Brand name Effexor.
An antidepressant medication of the serotonin-norepinephrine reuptake inhibitor (SNRI) class.
Oral agent used to treat major depressive disorder, generalized anxiety disorder, panic disorder, and social phobia, and vasomotor symptoms.
Categorized as a serotonin-norepinephrine reuptake inhibitor (SNRI), but it has been referred to as a serotonin-norepinephrine-dopamine reuptake inhibitor.
It blocks the transporter “reuptake” proteins for key neurotransmitters affecting mood, thereby leaving more active neurotransmitters in the synapse.
The neurotransmitters affected are serotonin and norepinephrine.
In high doses it weakly inhibits the reuptake of dopamine,
Pregnancy category US: C (Risk not ruled out)
Bioavailability 42±15%.
Protein binding 27±2%, parent compound, 30±12% active metabolite, desvenlafaxine
About 50% of the parent compound is metabolized on first pass through the liver.
Elimination half-life 5±2 h for the parent compound for immediate release preparations, 15±6 h for extended release preparations,11±2 h for the active metabolite.
Excretion by Kidney 87%; 5% as unchanged drug; 29% as desvenlafaxine and 53% as other metabolites.
Common side effects include: loss of appetite, constipation, dry mouth, dizziness, sweating, and sexual problems.
Severe side effects include: an increased risk of suicide, mania, and serotonin syndrome.
Antidepressant withdrawal syndrome may occur.
Use during the later part of pregnancy can harm the baby.
May be used for the treatment of diabetic neuropathy and migraine prophylaxis.
Reduces the severity of hot flashes in menopausal women and men on hormonal therapy for the treatment of prostate cancer.
Used as a treatment to reduce episodes of cataplexy, a form of muscle weakness, in patients with the sleep disorder narcolepsy.
May have efficacy in the treatment of attention deficit-hyperactivity disorder (ADHD), and post-traumatic stress disorder (PTSD).
A comparative meta-analysis of 21 major antidepressants found that venlafaxine, amitriptyline, escitalopram, mirtazapine, and paroxetine, were more effective than other antidepressants.
Venlafaxine was similar in efficacy to the atypical antidepressant bupropion.
Efficacy in children has not established.
It should not be used in conjunction with a monoamine oxidase inhibitor (MAOI).
It can cause potentially fatal serotonin syndrome.
Can increase eye pressure, so those with glaucoma may require more frequent eye checks.
The FDA requires all antidepressants, including venlafaxine, to carry a black box warning 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, it reduced the risk of suicidal thoughts and behavior.
However, a study conducted in Finland followed more than 15,000 patients for 3.4 years, it increased suicide risk by 60% as compared to no treatment, while fluoxetine (Prozac) halved the suicide risk.
Other clinical trials showed the incidence of suicidal behaviour among the adults on venlafaxine to be not significantly different from fluoxetine or placebo.
It is contraindicated in children, adolescents and young adults as analysis of clinical trials revealed a significant 5-fold increase in suicidal ideation and behaviour in persons younger than 25.
A different analysis, revealed it was no better than placebo among children (7–11 years old), but improved depression in adolescents (12–17 years old).
People stopping the drug commonly experience discontinuation symptoms such as dysphoria, headaches, nausea, irritability, emotional lability, sensation of electric shocks, and sleep disturbance.
Has a higher rate of moderate to severe discontinuation symptoms relative to other antidepressants.
Discontinuing venlafaxine, the levels of both serotonin and norepinephrine decrease, leading to the suggestion that the discontinuation symptoms could result from an overly rapid reduction of neurotransmitter levels.
The development of a serotonin syndrome may occur with treatment, particularly with concomitant use of serotonergic drugs, including: but not limited to SSRIs and SNRIs, many hallucinogens such as tryptamines and phenethylamines, dextromethorphan, tramadol, tapentadol, meperidine and triptans and with drugs that impair metabolism of serotonin, including MAOIs.
Venlafaxine-induced serotonin syndrome has also been reported when venlafaxine has been taken in isolation in overdose, at mid-range dosages, and by low-dose.
Use in pregnancy doubles the risk of miscarriage, and is associated with several birth defects including anencephaly, cleft palate, septal heart defects and coarctation of the aorta.
However, prospective studies have not shown any statistically significant congenital malformations.
It is to be taken with caution when using St John’s wort.
It may lower the seizure threshold.
Coadministration with other drugs that lower the seizure threshold such as bupropion and tramadol should be done with caution.
Not recommended for the treatment of major depressive episodes in bipolar disorder as it can induce mania or mixed episodes.
Rarely associated with drug-induced akathisia.
Used with caution in hypertensive patients.
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.
It is usually reserved as a second-line treatment for depression due to 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 overdose, and management is generally supportive, providing treatment for the immediate symptoms.
Administration of activated charcoal can prevent absorption of the drug.
It is difficult to help in overdose situations with forced diuresis, hemodialysis, exchange transfusion, or hemoperfusion due to the drug’s high volume of distribution.
It 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, now marketed as a separate medication named Pristiq.
Side effects, however, are reported to be more severe in CYP2D6 poor metabolizers.
Steady-state concentrations of venlafaxine and its metabolite are attained in the blood within 3 days.
Therapeutic effects are usually achieved within 3 to 4 weeks.
Excretion of venlafaxine and its metabolites is primarily via the kidneys.
Its half-life is relatively short, so patients must adhere to a strict medication routine, to avoid missing a dose.
A single missed dose can result in withdrawal symptoms.
It is a substrate of P-glycoprotein (P-gp), which pumps it out of the brain.
The majority of people (about 70% of Europeans and 90% of East Asians) have the TT variant.
It is structurally and pharmacologically related to the opioid analgesic tramadol, and more distantly to opioid tapentadol, but not to any of the conventional antidepressant drugs, including tricyclic antidepressants, SSRIs, MAOIs, or RIMAs.
The extended release version distributes the release of the drug into the gastrointestinal tract over a longer period than normal venlafaxine, Andy in a lower peak plasma concentration.
The extended release formula has a lower incidence of nausea as a side effect, resulting in better compliance.
Effexor XR 75 mg and 150 mg capsules
Antidepressant that is biotransformed to its active and inactive forms by CYP2D6 enzyme.
Available in immediate release and extended release forms.
May increase metanephrine and catecholamine levels as a result of decreased reuptake of norepinephrine.
It is a more potent than the selective serotonin-reuptake inhibitors (SSRIs) as a norepinephrine reuptake inhibitor.