Preface

The following work is an extended and slightly re-worked version of a project essay that was submitted in 2016 in partial requirement of the conditions to pass the London Diploma in Psychosexual and Relationship Therapy.

Introduction

Sexual functioning is a biopsychosocial process that involves the complex integration of physiological, psychological, relationship, and cultural factors (Bancroft, 2009; Rowland, 2006). Selective serotonin reuptake inhibitors (SSRI) are a class of medication prescribed mainly for the treatment of depression and anxiety whose pharmacological effects on serotonin reuptake also have an impact on sexual functioning. While SSRIs could be expected to impact primarily on physiological aspects of sexual function, psychological (e.g. mood and cognitive appraisal) and social (e.g. relationship and cultural) factors are also important. The focus of this essay therefore is a review of the research literature concerning the impact of SSRIs on sexual functioning in terms of clinical assessment, formulation, and treatment of SSRI-induced sexual dysfunction.

The physiology of sexual function

In order to contextualise the role of serotonin in sexual functioning, the following is a description of some key components of the physiology of sexual functioning. The psychophysiology of sex is a complicated integration of endocrine, neurotransmitter and central nervous system (CNS) influences. Endocrine influences include androgens, oestrogens, progesterone, prolactin, oxytocin, cortisol and pheromones. Neurotransmitters and neuropeptides include nitric oxide (NO), serotonin (5HT), dopamine (DA), adrenaline (epinephrine), noradrenaline (norepinephrine) (NA), endogenous opioids, acetylcholine (ACh), histamine and γ-aminobutyric acid (GABA). Relevant CNS systems include brainstem regions, the hypothalamus and the forebrain (Meston & Frohlich, 2000).

Stahl (2001) describes a simplified model of the neuropharmacology of human sexual function in relation to three sequential phases: libido, arousal, and orgasm. Libido is related to the subjective experience of desire and is mediated by the mesolimbic dopamine reward pathway. This pathway is instrumental in directing behaviour towards all activities that are considered rewarding, including sex. Stahl suggests that dopamine, testosterone and oestrogen promote libido whereas prolactin can reduce it. However, evidence for the role of prolactin in inhibiting sexual interest is mixed and most research indicates that oestrogens have little direct influence on sexual desire in either males or females (Meston and Frohlich, 2000).

Arousal in the peripheral genitalia, that is erection in men and swelling and vaginal lubrication in women, is mediated by the neurotransmitters NO and ACh; orgasm, which is accompanied by ejaculation in men, is both a central (spinal) and a peripheral reflex in the genitalia. It is promoted by noradrenaline and inhibited by serotonin (Stahl, 2001). Oxytocin appears to be related to the intensity but not duration of orgasm in men and women. It also influences sexual desire to the extent that oxytocin-induced positive mood has an effect on sexual interest (Meston & Frohlich, 2000).

The dual control model of sexual functioning proposes that different neurochemical pathways control excitatatory and inhibitory mechanisms (Janssen & Bancroft, 2007). Excitation occurs in response to sexual cues and physical stimulation causing regions of the hypothalamus and limbic system to promote the release of 1) noradrenaline and oxytocin, which lead to physiological arousal, and 2) dopamine and melanocortins, which focus attention and promote desire. Steroid hormones, such as the androgen testosterone, prime the brain to be selectively responsive to sexual incentives by binding to specific hormone receptor complexes that cause sexually excitatory neurotransmitters to be synthesised.

Dopamine contributes to sexual arousal and desire through three major systems: the mesolimbic/mesocortical system, the nigrostriatal system, and the diencephalic system. Dopamine operates both to direct attention to sexual stimuli and controls the degree of incentive (motivation) to pursue both appetitive (anticipatory) and consummatory sexual activity. It also regulates autonomic activity, which acts on both inhibitory and excitatory pathways. The role of dopamine is of particular interest in understanding the impact of SSRIs on sexual function as it has been suggested that dopamine and serotonin are mutually inhibitory (Pfaus, 2009).

Excitation systems blunt the mechanisms that cause or maintain inhibition, thus inhibiting inhibition. Inhibition has both a social and a biological basis. For example, in response to inhibitory social or cultural cues and a corresponding negative emotional state such as guilt, the prefrontal cortex can suppress sexually excitatory mechanisms. The prefrontal cortex controls higher cortical functions such as cognitive executive functions that mediate between competing drives (e.g. biological and social) or in response to non-reward (e.g. sexual dissatisfaction) and can suppress the pursuit of sexual rewards, for example by directing attention away from sexual stimuli. At a biological level, inhibition can be activated by sexual reward (e.g. orgasm) and by satiety (satisfaction). Following orgasm, the cortex, limbic system, hypothalamus and midbrain release endogenous opioids that produce a sense of euphoria; endocannabinoids that produce a sedating effect that reduces sensitivity to anxiety-provoking or stressful stimuli; and serotonin (5-HT), which induces sexual refractoriness and satiety, i.e. a sense of fulfilment and relaxation (Pfaus, 2009).

All aspects of the monoamine system are therefore relevant to sexual functioning. The monoamine system comprises three neurotransmitters, the two catecholamines dopamine and noradrenaline, plus serotonin. All the monoamines operate both within the central nervous system and in the periphery. Dopamine regulates movement, attention and working memory, and motivational behaviour; noradrenaline acts on the adrenergic (sympathetic) arm of the autonomic nervous system and mediates cardiovascular effects, arousal, concentration, learning, and memory. For the purposes of this work, however, the main focus is on the brain serotonin system, as that is the system that is most affected physiologically by SSRI medication. Serotonin is involved in a number of physiological processes including regulation of smooth muscle function and blood pressure regulation. In the CNS it operates on a wide variety of systems including mood, appetite, sleep, cognition, perception, motor activity, temperature regulation, pain control, sexual behaviour, and hormone secretion.

As can be seen in Figure 1, serotonin neurons arise from Raphe nuclei in the brainstem and project extensively to the brainstem, midbrain, and forebrain sites, including the hypothalamus, limbic system, hippocampus, and cortex, and down the spinal cord to lower lumbar and sacral regions that control genital reflexes (Pfaus, 2009). In the 1960s Meyerson concluded that brain serotonin was responsible for sexual inhibition because studies where serotonin production was itself inhibited produced increases in sexual behaviour in male rats that were otherwise sexually sluggish or castrated. Again, in studies of male rats, serotonin inhibited the resumption of sexual behaviour after ejaculation and decreased sexual motivation and desire. These effects match the familiar pattern of delayed, inhibited or absent orgasm that can be seen in humans taking SSRIs. These effects have led to the theory that serotonin causes sexual inhibition when the subject has reached a point of sexual satiety, for example after orgasm or following sexual exhaustion, independent of levels of sexual hormones (Pfaus, 2009).

It is suggested that, as part of a complex process of neurotransmitter release, serotonin release plays a part in redirecting motivation after orgasm to non-sexual rewards. This matches a pattern suggested by Bancroft and Janssen (2000) of overactive inhibition of sexual function by hyperfunctional serotonin activity induced by SSRis. Indeed, where SSRIs are used to help manage paraphilias or to treat premature ejaculation their mode of action is thought to be the blunt instrument of inhibiting potentially hyperactive excitatory systems. However, the picture is more complicated because of the wide variety of serotonin receptors and the fact that serotonin operates both centrally and at the periphery. There appears to be evidence that serotonin₂receptors impair sexual functioning whereas stimulation of serotonin_1Areceptors facilitates sexual functioning. This complexity perhaps helps partly to explain why the psychostimulant MDMA (ecstasy), which increases the amount of serotonin available in the synapse across receptors, can either increase sexual arousal or impair sexual functioning (Dean, 2004). 95% of serotonin receptors are located in the periphery where serotonin produces vasodilation and vasoconstriction on the smooth muscles of the vascular system and in the genitals, and is also active in genital nerve functions (Meston & Frohlich, 2000)

In summary, sexual excitation is stimulated jointly by steroid hormones, such as the androgens, and by the expectancy or desirability of sexual reward. This hormonal and social milieu activates central neural pathways for sexual excitation involving the hypothalamic activation of dopamine transmission. Widespread dopamine transmission throughout the limbic and cortical structures focuses attention on sexual stimuli that are perceived as rewarding and engages behaviour designed to approach and consummate sexual activity. Sexual excitation is controlled both by the sympathetic (increased heart rate) and parasympathetic (increased blood flow to genitals) branches of the autonomic nervous system accounting for the phenomenon of sexual arousal following the experience of fear or anger through an “excitation transfer” (Bancroft et al., 2003). One conceptualisation of sexual arousal is a combination of relatively mild fear-related stimuli (e.g. fear of rejection) that activates sympathetic arousal concurrent with feelings of safety with another person, which activates parasympathetic arousal (Salu, 2011).

Inhibitory sexual pathways, on the other hand, involve opioid, endocannabinoid and serotonergic feedback to the excitatory pathway. Inhibited sexual desire constitutes the behavioural patterns and feelings associated with sexual reward, satiety, refractoriness and exhaustion. Hyperstimulation of serotonergic outflow, whether through SSRI medication or in response to environmental challenges, therefore has the effect of causing a predisposition to sexual dysfunction across the desire, arousal and orgasmic phases of sexual functioning.

One controversial effect of this understanding is the licensing of the medication flibanserin in the USA for the treatment of hypoactive sexual desire disorder (HSDD) in women, which appears to act by blocking serotonergic outflow and thus inhibiting inhibition. This mode of action is thought to be considerably safer than trying to increase excitation through increasing noradrenaline or dopamine release (or inhibiting dopamine reuptake, as does cocaine and amphetamine) which can cause hypersexualisation, drug dependence, hypomanic episodes and sensitisation to psychosis (Pfaus, 2009). This mechanism helps to explain the common effect of disinhibition through the use of alcohol, which, despite being a central nervous system depressant, operates to enable excitatory mechanisms to function in situations that might otherwise arouse disabling levels of anxiety, certainly with regard to sexual approach (appetitive) behaviour, whilst in higher doses disabling sexually consummatory behaviour (e.g. as a consequence of erectile dysfunction).

SSRIs and the treatment of mental health problems

In the UK and around the world a variety of psychotropic medicines are prescribed for mental health problems. One very popular class of psychotropic medication is selective serotonin reuptake inhibitors (SSRIs). SSRIs selectively inhibit the reuptake of serotonin, a monoamine neurotransmitter in the central and peripheral nervous systems. SSRIs increase synaptic levels of serotonin by disabling the serotonin reuptake transporter from relocating secreted serotonin to the presynaptic terminal. The complexity of serotonergic actions can be seen in Figure 2, which contains a detailed description of the biosynthesis and neurotransmission of serotonin and shows both the diversity of serotonin receptor sites, and how the reuptake of serotonin is blocked by SSRIs (Wong et al., 2005).

SSRIs are widely used in the pharmacological treatment of depression, anxiety disorders and some personality disorders (Medicines and Healthcare Products Regulatory Agency, 2014). They are sometimes also prescribed for premenstrual dysphoric disorder, fibromyalgia, irritable bowel syndrome and rapid ejaculation (Joint Formulary Committee, n.d.). In the central nervous system (CNS) serotonin neurotransmission is thought to be responsible for the regulation of mood, sleep and appetite, as well as having a role in sexual satiety and refractoriness (Pfaus, 2009). Whilst it is too simplistic to state that deficient serotonin is the cause of depression and anxiety, an increase in serotonin may improve symptoms.

SSRIs are not the only medication prescribed for depression; older classes of antidepressant medication include tricyclic antidepressants and monoamine oxidase inhibitors (MAOIs). In addition, there are a number of other medications including agomelatine, duloxetine, mirtazapine, reboxetine and venlafaxine whose mode of operation is somewhat different to the SSRIs (Joint Formulary Committee, n.d.).

Different antidepressant medications are thought to achieve their effects via different routes and different pharmacodynamic mechanisms. SSRIs act by inhibiting the reuptake of serotonin into the presynaptic cell, increasing the levels of serotonin available for binding to postsynaptic receptors and/or prolonging the effects of serotonin. Tricyclic and related antidepressants block the re-uptake of both serotonin and noradrenaline. Monoamine oxidase, which metabolises monamines such as serotonin, is inhibited by MAOIs thereby causing an accumulation of monoamine neurotransmitters. Agomelatineis a melatonin receptor agonist and a selective serotonin-receptor antagonist. Mirtazapine is a presynaptic alpha2-adrenoreceptor antagonist that increases central noradrenergic and serotonergic neurotransmission. Reboxetineis a selective inhibitor of noradrenaline re-uptake. Venlafaxineis a serotonin and noradrenaline re-uptake inhibitor (SNRI).

The fact that there are so many routes through which antidepressant medication of various classes works suggests that the pathophysiology of depression and anxiety is itself complex. Given that anxiety and depression share so many features, including fatigue, impaired concentration, irritability, sleep disturbance, and somatization in addition to subjective experiences of nervousness, worry, and restlessness (Ninan, 1999) there is a suggestion that they share a pathophysiology and that there is a complex interaction between the two. One finding suggests that 68% of people with co-morbid anxiety and depression were anxious for over 10 years prior to the development of depression (Gulley & Nemeroff, 1993)

Ressler and Nemeroff (2000) state that a number of neural mechanisms are implied in depression including noradrenaline (NA) and serotonin (5HT) dysfunction, abnormalities in corticotropin-releasing factor (CRF) stress responses, and dysfunction in the limbic system’s capacity to mediate fear and stress responses. When in a non-depressed (i.e. euthymic) state, perceptions of stress or danger cause the amygdala and hypothalamus to release CRF, which stimulates the locus coeruleus (LC) to release NA. This release, which is the basis of the fight/flight response, is inhibited by the raphe nuclei (RN) that produce serotonin, because serotonin promotes tolerance to aversive stimuli and inhibits stress responses. In turn the hippocampus, which codes memories with emotional tags, is sensitised by NA, which tends to increase memories of aversive events, and desensitised by serotonin. The pre-frontal cortex, which has a role in extinguishing fearful memories and therefore promotes tolerance of aversive circumstances, also appears to have a top-down role in mediating the amygdala’s activation or inhibition of NA and serotonin.

In depression and anxiety however, the LC-NA system is hypersensitive to stress and fear associated with aversive stimuli, and the RN-5HT system is hyposensitive, in part due to top-down prefrontal cortex dysregulation, decreasing the inhibition of stress responses and aversion tolerance. The disruption of the RN-5HT system in turn contributes to dysregulation of sleep, attention, concentration, appetite and libido. With the decrease in re-uptake of serotonin caused by SSRI medication, more serotonin is available, thus potentially reinstating the RN-5HT system’s ability to inhibit fear responses and reduce aversion sensitivity. This would contrast with psychotherapy’s potential positive impact on top-down cortical regulation of the amygdala’s responsiveness to perceptions of threat and danger (Ressler & Nemeroff, 2000).

This makes conceptual sense with the cognitive specificity of anxiety relating to appraisals of danger and capacity to cope, as opposed to the cognitive specificity of depression relating to perceptions of loss and powerlessness, specifically being trapped in an intolerable environment and defeated in one’s attempts to escape it or to achieve significant goals. Anxiety thus represents the state of hypersensitivity to danger and under-estimation of coping responses, whilst depression is the state of emotional distress and physiological down-regulation associated with helplessness and hopelessness (Taylor et al., 2011).

The British National Formulary advises that there is little to choose between the different classes of antidepressant drugs in terms of efficacy, so choice should be based on the individual patient’s requirements, including the presence of concomitant disease, existing therapy, suicide risk, and previous response to antidepressant therapy. The heterogeneity of neurological mechanisms does however have important implications in terms of side-effects, toxicity in overdose, and discontinuation effects. SSRIs are considered first-line for treating depression because they have similar efficacy to tricyclic medication but are better tolerated and are safer in overdose than other classes of antidepressants. For example, in patients with unstable angina or who have had a recent myocardial infarction, sertraline has been shown to be safe (Joint Formulary Committee, n.d.).

Aside from sexual side effects other adverse reactions from SSRIs include nervousness and agitation, sleep disturbances, and gastrointestinal symptoms. There is also the danger of activation, an acute onset (within a few hours) cluster of symptoms that include increased activity level, impulsivity, insomnia, or disinhibition without manic symptoms (Preston et al., 2010; Riddle et al, 1991). This is distinguished from switching, which is the onset of a manic episode typically after several weeks use. The most serious potential side effect is serotonin syndrome, which is a potentially fatal toxic excess of serotonin. Its main symptoms are as follows:

• Cognitive effects: headache, agitation, hypomania, mental confusion, hallucinations, coma
• Autonomic effects: shivering, sweating, hyperthermia, vasoconstriction, tachycardia, nausea, diarrhoea.
• Somatic effects: myoclonus (muscle twitching), hyperreflexia (manifested by clonus), tremor.

Medical practitioners in the UK are currently able to prescribe six SSRIs (Joint Formulary Committee, n.d.). They are:

• fluoxetine (brand names Prozac, Oxactin)
• paroxetine (Seroxat)
• citalopram (Cipramil)
• escitalopram (Cipralex)
• sertraline (Lustral)
• fluvoxamine (Faverin)

Pharmacological capacity of SSRIs to produce sexual dysfunction

The fifth edition of the American Psychiatric Association’s (APA) Diagnostic and Statistical Manual of Mental Disorders (DSM-5) (APA, 2013) lists nine categories of sexual dysfunction. The disorder of greatest relevance to this work is substance/medication-induced sexual dysfunction (SMISD). The diagnostic criteria for SMISD are as follows:

• • Criterion A: A clinically significant disturbance in sexual function is predominant in the clinical picture.
  • Criterion B: There is evidence from the history, physical examination, or laboratory findings of both (1) and (2):
  • Criterion C: The symptoms in Criterion A developed during or soon after substance intoxication or withdrawal or after exposure to a medication.
  • Criterion D: The involved substance/medication is capable of producing the symptoms in Criterion A.
  • Criterion E: The disturbance is not better explained by a sexual dysfunction that is not substance/medication-induced. Such evidence of an independent sexual dysfunction could include the following:
    • The symptoms precede the onset of the substance/medication use; the symptoms persist for a substantial period of time (e.g., about 1 month) after the cessation of acute withdrawal or severe intoxication; or there is other evidence suggesting the existence of an independent non-substance/medication-induced sexual dysfunction (e.g., a history of recurrent non-substance/medication-related episodes).
  • Criterion D: The disturbance does not occur exclusively during the course of a delirium.
  • Criterion E: The disturbance causes clinically significant distress in the individual.

Meston and Frohlich (2000) state that it is not known exactly why SSRIs produce sexual side effects. There are at least 14 different serotonin receptors that have been classified into seven distinct groups (Wong et al, 2005) with accompanying subgroups (e.g. serotonin_1A, serotonin_1B etc.). Differing serotonin receptors can affect sexual functioning in various ways. Activation of all serotonin₂ receptors impairs all aspects of sexual functioning in both men and women, whilst activation of serotonin_1A receptors facilitates sexual excitation, although animal studies suggest that these effects may vary between the sexes (Pfaus, 2009). Serotonergic innervation is also found outside the CNS in women’s sexual organs where it acts as a vasodilator and vasoconstrictor. Because vasocongestion of genital tissue is a key aspect of sexual arousal it is likely that serotonin also has an effect in producing sexual arousal in the periphery (Frohlich & Meston, 2000) where excess serotonin can reduce genital sensation (Mkele, 2014).

Prabhakar and Balon (2010) state that, despite their selectivity, no SSRIs are exclusive to the serotonergic system and other neurotransmitter systems can also be affected including noradrenaline, dopamine and acetylcholine, all of which are involved in sexual functioning. For example, noradrenaline both activates general sympathetic arousal and disinhibits dopaminergic pathways that direct attention to sexual incentives, while excess serotonin could lead indirectly to a loss of sexual interest as serotonin can inhibit dopamine, the neurotransmitter that directs attention and motivation to sexual cues. Citalopram, escitalopram, and fluvoxamine act on the serotonin system alone; fluoxetine and sertraline also operate on the noradrenaline and dopamine systems, and paroxetine operates on serotonin, noradrenaline and acetylcholine systems (Pfaus, 2009).

Serotonergic, adrenergic and cholinergic systems are all implicated in the production of nitric oxide, which is responsible for smooth muscle relaxation (via catalysis of cyclic guanosine monophosphate) and thus vasocongestion in the genitals (Prabhakar & Balon, 2010). SSRIs are highly differentiated in chemical structure, sharing almost no molecular features, (Sadock & Sadock, 2011), and thus differ in the specificity of the receptors that they target; for example, paroxetine and sertraline are both highly selective for serotonin_1A receptors, whereas fluoxetine is less so (Prabhakar & Balon, 2010). SSRIs that increase serotonergic activity but do not inhibit serotonin₂receptors are associated with sexual side effects, while non-SSRI antidepressants that do inhibit serotonin₂ receptors such as mirtazapine and nefazodone, have a lower likelihood of sexual side effects (Meston & Frohlich, 2000).

Lane (1997) states that the effects of SSRIs on sexual functioning are clearly dose-related and may vary amongst those affected due to the extent to which SSRIs’ propensity for accumulation over time leads to increased plasma levels. Whilst SSRIs have multiple effects on physiological components of sexual functioning the overall picture is of a propensity for suppression of sexual excitement by hyperfunctional serotonin activity in the central nervous system (Pfaus, 2009). We can therefore conclude that SSRIs do have the biochemical potential to bring about physiological changes in central and peripheral nervous systems that affect sexual functioning, but the picture is both complicated, might differ by gender, and is by no means entirely understood.

Impact on phases of sexual functioning

Sexual dysfunction can be caused by a myriad of interacting factors including physical conditions (such as vascular disease), psychological and relationship factors, and medication-induced effects (Baldwin, 2001) and it can be difficult to separate the effects of one from another (Metz & McCarthy, 2007). In terms of the specificity of the impact of SSRI medication on different aspects of sexual functioning, the norm in studies has been to use a phase-based approach to sexual functioning. Balon (2006), for example, proposed that SSRIs may have a negative impact on any or all phases of the sexual response cycle, causing decreased or absent libido and impaired arousal, and erectile dysfunction, but are most strongly associated with delayed ejaculation and absent or delayed orgasm. DSM-5 (APA, 2013) reiterates the latter point, noting that the most commonly reported side effect is difficulty with orgasm or ejaculation and that problems with desire and erection are less frequent.

The picture is potentially more nuanced than that description might suggest. Frank et al. (2008), for example, reported that in women the most common side effects of SSRIs are decreased desire as well as delayed or absent orgasm, suggesting potential gender differences. Clayton et al (2002) reported that the primary sexual side effect was anorgasmia, i.e.difficulty achieving an orgasm despite adequate arousal and that erectile dysfunction was rare. Rosen et al. (1999) suggested that whilst sexual desire and arousal difficulties were frequently reported, SSRI use has not been consistently shown to be associated with those specific disorders. Rosen and Marin (2003) however stated that up to 90% of men in one study of SSRI-induced sexual dysfunction reported erectile dysfunction and associated secondary dysfunctions, although they also pointed out that this could occur as a result of an inability to sustain an erection for long enough to ejaculate due to the primary sexual side-effect of increased ejaculatory latency time.

In a study of 15 patients who reported SSRI-induced sexual side-effects 80% reported emotional blunting including significantly less ability to cry, to care about others’ feelings, to have erotic dreams, to experience creativity, to feel sadness, surprise, anger, to give expression of their feelings, to worry over things or situations, and to experience sexual pleasure and interest in sex. These reports were not correlated with severity of depression, suggesting that they were a consequence of the medication rather than depressive symptoms. It has been recommended that more attention be paid to the role of emotional blunting on treatment non-compliance and quality of life (Opbroek et al, 2002). Fisher and Thomson (2007) cite a case study of a woman who reported feeling less “in love” with her boyfriend following SSRI treatment and of a man whose romantic feelings for his wife declined drastically. They suggested that reduction in romantic attraction was as a consequence of emotional blunting caused by an excess of serotonin suppressing dopamine, noradrenaline and testosterone. However, further evidence would be needed to validate this hypothesis.

Other adverse effects included reports of priapism (Rosen et al., 1999) genital anaesthesia (decreased sensitivity) and ejaculatory anhedonia (ejaculation without pleasure) but prevalence rates were not clearly known nor are there any specific treatments (Preston et al, 2010). Csoka, et al., (2008) on the other hand stated that reports of genital anaesthesia (as well as low libido and anorgasmia) are very common.

DSM-5 reports that the development and course of sexual side effects from antidepressant medication varies. The onset of sexual side effects can occur in as few as 8 days after commencing pharmacological treatment. While approximately 30% of individuals with mild to moderate delay in orgasm will experience a spontaneous remission of the problem within six months, most will not and in some people SSRI-induced sexual dysfunction can persist after the medication is discontinued. Csoka et al. (2008) reported three such cases: a 29-year-old with apparently permanent erectile dysfunction after taking fluoxetine 20mg once daily for a 4-month period; a 44-year-old with persistent loss of libido, genital anaesthesia, ejaculatory anhedonia, and erectile dysfunction after taking 20mg of once-daily citalopram for 18 months; and, a 28-year-old with persistent loss of libido, genital anaesthesia, and ejaculatory anhedonia after taking several different SSRIs over a 2-year period. The authors reported that there had been no prior psychological issues related to sexuality in any of the men and all other common causes of sexual dysfunction (e.g. decreased testosterone, increased prolactin, or diabetes) had been ruled out.

Depression is well known to be both a relapsing and a recurring condition, which in itself places great strain on both the individual and their intimate partner relationship. Cyranowski et al. (2004) examined interactions between recurrent depression, SSRI treatment and sexual partner availability in a group of women with recurrent depression over the course of 1 year. While depression was associated with reduced sexual desire, sexual thoughts and fantasy, sexual arousal, orgasmic function, and a more global evaluation of sexual functioning, SSRI treatment was only associated with orgasmic difficulty. Having an available sexual partner was associated with increased sexual arousal, orgasmic function and sexual behaviour. these findings suggest that depression, SSRI medication, and partner availability interact in complex ways, but that loss of orgasmic function in some women might be considered less troubling when compared with the potentially anti-depressant effects of an otherwise satisfying sexual relationship. However, that that would of course depend on what it was that the woman found sexually satisfying other than the capacity to have an orgasm.

Antidepressants can increase libido when it has been decreased by depression by treating successfully the underlying depression that inhibited sex drive (Preston et al. 2010). In a prospective study of 25 chronically depressed patients (14 women, 11 men) who were prescribed sertraline or paroxetine,desire, psychological arousal, and overall sexual functioning significantly improved in women; orgasm delay, orgasm satisfaction, and overall sexual functioning significantly worsened in men (Piazza et al, 2014). The women in the study showed greater sexual dysfunction when baseline measures were taken and, whilst not specifically reporting on changes in orgasmic capability, it is possible that improved sexual functioning in women was due to improvement in symptoms of depression that led to a more satisfying intimate partner relationship.

In qualitative research Darrouzet-Nardi and Hatch (2014) observed that women who experienced loss of desire or delayed or absent orgasm whilst taking SSRIs had to navigate a series of gendered scripts about the role of sex. The authors reported that while some women reported concern at their inability to live up to their male partner’s expectations, others felt social pressure to live up to a contemporary image of female sexuality that encourages women to enjoy sex and to embrace their own desires. Women who feared letting down their partner reported employing strategies such as the use of alcohol to heighten desire, faking sexual responsiveness, continuing to have sex despite a lack of desire, or switching medication to achieve greater sexual responsiveness. Women who mourned the loss of their sexual selves reported a sense of being “abnormal” and grieving the loss of an important part of themselves that contributed to their identity. One participant stated that, “Something is wrong. I feel like a human with that essence that’s not there…Something’s broken.” and another that, “I almost feel like I was losing the sexual side of myself…and I kind of lost that positive self-image. That was just shitty. That’s part of who you are, part of your essence, what you think of yourself, and I was losing that because of something I was taking” (n.p).

There is as yet no similar study on the impact on men of SSRI-induced sexual dysfunction, but it is conceivable that in heterosexual couples a female partner’s anorgasmia could undermine a man’s sexual identity if the man defines his masculinity at least in part by female sexual responsiveness as an indicator of his skill as a lover. Similarly, research on delayed ejaculation shows that men can feel thwarted, anxious and sexually incompetent and can cause frustration in both partners, especially if they wish to conceive (Hartmann & Waldinger, 2005).

Prevalence of SSRI-induced sexual dysfunction

Sexual dysfunction is thought to be a relatively common adverse side effect of many of the antidepressants in common use and rates of sexual dysfunction observed in clinical practice may be higher than those reported in product information sheets (Gregorian et al, 2002). DSM-5 reports that the prevalence of SSRI sexual side effects is between 25% and 80%. Montgomery et al. (2002) suggest five reasons why frequency of sexual dysfunction varies so widely between studies:

1. There is a lack of a reliable baseline of sexual dysfunction in the general population
2. People with mental health problems have elevated levels of sexual dysfunction due to the impact of the mental disturbance on behaviour and relationships
3. Social and cultural influences have an impact on sexual behaviour and also change over time
4. Self-report of sexual dysfunctions is frequently underreported, sometimes by up to 60% compared to direct questions
5. Methodological flaws are common in studies (e.g. not using validated rating scores, or randomised, placebo-controlled double-blind studies).

Balon (2006) added a sixth category, which is the lack of attention paid to comorbidity of other mental health problems, substance abuse, physical health problems, or other medication, any or all of which could have an effect on sexual functioning so that a realistic prevalence of dysfunction would probably lie between 30% and 50%.

Montogmery et al (2002) stated that there is no robust evidence of differences in incidence of sexual dysfunction associated with different SSRIs. DSM-5 states that the antidepressants mirtazapine and bupropion, neither of which are SSRIs, appear not to be associated with medication-related side effects (APA, 2013). Clayton et al (2002) state that the following non-SSRI antidepressants have lower rates than SSRIs, rather than no impact: bupropion (22-25%); nefazodone (28%) venlafaxine and mirtazapine (36%-43%).

In a study of over 6,000 outpatients receiving either SSRI or the closely related SNRI (serotonin-noradrenaline reuptake inhibitor) medication but who didn’t report a level of sexual dysfunction that met the criteria for a global sexual dysfunction, 95.6% of women and 97.9% of men exhibited some impairment in at least one phase of sexual functioning. Men were significantly more likely than women to experience dysfunction in the desire phase and the orgasmic phase but were significantly less likely than women to experience dysfunction in the arousal phase; men reported a disproportionately high incidence of sexual side effects, whilst severity was reportedly worse for women (Clayton et al., 2006). In a study of 1022 outpatients Montejo et al. (2001) reported that men had a higher frequency of sexual dysfunction (62.4%) than women (56.9%), although women had higher severity with 40% finding it very difficult to tolerate the level of sexual dysfunction. Differences in severity for women were hypothesised to occur because serotonin is metabolised more slowly by women (Meston & Gorzalka, 1992; Frohlich & Meston, 2000), but could also be the result of more women than men taking antidepressant medication for longer as women have higher rates of diagnosis for the conditions for which SSRIs are prescribed (Hensley & Nurnberg, 2000).

One potentially serious consequence of sexual side effects is medication noncompliance, which increases the risk that the individual continues to suffer with an untreated mental health problem (Lane, 1997). This can have serious or even fatal consequences: the World Health Organisation (WHO) reported that severe mental health problems can reduce life expectancy by 10-25 years and the risk of dying associated with depression is 1.8 times greater than for the non-depressed (WHO, n.d.). Although SSRIs are generally tolerated better than older antidepressants and are less toxic in overdose (Ferguson, 2001) the issue of the tolerability of side effects is of central importance to patient care.

DSM-5 reports that 30% of cases of antidepressant-induced sexual dysfunction are clinically significant, meaning that they have persisted for approximately six months and cause clinically significant distress. If 30-50% of people taking SSRI medication report sexual side effects and approximately 30% of that population find them difficult to tolerate then a cautious estimate suggests 9% of people prescribed SSRIs experience clinically significant sexual side effects. With over 57m prescriptions for antidepressant use in England in 2014 (Health & Social Care Information Centre, n.d.) and an estimated 9% of the 52m adults in Britain taking antidepressant medication in 2015 (Lewer et al., 2015) that produces an estimated 4.68m people taking antidepressants (the vast majority of which are SSRIs) suggesting that approximately 420,000 people find these sexual side effects highly distressing. Sexual dysfunction is under-recognised and underreported generally, especially among women (Hensley & Nurnberg, 2002), and inadequately assessed and underestimated by physicians (Clayton et al, 2002), suggesting that there is a far greater prevalence of untreated sexual misery in people prescribed SSRI medication than has previously been recognised and that it affects women’s sexual functioning disproportionately.

However, rates of sexual dysfunction in the general population are high. In a 2003 UK survey a total of 34.8% of men and 53.8% of women who had at least one heterosexual partner in the previous year reported at least one sexual problem lasting at least one month; where the problem lasted for at least six months the rates were lower: 6.2% for men and 15.6% for women, with the most common problems being rapid ejaculation for men and lack of interest in sex for women (Mercer et al, 2003). Sexual functioning varies across the lifecycle and expectations change as key events occur in the lives of individuals and families, leading to a range of positive and negative emotional responses that can also influence sexual functioning (Balon, 2006).

Depression itself is often associated with sexual dysfunction. In one study 72% of patients with depression reported loss of libido (Casper et al, 1985), making it difficult to establish a clear temporal link between the onset of the sexual dysfunction and the initiation and discontinuation of medication. Clayton et al. (2002) conducted a large study in which careful histories were taken from both the patient and a significant other. They concluded that a large number of sexual symptoms, in particular hypoactive desire, appeared to be related to depression as it was evident prior to commencing medication. Decreased libido was most often reported, but also difficulties with arousal that can lead to vaginal dryness in women and erectile dysfunction in men, whilst absent or delayed orgasm were also prevalent (Kennedy & Rizvi, 2009). In a prospective study of sexual dysfunction associated with depression, 50% of women and 42% of men reported decreased sexual interest prior to starting treatment (Kennedy et al., 1999). Delayed ejaculation and orgasm were not however usually associated with depression (Balon, 2006).

Whilst SSRIs are a first-line treatment for moderate to severe presentations of depression (National Institute for Health and Clinical Excellence, 2009) and efficacy rates in clinical trials average between 50-70%, effectiveness in real world studies show a lower response (47%) and complete remission in only 28-33% of patients (Rush et al, 2006) while medication noncompliance can also lead to ineffective pharmacotherapy. Although many studies only utilise participants who are in remission, it is likely that in the real world, patients present with a mixture of SSRI-induced sexual dysfunction and the adverse sexual consequences of ineffectively treated depression.

Treatment for SSRI associated sexual dysfunction

Rothschild (2000) stated that many people with depression care about their sexual function but may be reluctant to report difficulties and could therefore become covertly noncompliant with medication and thus risk relapse. It has been estimated that as many as 42% of patients wait passively for spontaneous remission of sexual dysfunction related to SSRI medication (Clayton & Montejo, 2006) despite the availability of a range of management or treatment options that have been tried and evaluated. It is therefore recommended that practitioners proactively enquire about such effects, monitor them through treatment, and discuss potential treatments (Segraves, 1998).

Balon (2006) suggested that practitioners take a baseline assessment of sexual functioning to compare with later reports after commencing SSRI treatment, rather than rely on patients’ memories of pre-SSRI sexual functioning. Assessment should include the following:

1. Pre-treatment and, if possible, premorbid sexual functioning
2. Comorbid psychiatric disorders and substance use (including tobacco)
3. Medical disorders
4. All concurrent medications, including the over-the-counter drugs 
(for example, cimetidine is associated with sexual dysfunction)
5. Sexual functioning during the depressive episode but before 
initiation of antidepressant treatment
6. The potential interpersonal context of the sexual dysfunction (relationship discord, etc.)

Boyarsky and Hirschfeld (2000) suggest that using a validated self-report scale such as the Arizona Sexual Experiences Scale (McGahuey et al, 2000) is helpful, nonintrusive and quick and easy to complete.

Balon (2006) suggested that an individualised treatment for SSRI-induced sexual dysfunction is more art than science and should not be limited to biological interventions but should consider psychological factors and fluctuations in sexual functioning that could help make SSRI-related sexual dysfunction more manageable. Suggestions included; 1) life style interventions to increase healthy behaviours, for example tackling obesity or substance misuse; 2) promoting exercise to enhance self-image, a sense of well being, and the health of the physiological systems that influence sexual functioning; and, 3) psychosexual therapy to help cope with the dysfunction, reduce symptom severity, or help prevent symptoms worsening. In addition, educating and encouraging the client towards more diverse sexual practices such as masturbation, mutual masturbation, use of vibrators and fantasies could be helpful adjuncts.

Psychosexual therapy based on cognitive behaviour therapy (CBT) might help provide a practical therapeutic intervention for addressing unhelpful behaviours, assumptions and beliefs that interfere with a constructive adaptation to the dysfunction. It might also be effective to use an evidence-based psychotherapy such as CBT for the underlying depression or anxiety thus allowing medication dosage to be reduced or discontinued. Not every person will respond to a psychological intervention for their underlying mental health problem, but a significant number will, such that NICE no longer recommends antidepressant medication for mild presentations of depression (National Institute for Health and Clinical Excellence, 2009).

Segraves and Balon (2003) recommend a range of management strategies for SSRI-induced sexual dysfunction. Whilst many of these are primarily aimed at medical practitioners, psychosexual therapists can use this information to hold collaborative discussions with relevant medical professionals.Management strategies for SSRI-induced sexual dysfunction (Balon, 2006; Balon, 2009; Segraves & Balon, 2003) include the following:

1. Start with an antidepressant that is not associated with sexual dysfunction. Rothschild (1995) suggested that starting treatment with bupropion (noradrenaline-dopamine reuptake inhibitor), mirtazapine (noradrenaline antagonist, serotonin antagonist), or nefazodone (serotonin antagonist reuptake inhibitor) may be a useful strategy for sexually active patients.
2. Switch to an antidepressant that has a lower incidence of sexual dysfunction. Several studies have documented the usefulness of switching to an antidepressant with a lower incidence of sexual dysfunction, such as bupropion, mirtazapine, and nefazodone. This strategy may work with some patients, but it may be difficult to implement in cases where several other antidepressants have been tried and the offending agent is the only one that has been helpful in alleviating depression.
3. Wait for spontaneous remission of dysfunction or for tolerance to develop. This approach may require a long wait, which is not always acceptable to the patient; the effectiveness of this strategy is low.
4. Reduce the dose of antidepressant to the minimal effective dose. With some antidepressants, associated sexual dysfunction seems to be dose dependent, and decreasing the dose might be helpful. However, this approach requires careful, continuous assessment of depressive symptoms, as depression may recur after the dose is lowered.
5. Introduce drug holidays or partial drug holidays. The antidepressant can be discontinued (holiday) or the dose decreased (partial holiday) for a brief period (e.g., 2–3 days), with sexual activity scheduled at the end of the period. In one study (Rothschild, 1995), this approach was found to be successful with shorter-half-life SSRIs such as paroxetine and sertraline but not with fluoxetine. This approach carries risks, however, as withdrawal symptoms may occur, anxiety may worsen, and nonadherence may be encouraged.
6. Suggest that sexual activity be scheduled around the daily dose of antidepressant, so that sexual activity occurs just before the patient takes the entire daily dose of the antidepressant. The evidence of efficacy for this strategy is limited. It may work with some short-half-life antidepressants.
7. Add “antidotes” or “augmenting” agents. Numerous antidotes or augmenting agents have been described as useful in alleviating SSRI-associated sexual dysfunction. Although most of the literature consists of case reports, results of several studies of the efficacy of such agents have been reported (Taylor et al., 2005).
8. Make lifestyle adjustments or changes
9. Use psychosexual therapy.

Taylor et al (2005) analysed 15 trials and concluded that the following agents have been reported to be useful: amantadine, bethanechol, bromocriptine, bupropion, cyproheptadine, dextroamphetamine, ginkgo biloba, granisetron, loratadine, methylphenidate, mianserin, mirtazapine, nefazodone, neostigmine, pemoline, pramipexole, ropinirole, sildenafil, tadalafil, trazodone, vardenafil, and yohimbine but that the only evidence-based or proven management approaches to the management of SSRI-induced sexual dysfunction were 1) PDE5 inhibitors for erectile dysfunction; 2) adding bupropion (a central nervous system stimulant) for decreased libido; and 3) switching to nefazodone for overall sexual dysfunction. These results matched in large part the prescribing practices of experienced clinicians (Balon, 2006). It should be noted that some of these strategies would not be recommended under UK prescribing guidelines; for example, in the UK bupropion is only licenced for use in smoking cessation programmes, not as an antidepressant and the prescribing of nefazodone has been discontinued in several countries, including the USA, due to the risk of potentially fatal hepatotoxicity (liver damage) (Stewart, 2002).

Since the Taylor et al (2005) review there have been a number of further studies. Preston et al. (2010) reported that the best-supported treatments for sexual side effects were the addition of 150-300mg of the antidepressant bupropion, which can lead to improvement within a few weeks, although it can have a range of side effects including increasing the risk of seizures. When prescribed as an antidepressant bupropion can have prosexual effects including increased libido, level of arousal, and intensity of orgasm beyond levels experienced premorbidly (Modell et al., 1997).

Preston et al. (2010) reported that 50-100mg of sildenafil citrate (Viagra) 1 hour before planned sexual activity can be helpful both to men and women. Despite having been approved for treating erectile dysfunction, it appears to increase the ability of both men and women to achieve orgasm. Nurnberg et al. (2003) had previously reported that 54.5% of men who took at least one dose of sildenafil reported that their sexual functioning was “much” or “very much” improved. Interestingly erectile function, arousal, ejaculation, orgasm, and overall satisfaction improved significantly in sildenafil compared with placebo patients, while depression scores remained in remission. In a further study Nurnberg et al. (1999) evaluated the effects of two doses of sildenafil (initially 50mg then increased to 100mg if there was only partial or no response) for women patients with antidepressant-induced sexual dysfunction. The nine patients, all of whom had experienced either anorgasmia or delayed orgasm with or without associated disturbances, reported significant reversal of sexual dysfunction, usually with the first dose of 50 mg of sildenafil.

Future treatment may make use of pharmacogenetic studies that are now showing some promise in identifying gene markers for serotonin metabolism that could predict a patient’s response to SSRI medication, opening the way for patients to be better informed about the likely side-effect profile they will experience and for clinicians to tailor prescriptions to clients’ lifestyle and preferences (Osis & Bishop, 2010). Finally, Gregorian et al (2002) noted that management of SSRI side effects has financial implications as additional healthcare resources will be needed. Although referring to a North American, managed-care setting, in the UK this could include more visits to general practitioners, increased prescribing and monitoring costs, or the need for more specialized treatment, raising questions of clinical and financial priorities.

Treatment of rapid ejaculation and paraphilias

On occasion the sexual side effects of SSRIs have potential benefits. In the UK paroxetine, sertraline and fluoxetine are prescribed off-label for rapid ejaculation, although their mode of action requires them to be taken daily to have an effect. Although improvement can be seen after a few days it is more evident after 1-2 weeks and can be continued for some years (Hatzimouratidis et al., 2010). Waldinger et al. (1998) conducted two studies on the impact of various SSRIs (fluoxetine, fluvoxamine, paroxetine, and sertraline) on rapid ejaculation. They reported that paroxetine delayed ejaculation most strongly, raising the intra-vaginal ejaculation latency time (IELT) on average from 20 seconds to 110 seconds. They also reported that in their second study using only paroxetine this effect was also true for men whose IELT was initially longer than one minute (average 83 seconds) and caused a 480% increase to 602 seconds.

In Europe the potent, fast-acting SSRI Dapoxetine is the only medication approved for the treatment of rapid ejaculation, and it has been authorised by some UK some health authorities. Dapoxetine can be taken an hour prior to intercourse and clinical trials have shown that it can increase IELT significantly in 51-58% of men by, at best, 388% (54 seconds to 210 seconds) although Hatzimouratidis et al. (2010) suggest that on discontinuation there is likely to be a recurrence of the dysfunction and not all men will benefit. Side effects include nausea, dizziness, diarrhoea, and headache although only 3.9% to 8.2% of men stopped using the medication as a consequence, suggesting that satisfaction outweighed the burden of these adverse effects.

Hill et al. (2003) described how in Germany SSRIs, as well as anti-androgens, are sometimes used as a treatment for paraphilia and for sexual offenders and can lead to marked reduction in sexual fantasies, desire, masturbation, and sexually deviant behaviour. The authors described possible mechanisms as follows: 1) general inhibition of sexual activity; 2) reduction of impulsiveness; 3) reduction of obsessive-compulsive characteristics; 3) reduction of underlying depression; and 4) indirect reduction of testosterone. However, in a study of male outpatients the authors also noted adverse effects: 69% suffered from reduced desire, 37% suffered from erectile dysfunction, and 37% also experienced delayed ejaculation or orgasm. These outcomes are problematic not just because of the potential distress they may cause but because optimal pharmacotherapy of paraphilias should only selectively affect the paraphilic thinking and behaviour whilst leaving other aspects of sexual functioning intact. Clearly there are important ethical and legal issues related to the use of SSRIs as part of the criminal justice system that unfortunately are beyond the scope of this work (for a discussion see Stewart, 2012).

Discussion

In terms of the validity of the research findings summarised in this project, the majority of the studies date from before publication of DSM-5 in 2013, which can make their interpretation difficult in the light of contemporary theories of sexual function. Whipple and Brash McGreer (1997) and Basson (2001) both suggest that sexual satisfaction or dissatisfaction plays a large part (for women especially) in subsequent desire and/or willingness to become aroused, so the clinical picture might be further complicated by the successful pharmacological treatment of the underlying depression resolving one sexual dysfunction (e.g. improvement in mood leading to increased sexual interest), only to induce a separate dysfunction (e.g. delayed or absent orgasm) that leads to sexual dissatisfaction and demoralisation that, in turn, leads to avoidance of sex and a recurrence of decreased sexual desire. This project therefore concludes that it would be helpful for further research to employ more contemporary models of sexual function with an emphasis on qualitative accounts of coping and resilience.

Weighing up the benefits of SSRI treatment versus its costs is a clinically sensitive subject: SSRIs clearly have a vital role in the management of some mental health conditions given the potentially fatal consequences of untreated depression, the misery of severe anxiety disorders such as OCD and the interpersonal chaos of personality disorder. All these conditions are likely to affect not just the sufferer but also those closest to them, including children. On the other hand, it is possible that a negative impact on sexual functioning that leads to relationship distress could itself exacerbate depressive symptoms or precipitate a relapse. Sexual functioning is best seen as a biopsychosocial phenomenon (Bancroft, 2009) therefore there is likely to be a complex interplay between physiological, intrapsychic, relationship and social factors. Mental health problems are also biopsychosocial phenomena, for example depression is at times precipitated or exacerbated by relationship stress (Beach, 1990) leading to a reduction in positive relationship behaviours and an increase in negative behaviours (Beach, 1990); a cyclical pattern of stress generation (Hamman, 2005); and a negative cycle of excessive reassurance seeking (Joiner, 1994). A key mediating factor for the role of relationship distress in depression is the perception of powerlessness; specifically feeling trapped in painful circumstance’s and defeated in one’s attempts to overcome adversity (Taylor et al., 2011).

It is possible that by inhibiting certain specific aspects of sexual functioning (e.g. orgasmic potential) there are changes in the salience of sexual incentives that manifest as reduced desire. This reduction in drive or libido leads to behavioural inhibition (non-initiation and non-responsiveness to sexual advances) that in turn could precipitate or exacerbate relationship problems that diminish the opportunity for intimate rewards that would themselves have antidepressant effects. Therefore, improving a distressed relationship may be one way to help either reduce SSRI use or to manage sexual side effects more effectively. Further research would be needed to determine whether this multi-stage meditational pathway does occur in a significant number of patients who report SSRI-induced sexual dysfunction.

Sexual functioning contributes both to a sense of personal identity and to relationship satisfaction where it can be thought of as energising the affiliative bond in a couple; sex can be a consolation and a balm and when it is dysfunctional it has a disproportionately high impact on perceived relationship distress, compared to the contribution it makes when it forms part of a satisfying intimate team (Metz & McCarthy, 2007). Psychosexual practitioners would be well advised always to enquire of patients who have been prescribed SSRI medication about the underlying clinical condition, what effect it had on sexual functioning prior to SSRI administration and any subsequent sexual effects. They could also usefully enquire as to the impact of the sexual dysfunction on identity and on an intimate partner relationship or on hidden gains to the dysfunction; it is feasible that depression and/or sexual dysfunction play a role in giving permission for a partner to withdraw from the sexual aspects of a dissatisfying relationship. Before addressing the problem of SSRI-induced sexual dysfunction it would be worth enquiring whether the cure might be worse than the “disease”. Where sexual dysfunction is a source of distress therapists can then work in a collaborative manner with biomedical practitioners to mitigate the effects of sexual dysfunction on the individual and their intimate partner relationship.

Reading List

Source texts can be found in the Reference section. Interested practitioners looking for a summary of the main findings might find the following texts helpful:

For a general overview of the neurophysiology of sexual function:

Janssen, E., & Bancroft, J. (2007). The dual-control model: The role of sexual inhibition and excitation in sexual arousal and behavior. In E. Janssen (Ed). (2006). The psychophysiology of sex. Bloomington, IN: Indiana University Press.

Meston, C. M., & Frohlich, P. F. (2000). The neurobiology of sexual function. Archives of General Psychiatry, 57(11), 1012-1030.

Pfaus, J. G. (2009). Reviews: Pathways of sexual desire. The Journal of Sexual Medicine, 6(6), 1506-1533.

For a review of SSRIs and sexual dysfunction (including treatment options):

American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders: DSM-5: Sexual dysfunctions. Washington, D.C: American Psychiatric Association.

Balon, R. (2006). SSRI-associated sexual dysfunction. American Journal of Psychiatry.

Segraves, R. T., & Balon, R. (2003). Sexual pharmacology: Fast facts. New York, NY: WW Norton & Co.

Prabhakar, D., & Balon, R. (2010). How do SSRIs cause sexual dysfunction? Understanding key mechanisms can help improve patient adherence, prognosis. Current Psychiatry, 9(12), 30.

Taylor, M. J., Rudkin, L., & Hawton, K. (2005). Strategies for managing antidepressant-induced sexual dysfunction: systematic review of randomised controlled trials. Journal of affective disorders, 88(3), 241-254.

References

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Balon, R. (2009). Medications and sexual function and dysfunction. In: R. Balon & R.T. Segraves (Eds.) Clinical manual of sexual disorders. American Psychiatric Publishing, 95-115.

Bancroft, J. (2009). Human sexuality and its problems. (3rd ed.). Churchill Livingstone Elsevier.

Bancroft, J., & Janssen, E. (2000). The dual control model of male sexual response: A theoretical approach to centrally mediated erectile dysfunction. Neuroscience & Biobehavioral Reviews, 24(5), 571-579.

Bancroft, J., Janssen, E., Strong, D., Carnes, L., Vukadinovic, Z., & Long, J. S. (2003). The relation between mood and sexuality in heterosexual men. Archives of Sexual Behavior, 32(3), 217-230.

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Hill, A., Briken, P., Kraus, C., Strohm, K., & Berner, W. (2003). Differential pharmacological treatment of paraphilias and sex offenders. International Journal of Offender Therapy and Comparative Criminology, 47(4), 407-421.

Janssen, E., & Bancroft, J. (2007). The dual-control model: The role of sexual inhibition and excitation in sexual arousal and behavior. In E. Janssen (Ed). (2006). The psychophysiology of sex. Indiana University Press.

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Prabhakar, D., & Balon, R. (2010). How do SSRIs cause sexual dysfunction? Understanding key mechanisms can help improve patient adherence, prognosis. Current Psychiatry, 9(12), 30.

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