Medication-Overuse Headache

• Also known as analgesic rebound headache, drug-induced headache, or medication-misuse headache.
• Commonly associated with the transformation from episodic to chronic headache disorders.

Etiology:

• Classified as a secondary headache in ICHD-3 (2018).
• Characterized by headache on
  • ≥15 days/month for ≥3 months
  • due to overuse of specific medications.

Main Risk Factors with Odds Ratio

• Demographic
  • Age (less than 50 years)–1.8
  • Female–1.9
  • Low educational level–1.9
• Self-reported complaints
  • Chronic musculoskeletal complaints–1.9
  • Gastrointestinal complaints–1.6
  • Anxiety or depression–4.7
• Lifestyle
  • Smoking–1.8
  • Physical inactivity–2.7
  • Metabolic syndrome–5.3
  • High daily caffeine intake (greater than 540mg versus less than 240mg)–1.4
• Medication
  • Tranquilizers–5.2
  • Aspirin–0.5
  • Ibuprofen–0.7
  • Opioids–2.3
• Chronic medication overuse, with varying risk profiles for different analgesic classes.

Epidemiology:

• Prevalence estimated at 0.5-2.6%, higher in certain regions and headache centers.
• MOH often associated with migraine (80% of cases) and affects individuals aged 30-50 with a female predominance.
• Various risk factors, including demographic, lifestyle, and medication-related factors.

Pathophysiology:

• Central sensitization plays a major role.
• Involves functional and structural changes in the central nervous system.
• Genetic predisposition and polymorphisms in certain genes may contribute.

History and Physical:

• Characteristics
  1. Variable type, severity, and location of Headache
  2. Resembles the pre-existing primary headache syndrome.
  3. Often more intense and frequent than before medication overuse.
  4. Unfortunate cycle of medication overuse leading to increased headache frequency.
  5. Medication intended for primary headache treatment becomes the cause of headaches.
• Timing
  1. Occur in the early morning (2am – 5am) daily
• Palliative
  1. Headaches resolve after Pain Medication discontinued
  2. Refractory to prophylactic medications
• Provocative factors
  1. Headache is easily precipitated
  2. may report morning headaches and neck pain due to overnight drug withdrawal or poor sleep quality.
  3. Withdrawal symptoms on stopping Pain Medications
• Medications
  • Ergotamine (≥10 days/month for ≥3 months)
  • Triptans (≥10 days/month for ≥3 months)
  • ASA – Aspirin (≥15 days/month for ≥3 months)
  • NSAIDs (≥15 days/month for ≥3 months)
  • Acetaminophen/paracetamol (≥15 days/month for ≥3 months)
  • Opioids (≥10 days/month for ≥3 months)
  • Combination analgesics (≥10 days/month for ≥3 months)
• Associated features
  • Nausea and other gastrointestinal symptoms
  • Asthenia
  • Anxiety
  • Depression
  • Irritability
  • Memory and concentration problems
  • Neck Pain
  • Vasomotor symptoms (Rhinorrhea, nasal congestion)
• Common presentations
  • Often presents to ER requesting Opioids
• Autonomic and Gastrointestinal Symptoms:
  • MOH can lead to skin hypersensitivity, autonomic symptoms (runny nose, tearing), and gastrointestinal symptoms (nausea, vomiting, diarrhea).
• Multiple Medication Use:
  • About 90% of MOH patients use multiple medications for headache relief.
• Dependency-Like Behavior:
  • More common in those who overuse opioids and triptans than with aspirin or ibuprofen.
  • Associated with a substance-related disorder spectrum.
  • Question- “How many times in a year have used an illegal drug or used a prescription medication for non-medical use?” : Interpretation: Drug Use Disorder(Test Sensitivity: 100%, Test Specificity: 74%)
• Psychiatric Comorbidities:
  • Frequent association with psychiatric mood disorders such as anxiety and depression.
  • Some patients meet criteria for depression (40%) and anxiety (58%).
• Family History and Genetic Predisposition:
  • Higher risk if there is a family history of MOH or substance abuse (drug or alcohol).
  • Genetic factors, including polymorphisms in genes like ACE, BDNF, COMT, and SERT.
• Associations with Other Conditions:
  • Associations with chronic musculoskeletal complaints, gastrointestinal complaints, and lifestyle factors (smoking, physical inactivity, metabolic syndrome).
• Effect of Medication Discontinuation:
  • Generally, MOH resolves upon cessation of the overused medication.
  • No longer a requirement for the headache pattern to return to the previous state within two months.

Treatment/Management:

• Emphasis on
  • patient education
  • effective prophylaxis
  • discontinuation of overused analgesic
  • follow-up.
• Strategies include replacing
  • overused medication
  • continuing overused medication during initial treatment
  • bridge therapy
• Prevention through patient education crucial.
• Specific transitional strategies include:
  • Replacing overused medication with alternative symptomatic therapy.
  • Continuing overused medication during initial treatment.
  • Using bridge therapy (temporary medication).
  • Discontinuing overused medication before starting prophylactic therapy.
• Analgesic Withdrawal
  1. Most medications may be stopped abruptly
     1. Non-Opioid Analgesics (e.g. nsaids)
     2. Triptans
  2. Gradually taper over 5 weeks (risk of withdrawal)
     1. Opioids
     2. Barbiturates
     3. Ergot alkaloids
     4. Benzodiazepines
     5. Caffeine
• Provide non-Opioid rescue medications during withdrawal
  • Antiemetics (Metoclopramide, Promethazine)
  • Antihistamines (Diphenhydramine or Hydroxyzine)
  • Most effective adjunctive withdrawal agents
    1. Prednisone 60 mg daily for 5 days (caution, due to adverse effects)
    2. Migraine Prophylaxis agents
       1. Topiramate (Topomax) 100-200 mg daily
       2. Amitriptyline 50 mg daily
• Prevention
  • Maximize Migraine Prophylaxis
  • Limit acute Migraine abortive medications to 10 days per month or 2 days per week
  • Long acting NSAIDs may be less likely than other simple Analgesics to cause Rebound Headaches
  • Get control of Migraine Headaches soon after episode onset (e.g. start Triptan at higher, effective dose early)

Differential Diagnosis:

• Considerations include various chronic daily headaches, such as migraine, tension-type headache, and secondary causes like head trauma.

Prognosis:

• Patient motivation is key to successful treatment.
• Withdrawal phase success rates of >50%, with relapse rates after 6 years ranging from 40-50%.
• Behavioral therapy can reduce relapse rates.

Complications:

• Side effects from medications, dependence, and toxicity.
• NSAIDs may cause upper gastrointestinal bleeding.