Sexual dysfunction with antidepressants

Sexual function One of the potential benefits of hypericum is the apparent reduced or lack of adverse effects upon sexual function, compared to pharmaceutical antidepressants. The SSRIs are particularly notorious for inhibition of sexual function, whereas antidepressants with dopaminergic actions (e.g., bupropion) do not, and may actually enhance sexual function (Rosen et al. 1999 Piazza et al. 1997). Anecdotal reports and the fact that there are no clinical reports of sexual dysfunction with hypericum is encouraging, but it remains to be tested empirically. 

Nurnberg HG, Hensley PL, Gelenberg AJ, Fava M, Lauriello J, Paine S. Treatment of antidepressant-associated sexual dysfunction with sildenafil. J Am Med Assoc 2003 289 56-64. 

After more than a decade of use, bupropion (24) is considered a safe and effective antidepressant, suitable for use as first-line treatment. In addition, it is approved for smoking cessation and seasonal affective disorder. It is also prescribed off-label to treat the sexual dysfunction induced by SSRIs. Bupropion is often referred to as an atypical antidepressant and has much lower affinity for the monoamine transporters compared with other monoamine reuptake inhibitors. The mechanism of action of bupropion is still uncertain but may be related to inhibition of dopamine and norepinephrine reuptake transporters as a result of active metabolites [71,72]. In a recently reported clinical trial, bupropion extended release (XL) had a sexual tolerability profile significantly better than that of escitalopram with similar re-... 

The most commonly used therapies for anxiety and depression are selective serotonin reuptake inhibitors (SSRIs) and the more recently developed serotonin noradrenaline reuptake inhibitors (SNRIs). SSRIs, which constitute 60% of the worldwide antidepressant and antianxiety market, are frequently associated with sexual dysfunction, appetite disturbances and sleep disorders. Because SSRIs and SNRIs increase 5-HT levels in the brain, they can indirectly stimulate all 14 serotonergic receptor subtypes [2,3], some of which are believed to lead to adverse side effects associated with these drugs. Common drugs for short-term relief of GAD are benzodiazepines. These sedating agents are controlled substances with addictive properties and can be lethal when used in combination with alcohol. The use of benzodiazepines is associated with addiction, dependency and cognitive impairment. 

Loss of Interest in Sex. One of the prominent symptoms of depression is anhe-donia, a lack of interest or pleasure in life. Anhedonia is commonly manifested by a decreased libido or a lack of interest in sex. This is different from the sexual dysfunction of delayed ejaculation, delayed orgasm, or anorgasmia seen with all antidepressants that block serotonin reuptake. The problem, however, is that loss of... 

Take a Medication Holiday. Some side effects are not a problem on a daily basis nonetheless, they can be qnite distnrbing. The best examples are sexual side effects of some antidepressants or the possible effects of stimulants upon the growth of children with ADHD. One approach has been to skip taking the medication for a brief period of time. For example, those with antidepressant-induced sexual dysfunction have sometimes circnmvented this problem by skipping a single day s dose when they plan to have sex. In a similar fashion, parents concerned with the effects of stimulants on their child s growth may have their child skip doses on the week-... 

When we talk about serotonin-blocking medications, a point of clarification must be made. In most cases, medications do not block overall serotonin activity but instead block the activity at one of the many serotonin receptor types. For example, the antidepressants trazodone, nefazodone, and mirtazapine increase total serotonin activity yet they block certain of the serotonin receptors. Mirtazapine increases both serotonin and norepinephrine activity by interfering with the alpha-2 receptor. By also blocking the serotonin-2 and serotonin-3 receptors, mirtazapine avoids the sexual dysfunction and GI side effects commonly experienced with other serotoninboosting medications. We cannot truly call these serotonin-blocking medications, because they are serotonin-boosting medications that selectively block certain serotonin receptors. 

Side effects, mainly due to serotonin reuptake inhibition include G1 upset, nervousness, and sexual dysfunction. SSRls are associated with an increased risk of falls. Hyponatraemia due to SIADH is an uncommon, but important side effect in elderly patients. Selective serotonin and norepinephrine reuptake inhibitors (S SNRls) such as venlafaxine and duloxetine are also useful in older patients. Other heterocyclic antidepressants of importance in older patients because of relative safety include bupro-prion and mirtazepine. They are reserved for patients with resistance to or intolerance of SSRls. Currently, trazodone is used mostly for sleep disturbance in depression in doses of 50-100 mg at bedtime. The monoamine oxidase inhibitors phenelzine. 

Michelson, D., Bancroft, J., Targum, S., Kim, Y., and Tepner, R. (2000) Female sexual dysfunction associated with antidepressant administration a randomized, placebo-controlled study of pharmacologic intervention. Am J Psychiatry 157 239—243. 

Montejo, A.L., Llorca, G., Izquierdo, J.A., and Rico-Villademoros, F. (2001) Incidence of sexual dysfunction associated with antidepressant agents a prospective multicenter study of 1022 outpatients. Spanish Working Group for the Study of Psychotropic-Related Sexual Dysfunction. / Clin Psychiatry 62 10-21. 

Treatment with SSRIs is started at or near their therapeutic antidepressant doses. The most significant disadvantage of these medications is a high incidence of treatment-emergent sexual dysfunction (see Sexual Dysfunction subsection later in this section), which often persists for as long as the patient continues taking the medication. 

When significant sexual dysfunction persists for more than 1 month despite a positive response to treatment, a reduction in the dose should be considered. In some cases, this results in a diminution of the symptoms without loss of therapeutic benefit. However, sometimes there is no therapeutic dose that does not cause sexual side effects. In such cases, two strategies are available the antidepressant can be replaced with an alternative, or other dmgs can be prescribed concomitantly to counteract the side effect. The decision... 

Sedation is uncommon and instead many patients will find that these drugs may impair sleep, which is why the dose is best taken in the morning. There is also little effect on psychomotor function. Occasional patients have a small reduction in heart rate but otherwise effects on the cardiovascular system are rare. Epileptic convulsions can occur but are rare and much less common than with tricyclic antidepressants. There is some evidence for potentiation of electroconvulsive therapy (ECT)-induced seizures. Sexual dysfunction is reported, principally delayed ejaculation and anorgasmia. 

Adverse effects of various antidepressants are summarized in Table 30-5. Most common unwanted effects are minor, but they may seriously affect patient compliance the more seriously depressed the patient is, the more likely it is that unwanted effects will be tolerated. Most normal persons find that even moderate doses of many antidepressants cause disagreeable symptoms, especially the classic tertiary amine tricyclics amitriptyline, imipramine, clomipramine, and doxepin. With the SSRIs, transient nausea is the most frequent complaint, and decreased libido and sexual dysfunction create the greatest concerns during maintenance treatment. 

In their review of 12 reported cases, Barnhart et al. (2004) found three cases associated with fluvoxamine, seven with fluoxetine, and two with paroxetine. The apathy states improved or resolved with dose reduction or discontinuation. The authors believed that the syndrome frequently goes undetected despite its significant clinical impact. Opbroek et al. (2002) reported that 80% of patients with SSRI-induced sexual dysfunction reported suffering from treatment-emergent emotional blunting. This is consistent with my clinical observations that so-called sexual dysfunction in patients receiving antidepressants often involves a more generalized loss of interest in both sex and loved ones. 

Overstimulation is a common problem with all SSRIs and most of the newer antidepressants. For Paxil, as in the Prozac studies, agitation and insomnia were among the reasons for the dropouts. As documented on its official label, Paxil displays a similar pattern of stimulant effects insomnia, tremor, nervousness, and anxiety. Like Zoloft, it also produces more somnolence and more sexual dysfunction than Prozac. In fact, somnolence (23.3%) is almost twice as frequent as insomnia (13.3%). 

These data suggest that antidepressant-induced sexual dysfunction is more likely to be associated with agents that greatly potentiate 5HT neurotransmission. This notion is supported by the results of a 6-week doubleblind study of 24 men with premature ejaculation, in which paroxetine (20 mg/day) increased latency to ejaculation six-fold while mirtazapine (30 mg/day) had minimal effect (4). In a randomized, 8-week, double-blind, placebo-controlled study in 450 patients with major depression, fluoxetine (20 -0 mg/day) significantly impaired sexual function, while the noradrenaline re-uptake inhibitor reboxetine had no effect (5). 

In a double-blind, placebo-controlled study in 90 patients with sexual dysfunction who were taking a variety of 5HT re-uptake inhibitor antidepressants, sildenafil (50-100 mg) produced improvement in all aspects of the sexual response in 54% of antidepressant-treated patients compared with a placebo response rate of 4.4% (NNT = 2) (6). This suggests that sildenafil is an effective treatment for antidepressant-induced sexual dysfunction. 

There are many other ways in which SSRIs can interfere with sexual function, for example by causing loss of sexual interest and erectile difficulties. In an open, prospective study of 1000 Spanish patients taking a variety of antidepressants, there was an overall incidence of sexual dysfunction of 59% (15). The highest rates, 60-70%, were found with SSRIs (including fluvoxamine) and venlafax-ine. The lowest rates were found with mirtazepine (24%), nefazodone (8%), and moclobemide (4%). Spontaneous resolution of this adverse effect was uncommon - 80% of subjects had no improvement in sexual function over 6 months of treatment. 

Duloxetine has recently been marketed as an antidepressant in Europe. It inhibits the re-uptake of serotonin and noradrenaline, with minimal effects on other neurotransmitter mechanisms. It is therefore classified as a serotonin and noradrenaline re-uptake inhibitor (SNRI) and is grouped with venlafaxine. The adverse effect profile of duloxetine appears to be similar to that of the SSRIs and venlafaxine. In placebo-controlled trials the most common adverse effects were nausea (37%), dry mouth (32%), dizziness (22%), somnolence (20%), insomnia (20%), and diarrhea (14%). Sexual dysfunction has also been reported. Current data suggest that, unlike venlafaxine, duloxetine does not increase the blood pressure, but further post-marketing surveillance studies will be needed to confirm this (1). 

Antidepressants do constitute the main cause for new sexual dysfunction seen in the average outpatient (Balon Harvey, 1995). Although various kinds of sexual dysfunction may be seen in the context of antidepressant therapy (Table 3.11), the most common manifestations seen in clinical practice are erectile dysfunction, partial or complete anorgasmia, and delayed ejaculation. Resolution of these side effects is critical to ensure treatment adherence and remission and to reduce the stress of the depressive episode on the patient s relationship with a spouse or significant other. When an antidepressant treatment achieves symptom remission but is complicated by sexual dysfunction as a side effect, several strategies have been used to deal with the problem, although the success of each varies from patient to patient (Table 3.12). 

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