Anxiolytics - Hyperexcision

Last updated: March 9, 2025

Table Of Contents

Overview
Benzodiazepines
Barbiturates
Benzodiazepine-like Hypnotics
Other Anxiolytics
Benzodiazepine Abuse
Benzodiazepine Withdrawal

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
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

Reference Intervals ›

Biochemistry

ACTH	P: <80 ng/L
ALT	P: 5–35 U/L
Albumin	P: 35–50 g/L
Aldosterone	P: 100–500 pmol/L
Alk. phosphatase	P: 30–130 U/L
α-Amylase	P: 0–180 IU/dL
α-Fetoprotein	S: <10 kU/L
Angiotensin II	P: 5–35 pmol/L
ADH	P: 0.9–4.6 pmol/L
AST	P: 5–35 U/L
Bicarbonate	P: 24–30 mmol/L
Bilirubin	P: 3–17 μmol/L
BNP	P: <50 ng/L
CRP	P: <10 mg/L
Calcitonin	P: <0.1 mcg/L
Calcium (ionized)	P: 1.0–1.25 mmol/L
Calcium (total)	P: 2.12–2.60 mmol/L
Chloride	P: 95–105 mmol/L
Cholesterol	P: <5.0 mmol/L
VLDL	P: 0.128–0.645 mmol/L
LDL	P: <2.0 mmol/L
HDL	P: 0.9–1.93 mmol/L
Cortisol AM	P: 450–700 nmol/L
Cortisol Midnight	P: 80–280 nmol/L
CK ♂	P: 25–195 U/L
CK ♀	P: 25–170 U/L
Creatinine	P: 70–100 μmol/L
Ferritin	P: 12–200 mcg/L
Folate	S: 2.1 mcg/L
FSH	P: 2–8 U/L ♂; >25 menopause
GGT ♂	P: 11–51 U/L
GGT ♀	P: 7–33 U/L
Glucose (fasting)	P: 3.5–5.5 mmol/L
Growth hormone	P: <20 mu/L
HbA1C (DCCT)	B: 4–6%
HbA1C (IFCC)	B: 20–42 mmol/mol
Iron ♂	S: 14–31 μmol/L
Iron ♀	S: 11–30 μmol/L
Lactate (venous)	P: 0.6–2.4 mmol/L
Lactate (arterial)	P: 0.6–1.8 mmol/L
LDH	P: 70–250 U/L
LH	P: 3–16 U/L
Magnesium	P: 0.75–1.05 mmol/L
Osmolality	P: 278–305 mosmol/kg
PTH	P: 0.8–8.5 pmol/L
Potassium	P: 3.5–5.3 mmol/L
Prolactin ♂	P: <450 U/L
Prolactin ♀	P: <600 U/L
PSA	P: 0–4 mcg/mL
Protein (total)	P: 60–80 g/L
Red cell folate	B: 0.36–1.44 μmol/L
Renin (erect)	P: 2.8–4.5 pmol/mL/h
Renin (recumbent)	P: 1.1–2.7 pmol/mL/h
Sodium	P: 135–145 mmol/L
TBG	P: 7–17 mg/L
TSH	P: 0.5–4.2 mU/L
T4	P: 70–140 nmol/L
Free T4	P: 9–22 pmol/L
TIBC	S: 54–75 μmol/L
Triglycerides	P: 0.50–2.3 mmol/L
T3	P: 1.2–3.0 nmol/L
Troponin T	P: <0.1 mcg/L
Urate ♂	P: 210–480 μmol/L
Urate ♀	P: 150–390 μmol/L
Urea	P: 2.5–6.7 mmol/L
Vitamin B12	S: 0.13–0.68 nmol/L
Vitamin D	S: 50 nmol/L

Arterial Blood Gases

pH	7.35–7.45
PaCO₂	4.7–6.0 kPa
PaO₂	>10.6 kPa
Base excess	±2 mmol/L

Urine

Cortisol (free)	<280 nmol/24h
Hydroxyindole acetic acid	16–73 μmol/24h
Hydroxymethylmandelic acid	16–48 μmol/24h
Metanephrines	0.03–0.69 μmol/mmol cr.
Osmolality	350–1000 mosmol/kg
17-Oxogenic steroids ♂	28–30 μmol/24h
17-Oxogenic steroids ♀	21–66 μmol/24h
17-Oxosteroids ♂	17–76 μmol/24h
17-Oxosteroids ♀	14–59 μmol/24h
Phosphate (inorganic)	15–50 mmol/24h
Potassium	14–120 mmol/24h
Protein	<150 mg/24h
Protein/creatinine ratio	<3 mg/mmol
Sodium	100–250 mmol/24h

Haematology

WCC	4.0–11.0 ×10⁹/L
RBC ♂	4.5–6.5 ×10¹²/L
RBC ♀	3.9–5.6 ×10¹²/L
Hb ♂	130–180 g/L
Hb ♀	115–160 g/L
PCV ♂	0.4–0.54 L/L
PCV ♀	0.37–0.47 L/L
MCV	76–96 fL
MCH	27–32 pg
MCHC	300–360 g/L
RDW	11.6–14.6%
Neutrophils	2.0–7.5 ×10⁹/L (40–75%)
Lymphocytes	1.0–4.5 ×10⁹/L (20–45%)
Eosinophils	0.04–0.44 ×10⁹/L (1–6%)
Basophils	0–0.10 ×10⁹/L (0–1%)
Monocytes	0.2–0.8 ×10⁹/L (2–10%)
Platelets	150–400 ×10⁹/L
Reticulocytes	0.8–2.0% / 25–100 ×10⁹/L
Prothrombin time	10–14 s
APTT	35–45 s

Paediatric

Pulse Rate (bpm)
Neonate	140–160
Infant <1yr	120–140
1–5 years	110–130
5–12 years	80–120
>12 years	70–100
Respiratory Rate (tachypnoea)
0–2 months	≥60/min
2–12 months	≥50/min
1–5 years	≥40/min
>5 years	≥30/min
Blood Pressure (mmHg)
Term	65/45
1 year	75/50
4 years	85/60
8 years	95/65
10 years	100/70
Weight Formulas
3–12 months	(a + 9)/2 kg
1–6 years	2a + 8 kg
>6 years	(7a − 5)/2 kg
Haemoglobin (g/dL)
Term newborn	13–20
1 month	11–18
2 months	10–15
1–2 years	10–13
>2 years	11–14
MUAC (6 months–5 years)
Obese	>17.5 cm
Normal	13.5–17.4 cm
At risk	12.5–13.4 cm
Moderate malnutrition	11.5–12.4 cm
Severe malnutrition	<11.5 cm
Developmental Milestones
Social smile	1.5 months
Head control	4 months
Sits unsupported	7 months
Crawls	10 months
Stands unsupported	10–12 months
Walks	12–13 months
Talks	18 months
CSF WBC (/mm³)
Term newborn	0–25
>2 weeks	0–5

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