Treatment-emergent sexual dysfunctions due to antidepressants: A primer on assessment and management strategies

Abstract

Antidepressants (ADs) are among the most commonly prescribed drugs worldwide. Persons with mental illness taking ADs commonly report sexual dysfunction (SD) related to treatment. A brief discussion on the neurobiology of sexual functioning and mechanism of treatment-emergent SD (TESD) was performed. The incidence of prevalence of TESD in various studies has been reviewed. TESD impacts patients as it frequently leads to nonadherence, while psychiatrists have challenges in proceeding forward with treatment in such patients. Assessment of patients with suspected TESD is described with a focus on practical tips for clinicians. Five strategies (watchful waiting, drug holiday, downward titration, switching, and add-on therapy) to manage TESD have been extensively discussed with evidence in the literature. Each strategy comes with its own bag of advantages and drawbacks, which have been pointed out for simplicity. A detailed discussion on individual pharmacological strategies is given, and options for non-pharmacological management that can be tried are enlisted. Common clinical case scenarios have been discussed to incorporate the implementation of this literature.

INTRODUCTION

Antidepressants (ADs) medications are a group of medications that are used to treat various types of psychiatric disorders, including major depressive disorders, obsessive-compulsive disorders (OCDs), post-traumatic disorders, panic disorders, generalized anxiety disorders, and impulse control disorders.[1,2,3,4] These medications are both effective and generally well tolerated. They do, however, have some side effects. Sexual Dysfunctions (SD) are common side effect and has a negative impact on treatment compliance.[5,6,7]

MATERIAL AND METHODS

This article is a narrative review of treatment-emergent sexual dysfunctions (TESDs) due to antidepressants (ADs). The authors AT and AA have conducted search in PubMed, Google Scholar, EMBASE, and Cochrane Central Trials Register for articles based on “antidepressant,” “sexual side effects,” “treatment emergent sexual dysfunctions,” “assessment,” and/or “management.” The search strategy was designed to encompass human trials published in the English language between January 1980 and July 2022. A narrative synthesis approach was employed to integrate and summarize the findings from the selected studies. The emphasis is kept on highlighting clinically relevant information.

Incidence and prevalence

A meta-analysis conducted by Seretti and Chisea compared the rates of SD of individual ADs. The article reviewed 31 studies over 20 years. TESD rates with AD use range between 25.8% and 80.3% of patients.[8] A recent naturalistic Psychotropic-Related Sexual Dysfunction Questionnaire PRSexDQ-SALSEX I study on 2144 patients reported that around 79% of the patients on a commonly prescribed AD showed SDs, which is again a significant number.[9]

Impact of antidepressant-induced SD

The SD due to ADs can have a significant negative impact on prognosis as it can be a major reason for treatment discontinuation, as studied in a meta-analysis of 62 randomized controlled trials (RCTs) of 6000+ patients, that reported a 14% and 18% of total patients dropping out after taking selective serotonin reuptake inhibitors (SSRIs) and tricyclic ADs (TCAs), respectively.[5] SD has been cited as a major reason for treatment discontinuation. A survey of 51 patients taking psychotropic medications reported that 42% of men and 15% of women become noncompliant due to reported sexual side effects.[6] A follow-up study of 264 patients taking TCA or SSRI for various mental health conditions reported that 27% of patients became noncomplaints due to reported side effects. 5% of patients cited SD as the reason for discontinuation. However, the study did not discriminate between antipsychotic and AD uses among the subjects.[10] SD can also be a source of concern, which can worsen the depressive illness, resulting in a poorer outcome.[7] Researchers stress that SD, if untreated, can have effects on the already poor quality of life, affect interpersonal relations, and negate self-esteem of patient.[11,12] Hence, it becomes utmost necessary to study and treat this common clinical concern.

SD and causes

SD as per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), is defined as “a clinically significant disturbance in a person’s ability to respond sexually or to experience sexual pleasure that happens for a period of over 6 months.”[13] The duration criteria are not applicable for substance- or medication-induced SD. A normal sexual response cycle consists of three phases: sexual desire, arousal, and orgasm. Any stage of the sexual response cycle may be susceptible to SD. SD can be broken down into these phases. Various causal factors have been implicated in SD. SD due to AD is among the most common causes of SD.

Neurobiology of sexual functioning

Human sexual interaction is a complex activity governed by cognitive behavior control, which is driven by a multitude of sensory, endocrine, central, and peripheral neural mechanisms and genetic factors.[14] Sexual behavior has been linked to a number of brain regions, which include the thalamus for sensory input, reward system for motivation, hypothalamus for autonomic response, amygdala for emotional appraisal, prefrontal cortex and cingulate cortex for modulating sexual behavior, and insula cortical for awareness of the tumescence.[15] Multiple neurotransmitters are involved in the regulation of the sexual response cycle, including serotonin, norepinephrine, dopaminergic, cholinergic, and histaminic systems.[14]

Mechanism of SD by antidepressants

The majority of ADs alter serotonin levels. Serotonin levels that are higher are generally thought to reduce sexual function. Dopamine and norepinephrine pathways, which are both involved in the arousal and desire phases of the sexual response cycle, are targeted by serotoninergic nerve terminals, which suppress their activity.[7,16] Certain SSRIs (such as paroxetine) inhibit nitric oxide production, which is essential in causing vasodilatation resulting in erection. Effects on the autonomic nervous system via interaction with adrenergic and cholinergic receptors also disturb adrenergic-cholinergic balance. Thereby, through their effects on nitric oxide production and cholinergic and alpha1 receptors these drugs may alter sexual functioning.[7,16,17]

A certain subgroup of patients with preexisting risk factors seems to be at a higher risk of AD-induced SD: These include patients with medical comorbidities, substance use disorders, hormonal imbalance, and psychosocial stressors in interpersonal domains with their partners.[18] Some genetic polymorphisms are thought to mediate the genetic basis of these treatment-emergent sexual side effects.[16]

Risk with different ADs

SD has been reported with all classes of AD medication. Studies have shown that SSRIs and serotonin norepinephrine reuptake inhibitors (SNRIs) are associated with higher rates of SD (citalopram, fluoxetine, paroxetine, sertraline, and venlafaxine) as compared to placebo, whereas newer ADs such as amineptine, agomelatine, bupropion, moclobemide, nefazodone, and mirtazapine were associated with a lower incidence of SD. The remaining ADs show an intermediate risk of SD, and this subset includes fluvoxamine, escitalopram, duloxetine, and imipramine, as shown in Figure 1.[7,8,16,19,20,21]

Figure 1.

Comparison of percentage of sexual dysfunction with different commonly used antidepressants as reported by authors of the SALSEX 1 study[9]

Assessment

Clinicians in a routine practice often do not consider SDs in the presence of other common psychiatric disorders at first. SD can occur as one of the symptoms of the primary disorder itself, which commonly goes unnoticed initially. The patient may experience SD as a consequence of various psychosocial stressors or medical issues. Additionally, as SD is a taboo subject, people often fail to report it spontaneously, which can be a barrier to providing comprehensive health care. Practitioners are often faced with the challenge of managing AD-induced SD without compromising the mental health of the patient. Hence, a regular practice to obtain sexual history in a culturally sensitive manner on every clinical visit, even if the primary complaint is different, can go a long way.

Frequently, sexual complaints are reported or revealed after the patient has already initiated a course of AD. In such cases, if SD due to AD is suspected, do not jump to the conclusion that it is AD-induced only. A simple approach to confidently diagnose AD emergent SD involves the following steps (see Figure 2). Think once, is it AD medications or something else? If pretreatment evaluation of sexual functioning is not performed or is not available, a baseline assessment can be performed retrospectively, to get an idea of whether the SD was present before or has emerged following the initiation of AD.

Figure 2.

Flowchart of assessment of suspected AD emergent sexual dysfunction

If SDs suggestive of TESD are present at any point of time, a basic evaluation of the patient is mandatory to rule out all the possible etiologies that may lead to SDs.

Practical tips on asking about sexual functioning suggested are as follows:[22]

1. Permission may be taken from the patient for the evaluation of sexual areas.

2. An initial question can be such as “Sometimes, people have some sexual concerns/issues when using this medicine, do you wish to talk about this now?” OR “As occasionally people report sexual issues during treatment, if you wish, we can talk about it.”

3. Further questioning can proceed as per the comfort level of the patient.

4. One may simply ask straight questions such as “How has your sexual life been since you started taking the medication?” OR “Have you noticed any problems in your sexual desire, your orgasms/ejaculation, or your arousal capacity since you started taking the medication?”

5. A thorough assessment of SD has to be performed if yes to the above questions.

After specifying and diagnosing SD in a patient on psychotropic medications, the following areas should be assessed for planning effective and comprehensive management of patient’s sexual functioning.[22]

1. Rule out the ongoing psychosocial stressors: interpersonal conflicts, familial, financial, social, and occupational.

2. Take marital history to rule out the possible causes: partner problem, poor communication regarding sex, inadequate lubrication, trust issues, intimacy problem, pressure from partner, and any conflicts.

3. Look for the myths and concerns related to sexual health that may be leading to SD.

4. Look for any traumatic or phobic sexual experiences, difficulty fantasizing, and orientation.

5. Check for comorbid psychiatric disorders.

6. Check for comorbid medical illnesses that may cause SDs, such as diabetes mellitus, hypertension, hypothyroidism, obesity, hyperlipidemia, and cardiovascular problems.

7. Evaluate history of substance abuse, such as alcohol and opioid.

8. Take the history of other prescribed drugs, which may be causing or adding to the SD.

Following that, a thorough history of coexisting factors associated with SD has been evaluated. A general and focused examination should be performed, including the following:

1. Checking the vitals of the patient with an aim to identify undiagnosed hypertension or other medical illnesses.

2. In cases where the patient complains of issues with the size or shape of genitalia, or when there is a suspicion of neurological or vascular pathology, a detailed physical examination of the anatomy of the genitals, secondary sexual characteristics, cremasteric reflex, bulbocavernosus reflex, and peripheral pulses may be required and should not be deferred.

If required, one may investigate for the possibility of medical causes, including metabolic syndrome, hypogonadism, or any other, as the clinical history and examination may suggest. These investigations commonly include blood sugar levels, hemoglobin (Hb) A1c, lipid profile, thyroid function tests, prolactin levels, early morning luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels.[23]

A detailed evaluation of SD can be easily assisted with the use of appropriate scales that assess sexual functioning in detail. A number of scales have been validated for assessing SD, such as the International Index of Erectile Dysfunction and Sexual Functioning Questionnaire.[24,25,26,27,28,29,30] The details on the psychometric properties, limitations, and characteristics of the scale can be found in the review by Grover and Shouan.[31]

Management

The treatment of the AD-induced SD requires the clinician to balance the mental well-being of the patient and simultaneously manage the SD. For doing so, it is very important for the clinician to understand the relevance of SD in each case as well as the costs incurred in treating it. If the patient is married and has troubled relationship because of the SD, then they need to be managed differently as compared to those patients in whom the AD treatment has to be given for a relatively shorter duration as per the patient’s clinical status and sexual context.

Patients who experience such adverse effects are likely to require frequent follow-up to manage these symptoms. Various strategies have been suggested for the treatment of AD-induced SD. The major aspects to be dealt with in patients of TESD include a) pharmacological strategies; b) non-pharmacological strategies for SD, including psychoeducation; and c) control of other factors impacting sexual functioning, such as health lifestyle, treating substance abuse, managing weight, interpersonal relationship, partner intimacy, and stress management. These nonspecific interventions remain a cornerstone of managing any patient with SD, and their importance cannot be overemphasized. Detailed management of these factors is beyond the scope of this article. We suggest referring to Clinical Practice Guidelines for Management of Sexual Dysfunction[23] and Indian Psychiatric Society Textbook of Sexuality and Sexual Medicine[32] for further reading [Figure 2].

Non-pharmacological strategies for TESD

A number of non-pharmacological strategies have been found to be effective for SD in general. A detailed discussion on these strategies is beyond the scope of this article. Some of the strategies include the following:[23,32]

1. Psychoeducation

   Psychoeducating the patient before initiation of AD is a good clinical practice. After the occurrence of TESD, educating about the incidence, reversibility, and various management options available for TESD alleviates the patient’s anxiety. Addressing prevailing myths about sexual functioning is also needed. Evaluating the acceptance of TESD by partners and educating them as well can be beneficial to decision-making and positive doctor-patient relationships.[33]

2. General measures for psychosexual health

   1. Physical exercise

      A small RCT has shown effectiveness in improving sexual desire in women suffering from TESD.[34]

   2. Relaxation exercises such as Jacobson’s progressive muscular relaxation technique, Benson Henry’s relaxation technique, and relaxation combined with a biofeedback machine may be particularly helpful for those individuals having anxiety before initiation of sexual intercourse.

3. General techniques applicable to the majority of SD

   1. Kegel’s exercise

   2. Sensate focus—including both nongenital and genital sensate focuses either with the partner or alone

4. Specific techniques for a subset of patients with SD

   1. Directed masturbation

   2. Coital alignment technique

   3. Good enough sex

5. Specific measures for premature ejaculation

   1. Start-stop technique

   2. Squeeze technique

6. General psychological measures for improving relational intimacy—improving communication among partners

7. Specific psychotherapeutic measures

   1. Cognitive-behavioral therapy—it is effective for a number of psychiatric disorders, including SD.[35]

   2. Behavioral therapy

   3. Mindfulness-based therapy

   4. Dual sex therapy.

Pharmacological strategies for TESD

Various strategies to manage antidepressant-induced sexual side effects

Watchful Waiting

It means waiting for the time when SD will resolute on its own. However, this spontaneous resolution occurs in only some cases.[36,37] In most cases, AD regimes may be short term. Therefore, clients may opt to endure the effects of SD for a short period, until their treatment ends.

Advantages

• No additional medication or intervention is needed, hence no additional side effects.

• No added cost.

Disadvantages

• The patient may become nonadherent and at risk of relapse.

• SD may persist in a large proportion of individuals.

Evidence in literature

• Two large-scale studies have reported rates of partial recovery in the range of 14–20% at 6 months and rates of complete recovery in between 6 and 10%.[36,37]

Suitable candidates

• The patient’s psychiatric condition is responding well, and there are no other intolerable side effects.

• Patients in whom the immediate management of side effects is not necessary as per the context of the patient’s life situation (unmarried, not sexually active currently, or no such plan in the near future).

• Consider patients with mild SD, with little impairment or distress to the patient.[38]

• Patients with the first episode of depression relatively require a shorter duration of treatment and some side effects that are acceptable to the patients.

• The patient’s plan is to stop medication in the next few months.

How to implement

• Psycho-educate the patient about the reversible nature of the side effects, the possibility, and the rates of spontaneous remission.

• Reassure about the availability of several other treatment options if the side effect persists and the need arises.

• Explain the relative cost-benefit ratio in an individualized manner and take a joint decision.

Drug Holiday

Another strategy to treat TESD involves giving short-term interruptions to continuous medication use. It is a high-risk treatment option where medication is omitted a few days before, anticipated sexual activity. The longer the drug holiday, the higher the risk of depressive symptoms recurring. Alternative approaches involve using the drug at a lower dose (approximately half) during periods of anticipated or planned sexual activity.

Advantages

• May relieve SD adverse effects at scheduled time.

Disadvantages

• Risk of relapse and discontinuation symptoms, which may threaten overall treatment success.

• Not possible for long-acting drugs such as fluoxetine.

• Setting deadlines for sexual activity itself can be anxiety-provoking.

• Can improve erection or arousal dysfunction but has no effect on sexual desire.

Evidence in literature

• Evidence is limited to a single uncontrolled trial of 30 patients who had reported improvement in SD with drug holiday.[39]

Selection of patient

• The patient who is otherwise maintained on the medication and indulges in sexual activity very infrequently.

• Long-distance relationship (infrequent intimation with a partner).

• Primary SD is anorgasmia.

How to implement

• Psycho-educate the patient regarding the side effect and success rates of drug holiday techniques.

• Warn regarding the possibility of discontinuation symptoms and risk of relapse.

• Discontinue medication 48–72 hours before the planned sexual encounter.

Downward Titration

Reducing the dose of offending AD may help in combating AD-induced SD as studies support the notion that the side effects are dose related.[40] However, the likelihood of having SD also depends on pharmacodynamic and genetic factors. Hence, some patients can have these side effects even at low doses. So, this strategy would not be useful for such patients.[20] Besides this, all major guidelines suggest continuing the same AD at the same dose during the maintenance phase.[41,42]

Advantages

• May reverse SD

• Cost-saving approach.

Disadvantages

• This may increase the risk of relapse.

• This may cause a loss of effectiveness of AD.

• Sudden reduction may produce discontinuation or withdrawal symptoms in some patients.

Evidence in literature

• Dose reduction by 50% in 30 patients suffering from TESD on SSRI treatment resulted in improvement in sexual functioning to at least some extent in 23 patients. Of the 24 patients taken off medications after complete remission of symptoms, all of them reported complete resolution of SD.[37]

Selection of patients

• Patients who have attained remission in their depressive symptoms and plan on the eventual complete withdrawal of AD

• Patients taking higher doses of ADs

• Other side effects also co-occurring

• Patient preference to discontinue the drug.

How to implement

• Dose reduction of AD should be gradual preferably over 4 weeks or more to avoid relapse.[43]

• The dose should be reduced in smaller steps with monitoring for relapse of symptoms of illness before each subsequent reduction in dose.

• The dose should not be reduced below the minimum effective dose if maintenance treatment is necessary.

Switching

Another strategy is switching ADs to one with a lower propensity for sexual side effects; however, no well-conducted trial has studied this strategy. Switching within the same group such as from one SSRI to another SSRI is usually of no benefit as all SSRIs have similar incidence of SD.[20,37] Switching to an AD with a lesser propensity to cause sexual side effects can be useful.[19,20,44] Drugs that can be used for switching are described in Table 1.

Table 1.

Antidepressant medications with low risk of causing sexual dysfunction[25,31,49,50,51]

Add-on medication		Mechanism of action[52]		Dosage		Evidence		Comment		Side effects
Agomelatine[50,53]		Melatonin receptor agonist, 5-HT2C antagonist		25–50 mg/day		Moderate to high level		Anxiolytic and sedative action		Nausea, headache
Bupropion[4,16,45]		Norepinephrine and dopamine transporter inhibition		150–450 mg/day		Moderate level		Additional anti-craving effect in nicotine dependence. Might not be as effective as a single antidepressant		Seizure risk Increased anxiety and tremors, insomnia
Mirtazapine[46,47,54]		5-HT2A, 5-HT2C, 5-HT3 antagonist H1 antagonist, α2 blockade		15–45 mg/day		Low to moderate level		Prominent anxiolytic and sedative action		Weight gain, dyslipidemia
Desvenlafaxine[55,56]		Norepinephrine and serotonin transporter inhibition		50–150 mg/day		Low to moderate level		Well tolerated by most patients. Good antidepressant efficacy		Nausea, sleep disturbances
Vortioxetine[48]		5-HT1A agonist, 5-HT1B partial agonist, 5-HT1D, 5-HT3, 5-HT7 antagonist		10–20 mg/day		Moderate to high level		Cognitive symptoms also improved		Nausea, vomiting, diarrhea
Vilazodone[57,58]		SERT inhibitor 5-HT1A partial agonist		20–40 mg/day		Low level		Metabolically friendly		Diarrheal, nausea frequent
Moclobemide[49,59]		Reversible MAO-A inhibitor		300–600 mg/day		Low level		Antidepressant efficacy is high		Requires a long washout period when switching

Advantages

• The advantage of removing the offending agent

• Do not add to cost.

Disadvantages

• Risk for relapse. The newer AD may or may not be effective.

• Other ADs may have their own side effects.

Evidence in literature

• RCTs have found evidence for improvement in SSRI-induced SD when patients were switched to bupropion.[45]

• Mirtazapine when used as a substitute of SSRI showed 58% of patients returning to normal sexual functioning in a small open-label study.[46] In another open-label study, switching to mirtazapine in 11 patients resolved their SD.[47]

• Large-scale RCT for switch to vortioxetine has shown strong evidence of improved sexual functioning.[48]

• Moclobemide has been tried successfully in a small case series as a switch strategy from fluoxetine.[49]

• Switch to agomelatine from SSRI or SNRI had resolved SD in 44% of patients.[50]

Selection of patients

• No or minimal response on current offending AD

• Have other significant adverse effects as well.

• Patient preference.

How to implement

• Switching to another AD depends on a variety of factors, including the current AD, the new AD to be switched to, the half-life of current AD, and drug interaction between the two ADs.

• Cross-tapering is recommended from switching to drugs such as agomelatine and mirtazapine.[59]

• The direct switch can be performed for vortioxetine and desvenlafaxine.[59]

• Switching to moclobemide requires SSRI to be gradually tapered and stopped. A washout period of 1–2 weeks for most SSRIs before monoamine oxidase inhibitors (MAOIs) can be started.[59]

• If fluoxetine is used in a patient, it is generally advisable to first stop the drug and wait for a washout period of 4–7 days before starting desvenlafaxine and vortioxetine and 5–6 weeks before starting moclobemide.[59]

Add-on Therapy

One of the well-studied approaches for AD-induced SD is adding another agent to ongoing treatment. This may give the potential benefits of continuing to manage the depressive illness with an efficacious AD while reducing the potential for SD. Add-on therapy may include a second AD as an augmenting agent or a non-AD medication as an adjunctive agent.[60] A summary of drugs used as add-on therapy is given in Table 2.

Table 2.

Options for add-on drugs for TESD[20,44,60,62]

Add-on medication		Mechanism of action		Dosage		Evidence		Comment		Side effects
Amantadine[60,72]		Dopamine agonist		100–400 mg/day		Low level		Intermittent treatment 48 hours before sexual intercourse. Improves sexual pleasure in women		Insomnia, nausea, and vomiting
Mirtazapine		Antagonist on 5-HT2 and 5-HT3 receptors Presynaptic α2-receptor blockade		7.5–45 mg/day		Low- to moderate-quality evidence		Generally effective and well tolerated Improve depressive and SD		Weight gain, sedation
Bupropion[45,60]		NET reuptake inhibitor, DA reuptake inhibitor		150–300 mg		Moderate- to high-quality level of evidence Promising evidence in women		Improves desire, arousal, lubrication, orgasm, and sexual satisfaction APA recommended		Seizure risk Increased anxiety and tremors
Buspirone		5HT1A receptor agonist		15–45 mg/day		Low level		Offsets SSRI-induced erectile dysfunction. APA recommended		Dizziness, gastrointestinal side effects
Bethanechol		Acetylcholine agonist		20 mg/day		Low level		Useful in patients taking TCAs to counteract anticholinergic effects		Diarrhea, hypotension, flushing Exacerbation of asthma
Cyproheptadine[60]		Anti-histamine and 5HT blocker		4–12 mg		Low level		As-needed use 2–4 h before sexual intercourse		Sedation, weight gain, can reduce the effectiveness of AD
Testosterone gel/cream[20]		Testosterone hormone		Local application		Low level		Effective in patients with low testosterone levels		Local irritation
Sildenafil, tadalafil[60,62]		Phosphodiesterase inhibitor		Sildenafil—25–100 mg/day Tadalafil—10–20 mg/day		Moderate to high, best among all add-on therapy		Role in reducing the adverse sexual effects in both males and females APA recommended		Headache, flushing, and dyspepsia
Ginkgo biloba[60,75]		Herbal medication		60–240 mg/day		Conflicting evidence		More responses in females		Gastrointestinal symptoms, headache, and activating side effects

Advantages

• Dose sparing effect for offending AD

• Helps in the resolution of symptoms and counters the SD simultaneously without increasing the dose of offending AD.

Disadvantages

• Cost issues

• Add-on medication may have individual side effects

• Risk of drug interactions that has not been tested in any systematic studies.

Selection of patient

• The patient who has a partial response to offending AD.

Evidence in literature

• An antidote to SSRI-induced SD has been tried in a small open-label study with 69% of patients reporting improvement in sexual functioning.[61] A 2013 Cochrane meta-analysis on managing SD induced by AD medication found positive evidence for the addition of 300 mg of bupropion.[62]

• Phosphodiesterase 5 (PDE-5) inhibitors have been found to be effective in a large number of trials and in the Cochrane review for both men and women.[62,63,64,65,66] Among men, it is the most effective adjunctive treatment available.[62]

• Mirtazapine has been found to resolve SD in 48% of patients in an open-label study.[67]

• Buspirone has been evaluated in a retrospective study to improve sexual functioning in 69% of patients.[68]

• Evidence of cyproheptadine is limited to a few case reports only.[69,70,71]

• Older case reports have found beneficial effects of intermittent amantadine.[72]

• Bethanechol has been found to be effective in a small RCT on patients taking clomipramine.[73]

• Testosterone gel has been studied in an RCT with substantial improvement in sexual functioning.[74]

• Ginkgo biloba showed 76–91% response rates in female and male SD due to AD use,[75] but other studies did not find it better than placebo.[76,77]

Choice of strategy for managing TESD can be chosen, as shown in Figure 3.

Figure 3.

Flowchart of specific management strategies for AD emergent sexual dysfunction (alphabets in brackets denote the bullet of management strategies section that discusses the strategy in detail)

Case scenarios

Case 1

A 30-year-old man was diagnosed with recurrent depression, current episode severe with suicidal ideations, history of two lethal suicidal attempts, on treatment lithium 800 mg/day, desvenlafaxine 100 mg/day, clonazepam 1.5 mg/day, and zolpidem 10 mg at bedtime for last 5 months, reporting 70% improvement in depressive symptoms and complains of inability to achieve orgasm and delayed ejaculation for last 3 months, and affecting his relationship with his wife. The patient wishes to discontinue medications to improve his sexual health.

CASE DISCUSSION 1

In the above case, sexual side effects have started after 2 months of the initiation of medication, but the history of other factors that might precipitate SD is not mentioned. Hence, a thorough assessment, as mentioned above, must be performed. If it is AD-induced SD, then what is to be done next?

In this case, the patient is married and has troublesome sexual side effects. Therefore, it becomes important to manage SD simultaneously. Offending drugs to cause SD in this case can be desvenlafaxine and clonazepam. Suggested management strategies discussed in Table 3.

Table 3.

Suggested management strategies for case 1

Specific management		Other management strategies
Educating the patient about the possible effect of depression on sexuality, and high possibility of relapse of drug discontinuation needs to be discussed The patient has shown a good response to desvenlafaxine (100 mg), but still has some depressive symptoms Hence, in this case augmentation with medications such as mirtazapine, bupropion, or buspirone can be a good strategy. They both can take care of residual depressive symptoms and problematic SD as well		Reassure the patient that these side effects are reversible and treatable as well We can also reduce the dose of clonazepam if the anxiety is managed Nonpharmacological strategies for improving intimacy, sexual stimulation, and improving communication with a partner on sexual issues will help in allaying some of the anxiety around sexual issues

Case 2

A 25-year-old man is on treatment T. escitalopram 20 mg Per day and T clonazepam 0.5 mg + propranolol 20 mg Twice a day for the last 6 months for the first depressive episode. Patient and informants report 100% improvement in depressive complaints. The patient also complains of decreased libido since the starting of AD medications. There is no history of any medical comorbidities, previous psychiatric illness, or any substance use.

CASE DISCUSSION 2

As per the history, it is suggested that the patient is having treatment-induced SDs. Other causes have been ruled out. The patient has already taken medication for 6 months and currently seems to be in the remission stage.

Treatment for the first depressive episode is recommended for 6–9 months after remission. Both escitalopram and propranolol can cause SD. Suggested management strategies discussed in Table 4.

Table 4.

Suggested management strategies for case 2

Specific management		Other management strategies
He has already taken treatment for 6 months and symptom free. So, the next plan of treatment would be a gradual tapering of medication in the next 3–4 months. Sudden discontinuation has a high risk of relapse. Then, gradually can taper and stop escitalopram in the next 2–3 months The option of PDE-5 inhibitors can be discussed for the time being		Reassure the patient that these side effects are reversible We can first reduce anti-anxiety medication (as propranolol can also be an offender) as the patient is symptom free

Case 3

A 30-year-old woman suffering from obsessive-compulsive disorder (OCD) for the last 10 years started on treatment T. fluoxetine 60 mg/day, T. risperidone 2 mg/day, and T. clonazepam 1 mg/day 2 years back and has improved by 50% on current treatment. She has complaints of reduced libido and decreased arousal during solo sexual activity. Her medical history is not significant, and she consumes no substances. She is currently unmarried and not in any relationship. She plans to marry in the near future.

CASE DISCUSSION 3

There is a history of response present on fluoxetine but not in remission. She might have to take treatment for a long duration considering her long duration of illness. There may be three offending drugs here—risperidone, fluoxetine, and clonazepam.

Other assessments should be conducted to evaluate the temporal relationship between the use of medications and the onset of SD. The management plan would depend on the life context of the patient (whether married or not, hampering her sexual life or not, should foresee the situation that whether emergent treatment is required or not). Suggested management strategies discussed in Table 5.

Table 5.

Suggested management strategies for case 3

Specific management		Other management strategies
Option of augmentation with mirtazapine (7.5–45 mg) and bupropion (150–450 mg) can be given to alleviate SD Tab. tadalafil can be added for early effect if required once she plans to be sexually active		Reassure the patient that these side effects are reversible Reduce anti-anxiety medication (as clonazepam is also one offender) if the patient is anxiety free Risperidone can be switched with aripiprazole (5–10 mg/day) for augmentation Neuromodulation strategies can be tried to better control her OCD and possibly reduce medications Strategies of directed masturbation and mindfulness can be taught as these might have additive benefit in improving sexuality

CONCLUSION

SD is more common in patients on AD drugs than is usually observed in clinical practice. Being a great source of distress and a frequent cause of discontinuation, regular questioning and clinician’s awareness about TESD are essential. Each case of TESD should be thoroughly assessed, and basic management should include psychoeducation, improving lifestyle factors, partner intimacy, and relaxation training. Specific management strategies must be tailored to each situation and patient preference. By following a step-by-step detailed management practice, this challenging situation can be effectively dealt with.