Valium Description:

Valium is a derivative of benzodiazepine. Manufactured by Roche and marketed under the brand names Valium, Seduxen and Apozepam, diazepam possesses anxiolytic, anticonvulsant, skeletal muscle relaxant, amnestic and sedative properties. This makes it useful for treating insomnia,anxiety, muscle spasms and some types of epilepsy. It is also used before certain medical procedures (such as endoscopies) to reduce tension and anxiety, and in some procedures to induce amnesia.

Diazepam is listed as a core medicine in the World Health Organization’s (WHO) “Essential Drugs List.” The drug is used to treat a wide range of conditions and is one of the most frequently administered and prescribed benzodiazepines.

Diazepam was the second benzodiazepine developed by Leo Sterbach, and was approved for use in 1963. It is five times more potent than its predecessor, chlordiazepoxide, and quickly surpassed it in terms of sales.

The benzodiazepines rose in popularity as an improvement upon barbiturates, which have a comparatively narrow therapeutic index, and are far more sedating at therapeutic doses. The benzodiazepines are also far less dangerous; death rarely results from diazepam overdose, except in cases where it is ingested with large quantities of other depressants (such as other sedatives or alcohol).

Classification:

Schedule IV controlled psycholeptic

Clinical Pharmacology:

In animals, Valium appears to have an effect on areas of the limbic system, thalamus and hypothalamus, and induces anxiolytic effects. Its actions are a result of the enhancement of GABAactivity. Diazepam binds to specific benzodiazepine sites on subunits of GABA receptors, which are markedly different than those which endogenous GABA molecules bind to.

In humans, tolerance to the drug’s sedative effects can develop over the course of a few weeks, but tolerance to the anxiolytic effects usually does not develop. Lorazepam, alprazolam, and clonazepam exhibit stronger effects in comparison to diazepam, but carry a higher risk of abuse, misuse, tolerance and dependence. Most of diazepam is metabolized; very little is excreted unchanged.

Indications and Dosage:

Diazepam is indicated for the treatment of insomnia, anxiety, and symptoms of acute alcohol or opiate withdrawal. Anxiety or tension associated with the stress of day to day life normally would not require treatment with an anxiolytic. In acute alcohol withdrawal, Valium may prove useful in the symptomatic relief of acute agitation, impending or acute delirium, hallucinations and tremors.

The drug is rarely used as a primary drug for the long-term treatment of epilepsy, due to the fact that tolerance to the drug’s anticonvulsant effects usually develops within 6 to 12 months of treatment, effectively rendering it useless for this purpose.

Diazepam has some off-label indications as well, including treatment of insomnia (short-term), treatment of tetanus – in conjunction with other measures of intensive-treatment, initial management of mania – along with first-line drugs such as lithium, treatment of stiff-person syndrome, treatment of painful muscle conditions, treatment of spastic muscular paresis, treatment of overdosage by hallucinogens or CNS stimulants and treatment of drug-induced seizures, among other uses.

Dosage should be individualized for maximum efficacy, depending on the condition treated, the severity of symptoms, body weight, and any co-morbid conditions the individual may have.

Adult dosage recommendations are as follows for the primary indications:

  • Insomnia – Up to 30mg orally, as a single dose, at bedtime.
  • Anxiety/panic attacks – Dosage differs depending upon severity of symptoms. For panic attacks, diazepam is taken “as needed”.
    • Oral – 2mg to 10mg oral, 2 to 4 times daily.
    • IV/IM – 2mg to 10mg. Repeat in 3 to 4 hours, if necessary.
  • Pediatric dosage recommendations, primary indications only, are as follows:
    • Initiate therapy with lowest effective dose.
    • Oral: Initial dose of 40 to 200µg/kg of bodyweight, repeat as tolerated up to 4 times per day.
    • Rectal suppository: 40 to 200µg/kg of bodyweight, repeat as tolerated up to 4 times per day.

Diazepam should not be administered to children under 6 months of age.

Valium Side Effects and Interactions:

The most common side effects Valium include drowsiness, impaired motor functions, impaired coordination, impaired balance, dizziness, fatigue, depression, anterograde amnesia and reflex tachycardia. These symptoms are common with most benzodiazepines.

Rare side effects can include nervousness, confusion, constipation, diplopia, dysarthria, headache, hypotension, incontinence, jaundice, changes in sex drive, nausea, changes in salivation, rash, slurring of speech, tremor, urinary retention, vertigo, irritability, insomnia, muscle cramps, and in severe cases, rage and/or violence. If these side effects develop, diazepam treatment should be discontinued.

If Valium is given with other drugs, attention should be paid to the possible pharmacological interactions. Special care should be taken with barbiturates, narcotics, antidepressants and phenothiazines.

Diazepam increases the depressive effects of alcohol, other sedatives/hypnotics, narcotics, and muscle relaxants. Opiates’ euphoric effects may increase, leading to increased risk of psychological dependence.

Oral contraceptives (“the pill”) significantly decrease the elimination of desmethyldiazepam, a major metabolite of Valium. Antipsychotics and MAOIs may interact with diazepam. Smoking tobacco can enhance the elimination of diazepam and decrease its action.

Other drugs that may interact with diazepam include antipsychotics, MAOIs, ranitidine, and tobacco. Foods that acidify the urine can lead to faster absorption and elimination of Valium, and thus decrease its levels and activity. Foods that alkalinize the urine can lead to slower absorption and elimination of diazepam, increasing drug levels and activity.

Information for Parents and Kids:

The safety and efficacy of diazepam has not been established in children under age 18. The standard dosage for children is 1 to 2.5mg, 3 or 4 times a day, with gradual increases as needed and tolerated. Diazepam should not be administered to children under the age of 6 months.

Warnings and Precautions:

Diazepam has no value in the treatment of psychotic patients and should not be employed in lieu of appropriate treatment. As with most drugs that stimulate the CNS, patients receiving Valium should use caution when engaging in hazardous occupations requiring complete mental alertness such as operating machinery or driving.

As with other anticonvulsants, when diazepam is used as an adjunct in the treatment of convulsive disorders, the possibility of an increase in the frequency and/or severity of seizures may require increasing the standard dosage. Abrupt cessation of diazepam in such cases may be associated with a temporary increase in frequency and/or severity of seizures.

Individuals should be advised against consuming alcohol and other CNS-depressant drugs while taking Valium, due to the depressant effects the drug already has on the central nervous system (CNS).

Withdrawal:

Therapeutic doses of Valium for 6 weeks or longer can result in physical dependence, with symptoms of withdrawal syndrome occurring when the drug is discontinued. With larger doses, physical dependence will develop more rapidly.

After taking diazepam for several weeks, the drug should never be abruptly stopped. The dose should be gradually lowered, over a period of 2 to 4 weeks, in order to minimize withdrawal symptoms.

Symptoms of withdrawal are usually minimal, and increase in severity over the first 5 to 9 days after the drug is discontinued. Diazepam’s long half-life and active metabolites delay the onset of these symptoms. Valium’s withdrawal symptoms are similar to those of other CNS depressants, such as alcohol and barbiturates, and can include anxiety, dysphoria (an emotional state characterized by anxiety, unease, or depression), irritability, insomnia, confusion, muscle spasms, abdominal cramps, tremors, anorexia (i.e. loss of appetite), hypotension, hyperthermia/sweating, nausea/vomiting, and in severe cases symptoms can include convulsions or death.

The more severe side effects normally only occur in people who had been taking excessive amounts of the drug for extended periods of time. Usually only the milder symptoms develop in patients discontinuing the standard therapeutic-level dosages after several months of treatment.

Over-dosage & Contraindications:

Symptoms of diazepam overdosage include mental confusion, somnolence/difficulty staying awake, hypotension, impaired motor functions (impaired reflexes/coordination, loss of balance, dizziness) and coma.

Though not usually fatal when taken alone, a Valium overdose is a medical emergency and generally requires immediate attention. The antidote for an overdose of diazepam (or any other benzodiazepine) is flumazenil. This drug is only used in occurrences where severe respiratory depression or cardiovascular complications are present. Flumazenil is a short-acting drug and the effects of diazepam may last for days, as such, several doses of flumazenil may be necessary. Artificial respiration and stabilization of cardiovascular functions may also be necessary.

Though not normally indicated, activated charcoal can be used for decontamination of the stomach following an overdose. Emesis (vomiting) is contraindicated.

One case noted a patient that had taken 300mg of diazepam that resulted in prolonged sleep and consecutive drowsiness for several days without serious impairment of cardiac or respiratory functions. Overdoses of Valium with alcohol and/or other depressants can be fatal.

Recreational Use

Diazepam is not used recreationally as much as alprazolam or flunitrazepam. The drug is often found as an adulterant in heroin, possibly because diazepam greatly amplifies the effects of opioids. In some instances, diazepam is used by stimulant abusers to ‘come down’ and induce sleep and also by LSD users (or those taking other hallucinogens) to help ease their trip without unpleasant after-effects.

Valium is contraindicated in people with a known hypersensitivity to the drug and in pediatric patients under 6 months old. It may be used in patients with open angle glaucoma who are receiving appropriate therapy, but is contraindicated in acute narrow angle glaucoma.

Diazepam should be avoided, when possible, in people with conditions such as Ataxia, severe hepatic deficiencies (e.g. hepatitis and cirrhosis), severe renal deficiencies (e.g. individuals on dialysis), severe sleep apnea, severe hypoventilation (respiratory depression), severe depression (especially when accompanied by suicidality), acute intoxication with narcotics, alcohol, or other psychoactive substances), or patients with Myasthenia gravis.

Special caution should be exercised when administering diazepam to patients less than 18 years of age. In these individuals, treatment is usually only indicated in the presence of epilepsy and pre/postoperative treatment. The smallest possible effective dose should be used for this group of patients.

In elderly and very ill patients, there is a possibility that apnea and/or cardiac arrest may occur. Concomitant use of other CNS depressants increases the risk. The smallest possible dose should be used for this group as well.

Diazepam can lead to physiological tolerance, and psychological and/or physical dependence. At a particularly high risk for misuse, abuse and dependence are:

  • Individuals with a history of alcohol or drug abuse/dependence
  • Emotionally unstable patients
  • Those with severe personality disorders, such as Borderline Personality Disorder (BPD)
  • Persons with chronic pain or other physical disorders

These patients being treated with Valium should be monitored very closely during therapy for signs of abuse and dependence development. Treatment should be discontinued if these signs are observed. Long-term therapy in these individuals is not recommended.

Generic Name: diazepam

Chemical Formula: C16H13ClN2O

Routes of Administration: oral/intravenous

Elimination Half Life: 20-100 hours (normal half life range is 20-50 hours)

Legal Status: by prescription only

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