Table. Attack Characteristics of Patients With Cluster Headachesa.
| Patient No./Sex | Type of Intervention | Headache Characteristics/Peak Intensityb | Autonomic Symptoms/Agitation | Time to Onset (Duration), min | Mimics Usual Cluster Attackc | Time to Peak From Onset, min | Immediate Rescue Therapy (Time, d)/Effectd | Preventive Treatment | Disease Duration, y |
|---|---|---|---|---|---|---|---|---|---|
| Episodic Cluster Headache in Active Phase Group | |||||||||
| ECHA01/M | Usual | Right/10 | Conjunctival redness; lacrimation; rhinorrhea | NA | NA | NA | Sumatriptan, 6-mg subcutaneous injection | Verapamil, 400 mg | 28 |
| CGRPe | Left/1 | Lacrimation; ptosis; miosis | 70 (15) | Yes | 0 | No | Verapamil, 400 mg | NA | |
| Placebo | None | None | NA | NA | NA | NA | Verapamil, 400 mg | NA | |
| ECHA 02/M | Usual | Left/9 | Conjunctival redness; lacrimation; agitation | NA | NA | NA | Sumatriptan, 6-mg subcutaneous injection; oxygen | None | 7 |
| CGRP | None | None | NA | NA | NA | NA | None | NA | |
| Placeboe | Left/2 | Lacrimation; agitation | 20 (80) | Yes | 0 | No | None | NA | |
| ECHA 03/M | Usual | Left/10 | Conjunctival redness; miosis; forehead and facial sweating; ptosis; agitation | NA | NA | NA | None | None | 3 |
| CGRPe | Left/3 | Ptosis | 30 (10) | Yes | 0 | No | None | NA | |
| Placebo | None | None | NA | NA | NA | NA | None | NA | |
| ECHA 04/F | Usual | Right/10 | Conjunctival redness; lacrimation; rhinorrhea; nasal congestion; agitation | NA | NA | NA | Sumatriptan, 6-mg subcutaneous injection | None | 4 |
| CGRPe | Right/10 | Nasal congestion; ptosis; agitation | 20 (40) | Yes | 30 | Sumatriptan, 6-mg subcutaneous injection; oxygen (14, 16)/yes | None | NA | |
| Placebo | None | None | NA | NA | NA | NA | None | NA | |
| ECHA 05/F | Usual | Right/10 | Conjunctival redness; lacrimation; rhinorrhea; agitation | NA | NA | NA | Oxygen | None | 15 |
| CGRPe | Right/10 | Nasal congestion; ptosis; agitation | 60 (70) | Yes | 10 | Oxygen (63)/NA | None | NA | |
| Placebo | None | None | NA | NA | NA | NA | None | NA | |
| ECHA 06/F | Usual | Right/10 | Conjunctival redness; miosis; ptosis; forehead and facial sweating | NA | NA | NA | Sumatriptan, 6-mg subcutaneous injection; rizatriptan, 10 mg | Verapamil, 560 mg | 2 |
| CGRPe | Right/10 | Conjunctival redness; lacrimation; forehead and facial sweating; ptosis; agitation | 13 (40) | Yes | 20 | Sumatriptan, 6-mg subcutaneous injection (18)/yes | Verapamil, 560 mg | NA | |
| Placebo | None | None | NA | NA | NA | NA | Verapamil, 560 mg | NA | |
| ECHA 09/M | Usual | NA/8 | Conjunctival redness; ptosis; agitation | NA | NA | NA | Sumatriptan, 6-mg subcutaneous injection | Greater occipital nerve blockade | 16 |
| CGRPe | Left/7 | Lacrimation; ptosis; agitation | 20 (60) | Yes | 30 | Sumatriptan, 6-mg subcutaneous injection (45, 65)/yes | None | NA | |
| Placebo | None | Lacrimation | NA | NA | NA | NA | None | NA | |
| ECHA 10/M | Usual | Right/8 | Conjunctival redness; eyelid edema; rhinorrhea; ptosis; forehead and facial sweating | 30 (40) | Yes | 10 | None | None | 20 |
| CGRPe | Right/3 | Ptosis | 30 (40) | Yes | 10 | No | None | NA | |
| Placebo | Right/1 | None | 10 (110) | No | 0 | None | None | NA | |
| ECHA 11/M | Usual | Right/10 | Conjunctival redness; lacrimation; miosis; nasal congestion rhinorrhea; ptosis; agitation | NA | NA | NA | Sumatriptan, 6-mg subcutaneous injection; oxygen | Verapamil, 400 mg | 5 |
| CGRPe | Right/4 | Agitation | 60 (20) | Yes | 10 | Oxygen (64)/yes | Verapamil, 400 mg | NA | |
| Placebo | None | None | NA | NA | NA | NA | Verapamil, 400 mg | NA | |
| Chronic Cluster Headache Group | |||||||||
| CCH01/M | Usual | Right/9 | Agitation | NA | NA | NA | Oxygen | Verapamil, 240 mg | 6 |
| CGRP | NA | NA | NA | NA | NA | NA | Verapamil, 240 mg | NA | |
| Placebo | NA | NA | NA | NA | NA | NA | Verapamil, 240 mg | NA | |
| CCH02/M | Usual | Left/6 | Conjunctival redness; eyelid edema; nasal congestion; rhinorrhea; ptosis; agitation | NA | NA | NA | Sumatriptan, 6-mg subcutaneous injection; voltaren, 25-mg subcutaneous injection | None | 27 |
| CGRPe | Left/10 | Lacrimation; rhinorrhea; eyelid edema; forehead and facial sweating; agitation | 20 (15) | Yes | 20 | Voltaren, 25-mg subcutaneous injection | None | NA | |
| Placebo | NA | Eyelid edema | NA | NA | NA | NA | None | NA | |
| CCH03/M | Usual | Left/10 | Conjunctival redness; miosis; ptosis; agitation | NA | NA | NA | Sumatriptan, 6-mg subcutaneous injection; oxygen | Verapamil, 440 mg | 11 |
| CGRP | NA | NA | NA | NA | NA | NA | Verapamil, 440 mg | NA | |
| Placebo | NA | Eyelid edema | NA | NA | NA | NA | Verapamil, 440 mg | NA | |
| CCH04/M | Usual | Right/1 0 | Conjunctival redness; lacrimation; nasal congestion; rhinorrhea; agitation | NA | NA | NA | None | Verapamil, 480 mg | 12 |
| CGRPe | Right/3 | Conjunctival redness; nasal congestion | 20 (30) | Yes | 0 | None | Verapamil, 480 mg | NA | |
| Placebo | Right/1 | None | 20 (20) | No | 0 | None | Verapamil, 480 mg | NA | |
| CCH05/F | Usual | Right/NA | Lacrimation; nasal congestion; rhinorrhea; agitation | NA | NA | NA | Oxygen | Verapamil, 100 mg | 2 |
| CGRPe | Right/10 | Conjunctival redness; lacrimation; nasal congestion; eyelid edema; ptosis; agitation | 10 (30) | Yes | 10 | Sumatriptan, 6-mg subcutaneous injection; oxygen (35)/yes | Verapamil, 100 mg | NA | |
| Placebo | NA | NA | NA | NA | NA | NA | Verapamil, 100 mg | NA | |
| CCH06/F | Usual | Left/9 | Conjunctival redness; lacrimation; miosis; eyelid edema; rhinorrhea; ptosis; agitation | NA | NA | NA | Sumatriptan, 6-mg subcutaneous injection; oxygen; sumatriptan, 100 mg orally | NA | 10 |
| CGRP | NA | NA | NA | NA | NA | NA | NA | NA | |
| Placebo | NA | NA | NA | NA | NA | NA | NA | NA | |
| CCH07/M | Usual | Right/7 | Conjunctival redness; nasal congestion; agitation | NA | NA | NA | Sumatriptan, 6-mg subcutaneous injection | Verapamil, 400 mg | 13 |
| CGRP | NA | NA | NA | NA | NA | NA | Verapamil, 400 mg | NA | |
| Placebo | NA | NA | NA | NA | NA | NA | Verapamil, 400 mg | NA | |
| CCH08/M | Usual | Left/10 | Conjunctival redness; lacrimation; rhinorrhea; ptosis; agitation | NA | NA | NA | Oxygen | Verapamil, 240 mg | 4 |
| CGRP | NA | NA | NA | NA | NA | NA | Verapamil, 240 mg | NA | |
| Placebo | NA | NA | NA | NA | NA | NA | Verapamil, 240 mg | NA | |
| CCH09/M | Usual | Left/5 | Lacrimation; conjunctival redness; ptosis; agitation | NA | NA | NA | Oxygen | Verapamil, 600 mg | 3 |
| CGRPe | Left/3 | Conjunctival redness; lacrimation; agitation | 30 (70) | Yes | 10 | None | Verapamil, 600 mg | NA | |
| Placebo | NA | NA | NA | NA | NA | NA | Verapamil, 600 mg | NA | |
| CCH10/M | Usual | Left/9 | Lacrimation | NA | NA | NA | Sumatriptan, 6-mg subcutaneous injection; oxygen | None | 6 |
| CGRP | Bilateral/1 | None | 10 (20) | No | 0 | None | None | NA | |
| Placebo | NA | NA | NA | NA | NA | NA | None | NA | |
| CCH11/M | Usual | Left,right/8 | Nasal congestion; rhinorrhea; agitation | NA | NA | NA | Oxygen; sumatriptan, 100-mg orally | Verapamil, 240 mg; lithium, 200 mg |
35 |
| CGRPe | NA/1 | None | 60 (30) | Yes | 0 | None | Verapamil, 240 mg; lithium, 200 mg |
NA | |
| Placebo | NA | NA | NA | NA | NA | NA | Verapamil, 240 mg; lithium, 200 mg |
NA | |
| CCH12/F | Usual | Left/NA | Lacrimation; eyelid edema; rhinorrhea; nasal congestion; forehead and facial sweating; ptosis; agitation | NA | NA | NA | Sumatriptan, 6-mg subcutaneous injection; sphenopalatine ganglion neurostimulator | Melatonin, 4 mg | 10 |
| CGRPe | Left/10 | Conjunctival redness; lacrimation; rhinorrhea; nasal congestion; eyelid edema; forehead and facial sweating; ptosis; agitation | 13 (40) | Yes | 10 | Sphenopalatine ganglion neurostimulator | Melatonin, 4 mg | NA | |
| Placebo | NA | NA | NA | NA | NA | NA | Melatonin, 4 mg | NA | |
| CCH13/M | Usual | Right/9 | Lacrimation; conjunctival redness; eyelid edema; nasal congestion; rhinorrhea; forehead and facial sweating; ptosis; agitation | NA | NA | NA | Oxygen | None | 26 |
| CGRP | NA | NA | NA | NA | NA | NA | None | NA | |
| Placebo | NA | Agitation | NA | NA | NA | NA | None | NA | |
| CCH14/M | Usual | Right/10 | Conjunctival redness; lacrimation; nasal congestion; rhinorrhea; agitation | NA | NA | NA | Sumatriptan, 100-mg orally | None | 5 |
| CGRPe | Right/5 | Conjunctival redness | 60 (30) | Yes | 10 | Oxygen (60)/yes | None | NA | |
| Placebo | NA | NA | NA | NA | NA | NA | None | NA | |
| Episodic Cluster Headache in Remission Group | |||||||||
| ECHR01/M | Usual | Right/NA | Conjunctival redness; lacrimation; rhinorrhea; agitation | NA | NA | NA | Sumatriptan, 6-mg subcutaneous injection | None | 1 |
| CGRP | Bilateral/1 | Lacrimation | 20 (10) | No | 0 | None | None | NA | |
| Placebo | Bilateral/1 | None | 20 (10) | No | 0 | None | None | NA | |
| ECHR02/M | Usual | Right/10 | Conjunctival redness; lacrimation; miosis; eyelid edema; rhinorrhea; nasal congestion; forehead and facial sweating; agitation | NA | NA | NA | Sumatriptan, 6-mg subcutaneous injection; oxygen | Verapamil, 400 mg | 4 |
| CGRP | NA | NA | NA | NA | NA | NA | Verapamil, 400 mg | NA | |
| Placebo | NA | NA | NA | NA | NA | NA | Verapamil, 400 mg | NA | |
| ECHR03/M | Usual | Right/10 | Conjunctival redness; eyelid edema; ptosis; agitation | NA | NA | NA | Sumatriptan, 6-mg subcutaneous injection | None | 12 |
| CGRP | NA | Nasal congestion | NA | NA | NA | NA | None | NA | |
| Placebo | NA | NA | NA | NA | NA | NA | None | NA | |
| ECHR04/M | Usual | Left/10 | Conjunctival redness; miosis; forehead and facial sweating; ptosis; agitation | NA | NA | NA | None | None | 3 |
| CGRP | NA | NA | NA | NA | NA | NA | None | NA | |
| Placebo | NA | NA | NA | NA | NA | NA | None | NA | |
| ECHR05/M | Usual | Right/NA | Conjunctival redness; lacrimation; rhinorrhea; ptosis; agitation | NA | NA | NA | sumatriptan, 6-mg subcutaneous injection; oxygen | None | 14 |
| CGRP | NA | NA | NA | NA | NA | NA | None | NA | |
| Placebo | NA | NA | NA | NA | NA | NA | None | NA | |
| ECHR06/ M | Usual | Right/9 | Conjunctival redness; lacrimation; miosis; nasal congestion; forehead and facial sweating; ptosis; agitation | NA | NA | NA | Sumatriptan, 6-mg subcutaneous injection | Verapamil, 800 mg | 15 |
| CGRP | NA | Ptosis | NA | NA | NA | NA | Verapamil, 800 mg | NA | |
| Placebo | NA | Ptosis | NA | NA | NA | NA | Verapamil, 800 mg | NA | |
| ECHR08/M | Usual | Right/7 | Lacrimation; ptosis; agitation | NA | None | None | 17 | ||
| CGRP | NA | NA | NA | NA | NA | NA | None | NA | |
| Placebo | NA | NA | NA | NA | NA | NA | None | NA | |
| ECHR10/M | Usual | Right/9 | Conjunctival redness; lacrimation; eyelid edema; rhinorrhea; ptosis; agitation | NA | NA | NA | Sumatriptan, 6-mg subcutaneous injection; oxygen | None | 15 |
| CGRP | NA | Eyelid edema | NA | NA | NA | NA | None | NA | |
| Placebo | NA | NA | NA | NA | NA | NA | None | NA | |
| ECHR12/M | Usual | Right/9 | Conjunctival redness; lacrimation; rhinorrhea; agitation | NA | NA | NA | None | None | 8 |
| CGRP | Right/2 | None | 40 (50) | No | 0 | None | None | NA | |
| Placebo | NA | NA | NA | NA | NA | NA | None | NA | |
Abbreviations: CCH, chronic cluster headache; CGRP, calcitonin gene-related peptide; ECHA, episodic cluster headache in active phase; ECHR, episodic cluster headache remission phase; NA, not applicable.
a
Cerebral autonomic symptoms, restlessness, and immediate treatment is reported from 0 to 90 minutes after 20 minutes of intravenous infusion of calcitonin CGRP (1.5 μg/min) or placebo.
b
Patients rated the intensity of their headache on an 11-point scale, with 0 indicating no headache; 1, a very mild headache (including a sensation of pressing or throbbing or otherwise altered sensation in the head not associated with pain); 5, headache of moderate intensity; and 10, the worst headache imaginable.
c
Clusterlike attack is defined according to criteria described in the Methods section.
d
Therapy effect: more than 50% reduction in pain intensity over 2 hours.
e
Patient developed a clusterlike attack on study days.