caffeine and Headache, Tension studies

Research Excerpts

Excerpt	Relevance	Reference
"The main aim of this study was to confirm in an Italian population affected by tension-type headache (TTH) the good profile of safety and tolerability of the combination paracetamol 1,000 mg-caffeine 130 mg (PCF) observed in previous studies, by a comparison with naproxen sodium 550 mg (NAP) and placebo (PLA)."	9.13	Tolerability and efficacy of a combination of paracetamol and caffeine in the treatment of tension-type headache: a randomised, double-blind, double-dummy, cross-over study versus placebo and naproxen sodium. ( Del Bene, E; Di Loreto, G; Di Trapani, G; Dionisio, P; Granella, F; LaPegna, G; Pini, LA; Prudenzano, MP; Sarchielli, P; Savi, L; Zanchin, G, 2008)
"In this double-blind, randomized, parallel group, multicentre study the efficacy of a fixed combination of indomethacin, prochlorperazine, and caffeine (IndoProCaf) and nimesulide were compared over an 8-h period in the treatment of two consecutive episodes of tension-type headache (TTH)."	9.11	Efficacy of a fixed combination of indomethacin, prochlorperazine, and caffeine in the treatment of episodic tension-type headache: a double-blind, randomized, nimesulide-controlled, parallel group, multicentre trial. ( Centonze, V; Cerbo, R; Grazioli, I; Sternieri, E; Tavolato, B; Trenti, T; Uslenghi, C, 2005)
"Simple analgesics such as ibuprofen, aspirin, and acetaminophen have long been used in the treatment of tension-type headache."	9.09	The use of ibuprofen plus caffeine to treat tension-type headache. ( Diamond, S; Freitag, FG, 2001)
"Four randomized, controlled trials of identical design in 1,900 patients with episodic tension-type headache comparing acetylsalicylic acid, acetaminophen and caffeine vs."	8.90	Use of a fixed combination of acetylsalicylic acid, acetaminophen and caffeine compared with acetaminophen alone in episodic tension-type headache: meta-analysis of four randomized, double-blind, placebo-controlled, crossover studies. ( Diener, HC; Gold, M; Hagen, M, 2014)
" Additional studies are needed to assess the relationship between caffeine dosing and clinical benefits in patients with TTH and migraine."	6.55	Caffeine in the management of patients with headache. ( Diener, HC; Garas, SY; Lipton, RB; Patel, K; Robbins, MS, 2017)
"The results of this subgroup analysis confirm that the fixed combination of ASA (250 mg), paracetamol (200 mg), and caffeine (50 mg) is effective and well tolerated in a broad spectrum from mild to severe migraine and tension-type headache severity independently of the headache diagnosis."	5.15	The efficacy and tolerability of a fixed combination of acetylsalicylic acid, paracetamol, and caffeine in patients with severe headache: a post-hoc subgroup analysis from a multicentre, randomized, double-blind, single-dose, placebo-controlled parallel g ( Aicher, B; Diener, HC; Peil, H, 2011)
" In a randomized double-blind study including individuals with either migraine or tension-type headache (TTH) we showed significant superiority of the fixed combination of acetylsalicylic acid + paracetamol + caffeine over the combination without caffeine, the single preparations, and placebo in the treatment of headache."	5.14	Headache classification by history has only limited predictive value for headache episodes treated in controlled trials with OTC analgesics. ( Aicher, B; Diener, HC; Lipton, RB; Pageler, L; Peil, H; Pfaffenrath, V, 2009)
"The main aim of this study was to confirm in an Italian population affected by tension-type headache (TTH) the good profile of safety and tolerability of the combination paracetamol 1,000 mg-caffeine 130 mg (PCF) observed in previous studies, by a comparison with naproxen sodium 550 mg (NAP) and placebo (PLA)."	5.13	Tolerability and efficacy of a combination of paracetamol and caffeine in the treatment of tension-type headache: a randomised, double-blind, double-dummy, cross-over study versus placebo and naproxen sodium. ( Del Bene, E; Di Loreto, G; Di Trapani, G; Dionisio, P; Granella, F; LaPegna, G; Pini, LA; Prudenzano, MP; Sarchielli, P; Savi, L; Zanchin, G, 2008)
"We investigated efficacy, safety, and tolerability of two tablets of the fixed combination of 250 mg acetylsalicylic acid (ASA) + 200 mg paracetamol + 50 mg caffeine (Thomapyrin) in comparison with two tablets of 250 mg ASA + 200 mg paracetamol, two tablets of 500 mg ASA, two tablets of 500 mg paracetamol, two tablets of 50 mg caffeine, and placebo in patients who were used to treating their episodic tension-type headache or migraine attacks with non-prescription analgesics."	5.11	The fixed combination of acetylsalicylic acid, paracetamol and caffeine is more effective than single substances and dual combination for the treatment of headache: a multicentre, randomized, double-blind, single-dose, placebo-controlled parallel group st ( Aicher, B; Diener, HC; Pageler, L; Peil, H; Pfaffenrath, V, 2005)
"In this double-blind, randomized, parallel group, multicentre study the efficacy of a fixed combination of indomethacin, prochlorperazine, and caffeine (IndoProCaf) and nimesulide were compared over an 8-h period in the treatment of two consecutive episodes of tension-type headache (TTH)."	5.11	Efficacy of a fixed combination of indomethacin, prochlorperazine, and caffeine in the treatment of episodic tension-type headache: a double-blind, randomized, nimesulide-controlled, parallel group, multicentre trial. ( Centonze, V; Cerbo, R; Grazioli, I; Sternieri, E; Tavolato, B; Trenti, T; Uslenghi, C, 2005)
"Simple analgesics such as ibuprofen, aspirin, and acetaminophen have long been used in the treatment of tension-type headache."	5.09	The use of ibuprofen plus caffeine to treat tension-type headache. ( Diamond, S; Freitag, FG, 2001)
"Six randomized, double-blind, two-period crossover studies, conducted under similar protocols, compared the efficacy of two analgesic combinations containing caffeine with an acetaminophen 1000 mg control and with a placebo in outpatients with episodic tension-type headaches."	5.07	Caffeine as an analgesic adjuvant in tension headache. ( Armellino, JJ; Beaver, WT; Friedman, M; Gillings, DB; Migliardi, JR, 1994)
"Four randomized, controlled trials of identical design in 1,900 patients with episodic tension-type headache comparing acetylsalicylic acid, acetaminophen and caffeine vs."	4.90	Use of a fixed combination of acetylsalicylic acid, acetaminophen and caffeine compared with acetaminophen alone in episodic tension-type headache: meta-analysis of four randomized, double-blind, placebo-controlled, crossover studies. ( Diener, HC; Gold, M; Hagen, M, 2014)
" Most of these patients suffer from migraine, tension-type headache, or a combination of the two; they tend to self-medicate using over the counter combination headache preparations, particularly acetylsalicyclic acid (ASA) and acetaminophen coformulated with caffeine, which is one of the most commonly used combination analgesics in these patients worldwide."	4.86	Efficacy of fixed combinations of acetylsalicyclic acid, acetaminophen and caffeine in the treatment of idiopathic headache: a review. ( Anneken, K; Evers, S; Husstedt, IW, 2010)
" Additional studies are needed to assess the relationship between caffeine dosing and clinical benefits in patients with TTH and migraine."	2.55	Caffeine in the management of patients with headache. ( Diener, HC; Garas, SY; Lipton, RB; Patel, K; Robbins, MS, 2017)
"Models of sleep physiology and insomnia are discussed, along with the potential implications for the chronification of migraine and tension-type headache."	2.48	Chronic headaches and insomnia: working toward a biobehavioral model. ( Ong, JC; Park, M, 2012)

Research

Studies (26)

Authors

Clinical Trials (1)

Trial Overview

Trial Outcomes

Duration of Headache Free Period at 7 Days

Number of Participants With Development of Hypertensive Disease of Pregnancy Within 28 Days

Number of Participants With Development of Hypertensive Disease of Pregnancy Within 7 Days

Number of Participants With Injection Site Complication (Infection, Hematoma, and Ecchymosis)

Number of Participants With Need for Admission for Treatment of Headache

Number of Participants With Need for Crossover Treatment

Number of Participants With Need for Neurology Consult

Number of Participants With Need for Representation for Treatment of Headache With 28 Days

Timeframe	Studies, this research(%)	All Research%
pre-1990	2 (7.69)	18.7374
1990's	3 (11.54)	18.2507
2000's	12 (46.15)	29.6817
2010's	8 (30.77)	24.3611
2020's	1 (3.85)	2.80

Authors	Studies
Whiting, J	1
Kilgour, P	1
Lipton, RB	2
Diener, HC	5
Robbins, MS	1
Garas, SY	1
Patel, K	1
Khairoalsindi, OA	1
Saber, WK	1
Althubaiti, NA	1
Alshareef, EF	1
Almekhlafi, MA	1
Gold, M	1
Hagen, M	1
Pini, LA	1
Del Bene, E	1
Zanchin, G	1
Sarchielli, P	1
Di Trapani, G	1
Prudenzano, MP	1
LaPegna, G	1
Savi, L	1
Di Loreto, G	1
Dionisio, P	1
Granella, F	1
Pfaffenrath, V	2
Pageler, L	2
Peil, H	3
Aicher, B	3
Anneken, K	1
Evers, S	1
Husstedt, IW	1
Haag, G	2
Hoy, SM	1
Scott, LJ	1
Ong, JC	1
Park, M	1
FRIEDMAN, AP	1
RYAN, RE	1
Holzhammer, J	1
Wöber, C	1
Cerbo, R	1
Centonze, V	1
Grazioli, I	1
Tavolato, B	1
Trenti, T	1
Uslenghi, C	1
Sternieri, E	1
Gupta, VK	1
Koch, GG	1
Amara, IA	1
MacMillan, J	1
Migliardi, JR	1
Armellino, JJ	1
Friedman, M	1
Gillings, DB	1
Beaver, WT	1
Amelin, AV	1
Sorokoumov, VA	1
Rabello, GD	1
Forte, LV	1
Galvão, AC	1
Diamond, S	2
Balm, TK	1
Freitag, FG	2
Schoenen, J	1
Sparano, N	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
Acute Headache Treatment in Pregnancy: Improvement in Pain Scores With Occipital Nerve Block vs PO Acetaminophen With Caffeine A Randomized Controlled Trial[NCT03951649]	Phase 4	62 participants (Actual)	Interventional	2020-02-10	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Intervention	days (Median)
Occipital Nerve Block	6
Oral Acetaminophen/Caffeine Group	1

Intervention	Participants (Count of Participants)
Occipital Nerve Block	9
Oral Acetaminophen/Caffeine Group	4

Intervention	Participants (Count of Participants)
Occipital Nerve Block	7
Oral Acetaminophen/Caffeine Group	2

Intervention	Participants (Count of Participants)
Occipital Nerve Block	0
Oral Acetaminophen/Caffeine Group	2

Intervention	Participants (Count of Participants)
Occipital Nerve Block	0
Oral Acetaminophen/Caffeine Group	0

Intervention	Participants (Count of Participants)
Occipital Nerve Block	9
Oral Acetaminophen/Caffeine Group	14

Intervention	Participants (Count of Participants)
Occipital Nerve Block	4
Oral Acetaminophen/Caffeine Group	2

Emergency department for treatment of headache since treatment asked at 28 day follow up (NCT03951649)
Timeframe: 28 days

Number of Participants With Need for Second Line Treatment

Number of Participants With Response to Occipital Nerve Block in Pregnancy

Intervention	Participants (Count of Participants)
Occipital Nerve Block	5
Oral Acetaminophen/Caffeine Group	1

Intervention	Participants (Count of Participants)
Occipital Nerve Block	5
Oral Acetaminophen/Caffeine Group	5

Based on guidelines from the International Headache Society the primary outcome is the portion of women who experience resolution of headache or improvement of headache to mild range (VRS ≤ 3) at 2 hours following treatment with Occipital nerve block as compared to acetaminophen/caffeine cocktail. (NCT03951649)
Timeframe: 60-300 min

Response to Cross Over Treatment at 60 Min

Intervention	Participants (Count of Participants)
Occipital Nerve Block	20
Oral Acetaminophen/Caffeine Group	16

"Visual/verbal Rating Score (VRS). VRS is used to assess pain in patients. With 0 representing no pain at all and 10 representing worst possible pain.~Total Minimum score=0 Total Maximum score=10~Higher values represent worse pain. If VRS=0, then the headache pain is considered resolved." (NCT03951649)
Timeframe: 60 min

Response to Second Line Treatment at 60 Min

Intervention	score on a scale (Median)
Occipital Nerve Block	6
Oral Acetaminophen/Caffeine Group	3

Response to Treatment Within 2 Hours

Article	Year
BET 2: Caffeine as an analgesic adjunct in tension-type headache and migraine. Emergency medicine journal : EMJ, 2021, Volume: 38, Issue:8 Topics: Caffeine; Evidence-Based Emergency Medicine; Humans; Migraine Disorders; Pain Management; Tension-Ty	2021
Caffeine in the management of patients with headache. The journal of headache and pain, 2017, Oct-24, Volume: 18, Issue:1 Topics: Abdominal Pain; Acetaminophen; Adult; Analgesics; Aspirin; Caffeine; Central Nervous System Stimulan	2017
Use of a fixed combination of acetylsalicylic acid, acetaminophen and caffeine compared with acetaminophen alone in episodic tension-type headache: meta-analysis of four randomized, double-blind, placebo-controlled, crossover studies. The journal of headache and pain, 2014, Nov-19, Volume: 15 Topics: Acetaminophen; Analgesics; Aspirin; Caffeine; Double-Blind Method; Drug Therapy, Combination; Humans	2014
Efficacy of fixed combinations of acetylsalicyclic acid, acetaminophen and caffeine in the treatment of idiopathic headache: a review. European journal of neurology, 2010, Volume: 17, Issue:4 Topics: Acetaminophen; Analgesics, Non-Narcotic; Animals; Aspirin; Caffeine; Drug Combinations; Humans; Tens	2010
Indomethacin/prochlorperazine/caffeine: a review of its use in the acute treatment of migraine and in the treatment of episodic tension-type headache. CNS drugs, 2011, Volume: 25, Issue:4 Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Antiemetics; Caffeine; Central Nervous System Stimul	2011
Chronic headaches and insomnia: working toward a biobehavioral model. Cephalalgia : an international journal of headache, 2012, Volume: 32, Issue:14 Topics: Actigraphy; Adaptation, Psychological; Caffeine; Chronobiology Phenomena; Comorbidity; Headache Diso	2012
[Self-medication of migraine and headache]. MMW Fortschritte der Medizin, 2006, Nov-23, Volume: 148, Issue:47 Topics: Acetaminophen; Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Caffeine;	2006
[Treatment of tension headache]. Revue neurologique, 2000, Volume: 156 Suppl 4 Topics: Anti-Inflammatory Agents, Non-Steroidal; Antidepressive Agents, Tricyclic; Caffeine; Drug Combinatio	2000

Article	Year
Tolerability and efficacy of a combination of paracetamol and caffeine in the treatment of tension-type headache: a randomised, double-blind, double-dummy, cross-over study versus placebo and naproxen sodium. The journal of headache and pain, 2008, Volume: 9, Issue:6 Topics: Acetaminophen; Adolescent; Adult; Aged; Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Ster	2008
Headache classification by history has only limited predictive value for headache episodes treated in controlled trials with OTC analgesics. Cephalalgia : an international journal of headache, 2009, Volume: 29, Issue:2 Topics: Acetaminophen; Adolescent; Adult; Aged; Analgesics, Non-Narcotic; Aspirin; Caffeine; Double-Blind Me	2009
The efficacy and tolerability of a fixed combination of acetylsalicylic acid, paracetamol, and caffeine in patients with severe headache: a post-hoc subgroup analysis from a multicentre, randomized, double-blind, single-dose, placebo-controlled parallel g Cephalalgia : an international journal of headache, 2011, Volume: 31, Issue:14 Topics: Acetaminophen; Adolescent; Adult; Aged; Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Ster	2011
The fixed combination of acetylsalicylic acid, paracetamol and caffeine is more effective than single substances and dual combination for the treatment of headache: a multicentre, randomized, double-blind, single-dose, placebo-controlled parallel group st Cephalalgia : an international journal of headache, 2005, Volume: 25, Issue:10 Topics: Acetaminophen; Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Caffeine;	2005
Efficacy of a fixed combination of indomethacin, prochlorperazine, and caffeine in the treatment of episodic tension-type headache: a double-blind, randomized, nimesulide-controlled, parallel group, multicentre trial. European journal of neurology, 2005, Volume: 12, Issue:10 Topics: Administration, Oral; Adolescent; Adult; Aged; Analysis of Variance; Antipsychotic Agents; Caffeine;	2005
Evaluation of alternative statistical models for crossover studies to demonstrate caffeine adjuvancy in the treatment of tension headache. Journal of biopharmaceutical statistics, 1994, Volume: 4, Issue:3 Topics: Caffeine; Cross-Over Studies; Drug Therapy, Combination; Humans; Models, Statistical; Multivariate A	1994
Caffeine as an analgesic adjuvant in tension headache. Clinical pharmacology and therapeutics, 1994, Volume: 56, Issue:5 Topics: Acetaminophen; Adolescent; Adult; Aged; Aspirin; Caffeine; Cross-Over Studies; Double-Blind Method;	1994
Ibuprofen plus caffeine in the treatment of tension-type headache. Clinical pharmacology and therapeutics, 2000, Volume: 68, Issue:3 Topics: Administration, Oral; Adult; Aged; Analgesics, Non-Narcotic; Caffeine; Central Nervous System Stimul	2000
The use of ibuprofen plus caffeine to treat tension-type headache. Current pain and headache reports, 2001, Volume: 5, Issue:5 Topics: Adolescent; Adult; Aged; Analgesics, Non-Narcotic; Caffeine; Central Nervous System Stimulants; Doub	2001

Article	Year
Primary headache characters and coping strategies among medical students of Umm Al-Qura University in the Western Region of Saudi Arabia. Neurosciences (Riyadh, Saudi Arabia), 2018, Volume: 23, Issue:4 Topics: Adult; Analgesics; Caffeine; Female; Headache; Humans; Male; Migraine Disorders; Saudi Arabia; Sleep	2018
Comments on 'Efficacy of fixed combinations of acetylsalicylic acid, acetaminophen and caffeine in the treatment of idiopathic headache: a review'. European journal of neurology, 2010, Volume: 17, Issue:11 Topics: Acetaminophen; Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Caffeine;	2010
Headache. Pharmacological approach to treatment. California medicine, 1961, Volume: 95 Topics: Caffeine; Headache; Headache Disorders; Humans; Hypnotics and Sedatives; Migraine Disorders; Tension	1961
TENSION HEADACHE: A NEW AGENT FOR ITS SYMPTOMATIC RELIEF. Headache, 1965, Volume: 5 Topics: Aspirin; Barbiturates; Caffeine; Diagnosis; Drug Therapy; Headache; Humans; Mental Disorders; Phenac	1965
[Alimentary trigger factors that provoke migraine and tension-type headache]. Schmerz (Berlin, Germany), 2006, Volume: 20, Issue:2 Topics: Cacao; Caffeine; Dehydration; Digestive System Diseases; Humans; Migraine Disorders; Substance Withd	2006
Amphetamine, migraine, and brain noradrenergic activation: contradictions in headache research. Headache, 2006, Volume: 46, Issue:1 Topics: Brain; Brain Chemistry; Caffeine; Central Nervous System Stimulants; Contraindications; Cross-Over S	2006
[The efficacy of Solpadeine in patients with primary forms of headache]. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova, 1997, Volume: 97, Issue:9 Topics: Acetaminophen; Adult; Analgesics; Caffeine; Codeine; Drug Combinations; Drug Evaluation; Female; Hum	1997
[Clinical evaluation of the efficacy of the paracetamol and caffeine combination in the treatment of tension headache]. Arquivos de neuro-psiquiatria, 2000, Volume: 58, Issue:1 Topics: Acetaminophen; Adult; Aged; Aged, 80 and over; Analgesics, Non-Narcotic; Caffeine; Central Nervous S	2000
Is the combination of ibuprofen and caffeine effective for the treatment of a tension-type headache? The Journal of family practice, 2001, Volume: 50, Issue:1 Topics: Analgesics, Non-Narcotic; Caffeine; Central Nervous System Stimulants; Double-Blind Method; Drug The	2001

caffeine and Headache, Tension