Overview
| Anxiolytics | Nota bene |
|---|---|
| Benzodiazepines | Widely used for panic disorders, anxiety disorders, Insomnia and Status epilepticus |
| Barbiturates | Rarely used. First-line for infantile seizures, and second-line for status epilepticus. Were originally used for insomnia and panic disorders but fell out of favour due to high toxicity (can be abused in suicide attempts) |
| Benzodiazepine-like hypnotics | Widely used for insomnia. Lower abuse profile. |
| Buspirone | A partial 5HT-1A agonist that is used in GAD and to augment antidepressants in MDD or OCD. It is not useful in Panic disorders due to its slow onset of action. Useful for patients with comorbid alcohol use disorder (does not interact with alcohol) |
Benzodiazepines
Benzodiazepines work by increasing the frequency of GABA-a CL channel opening (not the duration or opening, but frequency of opening). They have a faster onset of action than antidepressants and can be used in the interim for treatment of anxiety. Many patients become dependent on benzodiazepines and develop tolerance. They have a high potential for abuse and should not be prescribed for more than 4 weeks at a time.
Midazolam (Versed), diazepam (valium), lorazepam (Ativan), temazepam (Resroril), triazolam (Halcion), alprazolam (Xanax), clonazepam (Klonopin), chlordiazepoxide
Classification
| Classification | Half-life | Examples |
|---|---|---|
| Long acting | > 20 hours | Diazepam, clonazepam |
| Intermediate acting | 6 – 20 hours | Alprazolam, lorazepam, oxazepam, temazepam |
| Short acting | < 6 hours | Triazolam, midalozam |
Selected Benzodiazepines
| Benzodiazepine | Nota bene |
|---|---|
| Diazepam | Has a rapid onset and is used to treat and prevent alcohol withdrawal, anxiolysis and for seizures |
| Clonazepam | Has a longer half-life which asllows for once or twice daily dosing. Avoid use in renal dysfunction. Used to treat anxiety (including panic attacs) |
| Alprazolam | Has the shortest onset of actions. Has a high abuse potential due to this (and since it causes euphoria). Used to treat anxiety (including panic attacks) |
| Lorazepam | Not metabolized by the liver. Can be used to treat alcohol withdrawal, panic attacks and agitation |
| Triazolam | Used to treat insomnia. Has a risk of anterograde amnesia and sleep-related activity |
| Midazolam | Has a very short half-life. Primarily used in anaesthesia (medical and surgical setting) |
- Indications for prescribing benzodiazepines
- Sedation
- Hypnotic
- Anxiolytic
- Anticonvulsant
- Muscle relaxant
- Which Benzodiazepines are fast acting and are thus useful for panic attacks and status epilepticus (acts fast, wears off fast)?
- Midazolam
- Diazepam
- Lorazepam
- Which Benzodiazepines are preferred for **severe insomnia, anxiety disorders (**and panic attacks too)?
- Temazepam
- Triazolam
- Alprazolam
- Which Benzodiazepines are preferred for long-term management of panic disorders and in alcohol withdrawal (acts slow, lasts long at lower levels)?
- Clonazepam
- Chlordiazepoxide (very commonly used for alcohol withdrawal)
- Side effects of benzodiazepines
- Sedation
- Abuse/addiction (not as much as barbiturates)
- Overdose → respiratory depression (will have to take a large amount OR in combination with other sedatives such as Alcohol)
- Impaired intellectual function
- Anterograde amnesia
- Withdrawal (can be life threatenign and cause seizures)
- Trivia: What is the antidote for Benzodiazepine poisoning
- Flumazenil (not used frequently)
Barbiturates
Barbiturates (rarely used) are first-line for infantile seizures, and second-line for Status epileptics. They were originally used for insomnia and panic disorders but fell out of favour due to high toxicity (can be used in suicide attempts). They work by increasing the duration of opening of chloride channels.
butalbitol, phenobarbital, amobarbitol, pentobarbital
Benzodiazepine-like Hypnotics
Tjese are the treatment of choice for insomnia (preferred over Benzodiazepines and antihistamines)
Zolpidem, Zaleplon, Eszopiclone.
- What is the best initial treatment for insomnia?
- Behavioural adjustment (sleep changes; good sleep hygiene)
- Dark room
- No naps during the day
- Blue-light filter
- Behavioural adjustment (sleep changes; good sleep hygiene)
- Which benzodiazepine-like hypnotic is useful for patients who have trouble maintaining sleep?
- Eszopiclone
Other Anxiolytics
| Anxiolytic | Nota bene |
|---|---|
| Buspirone (BuSpar) | Has a slower onset of action than benzodiazepine. Does not potentiate the CNS depression of alcohol and hence is useful in alcoholics. Often used in combination with SSRIs for the treatment of GAD. |
| Hydroxyzine (Atarax) | Antihistamine. Useful for patients that require a quick-acting, short-term medication but cannot take benzodiazepines. Has anticholinergic effects. |
| Propranolol | Useful for treating the autonomic effects of panic attacks or social phobia. Can also be used to treat akathisia. |
| Diphenhydramine (Benadryl) | An antihistamine that has moderate anticholinergic effect. |
| Ramelteon (Rozerem) | Selective MT1 and MT2 agonist. Has no tolerance or depression |
Benzodiazepine Abuse
Benzodiazepines are generally given as prescription medications. Abuse is commonly seen in suicide attempts.
- Signs and symptoms of acute intoxication
- Behavioural disinhibition
- Somnolence
- Severe sedation
- Respiratory depression
- Treatment of acute intoxication
- Supportive care
- Monitor pulse oximetry (due to risk of respiratory depression) and blood pressure
- Intubate if respiratory depression occurs
- Activated charcoal and gastric lavage to prevent further absorption if the drug was ingested within 4 – 6 hours prior
- Flumazenil: an antidote, not used commonly in the emergency department. Has a very short-half life and should be used with caution during overdose since it may precipitate seizures
- For barbiturates, sodium bicarbonate can be given to alkalinize urine and promote renal excretion
Benzodiazepine Withdrawal
Patients usually develop tolerance and dependence to benzodiazepines. If they are withdrawn too quickly a patient can develop benzodiazepine wIthdrawal syndrome (this is very similar to alcohol withdrawal). Withdrawal from benzodiazepines has the highest mortality rate.
Benzodiazepines should therefore only be prescribed for a short period of time (2 – 4 weeks). The dose should then be tapered in steps of about 1/10 – 1/4 (1/8) of the daily dose every fortnight.
- Signs and symptoms of withdrawal
- Anxiety
- Insomnia
- Irritability
- Hyperactivity
- Seizures
- Decreased appetite
- Tremors
- Perceptual disturbances and psychosis
- Tinnitus
- Treatment of withdrawal (Benzodiazepine taper)
- Long-acting benzodiazepines (clonazepam, chlordiazepoxide, diazepam) taper – more commonly prescribed to alcoholics going through withdrawal)
- Benzodiazepine withdrawal protocol for patients experiencing difficulty
- Switch to the equivalent dose of diazpam
- Reduce the dose of diazepam every 2 – 3 weeks in steps of 2 or 2.5 mg
- Time needed for withdrawal may vary from 4 weeks to a year or more
