Venlafaxine, sold under the brand name Effexor among others, is an

antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common Side effect, side-effects of antidepressants include Xerostomia, dry mouth, weig ...

medication of the serotonin-norepinephrine reuptake inhibitor (SNRI) class. It is used to treat

major depressive disorder Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Intro ...

, generalized anxiety disorder, panic disorder, and social anxiety disorder. It may also be used for chronic pain. It is taken by mouth. It is also available as the salt venlafaxine besylate in an extended-release formulation (Venbysi XR). Common side effects include loss of appetite, constipation, dry mouth, dizziness, sweating, insomnia, drowsiness and sexual problems. Severe side effects include an increased risk of

suicide Suicide is the act of intentionally causing one's own death. Mental disorders (including depression, bipolar disorder, schizophrenia, personality disorders, anxiety disorders), physical disorders (such as chronic fatigue syndrome), and ...

mania Mania, also known as manic syndrome, is a mental and behavioral disorder defined as a state of abnormally elevated arousal, affect, and energy level, or "a state of heightened overall activation with enhanced affective expression together wi ...

, and serotonin syndrome. Antidepressant withdrawal syndrome may occur if stopped. There are concerns that use during the later part of

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ...

can harm the baby. How it works is not entirely clear, but it seems to be related to the potentiation of the activity of some neurotransmitters in the brain. Venlafaxine was approved for medical use in the United States in 1993. It is available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ...

. In 2020, it was the 43rd most commonly prescribed medication in the United States with more than 15million prescriptions.

Medical uses

Venlafaxine is used primarily for the treatment of depression, general anxiety disorder, social phobia, panic disorder, and vasomotor symptoms. Venlafaxine has been used

off label Off-label use is the use of pharmaceutical drugs for an unapproved indication or in an unapproved age group, dosage, or route of administration. Both prescription drugs and over-the-counter drugs (OTCs) can be used in off-label ways, although m ...

for the treatment of

diabetic neuropathy Diabetic neuropathy is various types of nerve damage associated with diabetes mellitus. Symptoms depend on the site of nerve damage and can include motor changes such as weakness; sensory symptoms such as numbness, tingling, or pain; or autonomic c ...

and

migraine Migraine (, ) is a common neurological disorder characterized by recurrent headaches. Typically, the associated headache affects one side of the head, is pulsating in nature, may be moderate to severe in intensity, and could last from a few hou ...

prevention. It may work on pain via effects on the opioid receptor. It has also been found to reduce the severity of 'hot flashes' in menopausal women and men on hormonal therapy for the treatment of prostate cancer. Due to its action on both the serotoninergic and adrenergic systems, venlafaxine is also used as a treatment to reduce episodes of cataplexy, a form of muscle weakness, in patients with the sleep disorder

narcolepsy Narcolepsy is a long-term neurological disorder that involves a decreased ability to regulate sleep–wake cycles. Symptoms often include periods of excessive daytime sleepiness and brief involuntary sleep episodes. About 70% of those affect ...

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

attention deficit-hyperactivity disorder Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inappr ...

(ADHD). Clinical trials have found possible efficacy in those with

post-traumatic stress disorder Post-traumatic stress disorder (PTSD) is a mental and behavioral disorder that can develop because of exposure to a traumatic event, such as sexual assault, warfare, traffic collisions, child abuse, domestic violence, or other threats o ...

(PTSD). Case reports, open trials and blinded comparisons with established medications have suggested the efficacy of venlafaxine in the treatment of

obsessive–compulsive disorder Obsessive–compulsive disorder (OCD) is a mental and behavioral disorder in which an individual has intrusive thoughts and/or feels the need to perform certain routines repeatedly to the extent where it induces distress or impairs general ...

Depression

A comparative meta-analysis of 21 major antidepressants found that venlafaxine,

agomelatine Agomelatine, sold under the brand names Valdoxan and Thymanax, among others, is an atypical antidepressant most commonly used to treat major depressive disorder and generalized anxiety disorder. One review found that it is as effective as other a ...

amitriptyline Amitriptyline, sold under the brand name Elavil among others, is a tricyclic antidepressant primarily used to treat cyclic vomiting syndrome (CVS), major depressive disorder and a variety of pain syndromes from neuropathic pain to fibromyalgi ...

, escitalopram,

mirtazapine Mirtazapine, sold under the brand name Remeron amongst others, is an atypical antidepressant, and as such is used primarily to treat depression. Its effects may take up to four weeks, but can also manifest as early as one to two weeks. It is o ...

, paroxetine, and vortioxetine were more effective than other antidepressants, although the quality of many comparisons was assessed as low or very low. Venlafaxine was similar in efficacy to the atypical antidepressant

bupropion Bupropion, sold under the brand names Wellbutrin and Zyban among others, is an atypical antidepressant primarily used to treat major depressive disorder and to support smoking cessation. It is also popular as an add-on medication in the cas ...

; however, the remission rate was lower for venlafaxine. In a double-blind study, patients who did not respond to an SSRI were switched to either venlafaxine or another SSRI (

citalopram Citalopram, sold under the brand name Celexa among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used to treat major depressive disorder, obsessive compulsive disorder, panic disorder, and so ...

); similar improvement was observed in both groups. Studies have not established its efficacy for use by children. In children and adolescents with depression, venlafaxine increases the risk of suicidal thoughts or attempts. Studies have shown that the extended release is superior to the immediate release form of venlafaxine. A meta-analysis has shown that efficacy of venlafaxine is not correlated with baseline severity of depression.

Dosage

Venlafaxine has been shown to have an optimal efficacy and tolerability towards the lower end of the licensed dose range.

Contraindications

Venlafaxine is not recommended in patients hypersensitive to it, nor should it be taken by anyone who is allergic to the inactive ingredients, which include

gelatin Gelatin or gelatine (from la, gelatus meaning "stiff" or "frozen") is a translucent, colorless, flavorless food ingredient, commonly derived from collagen taken from animal body parts. It is brittle when dry and rubbery when moist. It may also ...

cellulose Cellulose is an organic compound with the formula , a polysaccharide consisting of a linear chain of several hundred to many thousands of β(1→4) linked D-glucose units. Cellulose is an important structural component of the primary cell wa ...

, ethylcellulose,

iron oxide Iron oxides are chemical compounds composed of iron and oxygen. Several iron oxides are recognized. All are black magnetic solids. Often they are non-stoichiometric. Oxyhydroxides are a related class of compounds, perhaps the best known of wh ...

titanium dioxide Titanium dioxide, also known as titanium(IV) oxide or titania , is the inorganic compound with the chemical formula . When used as a pigment, it is called titanium white, Pigment White 6 (PW6), or CI 77891. It is a white solid that is insolu ...

and hypromellose. It should not be used in conjunction with a

monoamine oxidase inhibitor Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, esp ...

(MAOI), as it can cause potentially fatal serotonin syndrome. Venlafaxine might interact with

tramadol Tramadol, sold under the brand name Ultram among others, is an opioid pain medication used to treat moderate to moderately severe pain. When taken by mouth in an immediate-release formulation, the onset of pain relief usually begins within an ...

or other opioids, trazodone, so caution is needed while mixing multiple serotonergic agents together.

Adverse effects

Venlafaxine can increase eye pressure, so those with

glaucoma Glaucoma is a group of eye diseases that result in damage to the optic nerve (or retina) and cause vision loss. The most common type is open-angle (wide angle, chronic simple) glaucoma, in which the drainage angle for aqueous humor, fluid withi ...

may require more frequent eye checks. A 2017 meta-analysis estimated venlafaxine discontinuation rate to 9.4%.

Suicide

The US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

(FDA) requires all antidepressants, including venlafaxine, to carry a

black box warning In the United States, a boxed warning (sometimes "black box warning", colloquially) is a type of warning that appears on the package insert for certain prescription drugs, so called because the U.S. Food and Drug Administration specifies that i ...

with a generic warning about a possible suicide risk. A 2014 meta analysis of 21 clinical trials of venlafaxine for the treatment of depression in adults found that compared to placebo, venlafaxine reduced the risk of suicidal thoughts and behavior. A study conducted in Finland followed more than 15,000 patients for 3.4 years. Venlafaxine increased suicide risk by 60% (statistically significant), as compared to no treatment. At the same time,

fluoxetine Fluoxetine, sold under the brand names Prozac and Sarafem, among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used for the treatment of major depressive disorder, obsessive–compulsive diso ...

(Prozac) halved the suicide risk. In another study, the data on more than 200,000 cases were obtained from the UK general practice research database. At baseline, patients prescribed venlafaxine had a greater number of risk factors for suicide (such as prior suicide attempts) than patients treated with other anti-depressants. The patients taking venlafaxine had significantly higher risk of suicide than the ones on

(Celexa). After adjusting for known risk factors, venlafaxine was associated with an increased risk of suicide relative to fluoxetine and dothiepin that was not statistically significant. A statistically significant greater risk for attempted suicide remained after adjustment, but the authors concluded that it could be due to residual confounding. The study was sponsored by Wyeth, which produces and markets venlafaxine. 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 or

placebo A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like Saline (medicine), saline), sham surgery, and other procedures. In general ...

. Venlafaxine is contraindicated in children, adolescents and young adults. In children and adolescents with depression, venlafaxine increases the risk of suicidal thoughts or attempts.

Discontinuation syndrome

People stopping venlafaxine commonly experience discontinuation symptoms such as dysphoria,

headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of th ...

irritability Irritability (also called as crankiness) is the excitatory ability that living organisms have to respond to changes in their environment. The term is used for both the physiological reaction to stimuli and for the pathological, abnormal or excessi ...

, emotional lability, sensation of electric shocks, and sleep disturbance. Venlafaxine has a higher rate of moderate to severe discontinuation symptoms relative to other antidepressants (similar to the SSRI paroxetine). The higher risk and increased severity of discontinuation syndrome symptoms relative to other antidepressants may be related to the short

half-life Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable ...

of venlafaxine and its active metabolite. After discontinuing venlafaxine, the levels of both serotonin and

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad ...

decrease, leading to the hypothesis that the discontinuation symptoms could result from an overly rapid reduction of neurotransmitter levels.

Serotonin syndrome

The development of a potentially life-threatening serotonin syndrome (also more recently classified as "serotonin toxicity") may occur with venlafaxine treatment, particularly with concomitant use of serotonergic drugs, including but not limited to SSRIs and SNRIs, many hallucinogens such as

tryptamine Tryptamine is an indolamine metabolite of the essential amino acid, tryptophan. The chemical structure is defined by an indole ─ a fused benzene and pyrrole ring, and a 2-aminoethyl group at the second carbon (third aromatic atom, with the f ...

s and

phenethylamine Phenethylamine (PEA) is an organic compound, natural monoamine alkaloid, and trace amine, which acts as a central nervous system stimulant in humans. In the brain, phenethylamine regulates monoamine neurotransmission by binding to trace am ...

s (e.g., LSD/ LSA,

DMT ''N'',''N''-Dimethyltryptamine (DMT or ''N'',''N''-DMT, SPL026) is a substituted tryptamine that occurs in many plants and animals, including human beings, and which is both a derivative and a structural analog of tryptamine. It is used as a ...

MDMA 3,4-Methylenedioxymethamphetamine (MDMA), commonly seen in tablet form (ecstasy) and crystal form (molly or mandy), is a potent empathogen–entactogen with stimulant properties primarily used for recreational purposes. The desire ...

mescaline Mescaline or mescalin (3,4,5-trimethoxyphenethylamine) is a naturally occurring psychedelic protoalkaloid of the substituted phenethylamine class, known for its hallucinogenic effects comparable to those of LSD and psilocybin. Biological ...

dextromethorphan Dextromethorphan (DXM) is a medication most often used as a cough suppressant in over-the-counter cold and cough medicines. It is sold in syrup, tablet, spray, and lozenge forms. In 2022, the FDA approved a formulation of it combined with b ...

(DXM),

tapentadol Tapentadol, brand names Nucynta among others, is a centrally acting opioid analgesic of the benzenoid class with a dual mode of action as an agonist of the μ-opioid receptor and as a norepinephrine reuptake inhibitor (NRI). Analgesia occurs wit ...

pethidine Pethidine, also known as meperidine and sold under the brand name Demerol among others, is a synthetic opioid pain medication of the phenylpiperidine class. Synthesized in 1938 as a potential anticholinergic agent by the German chemist Otto Eis ...

(meperidine) and triptans and with drugs that impair metabolism of serotonin (including MAOIs) . 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) 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. 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). A case of a patient with serotonin syndrome induced by low-dose venlafaxine (37.5 mg per day) has also been reported.

Pregnancy

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 of

miscarriage Miscarriage, also known in medical terms as a spontaneous abortion and pregnancy loss, is the death of an embryo or fetus before it is able to survive independently. Miscarriage before 6 weeks of gestation is defined by ESHRE as biochemica ...

. Consequently, venlafaxine should only be used during pregnancy if clearly needed. A large case-control study done as part of the National Birth Defects Prevention Study and published in 2012 found a significant association of venlafaxine use during pregnancy and several birth defects including anencephaly, cleft palate, septal heart defects and coarctation of the aorta. Prospective studies have not shown any statistically significant

congenital malformation A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities c ...

s. There have, however, been some reports of self-limiting effects on newborn infants. As with other serotonin reuptake inhibitors (SRIs), these effects are generally short-lived, lasting only 3 to 5 days, and rarely resulting in severe complications.

Drug interactions

Venlafaxine should be taken with caution when using St John's wort. Venlafaxine may lower the seizure threshold, and coadministration with other drugs that lower the seizure threshold such as

and

should be done with caution and at low doses.

Bipolar disorder

Venlafaxine is neither recommended nor approved for the treatment of major depressive episodes in

bipolar disorder Bipolar disorder, previously known as manic depression, is a mental disorder characterized by periods of Depression (mood), depression and periods of abnormally elevated Mood (psychology), mood that last from days to weeks each. If the elevat ...

, as it can induce

or mixed episodes. Venlafaxine appears to be more likely than the

SSRIs Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs increase the extracellu ...

and

to induce mania and mixed episodes in bipolar patients.

Liver injury

A rare but serious side effect of venlafaxine is liver injury. It reaches male and female patients with a median age of 44y. Cessation of venlafaxine is one of the appropriate measure of management. The mechanism of venlafaxine-related liver injury is unclear but may be related to a CYP2D6 polymorphism.

Abuse as recreational drug

Venlafaxine can be abused as recreational drug, with damages that can manifest within a month. Hard data regarding prevalence of abuse are not easy to find. Abusers reported usage of extremely high dosage, 5 to 10 times of acceptable clinical dosage. The adverse side effects were strong cases of the listed side effects. As standard measure treatment is to be supervised by a doctor with relevant education, such as neurologist or psychiatrist.

Other

In rare cases, drug-induced akathisia can occur after use in some people. Venlafaxine should be used with caution in hypertensive patients. Venlafaxine must be discontinued if significant

hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high b ...

persists. It can also have undesirable cardiovascular effects.

Overdose

Most patients overdosing with venlafaxine develop only mild symptoms. Plasma venlafaxine concentrations in overdose survivors have ranged from 6 to 24 mg/L, while postmortem blood levels in fatalities are often in the 10–90 mg/L range. 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. It is usually reserved as a second-line treatment for depression due to a combination of its superior efficacy to the first-line treatments like fluoxetine, paroxetine and citalopram and greater frequency of side effects like nausea, headache, insomnia, drowsiness, dry mouth, constipation, sexual dysfunction, sweating and nervousness. There is no specific antidote for venlafaxine, and management is generally supportive, providing treatment for the immediate symptoms. Administration of

activated charcoal "Activated" is a song by English singer Cher Lloyd. It was released on 22 July 2016 through Vixen Records. The song was made available to stream exclusively on ''Rolling Stone'' a day before to release (on 21 July 2016). Background In an inter ...

can prevent absorption of the drug. Monitoring of cardiac rhythm and vital signs is indicated. Seizures are managed with

benzodiazepine Benzodiazepines (BZD, BDZ, BZs), sometimes called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, ...

s or other anticonvulsants. Forced diuresis, hemodialysis,

exchange transfusion An exchange transfusion is a blood transfusion in which the patient's blood or components of it are exchanged with (replaced by) other blood or blood products. The patient's blood is removed and replaced by donated blood or blood components. This ...

, or

hemoperfusion Hemoperfusion or hæmoperfusion (see spelling differences) is a method of filtering the blood extracorporeally (that is, outside the body) to remove a toxin. As with other extracorporeal methods, such as hemodialysis (HD), hemofiltration (HF), ...

are unlikely to be of benefit in hastening the removal of venlafaxine, due to the drug's high

volume of distribution In pharmacology, the volume of distribution (VD, also known as apparent volume of distribution, literally, ''volume of dilution'') is the theoretical volume that would be necessary to contain the total amount of an administered drug at the same c ...

Mechanism of action

Pharmacology

Venlafaxine is usually categorized as a serotonin-norepinephrine reuptake inhibitor (SNRI), but it has also been referred to as a serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI). It is described as 'synthetic phenethylamine bicyclic derivative with antidepressant activity'. It works by blocking the transporter "reuptake" proteins for key

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neu ...

s affecting mood, thereby leaving more active neurotransmitters in the

synapse In the nervous system, a synapse is a structure that permits a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or to the target effector cell. Synapses are essential to the transmission of nervous impulses from ...

. The neurotransmitters affected are

serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and va ...

and

. Additionally, in high doses it weakly inhibits the reuptake of

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 80% o ...

, since dopamine is inactivated by norepinephrine reuptake in the

frontal cortex The frontal lobe is the largest of the four major lobes of the brain in mammals, and is located at the front of each cerebral hemisphere (in front of the parietal lobe and the temporal lobe). It is parted from the parietal lobe by a groove be ...

. The frontal cortex largely lacks dopamine transporters; therefore venlafaxine can increase dopamine neurotransmission in this part of the brain. Venlafaxine indirectly affects opioid receptors as well as the alpha2-adrenergic receptor, and was shown to increase pain threshold in mice. These benefits with respect to pain were reversed with

naloxone Naloxone, sold under the brand names Narcan (4 mg) and Kloxxado (8 mg) among others, is a medication used to reverse or reduce the effects of opioids. It is commonly used to counter decreased breathing in opioid overdose. Effects begin withi ...

, an opioid antagonist, thus supporting an opioid mechanism.

Pharmacokinetics

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 the CYP2D6 isoenzyme to

desvenlafaxine Desvenlafaxine, sold under the brand name Pristiq among others, is a medication used to treat depression. It is an antidepressant of the serotonin-norepinephrine reuptake inhibitor (SNRI) class and is taken by mouth. It is recommended that the ...

(''O''-desmethylvenlafaxine, now marketed as a separate medication named Pristiq), which is just as potent an SNRI as the parent compound, meaning that the differences in metabolism between extensive and poor metabolisers are not clinically important in terms of efficacy. Side effects, however, are reported to be more severe in CYP2D6 poor metabolisers. Steady-state concentrations of venlafaxine and its

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, ...

are attained in the

blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the cir ...

within 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 is via the kidneys. The

of venlafaxine is relatively short, so patients are directed to adhere to a strict medication routine, avoiding missing a dose. Even a single missed dose can result in withdrawal symptoms. Venlafaxine is a substrate of

P-glycoprotein P-glycoprotein 1 (permeability glycoprotein, abbreviated as P-gp or Pgp) also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1) or cluster of differentiation 243 (CD243) is an important protein ...

(P-gp), which pumps it out of the brain. The gene encoding P-gp, ABCB1, has the SNP rs2032583, with

allele An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution. ::"The chrom ...

s C and T. The majority of people (about 70% of Europeans and 90% of East Asians) have the TT variant. A 2007 study found that carriers of at least one C allele (variant CC or CT) are 7.72 times more likely than non-carriers to achieve

remission Remission often refers to: *Forgiveness Remission may also refer to: Healthcare and science *Remission (medicine), the state of absence of disease activity in patients with a chronic illness, with the possibility of return of disease activity *R ...

after 4 weeks of treatment with

, paroxetine or venlafaxine (all P-gp substrates). The study included patients with

mood disorder A mood disorder, also known as an affective disorder, is any of a group of conditions of mental and behavioral disorder where a disturbance in the person's mood is the main underlying feature. The classification is in the '' Diagnostic and St ...

s other than major depression, such as bipolar II; the ratio is 9.4 if these other disorders are excluded. At the 6-week mark, 75% of C-carriers had remitted, compared to only 38% of non-carriers.

Chemistry

The IUPAC name of venlafaxine is 1- -(dimethylamino)-1-(4 methoxyphenyl)ethylyclohexanol, though it is sometimes referred to as (±)-1- -[a-(dimethylamino)methyl''p''-methoxybenzyl.html" ;"title="-(dimethylamino)methyl.html" ;"title="-[a-(dimethylamino)methyl">-[a-(dimethylamino)methyl''p''-methoxybenzyl">-(dimethylamino)methyl.html" ;"title="-[a-(dimethylamino)methyl">-[a-(dimethylamino)methyl''p''-methoxybenzylyclohexanol. It consists of two enantiomers present in equal quantities (termed a racemic mixture), both of which have the empirical formula of C₁₇H₂₇NO₂. It is usually sold as a mixture of the respective hydrochloride

salt Salt is a mineral composed primarily of sodium chloride (NaCl), a chemical compound belonging to the larger class of salts; salt in the form of a natural crystalline mineral is known as rock salt or halite. Salt is present in vast quant ...

s, (''R''/''S'')-1- -(dimethylamino)-1-(4 methoxyphenyl)ethylyclohexanol hydrochloride, C₁₇H₂₈ClNO₂, which is a white to off-white crystalline solid. Venlafaxine is structurally and pharmacologically related to the atypical opioid

analgesic An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...

, and more distantly to the newly released opioid

, but not to any of the conventional antidepressant drugs, including

tricyclic antidepressant Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants, which is important for the management of depression. They are second-line drugs next to SSRIs. TCAs were discovered in the early 1950s and wer ...

, MAOIs, or RIMAs. Venlafaxine extended release is chemically the same as normal venlafaxine. The extended release (controlled release) version distributes the release of the drug into the

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...

over a longer period than normal venlafaxine. This results in a lower peak plasma concentration. Studies have shown that the extended release formula has a lower incidence of

as a side effect, resulting in better compliance.

Society and culture

Venlafaxine was originally marketed as Effexor in most of the world; generic venlafaxine has been available since around 2008 and extended release venlafaxine has been available since around 2010. As of January 2020, venlafaxine is marketed under many brand names worldwide, many with alternative extended release forms (not shown): Adefaxin, Alenthus, Altven, Alventa, Amfax, Anapresin, Ansifix, Arafaxina, Argofan, Arrow Venlafaxine, Axone, Axyven, Benolaxe, Blossom, Calmdown, Dalium, Defaxine, Depefex, Depretaxer, Deprevix, Deprexor, Deprixol, Depurol, Desinax, Dislaven, Dobupal, Duofaxin, Easyfor, Ectien, Eduxon, Efastad, Efaxin, Efaxine, Efectin, Efegen, Efevelon, Efevelone, Efexiva, Efexor, Effegad, Effexine, Effexor, Elafax, Elaxine, Elify, Enpress, Enlafax, Envelaf, Falven, Faxigen, Faxine, Faxiprol, Faxiven, Faxolet, Flavix, Flaxen, Fobiless, Ganavax, Idixor, Idoxen, Intefred, Illovex, Lafactin, Lafaxin, Lanvexin, Laroxin, Levest, Limbic, Linexel, Maxibral, Mazda, Melocin, Memomax, Mezine, Neoxacina, Neoxacina, Nervix, Norafexine, Norezor, Norpilen, Noviser, Nulev, Odiven, Olwexya, Oriven, Paxifar, Politid, Pracet, Prefaxine, Psiseven, Quilarex, Rafax, Senexon, Sentidol, Sentosa, Serosmine, Seroxine, Sesaren, Subelan, Sulinex, Sunveniz, Sunvex, Symfaxin, Tedema, Tifaxin, Tonpular, Trevilor, Tudor, Vafexin, Valosine, Vandral, Velaf, Velafax, Velahibin, Velaxin, Velaxor, Velept, Velpine, Venax, Venaxin, Venaxx, Vencarm, Vencontrol, Vendep, Venegis, Venex, Venexor, Venfalex, Venfax, Ven-Fax, Venfaxine, Venforin, Venforspine, Veniba, Veniz, Venjoy, Venla, Venlabax, Venlablue, Venlabrain, Venladep, Venladex, Venladoz, Venlaf, Venlafab, Venlafaxin, Venlafaxina, Venlafaxine, Venlagamma, Venlalic, Venlamax, Venlamylan, Venlaneo, Venlapine, Venla-Q, Venlasand, Venlatrin, Venlavitae, Venlax, Venlaxin, Venlaxine, Venlaxor, Venlazid, Venlectine, Venlifax, Venlift, Venlix, Venlobax, Venlofex, Venlor, Venorion, Venozap, Vensate, Ventab, Venxin, Venxor, Vextor, Venzip, Vexamode, Vfax, Viepax, ViePax, Voxafen, Zacalen, Zanfexa, Zaredrop, Zarelis, Zarelix, and Zenexor.

Veterinary effects

Veterinary overdose in dogs is very well treated by Cyproheptadine HCl. Venlafaxine is highly toxic to Bacillariophyta and Chlorophyta phytoplankton.

References

External links

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