venlafaxine

5/24/2018 Venlafaxine

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VenlafaxineFrom Wikipedia, the free encyclopedia

Venlafaxine

Systematic (IUPAC)name

(RS)-1-[2-dimethylamino-1-(4-methoxyphenyl)-ethyl]cyclohexanol

Clinical data

Trade names Efexor, Effexor

AHFS/Drugs.com

monograph

Licence data US Daily Med:link

Pregnancy cat.

B2 (AU)C (US)
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Legal status

Prescription Only (S4)(AU)-only(CA)POM(UK)-

only(US)

Routes Oral

Pharmacokinetic data

Bioavailability

4215%[1]

Protein binding

272% (parent compound), 3012% (active

metabolite,desvenlafaxine)[2]

Metabolism Hepatic(~50% of the parent compound is metabolised

on first pass through the liver)[1][2]

Half-life 52 hours (parent compound for immediate release

preparations), 156 hours (parent compound for

extended release preparations), 112 hours (active

metabolite)[1][2]

Excretion Renal(87%; 5% as unchanged drug; 29%

asdesvenlafaxineand 53% as other metabolites)[1][2]

Identifiers

CAS number 93413-69-5

ATC code N06AX16

PubChem CID 5656

DrugBank

DB00285

ChemSpider

5454

UNII GRZ5RCB1QG

ChEBI CHEBI:9943
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ChEMBL CHEMBL637

Chemical data

Formula C17H27NO2

Mol. mass 277.402 g/mol

SMILES[show]

InChI[show]

(what is this?) (verify)

Venlafaxine(brand name:Effexoror Efexor) is anantidepressantof theserotonin-norepinephrine

reuptake inhibitor(SNRI) class.[3][4][5]First introduced byWyethin 1993, now marketed byPfizer,it

islicensedfor the treatment ofmajor depressive disorder(MDD), as a treatment forgeneralized anxiety

disorder,andcomorbidindicationsin certainanxiety disorderswith depression. In 2007, venlafaxine was

the sixth most commonly prescribed antidepressant on the U.S. retail market, with 17.2 million

prescriptions.[6]

Contents

[hide]

1 Medical uses

o 1.1 Depression

2 Adverse effects

o 2.1 Suicide

o 2.2 Dose dependency of adverse events

o 2.3 Discontinuation syndrome

o 2.4 Serotonin syndrome

o 2.5 Serotonin toxicity and discontinuation syndrome

o 2.6 Contraindications

2.6.1 Glaucoma

2.6.2 Pregnant women

o 2.7 Drug interactions

o

2.8 Other 3 Overdose
http://en.wikipedia.org/wiki/ChEMBLhttps://www.ebi.ac.uk/chembldb/index.php/compound/inspect/CHEMBL637https://www.ebi.ac.uk/chembldb/index.php/compound/inspect/CHEMBL637http://en.wikipedia.org/wiki/Chemical_formulahttp://en.wikipedia.org/wiki/Chemical_formulahttp://en.wikipedia.org/wiki/Carbonhttp://en.wikipedia.org/wiki/Carbonhttp://en.wikipedia.org/wiki/Hydrogenhttp://en.wikipedia.org/wiki/Hydrogenhttp://en.wikipedia.org/wiki/Hydrogenhttp://en.wikipedia.org/wiki/Nitrogenhttp://en.wikipedia.org/wiki/Nitrogenhttp://en.wikipedia.org/wiki/Nitrogenhttp://en.wikipedia.org/wiki/Nitrogenhttp://en.wikipedia.org/wiki/Molecular_masshttp://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specificationhttp://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specificationhttp://en.wikipedia.org/wiki/International_Chemical_Identifierhttp://en.wikipedia.org/wiki/International_Chemical_Identifierhttp://en.wikipedia.org/wiki/International_Chemical_Identifierhttp://en.wikipedia.org/wiki/Wikipedia:WikiProject_Chemicals/Chembox_validationhttp://en.wikipedia.org/w/index.php?title=Special:ComparePages&rev1=459442662&page2=Venlafaxinehttp://en.wikipedia.org/w/index.php?title=Special:ComparePages&rev1=459442662&page2=Venlafaxinehttp://en.wikipedia.org/w/index.php?title=Special:ComparePages&rev1=459442662&page2=Venlafaxinehttp://en.wikipedia.org/wiki/Brand_namehttp://en.wikipedia.org/wiki/Brand_namehttp://en.wikipedia.org/wiki/Brand_namehttp://en.wikipedia.org/wiki/Antidepressanthttp://en.wikipedia.org/wiki/Antidepressanthttp://en.wikipedia.org/wiki/Antidepressanthttp://en.wikipedia.org/wiki/Serotonin-norepinephrine_reuptake_inhibitorhttp://en.wikipedia.org/wiki/Serotonin-norepinephrine_reuptake_inhibitorhttp://en.wikipedia.org/wiki/Serotonin-norepinephrine_reuptake_inhibitorhttp://en.wikipedia.org/wiki/Serotonin-norepinephrine_reuptake_inhibitorhttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid3790168-3http://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid3790168-3http://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid11750180-5http://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid11750180-5http://en.wikipedia.org/wiki/Wyethhttp://en.wikipedia.org/wiki/Wyethhttp://en.wikipedia.org/wiki/Wyethhttp://en.wikipedia.org/wiki/Pfizerhttp://en.wikipedia.org/wiki/Pfizerhttp://en.wikipedia.org/wiki/Pfizerhttp://en.wikipedia.org/wiki/Licensedhttp://en.wikipedia.org/wiki/Licensedhttp://en.wikipedia.org/wiki/Licensedhttp://en.wikipedia.org/wiki/Major_depressive_disorderhttp://en.wikipedia.org/wiki/Major_depressive_disorderhttp://en.wikipedia.org/wiki/Major_depressive_disorderhttp://en.wikipedia.org/wiki/Generalized_anxiety_disorderhttp://en.wikipedia.org/wiki/Generalized_anxiety_disorderhttp://en.wikipedia.org/wiki/Generalized_anxiety_disorderhttp://en.wikipedia.org/wiki/Generalized_anxiety_disorderhttp://en.wikipedia.org/wiki/Comorbidhttp://en.wikipedia.org/wiki/Comorbidhttp://en.wikipedia.org/wiki/Indication_(medicine)http://en.wikipedia.org/wiki/Indication_(medicine)http://en.wikipedia.org/wiki/Indication_(medicine)http://en.wikipedia.org/wiki/Anxiety_disordershttp://en.wikipedia.org/wiki/Anxiety_disordershttp://en.wikipedia.org/wiki/Anxiety_disordershttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-6http://en.wikipedia.org/wiki/Venlafaxine#cite_note-6http://en.wikipedia.org/wiki/Venlafaxine#cite_note-6http://en.wikipedia.org/wiki/Venlafaxinehttp://en.wikipedia.org/wiki/Venlafaxinehttp://en.wikipedia.org/wiki/Venlafaxinehttp://en.wikipedia.org/wiki/Venlafaxine#Medical_useshttp://en.wikipedia.org/wiki/Venlafaxine#Medical_useshttp://en.wikipedia.org/wiki/Venlafaxine#Depressionhttp://en.wikipedia.org/wiki/Venlafaxine#Depressionhttp://en.wikipedia.org/wiki/Venlafaxine#Adverse_effectshttp://en.wikipedia.org/wiki/Venlafaxine#Adverse_effectshttp://en.wikipedia.org/wiki/Venlafaxine#Suicidehttp://en.wikipedia.org/wiki/Venlafaxine#Suicidehttp://en.wikipedia.org/wiki/Venlafaxine#Dose_dependency_of_adverse_eventshttp://en.wikipedia.org/wiki/Venlafaxine#Dose_dependency_of_adverse_eventshttp://en.wikipedia.org/wiki/Venlafaxine#Discontinuation_syndromehttp://en.wikipedia.org/wiki/Venlafaxine#Discontinuation_syndromehttp://en.wikipedia.org/wiki/Venlafaxine#Serotonin_syndromehttp://en.wikipedia.org/wiki/Venlafaxine#Serotonin_syndromehttp://en.wikipedia.org/wiki/Venlafaxine#Serotonin_toxicity_and_discontinuation_syndromehttp://en.wikipedia.org/wiki/Venlafaxine#Serotonin_toxicity_and_discontinuation_syndromehttp://en.wikipedia.org/wiki/Venlafaxine#Contraindicationshttp://en.wikipedia.org/wiki/Venlafaxine#Contraindicationshttp://en.wikipedia.org/wiki/Venlafaxine#Glaucomahttp://en.wikipedia.org/wiki/Venlafaxine#Glaucomahttp://en.wikipedia.org/wiki/Venlafaxine#Pregnant_womenhttp://en.wikipedia.org/wiki/Venlafaxine#Pregnant_womenhttp://en.wikipedia.org/wiki/Venlafaxine#Drug_interactionshttp://en.wikipedia.org/wiki/Venlafaxine#Drug_interactionshttp://en.wikipedia.org/wiki/Venlafaxine#Otherhttp://en.wikipedia.org/wiki/Venlafaxine#Otherhttp://en.wikipedia.org/wiki/Venlafaxine#Overdosehttp://en.wikipedia.org/wiki/Venlafaxine#Overdosehttp://en.wikipedia.org/wiki/Venlafaxine#Overdosehttp://en.wikipedia.org/wiki/Venlafaxine#Otherhttp://en.wikipedia.org/wiki/Venlafaxine#Drug_interactionshttp://en.wikipedia.org/wiki/Venlafaxine#Pregnant_womenhttp://en.wikipedia.org/wiki/Venlafaxine#Glaucomahttp://en.wikipedia.org/wiki/Venlafaxine#Contraindicationshttp://en.wikipedia.org/wiki/Venlafaxine#Serotonin_toxicity_and_discontinuation_syndromehttp://en.wikipedia.org/wiki/Venlafaxine#Serotonin_syndromehttp://en.wikipedia.org/wiki/Venlafaxine#Discontinuation_syndromehttp://en.wikipedia.org/wiki/Venlafaxine#Dose_dependency_of_adverse_eventshttp://en.wikipedia.org/wiki/Venlafaxine#Suicidehttp://en.wikipedia.org/wiki/Venlafaxine#Adverse_effectshttp://en.wikipedia.org/wiki/Venlafaxine#Depressionhttp://en.wikipedia.org/wiki/Venlafaxine#Medical_useshttp://en.wikipedia.org/wiki/Venlafaxinehttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-6http://en.wikipedia.org/wiki/Anxiety_disordershttp://en.wikipedia.org/wiki/Indication_(medicine)http://en.wikipedia.org/wiki/Comorbidhttp://en.wikipedia.org/wiki/Generalized_anxiety_disorderhttp://en.wikipedia.org/wiki/Generalized_anxiety_disorderhttp://en.wikipedia.org/wiki/Major_depressive_disorderhttp://en.wikipedia.org/wiki/Licensedhttp://en.wikipedia.org/wiki/Pfizerhttp://en.wikipedia.org/wiki/Wyethhttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid11750180-5http://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid3790168-3http://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid3790168-3http://en.wikipedia.org/wiki/Serotonin-norepinephrine_reuptake_inhibitorhttp://en.wikipedia.org/wiki/Serotonin-norepinephrine_reuptake_inhibitorhttp://en.wikipedia.org/wiki/Antidepressanthttp://en.wikipedia.org/wiki/Brand_namehttp://en.wikipedia.org/w/index.php?title=Special:ComparePages&rev1=459442662&page2=Venlafaxinehttp://en.wikipedia.org/wiki/Wikipedia:WikiProject_Chemicals/Chembox_validationhttp://en.wikipedia.org/wiki/International_Chemical_Identifierhttp://en.wikipedia.org/wiki/International_Chemical_Identifierhttp://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specificationhttp://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specificationhttp://en.wikipedia.org/wiki/Molecular_masshttp://en.wikipedia.org/wiki/Nitrogenhttp://en.wikipedia.org/wiki/Nitrogenhttp://en.wikipedia.org/wiki/Hydrogenhttp://en.wikipedia.org/wiki/Carbonhttp://en.wikipedia.org/wiki/Chemical_formulahttps://www.ebi.ac.uk/chembldb/index.php/compound/inspect/CHEMBL637http://en.wikipedia.org/wiki/ChEMBL


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o 3.1 Gastrointestinal effects

o 3.2 Management of overdose

4 Mechanism of action

o 4.1 Pharmacokinetics

5 Chemistry

6 Available forms

o 6.1 Extended release

o 6.2 Generic

7 References

8 External links

o 8.1 Drug information

o 8.2 Diagnostic tools

o 8.3 Patient experiences

Medical uses[edit]

Venlafaxine is used primarily for the treatment ofdepression,general anxiety disorder,social phobia,panic

disorderandvasomotor symptoms.[7]

At low doses (150 mg/day),

it acts on serotonergic and noradrenergic systems, whereas at high doses (>300 mg/day), it also affects

dopaminergic neurotransmission.

[8]

Many doctors are starting to prescribe venlafaxine "off label" for the treatment o fdiabetic neuropathy(in a

similar manner toduloxetine)andmigraineprophylaxis (in some people, however, venlafaxine can

exacerbate or cause migraines). Studies have shown venlafaxine's effectiveness for these conditions .[9][10]It

has also been found to reduce the severity of 'hot flushes' i nmenopausalwomen and men on hormonal

therapy for the treatment of prostate cancer.[11][12]

Substantial weight loss in patients with major depression, generalized anxiety disorder, and social

phobiahave been noted, but the manufacturer does not recommend use as ananorecticeither alone or in

combination withphentermineor other amphetamine-like drugs.[13]Venlafaxine hydrochloride is in the

phenethylamine class of modern chemicals, which includes amphetamine,

methylenedioxymethamphetamine (MDMA), and methamphetamine. This chemical structure likely lends to

its activating properties; however, some patients find venlafaxine highly sedating, despite its more common

stimulatory effects.

Venlafaxine is not recommended nor approved for the treatment of major depressive episodes inbipolar

disorderas it can inducemaniaormixed episodes.Venlafaxine appears to be more likely than

theSSRIsandbupropionto induce mania and mixed episodes in bipolar patients.[14]
http://en.wikipedia.org/wiki/Venlafaxine#Gastrointestinal_effectshttp://en.wikipedia.org/wiki/Venlafaxine#Gastrointestinal_effectshttp://en.wikipedia.org/wiki/Venlafaxine#Management_of_overdosehttp://en.wikipedia.org/wiki/Venlafaxine#Management_of_overdosehttp://en.wikipedia.org/wiki/Venlafaxine#Mechanism_of_actionhttp://en.wikipedia.org/wiki/Venlafaxine#Mechanism_of_actionhttp://en.wikipedia.org/wiki/Venlafaxine#Pharmacokineticshttp://en.wikipedia.org/wiki/Venlafaxine#Pharmacokineticshttp://en.wikipedia.org/wiki/Venlafaxine#Chemistryhttp://en.wikipedia.org/wiki/Venlafaxine#Chemistryhttp://en.wikipedia.org/wiki/Venlafaxine#Available_formshttp://en.wikipedia.org/wiki/Venlafaxine#Available_formshttp://en.wikipedia.org/wiki/Venlafaxine#Extended_releasehttp://en.wikipedia.org/wiki/Venlafaxine#Extended_releasehttp://en.wikipedia.org/wiki/Venlafaxine#Generichttp://en.wikipedia.org/wiki/Venlafaxine#Generichttp://en.wikipedia.org/wiki/Venlafaxine#Referenceshttp://en.wikipedia.org/wiki/Venlafaxine#Referenceshttp://en.wikipedia.org/wiki/Venlafaxine#External_linkshttp://en.wikipedia.org/wiki/Venlafaxine#External_linkshttp://en.wikipedia.org/wiki/Venlafaxine#Drug_informationhttp://en.wikipedia.org/wiki/Venlafaxine#Drug_informationhttp://en.wikipedia.org/wiki/Venlafaxine#Diagnostic_toolshttp://en.wikipedia.org/wiki/Venlafaxine#Diagnostic_toolshttp://en.wikipedia.org/wiki/Venlafaxine#Patient_experienceshttp://en.wikipedia.org/wiki/Venlafaxine#Patient_experienceshttp://en.wikipedia.org/w/index.php?title=Venlafaxine&action=edit&section=1http://en.wikipedia.org/w/index.php?title=Venlafaxine&action=edit&section=1http://en.wikipedia.org/w/index.php?title=Venlafaxine&action=edit&section=1http://en.wikipedia.org/wiki/Major_depressive_disorderhttp://en.wikipedia.org/wiki/Major_depressive_disorderhttp://en.wikipedia.org/wiki/Major_depressive_disorderhttp://en.wikipedia.org/wiki/General_anxiety_disorderhttp://en.wikipedia.org/wiki/General_anxiety_disorderhttp://en.wikipedia.org/wiki/General_anxiety_disorderhttp://en.wikipedia.org/wiki/Social_phobiahttp://en.wikipedia.org/wiki/Social_phobiahttp://en.wikipedia.org/wiki/Social_phobiahttp://en.wikipedia.org/wiki/Panic_disorderhttp://en.wikipedia.org/wiki/Panic_disorderhttp://en.wikipedia.org/wiki/Panic_disorderhttp://en.wikipedia.org/wiki/Panic_disorderhttp://en.wikipedia.org/wiki/Vasomotor_symptomshttp://en.wikipedia.org/wiki/Vasomotor_symptomshttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-AHFS-7http://en.wikipedia.org/wiki/Venlafaxine#cite_note-AHFS-7http://en.wikipedia.org/wiki/Venlafaxine#cite_note-AHFS-7http://en.wikipedia.org/wiki/Venlafaxine#cite_note-8http://en.wikipedia.org/wiki/Venlafaxine#cite_note-8http://en.wikipedia.org/wiki/Venlafaxine#cite_note-8http://en.wikipedia.org/wiki/Diabetic_neuropathyhttp://en.wikipedia.org/wiki/Diabetic_neuropathyhttp://en.wikipedia.org/wiki/Diabetic_neuropathyhttp://en.wikipedia.org/wiki/Duloxetinehttp://en.wikipedia.org/wiki/Duloxetinehttp://en.wikipedia.org/wiki/Duloxetinehttp://en.wikipedia.org/wiki/Migrainehttp://en.wikipedia.org/wiki/Migrainehttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-9http://en.wikipedia.org/wiki/Venlafaxine#cite_note-9http://en.wikipedia.org/wiki/Venlafaxine#cite_note-9http://en.wikipedia.org/wiki/Menopausehttp://en.wikipedia.org/wiki/Menopausehttp://en.wikipedia.org/wiki/Menopausehttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-11http://en.wikipedia.org/wiki/Venlafaxine#cite_note-11http://en.wikipedia.org/wiki/Venlafaxine#cite_note-11http://en.wikipedia.org/wiki/Social_phobiahttp://en.wikipedia.org/wiki/Social_phobiahttp://en.wikipedia.org/wiki/Social_phobiahttp://en.wikipedia.org/wiki/Social_phobiahttp://en.wikipedia.org/wiki/Anorectichttp://en.wikipedia.org/wiki/Anorectichttp://en.wikipedia.org/wiki/Anorectichttp://en.wikipedia.org/wiki/Phenterminehttp://en.wikipedia.org/wiki/Phenterminehttp://en.wikipedia.org/wiki/Phenterminehttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-Medicinedatasheet-Wyeth-13http://en.wikipedia.org/wiki/Venlafaxine#cite_note-Medicinedatasheet-Wyeth-13http://en.wikipedia.org/wiki/Venlafaxine#cite_note-Medicinedatasheet-Wyeth-13http://en.wikipedia.org/wiki/Bipolar_disorderhttp://en.wikipedia.org/wiki/Bipolar_disorderhttp://en.wikipedia.org/wiki/Bipolar_disorderhttp://en.wikipedia.org/wiki/Bipolar_disorderhttp://en.wikipedia.org/wiki/Maniahttp://en.wikipedia.org/wiki/Maniahttp://en.wikipedia.org/wiki/Maniahttp://en.wikipedia.org/wiki/Mixed_episodeshttp://en.wikipedia.org/wiki/Mixed_episodeshttp://en.wikipedia.org/wiki/Mixed_episodeshttp://en.wikipedia.org/wiki/Selective_serotonin_reuptake_inhibitorhttp://en.wikipedia.org/wiki/Selective_serotonin_reuptake_inhibitorhttp://en.wikipedia.org/wiki/Selective_serotonin_reuptake_inhibitorhttp://en.wikipedia.org/wiki/Bupropionhttp://en.wikipedia.org/wiki/Bupropionhttp://en.wikipedia.org/wiki/Bupropionhttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-14http://en.wikipedia.org/wiki/Venlafaxine#cite_note-14http://en.wikipedia.org/wiki/Venlafaxine#cite_note-14http://en.wikipedia.org/wiki/Venlafaxine#cite_note-14http://en.wikipedia.org/wiki/Bupropionhttp://en.wikipedia.org/wiki/Selective_serotonin_reuptake_inhibitorhttp://en.wikipedia.org/wiki/Mixed_episodeshttp://en.wikipedia.org/wiki/Maniahttp://en.wikipedia.org/wiki/Bipolar_disorderhttp://en.wikipedia.org/wiki/Bipolar_disorderhttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-Medicinedatasheet-Wyeth-13http://en.wikipedia.org/wiki/Phenterminehttp://en.wikipedia.org/wiki/Anorectichttp://en.wikipedia.org/wiki/Social_phobiahttp://en.wikipedia.org/wiki/Social_phobiahttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-11http://en.wikipedia.org/wiki/Venlafaxine#cite_note-11http://en.wikipedia.org/wiki/Menopausehttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-9http://en.wikipedia.org/wiki/Venlafaxine#cite_note-9http://en.wikipedia.org/wiki/Migrainehttp://en.wikipedia.org/wiki/Duloxetinehttp://en.wikipedia.org/wiki/Diabetic_neuropathyhttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-8http://en.wikipedia.org/wiki/Venlafaxine#cite_note-AHFS-7http://en.wikipedia.org/wiki/Vasomotor_symptomshttp://en.wikipedia.org/wiki/Panic_disorderhttp://en.wikipedia.org/wiki/Panic_disorderhttp://en.wikipedia.org/wiki/Social_phobiahttp://en.wikipedia.org/wiki/General_anxiety_disorderhttp://en.wikipedia.org/wiki/Major_depressive_disorderhttp://en.wikipedia.org/w/index.php?title=Venlafaxine&action=edit&section=1http://en.wikipedia.org/wiki/Venlafaxine#Patient_experienceshttp://en.wikipedia.org/wiki/Venlafaxine#Diagnostic_toolshttp://en.wikipedia.org/wiki/Venlafaxine#Drug_informationhttp://en.wikipedia.org/wiki/Venlafaxine#External_linkshttp://en.wikipedia.org/wiki/Venlafaxine#Referenceshttp://en.wikipedia.org/wiki/Venlafaxine#Generichttp://en.wikipedia.org/wiki/Venlafaxine#Extended_releasehttp://en.wikipedia.org/wiki/Venlafaxine#Available_formshttp://en.wikipedia.org/wiki/Venlafaxine#Chemistryhttp://en.wikipedia.org/wiki/Venlafaxine#Pharmacokineticshttp://en.wikipedia.org/wiki/Venlafaxine#Mechanism_of_actionhttp://en.wikipedia.org/wiki/Venlafaxine#Management_of_overdosehttp://en.wikipedia.org/wiki/Venlafaxine#Gastrointestinal_effects


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Due to its action on both theserotoninergicandadrenergicsystems, venlafaxine is also used as a

treatment to reduce episodes ofcataplexy,a form of muscle weakness, in patients with the sleep

disordernarcolepsy.[15]

Venlafaxine was found in one study to be equal to clomipramine(anafranil) in the treatment ofObsessive-compulsive disorder(OCD) with fewer side effects.[16]

Some open-label and three double-blind studies have suggested the efficacy of venlafaxine in the

treatment ofattention deficit-hyperactivity disorder(ADHD).[17][18][19][20][21]

Due to its tendency to increase blood pressure and its modulative effects on theautonomic nervous

system,venlafaxine is often used to treatorthostatic intoleranceandpostural orthostatic tachycardia

syndrome.[22]

Depression[edit]

Multipledouble blindstudies show venlafaxine's effectiveness in treating depression. Venlafaxine has

similar efficacy to thetricyclic antidepressantsamitriptyline(Elavil) andimipramine,and is better tolerated

than amitriptyline. Its efficacy is similar to or better thansertraline(Zoloft) andfluoxetine(Prozac),

depending on the criteria and rating scales used. Higher doses of venlafaxine are more effective, and more

patients achievedremissionor were "very much improved". The efficacy was similar if the number of

patients who achieved "response" or were "improved" was considered. A meta-analysiscomparing

venlafaxine and combined groups ofSSRIor tricyclic antidepressants showed venlafaxine's

superiority.[23]Judged by the same criteria, venlafaxine was similar in efficacy to the atypical

antidepressantbupropion(Wellbutrin); however, the remission rate was significantly lower for

venlafaxine.[24]In a double-blind study, patients who did not respond to an SSRI were switched to

venlafaxine orcitalopram.Similar improvement was observed in both groups.[25]

Adverse effects[edit]

Incidence of adverse effects[1][2][26]

Very common (>10% incidence) adverse effects include:

Headache an often transient side effect that is common to most serotonin reuptake inhibitorsand

that most often occurs at the beginning of therapy or after a dose escalation.

Nauseaan adverse effect that is more common with venlafaxine than with theSSRIs.Usually

transient and less severe in those receiving the extended release formulations.

Insomnia

Asthenia(weakness)

Dizziness

Ejaculation disorder sexual side effects can be seen with virtually any antidepressant, especially

those that inhibit the reuptake of serotonin (including venlafaxine).[27]
http://en.wikipedia.org/wiki/Serotoninergichttp://en.wikipedia.org/wiki/Serotoninergichttp://en.wikipedia.org/wiki/Serotoninergichttp://en.wikipedia.org/wiki/Adrenergichttp://en.wikipedia.org/wiki/Adrenergichttp://en.wikipedia.org/wiki/Adrenergichttp://en.wikipedia.org/wiki/Cataplexyhttp://en.wikipedia.org/wiki/Cataplexyhttp://en.wikipedia.org/wiki/Cataplexyhttp://en.wikipedia.org/wiki/Sleep_disorderhttp://en.wikipedia.org/wiki/Sleep_disorderhttp://en.wikipedia.org/wiki/Sleep_disorderhttp://en.wikipedia.org/wiki/Narcolepsyhttp://en.wikipedia.org/wiki/Narcolepsyhttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-15http://en.wikipedia.org/wiki/Venlafaxine#cite_note-15http://en.wikipedia.org/wiki/Venlafaxine#cite_note-15http://en.wikipedia.org/wiki/Clomipraminehttp://en.wikipedia.org/wiki/Clomipraminehttp://en.wikipedia.org/wiki/Clomipraminehttp://en.wikipedia.org/wiki/Obsessive-compulsive_disorderhttp://en.wikipedia.org/wiki/Obsessive-compulsive_disorderhttp://en.wikipedia.org/wiki/Obsessive-compulsive_disorderhttp://en.wikipedia.org/wiki/Obsessive-compulsive_disorderhttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid12444814-16http://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid12444814-16http://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid12444814-16http://en.wikipedia.org/wiki/Attention_deficit-hyperactivity_disorderhttp://en.wikipedia.org/wiki/Attention_deficit-hyperactivity_disorderhttp://en.wikipedia.org/wiki/Attention_deficit-hyperactivity_disorderhttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-17http://en.wikipedia.org/wiki/Venlafaxine#cite_note-17http://en.wikipedia.org/wiki/Venlafaxine#cite_note-19http://en.wikipedia.org/wiki/Venlafaxine#cite_note-21http://en.wikipedia.org/wiki/Venlafaxine#cite_note-21http://en.wikipedia.org/wiki/Autonomic_nervous_systemhttp://en.wikipedia.org/wiki/Autonomic_nervous_systemhttp://en.wikipedia.org/wiki/Autonomic_nervous_systemhttp://en.wikipedia.org/wiki/Autonomic_nervous_systemhttp://en.wikipedia.org/wiki/Orthostatic_intolerancehttp://en.wikipedia.org/wiki/Orthostatic_intolerancehttp://en.wikipedia.org/wiki/Orthostatic_intolerancehttp://en.wikipedia.org/wiki/Postural_orthostatic_tachycardia_syndromehttp://en.wikipedia.org/wiki/Postural_orthostatic_tachycardia_syndromehttp://en.wikipedia.org/wiki/Postural_orthostatic_tachycardia_syndromehttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-22http://en.wikipedia.org/wiki/Venlafaxine#cite_note-22http://en.wikipedia.org/wiki/Venlafaxine#cite_note-22http://en.wikipedia.org/w/index.php?title=Venlafaxine&action=edit&section=2http://en.wikipedia.org/w/index.php?title=Venlafaxine&action=edit&section=2http://en.wikipedia.org/w/index.php?title=Venlafaxine&action=edit&section=2http://en.wikipedia.org/wiki/Double_blindhttp://en.wikipedia.org/wiki/Double_blindhttp://en.wikipedia.org/wiki/Double_blindhttp://en.wikipedia.org/wiki/Tricyclic_antidepressanthttp://en.wikipedia.org/wiki/Tricyclic_antidepressanthttp://en.wikipedia.org/wiki/Amitriptylinehttp://en.wikipedia.org/wiki/Amitriptylinehttp://en.wikipedia.org/wiki/Amitriptylinehttp://en.wikipedia.org/wiki/Imipraminehttp://en.wikipedia.org/wiki/Imipraminehttp://en.wikipedia.org/wiki/Imipraminehttp://en.wikipedia.org/wiki/Sertralinehttp://en.wikipedia.org/wiki/Sertralinehttp://en.wikipedia.org/wiki/Sertralinehttp://en.wikipedia.org/wiki/Fluoxetinehttp://en.wikipedia.org/wiki/Fluoxetinehttp://en.wikipedia.org/wiki/Fluoxetinehttp://en.wikipedia.org/wiki/Remission_(medicine)http://en.wikipedia.org/wiki/Remission_(medicine)http://en.wikipedia.org/wiki/Remission_(medicine)http://en.wikipedia.org/wiki/Meta-analysishttp://en.wikipedia.org/wiki/Meta-analysishttp://en.wikipedia.org/wiki/Meta-analysishttp://en.wikipedia.org/wiki/SSRIhttp://en.wikipedia.org/wiki/SSRIhttp://en.wikipedia.org/wiki/SSRIhttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid11098413-23http://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid11098413-23http://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid11098413-23http://en.wikipedia.org/wiki/Bupropionhttp://en.wikipedia.org/wiki/Bupropionhttp://en.wikipedia.org/wiki/Bupropionhttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid16974189-24http://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid16974189-24http://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid16974189-24http://en.wikipedia.org/wiki/Citalopramhttp://en.wikipedia.org/wiki/Citalopramhttp://en.wikipedia.org/wiki/Citalopramhttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid18408525-25http://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid18408525-25http://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid18408525-25http://en.wikipedia.org/w/index.php?title=Venlafaxine&action=edit&section=3http://en.wikipedia.org/w/index.php?title=Venlafaxine&action=edit&section=3http://en.wikipedia.org/w/index.php?title=Venlafaxine&action=edit&section=3http://en.wikipedia.org/wiki/Venlafaxine#cite_note-TGA-1http://en.wikipedia.org/wiki/Venlafaxine#cite_note-MS-26http://en.wikipedia.org/wiki/Venlafaxine#cite_note-MS-26http://en.wikipedia.org/wiki/Serotonin_reuptake_inhibitorhttp://en.wikipedia.org/wiki/Serotonin_reuptake_inhibitorhttp://en.wikipedia.org/wiki/Serotonin_reuptake_inhibitorhttp://en.wikipedia.org/wiki/Nauseahttp://en.wikipedia.org/wiki/Nauseahttp://en.wikipedia.org/wiki/Selective_serotonin_reuptake_inhibitorshttp://en.wikipedia.org/wiki/Selective_serotonin_reuptake_inhibitorshttp://en.wikipedia.org/wiki/Selective_serotonin_reuptake_inhibitorshttp://en.wikipedia.org/wiki/Astheniahttp://en.wikipedia.org/wiki/Astheniahttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-Maudsley-27http://en.wikipedia.org/wiki/Venlafaxine#cite_note-Maudsley-27http://en.wikipedia.org/wiki/Venlafaxine#cite_note-Maudsley-27http://en.wikipedia.org/wiki/Venlafaxine#cite_note-Maudsley-27http://en.wikipedia.org/wiki/Astheniahttp://en.wikipedia.org/wiki/Selective_serotonin_reuptake_inhibitorshttp://en.wikipedia.org/wiki/Nauseahttp://en.wikipedia.org/wiki/Serotonin_reuptake_inhibitorhttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-MS-26http://en.wikipedia.org/wiki/Venlafaxine#cite_note-TGA-1http://en.wikipedia.org/wiki/Venlafaxine#cite_note-TGA-1http://en.wikipedia.org/w/index.php?title=Venlafaxine&action=edit&section=3http://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid18408525-25http://en.wikipedia.org/wiki/Citalopramhttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid16974189-24http://en.wikipedia.org/wiki/Bupropionhttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid11098413-23http://en.wikipedia.org/wiki/SSRIhttp://en.wikipedia.org/wiki/Meta-analysishttp://en.wikipedia.org/wiki/Remission_(medicine)http://en.wikipedia.org/wiki/Fluoxetinehttp://en.wikipedia.org/wiki/Sertralinehttp://en.wikipedia.org/wiki/Imipraminehttp://en.wikipedia.org/wiki/Amitriptylinehttp://en.wikipedia.org/wiki/Tricyclic_antidepressanthttp://en.wikipedia.org/wiki/Double_blindhttp://en.wikipedia.org/w/index.php?title=Venlafaxine&action=edit&section=2http://en.wikipedia.org/wiki/Venlafaxine#cite_note-22http://en.wikipedia.org/wiki/Postural_orthostatic_tachycardia_syndromehttp://en.wikipedia.org/wiki/Postural_orthostatic_tachycardia_syndromehttp://en.wikipedia.org/wiki/Orthostatic_intolerancehttp://en.wikipedia.org/wiki/Autonomic_nervous_systemhttp://en.wikipedia.org/wiki/Autonomic_nervous_systemhttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-21http://en.wikipedia.org/wiki/Venlafaxine#cite_note-19http://en.wikipedia.org/wiki/Venlafaxine#cite_note-19http://en.wikipedia.org/wiki/Venlafaxine#cite_note-17http://en.wikipedia.org/wiki/Venlafaxine#cite_note-17http://en.wikipedia.org/wiki/Attention_deficit-hyperactivity_disorderhttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid12444814-16http://en.wikipedia.org/wiki/Obsessive-compulsive_disorderhttp://en.wikipedia.org/wiki/Obsessive-compulsive_disorderhttp://en.wikipedia.org/wiki/Clomipraminehttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-15http://en.wikipedia.org/wiki/Narcolepsyhttp://en.wikipedia.org/wiki/Sleep_disorderhttp://en.wikipedia.org/wiki/Sleep_disorderhttp://en.wikipedia.org/wiki/Cataplexyhttp://en.wikipedia.org/wiki/Adrenergichttp://en.wikipedia.org/wiki/Serotoninergic


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Somnolence

Dry mouth

Sweating

Failing Memory[28]

Common (110% incidence) adverse effects include:

Constipation

Nervousness

Abnormal vision

Anorgasmia

Hypertension

Impotence Paresthesia

Tremor

Vasodilation

Vomiting

Weight loss

Chills

Palpitations

Confusion

Depersonalisation

Night sweats

Menstrual disorders associated with increased bleeding or increased irregular bleeding

(e.g.menorrhagia,metrorrhagia)

Urinary frequency increased

Abnormal dreams

Decreased libido

Increased muscle tonus

Yawning

Sweating

Abnormality of accommodation

Abnormal ejaculation/orgasm (males)

Urinary hesitancy

Serum cholesterol increased (especially when treatment is prolonged and it may be dose-dependent)

Uncommon (0.1-1% incidence) adverse effects include:
http://en.wikipedia.org/wiki/Somnolencehttp://en.wikipedia.org/wiki/Somnolencehttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid15260908-28http://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid15260908-28http://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid15260908-28http://en.wikipedia.org/wiki/Anorgasmiahttp://en.wikipedia.org/wiki/Anorgasmiahttp://en.wikipedia.org/wiki/Paresthesiahttp://en.wikipedia.org/wiki/Paresthesiahttp://en.wikipedia.org/wiki/Menorrhagiahttp://en.wikipedia.org/wiki/Menorrhagiahttp://en.wikipedia.org/wiki/Metrorrhagiahttp://en.wikipedia.org/wiki/Metrorrhagiahttp://en.wikipedia.org/wiki/Metrorrhagiahttp://en.wikipedia.org/wiki/Metrorrhagiahttp://en.wikipedia.org/wiki/Menorrhagiahttp://en.wikipedia.org/wiki/Paresthesiahttp://en.wikipedia.org/wiki/Anorgasmiahttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid15260908-28http://en.wikipedia.org/wiki/Somnolence


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Face oedema

Intentional injury (self-harm)

Malaise

Moniliasis

Neck rigidity

Pelvic pain

Photosensitivityreaction

Suicide attempt

Withdrawal syndrome

Hypotension

Postural hypotension

Syncope

Tachycardia

Bruxism

Ecchymosis

Mucous membrane bleeding

Gastrointestinal bleeding

Abnormal liver function tests

Hyponatraemia

Weight gain

Apathy

Hallucinations

Myoclonus

Rash

Abnormal orgasm (females)

Urinary retention(the inability to pass urine)

Angioedema

Agitation

Impaired coordination & balance

Alopecia(hair loss)

Tinnitus(hearing bells)

Proteinuria(protein in urine)

Rare (0.010.1% incidence) adverse effects include:

Syndrome of inappropriate antidiuretic hormone secretion(SIADH)

Thrombocytopenia
http://en.wikipedia.org/wiki/Moniliasishttp://en.wikipedia.org/wiki/Moniliasishttp://en.wikipedia.org/wiki/Photosensitivityhttp://en.wikipedia.org/wiki/Photosensitivityhttp://en.wikipedia.org/wiki/SSRI_discontinuation_syndromehttp://en.wikipedia.org/wiki/SSRI_discontinuation_syndromehttp://en.wikipedia.org/wiki/Syncope_(medicine)http://en.wikipedia.org/wiki/Syncope_(medicine)http://en.wikipedia.org/wiki/Tachycardiahttp://en.wikipedia.org/wiki/Tachycardiahttp://en.wikipedia.org/wiki/Bruxismhttp://en.wikipedia.org/wiki/Bruxismhttp://en.wikipedia.org/wiki/Ecchymosishttp://en.wikipedia.org/wiki/Ecchymosishttp://en.wikipedia.org/wiki/Hyponatraemiahttp://en.wikipedia.org/wiki/Hyponatraemiahttp://en.wikipedia.org/wiki/Myoclonushttp://en.wikipedia.org/wiki/Myoclonushttp://en.wikipedia.org/wiki/Urinary_retentionhttp://en.wikipedia.org/wiki/Urinary_retentionhttp://en.wikipedia.org/wiki/Angioedemahttp://en.wikipedia.org/wiki/Angioedemahttp://en.wikipedia.org/wiki/Alopeciahttp://en.wikipedia.org/wiki/Alopeciahttp://en.wikipedia.org/wiki/Tinnitushttp://en.wikipedia.org/wiki/Tinnitushttp://en.wikipedia.org/wiki/Proteinuriahttp://en.wikipedia.org/wiki/Proteinuriahttp://en.wikipedia.org/wiki/Syndrome_of_inappropriate_antidiuretic_hormone_secretionhttp://en.wikipedia.org/wiki/Syndrome_of_inappropriate_antidiuretic_hormone_secretionhttp://en.wikipedia.org/wiki/Thrombocytopeniahttp://en.wikipedia.org/wiki/Thrombocytopeniahttp://en.wikipedia.org/wiki/Thrombocytopeniahttp://en.wikipedia.org/wiki/Syndrome_of_inappropriate_antidiuretic_hormone_secretionhttp://en.wikipedia.org/wiki/Proteinuriahttp://en.wikipedia.org/wiki/Tinnitushttp://en.wikipedia.org/wiki/Alopeciahttp://en.wikipedia.org/wiki/Angioedemahttp://en.wikipedia.org/wiki/Urinary_retentionhttp://en.wikipedia.org/wiki/Myoclonushttp://en.wikipedia.org/wiki/Hyponatraemiahttp://en.wikipedia.org/wiki/Ecchymosishttp://en.wikipedia.org/wiki/Bruxismhttp://en.wikipedia.org/wiki/Tachycardiahttp://en.wikipedia.org/wiki/Syncope_(medicine)http://en.wikipedia.org/wiki/SSRI_discontinuation_syndromehttp://en.wikipedia.org/wiki/Photosensitivityhttp://en.wikipedia.org/wiki/Moniliasis


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Prolonged bleeding time

Seizures

Mania

Neuroleptic malignant syndrome(NMS)

Serotonin syndrome

Akathisia/psychomotor restlessness

Urinary incontinence

Very rare (


9/22

consideration the fact that venlafaxine was generally prescribed for more severe depression, venlafaxine

was associated with 1.61.7 times more suicides than fluoxetine or citalopram. This difference was no

longer statistically significant due to the rarity of completed suicides. However, for the attempted suicides

(more frequent event) the 1.21.3 times higher risk for venlafaxine still stayed statistically significant after

the adjustment.[30]

An analysis of clinical trials by the FDA statisticians showed the incidence of suicidal behaviour among the

adults on venlafaxine to be not significantly different from fluoxetine orplacebo.[31]

Venlafaxine is contraindicated in children, adolescents and young adults. According to the FDA analysis of

clinical trials[31]venlafaxine caused a statistically significant 5-fold increase in suicidal ideation and

behaviour in persons younger than 25. In another analysis, venlafaxine was no better than placebo among

children (711 years old), but improved depression in adolescents (1217 years old). However, in both

groups, hostility and suicidal behaviour increased in comparison to those receiving a placebo .[32]

In a study

involving antidepressants that had failed to produce results in depressed teenagers, teens

whoseSSRItreatment had failed who were randomly switched to either another SSRI or to venlafaxine

showed an increased rate of suicide on venlafaxine. Among teenagers who were suicidal at the beginning

of the study, the rate of suicidal attempts andself-harmwas significantly higher, by about 60%, after the

switch to venlafaxine than after the switch to an SSRI.[33]

Dose dependency of adverse events[edit]

A comparison of adverse event rates in a fixed-dose study comparing venlafaxine 75, 225, and 375 mg/day

withplaceborevealed a dose dependency for some of the more common adverse events associated with

venlafaxine use. The rule for including events was to enumerate those that occurred at an incidence of 5%

or more for at least one of the venlafaxine groups and for which the incidence was at least twice the

placebo incidence for at least one venlafaxine group. Tests for potential dose relationships for these events

(Cochran-Armitage test, with a criterion of exact 2-sided p-value 0.05) suggested a dose-dependency for

several adverse events in this list, including chills, hypertension,anorexia (symptom),nausea, agitation,

dizziness, somnolence, tremor, yawning, sweating, and abnormal ejaculation.[13]

Discontinuation syndrome[edit]

Main article:SSRI discontinuation syndrome

Patients stopping venlafaxine commonly experienceSSRI discontinuation syndrome,i.e.withdrawal

symptoms.Such symptoms may occur when abruptly ceasing the medication, decreasing one's dose too

quickly, or even after missing a regular dose. Withdrawal symptoms may include agitation, anorexia,

anxiety, confusion, impaired coordination, diarrhea,, dizziness, dry mouth, dysphoric mood, fasciculation,

fatigue, headaches, hypomania, insomnia, nausea, nervousness, nightmares, sensory disturbances

described as"brain zaps"(shock-like electrical sensations), somnolence, sweating, tremor, vertigo, and

vomiting.
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The high risk of discontinuation syndrome symptoms may reflect venlafaxine's short half-life.[34]Missing

even a single dose can induce discontinuation effects in some patients .[35][36]

Discontinuation is similar in nature, but not identical to those of SSRIs such

asparoxetine(PaxilorSeroxat). Sudden discontinuation of venlafaxine particularly seemed to causediscontinuation symptoms during the first 3 days in a study of 18 patients .[37]As reported in 2001 by

Haddad in the journal Drug Safety, "another strategy to consider is switching to fluoxetine, which may

suppress the discontinuation symptoms, but which has little tendency to cause such symptoms itself," and

then discontinuing that.[34]

Norepinephrinemay also have a significant role in discontinuation symptoms.[36]During withdrawal from

venlafaxine, the levels of both serotonin and norepinephrine decrease, rather than increase, and this would

appear to rule out toxic (too high) levels of these neurotransmitters as a likely cause of the withdrawal

symptoms. The withdrawal symptoms can be hypothesized to result from an overly rapid deprivation of

neurotransmitter levels.

Although many other drugs can cause withdrawal symptoms which are not associated with addiction or

dependencefor example,anticonvulsants,beta-blockers,nitrates,diuretics,centrally acting

antihypertensives,sympathomimetics,heparin,tamoxifen,dopaminergic agents,antipsychotics,

andlithium[34]addiction or dependence is a more common effect described for drugs that (are thought to,

or may) improve mental well-being.[38]

Serotonin syndrome[edit]

The development of a potentially life-threateningserotonin syndrome(also more recently classified as

"serotonin toxicity")[39]may occur with venlafaxine treatment, particularly with concomitant use of

serotonergic drugs, including but not limited toSSRIsandSNRIs,many hallucinogens such

astryptaminesandphenethylamines(e.g.,LSD/LSA,DMT,MDMA,mescaline),dextromethorphan(DXM)/d

extrorphan(DXO),tramadol,tapentadol,pethidine(meperidine) andtriptansand with drugs that impair

metabolism of serotonin (includingMAOIs). Serotonin syndrome symptoms may include mental status

changes (e.g. agitation, hallucinations, coma), autonomic instability (e.g. tachycardia, labile blood pressure,

hyperthermia), neuromuscular aberrations (e.g. hyperreflexia, incoordination) and/or gastrointestinal

symptoms (e.g. nausea, vomiting, diarrhea). Venlafaxine-induced serotonin syndrome has also been

reported when venlafaxine has been taken in isolation in overdose.[40]An abortive serotonin syndrome

state, in which some but not all of the symptoms of the full serotonin syndrome are present, has been

reported with venlafaxine at mid-range dosages (150 mg per day)[41]A case of a patient with serotonin

syndrome induced by low-dose venlafaxine (37.5 mg per day) has also been reported.[42]

Serotonin toxicity and discontinuation syndrome[edit]

Venlafaxine may be particularly hazardous to those individuals who are susceptible to both venlafaxine-

induced serotonin toxicity (also known as serotonin syndrome) andSSRI discontinuation syndrome.Insuch cases, individuals who have developed the potentially fatal serotonin toxicity and/or may be at risk of
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a.org/wiki/Triptanhttp://en.wikipedia.org/wiki/MAOIhttp://en.wikipedia.org/wiki/MAOIhttp://en.wikipedia.org/wiki/MAOIhttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-Kolecki-40http://en.wikipedia.org/wiki/Venlafaxine#cite_note-Kolecki-40http://en.wikipedia.org/wiki/Venlafaxine#cite_note-Kolecki-40http://en.wikipedia.org/wiki/Venlafaxine#cite_note-41http://en.wikipedia.org/wiki/Venlafaxine#cite_note-41http://en.wikipedia.org/wiki/Venlafaxine#cite_note-41http://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid12549949-42http://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid12549949-42http://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid12549949-42http://en.wikipedia.org/w/index.php?title=Venlafaxine&action=edit&section=8http://en.wikipedia.org/w/index.php?title=Venlafaxine&action=edit&section=8http://en.wikipedia.org/w/index.php?title=Venlafaxine&action=edit&section=8http://en.wikipedia.org/wiki/SSRI_discontinuation_syndromehttp://en.wikipedia.org/wiki/SSRI_discontinuation_syndromehttp://en.wikipedia.org/wiki/SSRI_discontinuation_syndromehttp://en.wikipedia.org/wiki/SSRI_discontinuation_syndromehttp://en.wikipedia.org/w/index.php?title=Venlafaxine&action=edit&section=8http://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid12549949-42http://en.wikipedia.org/wiki/Venlafaxine#cite_note-41http://en.wikipedia.org/wiki/Venlafaxine#cite_note-Kolecki-40http://en.wikipedia.org/wiki/MAOIhttp://en.wikipedia.org/wiki/Triptanhttp://en.wikipedia.org/wiki/Pethidinehttp://en.wikipedia.org/wiki/Tapentadolhttp://en.wikipedia.org/wiki/Tramadolhttp://en.wikipedia.org/wiki/Dextrorphanhttp://en.wikipedia.org/wiki/Dextrorphanhttp://en.wikipedia.org/wiki/Dextromethorphanhttp://en.wikipedia.org/wiki/Mescalinehttp://en.wikipedia.org/wiki/MDMAhttp://en.wikipedia.org/wiki/Dimethyltryptaminehttp://en.wikipedia.org/wiki/Lysergic_acid_amidehttp://en.wikipedia.org/wiki/LSDhttp://en.wikipedia.org/wiki/Phenethylaminehttp://en.wikipedia.org/wiki/Tryptaminehttp://en.wikipedia.org/wiki/Serotonin-norepinephrine_reuptake_inhibitorhttp://en.wikipedia.org/wiki/SSRIhttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-Dunkley-39http://en.wikipedia.org/wiki/Serotonin_syndromehttp://en.wikipedia.org/w/index.php?title=Venlafaxine&action=edit&section=7http://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid9081020-38http://en.wikipedia.org/wiki/Lithium_pharmacologyhttp://en.wikipedia.org/wiki/Lithium_pharmacologyhttp://en.wikipedia.org/wiki/Antipsychoticshttp://en.wikipedia.org/wiki/Tamoxifenhttp://en.wikipedia.org/wiki/Heparinhttp://en.wikipedia.org/wiki/Sympathomimetichttp://en.wikipedia.org/wiki/Diuretichttp://en.wikipedia.org/wiki/Beta-blockershttp://en.wikipedia.org/wiki/Anticonvulsantshttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-PMC1681629-36http://en.wikipedia.org/wiki/Norepinephrinehttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid11347722-34http://en.wikipedia.org/wiki/Venlafaxine#cite_note-AmJPsych1997-fava-37http://en.wikipedia.org/wiki/Seroxathttp://en.wikipedia.org/wiki/Paxilhttp://en.wikipedia.org/wiki/Paroxetinehttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-ANZ_JPsych1998-parker-35http://en.wikipedia.org/wiki/Venlafaxine#cite_note-ANZ_JPsych1998-parker-35http://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid11347722-34http://en.wikipedia.org/wiki/Biological_half-life


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doing so, may find cessation or dose reduction unachievable, placing them at continuing risk. As it is not

possible to determine which patients are likely to develop the most severe symptoms of the discontinuation

syndrome before cessation or dose reduction is attempted, this dual risk requires that all patients be closely

monitored during any increase in dosage (when the patient is most at risk of developing serotonin

toxicity)[43]and that such increases be carried out in the smallest incremental steps possible. Additionally,

patients who recommence venlafaxine or revert to a higher dosage following a failed attempt to discontinue

the drug or reduce dosage are another group with an increased risk of developing serotonin toxicity .[38]

Contraindications[edit]

Studies of venlafaxine in paediatric age groups have not established its efficacy .[44]Venlafaxine is not

recommended in patientshypersensitiveto it, nor should it be taken by anyone who is allergic to the

inactive ingredients, which includegelatin,cellulose,ethylcellulose,iron oxide,titanium

dioxideandhypromellose.It should not be used in conjunction with amonoamine oxidase inhibitor(MAOI),as it can cause potentially fatalserotonin syndrome.[1][2][27]

Glaucoma[edit]

Venlafaxine can increase eye pressure, so those withglaucomamay require more frequent eye checks.[13]

Pregnant women[edit]

There are few well-controlled studies of venlafaxine in pregnant women. A study released in May 2010 by

the Canadian Medical Association Journal suggests use of venlafaxine doubles the risk

ofmiscarriage.

[45][46]

Consequently, venlafaxine should only be used during pregnancy if clearlyneeded.[13]Prospective studies have not shown any statistically significantcongenital

malformations.[47]There have, however, been some reports of self-limiting effects on newborn infants.[48]As

with otherserotonin reuptake inhibitors(SRIs), these effects are generally short-lived, lasting only 3 to 5

days,[49]and rarely resulting in severe complications.[50]

Drug interactions[edit]

Venlafaxine should be taken with caution when usingSt John's wort.[51]Venlafaxine may lower the seizure

threshold, and coadministration with other drugs that lower the seizure threshold such

asbupropionandtramadolshould be done with caution and at low doses.[52]

Other[edit]

There have been false positivephencyclidine(PCP) results caused by larger doses of venlafaxine, with

certain on-site routine urine-based drug tests.[53][54]

Overdose[edit]

Most patients overdosing with venlafaxine develop only mild symptoms. However, severe toxicity is

reported, with the most common symptoms beingCNS depression,serotonin toxicity,seizure,orcardiac

conductionabnormalities.[55]Venlafaxine seems to be more dangerous in overdose than the SSRIs, except
http://en.wikipedia.org/wiki/Venlafaxine#cite_note-43http://en.wikipedia.org/wiki/Venlafaxine#cite_note-43http://en.wikipedia.org/wiki/Venlafaxine#cite_note-43http://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid9081020-38http://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid9081020-38http://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid9081020-38http://en.wikipedia.org/w/index.php?title=Venlafaxine&action=edit&section=9http://en.wikipedia.org/w/index.php?title=Venlafaxine&action=edit&section=9http://en.wikipedia.org/w/index.php?title=Venlafaxine&action=edit&section=9http://en.wikipedia.org/wiki/Venlafaxine#cite_note-44http://en.wikipedia.org/wiki/Venlafaxine#cite_note-44http://en.wikipedia.org/wiki/Venlafaxine#cite_note-44http://en.wikipedia.org/wiki/Hypersensitivityhttp://en.wikipedia.org/wiki/Hypersensitivityhttp://en.wikipedia.org/wiki/Hypersensitivityhttp://en.wikipedia.org/wiki/Gelatinhttp://en.wikipedia.org/wiki/Gelatinhttp://en.wikipedia.org/wiki/Gelatinhttp://en.wikipedia.org/wiki/Cellulosehttp://en.wikipedia.org/wiki/Cellulosehttp://en.wikipedia.org/wiki/Cellulosehttp://en.wikipedia.org/wiki/Iron_oxidehttp://en.wikipedia.org/wiki/Iron_oxidehttp://en.wikipedia.org/wiki/Iron_oxidehttp://en.wikipedia.org/wiki/Titanium_dioxidehttp://en.wikipedia.org/wiki/Titanium_dioxidehttp://en.wikipedia.org/wiki/Titanium_dioxidehttp://en.wikipedia.org/wiki/Titanium_dioxidehttp://en.wikipedia.org/wiki/Hypromellosehttp://en.wikipedia.org/wiki/Hypromellosehttp://en.wikipedia.org/wiki/Hypromellosehttp://en.wikipedia.org/wiki/Monoamine_oxidase_inhibitorhttp://en.wikipedia.org/wiki/Monoamine_oxidase_inhibitorhttp://en.wikipedia.org/wiki/Serotonin_syndromehttp://en.wikipedia.org/wiki/Serotonin_syndromehttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-TGA-1http://en.wikipedia.org/wiki/Venlafaxine#cite_note-TGA-1http://en.wikipedia.org/wiki/Venlafaxine#cite_note-Maudsley-27http://en.wikipedia.org/wiki/Venlafaxine#cite_note-Maudsley-27http://en.wikipedia.org/w/index.php?title=Venlafaxine&action=edit&section=10http://en.wikipedia.org/w/index.php?title=Venlafaxine&action=edit&section=10http://en.wikipedia.org/w/index.php?title=Venlafaxine&action=edit&section=10http://en.wikipedia.org/wiki/Glaucomahttp://en.wikipedia.org/wiki/Glaucomahttp://en.wikipedia.org/wiki/Glaucomahttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-Medicinedatasheet-Wyeth-13http://en.wikipedia.org/wiki/Venlafaxine#cite_note-Medicinedatasheet-Wyeth-13http://en.wikipedia.org/wiki/Venlafaxine#cite_note-Medicinedatasheet-Wyeth-13http://en.wikipedia.org/w/index.php?title=Venlafaxine&action=edit&section=11http://en.wikipedia.org/w/index.php?title=Venlafaxine&action=edit&section=11http://en.wikipedia.org/w/index.php?title=Venlafaxine&action=edit&section=11http://en.wikipedia.org/wiki/Miscarriagehttp://en.wikipedia.org/wiki/Miscarriagehttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-45http://en.wikipedia.org/wiki/Venlafaxine#cite_note-45http://en.wikipedia.org/wiki/Venlafaxine#cite_note-45http://en.wikipedia.org/wiki/Venlafaxine#cite_note-Medicinedatasheet-Wyeth-13http://en.wikipedia.org/wiki/Venlafaxine#cite_note-Medicinedatasheet-Wyeth-13http://en.wikipedia.org/wiki/Venlafaxine#cite_note-Medicinedatasheet-Wyeth-13http://en.wikipedia.org/wiki/Congenital_malformationhttp://en.wikipedia.org/wiki/Congenital_malformationhttp://en.wikipedia.org/wiki/Congenital_malformationhttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-47http://en.wikipedia.org/wiki/Venlafaxine#cite_note-47http://en.wikipedia.org/wiki/Venlafaxine#cite_note-47http://en.wikipedia.org/wiki/Venlafaxine#cite_note-48http://en.wikipedia.org/wiki/Venlafaxine#cite_note-48http://en.wikipedia.org/wiki/Venlafaxine#cite_note-48http://en.wikipedia.org/wiki/Serotonin_reuptake_inhibitorhttp://en.wikipedia.org/wiki/Serotonin_reuptake_inhibitorhttp://en.wikipedia.org/wiki/Serotonin_reuptake_inhibitorhttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-49http://en.wikipedia.org/wiki/Venlafaxine#cite_note-49http://en.wikipedia.org/wiki/Venlafaxine#cite_note-49http://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid15900008-50http://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid15900008-50http://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid15900008-50http://en.wikipedia.org/w/index.php?title=Venlafaxine&action=edit&section=12http://en.wikipedia.org/w/index.php?title=Venlafaxine&action=edit&section=12http://en.wikipedia.org/w/index.php?title=Venlafaxine&action=edit&section=12http://en.wikipedia.org/wiki/Hypericum_perforatumhttp://en.wikipedia.org/wiki/Hypericum_perforatumhttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-51http://en.wikipedia.org/wiki/Venlafaxine#cite_note-51http://en.wikipedia.org/wiki/Venlafaxine#cite_note-51http://en.wikipedia.org/wiki/Bupropionhttp://en.wikipedia.org/wiki/Bupropionhttp://en.wikipedia.org/wiki/Bupropionhttp://en.wikipedia.org/wiki/Tramadolhttp://en.wikipedia.org/wiki/Tramadolhttp://en.wikipedia.org/wiki/Tramadolhttp://en.wikipedia.org/wiki/Venlafaxine#cite_note-pmid18072153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perhapscitalopramwhich is more dangerous than the other SSRIs in overdose. Despite this it appears less

dangerous thanbupropion,thetricyclic antidepressantsand the irreversiblemonoamine oxidase

inhibitors.[27][56]Deaths have been reported following very large doses.[57][58]Plasma venlafaxine

concentrations in overdose survivors have ranged from 6 to 24 mg/l, while postmortem blood levels in

fatalities are often in the 1090 mg/l range.[59]

On May 31, 2006, theMedicines and Healthcare Products Regulatory Agency(MHRA) UK concluded its

review of the latest safety evidence relating to venlafaxine, and particularly looked at the risks associated

with overdose. The advice was: the need for specialist supervision in those severely depressed or

hospitalized patients who need doses 300 mg or more; cardiac contraindications are more targeted

towards high risk groups; patients with uncontrolledhypertensionshould not take venlafaxine, and blood

pressure monitoring is recommended for all patients; and updated advice on possible drug interactions.[60]

On 17 October 2006, Wyeth and the FDA notified healthcare professionals of revisions to the

Overdosage/Human Experience section of the prescribing information for Effexor (venlafaxine) indicated for

treatment of major depressive disorder. In post-marketing experience, there have been reports of overdose

with venlafaxine, occurring predominantly in combination with alcohol and/or other drugs. Published

retrospective studies report that venlafaxine overdosage may be associated with an increased risk of fatal

outcome compared to that observed with SSRI antidepressant products, but lower than that for tricyclic

antidepressants. Healthcare professionals are advised to prescribe Effexor and Effexor XR in the smallest

quantity of capsules consistent with good patient management to reduce the risk of overdose.[61]

A report in theBritish Medical Journalin 2002 by Dr. Nicholas Buckley and colleagues at the Department of

Clinical Pharmacology and Toxicology,Canberra Hospital,Australia, studying fatal toxicity index (deaths

per million prescriptions), found that venlafaxine's fatal toxicity is higher than that of otherserotoninergic

antidepressants,but it is similar to that of some of the less toxic tricyclic antidepressants.Overall, they

found serious toxicity could occur following venlafaxine overdose with reports of deaths, arrythmias, and

seizures. They did, however, state that this type of data is open to criticism, pointing out that mortality data

may be influenced by previous l iterature and that "less toxic" drugs may be preferentially prescribed to

patients at higher risk of poisoning and suicide, but they are also less likely to be listed as the sole cause of

death from overdose. It also assumed that drugs are taken in overdose with similar frequency and in similaramounts. They suggested "clinicians need to consider whether factors in their patients reduce or

compensate for this risk before prescribing venlafaxine."[62]

The 27 February 2007 Vancouver Sun reported that the BC Drug and Poison Information Centre had

alerted doctors that the drug poses a significant risk of death from overdose, saying that venlafaxine

"appears more toxic than it was originally hoped".[63]A doctor from the Department of Pharmacy Services

College of Pharmacy, at the Medical University of South Carolina, reported on the death of a 39-year-old

patient with a 30 g overdose.[57]To put this into perspective, a patient would have to take over 66 of the

infrequently prescribed 450 mg high dosage pills, or 400 of the commonly prescribed 75 mg pills.

Gastrointestinal effects[edit]
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Two cases are known of patients who deliberately overdosed on a huge quantity of venlafaxine, resulting in

their stomach or intestines respectively being blocked by a mass of tablets (pharmaco -bezoar). The first

patient died; the second recovered after the blocked part of her colon was surgically removed. The second

patient's physicians speculate that the vasoconstrictive effects of venlafaxine contributed to

tissueischaemia(lack of blood supply) in the affected part of the intestine .[64]

Management of overdose[edit]

There is no specificantidotefor venlafaxine, and management is generally supportive, providing treatment

for the immediate symptoms. Administration ofactivated charcoalcan prevent absorption of the drug.

Monitoring of cardiac rhythm and vital signs is indicated. Seizures are managed withbenzodiazepinesor

other anticonvulsants.Forced diuresis,hemodialysis,exchange transfusion,orhemoperfusionare unlikely

to be of benefit in hastening the removal of venlafaxine, due to the drug's highvolume of distribution.[65]

Mechanism of action[edit]

Venlafaxine is abicyclicantidepressant, and usually categorized as aserotonin-norepinephrine reuptake

inhibitor(SNRI), but it has been referred to as aserotonin-norepinephrine-dopamine reuptake

inhibitor(SNDRI).[66][67]It works by blocking thetransporter "reuptake" proteinsfor

keyneurotransmittersaffecting mood, thereby leaving more active neurotransmitters in thesynapse.The

neurotransmitters affected areserotoninandnorepinephrine.Additionally, in high doses it weakly inhibits

the reuptake ofdopamine,[68]with recent evidence showing that thenorepinephrine transporteralso

transports somedopamineas well, since dopamine is inactivated by norepinephrine reuptake in thefrontal

cortex.The frontal cortex largely lacks dopamine transporters; therefore, venlafaxine can increase

dopamine neurotransmission in this part of the brain.[69][70]Venlafaxine interacts with opioid receptors (mu-,

kappa1- kappa3- and delta-opioid receptor subtypes) as well as the alpha2-adrenergic receptor, and was

shown to increase pain threshold in mice. When mice were tested with a hotplate analgesia meter (to

measure pain), both venlafaxine andmirtazapineinduced a dose-dependent, naloxone-reversible

antinociceptive effect followingintraperitonealinjection. These findings suggest venlafaxine's seemingly

superior efficacy in severe depression as narcotics become increasingly used as a measure of last resort

for refractory cases.[71]

Pharmacokinetics[edit]

Venlafaxine is well absorbed, with at least 92% of an oral dose being absorbed into systemic circulation. It

is extensively metabolized in the liver via theCYP2D6isoenzymetodesvenlafaxine(O-

desmethylvenlafaxine), which is just as potent a SNRI as the parent compound, meaning that the

differences in metabolism between extensive andpoor metabolisersare not clinically important in terms of

efficacy. Side effects, however, are reported to be more severe inCYP2D6poor metabolisers.[72]Steady-

state concentrations of venlafaxine and itsmetaboliteare attained in thebloodwithin 3 days. Therapeutic

effects are usually achieved within 3 to 4 weeks. No accumulation of venlafaxine has been observed during

chronic administration in healthy subjects. The primary route of excretion of venlafaxine and its metabolites
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venlafaxine

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