Zolpidem

Zolpidem is a hypnotic drug with sedative action. It is a benzodiazepine-like compound belonging to the imidazopyridine family.

Zolpidem - Chemical Structure

Indications

For what it uses

Zolpidem is indicated for the short-term treatment of insomnia.

Warnings

Benzodiazepine-like substances such as zolpidem - as well as benzodiazepines - are indicated for the treatment of insomnia only when it is a serious and debilitating disorder for the patient.

Extreme caution should be used when administering zolpidem in patients with a history of alcohol and / or drug abuse.

The duration of treatment with zolpidem should be as short as possible.

After prolonged use of zolpidem, tolerance may develop. In other words, the hypnotic effects induced by the drug are reduced.

Since zolpidem could cause respiratory depression, great caution should be used when administering the drug in patients with chronic respiratory failure.

Zolpidem should not be used alone to treat anxiety associated with depression.

The use of zolpidem should be avoided in patients with severe hepatic impairment.

Zolpidem should not be used as a primary treatment for psychoses.

If insomnia persists despite taking zolpidem, the patient must be re-evaluated, as this insomnia could be a symptom of depression.

Zolpidem compromises the ability to drive or use machines, therefore, these activities must be avoided.

Interactions

The sedative effect of zolpidem is increased by alcohol, therefore, during drug therapy this combination should be avoided.

The central nervous system depressive effect induced by zolpidem may be increased by concomitant administration of the following drugs:

Antipsychotic drugs;
Hypnotic, anxiolytic and sedative drugs;
Antidepressant drugs;
Opioid analgesics ;
Antiepileptic drugs;
Anesthetic drugs;
Sedative antihistamine drugs.

Furthermore, cases of visual hallucinations have been reported when zolpidem was administered concomitantly with antidepressants, such as bupropion, desipramine, fluoxetine, venlafaxine and sertraline .

Concomitant use of zolpidem and fluvoxamine (an antidepressant) may cause an increase in the plasma concentration of zolpidem itself, therefore, this association is not recommended.

Co-administration of zolpidem and ciprofloxacin (an antibiotic) may increase the plasma concentration of zolpidem. This association must be avoided.

Rifampicin (an antibiotic) decreases the therapeutic efficacy of zolpidem.

Ketoconazole may decrease the elimination rate of zolpidem and - consequently - may increase its plasma concentration.

Side effects

Zolpidem - like all drugs - can induce various types of side effects, but not all patients experience them.

The following are the main adverse effects that may occur during zolpidem therapy.

Addiction

The use of zolpidem can lead to the development of physical and mental dependence.

The risk of developing dependence is directly proportional to the dose of drug administered and to the duration of the treatment.

Patients with a history of alcohol and / or drug abuse are at greater risk of developing addiction.

Once physical dependence has been established, abrupt cessation of treatment causes withdrawal symptoms. These symptoms are:

derealization;
depersonalization;
Extreme anxiety;
Confusion;
agitation;
Irritability;
Headache;
Numbness and tingling in the extremities;
Hallucinations;
Epileptic attacks;
Muscle pains;
Hypersensitivity and intolerance to sounds (hyperacusis);
Hypersensitivity to light and physical contact.

Anterograde amnesia

Treatment with zolpidem can cause anterograde amnesia.

The development of this type of amnesia usually takes place a few hours after drug administration. Therefore, after taking the drug, patients should be able to sleep continuously for at least 8 hours.

Rebound insomnia

Rebound insomnia may occur upon discontinuation of zolpidem therapy. That is to say, the symptoms that led to the use of the drug are reappeared in an aggravated form.

Rebound symptoms can be accompanied by mood swings, anxiety and restlessness.

The risk of developing these symptoms is greater when the treatment is stopped abruptly, therefore, the interruption of therapy must take place gradually.

Psychiatric disorders

So-called paradox symptoms can occur during treatment with zolpidem. These symptoms are:

agitation;
Restlessness;
Aggravation of insomnia;
Irritability;
Aggression;
Anger;
Delusions;
Hallucinations;
Psychosis;
Nightmares;
Abnormal behavior.

If these symptoms occur, treatment with zolpidem should be discontinued.

Furthermore, zolpidem can cause confusion, depression and libido changes.

Sleepwalking

Cases of somnambulism and associated behaviors, such as driving vehicles in sleep, telephoning, cooking, eating food and having sex, followed by amnesia of the event, have been reported during zolpidem therapy.

Nervous system disorders

Treatment with zolpidem can cause headaches, dizziness and decreased consciousness.

Eye disorders

Zolpidem therapy can cause diplopia (double vision).

Gastrointestinal disorders

Treatment with zolpidem can cause abdominal pain, nausea, vomiting and diarrhea.

Lung and respiratory tract disorders

Zolpidem therapy can cause respiratory depression and upper and lower respiratory tract infections.

Skin and subcutaneous tissue disorders

Treatment with zolpidem can cause rashes, hives, itching and hyperhidrosis.

Other side effects

Other side effects that may occur during treatment with zolpidem are:

Increased levels of liver enzymes in the bloodstream;
Back pain;
Muscle weakness;
Fatigue;
Changes in gait;
Angioedema.

Overdose

In the event of an overdose of zolpidem - either alone, or in association with other drugs depressing the central nervous system - one can see a reduction in the state of consciousness down to the coma. Cases of overdosage with fatal outcomes have also been reported.

If the patient is conscious, vomiting should be induced within an hour of taking the drug. If, on the other hand, the patient is unconscious, a gastric lavage should be performed.

If no improvement is noted following gastric lavage, the administration of activated charcoal may be useful to reduce drug absorption.

If very severe symptoms appear, flumazenil (a benzodiazepine receptor antagonist) can be a useful antidote. At the same time, however, the administration of flumazenil may favor the onset of convulsions.

In any case, if you suspect you have taken an overdose of zolpidem, you must contact a doctor immediately and go to the nearest hospital.

Action mechanism

Zolpidem - just like benzodiazepines - is able to increase the signal of γ-aminobuttiric acid (GABA), more commonly called the GABAergic signal.

GABA is the most important inhibitory neurotransmitter of the brain and performs its biological functions through binding to specific receptors: GABA-A, GABA-B and GABA-C.

A specific binding site for benzodiazepines is present on the GABA-A receptor. Zolpidem - even if it is not a benzodiazepine - is able to bind to this specific site, thus activating the receptor and promoting the cascade of inhibitory signals induced by GABA.

However - although the agonistic effects of zolpidem against the GABA-A receptor are qualitatively similar to those of benzodiazepines - zolpidem has a weaker anticonvulsant effect but a greater sedative effect.

Mode of Use - Posology

Zolpidem is available for oral administration as tablets and oral drops.

The duration of treatment must be as short as possible. Generally, this duration varies from a few days up to a maximum of four weeks, including the period of gradual interruption of therapy.

The dose of zolpidem usually administered is 10 mg, to be taken just before bedtime.

In elderly patients, in debilitated patients and in patients with hepatic insufficiency, the usual dose of zolpidem has decreased to 5 mg.

The maximum daily dose that should never be exceeded is 10 mg of drug.

Pregnancy and breastfeeding

As a precautionary measure, zolpidem should not be given to pregnant women.

If zolpidem is given during the last period of pregnancy or during childbirth, adverse effects may occur in the newborn, including hypothermia, hypotonia and respiratory depression. In addition, children whose mothers have chronically taken zolpidem during pregnancy may develop physical dependence and show withdrawal symptoms in the post-natal period.

Because zolpidem is excreted in breast milk, breastfeeding mothers should not take the medicine.