PSSD (Post-SSRI Sexual Dysfunction) refers to a cluster of long-lasting sexual side effects that persist after discontinuation of SSRIs and some other classes of antidepressant medications. Sexual symptoms appear to coincide with a broader post-antidepressant syndrome, with persistent neurological symptoms commonly coexisting in individuals with PSSD. Taken individually, or collectively, these adverse effects often lead to profound negative consequences, ruining relationships and severely diminishing quality of life for those affected. This has resulted in suicide in some cases.

Although PSSD and other antidepressant-related disorders are receiving increased media attention and growing interest from the scientific community as of late, there remains a pervasive skepticism among health care providers attending to these patients due to lack of awareness of this condition and a general disbelief in adverse drug reactions enduring long after the offending substance is removed. This dilemma is exacerbated by the fact that affected individuals often experience symptoms emerging or intensifying upon cessation and the fact that symptoms, which were not present prior to commencing the medication, are so easily and wrongfully attributed to psychological disorders for which the medication was prescribed.


Common antidepressants potentially responsible
for persistent side effects:

  • fluoxetine (Prozac)
  • citalopram (Celexa)
  • escitalopram (Lexapro)
  • sertraline (Zoloft)
  • paroxetine (Paxil)
  • fluvoxamine (Luvox)
  • duloxetine (Cymbalta)
  • venlafaxine (Effexor)


Symptoms described by those suffering persistent antidepressant
side effects include the following:




Genital numbness (genital anesthesia)

Decreased or absent libido (sex drive)

Erectile dysfunction

Loss of morning, nocturnal, and spontaneous erections

Lack of vaginal lubrication

Loss of arousal of clitoris and nipples

“Soft glans syndrome” in men

Anorgasmia (difficulty reaching orgasm)

Sexual anhedonia and pleasureless orgasms

Watery semen and decreased semen volume

Emotional blunting and flat affect

Anhedonia (loss of ability to feel pleasure)

Memory impairment

Cognitive impairment

Derealization and depersonalization

Loss of visual imagination

Increased anxiety

Panic attacks


Altered dream state (loss of dreaming or frequent nightmares)

Suicidal ideation

Blurry vision and other visual disturbances



Chronic fatigue and physical weakness

Gastrointestinal disturbances, including diarrhea

Motor control dysfunction (Parkinsonism)


The understanding of antidepressants’ mechanism of action in treating depression remains incomplete and the peripheral effects, and mechanisms of adverse reactions, even more poorly understood. Those suffering relentlessly from PSSD and the long-term side effects of antidepressants are in desperate need of alleviation from symptoms which are predominantly unresponsive to treatment. This will require organized investigation focused on identifying the underlying biological mechanisms that trigger such adverse reactions and maintain their persistence.

Considering the widespread and ever-increasing use of antidepressant medications, it is crucial that factors predisposing patients to this syndrome are identified, and that the prevalence of lasting side effects from antidepressants is ascertained and applied toward future risk/benefit determinations.

It should be noted that PSSD and other persistent side effects differ from Antidepressant Discontinuation Syndrome in that the adverse reactions continue for an indefinite period long after cessation, as opposed to being a withdrawal effect lasting only a few weeks at most.


Related discussion in scientific literature:

Because described gene expression changes are complex, and can involve persistent modifications of chromatin structure, it has been suggested that chronic antidepressant use can result in persistently altered cerebral gene expression leading to compromised catecholaminergic neurotransmission and neuroendocrine disturbances, such as decreased testosterone levels, reduced fertility, and persistent sexual dysfunction.

— A. B. Csoka and M. Szyf, “Epigenetic side-effects of common pharmaceuticals: A potential new field in medicine and pharmacology,” Medical Hypotheses (2009).