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Treatment for Headache: Medications, NSAIDs, Opioids, Oxygen Therapy, Surgery

Most individuals suffer from mild to severe headache at some point in their life. Headache is classified as tension headache, cluster headache, and migraine. Migraine is the most debilitating symptom and is observed in 4.4% of the patient visiting the office of General Practitioner.1 The tension headache is the most common type of headache and lasts for a few minutes to several hours.2 Most patients use over the counter medication to treat a tension headache. Most headaches are treated with NSAIDs and Tylenol. Occasionally lower dosage of opioids are prescribed for a headache that is resistant to most anti-headache medication. Among headaches, migraine resists most medication but frequently responds to triptans and ergotamine. The better therapeutic outcome is observed following treatment using triptan than ergots.3

Medication Treatment for Headache


Sumatriptan is also known as a triptan. Triptan is prescribed for migraine and cluster headache. Triptans are prescribed as a nasal spray and intravenous therapy. Sumatriptan injection is very effective in the treatment of migraines and cluster headaches and works within 15 minutes. The nasal route of sumatriptan is effective in 30 minutes. In most of the cases, the effect of the nasal treatment lasts less than 45 minutes. Quality of pain relief is better with intravenous therapy than nasal spray treatment.3 Newer triptans with fewer side effects used are zolmitriptan (Zomig) in oral or nasal spray forms.

Treatment for Headache: Medications, NSAIDs, Opioids, Oxygen Therapy, Surgery

Side Effects of Sumatriptan Are As Follows:

  • Nausea.
  • Dizziness.
  • Muscle weakness.
  • Heaviness or pressure in the chest.
  • Tingling and numbness in the toes.
  • Rapid heart rate.

Complications of Sumatriptan:


Dehydroergotamine (DHE) is prescribed for migraine and cluster headache. Most of the patients suffering from cluster headache respond within 5 minutes with no pain. Ergotamine can be prescribed as tablets, suppositories, and nasal spray.

Side Effects of Ergotamine:

  • Tachycardia.
  • Nausea and vomiting.
  • Diarrhea.
  • Dizziness.
  • Muscle weakness.
  • Heaviness or pressure in the chest.
  • Tingling and numbness in the toes.

Complications of Ergotamine:

  • Stroke secondary to vasoconstriction of cerebral arterial blood vessels.
  • Heart attack and angina secondary to vasoconstriction of the coronary artery.
  • Hypertension caused by vasoconstriction of the peripheral arterial system.

Serotonin syndrome is a life-threatening condition. Sumatriptan increases the overall concentration of serotonin in the brain. Symptoms observed are tachycardia, nausea, vomiting, diarrhea, hallucination, anxiety, tremors, and restlessness.

Lidocaine (Local Anesthetics)

Lidocaine– is a local anesthetic and used in resistant cases to treat a cluster headache. Lidocaine nasal drops or nasal spray is recommended for optimum effects.4 A group of patients with a history of cluster headache may not respond to lidocaine treatment. Reports suggest that it is helpful for most patients within about 40 minutes.

Side Effects of Lidocaine:

  • Unpleasant taste.
  • Numbness of area treated.

Capsicum for Headache

Capsicum originated from hot pepper, and it is used for tension and cluster headache. Capsicum is applied over occipital skin and also inside the nose. It is a safe medication and available as over the counter product in pharmacy.

Side Effects of Capsicum:

Serious Side Effects of Capsicum:

  • Liver and kidney damage and
  • Bleeding disorder.
  • It is recommended to discontinue medications for two weeks to prevent post-op bleeding if a patient is scheduled for surgery

Calcium Channel Blockers for Headache

Calcium channel blockers influence the calcium channel of the smooth muscle of blood vessels. A calcium channel blocker is effective in treating hypertension and coronary vascular disease. Migraine or sinus headache and cluster headache is secondary to changes in the diameter of cerebral blood vessels. Calcium channel blocker causes changes in the width of a cerebral blood vessel resulting in a reduction of headache symptoms. Verapamil is a preferred calcium channel blocker used for preventive treatment of cluster and migraine headache.5, 6 Medication should be taken for 2 to 3 weeks to build maximum effects.

Side Effects of Calcium Channel Blockers:

  • Constipation.
  • Severe Hypertension – If discontinued abruptly.
  • Bradycardia and Hypertension – If overdose.
  • Heart Failure – History of congestive heart failure.

Lithium for Headache

Lithium (Eskalith, Lithane, Lithobid, Lethonate, Lithotabs), commonly used for bipolar disorder, may also help prevent cluster headaches. The patient usually receives benefit within two weeks of starting to take the drug, often within the first week. Lithium may be used alone or with other medications. Lithium can have many side effects, including trembling of hands, nausea, and increased thirst. Weight gain is a common side effect with long-term use.

Side Effects of Lithium:

  • Thinning of the hair and hair loss.
  • Mild tremor.
  • Loss of appetite.
  • Tiredness.
  • Nausea.
  • Severe allergic reactions.
  • Skin – Rash, hives, itching.
  • Respiratory system – Bronchospasm, dyspnea and tightness in the chest.
  • Cardiovascular system – Slow or irregular heartbeat.
  • Central nervous system – Confusion, restlessness, tremor, dizziness, faintness, bladder and bowel incontinence, numbness of the skin, ringing in the ear, restlessness, seizures and severe or persistent headache.
  • Musculoskeletal system – Tremors, involuntary muscle twitching, decrease muscle tone, and coordination.
  • Gastrointestinal system – Edema of oral cavity and tongue, nausea, and diarrhea.

Anti-Seizure Medication Treatment for Headache

Anti-seizure medications are used for the prevention and treatment of headache.7 Anti-seizure medications thought to reduce the occurrence of migraines by calming inflamed blood vessels in the brain, which may lead to migraine pain or sinus headache. However, none of these medications is a cure for migraines. Antiepileptics are a diverse group of medications used as antiseizure. Some of the medication within this large group is being used to treat a headache. In research, there were areas of hyper activities in the brain that were recognized in epilepsy and headache patients. Antiepileptic medications reduced the area of irritability by its molecular action at the voltage-gated sodium channel. The most common used antiepileptic in headache treatment is Topamax, Depakote, and Neurontin.

Topamax – The oral tablet is taken every day as prescribed, even if headache symptoms are absent.

Side Effects of Topamax:

  • Tachycardia.
  • Dyspnea – breathlessness or shortness of breath.
  • Chest pain.
  • Urine – bloody or cloudy.
  • Cognitive symptoms – thoughts of suicide or aggressive behavior.
  • Depression.
  • Depakote – Depakote (valproic acid) is available as capsule, tablet and syrup.

Side Effects of Depakote:

Side Effects of Neurontin:


Serious Allergic Reaction:

  • Skin – Rash, hives, itching.
  • Respiratory System – Bronchospasm, dyspnea and tightness in the chest.
  • Central Nervous System – Seizures and Tremors.
  • Musculoskeletal System – Tremors.

Corticosteroids for Headache

Corticosteroid drugs (also called steroids) are used in allergic reaction and autoimmune diseases anti-inflammatory medications. Corticosteroids are membrane stabilizing agents, prescribed for the headache to prevent irritability of cortical and subcortical centers. It enhances the effect of verapamil in the treatment of headaches and often prescribed with verapamil. Prednisone is being tried as short term breakthrough pain meds for cluster headache. It is usually prescribed as a tablet form prednisone and injection form decadron.

Side Effects of Corticosteroids:

  • Symptoms like diabetes increase blood sugar levels.
  • General Symptoms – Dry mouth, fatigue, weakness, blurred vision, facial swelling, infection, avascular necrosis and glaucoma.
  • Central Nervous System – Anxious, depression, confusion, insomnia, mania, psychosis.
  • Gastrointestinal System – Stomach bloating feeling, increase appetite, weight gain, abdominal pain, diarrhea and peptic ulcer.
  • Urination – Frequent urination.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) for Headache

  • NSAIDs are anti-inflammatory medication abbreviated as NSAIDs. NSAIDs are used for the treatment of headache in combination with other medications. Mild headaches are often treated by NSAIDs alone.
  • Analgesics – NSAIDs are not effective in severe pain and also pain caused by non-inflammatory etiology.
  • Most Prescribed NSAIDs – Aspirin, Ibuprofen (Motrin, Advil) and Naproxen (Aleve).
  • Side Effects – Complications caused by NSAIDs can be devastating if continued for a prolonged period.
  • Dose-dependent Side Effects – Dyspepsia, ulcer, perforation, upper gastrointestinal bleeding, and severe blood loss. A combination of aspirin and COX 2 inhibitor (Celebrex) may block the cardioprotective effects of aspirin.
  • Myocardial Infarction and Stroke – NSAIDs with COX2 inhibitor may increase risk. A combination of NSAIDs and COX 2 are not recommended in-patient with a history of myocardial infarction and heart attack.
  • Erectile Dysfunction.

NSAIDs Combinations With Other Medications Used In Headache

Most acute attacks of tension-type headaches get better without any treatment. Over-the-counter pain relievers such as acetaminophen or non-steroidal anti-inflammatory drugs (NSAIDs) can treat mild symptoms. Aspirin or ibuprofen (generic, Advil, other brands) are usually the first choices, followed by naproxen (generic, Aleve). Some patients may also find helpful medications that combine a pain reliever with caffeine.

  • Ibuprofen. (Advil, Motrin)
  • Naproxen. (Aleve, Naprelan, Naprosyn, Anaprox)
  • Acetaminophen/butalbital. (Bupap, Cephradine, Phrenilin)
  • Acetaminophen/butalbital/caffeine. (Esgic, Fioricet)
  • Aspirin/butalbital/caffeine. (Fiorinal)
  • Acetaminophen/butalbital/caffeine/codeine. (Fioricet with Codeine)
  • Acetaminophen/Dichloralphenazone/Sometheptene Mucate. (Midrin)
  • Acetaminophen/Phenyltoloxamine. (Percogesic)
  • Acetaminophen/Isometheptene mucate. (Prodrin)

Anti-Anxiety Medications for Headache

Sedatives are prescribed for selective cases of headache. The most common indication to use sedatives or anti-anxiety medications are Tension headache and prevent a recurrent episode. Buspirone (Buspar) and Alprazolam are prescribed as anti-anxiety medications.

Side Effects of Anti-Anxiety Medications:

  • Drowsiness.
  • Irritability.
  • Fatigue.
  • Low blood pressure.
  • Amnesia.

Opioid Medications for Headache

Opioids are used for treating tension headaches, which are not responding to NSAIDs and other medications. Acute and brief attack of headache most of the time gets better without any treatment. Patients may develop resistance and tolerance to opioid medication. Patients are advised to consider relaxation treatment, cognitive behavioral therapy, and lifestyle changes if failed to get pain relief with opioids. Daily attacks of headaches are treated with preventive medication such as NSAIDs, and NSAIDs combined with opiates or opioids. All other options of medications should be tried before introducing opioid prescriptions. Patients dependent on opioids for pain relief consume frequent pills for rapid pain relief and at the time may behave like a drug addict. Opioid dependence some time needs a higher dosage and frequent need for pain medications. These symptoms are because of opioid dependence to achieve pain relief and classified as Pseudoaddiction. Opioids do cause addiction in a few patients, and treatment of headache with opioids become difficult.

Side Effects of Opioids:

Common Side Effects of Opioids:

  • Nausea.
  • Vomiting.
  • Constipation.
  • Dry mouth.
  • Itching.
  • Miosis.

Less Common Side Effects of Opioids:

  • Skin – Itching, urticaria, hypothermia, and histamine-induced flushing.
  • Eyes – Miosis.
  • Gastrointestinal – Nausea, vomiting, dry mouth, constipation, and biliary spasm (colicky pain).
  • CNS – Depression, confusion, hallucination, delirium and dizziness.
  • Respiratory System.
  • Depression
  • CVS – Bradycardia and occasional may be tachycardia.
  • Orthostatic hypotension.
  • Kidney, Ureter, and Bladder (KUB) – Urinary retention and ureteric spasm.
  • Musculoskeletal – Muscle spasm.

Botox for Headache

Botulinum toxin A (Botox) injections are typically used to smooth wrinkles in the practice of plastic surgery. Botox is used for the treatment of headaches, including the prevention of cluster headaches.8 Research is still preliminary, and there is no sufficient evidence to support its efficacy. Botox is the treatment of choice for headache localized over frontal, occipital and cervical (neck) region. Headache over parietal (top of head), temporal area (side of head above the ear), between eyes and behind the ear does not respond to botox injection.

Frequent Common Side Effects:

  • General Symptoms – Irritated eyes, facial pain, flu-like symptoms, inability to focus the eyes, neck pain, redness, swelling, tenderness at the injection site; sensitivity to light, sweating, and tiredness.
  • CNS – Anxiety, arm or leg pain, back pain, dizziness, drowsiness, and headache.
  • Gastrointestinal System – Nausea, constipation, dry mouth, dry, and indigestion.
  • Respiratory System – Increased cough, mild sore throat, and runny nose.
  • Musculoskeletal – Stiff or weak muscles at or near the injection site.

Severe Allergic Reactions Need Immediate Medical Attention:

  • Skin – Swelling of the mouth, face, lips, or tongue; fever and chills.
  • Respiratory system – Unusual hoarseness, wheezing, chest pain, difficulty swallowing or breathing, persistent sore throat and shortness of breath.
  • Kidney Ureter Bladder – Blood in the urine; burning, numbness, or tingling; burning with urination; difficult, frequent, or painful urination, loss of bladder control, eyes-double or blurred vision, or other vision changes; drooping of the upper eyelid and eyelid swelling.
  • Central Nervous System – Fainting; seizures, headache, dizziness speech changes or problems and worsening migraines.
  • Cardiovascular System – Irregular heartbeat.
  • Musculoskeletal System – Loss of strength, paralysis, and severe or persistent muscle weakness.

Melatonins-(N-acetyl-5-methoxytryptamine) for Headache

Melatonin is found in animals, plants, and microbes. Melatonin is sold over the counter in the USA. In an animal research, melatonin was investigated against carcinogens. Melatonin prevents the initiation of the impairment of DNA by carcinogens. Impaired DNA otherwise would have initiated cancer growth.

Melatonin is being prescribed for migraines, as well as tension headache.9 Melatonin is widely used as an antioxidant in diseases such as immunodeficiency syndrome, autism, aging, Alzheimer disease, delirium mood disorder, alternative medicine, tinnitus, cancer and gallstone.

Oxygen Therapy for Headache

Oxygen therapy – Oxygen percentage in the atmosphere is 21%. Oxygen therapy can provide from 30% to 100% oxygen. Nasal oxygen therapy using nasal cannula offers 30 to 40% oxygen. A tight-fitting face mask or endotracheal tube can deliver up to 100% oxygen. Oxygen therapy has been used in congestive heart failure, chronic obstructive lung disease (COPD), and allergic reaction causing shortness of breath, convulsion, and hemorrhagic shock. Oxygen therapy up to 100% is used in cluster and tension headache on and often. The patient is advised to inhale oxygen for 15 minutes several times a day.

Surgery for Headache

  • Occipital Neuralgia- Pain over the back of the head (occipital area of a skull) is caused by irritation of the lesser and greater occipital nerve. Such pain is treated with radiofrequency ablation of bother lesser and greater occipital nerve.10
  • Deep Brain Stimulation: Chronic cluster and migraine headaches in a few patients are resistant to all treatments. These patients are imprisoned in the house suffering from an intense headache and unable to perform any regular activities. Severe pain may bring multiple thoughts of suicide. These patients are given a trial of deep brain stimulation as a last option of treatment. The published studies suggest that implants of the hypothalamic stimulator have a better outcome in treating a cluster headache.11
  • Gasserian (Trigeminal) Ganglion Radiofrequency Rhizotomy: Headache associated with trigeminal nerve irritation or pinch is treated with Gasserian ganglion neurotomy. Gasserian or trigeminal ganglion ablation is performed by using radiofrequency heat12 or glycerol. The trigeminal ganglion is identified during the procedure by sensory nerve stimulation. The trigeminal ganglion is treated with heat that is produced by radiofrequency waves. Pain carrying fibers are also often destroyed in few cases using glycerol as a chemical rhizotomy.
  • Microvascular Decompression of Trigeminal Nerve: Trigeminal nerve pain is observed in patients suffering from postherpetic neuralgia and traumatic injury of the trigeminal nerve. Chronic headache pain secondary to trigeminal neuralgia is treated with microvascular decompression of the trigeminal nerve.13 Blood vessels surrounding the trigeminal nerve are selectively ligated or cauterized. Such treatment eliminates the pressure over the trigeminal ganglion.

Craniotomy for Headache

A craniotomy is a surgical procedure performed to the exposed brain and subcortical part of the brain. It is a highly skilled procedure, which involves the removal of part of the skull bone and reattached at the end of surgery. Surgery is performed under the guidance of a CT scan. MRI images are studied before surgery as well as during operation.

Indication for Craniotomy Procedure:

  • Tumor and Metastasis – Excision.
  • Aneurysm – Clipping and reanastomosis.
  • Blood Clot – Evacuation and stoppage of bleeding.
  • Brain Abscess – Excision and drainage.
  • Skull Fracture – Repair.
  • Ischemic Brain Tissue – Excision.

Risk Involved:

  • Infection.
  • Bleeding.
  • Seizures.
  • Dural tear – CSF leak.
  • Neurological Deficit – sensory and motor nerve deficiency, paralysis.
  • The blood clot, thrombosis, and embolism.
  • Cognitive Deficiency – memory, emotional expression.

Cognitive Behavioral Treatments for Headache

Cognitive Behavior Therapy (CBT) is useful to assist change or modify behavior problems in patients suffering from chronic headaches or sinus headaches.

Following modification of behavior helps to reduce or eliminate headache:

Behavioral Treatment Is Classified As Follows:

  • Cognitively Oriented.
  • Behaviorally Oriented.
  • Imaginary Exposure Therapy Combines Both Approaches.
  • Principle of Behavioral Treatment:
  • Points out over generalizing of symptoms.
  • Magnifying negative feelings.
  • Minimizing positive thoughts.
  • Guiding to more realistic, effective concepts.
  • Assess, reconceptualized, and acquisition of positive skills.

The Goal of Behavioral Therapy:

Modify Undesired Behavior – The treatment is targetted to eliminate and reinforced the changed behavior. Such therapy is performed as individuals or as a group.

Therapy as a Treatment – CBT has also been used to treat a primary and secondary headache that is causing severe pain and not responding to any alternative treatment. CBT is an active treatment inpatient suffering from headaches and insomnia.

Combination of Behavioral Therapy with Cognitive Therapy- Several centers have tried simultaneous behavior and cognitive therapy that has provided better results.

Maladaptive Thinking- Maladaptive thinking causes stress to induce a headache. Behavioral therapy helps to modify or eliminate maladaptive thinking.

Systemic Desensitization –

Systematic desensitization involves gradually exposing a patient to anxiety-provoking stimuli until the anxiety response was extinguished, or eliminated.

Positive Reinforcement

Positive reinforcement improves behavior when compare with conditioning therapy. The therapy recommends punishment for repetitive harmful behavior and rewards for improvement in behavior.

Behavioral therapies can be a helpful accompaniment to drug treatment. These approaches can help with pain management and enable patients to feel more in control of their condition.


  1. The diagnosis and treatment of chronic migraine Mark W. Weatherall, Ther Adv Chronic Dis. 2015 May; 6(3): 115–123. 
  2. Tension type headache Debashish Chowdhury, Ann Indian Acad Neurol. 2012 Aug; 15(Suppl 1): S83–S88.
  3. Triptans in the Acute Treatment of Migraine: A Systematic Review and Network Meta-Analysis. Cameron C1,2Kelly S2Hsieh SC2Murphy M2Chen L2Kotb A2Peterson J2Coyle D1Skidmore B2Gomes T3Clifford T1,4Wells G1,2., Headache. 2015 Jul-Aug;55 Suppl 4:221-35.
  4. Intranasal lidocaine for cluster headache. Robbins L1., Headache. 1995 Feb;35(2):83-4.
  5.  Verapamil for cluster headache. Clinical pharmacology and possible mode of action. Tfelt-Hansen P1Tfelt-Hansen J., Headache. 2009 Jan;49(1):117-25. doi: 10.1111/j.1526-4610.2008.01298.x.
  6.  Clin Neuropharmacol.1986;9(4):311-28. Calcium channel antagonists and the treatment of migraine. Greenberg DA.
  7. Antiepileptic drugs: how they work in headache. Cutrer FM1., Headache. 2001 Nov-Dec;41 Suppl 1:S3-10.
  8. Botulinum toxin in the management of chronic migraine: clinical evidence and experience Claus M EscherLejla ParackaDirk Dressler, and Katja Kollewe, Ther Adv Neurol Disord. 2017 Feb; 10(2): 127–135.
  9. The therapeutic potential of melatonin in migraines and other headache types. Gagnier JJ1., Altern Med Rev. 2001 Aug;6(4):383-9.
  10. Treatment of Occipital Neuralgia by Thermal Radiofrequency Ablation Lance M. Hoffman, MD,1 Alaa Abd-Elsayed, MD, MPH,2 Tim J. Burroughs, MD,1 and Harsh Sachdeva, MD1 , Ochsner J. 2018 Fall; 18(3): 209–214.
  11. Deep brain stimulation in headache. Leone M1., Lancet Neurol. 2006 Oct;5(10):873-7.
  12. Long-term results of radiofrequency rhizotomy in the treatment of cluster headache. Taha JM1Tew JM Jr., Headache. 1995 Apr;35(4):193-6.
  13. Microvascular Decompression for Trigeminal Neuralgia: A regional unit’s experience Cathal HannanAlireza Shoakazemi, and Gavin Quigley, Ulster Med J. 2018 Jan; 87(1): 30–33.

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Team PainAssist
Team PainAssist
Written, Edited or Reviewed By: Team PainAssist, Pain Assist Inc. This article does not provide medical advice. See disclaimer
Last Modified On:June 28, 2019

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