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Serotonergic activity estimated by EEG loudness-dependent auditory evoked potentials as a predictor of sexual SSRI side effects.

G. D. Ketilsdottir,C. Ip,V. Frokjaer,A. Giraldi,M. Jørgensen,K. R. Reveles Jensen

Published 2025 in Journal of Psychiatric Research

ABSTRACT

BACKGROUND Sexual disturbance is a common symptom of major depressive disorder (MDD) and may be aggravated by selective Serotonin Reuptake Inhibitors (SSRIs), potentially due to elevated serotonergic activity. Loudness Dependence of the Auditory Evoked Potential (LDAEP), an EEG-based biomarker inversely linked to serotonergic activity, may help predict sexual side-effects. We investigated whether pretreatment LDAEP is associated with SSRI-related sexual side-effects and pretreatment sexual function in unmedicated patients with MDD. METHOD LDAEP was obtained from 90 unmedicated patients with MDD (aged 18-56, 73 % female) before eight-week treatment with escitalopram. Sexual function was measured before and after treatment, together with sexual SSRI side-effects. We used linear and logistic regressions adjusted for age, sex, and pretreatment depressive sexual disturbances. RESULTS LDAEP was negatively associated with the degree of SSRI-related orgasmic dysfunction at week eight (ß = -0.27, 95 % CI [-0.53; -0.014], p = 0.039) and predicted orgasmic dysfunction with 87 % accuracy (AUC = 0.85, 95 % CI [0.74; 0.97], p = 0.009). LDAEP was also marginally negatively associated with the degree of SSRI-related decreased libido (ß = -0.23, 95 % CI [-0.45; 0.00], p = 0.050) but did not significantly predict reduced libido (AUC = 0.83, 95 % CI [0.68; 0.98], p = 0.086). LDAEP was not associated with pretreatment sexual function. CONCLUSION Low pretreatment LDAEP, indicating high serotonergic activity, was associated with increased SSRI-related sexual side-effects, predominantly difficulty reaching orgasm. With further validation, LDAEP could be a useful biomarker to guide antidepressant treatment to minimise sexual side-effects.

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