Sexual compulsivity and harmful drug use decreased in men who started PrEP in Amsterdam

Image: Lopolo/ Image is for illustrative purposes only.

A longitudinal study of mental health and substance use issues in gay and bisexual men and transgender women who took part in AmPrEP, the Amsterdam-based PrEP demonstration project in the Netherlands, found that some indicators of mental distress declined significantly after PrEP was initiated.

Roel Achterbergh and colleagues from Amsterdam’s large STI clinic – the base for AmPrEP – conducted a series of psychological assessments for different mental health and addiction issues throughout the study.

Using the format of brief, validated questionnaires, they asked AmPrEP participants about their levels of depression and anxiety; about the degree to which their alcohol and other drug use was experienced as problematic; and the degree to which they felt unable to control their sexual behaviour (sexual compulsivity). Participants also reported on their intake of alcohol and drugs and about anxiety specific to acquiring HIV.



A feeling of unease, such as worry or fear, which can be mild or severe. Anxiety disorders are conditions in which anxiety dominates a person’s life or is experienced in particular situations.


A mental health problem causing long-lasting low mood that interferes with everyday life.

event driven

In relation to pre-exposure prophylaxis (PrEP), this dosing schedule involves taking PrEP just before and after having sex. It is an alternative to daily dosing that is only recommended for people having anal sex, not vaginal sex. A double dose of PrEP should be taken 2-24 hours before anticipated sex, and then, if sex happens, additional pills 24 hours and 48 hours after the double dose. In the event of sex on several days in a row, one pill should be taken each day until 48 hours after the last sexual intercourse.


Studies aim to give information that will be applicable to a large group of people (e.g. adults with diagnosed HIV in the UK). Because it is impractical to conduct a study with such a large group, only a sub-group (a sample) takes part in a study. This isn’t a problem as long as the characteristics of the sample are similar to those of the wider group (e.g. in terms of age, gender, CD4 count and years since diagnosis).

longitudinal study

A study in which information is collected on people over several weeks, months or years. People may be followed forward in time (a prospective study), or information may be collected on past events (a retrospective study).

Questionnaires were conducted when people joined the study, at one and two years into it, and at the end of phase 1 of the study (which was up to three years after initiation.)

They found that depression and anxiety in themselves did not decrease; nor did problematic alcohol use. However, they found that problematic drug use (excluding alcohol) decreased significantly and sexual compulsivity decreased very significantly.

Anxiety specifically about HIV infection also decreased significantly. The amount of alcohol people drank (problematic or not) declined during the study, as did the use of two specific drugs (nitrites/poppers and ecstasy/MDMA), though use of other drugs did not decline.

More about the study

AmPrEP started in August 2015 and its first phase continued until September 2018 (it was later extended to June 2020). One of its hallmarks was that it offered people the choice of whether to take daily or ‘2-1-1’ event-driven PrEP and to change between them: 76% opted for daily, and 28.5% changed regimens at least once, with almost the same numbers switching from daily to event-driven as vice versa. No difference in mental health problems or outcomes was seen between users of daily and event-driven PrEP.

The researchers analysed data from 341 participants out of 376 enrolled into AmPrEP. Their average age was 40; two participants (1%) self-defined as transgender women and 15% as non-White; 77% had a university degree and 23% were unemployed. In the three months before joining the study, the participants had an average of 15 sexual partners and 37% used five or more types of drugs.

The questionnaires used to assess participants’ psychological health and behaviours were all short-form self-assessment questionnaires that have been used widely and calibrated for consistency against other assessment tools.

For problematic alcohol and drug use they used the AUDIT and DUDIT (Alcohol/Drug Use Disorders Identification Test) questionnaires (sample question: “How often during the last year have you found that you were not able to stop drinking once you had started? Never, less than monthly, monthly, weekly, daily or almost daily?”) These ten-item questionnaires have a maximal score of 40, with anything over 8 indicating a degree of use that may need discussing - the threshold used in AmPrEP.

For depression and anxiety they used the simple MHI-5 (Mental Health Inventory Five-question) depression and anxiety screening test, which asks five mixed questions about anxiety and depression and their opposites (calmness and happiness), with a maximal score of 100 indicating perfect mental health. AmPrEP used a score of under 60 as indicating some evidence for depression or anxiety.

The Sexual Compulsivity Scale (SCS) was developed in the mid-90s by the pioneering HIV and sexual behavioural scientist Seth Kalichman as a screening test. It asks ten questions with a score of zero to four, so a maximum score of 40 indicating severe sexual compulsivity. A sample question is: “My sexual thoughts and behaviours are causing problems in my life” – you can see the full list in table 1 of this paper. For AmPrEP, a score of 24 or more was regarded as indicating a degree of sexual compulsivity.

At baseline, 20% were assessed as having a depressive or anxiety disorder (as opposed, the researchers note, to 10.5% in the general Dutch population); 38% problematic drug use; 28% problematic drinking; and 23% a degree of sexual compulsivity.

Comparing those initial results with those after starting PrEP, there was no statistically significant change over time in the proportion with depression or anxiety (18% at last visit) or problematic drinking (22% at last visit).

However the decline in problematic drug use was significant (from 38% at baseline to 31% at last visit, p = 0.026) and the decline in sexual compulsivity was striking (from 23% to only 10% at last visit, p = <0.001).

There was also a 12% absolute decline in the proportion of people reporting any one or more of the four problems, from 64% to 52% (a nearly 20% relative decline).

Participants also became less concerned about acquiring HIV over time, with anxiety about HIV changing from a median score of three points to five points, when measured on a seven-point reverse-numbered scale from 7 = “not concerned at all” to 1 = “extremely concerned.”

The specific drugs mentioned by participants other than alcohol at baseline were erectile dysfunction drugs (used by 73%); nitrites/poppers (72%); ecstasy/MDMA (53%); GHB/GBL (42%); cannabis (35%); cocaine (30%); amphetamine (22%); ketamine (21%) and methamphetamine (10%). Only 4% said they had injected drugs. At last visit the proportion who drank frequently or fairly often had declined from 57% to 42%; the proportion using nitrites more than occasionally had declined from 58% to 50%; and the proportion using ecstasy more than occasionally from 19% to 12%. There was no specific increase or decline in the use of other drugs.

"The simultaneous decrease in drug use disorder and sexual compulsivity was unexpected”.

Because mental health conditions wax and wane over time, the researchers also looked at the risk for the four conditions developing or being resolved over time, and whether participant characteristics influenced whether they developed or recovered from problems.

Older participants (aged 45 or older) were twice as likely to develop one or more of the four problems over time compared with participants aged under 35. University educated participants were 70% less likely to develop sexual compulsivity problems than people with less education, but also 80% less likely to resolve this problem if they already had it. People with problematic drug use were more likely to go on to develop problematic drinking too, but not vice versa.

Participants scoring significantly for anxiety were over twice as likely as other participants to develop problematic drug use, and were 70% less likely to resolve problems of sexual compulsivity. This could be seen as strengthening the idea that anxiety about HIV transmission, and maybe generalised anxiety, are strongly linked to not being, or feeling, in control of one’s sexual behaviour.

Discussion and conclusions

The researchers emphasise that their interest in monitoring mental health, substance use and sexual compulsivity during their PrEP trial was motivated by fears that, far from the rates of these declining in their study participants, the reverse might happen.

In August 2015, when AmPrEP started, concerns were commonly expressed among healthcare workers and the gay community that PrEP might disinhibit users, leading to higher levels of sexual compulsivity and substance use, not to mention STIs, and that this would result in worse mental health problems.

They comment that “the simultaneous decrease in drug use disorder and sexual compulsivity was unexpected”. They hypothesise that PrEP relieved its users of the anxiety of catching HIV and that, in turn, this made them feel more in charge of their sexual behaviour (so less compulsive) and less in need of drugs to counteract the inhibiting effect of anxiety.

They emphasise, however, that their study does not show that PrEP caused the improvements in mental health and addiction indicators: AmPrEP also included a counselling session at every three-monthly visit and this, and the general attention of being part of a study, may have been what helped.

As the mental health surveys use the users’ own subjective self-assessment, it’s also possible that, especially in the case of sexual compulsivity, some of the changes might not actually be in people’s behaviour, but in how they felt about the behaviour.

The researchers also emphasise that there were significant unmet mental health needs among their study participants, regardless of any improvement after starting PrEP. More than half of participants still reported at least one of the four problems at their last visit, yet only 18% reported visiting a health professional for specific help with them, compared with 34% of the general Dutch population who have similar problems. In addition, 27% reported ever experiencing a drink- or drug-induced blackout; 6% reported intimate partner violence in the last five years; and 14% reported ever having a non-consensual sexual experience.

The study adds, however, to a number of other studies that find reduced levels of anxiety and other mental health issues in PrEP users, which are related to starting PrEP.