門診處方討論

　　　　　　　　報告者：顏靜卉

1/21 Venlafaxine 75mg/SR cap 1#PO QDHS

cyproheptadine 4mg/tab 1#PO BID

重鬱症

Cyproheptadine therapeutic uses in micromedex Cyproheptadine THERAPEUTIC USES

ACANTHOSIS NIGRICANS ALLERGIC REACTIONS ALLERGIC RHINITIS MIGRAINE HEADACHES NELSON'S SYNDROME PRURITUS SCHIZOPHRENIA SEROTONIN SYNDROME SPASTICITY - SPINAL CORD INJURIES

Cyproheptadine 之治療應用 合併兩種或多種會增加腦中 serotonergi

c 活性的藥物，可能會有 serotonin syndrome 的發生

單一治療也會誘發 serotonin syndrome的報告如 venlafaxine 、 sertraline 、 citalopram 、 sumatriptan 、 moclobemide 、 fluvoxamine 等

ADRAC 已收到 161 例血清胺症候群的通報，主要描述與併用 2 種或以上之血清胺製劑有關，特別是 SSRIs (68) ， tramadol (29) ， moclobemide (23) ， venlafaxine (18) ，三環抗憂鬱劑 (18) 及 St John’s wort (8) 。其中的 61 例，血清胺症候群的發生與單一的藥劑有關， SSRIs (40) ， moclobemide (5) ， venlafaxine (5) ， tramadol (5) 。

Australian Adverse Drug Reactions Bulletin

Volume 23, Number 1, February 2004

SEROTONIN SYNDROME

Serotonin syndrome 相關的症狀及診斷 -(1)

Diagnostic criteria: mental status changes, agitation, myoclonus, hyperrefl

exia, tremor, diaphoresis, shivering, diarrhea, incoordination, fever. Other effects: Cognitive: (coma, seizures, lethargy, disorientation, drowsiness, hallucinations); autonomic: (tachycardia, hypertension, hypotension, tachypnea, mydriasis, salivation); neuromuscular: (ataxia, rigidity, restlessness, chills, nystagmus, opisthotonos, trismus). DIC, acidosis, respiratory failure, ARDS, renal failure, rhabdomyolysis may develop in severe cases.

Serotonin syndrome 相關的症狀及診斷 -(2)

診斷 serotonin syndrome 並不具有特異性，血液中的 serotonin 值亦不能證明有相關性

沒有實驗室之檢驗可幫助診斷，此症候群常發生在改變治療的一天當中出現( 增加劑量或加上另一種血清胺製劑 )

Serotonin syndrome 相關的症狀及診斷 -(3)

Neuroleptic malignant syndrome (NMS) may be difficult to distinguish from serotonin syndrome. Besides associated with neuroleptics, NMS tends to have a slower onset and more prolonged duration of symptoms. NMS is more frequently associated with fever and muscle rigidity than serotonin syndrome, but not sufficiently different to be useful to distinguish from serotonin syndrome. Serotonin syndrome is more likely to have myoclonus and hyperreflexia.

臨床證據

1) Cyproheptadine is a non-specific 5-HT antagonist that has been shown to block development of serotonin syndrome in animals (Sternbach, 1991). Cyproheptadine has been used in the treatment of serotonin syndrome (Mills, 1997)(Horowitz & Mullins, 1999)(Goldberg & Huk, 1992)(Graudins et al, 1997).

2) One pharmacokinetic study reported that orally administered cyproheptadine (8 mg) resulted in higher serum levels than the same dose administered sublingually. For oral and sublingual routes, mean Cmax were 30 mcg/L and 4 mcg/L, mean Tmax were 4 hours and 9.6 hours, and mean AUC were 209 and 25 mcg.hr/L, respectively. The authors suggested that 8 milligrams of cyproheptadine administered sublingually is unlikely to be effective in treating serotonin syndrome (Gunja et al, 2004).

3) Of 5 probable or definite cases of serotonin syndrome treated with cyproheptadine, most cases had either a poor response or no response, with only one case having a good response. The authors suggested that the doses of cyproheptadine administered may have been too low to be beneficial, since blockade of brain serotonin receptors occurs at doses between 20 to 30 mg; the cases reported used doses of 4 to 16 mg (Gillman, 1999).

建議劑量 ADULT - 4 to 8 milligrams orally Max. dose:32 milligrams CHILD - 0.25 milligrams/kilogram/day Max.dose 12 milligrams/day

Serotonin syndrome 治療 propranolol phenothiazine(ex. risperidone 、 clozapine 、 chlo

rpromazine) dopamine receptor antagonist Benzodiazepine

結 論 Cyproheptadine in serotonin syndrom

e

FDA APPROVAL: Adult, no; pediatric, no EFFICACY: Adult, possibly effective DOCUMENTATION: Adult, poor

重鬱症

Paroxetine 0.5# PO BID

Cyproheptadine 1# PO BID

重鬱症

無法鑑別之擬身體化症

Cyproheptadine 1# PO BID

Imipramine 0.5# PO BID