Escitalopram-induced Hypersexuality—Imbalance of the Sexual Seesaw

Abstract

Selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacotherapy used in major depression, anxiety disorders and obsessive-compulsive disorder. Sexual dysfunctions in the form of reduced sexual desire, difficulty reaching orgasm, or inability to maintain an erection are commonly reported with SSRI use, either by the patient or by the spouse. SSRI-induced hypersexuality is very rarely reported in the literature. Sexual dysfunction predisposes loss of treatment compliance. A 25-year-old female developed intense sexual desire and compulsive masturbation with 15 mg/day of escitalopram which vanished with discontinuation of the drug. Various factors like serotonin, dopamine, norepinephrine, and nitric oxide are implicated in the development of hypersexuality, which is both drug and group-specific. Also, the effect is dose-dependent. A high level of psychosocial stress is attached to the sexual side effects of SSRIs. Considering the sensitivity in reporting sexual symptoms, it is prudent to initiate a talk on sexual functioning with all the patients on antidepressants, especially SSRIs.

Background

Selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacotherapy widely used in major depressive disorders, anxiety disorders, and obsessive-compulsive disorders. ¹ Sexual dysfunctions are commonly reported with SSRI use, either by the patient or by the spouse. Sexual dysfunction usually reported are reduced sexual desire, difficulty reaching orgasm, or inability to maintain an erection. Vaginal dryness, priapism, and genital anaesthesia are other reported side effects. ² Sexual dysfunction is the most common cause of loss of treatment adherence. ³ High serotonergic potency is directly proportional to the sexual side effects. Studies state that SSRIs cause sexual dysfunction in up to 70% of individuals, with escitalopram accounting for about 37%.^2,4

Though sexual dysfunction as hyposexuality has been a known side effect of SSRIs, hypersexuality as a potential side effect is less reported. Here we report a case of escitalopram-induced hypersexuality in a young female.

Case Report

A 25-year-old married female presented with complaints of sad mood, fatigue, frequent anger outbreaks for trivial reasons, and suicidal intent for about six months. She had little interest in caring for her children and doing routine household chores.

Her symptoms started after she discovered her husband’s extramarital and since then she had frequent altercations with her husband. She had ruminating thoughts and worries about her strained relationship with her husband which led to reduced sleep and impaired concentration.

She was diagnosed with severe depression without psychotic symptoms, ⁵ and started on Escitalopram, at a starting dose of 5 mg/day, and escalated to 10 mg/day within one week. She tolerated the medication well and was symptomatically improving. She, however, did not have a complete resolution of symptoms. The dose of escitalopram was raised to 15 mg/day after two months. Following dose escalation, she experienced increased sexual drive and preoccupation with sexual thoughts within five days. She claimed that she had an intense urge to masturbate throughout the day to release her sexual desire and she was finding excuses to isolate herself for the same. She claimed to fantasise about sexual acts with any random person. Despite her conflict with her husband, she insisted her husband engage in sexual intercourse and was acting out seductively towards him which was unusual of her. This change in her attitude and behaviour was extremely distressing. She was restless and agitated. She also continued to have weeping spells and suicidal ideas. She was evaluated for a possible manic switch with an antidepressant. However, she reported no elation of mood, increased activity, change in grooming, or grandiosity. Also, the symptoms did not qualify for a diagnosis of sexual obsession. Details of previous medication and psychoactive substance use history were taken which yielded no significant clue. She denied similar symptoms in the past.

Basic investigations, including complete blood count and thyroid profile, were normal. Considering the possibility of adverse reactions to the drug, the Naranjo Adverse Drug Reaction scale ⁶ was applied. She scored 8, which suggested a probable drug-induced reaction secondary to Escitalopram.

Hence, the offending drug (Escitalopram) was stopped and she was started on Mirtazapine. A low dose of risperidone was added as an adjuvant considering the intensity of anxiety. Oral benzodiazepine was also given to reduce her anxiety. Cognitive behavioural therapy was initiated. She showed symptomatic relief within two to three weeks.

Discussion

Sexual dysfunction caused by antidepressants tends to affect all the phases of the sex cycle. However, a gender-based difference in the clinical presentation was noted, with men reporting more desire and orgasm issues and females having reduced sexual arousal.^3,4 Orgasmic hypersexuality in the form of spontaneous orgasm, clitoral engorgement, and increased sexual desire and arousal were reported in females. ⁴ Hypersexuality is reported more in females than in males probably due to the distress caused by the acting out of the symptom. However, there has been no significant gender difference in patients with SSRI-induced sexual dysfunction. ⁷

Sexual dysfunction with SSRIs is dose-dependent.^2,8,9 The finding in our case was consistent with this, as she developed sexual symptoms only at a dose of 15 mg/day.

A single case of escitalopram-induced sexual hyperstimulation in a 40-year-old male was reported by Gursoy BK, ¹⁰ where escitalopram was stopped after the patient developed spontaneous erection and ejaculation at a dosage of 10mg/day and citalopram was prescribed. Citalopram, however, caused decreased sexual desire and delayed ejaculation. This shows the different effects caused by drugs with structural similarity.

Hypersexual adverse effects with SSRIs usually occur within two weeks of drug initiation. ¹¹ But, our patient had reported at the earliest of five days, which is probably due to the longer duration of treatment (two months) with 10 mg/day of escitalopram before raising it to 15 mg/day.

The probable mechanism underlying SSRI-induced hypersexuality has been attributed to serotonin receptors 5-HT2 and 5-HT3, dopamine and prolactin, and nitric oxide synthetase. Dopamine plays a vital role in the mediation of sexual drive and the parasympathetic system mediates the physiological response to arousal.^2,3,12

In addition to the above mechanisms, individual SSRI is proposed to cause hypersexuality in a different mechanism. Sertraline was found to have an effect on norepinephrine and dopamine receptors, and fluoxetine caused increased synaptic dopamine levels. ¹³ A case report of cross-reaction between bupropion and sertraline causing increased sexual desire was reported by Piyush das et al., ¹⁴ who suggested that the inhibitory action of sertraline on the metabolism of bupropion be the cause of hypersexuality.

Shiwen et al. ¹⁵ reported a case of increased sexual desire and compulsive masturbation in a middle-aged male following initiation of sertraline. This case was comparable to our patient as they shared similar symptomatology. However, it is to be noted that he had thyroid abnormalities during the same time span, unlike our patient. The impact of thyroid abnormalities on sexual dysfunction cannot be overseen.

Individual reports of hypersexual side effects like increased sexual desire and arousal with the use of different SSRIs were seen in a few case reports and series. However, they had confounding factors like substance use, psychotropic medications, brain injury, and medical illnesses.^15,16,17 Occasionally, episodes of spontaneous orgasm and arousal have been coupled with physical exercise, tumbling rides, and panic attacks in few other cases.^18,19,20

The probability of association between the adverse sexual symptoms and medication can be established using the Naranjo Adverse Drug Reaction probability scale. This scale grades the association as doubtful, possible, probable and definite based on various factors like temporal association, previous similar adverse reactions, resolution on withdrawal of the drug, reappearance on reinitiation of the drug, increase in severity on increase in drug dosage, etc. ⁶ The scale can be especially useful in doubtful association, multiple drug usage, and atypical adverse reactions.

The reversal of symptoms on discontinuation of the drug and reappearance of the symptoms on restarting the drug is an essential requirement for the diagnosis of drug-induced adverse reactions. However, considering the severity of distress associated with the symptom, rechallenging with the same drug or another drug from the same group was not attempted. A drug-free period was not attempted for the same reason. It is noteworthy, that there is a report of rechallenging the patient who developed hypersexual side effects at 50mg/day of sertraline with the same drug after failure with multiple other drugs. He did not develop the sexual side effects on the second attempt even at a dose of 100 mg/day. ¹¹

Among the antidepressants, fluoxetine, paroxetine, citalopram, and venlafaxine caused higher rates of SD than fluvoxamine, escitalopram, duloxetine, and imipramine. Mirtazapine, bupropion, and agomelatine had the least rates.^2,4 Hence, Mirtazapine was used to replace escitalopram in our patient to manage the depressive symptoms.

Conclusion

Hypersexuality is a less common but more troublesome side effect of Escitalopram. The effect is dose-dependent. A high level of psychosocial stress is attached to the clinical entity. There are multiple neurochemical mechanisms believed to be underlying, however, serotonin and dopamine play a key role in the development of drug-induced hypersexuality. Since hyposexuality is a component of depression, improvement of depressive symptoms and subsequent improvement in sexual function following antidepressant therapy can appear as paradoxical hypersexuality. Considering the sensitivity in reporting sexual symptoms, it is prudent to initiate a talk on sexual functioning with all the patients on antidepressants, especially SSRIs.