Insomnia

Insomnia (Difficulty Initiating or Maintaining Sleep)

Insomnia is often characterized by difficulty falling asleep, frequent nocturnal awakenings, early morning awakenings, and non-restorative sleep, which may result in daytime impairments in concentration and school or work performance. In comorbid (secondary) insomnia, social factors (e.g., family difficulties, bereavement), medications (e.g., antidepressants, β-agonists, corticosteroids, decongestants), and coexisting medical or psychiatric conditions (e.g., depression, bipolar disorder) may help to explain difficulties in initiating and maintaining sleep. Insomnia may be described as transient (less than 1 week), acute (1 to 4 weeks), or chronic (more than 1 month) in duration.
Non-pharmacologic Recommendations for Insomnia
Stimulus control procedures
Establish regular times to wake up and to go to sleep (including weekends).
Sleep only as much as necessary to feel rested.
Go to bed only when sleepy. Avoid long periods of wakefulness in bed. Use the bed only for sleep or intimacy; do not read or watch television in bed.
Avoid trying to force sleep; if you do not fall asleep within 20–30 minutes, leave the bed and perform a relaxing activity (e.g., read, listen to music, or watch television) until drowsy. Repeat this as often as necessary.
Avoid daytime naps.
Schedule worry time during the day. Do not take your troubles to bed.
Sleep hygiene recommendations
Exercise routinely (three to four times weekly) but not close to bedtime because this can increase wakefulness.
Create a comfortable sleep environment by avoiding temperature extremes, loud noises, and illuminated clocks in the bedroom.
Discontinue or reduce the use of alcohol, caffeine, and nicotine.
Avoid drinking large quantities of liquids in the evening to prevent nighttime trips to the restroom.
Do something relaxing and enjoyable before bedtime.
Pharmacologic Therapy
Benzodiazepine Receptor Agonists
The most commonly used treatments for insomnia have been the benzodiazepine receptor agonists (BZDRAs). BZDRAs are effective as sedative–hypnotics and are FDA-labeled for the treatment of insomnia. Traditional benzodiazepines have sedative, anxiolytic, muscle relaxant, and anticonvulsant properties; newer nonbenzodiazepine GABA agonists possess only sedative properties


Benzodiazepines
Benzodiazepines
Dose in mg
nonBenzodiazepines GABAA Agonists
Dose in mg
Diazepam
2–5
Zaleplon
10
Loprazolam
1
Zolpidem
5-10
Lorazepam
1
Zopiclone
3.75-7.5
Lormetazepam
0.5–1.5
eszopiclone
2-3
Nitrazepam
5–10


Temazepam
10–20

Miscellaneous Agents

Antihistamines (Diphenhydramine and doxylamine ) exhibit sedating properties and are included in many nonprescription sleep agents. They are effective in the treatment of mild insomnia and are generally safe. Patients quickly experience tolerance to sedative effects, and increasing the dose of antihistamines will not produce a linear increase in response. Antihistamines are considered to be less effective than benzodiazepines, and they have the disadvantages of anticholinergic side effects. Antidepressants are alternatives for patients with nonrestorative sleep who should not receive benzodiazepines, especially those who have depression, pain, or a risk of substance abuse. Sedating antidepressants such as amitriptyline, doxepin, and nortriptyline are effective for inducing sleep continuity, although daytime sedation and side effects can be significant. Anticholinergic activity, adrenergic blockade, and cardiac conduction prolongation can be problematic, especially in the elderly and in overdose situations.
Ramelteon is a melatonin receptor agonist approved for the treatment of sleep-onset insomnia. It is selective for the MT1 and MT2 melatonin receptors that are thought to regulate the circadian rhythm and sleep onset. The recommended dose is 8 mg taken at bedtime to induce sleep. Although generally well tolerated, the most common adverse events reported are headache, dizziness, and somnolence
Headache
Tension Headache
Everybody experiences the occasional tension headaches. They are caused by muscle contraction over the neck and scalp. Often they respond to simple analgesics available overthe- counter, such as paracetamol and NSAIDs. They may also respond to TCA drugs given as a single dose at night. NSAIDs may be indicated if the headache is associated with cervical spondylosis or neck injury.
Migraine
Migraine is a common, recurrent, severe headache that interferes with normal functioning. It is a primary headache disorder divided into two major subtypes, migraine without aura and migraine with aura.
The pathophysiology of migraine headache.
Vasodilation of intracranial extracerebral blood vessels (possibly the result of an imbalance in the brain stem) results in the activation of the perivascular trigeminal nerves that release vasoactive neuropeptides to promote neurogenic inflammation. Central pain transmission may activate other brain stem nuclei, resulting in associated symptoms (nausea, vomiting, photophobia, phonophobia).
Symptoms
• Migraine is characterized by recurring episodes of throbbing head pain, frequently unilateral, that when untreated can last from 4 to 72 hours. Migraine headaches can be severe and associated with nausea, vomiting, and sensitivity to light, sound, and/or movement. Not all symptoms are present at every attack.
Migraine Triggers
Behavioral: Fatigue, Menstruation or menopause, Sleep excess or deficit, Stress, Vigorous physical activity
Environmental: Flickering lights. High altitude, Loud noises, Strong smells, Tobacco smoke,Weather changes
Food: Caffeine intake or withdrawal, Chocolate, Citrus fruits, bananas, figs, raisins and Dairy products
Medications: Cimetidine, Estrogen or oral contraceptives, Indomethacin, Nifedipine, and Nitrates
General Approach to Treatment
Nonpharmacologic and pharmacologic interventions are available for the management of migraine headache; however, drug therapy remains the mainstay of treatment for most patients. Pharmacotherapeutic management of migraine can be acute (i.e., symptomatic or abortive) or preventive (i.e., prophylactic).
Pharmacologic Management of Acute Migraine
Analgesics and NSAIDs: Simple analgesics and NSAIDs are effective medications for the management of many migraine attacks. They offer a reasonable first-line choice for treatment of mild to moderate migraine attacks or severe attacks that have been responsive in the past to similar NSAIDs or nonopiate analgesics. Of the NSAIDs, aspirin, diclofenac, ibuprofen, ketorolac, naproxen sodium, tolfenamic acid, and the combination of acetaminophen plus aspirin and caffeine have demonstrated the most consistent evidence of efficacy
Opiate Analgesics: The use of narcotic analgesic drugs (e.g., meperidine, butorphanol, oxycodone, and hydromorphone) in migraine treatment is controversial, and evidence for use is generally negative. Use should generally be reserved for patients with moderate to severe infrequent headaches in whom conventional therapies are contraindicated or as “rescue medication” after patients have failed to respond to conventional therapies.
Antiemetics: Adjunctive antiemetic therapy is useful for combating the nausea and vomiting that accompany migraine headaches and the medications used to treat attacks (e.g., ergotamine tartrate). A single dose of an antiemetic, such as metoclopramide, chlorpromazine, or prochlorperazine, administered 15 to 30 minutes before ingestion of oral abortive migraine medications is often sufficient. Suppository preparations are available when nausea and vomiting are particularly prominent. Metoclopramide is also useful to reverse gastroparesis and improve absorption from the GI tract during severe attacks.
Ergot Alkaloids and Derivatives: Ergotamine tartrate (cafregote 2 mg at onset; then 1–2 mg every 30 minutes as needed Maximum dose is 6 mg/day or 10 mg/week) and dihydroergotamine (0.25–1 mg at onset IM or subcutaneous; repeat every hour as needed Maximum dose is 3 mg/day or 6 mg/week ) are useful and can be considered for the treatment of moderate to severe migraine attacks. these drugs are nonselective 5-HT1 receptor agonists that constrict intracranial blood vessels and inhibit the development of neurogenic inflammation in the trigeminovascular system
Serotonin Receptor Agonists (Triptans): Introduction of the 5-HT receptor agonists, or triptans, represented a significant advance in migraine pharmacotherapy. Sumatriptan (Optimal oral dose is 50–100 mg; maximum daily dose is 200 mg), Zolmitriptan (Optimal oral dose is 2.5 mg; maximum daily dose is 10 mg), and Frovatriptan (Optimal oral dose is 2.5-5 mg; maximum daily dose is 7.5 mg) are selective agonists of the 5-HT1B and 5-HT1D receptors. Relief of migraine headache is the result of three key actions: normalization of dilated intracranial arteries through enhanced vasoconstriction, inhibition of vasoactive peptide release from perivascular trigeminal neurons, and inhibition of transmission through second-order neurons ascending to the thalamus
Miscellaneous Nonspecific Medications
Corticosteroids can be considered as rescue therapy for status migrainous (a severe, continuous migraine that can last up to 1 week). IV or intramuscular dexamethasone at a dose of 10 to 25 mg has also been used as an adjunct to abortive therapy.
Intranasal lidocaine, one to four drops of a 4% solution, provides rapid pain relief within 15 minutes of administration, but headache recurrence is common.
IV valproate 500 to 1,000 mg and magnesium sulfate 1,000 mg are nonsedating options for use in acute migraine treatment.


Prophylactic Pharmacologic Therapy
To determine maximal clinical benefits, a therapeutic trial of 6 months is recommended when initiating treatment for episodic migraine prevention. Despite this recommendation, most migraine prevention studies have relatively brief treatment durations of only 12 to 16 weeks.
β-Adrenergic antagonists: β-Adrenergic antagonists are among the most widely used drugs for migraine prophylaxis. Metoprolol (100-200mg\day in divided doses), propranolol (40-160mg\day in divided doses), and timolol (20-160\day in divided doses) have established efficacy in controlled clinical trials, reducing the frequency of attacks by 50% in greater than 50% of patients.
Antidepressants: The beneficial effects of antidepressants in migraine are independent of their antidepressant activity and may be related to down-regulation of central 5-HT2 receptors, increased levels of synaptic norepinephrine, and enhanced endogenous opioid receptor actions.30 The tricyclic antidepressant (TCA) amitriptyline (20-50 mg) and SNRI venlafaxine (75-150mg) have demonstrated efficacy
Anticonvulsants: Anticonvulsant medications have emerged as important therapeutic options for migraine prophylaxis with valproate, divalproex,(500-1500mg) and topiramate (50-200) all having established efficacy
NSAIDs: are modestly effective for reducing the frequency, severity, and duration of migraine attacks, but potential GI and renal toxicity limit the daily or prolonged use of these agents. Consequently, NSAIDs have been used intermittently to prevent headaches that recur in a predictable pattern, such as menstrual migraine. Administration of NSAIDs in the perimenstrual period can be beneficial in women with true menstrual migraine. NSAIDs should be initiated 1 to 2 days prior to the expected onset of headache and continued during the period of vulnerability.
Triptans: Triptans are also useful for the prevention of menstrual migraine. Frovatriptan has established efficacy, while naratriptan and zolmitriptan are probably effective. The triptan is usually started 1 or 2 days before the expected onset of headache and continued during the period of vulnerability
Miscellaneous Prophylactic Agents:
riboflavin (vitamin B2) 400 mg daily
cyproheptadine (4 mg/day)
The calcium channel blockers, primarily verapamil, have been widely used for preventive treatment