Chronic serotonin syndrome: A retrospective study

Table 1 Details of patients with chronic serotonin syndrome

Age/sex	Details of the clinical characteristics			Serotonergic agent and its details	Investigations	Treatment and follow up
	Presenting complaint	Other symptoms and signs	Duration of illness
49, F	Generalized body pain, fatigue, restlessness, tremors	Dizziness, insomnia, tachycardia, rigidity, clonus	6-8 wk	Valproate for 2 yr for epilepsy, sertraline added 3 mo back for depression	CK- 566 U/L	Discontinued sertraline. Cyproheptadine (4 mg bid) was started. Marked improvement in 2 d. Complete response within 5 d. No recurrence in follow-up
57, M	Irritability, disturbed sleep, slowness in gait, disturbed bowel	Tremors, sexual dysfunctions, tachycardia, rigidity, clonus	3 mo	Tramadol and amitriptyline for paraesthesia for 1 yr	Normal	Discontinued drugs. Cyproheptadine (4 mg bid) was started. Response began within 48 h. Complete response within 7 d
32, F	Headache, generalized body pain, tremors	Intermittent diaphoresis, tachycardia, rigidity, clonus	2 mo	Valproate (500 mg bid) for 6 mo for epilepsy	CK- 1283 U/L	Marked improvement by cyproheptadine (4 mg tid). Valproate changed to levetiracetam. Follow- up was uneventful
46, F	Slowness in work and gait, bladder dysfunctions, dizziness, tremors	Dizziness, sexual dysfunctions, tachycardia, rigidity, clonus	3 mo	Amitriptyline and citalopram for 1 yr for bipolar disorder	Normal	Discontinued the offending drugs. Cyproheptadine (4 mg tid) for 3 wk. Response began in 48 h. Complete response within 10
58, M	Slowness in gait, pain and stiffness in the limbs and neck, tremors	Nystagmus, tachycardia, rigidity, clonus	10-12 wk	Tramadol, and fluoxetine for 4 mo for carpal tunnel syndrome	CK-879 U/L	Cyproheptadine (4 mg tid) for 2 wk. Response began in 2 d. Complete response within 5-7 d. No recurrence in follow-up
37, F	Tremors, irritability, fatigue, muscle pain, bowel disturbances	Tachycardia, hypertension, hypertonia, clonus	8-10 wk	Amitriptyline and valproate for chronic migraine for 6 mo	Normal	Started cyproheptadine (4 mg bid). Complete response within 4-6 d. Cyproheptadine was continued as an anti-migraine drug
31, M	Gait problems, stiff legs, bowel disturbances	Tremors, spasticity, clonus, diaphoresis	9-10 wk	Paroxetine (40 mg/d) for 6 mo for depression	CK-1279 U/L	Discontinued paroxetine. Cyproheptadine (6 mg tid) for 3 wk
47, M	Insomnia, dizziness, restlessness, bowel disturbance, episodic sweating	Tremor tachycardia, rigidity, clonus, hyperreflexia	3-4 mo	Sertraline and valproate for mood disorder for 9 mo	CK-634 U/L	Discontinued both drugs. Cyproheptadine (4 mg bid) for 4 wk
42, F	Generalized body pain, stiff body, constipation	Tremors, nystagmus, rigidity, stiff neck, hyperreflexia	8-10 wk	Tramadol and amitriptyline for 3 mo for pain after radius fracture	CK-1134 U/L	Started cyproheptadine (4 mg tid). Marked response in 7 d. Cyproheptadine was continued for 6 wk
54, M	Dystonic tremor, incoordination, stiffness in legs, episodic sweating	Tremors, nystagmus, rigidity, clonus, hyperreflexia	6-8 wk	Amitriptyline and tramadol for 3 mo for cervical spondylosis	Normal	Stopped both drugs. Started cyproheptadine (4 mg tid). Complete response in 7 d. Cyproheptadine was continued for 6 wk
61, M	Tremors, stiffness, incoordination, sexual dysfunction, insomnia	Nystagmus, rigidity, clonus, hypertension	4-5 mo	Addicted to tramadol for 2 yr for neuropathic pain	Normal	Marked improvement with cyproheptadine (4 mg tid). The patient did not stop tramadol and he continued cyproheptadine

F: Female; M: Male.

Table 2 Epidemiological profiles and clinical features of 14 patients with chronic serotonin syndrome

Parameters	n (%)
Age in yr, mean ± SD	44.1 ± 11.6
Sex, M:F	9:5 (1.8:1)
Duration of illness in wk	13.5 ± 5.8
Clinical characteristics
Tremor	14 (100)
Hyperreflexia	14 (100)
Clonus	13 (93)
Spasticity-rigidity	11 (79)
Tachycardia	9 (64)
Generalized pain	7 (50)
Insomnia	7 (50)
Irritability-restlessness	7 (50)
Stiffness	6 (43)
Diaphoresis	6 (43)
Gait disturbances	5 (36)
Bowel disturbances	5 (36)
Dizziness	4 (29)
Sexual dysfunctions	3 (21)
Nystagmus	3 (21)
Hypertension	2 (14)
Incoordination	2 (14)
Fatigue	2 (14)
Fulfilments of SS criteria
Hunter criteria	14 (100)
Sternbach’s criteria	11 (78)
Serotonergic agents implicated in 14 cases
Amitriptyline	6 (43)
Tramadol	5 (36)
Valproate	5 (36)
Paroxetine	2 (14)
Sertraline	2 (14)
Citalopram	1 (7)
Fluoxetine	1 (7)

F: Female; M: Male; SD: Standard deviation; SS: Serotonin syndrome.