What is Post-Selective Serotonin Reuptake Inhibitor (SSRI) syndrome?

From the Guidelines

Post-SSRI syndrome is a condition where sexual side effects persist after discontinuing selective serotonin reuptake inhibitor (SSRI) antidepressants, and currently, there is no established treatment protocol, but management typically involves a multidisciplinary approach including sexual therapy, psychological support, and symptom-targeted medications. The symptoms of Post-SSRI syndrome can include decreased libido, erectile dysfunction, genital numbness, delayed or absent orgasm, and reduced pleasure during sexual activity 1. Some clinicians try medications like bupropion (starting at 150mg daily, potentially increasing to 300mg), buspirone (15-30mg daily), or sildenafil (50-100mg as needed) to address specific symptoms. Key considerations for managing Post-SSRI syndrome include:

• A multidisciplinary approach including sexual therapy and psychological support
• Symptom-targeted medications, which may include bupropion, buspirone, or sildenafil
• Patient education on the variability of recovery time, which can range from months to years
• Open communication with healthcare providers to develop personalized management strategies The syndrome likely results from neuroplastic changes in serotonergic pathways and possible epigenetic modifications affecting sexual function 1. Some patients report benefits from supplements like maca root (1500-3000mg daily) or ginkgo biloba (120-240mg daily), though evidence is limited 1. It is essential to note that the use of SSRIs can lead to various side effects, including suicidal thinking and behavior, behavioral activation/agitation, hypomania, mania, sexual dysfunction, seizures, abnormal bleeding, and serotonin syndrome 1. Therefore, close monitoring for these side effects, especially in the first months of treatment and following dosage adjustments, is crucial. Additionally, slow up-titration and close monitoring (particularly in younger children) are recommended to minimize the risk of dose-related behavioral activation/agitation. Overall, the management of Post-SSRI syndrome requires a comprehensive and individualized approach, taking into account the patient's specific symptoms, medical history, and treatment goals.

From the Research

Definition and Recognition of Post-SSRI Syndrome

• Post-SSRI Sexual Dysfunction (PSSD) is a condition where patients experience sexual side effects after discontinuing Selective Serotonin Reuptake Inhibitors (SSRIs) or Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) 2, 3, 4.
• PSSD has been recognized by the European Medicines Agency as a medical condition that can persist after discontinuation of SSRIs and SNRIs 2, 4.

Symptoms of Post-SSRI Syndrome

• Common symptoms of PSSD include genital anesthesia, pleasure-less or weak orgasm, decreased sex drive, erectile dysfunction, and premature ejaculation 3, 4.
• Additional non-sexual symptoms have been reported, including anhedonia, apathy, and blunted affect 4.
• A case study reported symptoms of low libido, delayed ejaculation, erectile dysfunction, 'brain zaps', overactive bladder, and urinary inconsistency after discontinuation of the SNRI venlafaxine 2.

Pathophysiology and Risk Factors

• The underlying mechanisms of PSSD are unclear, but several theories have been proposed, including epigenetic gene expression, dopamine-serotonin interactions, serotonin neurotoxicity, and hormonal changes 3, 4.
• Precipitating factors for PSSD may include previous exposure to certain drugs, genetic predisposition, psychological stress, or chemical stressful reaction to antidepressants, along with pre-existing medical conditions affecting neuroplasticity 4.
• A study suggested that dysregulation in serotonergic activity, including 5-HT1A receptor downregulation, may play a role in the development of PSSD 2.

Diagnosis and Treatment

• The diagnosis of PSSD is achieved by excluding all other etiologies of sexual dysfunction 3, 4.
• Treatment of PSSD is challenging, and many strategies have been suggested, including serotonergic antagonists and dopaminergic agonists, but there is no definitive treatment 3, 4.
• Low-power laser irradiation and phototherapy have shown some promising results in treating PSSD 3.