Clinical Cases in Pharmacology Clinical Cases  ·  Psychiatry I  ·  Depression  ·  Managing SSRI-Induced Sexual Dysfunction
Psychiatry Vol. I, Case 0009 — Depression

Managing SSRI-Induced Sexual Dysfunction

Sertraline has kept his depression in remission for a year — the erectile and ejaculatory side effects it caused are now straining his marriage enough that stopping the drug is genuinely on the table.

Abbreviations, terms, and other agents mentioned in this case SSRI — selective serotonin reuptake inhibitor  ·  NDRI — norepinephrine-dopamine reuptake inhibitor  ·  PDE5 — phosphodiesterase type 5  ·  PHQ-9 — Patient Health Questionnaire-9, a depression severity scale
Presentation

M.R., a 41-year-old high-school football coach who has been married for twelve years, started sertraline just over a year ago for a moderate-to-severe depressive episode following his father's death, and reached full remission — PHQ-9 consistently under 4 — within the first three months at 150mg. He has no other chronic illness, no cardiac disease, and no prior antidepressant trials before this one; sertraline has, by every measure his psychiatrist tracks, worked.

What it has also done, since roughly the second month of treatment, is cause erectile difficulty and a marked delay in reaching orgasm severe enough that intercourse has become a source of frustration rather than intimacy for him and his wife. He raised it at his last two visits with visible reluctance, and this time said directly that he has already skipped several doses on weekends without telling anyone, and that if nothing changes he is seriously considering stopping the medication on his own regardless of what the team recommends.

That combination — a genuinely effective antidepressant and a side effect serious enough to be driving covert non-adherence — is the real problem in front of the team, not simply 'SSRI causes sexual dysfunction, manage it.' Stopping sertraline outright risks relapsing a depression that responded well and took months to remit; reducing the dose risks the same thing without any guarantee the sexual side effect improves proportionally, since the mechanism isn't cleanly dose-dependent for every patient. The real options are adding a second agent that counteracts the effect, switching to a different antidepressant with a lower sexual side-effect burden, or treating the sexual dysfunction directly and leaving the antidepressant regimen that is otherwise working alone.

M.R. · 41 PHQ-9 3, covert non-adherence
History
No other chronic illness, no cardiac disease; first depressive episode, precipitated by father's death
Treatment course
Sertraline 150mg x1 year; full remission by month 3, sustained since
Side effect
Erectile difficulty and delayed orgasm since month 2; worsening marital strain
Adherence
Patient reports skipping weekend doses without informing the team
PHQ-9
3, stable for the past 9 months

At the medication-management visit

Psychiatrist Opening

I don't want to lose sight of how hard-won this remission was — a full switch carries real relapse risk for a depression that took three months to control, and I'd rather solve the sexual side effect without touching a regimen that is otherwise working exactly as intended.

Clinical Pharmacologist Response

The mechanism supports treating this as a separate, addressable problem rather than a reason to abandon the drug. SSRI-induced sexual dysfunction is largely mediated through 5-HT2A/2C stimulation downstream of serotonin reuptake inhibition; bupropion's dopaminergic and noradrenergic activity works through an essentially unrelated pathway and has real trial evidence as an add-on specifically for this side effect, without requiring the SSRI dose to change. The positive trials used 150mg twice daily, so 300mg/day is the target if a starting dose doesn't do it.

A PDE5 inhibitor like sildenafil, taken as needed, addresses the erectile component directly through the nitric oxide-cGMP pathway and has decent evidence in exactly this setting, but it wouldn't touch the delayed-orgasm piece, which bupropion augmentation is more likely to help.

Psychiatric Pharmacist Final

Bupropion augmentation is the better first move given he has both symptoms, not just the erectile one — and it's worth being direct with him that this is a real treatment for a real side effect, not a workaround, since the reluctance he's shown in prior visits suggests he may not have felt that framing from us before. Sildenafil stays reasonable to add on top later if erectile difficulty specifically doesn't fully resolve.

Regimen selected
Sertraline (Continued)
SSRI · Unchanged, 150mg
Continued at the effective dose that achieved and has sustained his remission; not the source of the plan, the reason to protect it.
Bupropion XL (Augmentation)
NDRI · Added at 150mg XL each morning, titrating toward 300mg/day
Added specifically to counteract 5-HT2-mediated sexual dysfunction through an unrelated dopaminergic/noradrenergic mechanism, without altering the SSRI regimen that controls his mood; the supporting trials dosed 300mg/day, so 150mg is a starting point rather than the target.
Dose Reduction — Ruled Out
SSRI, alternate strategy
No reliable dose-response relationship for this side effect in most patients; risks losing efficacy without a guaranteed symptom improvement in exchange.
Sildenafil (PDE5 Inhibitor) — Held in Reserve
PDE5 Inhibitor, as-needed
Named as an add-on if erectile difficulty specifically persists after bupropion augmentation; addresses the vascular component directly but not the delayed-orgasm symptom.
Where this was left

Bupropion XL 150mg was added each morning alongside the unchanged sertraline 150mg, with an explicit conversation naming the covert dose-skipping directly and reframing the sexual side effect as a treatable problem in its own right rather than something to be endured or hidden.

If bupropion augmentation resolves both symptoms

The current combination continues, with sildenafil held in reserve rather than added preemptively.

If erectile difficulty persists despite augmentation

Sildenafil is added as needed on top of the current regimen, addressing the vascular component directly rather than escalating or switching the antidepressant regimen further.

M.R. left the visit having agreed to stop skipping doses on his own and to report back specifically on both symptoms separately at four weeks — the team wanted a real answer on each, not a single global impression of whether things felt better.

Educational content only — a composite teaching case, not a real patient encounter or a substitute for clinical guidance. About These Cases →