Depression Symptoms Treatment

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Pharmacotherapy

Drug therapy can be effective for short-term alleviation of insomnia but may not be sufficient for long-term management of chronic insomnia. Behavioral therapy, on the other hand, yields the most durable improvements in sleep patterns.

Benzodiazepines: Benzodiazepines are frequently prescribed to treat insomnia. These hypnotics reduce latency to sleep onset and total awakenings by increasing total sleep duration. Benzodiazepines enhance the effect of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) by increasing the affinity of GABA for its receptor. Benzodiazepines nonselectively bind to at least three benzodiazepine receptor subtypes (BNZ-1, BNZ-2, BNZ-3), which accounts for their sedative, anxiolytic, myorelaxant, and anticonvulsant properties. Five benzodiazepines (estazolam, flurazepam, quazepam, temazepam, and triazolam) have an FDA-approved indication for the management of insomnia. Dose, distinguishing pharmacokinetic properties (absorption rate, distribution, and elimination half-life), and risk-benefit ratio should be considered when selecting the most appropriate medication (Table 2). The lowest effective dose should be used to minimize side effects, and long-acting benzodiazepines with active metabolites should be avoided in the elderly.

Shorter-acting medications may be preferred for patients who need to be alert because of occupational or societal demands. Major side effects of short-acting benzodiazepines include rebound insomnia and anterograde amnesia. Intermediate- and longer-acting benzodiazepines are less effective for inducing sleep, but are indicated for sleep maintenance and decreasing nocturnal awakenings. Long-acting medications are best indicated for people with insomnia as well as concomitant daytime anxiety. Accumulation of active metabolites is problematic in elderly patients and those patients with impaired liver function. Benzodiazepines are contraindicated in patients with acute alcohol intoxication with depressed vital signs, a history of substance abuse. and during pregnancy. Benzodiazepines should be used cautiously in patients with chronic pulmonary insufficiency or untreated sleep apnea.

Zolpidem (Ambien): Zolpidem is a non-benzodiazepine hypnotic of the imidazopyridine class. It exhibits hypnotic effects with minimal myorelaxant, anticonvulsant, and anxiolytic properties, as it preferentially binds with the BNZ-1 receptor.Zolpidem is effective for reducing sleep latency and nocturnal awakenings and increasing total sleep time. Rebound effects are minimal. The incidence of adverse effects is low at recommended doses. Common side effects include drowsiness, dizziness, and headache.

Zaleplon (Sonata): Zaleplon, as with zolpidem, belongs to the imidazopyridine class of non-benzodiazepine hypnotics. The pharmacology of these two drugs is similar; however, zaleplon has an ultra-brief duration of effect. It is effective for reducing time to sleep onset, but is not as effective for reducing nighttime awakenings or increasing total sleep time. No next-day sedation or rebound insomnia is documented with zaleplon at recommended doses. Adverse effects include headache, dizziness, somnolence, and nausea.

Antidepressants

Tricyclic antidepressants (TCAs) such as amitriptyline, doxepin, and nortriptyline are effective for inducing sleep and improving sleep continuity. These agents should be used at their lowest effective dose to minimize anticholinergic effects and to minimize cardiac conduction prolongation, especially in the elderly. The overdose potential of TCAs is greater than with other hypnotic agents, and daytime sedation can be significant.

Trazodone is a potent sedating antidepressant. Trazodone improves sleep continuity and is an attractive option in persons prone to substance abuse, as addiction or tolerance is not a problem. Trazodone is also used in conjunction with stimulating antidepressants such as some SSRIs and bupropion in depressed patients with insomnia. Adrenergic blockade can result in oversedation and orthostatic hypotension, especially in elderly patients. The risk of priapism, a condition of painful, prolonged erection in men, is rare.

Antihistamines: Antihistamines are found in many over-the-counter sleep aids. These agents are effective for mild insomnia; however, next-day sedation may be a problem. Antihistamines commonly cause psychomotor impairment and anticholinergic effects. Tolerance may also develop with repeated use.

Alternative Medications

Valerian is a perennial plant that appears to increase GABA concentrations in animal studies, but its exact mechanism is not known. Valerian should not be used for the acute management of insomnia because its hypnotic effect is delayed for two to four weeks. Valerian appears to be well tolerated; however, it can cause headache and daytime sedation.

Melatonin is a neurohormone secreted by the pineal gland one to two hours before bedtime that helps to regulate circadian rhythm. The most common side effects associated with melatonin are sedation, drowsiness, and hypothermia.

Conclusion

Insomnia is a significant complaint among American adults. Insomnia can be successfully treated with medication or by behavioral modification aimed at improving sleep hygiene. A treatment regimen should be tailored based on duration and nature of symptoms after underlying conditions have been identified and/or treated. Attention to distinguishing pharmacokinetic properties (e.g., half-lives and active metabolites) among various treatment alternatives is important when selecting a medication, especially in the elderly population. A detailed patient history taken by the pharmacist may be the first step to identifying contributing factors of insomnia.