist or counsellor can help address anxiety, relationship concerns, or body image issues that compound the medication effects
• Changing lifestyle can indirectly improve sexual function and mood. This includes exercise, which boosts endorphins and improves body image, limiting alcohol, which can worsen sexual dysfunction
• Open communication with partners to reduce stress and pressure related to sexual performance

Summary 

While antidepressants are important for treating depression and other mental health conditions, they can sometimes affect sexual desire and function. This happens because they change the levels of brain chemicals and hormones that control mood and sex drive. These side effects vary depending on the type of antidepressant and the individual. It's important to work with a healthcare provider to find the right balance between mental health and sexual well-being.