Complete Treatment Guide For Secondary Headache: Medications, Radiation Treatment, Surgery

Primary headaches are migraine, tension and cluster headache. Headache is defined as secondary headache when primary cause of headache is excluded. Secondary headache is caused by inflammation or infection of the soft tissue lying within the skull, abnormal metabolism, brain injury or any space occupying disease within the skull. Treatment of secondary headache depends on cause of the headache.

Treatment involves NSAIDs, opioids, antidepressants, anti-anxiety medications and antibiotics.

• Sinusitis- Inflammation and infection of sinuses of the skull.
• Meningitis.
• Encephalitis.
• Brain Abscess.
• Giant Cell Arteritis.
• Toxoplasmosis.
• Trigeminal Neuralgia.

Treatment involves NSAIDs, opioids, chemotherapy, radiation treatment and surgery.

• Arterial Aneurysm.
• Intracerebral Bleeding And Hematoma.
• Subdural Bleeding And Hematoma.
• Arteriovenous Malformation.
• Brain Tumor.
• Chiari Malformation.
• Hydrocephalus.

Treatment involves NSAIDs, opioids, antidepressants, antianxiety medications intravenous fluid and epidural blood patch.

• Dehydration.
• Carbon Monoxide Poisoning.
• Hangover From Over Consumption Of Alcohol.
• Stroke.
• Spinal Headache.

Treatment involves NSAIDs, opioids, antidepressants, antianxiety medications, antibiotics and surgery.

• Brain Concussion.
• Brain Contusion.

1. Medications.
2. Radiation Treatment.
3. Surgery.
4. Cognitive Behavioral Therapy.

1. Nonsteroidal Anti-inflammatory Medications.
2. Opioids– Prescribed for headache and pain.
3. Antiepileptic/Anti-Seizure Medications.
4. Antidepressants.
5. Capsicum.
6. Anti-Anxiety Medications.
7. Corticosteroids.
8. Antibiotics- Prescribed for infection.
9. Chemotherapy- Prescribed to treat brain tumor.

NSAIDS are anti-inflammatory medication abbreviated as NSAIDs. Mild headaches are often treated by NSAIDs alone. Daily attack of headaches are treated with preventive medication such as NSAIDs,

• Most Prescribed NSAIDs: Aspirin, ibuprofen (Motrin, Advil) and naproxen (Aleve).
• NSAIDs Side Effects:
• Dyspepsia.
• Ulcer.
• Perforation.
• Upper Gastrointestinal Bleeding.
• Severe Blood Loss.
• Combination of NSAIDs and COX-2 are not recommended in patient with history of myocardial infarction and heart attack.
• Erectile Dysfunction.

Acute and brief attack of headache most of the time gets better without any treatment. Patients may develop resistance and tolerance to opioid medication.

• Patient dependent on opioids for pain relief at times may behave like drug addict.
• Opioid dependence some time needs higher dosage and frequent need of pain medications.
• These symptoms are because of opioid dependence to achieve pain relief and classified as Pseudoaddiction.
• Opioids do cause addiction in few patients and treatment of headache with opioids become difficult.

Side Effects of Opioid Medications:

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

Choice of Opioids:

i) Semisynthetic Derivatives : Hydrocodone, Hydromorphone, Oxycodone, Oxymorphone Diacetylmorphine (heroin), Dihydrocodeine, Nicomorphine,

ii) Synthetic Opioids

• Anilidopiperidines: Fentanyl, Sufentanil, Alfentanil, Remifentanil and Carfentanil.
• Phenylpiperidines: Meperidine, Allyprodine and Ketobemidone.
• Diphenylpropylamine Derivatives: Propxyphene, Dextromoramide, Methadone, Piritramide, Dipipanone, Difenoxin, Diphenoxylate and Loperamide.
• Benzomorphan Derivatives: Pentazocine, Phenazocine and Dezocine.
• Oripavine Derivatives: Buprenorphine and Etorphine.
• Morphinan Derivatives: Butorphanol, Levomethorphan, Nalbuphine and Levorphanol.
• Others: Tramadol, Tapentadol, Meptazinol.

Anti-seizure medications are thought to reduce the occurrence of migraines by calming inflamed blood vessels in the brain, which may lead to migraine pain. However, none of these medications is a cure for secondary headache. Antiepileptics are diverse group of medications. Most common used antiepileptic in headache treatment is gabapentine (Neurontin), Lyrica, Topamax and Depakote.

i) Gabapentin:

1. GABA agonist also known as Neurontin, Gabarone, Fanatrex, Gralise and Nupentin. Mechanism of action as an analgesic is not known.
2. Several pharmacological actions were observed such as GABA agonist, interaction with voltage gated calcium channel and it halts the formation of new synapses. Gabapentin is very effective in 1/3rd of fibromyalgia and chronic neuropathic pain. Neuropathic pain caused by cancer, HIV, radiation treatment and complex regional pain syndrome is treated with gabapentin.

ii) Pregabalin Also known as Lyrica.

1. Calcium Channel : Binds to voltage-dependent calcium channel and decreased release of neurotransmitter such as glutamate, noradrenaline, substance P, and calcitonin gene related peptide and gamma aminobutyric acid.
2. FDA Approved: Lyrica became the first medication approved specifically for treating fibromyalgia.
3. Nerve Pain: Lyrica may work by blocking nerve pain in patients with fibromyalgia.
4. Flexible Dosage: Lyrica has advantages of flexible dosing that can be adjusted according to persistent symptoms.

Antidepressants were “associated with improvements in pain, depression, fatigue, sleep disturbances, and health-related quality of life in patients with FMS.” Drugs that simultaneously increase the amount of two brain nerve transmitters, serotonin and norepinephrine; have been approved to treat fibromyalgia in adults. These drugs include duloxetine and milnacipran.

i) Tricyclic Antidepressants (Elavil)

• Serotonin-norepinephrine reuptake inhibitors.
• Elavil is a potent antihistaminic and anticholinergic medication.
• Elavil also inhibits sodium and calcium channel at cell membrane.
• Side effects secondary to antihistaminic action such as somnolence is beneficial in treating fibromyalgia.
• Tricyclic antidepressants appear to reduce fatigue, relieve muscle pain and spasm, and promote deep, restorative sleep in patients with fibromyalgia.
• Tricyclics work by interfering with a nerve transmitter chemical in the brain called serotonin. Tricyclic medications can cause tiredness and fatigue. Examples of tricyclic antidepressants commonly used in treating fibromyalgia include amitriptyline (Elavil) and doxepin (Sinequan).

ii) Prozac I :

• Prozac is selective serotonin reuptake inhibitor. Prozac does not inhibit norepinephrine or dopamine reuptake.
• Low dose with Elavil has been effective in symptomatic relief.
• The combination is also more effective in promoting restful sleep and improving an overall sense of well-being.
• Prozac can make patients more cheerful and awake. Useful in combination with Elavil.
• Prozac has also been shown to be effective when used alone for some patients with fibromyalgia.

iii) Trazadone (Desyrel) :

• Serotonin antagonist and reuptake inhibitor.
• It is anxiolytic and hypnotic.
• It has least anticholinergic effects such as dry mouth, constipation, tachycardia and sexual side effects, which are common with Elavil.
• Trazadone can be taken at bedtime to improve sleep when tricyclic antidepressants are not tolerated.

iv) Duloxetine (Cymbalta) :

• Increases amount of serotonin and norepinephrine in brain by inhibiting the uptake.
• Therapeutic dosage is effective in treating depression and neuropathic pain.
• Cymbalta also suppresses anxiety in-patient with history of fibromyalgia and neuropathic pain.

v) Milnacipran (Savella) :

• Similar to duloxetine inhibits reuptake of serotonin and norepinephrine.

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

Side Effects of Capsicum:

• Burning sensation over skin and nose.
• Sneezing and watery eyes.
• Stomach upset.
• Sweating.
• Flushing and running nose.
• Dermatitis.

Serious Side Effects:

• Liver and kidney damage.
• Stop using 2 weeks before surgery, may cause side effects of bleeding.

GABA Effects: Benzodiazepam enhances GABA effects such as sedative, hypnotic (sleep inducing), anxiolytic, anticonvulsant, muscle relaxant and amnestic action.

• Therapeutic Outcome: Benzodiazepam are therapeutically effective in treating anxiety, insomnia, agitation, seizures, muscle spasms and alcohol withdrawal.
• Duration: Benzodiazepam are short, intermediate or long acting depending on ½ life. Short acting is useful in insomnia and long acting in anxiety and fibromyalgia.
• Adenosine Reuptake Inhibitors: Benzodiazepam is also adenosine reuptake inhibitors and useful in treating convulsion and muscle spasm.

Corticosteroid drugs (also called steroids) are used in allergic reaction and autoimmune disease as anti-inflammatory medications.

• Corticosteroids are membrane stabilizing agents, prescribed for headache to prevent irritability of cortical and subcortical centers.
• It enhances the effect of Verapamil in treatment of headache and often prescribed with Verapamil. Prednisone has been tried as short term breakthrough pain meds for cluster headache.
• It is often prescribed as tablet form Prednisone and injection form Decadron.

Side Effects of Corticosteroids:

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

Primary brain tumor is gliomas and medulloblastoma.

Chemotherapy medication used to kill and slow down the growth of cancer cells. Blood brain barrier restrict and filters medication passing from blood to brain tissue. Chemotherapy is most effective after radiation treatment and surgery.

Route of Chemotherapy Administration:

• Oral: Not effective.
• Intravenous: Effective.
• Intraarterial: Very effective if injected in artery supplying blood to cancer tissue.
• Local Delivery: Medications delivered within brain tumor.
• Intrathecal: Cancer medications injected in the cerebrospinal fluid near cancer tissue.
• Interstitial Delivery: Wafer soaked with anti-cancer medication implanted into tumor cavity left behind after excision of tumor.

Most Commonly Used Chemotherapy:

• Temozolomide (Temodar).
• Carmustine (BCNU, BICNU).
• PCV Drug Regime : PCV Procarbazine (Matulane), Lomustine (CCNU), and Vincristine (Oncovin).
• Platinum: Based Drugs. Cisplatin (Platinol) and Carboplatin (Paraplatin).

Less Common Used Chemotherapy: Tamoxifen (Nolvadex) and paclitaxel (Taxol), which are used to treat breast cancer

• Topotecan (Hycamtin), which is used to treat ovarian and lung cancers.
• Vorinostat (Zolinza), which is approved for treatment of cutaneous T-cell lymphoma.
• Irinotecan (Campath) is another cancer drug that is being studied in combination treatment.

Antibiotics are prescribed for infection such as meningitis, encephalitis, and sinusitis.

Antibiotics are selected following blood examinations. A Blood examination is performed to evaluate antibiotic sensitivity test. Appropriate antibiotics and route of administration depends on cause of infection and anatomical area infected.

• Oxygen percentage in atmosphere is 21%. Oxygen therapy can provide from 30% to 100% oxygen.
• Nasal oxygen therapy using nasal cannula provides 30 to 40% oxygen. Tight fitting face mask or endotracheal tube can deliver up to 100% oxygen.
• Oxygen therapy has been used in secondary headache caused by 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. Patient is advised to inhale oxygen for 15 minutes several times a day.

High energy radiation kills the cancer cells and shrinks the tumor mass.

i) External- By Using Radiation Beam:

1. Intensity modulated radiation therapy.
2. Image Guided Radiation Therapy- Combined with CAT scan, MRI and PET scan.
3. Tomotherapy : Image guided intensity modulated radiation therapy.
4. Stereotactic Radiosurgery : Used in small tumor or brain metastasis. High dose radiation can be delivered using stereotactic method of positioning needle in tumor mass.
5. Proton Therapy : Radiation beam is delivered by proton and photon beams. Protons are charged particles.

ii) Internal by injecting radioactive iodine.

• Tumor and Metastasis : Excision.
• Aneurysm : Clipping and re-anastomosis.
• Blood Clot : Removal and stoppage of bleeding.
• Brain Abscess : Exploration and drainage of abscess.
• Skull Fracture : Repair.
• Ischemic Brain Tissue : Excision.
• Endovascular Coiling- Treat cerebral arterial aneurysm.

• Infection Bleeding Seizures.
• Dural Tear : CSF leak.
• Neurological Deficit : Sensory and motor nerve deficiency.
• Paralysis.
• Blood clot, thrombosis and embolism.
• Cognitive Deficiency : Memory and emotional expression.
• Endovascular Coiling.

Cognitive Behavior Therapy (CBT) is useful to assist change or modify behavior problems in-patient suffering with chronic headache.

• Undesired Behavior : Try to eliminate and reinforce the changed behavior.
• Mode of Various Therapies: Individuals and groups suffering with cluster headache and migraine.
• Therapy as a Treatment: CBT has also been used in organic disorder such as headache primary and secondary causing severe pain not responding to any treatment. Also very effective treatment for inpatient hospitalized patients complaining of headache and insomnia.
• Integration of behavioral therapy with cognitive therapy.
• Maladaptive thinking leads to change in affect and thus behavior.
• Computer based supervised therapy.
• Goal to change maladaptive thinking.

• Points out over generalizing of symptoms.
• Magnifying negative feelings.
• Minimizing positive thoughts.
• Guiding to more realistic effective concepts.
• Assess, reconceptualize and acquisition of positive skills.

i) Cognitively oriented.

ii) Behaviorally oriented.

iii) Imaginary exposure therapy combines both approaches.

• Systemic Desensitization: Systematic desensitization involves gradually exposing a patient to anxiety-provoking stimuli until the anxiety response was extinguished, or eliminated.
• Positive Reinforcement or reward improves behavior when compared with conditioning such as repetition of harmful behavior was punished and improvement in behavior was rewarded.
• Behavioral Treatments: 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.

Also Read:

• Diagnosis of Secondary Headache Based on Causes, Symptoms and Investigations