Post Selective Serotonin Reuptake Inhibitor (SSRI) Sexual Dysfunction (PSSD) is characterised by new onset sexual dysfunction whilst taking SSRI antidepressants that persists after discontinuation. Patients may present to neurology services reporting genital sensory impairment; however, the neurological basis of this symptom in PSSD remains poorly characterised. This study aimed to phenotype the neurological and pelvic neurophysiology findings in patients fulfilling PSSD diagnostic criteria, and to compare these with patients presenting with genital sensory impairment due to alternate causes.

This was a cross-sectional observational study of consecutive patients referred to a tertiary referral unit for assessment of genital sensory impairment, between May 2019 and May 2024. Patients were classified as having PSSD according to published diagnostic criteria (1). Clinical history, neurological examination and pelvic neurophysiology test results were reviewed. A focused sensory examination was carried out using von Frey hairs (vFH) and a Neurotip to assess tactile sensation and nociception respectively. Pelvic neurophysiology testing included tibial somatosensory evoked potentials (SEPs), S2 and S3 dermatomal SEPs, and pudendal SEPs, to evaluate sacral somatic sensory integrity (2). Statistical significance was assessed using Fisher's exact test (p<0.05).

Of 55 patients presenting with genital sensory impairment, nine patients (mean age 35 years [range 20-47], eight males) fulfilled the PSSD diagnostic criteria (1). All nine PSSD patients had abnormal findings on clinical sensory examination using neurotip or vFH. Sensory loss was most apparent over the glans, distal and mid-shaft of the penis, which was symmetrical and more pronounced on the ventral than dorsal surface (Figure 1). There were no statistically significant differences in neurotip (55.5% vs 56.5%, p=1.00) or vFH (66.6% vs 43.5%, p=0.281) abnormality rates between PSSD and non-PSSD patients. However, PSSD patients were significantly more likely to report ejaculatory dysfunction (75% vs 20%, p=0.0055) and had higher rates of sexual dysfunction (100% vs 65.2%, p=0.046). Pelvic neurophysiology findings were normal in eight of the nine PSSD patients (88.9%), with no significant group differences in pudendal SEP, tibial SEP, or dermatomal SEP abnormality rates.

There is a mismatch between clinically demonstrable genital sensory impairment on examination and normal objective pelvic neurophysiology results in patients with PSSD. Normal SEP studies effectively exclude a significant peripheral large-fibre neuropathy or central sensory pathway dysfunction - involving the dorsal columns - as the underlying cause. This mismatch suggests that the sensory impairment in PSSD reflects a central disturbance of erogenous sensation processing rather than peripheral nerve damage. Erogenous sensation involves integration of somatosensory input with higher-order limbic and reward circuits, which involves dopaminergic pathways. Sustained serotonergic activity from SSRI use may cause lasting dysregulation of these systems, disrupting the ability of peripheral tactile stimuli to activate the emotional and pleasure-based responses underpinning erogenous sensation. The predominance of sensory loss over the glans and distal shaft of the penis is consistent with known anatomical maps of erogenous sensitivity in males. The high frequency of ejaculatory dysfunction in PSSD patients may represent a useful clinical marker to distinguish PSSD from other causes of genital sensory impairment in the neurological setting.

This study provides the first detailed neurological characterisation of PSSD-related genital sensory impairment.    Neurophysiology findings are predominantly normal  and supports a centrally-mediated mechanism rather than a peripheral one. Awareness about PSSD amongst health care professionals as a cause of genital sensory impairment is important, as the association with prior SSRI use may not be immediately apparent.

Healy, D., Bahrick, A., Bak, M., Barbato, A., Calabrò, R.S., Chubak, B.M., Cosci, F., et al. (2022). Diagnostic criteria for enduring sexual dysfunction after treatment with antidepressants, finasteride and isotretinoin. International Journal of Risk & Safety in Medicine, 33(1), pp.65–76. doi: https://doi.org/10.3233/jrs-210023
Jalesh N. Panicker, Sara Simeoni, Sarah Wright, Claire Hentzen, Prasad Malladi. Applications of pelvic neurophysiology testing in clinical practice.  Clinical Neurophysiology Practice 11 (2026) 142–162.