Sertraline and Fentanyl: Interaction Details

a) A published case describes opioid related serotonin syndrome in a 58-year-old man who had a history of chronic back pain. He was stable while being treated for pain and depression. His drug regimen consisted of transdermal fentaNYL 75 mcg/hr patches, oxyCODONE 5 mg/acetaminophen 325 mg twice daily, celecoxib 200 mg twice daily, citalopram 40 mg once daily, and mirtazapine 50 mg at bedtime. He was additionally taking doxazosin 4 mg daily and zolpidem 12.5 mg as needed for insomnia. He described insufficient pain relief, and his fentaNYL treatment was adjusted so the patch was replaced every 2 days instead of every 3 days. Roughly 1 week after this fentaNYL increase, he reported anxiety, tremulousness, fever, and sweating. CloNIDine 0.2 mg every 4 hours was started without any symptom improvement. His symptoms persisted, and the next day he received haloperidol and LORazepam for anxiety and agitation. He stopped his fentaNYL patch and came to the emergency room with opiate withdrawal 2 days afterward. He was then diagnosed with serotonin syndrome even though his fentaNYL patch had been discontinued for 30 hours. Haloperidol, fentaNYL, oxyCODONE/acetaminophen, citalopram, and mirtazapine were all stopped immediately, with symptoms resolving completely by the next day. He was prescribed morphine sulfate in place of fentaNYL, and citalopram and mirtazapine were resumed with no return of serotoninergic symptoms at follow-up ².

b) Serotonin syndrome linked to fentaNYL use during an esophagogastroduodenoscopy was reported in a 39-year-old woman who was also taking sertraline 100 mg daily as an outpatient. She initially presented with hematemesis and a history of alcoholic cirrhosis. Before the esophagogastroduodenoscopy, an octreotide and pantoprazole drip was started, along with 2 doses of fentaNYL 50 micrograms and 2 doses of midazolam 1 mg. After the procedure she became somnolent and extremely rigid in all four extremities, and vecuronium and etomidate were administered for immediate intubation. The rigidity worsened with diffuse diaphoresis, horizontal roving eye movements, and a fever of 105 degrees F. Because of possible seizure activity, LORazepam 2 mg IV was given with no improvement, and a propofol drip was started for ongoing sedation during intubation. A CPK value of 2800 units/L and an ammonia level of 340 micromols/L indicated rhabdomyolysis. An acute intracranial process was excluded on a brain CT scan, and the neurology team diagnosed serotonin syndrome secondary to an interaction between fentaNYL and sertraline. Propofol was continued for sedation, and the patient received supportive care with a cooling blanket and cyproheptadine. After 3 days her temperature and CPK level normalized, and she was later extubated without further complications ⁶.

c) Serotonin syndrome after IV fentaNYL administration during surgical procedures was reported in 2 patients who were also taking SSRIs (sertraline and escitalopram). The first patient received IV fentaNYL (50 mcg), midazolam (2 mg), and 2 doses of propofol (60 mg and 40 mg) at an outpatient surgery center before a carpal tunnel release procedure. Postoperatively she started shivering and grew increasingly agitated, prompting transfer to the emergency department. On presentation she was combative, diaphoretic, confused, unable to follow commands, tachycardic, hypertensive, and had hyperreflexia and ankle clonus. Baseline creatinine kinase rose to 613 units/L on day 2 of hospitalization. The toxicology service treated her with escalating doses of benzodiazepines without improvement. She was then intubated and sedated with a continuous propofol infusion. After 2 days she was extubated, and by day 3 all symptoms had resolved and she was discharged home. The second patient was a 59-year-old woman admitted for an omentectomy for which she received IV fentaNYL 250 micrograms, etomidate, vecuronium, morphine, and cephazolin. After extubation she became hypoxic and acidotic and was reintubated and transferred to the ICU. On postoperative day 1 she was extubated and later became tachycardic and unable to follow commands. On examination she was agitated and diaphoretic, with patellar hyperreflexia and a bilateral 3 to 4 beat ankle clonus. Laboratory evaluation was notable for a peak creatine kinase of 1161 units/L on postoperative day 2. She was treated with LORazepam and cyproheptadine, with resolution of symptoms after 3 days ⁷.

d) A case of postoperative serotonin syndrome following fentaNYL given for general anesthesia and postoperative analgesia was reported in a 60-year-old woman who was also receiving PARoxetine. Her outpatient medications consisted only of PARoxetine and thyroxine for a history of depression and hypothyroidism. She was admitted for an extensive resection of a recurrent left chest wall myxofibrosarcoma and was given propofol and 200 mcg of fentaNYL for induction of anesthesia. She also received an additional 800 mcg of fentaNYL (intermittent 50 mcg boluses) intraoperatively and a subsequent fentaNYL infusion (100 to 200 mcg/hr) for postoperative sedation and analgesia (2545 mcg of fentaNYL received over 36 hours). The fentaNYL infusion was continued 36 hours postoperatively, at which point intermittent agitation, bilateral hypertonia and hyperreflexia, and bilateral inducible ankle clonus were noted on neurological examination. Symptoms were more pronounced in the lower limbs and on the right side of the body. A brain CT scan was unremarkable, and all other examination findings, including a thyroid function test, were within normal limits except for elevated blood pressure (180/90 mmHg), which resolved spontaneously 24 hours after the procedure. fentaNYL was discontinued, and 24 hours later there was marked improvement in neurological symptoms, with complete recovery by postoperative day 4. The patient was eventually discharged home with no further complications ⁸.

e) A 65-year-old woman treated with citalopram for depression developed serotonin syndrome after starting a fentaNYL patch. She had recently been diagnosed with myelodysplastic/myeloproliferative disease, and her regular drug regimen included RABEprazole, tolterodine, HYDROcodone, and over-the-counter NSAIDS. She was hospitalized when she presented with abdominal pain and worsening back pain, and a spontaneous retroperitoneal hemorrhage was found. During hospitalization her worsening back pain was treated with a fentaNYL transdermal patch (25 mcg/hr). Within 24 hours of starting fentaNYL, she progressively developed increasing confusion, agitation, combativeness, tremors in the upper extremities, myoclonic jerks, hyperreflexia, and unsteady gait, consistent with serotonin syndrome. Tachycardia was also noted (110 to 120 beats per minute). A CT scan and laboratory values showed no abnormalities. fentaNYL was discontinued, and all of her symptoms resolved within 24 to 36 hours. Her symptoms did not return when oxyCODONE was started for the back pain. In this case, the link between the serotonin syndrome and the coadministration of fentaNYL and citalopram was judged probable based on the Naranjo adverse event probability scale ⁹.