Introduction

Close to 100% of takers of a selective serotonin reuptake inhibitor (SSRI) have a degree of genital sensory change within 30 min of taking. These effects consist primarily of a reduced sensitivity, often termed ‘numbing’ by those affected but others have genital arousal (irritability). The reduced sensitivity is accompanied by an immediate delay of ejaculation in men and muting of orgasm in both men and women. After a period of treatment, orgasm may stop and there may be a loss of libido (Healy et al., Reference Healy, Le Noury and Mangin2018a).

The ‘numbing’ effect produced by SSRIs has similarities to the effect of rubbing lidocaine into the genital area, which was a prior treatment for premature ejaculation, and SSRIs in single doses are used for premature ejaculation now. The effect is also described in terms of a loss of pleasurable sensation. In some cases, there is an actual genital numbing equivalent to that produced by lidocaine.

These immediate onset sexual effects ordinarily lift when treatment stops. In 2006, reports appeared of a condition now termed post-SSRI sexual dysfunction (PSSD), in which the genital numbing, pleasureless or absent ejaculation/orgasm, and loss of libido remain and may become more pronounced after treatment stops (Bahrick, Reference Bahrick2006; Csoka and Shipko, Reference Csoka and Shipko2006). PSSD can persist for decades afterwards (Healy et al., Reference Healy, Le Noury and Mangin2018a, Reference Healy, Le Noury and Mangin2018b).

In 2001, persistent genital arousal disorder (PGAD), an enduring disorder of irritable genital sensation was described (Leiblum and Nathan, Reference Leiblum and Nathan2001). This condition is not linked to enhanced libido and does not stem from psychological issues. At present PGAD appears to affect women more than men. This condition seems more likely to happen around the menopause, and while closely related to discontinuation from SSRI medication, can also occur following trauma to the genital area (Healy et al., Reference Healy, Le Noury and Mangin2018a).

These genital effects do not occur on antidepressants that do not inhibit serotonin reuptake; other antidepressants and psychotropic drugs can cause erectile dysfunction but not the syndromes of numbness, pleasureless orgasm, loss of libido or persistent arousal.

Two other syndromes have been described which appear closely related to PSSD. One is post-finasteride syndrome (PFS). First described in 2011, this occurs in young men taking finasteride to stall hair loss (Irwig and Kolukula, Reference Irwig and Kolukula2011). It also occurs with other 5-α reductase inhibitors – dutasteride and saw palmetto. Genital anaesthesia, loss of libido and sexual dysfunction are features of this syndrome. Initial finasteride treatment can produce some sexual dysfunction, but this is less common when compared with SSRIs. It is unclear if the sexual dysfunction that appears on treatment is continuous with PFS or distinct from it.

A post-retinoid sexual dysfunction (PRSD) has also been described (Hogan et al., Reference Hogan, Le Noury, Healy and Mangin2014). This also includes genital anaesthesia, sexual dysfunction and loss of libido. There can be some sexual dysfunction on initial treatment in patients taking isotretinoin for acne, but it is not clear what continuity there may be between this and PRSD.

These enduring post-treatment syndromes may interface with tardive dyskinesia linked to antipsychotic drugs in the 1960s. Antipsychotics can cause dyskinesias on treatment, which ordinarily resolve when treatment is stopped. Dyskinesias can also emerge on withdrawal but clear up in time. Tardive dyskinesia is a syndrome that involves dyskinetic movements centred on the jaw and lower facial area, which can emerge on treatment but become more marked when treatment stops. The syndrome can endure for years or decades afterwards.

These legacy effects of antidepressants and antipsychotics have some interface with withdrawal syndromes linked to these drugs. Withdrawal to opioids and alcohol is viewed as limited to a few weeks, having features not found during administration of the drug and as ordinarily responding to re-institution of treatment. Antidepressant and antipsychotic withdrawal however is linked to dysthymia, which may appear to be continuous with the original problem but can be demonstrated in healthy volunteers given these drugs, as well as to other sensory and autonomic disturbances. These states can last for months or longer, opening up a possible link between enduring sexual syndromes and other legacy effects of antidepressants and antipsychotics (Healy and Tranter, Reference Healy and Tranter1999).

There are variations among antidepressants and antipsychotics in their likelihood of causing withdrawal problems and likelihood of causing tardive syndromes but the basis for these differences is not understood.