Benzodiazepines

GABA_A agonist (positive allosteric modulator)

Choosing a Benzo

Best Overall: Lorazepam: 0.5 to 3 mg/day divided q8-12 hr. PDR mentions can go up to 6 mg but that is rare (Side effects and withdrawal risks worse with high doses). It has few drug interactions or metabolites, a lower OD risk, and reasonable duration. Available as Loreev XR (brand only, but lowers misuse risk).

FDA-approved in Panic Disorder: Alprazolam (typical 2-5 mg/day), clonazepam (typical 1-2 mg/day).

Safest: Oxazepam (10-15 mg 3-4 times/day). This has lowest OD risk with opioids, and lowest risk of addiction when combined with stimulants (benzos should not be combined with stimulants, but if you inherit them, start by switching to oxazepam).

Lacking hepatic metabolism: Lorazepam, oxazepam, temazepam. These are ideal in elderly, hepatic impairment, and for avoiding drug interactions.

Best for alcohol withdrawal or benzo tapering: Diazepam and chlordiazepoxide preferable for their long half-lives, but if hepatic impairment use lorazepam. For benzo withdrawal, often best to use the same benzo they are on, especially with alprazolam.

Best for depression: Alprazolam speeds antidepressant meds up and treats core symptoms of depression, but should only be used short-term for that. Long-term use can cause depressive symptoms. The XR version is generic and has lower misuse risk.

Best for insomnia: Temazepam, lorazepam.

Least safe: Alprazolam, clonazepam, and diazepam have high risk of OD, misuse, diversion. Triazolam is notorious for causing disinhibition/aggression.

Safest in pregnancy. Avoid all benzos in pregnancy. Lorazepam is safest in breastfeeding.

Management

If using PRN for anxiety, tell patient to only take it if it improves their functioning and reduces avoidance (eg, don’t take it if you stay in bed all day).

Avoid in PTSD (worsens outcomes), borderline (rare disinhibition/aggression), delirium/dementia (worsens cognition), elderly, age < 18, taking opioids, antisocial personality.

Absolutely avoid in: History of benzo or opioid overdose. Elderly with history of falls or traffic accidents while on them (or high fall risk). Active substance misuse (especially opioids). Taking opioids with risk factors below.

Benzos-Opioids: When to Avoid the Combo to Minimize OD Risk
▪ ABSOLUTE CONTRAINDICATION
Active prescription misuse Active addiction to benzos, opioids, alcohol, or other sedatives
History of sedative overdose (on sleep meds, benzos, opioids)
On opioid replacement therapy that you aren’t managing (let them manage both; OR risk is particularly high with methadone)
▪ STRONG RELATIVE CONTRAINDICATIONS
Daily opioid dose ≥ 50 morphine milligram equivalents (particularly with long-acting opioids and benzos)
Age ≥ 65
History of sedative, alcohol, or opioid use disorder (in remission)
Borderline or antisocial personality disorder or unstable psychiatric disorder with OD or suicide risk
Respiratory disease (eg COPD, sleep apnea), systemic medical illness (eg HIV, organ failure, renal or hepatic impairment), or pregnancy

Benzo Conversion

Conversion doses (based on clonazepam) are approximate. Use the lower end if patient is at high risk of adverse effects, the higher range if at high risk of withdraway/anxiety. The schedule does not always match the half-life because duration in the blood stream may not match duration in brain.

Benzodiazepine	Half Life	Schedule	Clonazepam 1mg =
Triazolam	2-6 hr	QHS	0.5-1 mg
Oxazepam	4-15 hr	TID-QID	60 mg
Temazepam	8-22 hr	QHS	30-60 mg
Alprazolam	6-12 hr	BID-TID	1-2 mg
Lorazepam	10-20 hr	BID-TID	2-4 mg
Estazolam	10-24 hr	QHS	2-4 mg
Clonazepam	1-2 days	BID	1 mg
Quazepam	2-3 days + 1-6 days*	QHS	30-40 mg
Diazepam	1-4 days + 1-8 days*	BID-TID	20 mg
Clorazepate	< 30 min + 2-8 days*	BID-QID	30 mg
Chlordiazepoxide	½ – 2 days + 2-8 days*	BID-QID	50 mg
Flurazepam	2-3 hr + 2-10 days*	QHS	30-60 mg

*These benzos have active metabolites that extend their action over longer half-lives.

Benzo Withdrawal

Lower the dose every 1-4 weeks. Lower faster and by larger amounts in the beginning, then slower and by smaller amounts toward end. Can switch to diazepam, which has a long half life and allows smaller increments in dose (it comes as 2 mg, which equals 0.1 mg of clonazepam). For other benzos, you can obtain smaller doses with liquid or microdosing (liquifying med).

Time on Daily Benzo	Taper Duration
Less than 2 months	Taper may not be required. Reduce the benzo to “as needed” for 2-4 weeks, then stop
2-6 months	2 to 3 weeks
6-12 months	1-2 months
> 12 months	2-4 months (or longer if high dose or long duration)

Below is a handout for patients, and Ashton guides for exact tapering doses.

EMR Text