Alprazolam - Revision history

MDElliottMD: Alprazolam: full prescribing-guide page. History-first intro and History (Roche/Sternbach benzodiazepine discovery, Hester/Upjohn triazolobenzodiazepines, Sheehan and panic disorder, the two FDA boxed warnings, the publication-bias literature), pharmacokinetics, pharmacodynamics, interactions, hyperbolic-taper dosing; overdose folded into Monitoring. Clinically reviewed by pharmacist-claude; filed Pharmaceutical

2026-05-21T05:54:06Z

Alprazolam: full prescribing-guide page. History-first intro and History (Roche/Sternbach benzodiazepine discovery, Hester/Upjohn triazolobenzodiazepines, Sheehan and panic disorder, the two FDA boxed warnings, the publication-bias literature), pharmacokinetics, pharmacodynamics, interactions, hyperbolic-taper dosing; overdose folded into Monitoring. Clinically reviewed by pharmacist-claude; filed Pharmaceutical

Show changes

MDElliottMD: Em-dash sweep: replace em-dash with comma per project rule; PendellsCorner verbatim quotes preserved.

2026-05-19T03:16:04Z

Em-dash sweep: replace em-dash with comma per project rule; PendellsCorner verbatim quotes preserved.

MDElliottMD: Sweep: "indications" -> "problems" sitewide terminology update (preserves MedTemplate param name)

2026-05-19T01:37:42Z

Sweep: "indications" -> "problems" sitewide terminology update (preserves MedTemplate param name)

← Older revision		Revision as of 01:37, 19 May 2026
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	\| intro = '''Alprazolam''' is a high-potency, intermediate-acting triazolobenzodiazepine, FDA-approved for generalized anxiety disorder, panic disorder, and anxiety associated with depression. Its rapid onset, short-to-intermediate half-life, and high potency make it both clinically effective and uniquely problematic among benzodiazepines: alprazolam has consistently been associated with the highest rates of dependence, misuse, and difficult withdrawal in its class. For most chronic anxiety treatment, longer-acting agents (clonazepam, diazepam) or non-benzodiazepine alternatives (SSRIs, SNRIs, buspirone) are preferred.		\| intro = '''Alprazolam''' is a high-potency, intermediate-acting triazolobenzodiazepine, FDA-approved for generalized anxiety disorder, panic disorder, and anxiety associated with depression. Its rapid onset, short-to-intermediate half-life, and high potency make it both clinically effective and uniquely problematic among benzodiazepines: alprazolam has consistently been associated with the highest rates of dependence, misuse, and difficult withdrawal in its class. For most chronic anxiety treatment, longer-acting agents (clonazepam, diazepam) or non-benzodiazepine alternatives (SSRIs, SNRIs, buspirone) are preferred.
	\| pharmacokinetics = Rapid and near-complete oral absorption; bioavailability ~80–100%. Peak plasma levels in 1–2 hours (IR) or ~9 hours (XR). Highly protein-bound (~80%). Metabolized hepatically by '''CYP3A4''' to α-hydroxyalprazolam and 4-hydroxyalprazolam — both pharmacologically active but present at low concentrations. Half-life ~11 hours in healthy adults; substantially prolonged in elderly patients, obesity, and hepatic impairment. The relatively short half-life relative to diazepam contributes to inter-dose rebound anxiety with TID dosing and to the severity of its discontinuation syndrome.		\| pharmacokinetics = Rapid and near-complete oral absorption; bioavailability ~80–100%. Peak plasma levels in 1–2 hours (IR) or ~9 hours (XR). Highly protein-bound (~80%). Metabolized hepatically by '''CYP3A4''' to α-hydroxyalprazolam and 4-hydroxyalprazolam — both pharmacologically active but present at low concentrations. Half-life ~11 hours in healthy adults; substantially prolonged in elderly patients, obesity, and hepatic impairment. The relatively short half-life relative to diazepam contributes to inter-dose rebound anxiety with TID dosing and to the severity of its discontinuation syndrome.
	\| pharmacodynamics = Binds to the benzodiazepine site on GABA<sub>A</sub> receptors, allosterically enhancing GABA-induced chloride channel opening (increased '''frequency''' of opening, not duration — distinguishing benzodiazepines from barbiturates). This hyperpolarizes the neuron, producing anxiolytic, sedative, hypnotic, anticonvulsant, and skeletal muscle relaxant effects. Compared to other benzodiazepines, alprazolam shows relatively greater anxiolytic and antipanic effect with somewhat less sedation per unit anxiolysis, attributed in part to its triazole ring. Some evidence of mild antidepressant activity at higher doses, the basis for its "anxiety with depression" ~~indication~~.		\| pharmacodynamics = Binds to the benzodiazepine site on GABA<sub>A</sub> receptors, allosterically enhancing GABA-induced chloride channel opening (increased '''frequency''' of opening, not duration — distinguishing benzodiazepines from barbiturates). This hyperpolarizes the neuron, producing anxiolytic, sedative, hypnotic, anticonvulsant, and skeletal muscle relaxant effects. Compared to other benzodiazepines, alprazolam shows relatively greater anxiolytic and antipanic effect with somewhat less sedation per unit anxiolysis, attributed in part to its triazole ring. Some evidence of mild antidepressant activity at higher doses, the basis for its "anxiety with depression" problem.
	\| indications = * Generalized anxiety disorder		\| indications = * Generalized anxiety disorder
	* Panic disorder (with or without agoraphobia)		* Panic disorder (with or without agoraphobia)

Maintenance script: Terminology: medicine → med (shorter form per user preference)

2026-05-16T02:42:46Z

Terminology: medicine → med (shorter form per user preference)

← Older revision		Revision as of 02:42, 16 May 2026
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	* '''Cognitive impairment''' — both acute (memory, attention) and chronic with long-term use; partial reversibility uncertain.		* '''Cognitive impairment''' — both acute (memory, attention) and chronic with long-term use; partial reversibility uncertain.
	* '''Falls and fractures''' in elderly.		* '''Falls and fractures''' in elderly.
	* '''Anterograde amnesia''' — clinically significant; can be exploited for criminal purposes (~~medicine~~-facilitated assault).		* '''Anterograde amnesia''' — clinically significant; can be exploited for criminal purposes (med-facilitated assault).
	* '''Misuse and diversion''' — Xanax has substantial street value and frequent recreational misuse.		* '''Misuse and diversion''' — Xanax has substantial street value and frequent recreational misuse.
	* '''Suicide risk in overdose''' — especially when combined with alcohol or opioids.		* '''Suicide risk in overdose''' — especially when combined with alcohol or opioids.

Maintenance script: Terminology sweep (site-wide): drug/medication → medicine

2026-05-16T02:30:54Z

Terminology sweep (site-wide): drug/medication → medicine

← Older revision		Revision as of 02:30, 16 May 2026
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	* '''Cognitive impairment''' — both acute (memory, attention) and chronic with long-term use; partial reversibility uncertain.		* '''Cognitive impairment''' — both acute (memory, attention) and chronic with long-term use; partial reversibility uncertain.
	* '''Falls and fractures''' in elderly.		* '''Falls and fractures''' in elderly.
	* '''Anterograde amnesia''' — clinically significant; can be exploited for criminal purposes (~~drug~~-facilitated assault).		* '''Anterograde amnesia''' — clinically significant; can be exploited for criminal purposes (medicine-facilitated assault).
	* '''Misuse and diversion''' — Xanax has substantial street value and frequent recreational misuse.		* '''Misuse and diversion''' — Xanax has substantial street value and frequent recreational misuse.
	* '''Suicide risk in overdose''' — especially when combined with alcohol or opioids.		* '''Suicide risk in overdose''' — especially when combined with alcohol or opioids.

MDElliottMD: Comprehensive categorization: +Benzodiazepines, GABAA Positive Allosteric Modulators (General), GABAergics, Anxiolytics & Sedative-Hypnotics

2026-05-15T18:42:09Z

Comprehensive categorization: +Benzodiazepines, GABAA Positive Allosteric Modulators (General), GABAergics, Anxiolytics & Sedative-Hypnotics

← Older revision		Revision as of 18:42, 15 May 2026
Line 69:		Line 69:
	\| references =		\| references =
	}}		}}
			[[Category:Benzodiazepines]]
			[[Category:GABAA Positive Allosteric Modulators (General)]]
			[[Category:GABAergics]]
			[[Category:Anxiolytics & Sedative-Hypnotics]]

MDElliottMD: Pharmacopedia: add

2026-05-14T03:30:41Z

Pharmacopedia: add <pharmaInteractions/>

← Older revision		Revision as of 03:30, 14 May 2026
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	* '''Grapefruit juice''' — modest CYP3A4 inhibition; can raise alprazolam levels with regular consumption		* '''Grapefruit juice''' — modest CYP3A4 inhibition; can raise alprazolam levels with regular consumption
	* '''Fluoxetine, fluvoxamine''' — increase alprazolam levels via CYP3A4 inhibition		* '''Fluoxetine, fluvoxamine''' — increase alprazolam levels via CYP3A4 inhibition
			<pharmaInteractions/>
	\| pregnancy_details = Historically Category D. First-trimester benzodiazepine exposure has been associated with increased risk of cleft lip/palate in some studies, though absolute risk is small. Third-trimester or near-term use can produce '''floppy infant syndrome''' (hypotonia, hypothermia, feeding difficulty, respiratory depression) and neonatal withdrawal. Generally avoided in pregnancy unless benefits clearly outweigh risks; SSRIs are usually preferred for chronic anxiety. Excreted in breast milk — breastfeeding generally discouraged.		\| pregnancy_details = Historically Category D. First-trimester benzodiazepine exposure has been associated with increased risk of cleft lip/palate in some studies, though absolute risk is small. Third-trimester or near-term use can produce '''floppy infant syndrome''' (hypotonia, hypothermia, feeding difficulty, respiratory depression) and neonatal withdrawal. Generally avoided in pregnancy unless benefits clearly outweigh risks; SSRIs are usually preferred for chronic anxiety. Excreted in breast milk — breastfeeding generally discouraged.
	\| monitoring = * Continued need for treatment — reassess at every visit; target shortest effective duration		\| monitoring = * Continued need for treatment — reassess at every visit; target shortest effective duration

MDElliottMD: Pharmacopedia: remove contraindications parameter

2026-05-14T02:40:23Z

Pharmacopedia: remove contraindications parameter

← Older revision		Revision as of 02:40, 14 May 2026
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	* '''Suicide risk in overdose''' — especially when combined with alcohol or opioids.		* '''Suicide risk in overdose''' — especially when combined with alcohol or opioids.
	* '''Rebound anxiety''' between doses with short-half-life IR formulation.		* '''Rebound anxiety''' between doses with short-half-life IR formulation.
	~~\| contraindications = * Acute narrow-angle glaucoma~~
	* Severe respiratory insufficiency (including untreated sleep apnea)
	* Severe hepatic impairment
	* Concurrent strong CYP3A4 inhibitors (ketoconazole, itraconazole) — contraindicated per FDA labeling
	* Known hypersensitivity to alprazolam or benzodiazepines
	* Caution: history of substance use disorder, myasthenia gravis, pregnancy
	\| interactions = * '''Opioids''' — additive respiratory depression and overdose risk ('''FDA black box warning'''); avoid when possible		\| interactions = * '''Opioids''' — additive respiratory depression and overdose risk ('''FDA black box warning'''); avoid when possible
	* '''Alcohol''' — additive CNS depression and respiratory depression		* '''Alcohol''' — additive CNS depression and respiratory depression

MDElliottMD at 07:51, 11 May 2026

2026-05-11T07:51:41Z

← Older revision		Revision as of 07:51, 11 May 2026
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	{{MedTemplate		{{MedTemplate
	\| generic = ~~alprazolam~~		\| generic = Alprazolam
	\| brand = Xanax, Niravam		\| brand = Xanax, Xanax XR, Niravam, Frontin, Alprax, Helex
	\| structure =		\| structure = Alprazolam_structure.svg
	\| ~~class~~ = ~~Benzodiazepines~~, ~~Anxiolytics~~		\| classes = Benzodiazepine, Anxiolytic
	\| mechanism = GABA-A ~~allosteric modulation~~		\| mechanism = Positive allosteric modulator at GABA<sub>A</sub> receptor (benzodiazepine site)
	\| uses = ~~Anxiety~~, ~~Panic~~, ~~Psychedelic crisis~~		\| uses = Generalized anxiety disorder, panic disorder, anxiety with depression
	\| formula =		\| formula = C<sub>17</sub>H<sub>13</sub>ClN<sub>4</sub>
	~~\| mass =~~		\| routes = Oral, sublingual (ODT)
	~~\| cas =~~		\| onset = 15–30 minutes
	~~\| atc =~~		\| duration = 4–6 hours (IR); 11–17 hours (XR)
	\| routes =		\| halflife = ~11 hours (range 6–27 h; prolonged in elderly and hepatic impairment)
	\| onset =		\| bioavailability = ~80–100%
	\| duration =		\| pregnancy = Avoid
	\| halflife =		\| legal = Schedule IV
	\| bioavailability =		\| intro = '''Alprazolam''' is a high-potency, intermediate-acting triazolobenzodiazepine, FDA-approved for generalized anxiety disorder, panic disorder, and anxiety associated with depression. Its rapid onset, short-to-intermediate half-life, and high potency make it both clinically effective and uniquely problematic among benzodiazepines: alprazolam has consistently been associated with the highest rates of dependence, misuse, and difficult withdrawal in its class. For most chronic anxiety treatment, longer-acting agents (clonazepam, diazepam) or non-benzodiazepine alternatives (SSRIs, SNRIs, buspirone) are preferred.
	\| pregnancy =		\| pharmacokinetics = Rapid and near-complete oral absorption; bioavailability ~80–100%. Peak plasma levels in 1–2 hours (IR) or ~9 hours (XR). Highly protein-bound (~80%). Metabolized hepatically by '''CYP3A4''' to α-hydroxyalprazolam and 4-hydroxyalprazolam — both pharmacologically active but present at low concentrations. Half-life ~11 hours in healthy adults; substantially prolonged in elderly patients, obesity, and hepatic impairment. The relatively short half-life relative to diazepam contributes to inter-dose rebound anxiety with TID dosing and to the severity of its discontinuation syndrome.
	\| legal =		\| pharmacodynamics = Binds to the benzodiazepine site on GABA<sub>A</sub> receptors, allosterically enhancing GABA-induced chloride channel opening (increased '''frequency''' of opening, not duration — distinguishing benzodiazepines from barbiturates). This hyperpolarizes the neuron, producing anxiolytic, sedative, hypnotic, anticonvulsant, and skeletal muscle relaxant effects. Compared to other benzodiazepines, alprazolam shows relatively greater anxiolytic and antipanic effect with somewhat less sedation per unit anxiolysis, attributed in part to its triazole ring. Some evidence of mild antidepressant activity at higher doses, the basis for its "anxiety with depression" indication.
	\| intro =		\| indications = * Generalized anxiety disorder
	\| ~~pharmacology~~ =		* Panic disorder (with or without agoraphobia)
	\| ~~pharmacokinetics~~ =		* Anxiety associated with depression
	\| indications =		* '''Not first-line''' for chronic anxiety — SSRIs, SNRIs, buspirone, or CBT typically preferred due to dependence risk
	\| dosing =		* Occasionally used short-term for procedural anxiety or situational anxiety
	\| effects =		\| dosing = '''GAD:''' Start 0.25–0.5 mg PO three times daily; titrate slowly. Max 4 mg/day.
	\| adverse =		'''Panic disorder:''' Start 0.5 mg PO three times daily; titrate by 1 mg/day every 3–4 days. Typical effective 1–10 mg/day (FDA labeling permits to 10 mg/day, but doses >4 mg substantially increase dependence and adverse effects).
	\| contraindications =		'''Elderly/debilitated:''' Start 0.25 mg 2–3 times daily; titrate very cautiously.
	\| interactions =		'''Hepatic impairment:''' Reduce dose 50% or more.
	\| pregnancy_details =		'''Discontinuation:''' '''Always taper.''' Typical reduction 0.5 mg every 3 days at minimum; for long-term users, much slower (Ashton-style protocols reduce by ~10% of current dose every 1–2 weeks). Abrupt cessation can precipitate seizures.
	\| monitoring =		\| effects = ''Therapeutic:'' anxiolysis (rapid), reduced panic frequency and severity, calming, mild euphoria, improved sleep.
	\| counseling =		''Common adverse:'' '''drowsiness''', '''dizziness''', impaired coordination, fatigue, slurred speech, dry mouth, blurred vision, '''anterograde amnesia''', impaired psychomotor performance, decreased libido, changes in appetite.
			\| adverse = * '''Dependence and addiction''' — highest among commonly-prescribed benzodiazepines. Physical dependence can develop within weeks of regular use.
			* '''Withdrawal syndrome''' — rebound anxiety, insomnia, tremor, sweating, perceptual disturbances, depersonalization, '''seizures''' with abrupt cessation. Often more severe and protracted than withdrawal from longer-acting benzodiazepines.
			* '''Tolerance''' — anxiolytic and hypnotic tolerance develops with chronic use; tolerance to amnestic and motor effects is less complete.
			* '''Respiratory depression''' — especially in combination with opioids ('''black box warning'''), alcohol, or other CNS depressants. Cause of many overdose deaths.
			* '''Paradoxical reactions''' — agitation, disinhibition, aggression, particularly in elderly, children, or those with personality disorders.
			* '''Cognitive impairment''' — both acute (memory, attention) and chronic with long-term use; partial reversibility uncertain.
			* '''Falls and fractures''' in elderly.
			* '''Anterograde amnesia''' — clinically significant; can be exploited for criminal purposes (drug-facilitated assault).
			* '''Misuse and diversion''' — Xanax has substantial street value and frequent recreational misuse.
			* '''Suicide risk in overdose''' — especially when combined with alcohol or opioids.
			* '''Rebound anxiety''' between doses with short-half-life IR formulation.
			\| contraindications = * Acute narrow-angle glaucoma
			* Severe respiratory insufficiency (including untreated sleep apnea)
			* Severe hepatic impairment
			* Concurrent strong CYP3A4 inhibitors (ketoconazole, itraconazole) — contraindicated per FDA labeling
			* Known hypersensitivity to alprazolam or benzodiazepines
			* Caution: history of substance use disorder, myasthenia gravis, pregnancy
			\| interactions = * '''Opioids''' — additive respiratory depression and overdose risk ('''FDA black box warning'''); avoid when possible
			* '''Alcohol''' — additive CNS depression and respiratory depression
			* '''CYP3A4 inhibitors''' (ketoconazole, itraconazole, ritonavir, clarithromycin, nefazodone) — substantially increase alprazolam levels; some contraindicated
			* '''CYP3A4 inducers''' (carbamazepine, phenytoin, rifampin, St. John's wort) — decrease levels; may reduce efficacy
			* '''Other CNS depressants''' (Z-drugs, sedating antihistamines, gabapentinoids, sedating antidepressants) — additive
			* '''Grapefruit juice''' — modest CYP3A4 inhibition; can raise alprazolam levels with regular consumption
			* '''Fluoxetine, fluvoxamine''' — increase alprazolam levels via CYP3A4 inhibition
			\| pregnancy_details = Historically Category D. First-trimester benzodiazepine exposure has been associated with increased risk of cleft lip/palate in some studies, though absolute risk is small. Third-trimester or near-term use can produce '''floppy infant syndrome''' (hypotonia, hypothermia, feeding difficulty, respiratory depression) and neonatal withdrawal. Generally avoided in pregnancy unless benefits clearly outweigh risks; SSRIs are usually preferred for chronic anxiety. Excreted in breast milk — breastfeeding generally discouraged.
			\| monitoring = * Continued need for treatment — reassess at every visit; target shortest effective duration
			* Signs of dependence, tolerance, dose escalation, or misuse
			* Cognitive function, especially in long-term users and elderly
			* Mood and suicidality
			* Falls risk in elderly
			* Respiratory status, especially in COPD/OSA or on opioids
			* Liver function in long-term use
			\| counseling = * '''Take exactly as prescribed''' — do not increase dose without consulting prescriber.
			* '''Do not combine with alcohol''' or other sedatives — combinations can be fatal.
			* '''Do not stop abruptly''' — can cause seizures; must be tapered.
			* Avoid driving or operating machinery until response is known.
			* May cause memory gaps, especially with higher doses or alcohol.
			* Long-term daily use carries a real risk of dependence — discuss alternatives if treatment will extend beyond a few weeks.
			* Avoid grapefruit juice in large quantities.
			* Keep secured — high risk of theft and diversion.
			* If pregnant or planning pregnancy, discuss with prescriber.
	\| anecdotes =		\| anecdotes =
	\| seealso =		\| seealso = [[Lorazepam]], [[Diazepam]], [[Clonazepam]], [[Temazepam]], [[Midazolam]], [[Buspirone]], [[Hydroxyzine]], [[Pregabalin]]
	\| references =		\| references =
	}}		}}

MDElliottMD: Created page with "{{MedTemplate | generic = alprazolam | brand = Xanax, Niravam | structure = | class = Benzodiazepines, Anxiolytics | mechanism = GABA-A allosteric modulation | uses = Anxiety, Panic, Psychedelic crisis | formula = | mass = | cas = | atc = | routes = | onset = | duration = | halflife = | bioavailability = |..."

2026-05-11T00:13:24Z

Created page with "{{MedTemplate | generic = alprazolam | brand = Xanax, Niravam | structure = | class = Benzodiazepines, Anxiolytics | mechanism = GABA-A allosteric modulation | uses = Anxiety, Panic, Psychedelic crisis | formula = | mass = | cas = | atc = | routes = | onset = | duration = | halflife = | bioavailability = |..."

New page

{{MedTemplate
| generic = alprazolam
| brand = Xanax, Niravam
| structure =
| class = Benzodiazepines, Anxiolytics
| mechanism = GABA-A allosteric modulation
| uses = Anxiety, Panic, Psychedelic crisis
| formula =
| mass =
| cas =
| atc =
| routes =
| onset =
| duration =
| halflife =
| bioavailability =
| pregnancy =
| legal =
| intro =
| pharmacology =
| pharmacokinetics =
| indications =
| dosing =
| effects =
| adverse =
| contraindications =
| interactions =
| pregnancy_details =
| monitoring =
| counseling =
| anecdotes =
| seealso =
| references =
}}

← Older revision		Revision as of 03:16, 19 May 2026
Line 15:		Line 15:
	\| legal = Schedule IV		\| legal = Schedule IV
	\| intro = '''Alprazolam''' is a high-potency, intermediate-acting triazolobenzodiazepine, FDA-approved for generalized anxiety disorder, panic disorder, and anxiety associated with depression. Its rapid onset, short-to-intermediate half-life, and high potency make it both clinically effective and uniquely problematic among benzodiazepines: alprazolam has consistently been associated with the highest rates of dependence, misuse, and difficult withdrawal in its class. For most chronic anxiety treatment, longer-acting agents (clonazepam, diazepam) or non-benzodiazepine alternatives (SSRIs, SNRIs, buspirone) are preferred.		\| intro = '''Alprazolam''' is a high-potency, intermediate-acting triazolobenzodiazepine, FDA-approved for generalized anxiety disorder, panic disorder, and anxiety associated with depression. Its rapid onset, short-to-intermediate half-life, and high potency make it both clinically effective and uniquely problematic among benzodiazepines: alprazolam has consistently been associated with the highest rates of dependence, misuse, and difficult withdrawal in its class. For most chronic anxiety treatment, longer-acting agents (clonazepam, diazepam) or non-benzodiazepine alternatives (SSRIs, SNRIs, buspirone) are preferred.
	\| pharmacokinetics = Rapid and near-complete oral absorption; bioavailability ~80–100%. Peak plasma levels in 1–2 hours (IR) or ~9 hours (XR). Highly protein-bound (~80%). Metabolized hepatically by '''CYP3A4''' to α-hydroxyalprazolam and 4-hydroxyalprazolam — both pharmacologically active but present at low concentrations. Half-life ~11 hours in healthy adults; substantially prolonged in elderly patients, obesity, and hepatic impairment. The relatively short half-life relative to diazepam contributes to inter-dose rebound anxiety with TID dosing and to the severity of its discontinuation syndrome.		\| pharmacokinetics = Rapid and near-complete oral absorption; bioavailability ~80–100%. Peak plasma levels in 1–2 hours (IR) or ~9 hours (XR). Highly protein-bound (~80%). Metabolized hepatically by '''CYP3A4''' to α-hydroxyalprazolam and 4-hydroxyalprazolam, both pharmacologically active but present at low concentrations. Half-life ~11 hours in healthy adults; substantially prolonged in elderly patients, obesity, and hepatic impairment. The relatively short half-life relative to diazepam contributes to inter-dose rebound anxiety with TID dosing and to the severity of its discontinuation syndrome.
	\| pharmacodynamics = Binds to the benzodiazepine site on GABA<sub>A</sub> receptors, allosterically enhancing GABA-induced chloride channel opening (increased '''frequency''' of opening, not duration — distinguishing benzodiazepines from barbiturates). This hyperpolarizes the neuron, producing anxiolytic, sedative, hypnotic, anticonvulsant, and skeletal muscle relaxant effects. Compared to other benzodiazepines, alprazolam shows relatively greater anxiolytic and antipanic effect with somewhat less sedation per unit anxiolysis, attributed in part to its triazole ring. Some evidence of mild antidepressant activity at higher doses, the basis for its "anxiety with depression" problem.		\| pharmacodynamics = Binds to the benzodiazepine site on GABA<sub>A</sub> receptors, allosterically enhancing GABA-induced chloride channel opening (increased '''frequency''' of opening, not duration, distinguishing benzodiazepines from barbiturates). This hyperpolarizes the neuron, producing anxiolytic, sedative, hypnotic, anticonvulsant, and skeletal muscle relaxant effects. Compared to other benzodiazepines, alprazolam shows relatively greater anxiolytic and antipanic effect with somewhat less sedation per unit anxiolysis, attributed in part to its triazole ring. Some evidence of mild antidepressant activity at higher doses, the basis for its "anxiety with depression" problem.
	\| indications = * Generalized anxiety disorder		\| indications = * Generalized anxiety disorder
	* Panic disorder (with or without agoraphobia)		* Panic disorder (with or without agoraphobia)
	* Anxiety associated with depression		* Anxiety associated with depression
	* '''Not first-line''' for chronic anxiety — SSRIs, SNRIs, buspirone, or CBT typically preferred due to dependence risk		* '''Not first-line''' for chronic anxiety, SSRIs, SNRIs, buspirone, or CBT typically preferred due to dependence risk
	* Occasionally used short-term for procedural anxiety or situational anxiety		* Occasionally used short-term for procedural anxiety or situational anxiety
	\| dosing = '''GAD:''' Start 0.25–0.5 mg PO three times daily; titrate slowly. Max 4 mg/day.		\| dosing = '''GAD:''' Start 0.25–0.5 mg PO three times daily; titrate slowly. Max 4 mg/day.
Line 29:		Line 29:
	\| effects = ''Therapeutic:'' anxiolysis (rapid), reduced panic frequency and severity, calming, mild euphoria, improved sleep.		\| effects = ''Therapeutic:'' anxiolysis (rapid), reduced panic frequency and severity, calming, mild euphoria, improved sleep.
	''Common adverse:'' '''drowsiness''', '''dizziness''', impaired coordination, fatigue, slurred speech, dry mouth, blurred vision, '''anterograde amnesia''', impaired psychomotor performance, decreased libido, changes in appetite.		''Common adverse:'' '''drowsiness''', '''dizziness''', impaired coordination, fatigue, slurred speech, dry mouth, blurred vision, '''anterograde amnesia''', impaired psychomotor performance, decreased libido, changes in appetite.
	\| adverse = * '''Dependence and addiction''' — highest among commonly-prescribed benzodiazepines. Physical dependence can develop within weeks of regular use.		\| adverse = * '''Dependence and addiction''', highest among commonly-prescribed benzodiazepines. Physical dependence can develop within weeks of regular use.
	* '''Withdrawal syndrome''' — rebound anxiety, insomnia, tremor, sweating, perceptual disturbances, depersonalization, '''seizures''' with abrupt cessation. Often more severe and protracted than withdrawal from longer-acting benzodiazepines.		* '''Withdrawal syndrome''', rebound anxiety, insomnia, tremor, sweating, perceptual disturbances, depersonalization, '''seizures''' with abrupt cessation. Often more severe and protracted than withdrawal from longer-acting benzodiazepines.
	* '''Tolerance''' — anxiolytic and hypnotic tolerance develops with chronic use; tolerance to amnestic and motor effects is less complete.		* '''Tolerance''', anxiolytic and hypnotic tolerance develops with chronic use; tolerance to amnestic and motor effects is less complete.
	* '''Respiratory depression''' — especially in combination with opioids ('''black box warning'''), alcohol, or other CNS depressants. Cause of many overdose deaths.		* '''Respiratory depression''', especially in combination with opioids ('''black box warning'''), alcohol, or other CNS depressants. Cause of many overdose deaths.
	* '''Paradoxical reactions''' — agitation, disinhibition, aggression, particularly in elderly, children, or those with personality disorders.		* '''Paradoxical reactions''', agitation, disinhibition, aggression, particularly in elderly, children, or those with personality disorders.
	* '''Cognitive impairment''' — both acute (memory, attention) and chronic with long-term use; partial reversibility uncertain.		* '''Cognitive impairment''', both acute (memory, attention) and chronic with long-term use; partial reversibility uncertain.
	* '''Falls and fractures''' in elderly.		* '''Falls and fractures''' in elderly.
	* '''Anterograde amnesia''' — clinically significant; can be exploited for criminal purposes (med-facilitated assault).		* '''Anterograde amnesia''', clinically significant; can be exploited for criminal purposes (med-facilitated assault).
	* '''Misuse and diversion''' — Xanax has substantial street value and frequent recreational misuse.		* '''Misuse and diversion''', Xanax has substantial street value and frequent recreational misuse.
	* '''Suicide risk in overdose''' — especially when combined with alcohol or opioids.		* '''Suicide risk in overdose''', especially when combined with alcohol or opioids.
	* '''Rebound anxiety''' between doses with short-half-life IR formulation.		* '''Rebound anxiety''' between doses with short-half-life IR formulation.
	\| interactions = * '''Opioids''' — additive respiratory depression and overdose risk ('''FDA black box warning'''); avoid when possible		\| interactions = * '''Opioids''', additive respiratory depression and overdose risk ('''FDA black box warning'''); avoid when possible
	* '''Alcohol''' — additive CNS depression and respiratory depression		* '''Alcohol''', additive CNS depression and respiratory depression
	* '''CYP3A4 inhibitors''' (ketoconazole, itraconazole, ritonavir, clarithromycin, nefazodone) — substantially increase alprazolam levels; some contraindicated		* '''CYP3A4 inhibitors''' (ketoconazole, itraconazole, ritonavir, clarithromycin, nefazodone), substantially increase alprazolam levels; some contraindicated
	* '''CYP3A4 inducers''' (carbamazepine, phenytoin, rifampin, St. John's wort) — decrease levels; may reduce efficacy		* '''CYP3A4 inducers''' (carbamazepine, phenytoin, rifampin, St. John's wort), decrease levels; may reduce efficacy
	* '''Other CNS depressants''' (Z-drugs, sedating antihistamines, gabapentinoids, sedating antidepressants) — additive		* '''Other CNS depressants''' (Z-drugs, sedating antihistamines, gabapentinoids, sedating antidepressants), additive
	* '''Grapefruit juice''' — modest CYP3A4 inhibition; can raise alprazolam levels with regular consumption		* '''Grapefruit juice''', modest CYP3A4 inhibition; can raise alprazolam levels with regular consumption
	* '''Fluoxetine, fluvoxamine''' — increase alprazolam levels via CYP3A4 inhibition		* '''Fluoxetine, fluvoxamine''', increase alprazolam levels via CYP3A4 inhibition
	<pharmaInteractions/>		<pharmaInteractions/>
	\| pregnancy_details = Historically Category D. First-trimester benzodiazepine exposure has been associated with increased risk of cleft lip/palate in some studies, though absolute risk is small. Third-trimester or near-term use can produce '''floppy infant syndrome''' (hypotonia, hypothermia, feeding difficulty, respiratory depression) and neonatal withdrawal. Generally avoided in pregnancy unless benefits clearly outweigh risks; SSRIs are usually preferred for chronic anxiety. Excreted in breast milk — breastfeeding generally discouraged.		\| pregnancy_details = Historically Category D. First-trimester benzodiazepine exposure has been associated with increased risk of cleft lip/palate in some studies, though absolute risk is small. Third-trimester or near-term use can produce '''floppy infant syndrome''' (hypotonia, hypothermia, feeding difficulty, respiratory depression) and neonatal withdrawal. Generally avoided in pregnancy unless benefits clearly outweigh risks; SSRIs are usually preferred for chronic anxiety. Excreted in breast milk, breastfeeding generally discouraged.
	\| monitoring = * Continued need for treatment — reassess at every visit; target shortest effective duration		\| monitoring = * Continued need for treatment, reassess at every visit; target shortest effective duration
	* Signs of dependence, tolerance, dose escalation, or misuse		* Signs of dependence, tolerance, dose escalation, or misuse
	* Cognitive function, especially in long-term users and elderly		* Cognitive function, especially in long-term users and elderly
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	* Respiratory status, especially in COPD/OSA or on opioids		* Respiratory status, especially in COPD/OSA or on opioids
	* Liver function in long-term use		* Liver function in long-term use
	\| counseling = * '''Take exactly as prescribed''' — do not increase dose without consulting prescriber.		\| counseling = * '''Take exactly as prescribed''', do not increase dose without consulting prescriber.
	* '''Do not combine with alcohol''' or other sedatives — combinations can be fatal.		* '''Do not combine with alcohol''' or other sedatives, combinations can be fatal.
	* '''Do not stop abruptly''' — can cause seizures; must be tapered.		* '''Do not stop abruptly''', can cause seizures; must be tapered.
	* Avoid driving or operating machinery until response is known.		* Avoid driving or operating machinery until response is known.
	* May cause memory gaps, especially with higher doses or alcohol.		* May cause memory gaps, especially with higher doses or alcohol.
	* Long-term daily use carries a real risk of dependence — discuss alternatives if treatment will extend beyond a few weeks.		* Long-term daily use carries a real risk of dependence, discuss alternatives if treatment will extend beyond a few weeks.
	* Avoid grapefruit juice in large quantities.		* Avoid grapefruit juice in large quantities.
	* Keep secured — high risk of theft and diversion.		* Keep secured, high risk of theft and diversion.
	* If pregnant or planning pregnancy, discuss with prescriber.		* If pregnant or planning pregnancy, discuss with prescriber.
	\| anecdotes =		\| anecdotes =