Reference · 13 drugs

Implicated medications

Drugs whose persistent post-treatment effects the corpus covers, with their mechanism and what regulators' labels say about persistence.

A list of implicated drugs is not prescribing information

This page documents which medications the research concerns. It is not advice to start, stop or change any medication — talk to the prescribing clinician.

Drug classes

5-alpha reductase inhibitors

5ARI

Block conversion of testosterone to dihydrotestosterone (DHT) and 5-alpha reduction of progesterone, corticosteroids and other steroids, depleting neurosteroids such as allopregnanolone.

finasteride dutasteride

Selective serotonin reuptake inhibitors

SSRI

Block the serotonin transporter (SERT), raising synaptic serotonin; downstream effects include 5-HT1A desensitization, dopamine inhibition, and (per Xie 2026) allopregnanolone depletion via 5-alpha-reductase inhibition.

citalopram escitalopram fluoxetine fluvoxamine paroxetine sertraline

Serotonin-norepinephrine reuptake inhibitors

SNRI

Block SERT and the norepinephrine transporter (NET); included in the 2019 EMA persistence warning alongside SSRIs.

desvenlafaxine duloxetine milnacipran venlafaxine

Systemic retinoids

RETINOID

Isotretinoin is a 13-cis-retinoic acid retinoid that shrinks sebaceous glands; proposed links to sexual dysfunction include testicular steroidogenesis effects and mood effects (Health Canada review).

isotretinoin

SSRI/SNRI class labeling note

EMA PRAC (May 2019): product information for SSRIs/SNRIs amended with the sentence 'There have been reports of long-lasting sexual dysfunction where the symptoms have continued despite discontinuation of SSRIs/SNRI.' Ten substances named: citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, desvenlafaxine, duloxetine, milnacipran, venlafaxine. UK updated the same year; Australia TGA aligned 2024; Health Canada followed; US FDA had not added an equivalent persistence warning as of the sources found. Fluoxetine label warned since 2011 that 'symptoms of sexual dysfunction occasionally persist after discontinuation.'

Drugs

finasteride
5-alpha reductase inhibitor (5-ARI)
PFS
Brands: Propecia (1 mg, androgenic alopecia) · Proscar (5 mg, BPH)
Mechanism: Inhibits type II (and at 5 mg also type I/III) 5-alpha-reductase, blocking testosterone-to-DHT conversion and 5-alpha reduction of progesterone, cortisol, aldosterone and other steroids; this depletes neurosteroids including allopregnanolone (Melcangi CSF studies).
Labeling: FDA (April 2012): labels of finasteride 1 mg and 5 mg revised to indicate sexual side effects may persist after discontinuation. Propecia label notes 'sexual dysfunction that continued after discontinuation of treatment, including erectile dysfunction, libido disorders, ejaculation disorders, and orgasm disorders.'
Cited in:PFS-001 PFS-002 PFS-004 PFS-005 PFS-006 PFS-007 PFS-009 PFS-010 PFS-011 PFS-012 CROSS-001 CROSS-002
dutasteride
5-alpha reductase inhibitor (5-ARI)
PFS
Brands: Avodart (0.5 mg, BPH) · Jalyn (dutasteride + tamsulosin)
Mechanism: Dual inhibitor of 5-alpha-reductase types I and II; same downstream neurosteroid depletion as finasteride, with longer half-life.
Labeling: Included in the 5-ARI class warnings on persistent sexual dysfunction (see finasteride); Belknap PeerJ analysis covered finasteride and dutasteride together.
Cited in:PFS-001 PFS-012
citalopram
SSRI
PSSD
Brands: Celexa
Mechanism: SERT blockade; see class note.
Cited in:PSSD-001 PSSD-002 PSSD-006 CROSS-001 CROSS-002
escitalopram
SSRI
PSSD
Brands: Lexapro
Mechanism: S-enantiomer of citalopram; SERT blockade; see class note.
Cited in:PSSD-001 PSSD-002 CROSS-001 CROSS-002
fluoxetine
SSRI
PSSD
Brands: Prozac
Mechanism: SERT blockade; long half-life; see class note.
Labeling: US label since 2011 warned that 'symptoms of sexual dysfunction occasionally persist after discontinuation' (per Drug Safety review, 2025).
Cited in:PSSD-001 PSSD-002 CROSS-001 CROSS-002
fluvoxamine
SSRI
PSSD
Brands: Luvox
Mechanism: SERT blockade with sigma-1 activity; see class note.
Cited in:PSSD-001 CROSS-001 CROSS-002
paroxetine
SSRI
PSSD
Brands: Paxil
Mechanism: SERT blockade; most-studied SSRI in the corpus preclinical series — shown to perturb neurosteroidogenesis in rat brain (PSSD-009), bind a novel off-target protein (PSSD-010), alter colonic steroidogenesis and microbiota (PSSD-011), and produce persistent transcriptomic changes in hypothalamus/nucleus accumbens after withdrawal (PSSD-012).
Cited in:PSSD-009 PSSD-010 PSSD-011 PSSD-012 PSSD-001 PSSD-002
sertraline
SSRI
PSSD
Brands: Zoloft
Mechanism: SERT blockade with mild dopamine transporter activity; see class note.
Cited in:PSSD-001 PSSD-002 PSSD-006 CROSS-001 CROSS-002
desvenlafaxine
SNRI
PSSD
Brands: Pristiq
Mechanism: SERT + NET blockade; included in 2019 EMA persistence warning.
Cited in:PSSD-001 CROSS-002
duloxetine
SNRI
PSSD
Brands: Cymbalta
Mechanism: SERT + NET blockade; included in 2019 EMA persistence warning.
Cited in:PSSD-001 CROSS-001 CROSS-002
milnacipran
SNRI
PSSD
Brands: Savella
Mechanism: SERT + NET blockade (relatively more noradrenergic); included in 2019 EMA persistence warning.
Cited in:PSSD-001 CROSS-002
venlafaxine
SNRI
PSSD
Brands: Effexor
Mechanism: SERT + NET blockade (dose-dependent); included in 2019 EMA persistence warning; cited in Csoka 2008 case reports.
Cited in:PSSD-001 PSSD-004 CROSS-001 CROSS-002
isotretinoin
Retinoid (13-cis-retinoic acid)
PRSD
Brands: Accutane (original brand, discontinued) · Absorica · Absorica LD · Claravis · Amnesteem · Myorisan · Zenatane · Roaccutane (UK) · Epuris (Canada)
Mechanism: Shrinks sebaceous glands and alters keratinization for severe acne; proposed sexual-dysfunction links include effects on testicular steroidogenesis/testosterone and mood (Health Canada safety review); mechanism of persistent post-retinoid dysfunction not established.
Labeling: FDA label centers on teratogenicity under the iPLEDGE REMS. Erectile dysfunction is mentioned in the product information for Epuris (isotretinoin, Canada) and Soriatane (acitretin). Health Canada (2015) safety review assessed impotence reports with oral retinoids. UK MHRA tightened prescribing controls with monitoring of sexual side effects. No EU-style 'persists after discontinuation' sentence found for isotretinoin in the sources reviewed.
Cited in:CROSS-001 CROSS-002

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Drug classes

5-alpha reductase inhibitors

5ARI

Block conversion of testosterone to dihydrotestosterone (DHT) and 5-alpha reduction of progesterone, corticosteroids and other steroids, depleting neurosteroids such as allopregnanolone.

finasteride dutasteride

Selective serotonin reuptake inhibitors

SSRI

citalopram escitalopram fluoxetine fluvoxamine paroxetine sertraline

Serotonin-norepinephrine reuptake inhibitors

SNRI

Block SERT and the norepinephrine transporter (NET); included in the 2019 EMA persistence warning alongside SSRIs.

desvenlafaxine duloxetine milnacipran venlafaxine

Systemic retinoids

RETINOID

Isotretinoin is a 13-cis-retinoic acid retinoid that shrinks sebaceous glands; proposed links to sexual dysfunction include testicular steroidogenesis effects and mood effects (Health Canada review).

isotretinoin

SSRI/SNRI class labeling note

Drugs

finasteride

5-alpha reductase inhibitor (5-ARI)

PFS

Brands: Propecia (1 mg, androgenic alopecia) · Proscar (5 mg, BPH)

Mechanism: Inhibits type II (and at 5 mg also type I/III) 5-alpha-reductase, blocking testosterone-to-DHT conversion and 5-alpha reduction of progesterone, cortisol, aldosterone and other steroids; this depletes neurosteroids including allopregnanolone (Melcangi CSF studies).

Labeling: FDA (April 2012): labels of finasteride 1 mg and 5 mg revised to indicate sexual side effects may persist after discontinuation. Propecia label notes 'sexual dysfunction that continued after discontinuation of treatment, including erectile dysfunction, libido disorders, ejaculation disorders, and orgasm disorders.'

Cited in:PFS-001 PFS-002 PFS-004 PFS-005 PFS-006 PFS-007 PFS-009 PFS-010 PFS-011 PFS-012 CROSS-001 CROSS-002

dutasteride

5-alpha reductase inhibitor (5-ARI)

PFS

Brands: Avodart (0.5 mg, BPH) · Jalyn (dutasteride + tamsulosin)

Mechanism: Dual inhibitor of 5-alpha-reductase types I and II; same downstream neurosteroid depletion as finasteride, with longer half-life.

Labeling: Included in the 5-ARI class warnings on persistent sexual dysfunction (see finasteride); Belknap PeerJ analysis covered finasteride and dutasteride together.

Cited in:PFS-001 PFS-012

citalopram

SSRI

PSSD

Brands: Celexa

Mechanism: SERT blockade; see class note.

Cited in:PSSD-001 PSSD-002 PSSD-006 CROSS-001 CROSS-002

escitalopram

SSRI

PSSD

Brands: Lexapro

Mechanism: S-enantiomer of citalopram; SERT blockade; see class note.

Cited in:PSSD-001 PSSD-002 CROSS-001 CROSS-002

fluoxetine

SSRI

PSSD

Brands: Prozac

Mechanism: SERT blockade; long half-life; see class note.

Labeling: US label since 2011 warned that 'symptoms of sexual dysfunction occasionally persist after discontinuation' (per Drug Safety review, 2025).

Cited in:PSSD-001 PSSD-002 CROSS-001 CROSS-002

fluvoxamine

SSRI

PSSD

Brands: Luvox

Mechanism: SERT blockade with sigma-1 activity; see class note.

Cited in:PSSD-001 CROSS-001 CROSS-002

paroxetine

SSRI

PSSD

Brands: Paxil

Mechanism: SERT blockade; most-studied SSRI in the corpus preclinical series — shown to perturb neurosteroidogenesis in rat brain (PSSD-009), bind a novel off-target protein (PSSD-010), alter colonic steroidogenesis and microbiota (PSSD-011), and produce persistent transcriptomic changes in hypothalamus/nucleus accumbens after withdrawal (PSSD-012).

Cited in:PSSD-009 PSSD-010 PSSD-011 PSSD-012 PSSD-001 PSSD-002

sertraline

SSRI

PSSD

Brands: Zoloft

Mechanism: SERT blockade with mild dopamine transporter activity; see class note.

Cited in:PSSD-001 PSSD-002 PSSD-006 CROSS-001 CROSS-002

desvenlafaxine

SNRI

PSSD

Brands: Pristiq

Mechanism: SERT + NET blockade; included in 2019 EMA persistence warning.

Cited in:PSSD-001 CROSS-002

duloxetine

SNRI

PSSD

Brands: Cymbalta

Mechanism: SERT + NET blockade; included in 2019 EMA persistence warning.

Cited in:PSSD-001 CROSS-001 CROSS-002

milnacipran

SNRI

PSSD

Brands: Savella

Mechanism: SERT + NET blockade (relatively more noradrenergic); included in 2019 EMA persistence warning.

Cited in:PSSD-001 CROSS-002

venlafaxine

SNRI

PSSD

Brands: Effexor

Mechanism: SERT + NET blockade (dose-dependent); included in 2019 EMA persistence warning; cited in Csoka 2008 case reports.

Cited in:PSSD-001 PSSD-004 CROSS-001 CROSS-002

isotretinoin

Retinoid (13-cis-retinoic acid)

PRSD

Brands: Accutane (original brand, discontinued) · Absorica · Absorica LD · Claravis · Amnesteem · Myorisan · Zenatane · Roaccutane (UK) · Epuris (Canada)

Mechanism: Shrinks sebaceous glands and alters keratinization for severe acne; proposed sexual-dysfunction links include effects on testicular steroidogenesis/testosterone and mood (Health Canada safety review); mechanism of persistent post-retinoid dysfunction not established.

Labeling: FDA label centers on teratogenicity under the iPLEDGE REMS. Erectile dysfunction is mentioned in the product information for Epuris (isotretinoin, Canada) and Soriatane (acitretin). Health Canada (2015) safety review assessed impotence reports with oral retinoids. UK MHRA tightened prescribing controls with monitoring of sexual side effects. No EU-style 'persists after discontinuation' sentence found for isotretinoin in the sources reviewed.

Cited in:CROSS-001 CROSS-002