Key points from the evidence
The content of this evidence summary was up-to-date in July 2015. See summaries of product characteristics (SPCs), British national formulary (BNF) or the MHRA or NICE websites for up-to-date information.
No randomised controlled trials (RCTs) which evaluate the use of fluoxetine in the treatment of hypersexuality were found, nor any studies that compared fluoxetine with any of the hormonal treatments licensed to treat hypersexuality. Limited evidence from 3 small, short‑term observational studies suggests that fluoxetine may improve some measurements of hypersexuality and sexual preoccupation in men who have either been convicted of a sexual offence or who have a paraphilia or a non-paraphilic sexual addiction. However, these studies had a number of limitations which make it difficult to draw conclusions on the use of fluoxetine for this indication.
Regulatory status: off‑label. This topic was prioritised because of the potential for variation in practice and because there is uncertainty about the balance of risks and benefits of fluoxetine for the treatment of hypersexuality.
Hypersexuality is unusual or excessive concern with or indulgence in sexual activity. Sometimes hypersexuality is associated with a medical condition, such as dementia, or is an adverse effect of drug treatment, for example in Parkinson's disease.
The 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) notes that most people with atypical sexual interests such as hypersexuality do not have a mental health disorder. DSM‑5 aims to differentiate between atypical human behaviour and behaviour that causes mental distress to a person or makes the person a serious threat to the psychological and physical well‑being of other individuals. DSM‑5 states that certain criteria should be met for people with atypical sexual interests to be diagnosed with a paraphilic disorder.
People with hypersexuality may be treated with medication to reduce libido. These medications broadly fit within 2 categories: hormonal medications that have a testosterone‑suppressing effect and non‑hormonal medications that affect libido through other mechanisms. Hormonal drug therapy includes anti‑androgens (for example, cyproterone acetate) and gonadotropin‑releasing hormone (GnRH) analogues (for example, triptorelin). Non‑hormonal drug therapy includes antipsychotics (off‑label use) and selective serotonin reuptake inhibitors (off‑label use) [Khan et al. 2015].
Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) antidepressant (summaries of product characteristics). Fluoxetine is not licensed for the treatment of hypersexuality; therefore use for this indication is off‑label.
This evidence summary concentrates on the management of people with hypersexuality not associated with a medical condition including those in prison convicted of a sexual offence and people with a paraphilia or paraphilic disorder. No randomised controlled trials (RCTs) were found.
This evidence summary is based on 3 observational studies: 1 included 64 men who had been convicted of sexual offences (Winder et al. 2014), and the others included 20 men and 58 men respectively with a paraphilia (for example, paedophilia or sexual masochism) or non‑paraphilic sexual addiction (for example, compulsive masturbation) [Kafka and Prentky 1992 and Greenberg et al. 1996].
Winder et al. 2014 included 64 men convicted of a sexual offence (the majority of whom had committed sexual offences against children) who had been referred for treatment for hypersexuality: 36 received fluoxetine, 5 received cyproterone (after initial fluoxetine treatment was ineffective) and 7 received a combination of fluoxetine and cyproterone. Hypersexuality was measured by asking participants how many days in the previous week they had masturbated to orgasm. After 3 months' treatment, this was reduced from 3.67 days at baseline to 1.10 days in the fluoxetine group and from 3.97 days to 1.70 days in the cyproterone group. Sexual preoccupation was assessed by asking: 'how much time do you spend thinking about sex?' measured on a scale from 1 (low) to 7 (high). After 3 months' treatment there was a reduction from 4.71 at baseline to 2.00 in the fluoxetine group and from 5.60 to 2.80 in the cyproterone group. Sexual compulsivity was also assessed by asking relevant questions scored on a scale from 1 (not like me at all) to 4 (very much like me). The mean score reduced from 2.68 to 1.20 in the fluoxetine group and from 3.08 to 1.15 in the cyproterone group. For the combined group, there were statistically significant improvements from baseline in hypersexuality, sexual preoccupation and sexual compulsivity. The clinical significance of the findings however is unclear.
In Kafka and Prentky 1992 participants were self‑referred by responding to a newspaper advertisement inviting people to participate in a study evaluating the treatment of sexual addictions and compulsions. The majority of the participants (19 out of 20) reported chronic depressive symptoms lasting more than 2 years. Fluoxetine was started at an initial dose of 20 mg daily and titrated to a mean dose of 39 mg daily, but there was no comparator arm of the study. Sexual behaviour was assessed using an unpublished and un‑validated self‑assessment tool. Total sexual outlet (defined as the total number of sexual activities in the measured week that either led to orgasm or would have done so had voluntary restraint not been utilised) was calculated using data obtained from the assessment tool. There was a statistically significant reduction in mean total sexual outlet from 10.6 at baseline to 3.6 at week 12 (p<0.001).
Greenberg et al. 1996 included 58 men treated in a sexual behaviours clinic with 1 of 3 SSRIs (sertraline [n=25], fluoxetine [n=17] or fluvoxamine [n=16]). Outcomes included severity of sexual fantasies measured on a scale from 0 to 4. Results were presented for the whole group rather than for each individual SSRI, although it was reported that no differences were seen between them (no statistical analysis was provided). For the whole group, there were statistically significant decreases in the fantasy severity score from baseline to week 4 (p<0.001), from week 4 to week 8 (p<0.05) but not from week 8 to week 12 (no p value reported). The severity of fantasy score for the group was approximately 2 (moderate, frequent, disturbing, less able to stop) at baseline, approximately 1 (mild, occasional, not too disturbing, easily able to stop) at week 4 and approximately 0.75 at week 8.
Fluoxetine has a well‑documented adverse effect profile and the summaries of product characteristics (SPCs) contain a number of special warnings and precautions for use (for example: Prozac). From the studies discussed in this evidence summary, neither Winder et al. 2014 nor Kafka and Prentky 1992 reported any safety data. In Greenberg et al. 1996 adverse effects were reported for all 3 SSRIs combined rather than individually, although it was reported that no differences were seen between them. Similar to those listed in the SPCs, the most common adverse effects reported included insomnia, delayed ejaculation, headaches, drowsiness, reduced sex drive, diarrhoea, nausea and blurred vision.
Overall, the 3 small short‑term observational studies included in this evidence summary provide very limited data on the use of fluoxetine to treat hypersexuality. None of the studies included a control group and none were randomised or blinded and so they are all subject to bias and confounding factors. All of the studies used self‑reporting tools to assess sexual behaviour or sexual preoccupation and the validity of the results is unclear. Specialists who commentated on this evidence summary highlighted that more objective measures of hypersexuality and sexual preoccupation may have been more appropriate for this group of people. The reliability of using self‑reported data where there may be vested interests in reporting positives responses to treatment in terms of progressing with sentencing for instance is unclear.
All of the studies were in men (mean age around 40 years) and the majority of the participants (approximately 93%) had been convicted of a sexual offence or had a paraphilia. The studies provide no information on the use of fluoxetine to treat hypersexuality in the longer‑term. Kafka and Prentky 1992 assessed the effect of treatment on concomitant depressive symptoms; however the other 2 studies did not assess the effect of treatment on any concomitant mental health disorder.
Cyproterone acetate (Androcur) is licensed for the control of libido in severe hypersexuality or sexual deviation in the adult male. Triptorelin (Salvacyl) is licensed for the reversible reduction of testosterone to castrate levels in order to decrease sexual drive in adult men with severe sexual deviations. Cyproterone acetate (Androcur) costs approximately £376 for 12 months treatment at a dose of 50 mg twice a day. Triptorelin (Salvacyl) costs approximately £992 for 12 months treatment at the licensed dose of 11.25 mg (1 vial) every 12 weeks.
A plain English summary is available on the NICE website. This sets out the main points from the evidence summary in non‑technical language and may be especially helpful for people with hypersexuality who are thinking about trying fluoxetine.
About this evidence summary
'Evidence summaries: unlicensed or off‑label medicines' summarise the published evidence for selected unlicensed or off‑label medicines that are considered to be of significance to the NHS, where there are no clinically appropriate licensed alternatives. The summaries provide information for clinicians and patients to inform their decision‑making and support the construction and updating of local formularies.
The summaries support decision‑making on the use of an unlicensed or off‑label medicine for an individual patient, where there are good clinical reasons for its use, usually when there is no licensed medicine for the condition requiring treatment, or the licensed medicine is not appropriate for that individual.
The strengths and weaknesses of the relevant evidence are critically reviewed within this summary, but this summary is not NICE guidance.