Breast Feeding

• Some drug is found in mother’s breast milk

• Trace amounts may be present in nursing children whose mothers are on escitalopram

• If child becomes irritable or sedated, breast feeding or drug may need to be discontinued

• Immediate postpartum period is a high-risk time for depression, especially in women who have had prior depressive episodes, so drug may need to be reinstituted late in the third trimester or shortly after childbirth to prevent a recurrence during the postpartum period

• Must weigh benefits of breast feeding with risks and benefits of antidepressant treatment versus nontreatment to both the infant and the mother

• For many patients, this may mean continuing treatment during breast feeding

ESCITALOPRAM: THE ART OF PSYCHOPHARMACOLOGY

Potential Advantages

• Patients taking concomitant medications (few drug interactions and fewer even than with citalopram)

• Patients requiring faster onset of action

Potential Disadvantages

• More expensive than citalopram in markets where citalopram is generic

Primary Target Symptoms

• Depressed mood

• Anxiety

• Panic attacks, avoidant behavior, re-experiencing, hyperarousal

• Sleep disturbance, both insomnia and hypersomnia

Pearls

✽ May be among the best-tolerated antidepressants

• May have less sexual dysfunction than some other SSRIs

• May be better tolerated than citalopram

• Can cause cognitive and affective “flattening”

✽ R-citalopram may interfere with the binding of S-citalopram at the serotonin transporter

✽ For this reason, S-citalopram may be more than twice as potent as R,S-citalopram (i.e., citalopram)

• Thus, 10 mg starting dose of S-citalopram may have the therapeutic efficacy of 40 mg of R,S-citalopram

• Thus, escitalopram may have faster onset and better efficacy with reduced side effects compared to R,S-citalopram

• Some data may actually suggest remission rates comparable to dual serotonin and norepinephrine reuptake inhibitors, but this is not proven

✽ Escitalopram is commonly used with augmenting agents, as it is the SSRI with the least interaction at either CYP450 2D6 or 3A4, therefore causing fewer pharmacokinetically mediated drug interactions with augmenting agents than other SSRIs

• SSRIs may be less effective in women over 50, especially if they are not taking estrogen

• SSRIs may be useful for hot flushes in perimenopausal women

• Some postmenopausal women’s depression will respond better to escitalopram plus estrogen augmentation than to escitalopram alone

• Nonresponse to escitalopram in elderly may require consideration of mild cognitive impairment or Alzheimer disease

Suggested Reading

Baldwin DS, Reines EH, Guiton C, Weiller E. Escitalopram therapy for major depression and anxiety disorders. Ann Pharmacother 2007;41(10):1583–92.

Bareggi SR, Mundo E, Dell–Osso B, Altamura AC. The use of escitalopram beyond major depression: pharmacological aspects, efficacy and tolerability in anxiety disorders. Expert Opin Drug Metab Toxicol 2007;3(5):741–53.

Burke WJ. Escitalopram. Expert Opin Investig Drugs 2002;11(10):1477–86.

ESTAZOLAM

ESTAZOLAM: THERAPEUTICS

Brands

• ProSom

see index for additional brand names

Generic?

Yes

Class

• Benzodiazepine (hypnotic)

Commonly Prescribed for

(bold for FDA approved)

• Insomnia characterized by difficulty in falling asleep, frequent nocturnal awakenings, and/or early morning awakenings

• Catatonia

How the Drug Works

• Binds to benzodiazepine receptors at the GABA-A ligand-gated chloride channel complex

• Enhances the inhibitory effects of GABA

• Boosts chloride conductance through GABA-regulated channels

• Inhibitory actions in sleep centers may provide sedative hypnotic effects

How Long Until It Works

• Generally takes effect in less than an hour

If It Works

• Improves quality of sleep

• Effects on total wake-time and number of nighttime awakenings may be decreased over time

If It Doesn’t Work

• If insomnia does not improve after 7–10 days, it may be a manifestation of a primary psychiatric or physical illness such as obstructive sleep apnea or restless leg syndrome, which requires independent evaluation

• Increase the dose

• Improve sleep hygiene

• Switch to another agent

Best Augmenting Combos for Partial Response or Treatment Resistance

• Generally, best to switch to another agent

• Trazodone

• Agents with antihistamine actions (e.g., diphenhydramine, tricyclic antidepressants)

Tests

• In patients with seizure disorders, concomitant medical illness, and/or those with multiple concomitant long-term medications, periodic liver tests and blood counts may be prudent

ESTAZOLAM: SIDE EFFECTS

How Drug Causes Side Effects

• Same mechanism for side effects as for therapeutic effects – namely due to excessive actions at benzodiazepine receptors

• Actions at benzodiazepine receptors that carry over to next day can cause daytime sedation, amnesia, and ataxia

• Long-term adaptations in benzodiazepine receptors may explain the development of dependence, tolerance, and withdrawal

Notable Side Effects

✽ Sedation, fatigue, depression

✽ Dizziness, ataxia, slurred speech, weakness

✽ Forgetfulness, confusion

✽ Hyperexcitability, nervousness

• Rare hallucinations, mania

• Rare hypotension

• Hypersalivation, dry mouth

• Rebound insomnia when withdrawing from long-term treatment

Life-Threatening or Dangerous Side Effects

• Respiratory depression, especially when taken with CNS depressants in overdose

• Rare hepatic dysfunction, renal dysfunction, blood dyscrasias

Weight Gain

• Reported but not expected

Sedation

• Many experience and/or can be significant in amount

What to Do About Side Effects

• Wait

• To avoid problems with memory, take estazolam only if planning to have a full night’s sleep

• Lower the dose

• Switch to a shorter-acting sedative hypnotic

• Switch to a non-benzodiazepine hypnotic

• Administer flumazenil if side effects are severe or life-threatening

Best Augmenting Agents for Side Effects

• Many side effects cannot be improved with an augmenting agent

ESTAZOLAM: DOSING AND USE

Usual Dosage Range

• 1–2 mg/day at bedtime

Dosage Forms

• Tablet 1 mg scored, 2 mg scored

How to Dose

• Initial 1 mg/day at bedtime; increase to 2 mg/day at bedtime if ineffective

Dosing Tips

• Use lowest possible effective dose and assess need for continued treatment regularly

• Estazolam should generally not be prescribed in quantities greater than a 1-month supply

• Patients with lower body weights may require lower doses

• Risk of dependence may increase with dose and duration of treatment

Overdose

• No death reported in monotherapy; sedation, slurred speech, poor coordination, confusion, coma, respiratory depression

Long-Term Use

• Not generally intended for long-term use

• Evidence of efficacy up to 12 weeks

Habit Forming

• Estazolam is a Schedule IV drug

• Some patients may develop dependence and/or tolerance; risk may be greater with higher doses

• History of drug addiction may increase risk of dependence

How to Stop

• If taken for more than a few weeks, taper to reduce chances of withdrawal effects

• Patients with seizure history may seize upon sudden withdrawal

• Rebound insomnia may occur the first 1–2 nights after stopping

• For patients with severe problems discontinuing a benzodiazepine, dosing may need to be tapered over many months (i.e., reduce dose by 1% every 3 days by crushing tablet and suspending or dissolving in 100 mL of fruit juice and then disposing of 1 mL while drinking the rest; 3–7 days later, dispose of 2 mL, and so on). This is both a form of very slow biological tapering and a form of behavioral desensitization