Migraine & Comorbid Depression

subjective and objective data: migraine with aura, migraine without aura, chronic migraine.

subjective and objective data: migraine with aura, migraine without aura, chronic migraine.

migraine with aura: migraine associated with visual symptoms (flashing lights and lines)

Migraine without aura: throbbing headache lasting 4-72 hours with at least 5 attacks in a lifetime

1. At least 2 of 4:

   1. Unilateral location

   2. Pulsating or throbbing quality

   3. Moderate to severe intensity

   4. Aggravation by/causing avoidance of routine physical activity

2. At least 1 of the following:

   1. Nausea or vomiting

   2. Photophobia

   3. Phonophobia

Chronic migraine: >15 times per month

Triggers for migraines

Stress,

sleep deprivation,

hypoglycemia/fasting,

menses,

1st trimester pregnancy,

bright lights,

diet (cheese/cured meats, chocolate, MSG),

drugs (vasodilators (nitroglycerin, nifedipine),

OCs, alcohol, cocaine, analgesic overuse)

Goals of preventing & treating migraine

1. Treat headache pain quickly and prevent recurrence

2. Treat associated symptoms (N/V, photophobia)

3. Restore functional ability

4. Minimize use of rescue medications and avoid rebound headaches

5. Reduce migraine frequency, severity, and disability

6. Improve responsiveness of acute therapies

7. Improve functioning and quality of life

8. Prevent headache

9. Avoid escalation of headache medication use

10. Reduce headache-related distress and psychological symptoms

Treatment variables

severity

prior treatments

Women of childbearing age (teratogenic potential)

presence of nausea (affects ROA)

likely presence of depression

ROA

ADEs

Abortive and prophylactic treatment modalities

Migraine abortive: triptans (triptans), ergot derivatives (DHE, ergotamine), OTC (APAP, naproxen), combinations (excedrin, treximet, cafergot), CGRP antagonist (ubrogepant), 5-HTf1 antagonist (lasmiditan)

Migraine prophylaxis: divalproex, topiramate, propranolol LA, amitriptyline, CGRP antagonists (erenumab, fremanezumab, galcanezumab)

Antinausea: ondansetron, prochlorperazine

Benefits and drawbacks for abortive pharmacologic (NSAIDs, Excedrin, triptans, gepants, lasmiditan, ergots) and prophylactic pharmacologic (BBs, divalproex, topiramate, Anti-CGRPs) treatments

Abortive: taken within 30 min or onset of aura phase

Prophylactic: consider only if 4 or more attacks per month, CIs, failure of therapy, or overuse of acute therapy.

Drug	Benefits	Drawbacks
NSAIDs	OTC availability	Less effective for moderate to severe migraine
Excedrin (APAP, caffeine, aspirin)	Proven efficacy in mild to moderate migraine	Less effective for moderate to severe migraine
Triptans  (5-HT1B agonists)	Migraine-specific, effective for aura and nausea	Ischemic cardiovascular effects (stroke risk)
Gepants (CGRP antagonists)	Migraine specific, safe in CV disease	--
Lasmiditan  (5-HT1F agonist)	Migraine-specific, safe in CV disease	Serotonin syndrome, sedation (C-V)
Ergots	May be effective in resistant cases	Significant vascular and GI effects

• give 8wks to assess effectiveness

• consider premenstrual prophylaxis (LA NSAID or triptan x 4-5 days during perimenstrual period

Drug	Benefits	Drawbacks
Beta-blockers (propranolol)	DOC for post-MI and angina	Mild fatigue, CI in asthma, DM
Divalproex	Effective for comorbid epilepsy and bipolar. Low dose for migraine	CI in pregnancy, potential hepatic toxicity
Topiramate	Effective for comorbid epilepsy. Low doses for migraine.	Cognitive AEs, CNS depression, weight loss
Anti-CGRP MAbs	Migraine-specific, highly effective	Hypersensitivity, upper respiratory effects, injection site reactions, $$$

Subjective and objective data consistent with major depressive disorder

S/sx lasting at least 2 weeks:

• depressed mood

• loss of pleasure or interest

• insomnia or hypersomnia (frequently)

• agitation or retardation (frequently)

• fatigue/loss of energy (frequently)

• significant weight loss

• worthlessness or guilt

• diminished concentration, indecisiveness

• recurrent thoughts of death or recurrent suicidal ideation/attempt

Can be attributed to:

• hormonal factors,

• altered NT activity,

• stress,

• genetics,

• comorbid condition (endocrine disorder, anemia, infection, lupus, SUD, anxiety, metabolic disorder, CVD, neurologic disease, malignant disease),

• drug therapies (antihypertensives, OCs, steroids, etc)

Objective: PHQ-2/PHQ-9, suicide screening questions

Patient- and agent-related variables that impact the selection of antidepressant drug therapy.

Indication (psychiatric or medical comorbidity)

• Previous response or familial response

• Type of depression/severity of symptoms

• Pt. preference

• Financial considerations (brand vs. generic)

• Chronicity

• Side effect profile

• SI/risk of overdose

• Concurrent medical problems

• Potential drug interactions

• Adherence: Start low and go slow as side effects permit, Elderly pts.: 1⁄2 the usual adult dose

• Underlying anxiety disorder or suspected bipolar disorder: lower doses, ↓ initial anxiety and detect signs of switching

Therapeutic objectives for MDD

• Minimize depressive symptoms (sad, anhedonia, feelings of helplessness, suicidal thoughts, diminished concentration, weight loss)

• Reduce the depth and length of depression

• Prevent suicide

• Minimize disrupting effects on work

• Induce remission of depression and achieve euthymia

• Prevent recurrence

Time of onset of antidepressant effects & management

7-10 days: improved sleep and anxiety

7-21 days: improves self-care, thinking/concentration, energy lvl

2-6 weeks: improved mood, reduced suicidal ideation

Maintenance:

1. increase dose or use adjunct for partial responders (antipsychotics, lithium, buspirone)

2. Continue treatment for up to 1 year after remission is achieved

3. Maintenance treatment for patients with a history of recurrence (1-3 years or lifetime)

Migraine with comorbid depression (MID) therapeutic options: benefits and drawbacks

Drug/Drug Class	Benefits	Drawbacks
TCAs	Dual transmitter	Toxicity in overdose, anticholinergic
MAOIs	Option for treatment- resistant cases	Food and drug interactions
SSRIs	Well-tolerated, evidence for efficacy for MID	Some CYP interactions (sertraline 3A4inh), bleeding risk, sexual dysfunction, sertraline: gi, agitation, insomnia, first few wks increased migraine risk
SNRI	Dual transmitter, evidence for efficacy for MID	BP elevation Duloxetine 60mg/day: appetite dec, sexual function dec, hepatocellular injury moderate 2D6 inh
Bupropion	Activating, effective for smoking cessation	Seizure risk, CI bulimia/anorexia, MAOI or another bupropion product use
Mirtazapine	Helpful for insomnia and poor appetite	Metabolic syndrome

fill in the blank:

Sumatriptan
Rizatriptan
Propranolol LA
Divalproex
Topiramate
Amitriptyline
Sertraline
Escitalopram
Venlafaxine extended release
Bupropion

Sumatriptan	50 to 100 mg as a single dose; Maximum dose: 100 mg/dose; 200 mg per 24 hours
Rizatriptan	5 to 10 mg as a single dose; maximum daily dose of 30 mg per 24 hours
Propranolol LA	40 to 80 mg/day
Divalproex	500 mg mg once daily; up to 1 g/day
Topiramate	25 mg once daily increase dose in 25 to 50 mg increments; up to 100-200 mg/day
Amitriptyline	10 to 25 mg once daily at bedtime; up to 150 mg/day
Sertraline	50 mg once daily
Escitalopram	10mg/day, titrate to 20mg/day
Venlafaxine extended release	37.5 to 75 mg once daily
Bupropion	12hr SR: 100 mg once daily; 24hr XR: 150 once daily; up to 450 mg