Benzodiazepines 

Name	Duration of Action#	Time to peak	Approx dose equiv to 5mg diazepam	Trade names	Tablet strengths	Schedule
Alprazolam	Short½ life 12-15 hrs	1-2 hours (intermediate)	0.5 – 1mg	AlpraxKalmaXanax	0.25mg, 0.5mg, 1mg, 2mg	Schedule 8 Controlled Drug
Bromazepam	Intermed		3 – 6mg	Lexotan	3mg, 6mg	S4
Clobazam	Long		10 – 15mg	Frisium	10mg	S4
Clonazepam	Long½ life 18-50hrs	1-4 hours (intermediate)	0.25 – 0.5mg	RivotrilPaxam	0.5mg, 2mg	S4
Diazepam	Long½ life 20-80 hrs	0.5-6 hours (rapid)	5mg	AntenexDuceneValiumValpam	2mg, 5mg	S4
Flunitrazepam	Long		1 – 2mg	Hypnodorm	1mg	Schedule 8 Controlled Drug
Lorazepam	Intermed ½ life 10-20 hrs	1-2 hours (intermediate)	0.5 – 1mg	Ativan	1mg, 2.5mg	S4
Nitrazepam	Long		5mg	AlodormMogadon	5mg	S4
Oxazepam	Short½ life 5-11 hrs	3 hours (intermediate – slow)	30mg	AlepamMurelaxSerepax	15mg, 30mg	S4
Temazepam	Short		10 – 20mg	NormisonTemazeTemtabs	10mg	S4
Triazolam	Very short		0.25mg	Halcion	0.125mg	S4
Zolpidem	Very short		10mg	DormizoStildemStilnoxZolpibell	10mg (6.25mg &12.5mg modified release)	S4
Zopiclone	Very short		7.5mg	ImovaneImrest	7.5mg	S4
# Approximate duration of action: Very short < 6hoursShort 6-12 hoursIntermediate 12-24 hours Long > 24 hours Different sources quote varying equivalents. Figures in BOLD are recommended as safest and most consistent with references and clinical experience.

• beneficial for
  • acute relief of anxiety
  • social anxiety disorder
    • more effective than SSRIs
    • but may worsen symptoms in patients with comorbid depression or PTSD
    • choose lorazepam or oxazepam: both are metabolized through conjugation and do not produce active metabolites (fewer CYP 450 drug interactions).
  • depression
    • used to “bridge” patients who are starting an “antidepressant” for anxiety, since the therapeutic effects may be delayed, and patients may experience stimulating side effects initially.
• tolerance to the anxiolytic effects is uncommon
• avoid use in patients with a history of substance use disorder
• long-term use of benzodiazepines is not recommended due to
  • risk of dependence
  • risk of dependence is increased with the agents that are rapidly absorbed and with shorter half-lives, i.e., alprazolam and diazepam.
• In PREGNANCY
  • Benzodiazepines are category D drugs, primarily due to concerns with cleft lip/palate and urogenital and neurological malformations
    • however, recent literature does not show an increased risk of these[3].
  • When possible, avoid use during the first trimester
    • Minimize use; i.e., reserve for PRN use if possible
  • Weigh the benefit vs. the risk of continued therapy
  • if necessary, consider an agent with a short half-life, and use sparingly and intermittently
  • Consider initiating and/or maintaining patients on an antidepressant agent. With the exception of paroxetine (category D), all the antidepressants are in category C

ADVERSE DRUG REACTIONS

GENERAL

• Most benzodiazepines can cause these side effects due to their inhibitory effects on brain neurotransmission:
  • Anterograde amnesia
  • Confusion
  • Dizziness
  • Depression
  • Sedation
• Withdrawal symptoms from benzodiazepines (seizures, hallucinations, agitation, tremors) are most common when using benzodiazepines with shorter half-lives

COMMON

• Alprazolam: Changes in appetite (decrease or increase), weight gain, reduced mucosal production leading to xerostomia and constipation, confusion, sedation, cognitive impairment, memory impairment, irritability
• Chlordiazepoxide: Edema, constipation, nausea, confusion, sedation, cognitive impairment, memory impairment, irritability
• Clonazepam: Depression, ataxia, dizziness, confusion, sedation, cognitive impairment, memory impairment, irritability, upper respiratory infection, respiratory depression
• Diazepam: Hypotension, ataxia, dizziness, confusion, sedation, cognitive impairment
• Lorazepam: Depression, ataxia, dizziness, confusion, sedation, cognitive impairment
• Oxazepam: Dizziness, headache, sedation

OCCASIONAL

• Alprazolam: Decreased libido
• Chlordiazepoxide: Irregular menses, decreased libido
• Clonazepam: Suicidal ideation
• Diazepam: Muscle weakness, respiratory depression; rash and diarrhea can occur with rectal gel use
• Lorazepam: Delirium (especially in elderly patients), weakness

RARE

• Alprazolam: Stevens-Johnson Syndrome, liver failure
• Chlordiazepoxide: Agranulocytosis, liver failure
• Diazepam: Neutropenia
• Lorazepam: Acidosis

General

These symptoms tend to occur with the withdrawal of any central nervous system depressant-type drug (including alcohol).

• anxiety, panic attacks, depression and agoraphobia
• sleep disturbances
• irritability, difficulty in concentrating and remembering
• tremor and general shakiness
• sweating
• nausea, loss of appetite, loss of weight
• seizures (if taking greater than 50mg equivalent diazepam per day).

Specific to benzodiazepine withdrawal

• metallic taste
• distorted hearing – sounds appear unduly loud or strange
• feelings of depersonalisation and unreality
• distorted vision – patient may feel they are seeing things through a veil
• sense of smell and touch heightened and distorted
• pain, stiffness and muscular spasms, particularly in the face and scalp, which can result in headaches and muscle twitching
• paranoid thoughts and feelings

Stage	Psychological sx	Physiological sx
Acute withdrawal	Anxiety Panic attacks Depression Insomnia Poor memory   Other: poor [ ], anger, irritability, distorted perceptions	Agitation Tremor Headaches Weakness Dizziness   Other: N, V, D, C, palpitations, fatigue, flu-like sx
Protracted withdrawal	Anxiety Depression Insomnia Irritability Muscle aches   Other: restlessness, poor [ ] , memory problems	Diarrhoea Constipation Bloating
Potential withdrawal complications	Transient hallucinations Delirium Psychosis	1. Withdrawal seizures (1-2%)

Weaning BZ

1. Convert and switch BZ to equivalent dose of longer acting BZ eg. Diazepam or oxazepam
2. Reduce dose by 10% every 1-2 weeks with regular medical review, until 5mg diazepam dose reached
3. Once on 5mg diazepam daily reached, ¯ dose by 1mg decrements
4. Consider treatment agreement & reduction plan
5. If unable to tolerate the withdrawal of BZ in community – consider inpatient treatment with drug & alcohol service of residential withdrawal treatment