Addiction, Dependence, and Tolerance to Benzodiazepines

Key Points

1. Benzodiazepines are not recommended as first-line therapy for insomnia, panic disorders, and anxiety (including anxiety with depression).
2. Consider other treatment options, including non-pharmacological measures, for the respective indication.
3. Treatment duration should be limited to the shortest period of time.
4. Use patient-focused treatment plans to help educate patients about the risks and benefits of benzodiazepines.
5. Consider a multidisciplinary care model to achieve the best health outcome for your patient.

Class

They belong to the class of drugs anxiolytics (Sedatives) and hypnotics. Cause sedation with the concomitant relief from anxiety.

Type of Effects

Include sedation when taken in low to moderate doses. At high doses, they cause hypnosis and further at very high doses impair the brain function by severely depressing its electrical activity.

Benzodiazepines are the most widely used anxiolytics, by replacing barbiturates and meprobamate.

Effects on the Body

Sedation

They cause a calming effect with a concomitant anxiolytic effect. This response is due to the effect on the central nervous system, By decreasing the electrical activity. The sedative and anxiolytic effect is sometimes accompanied by the depressive effect on psychomotor and cognitive functions.

Hypnosis

Hypnosis also centrally mediates the function of benzodiazepines, which occur in high doses. They cause hypnosis by decreasing the latency of sleep (time to fall asleep), increasing Non-Rapid eye moment sleep, and decreasing Rapid Eye movement sleep.

Anesthesia

As shown previously at higher doses than required for hypnosis they depress the central nervous system to a point of stage 3 general anesthesia.

Anticonvulsant effect

Many benzodiazepines have the ability to prevent the generation of epileptiform electrical activity in the CNS. Selective agent having this tendency include lorazepam, diazepam, clonazepam and Nitrazepam.

Muscles Relaxation

At high doses, they may inhibit transmission at a muscular level by locally affecting neurons there. And also mediated by presynaptic inhibition of the spinal cord.

Effect on Respiration and CVS

This respiratory depression is due to medullary respiratory center suppression. Even at a normal dose, it may impair respiratory functions in a susceptible and respiratory patient. In contrast to Respiratory functions, CVS functions are not announced in normal people even at hypnotic doses. But may affect people with hypovolemic status, CVS diseases, and Heart failure. This action is due to the suppression of the medullary vasomotor area of the hindbrain.

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Anterograde amnesia

Short-term memory loss is due to the effect on CNS by the alpha1 GABA subtype. In this duration of maintained dose individuals become unaware of the environment.

Addiction

If used in high doses for a prolonged time they can cause dependency ( fall in Schedule 4 of controlled substances having a low potency to cause dependency and Addiction). This dependency is due to the effect on the reward pathway. Where the drugs cause an increase in the level of neurotransmitters, particularly dopamine (causing euphoria, a state of relaxation, and calmness). This stimulation of the reward pathway leads to Psychological dependency. 

Dependence

Dependency is also due to preventing the withdrawal effects associated with benzodiazepines like insomnia, anxiety, and central nervous system excitability that may lead to convulsions.

Practical steps for reducing benzodiazepine dependence

When judiciously used, benzodiazepines are therapeutically effective; however, health professionals and patients should be aware of the risk of addiction and dependence associated with long-term use.

To reduce the risk of benzodiazepine dependence and misuse:

1. Use only for appropriate indications.
2. Seek specialist advice before considering prescribing a benzodiazepine for panic disorder.
3. Consider managing underlying causes and use of behavioral and/or psychological interventions for insomnia and anxiety disorders.
4. Reserve for short-term use only for a duration of up to 2–4 weeks.
5. Assess efficacy at one week.
6. Only prescribe to well-known patients
7. Assess the risk-benefit ratio of long-term use of benzodiazepines and openly discuss withdrawing from benzodiazepines if appropriate.
8. Identify patients who take large doses of benzodiazepines to achieve an intoxicating effect and refer them to a specialist drug and alcohol service.

Tolerance to Benzodiazepines

Tolerance to benzodiazepines is not likely to be contributed by metabolic induction. Here increased metabolism plays little to no role in tolerance. Benzodiazepine tolerance is due to the down-regulation of receptors. Tolerance to benzodiazepines is not very abrupt and takes a long time to be generated.

Withdrawal of benzodiazepines includes symptoms like

Anxiety, depression, increased heart rate, insomnia, high blood pressure, excessive sweating, tremors, hallucination, seizures and convulsions.

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