'Venlafaxine hydrochloride' (Effexor) is an
antidepressant of the
serotonin-norepinephrine reuptake inhibitor (SNRI) class. It is prescribed for the treatment of
clinical depression and
anxiety disorders. Due to the side effects and suspicions that venlafaxine may cause suicide it is not recommended as a first line treatment. However, it is often effective for depression not responding to SSRI. Venlafaxine was first introduced by
Wyeth in
1993. It is the sixth antidepressant based on the amount of retail prescriptions in the US (17.1 million).
[1]
Trade names
Venlafaxine is marketed under the brand names:
★ Depurol (CL)
★ Dobupal (ES)
★ Efectin (AT, CZ, HR, HU, PL, RO, SI, YU)
★ Efexor Depot (FI, SE, DK)
★ Efexor XR (AU, NZ, ZA)
★ Efexor XL (GB,IE)
★ Efexor (AR, AU, BE, BR, CH, CL, CO, CR, CY, DK, DO, EC, EG, FI, GB, GT, HN, ID, IE, IL, IT, JO, KW, LB, LU, MT, MX, NL, NO, NZ, PA, PT, SE, SG, SV, TH, TR)
★ Effexor Paranova (DK)
★ Effexor (FR, IE, US)
★ Effexor XR (AU, CA, US)
★ Elafax (AR)
★ Faxine (IT)
★ Flavix (IN)
★ Nervix (CL)
★ Norpilen (CL)
★ Trevilor (DE)
★ Vandral (DK, ES)
★ Velafax (HR)
★ Venlafaxina Combino Pharm (ES)
★ Venlafaxina Dosa (AR)
★ Venlafaxina Masterfarm (ES)
★ Venlafaxina Ratiopharm (ES)
★ Venlafaxine-Apex (NL)
★ Venlax (CL)
★ Venlor (IN)
★ Viepax (IL)
Indications
Approved
Venlafaxine is used primarily for the treatment of
depression,
generalized anxiety disorder,
social anxiety disorder, and
panic disorder in adults.
Depression
Venlafaxine was shown to be effective for depression in multiple double blind studies. Venlafaxine is similar in efficacy to
trazodone and
tricyclic antidepressants amitriptiline (Elavil) and
imipramine and it was better tolerated than amitriptiline. Venlafaxine appears to have efficacy similar or somewhat better than
sertraline (Zoloft) and
fluoxetine (Prozac) depending on the criteria and rating scales used. In particular, higher doses of venlafaxine are more effective, and more patients achieved
remission or were "very much improved". At the same time the efficacy was similar if the number of patients who achieved "response" or were "improved" was considered. A
meta-analysis comparing venlafaxine and combined groups of
SSRI or tricyclic antidepressants indicated superiority of venlafaxine.
[2] Based on the same set of criteria, venlafaxine was similar in efficacy to an atypical antidepressant
bupropion (Wellbutrin); however, the remission rate was significantly lower for venlafaxine.
[3] Venlafaxine was also marginally inferior in efficacy to a newer SSRI
escitalopram (Lexapro) and had twice higher frequency of the side effects, in particular, nausea, ejaculation disorder, somnolence and sweating.
[4]
Interestingly, a popular magazine ''
Consumer Reports'', which originally rated venlafaxine as the most effective among six commonly prescribed antidepressants,
[5] no longer recommends it.
Fluoxetine,
citalopram and
bupropion have been chosen as Consumer Reports Best Buy drugs in the updated version of their guide, based upon effectiveness, safety, side effects, and cost.
[6]
Off-label / investigational uses
Many doctors are starting to prescribe venlafaxine "off label" for the treatment of
diabetic neuropathy (in a similar manner to
duloxetine) and
migraine prophylaxis (in some people, however, venlafaxine can exacerbate or cause migraines). Studies have shown venlafaxine's effectiveness for these conditions.
[7][8]
It has also been found to reduce the severity of 'hot-flashes' in
menopausal women.
[9][10]
Substantial weight loss in patients with major depression, generalized anxiety disorder, and social phobia has been noted, but the manufacturer does not recommend use as an
anorectic either alone or in combination with phentermine or other amphetamine-like drugs.
Venlafaxine hydrochloride is in the phenylthylamine class of modern chemicals, which includes amphetamine, methylendioxymethamphetamine (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 approved for the treatment of depressive phases of
bipolar disorder; this has some potential danger as venlafaxine can induce
mania,
mixed states, rapid cycling and/or
psychosis in some bipolar patients, particularly if they are not also being treated with a
mood stabilizer.
Venlafaxine is perhaps one of the most likely of all modern antidepressants to trigger manic and
hypomanic states.
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.
[11]
Contraindications
Venlafaxine is not recommended in patients
hypersensitive to venlafaxine. It should not be taken by anyone who is allergic to the inactive ingredients, which include gelatin, cellulose, ethylcellulose, iron oxide, titanium dioxide and hypromellose. It should never be used in conjunction with a
monoamine oxidase inhibitor (MAOI), due to the potential to develop a potentially deadly condition known as
serotonin syndrome. Caution should also be used in those with a seizure disorder. Venlafaxine is not approved for use in children or adolescents.
However, Wyeth does provide information on precautions if venlafaxine is prescribed to this age group for the treatment of non-approved conditions. Studies in these age groups have not established its efficacy or safety.
[12]
Liver, Kidney and Thyroid Disorders
The prescribed dosage of venlafaxine may have to be adjusted for those with liver, thyroid or kidney problems. It is crucial to inform a doctor of any such disorders before taking venlafaxine.
Glaucoma
Venlafaxine can increase eye pressure, so those with glaucoma should inform their doctors before taking venlafaxine. More frequent eye checks may be necessary.
Pregnancy, labor, and delivery
There are no adequate and well controlled studies with venlafaxine in pregnant women. Therefore, venlafaxine should only be used during pregnancy if clearly needed.
Prospective studies have not shown any statistically significant
congenital malformations.
[13] There have, however, been some reports of self-limiting effects on newborn infants.
[14] As with other Serotonin Reuptake Inhibitors, these effects are generally short, lasting only 3 to 5 days
[15] and rarely resulting in severe complications
[16]. Use of Venlafaxine in pregnancy (like other Serotonin Reuptake Inhibitors) should be considered on a case-by-case basis.
Heart Disease and Hypertension
The FDA has asked the sponsors of all SNRIs to include the potential risk for persistent
pulmonary hypertension(PPHN) in prescribing data as of
July 19,
2006. Medications containing Venlafaxine caused a mean heart rate increase of 4 b.p.m in clinical trials, along with a sustained increase in blood pressure in some.
Serotonin Syndrome
The development of a potentially life-threatening serotonin syndrome may occur with Effexor XR treatment, particularly with concomitant use of serotonergic drugs (including
SSRIs,
SNRIs, 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) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).
Adverse effects
As with most antidepressants, lack of
sexual desire is a common side effect. In trials,
delayed ejaculation and
delayed orgasm occurred in 8-16% of men. Interestingly, delayed orgasm occurred in only 2-8% of women in trials. Venlafaxine can raise blood pressure at high doses, so it is usually not the drug of choice for persons with
hypertension.
It has a higher rate of treatment emergent mania than many modern antidepressants, and many people find it to be a more activating medication (one that increases energy or wakefulness) than other antidepressants. Paradoxically, some users find it highly sedating and find that it must be taken in the evening.
There have been false positive
phencyclidine (PCP) results caused by Venlafaxine with certain on-site routine urine-based drug tests.
[1][2]. Positive on-site results should always be sent to a qualified
drug testing laboratory for confirmation ''before'' any action is taken against the employee.
Suicide Ideation/Risk
The FDA requires all antidepressants, including venlafaxine, to carry a black box with a generic warning about a possible suicide risk. In addition, the most recent research indicated that patients taking venlafaxine are at increased risk of suicide.
A study conducted in Finland followed more than 15,000 patients for 3.4 years. Venlafaxine increased suicide risk 1.6-fold (statistically significant), as compared to no treatment. At the same time,
fluoxetine (Prozac) halved the suicide risk.
[17]
In another study, the data on more than 200,000 cases was obtained from the UK general practice research database. The patients taking venlafaxine had significantly higher risk of completed suicide than the ones on
fluoxetine (Prozac) (2.8 times) or
citalopram (Celexa) (2.4 times). Even after taking into consideration the fact that venlafaxine was generally prescribed for more severe depression, venlafaxine was associated with 1.6-1.7 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 1.2-1.3 times higher risk for venlafaxine still stayed statistically significant after the adjustment.
[18]
An analysis of clinical trials by the FDA statisticians showed the incidence of suicidal behavior among the adults on venlafaxine to be not significantly different from fluoxetine or placebo.
[ Overview for December 13 Meeting of Psychopharmacologic Drugs Advisory Committee ] A possible explanation for this discrepancy is that suicidal patients are generally excluded from clinical trials, and so clinical trials are not quite representative of the real population of patients.
'Venlafaxine should not be used for the treatment of children, adolescents and young adults.' According to the FDA analysis of clinical trials
[ venlafaxine caused a 5-fold increase (statistically significant) of suicidal ideation and behavior in subjects younger than 25. In another analysis of two clinical trials, venlafaxine was no better than placebo among children (7-11 years old) and improved the depression in adolescents (12-17 years old). However, in both groups hostility and suicidal behavior were increased in comparison to the placebo treatment.[19]]
Serotonin Syndrome
Another risk is serotonin syndrome. This is a rare but serious side effect that can be caused by interactions with other central nervous system depressant drugs, and is potentially fatal.[20] This risk necessitates clear information to patients and proper medical history. For example, the drug abuse by at-risk patients of certain non-prescription drugs can cause this serious effect, and emphasizes the importance of good medical history sharing between general practitioners and psychiatrists, as both may prescribe venlafaxine. Involvement of family in awareness of risk factors is highlighted in Wyeth information sheets on Effexor.
Common side effects
NOTE: The percentage of occurrences for each side effect listed comes from clinical trial data provided by Wyeth Pharmaceuticals Inc. The percentages indicate the percentage of people that experienced the side effect in clinical trials.
★ Nausea (21-35%)
★ Headache (34%)
★ Apathy
★ Constipation
★ Ongoing Irritable Bowel Syndrome
★ Dizziness (11-20%)
★ Fatigue
★ Insomnia (15-23%)
★ Vertigo
★ Dry mouth (12-16%)
★ Sexual dysfunction (14-34%)
★ Sweating (10-14%)
★ Vivid dreams (3-7%)
★ Impulsive Actions
★ Increased blood pressure
★ Decreased Appetite (8-20%)
★ Electric shock-like sensations also called "Brain zaps"
★ Increased anxiety at the start of treatment
★ Akathisia (Agitation) (3-4%)
★ Memory Loss
Less common to rare side-effects
Note 'Rare' adverse effects occur in fewer than 1 in 1000 patients. 'Infrequent' adverse effects occur in 1 in 100 to 1 in 1000 patients.
★ Cardiac arrhythmia
★ Increased serum cholesterol
★ Gas or stomach pain
★ Abnormal vision
★ Nervousness, agitation or increased anxiety
★ Panic Attacks
★ Depressed feelings
★ Suicidal thoughts
★ Confusion
★ Neuroleptic malignant syndrome
★ Loss of appetite
★ Tremor
★ Drowsiness
★ Allergic skin reactions
★ External bleeding
★ Serious bone marrow damage (thrombocytopenia, agranulocytosis)
★ Hepatitis
★ Pancreatitis
★ Seizure
★ Tardive dyskinesia
★ Difficulty swallowing
★ Psychosis
★ Hair Loss
★ Hostility
★ Activation of mania/hypomania.
★ Weight Loss (of concern when treating patients suffering from anorexia nervosa)
★ Weight gain (effect not clear, but of concern when treating people who may have Body Dysmorphic Disorder).
★ Homicidal Thoughts
★ Aggression
★ Depersonalization
★ Visual Hallucinations
★ Swollen and/or bleeding gums
Dose dependency of adverse events
A comparison of adverse event rates in a fixed-dose study comparing venlafaxine 75, 225, and 375 mg/day with placebo revealed 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, nausea, agitation, dizziness, somnolence, tremor, yawning, sweating, and abnormal ejaculation.
Physical and Psychological Dependency
Main articles: SSRI discontinuation syndrome#Discontinuation of Venlafaxine
In vitro studies revealed that venlafaxine has virtually no affinity for opiate, benzodiazepine, phencyclidine (PCP), or N-methyl-D-aspartic acid (NMDA) receptors. It has no significant CNS stimulant activity in rodents. In primate drug discrimination studies, venlafaxine showed no significant stimulant or depressant abuse liability.
Notwithstanding these in-vitro and non-human research findings, some patients using venlafaxine may become dependent on this drug. This is especially noted if a patient misses a dose, but can also occur when reduction of dosage is done with a doctor's care. This may result in experiencing withdrawal symptoms described as severe discontinuation syndrome. The high risk of withdrawal symptoms may reflect venlafaxine's short half-life.
As the drug has direct impact on mood (''i.e.,'' anti-depressant), many users who have suffered the effects of attempted withdrawal from this drug define their dependency on the drug also as being addicted.[22] Although many other drugs can cause withdrawal symptoms which are not associated with addiction or dependence, for example, anticonvulsants, beta-blockers, nitrates, diuretics, centrally acting antihypertensives, sympathomimetics, heparin, tamoxifen, dopaminergic agents, antipsychotics, and lithium,
Dose range
Prescribed dosages are typically in the range of 75 to 225 mg per day, but higher dosages up to 450 mg are sometimes used for the treatment of severe or treatment-resistant depression. Venlafaxine is sometimes prescribed in 37.5 mg per day dosages in patients with anxiety. Low doses only work on the serotonin reuptake mechanism (presumed defective in those with anxiety) therefore avoiding the anxiety-inducing effects of norepinephrine reuptake experienced at higher doses. Because of its relatively short half-life of 5 hours, venlafaxine should be administered in divided dosages throughout the day. The extended release version (largely manufactured on spheronization equipment) eliminates this problem and has largely replaced the original in use.
''Effexor XR®'' 75 mg and 150 mg capsules
Available forms
Effexor is distributed in pentagon-shaped peach-colored tablets of 25 mg, 37.5 mg, 50 mg, 75 mg, and 100 mg. There is also an extended-release version distributed in capsules of 37.5 mg (gray/peach), 75 mg (peach), and 150 mg (brownish red).
Venlafaxine Extended Release (XR)
Venlafaxine extended release is chemically the same as normal venlafaxine. The extended release version (sometimes referred to as controlled release) controls the release of the drug into the gastrointestinal tract 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 patients suffering from nausea as a side effect resulting in a lower number of patients stopping their treatment due to nausea.[24]
Generic
Generic venlafaxine is available in the United States as of August 2006 and in Canada as of December 2006. A generic form of the extended-release version is available in Canada as of January 2007 and will become available in the United States in 2010.[5]
Overdose
Most patients overdosing with venlafaxine develop only mild symptoms. However, severe toxicity is reported with the most common symptoms being CNS depression, serotonin toxicity, seizure, or cardiac conduction abnormalities.[26] Venlafaxine's toxicity appears to be higher than other SSRIs, with a fatal toxic dose closer to that of the tricyclic antidepressants than the SSRIs. Doses of 900 mg or more are likely to cause moderate toxicity.
On May 31 2006, The Medicines and Healthcare products Regulatory Agency (MHRA) UK has concluded its review into all the latest safety evidence relating to venlafaxine particularly looked at the risks associated with overdose. The advice are, the need for specialist supervision in those severely depressed or hospitalized patients who need doses 300 mg or more; cardiac contra-indications are more targeted towards high risk groups; patients with uncontrolled hypertension should not take venlafaxine, and blood pressure monitoring is recommended for all patients; and updated advice on possible drug interactions.[29]
On October 17, 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 postmarketing 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.[30]
A report in the British Medical Journal in 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 other serotoninergic 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 literature 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 assumes that drugs are taken in overdose with similar frequency and in similar amounts. They suggested "clinicians need to consider whether factors in their patients reduce or compensate for this risk before prescribing venlafaxine."[31]
The February 27, 2007 Vancouver Sun reported that the BC Drug and Poison Information Centre has alerted doctors that the drug poses a significant risk of death from overdose, saying that venlafaxine "appears more toxic than it was originally hoped".[32] A doctor from the Department of Pharmacy Services College of Pharmacy, Medical University of South Carolina, Charleston, South Carolina, reported on the death of a 39-year-old patient with a 30 g overdose.
Management of Overdosage
There is no specific antidote for venlafaxine and management is generally supportive, providing treatment for the immediate symptoms. Administration of activated charcoal can prevent absorption of the drug. Monitoring of cardiac rhythm and vital signs is indicated. Seizures are managed with benzodiazepines or other anti-convulsants. Forced diuresis, hemodialysis, exchange transfusion, or hemoperfusion are unlikely to be of benefit in hastening the removal of venlafaxine, due to the drug's high volume of distribution.[33]
Mechanism of action
Venlafaxine is a bicyclic antidepressant, and is usually categorized as a serotonin-norepinephrine reuptake inhibitor (SNRI), but it has been referred to as a serotonin-norepinephrine-dopamine reuptake inhibitor.[34][35] It works by blocking the transporter "reuptake" proteins for key neurotransmitters affecting mood, thereby leaving more active neurotransmitters in the synapse. The neurotransmitters affected are serotonin (5-hydroxytryptamine) and norepinephrine (noradrenaline). Additionally, in high doses it weakly inhibits the reuptake of dopamine,[36] with recent evidence showing that the norepinephrine transporter also transports some dopamine as well, implying that SNRIs may also increase dopamine transmission. This is because SNRIs work by inhibiting reuptake, i.e. preventing the serotonin and norepinephrine transporters from taking their respective neurotransmitters back to their storage vesicles for later use. If the norepinephrine transporter normally recycles some dopamine too, then SNRIs will also enhance dopaminergic transmission. Therefore, the antidepressant effects associated with increasing norepinephrine levels may also be partly or largely due to the concurrent increase in dopamine (particularly in the prefrontal cortex).
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 O-desmethylvenlafaxine, which is just as potent a serotonin-norepinephrine reuptake inhibitor as the parent compound, meaning that the differences in metabolism between extensive and poor metabolizers are not clinically important. 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. 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.[37] The half-life of venlafaxine is relatively short, therefore patients are directed to adhere to a strict medication routine, avoiding missing a dose. Even a single missed dose can result in the withdrawal symptoms.[38]
Physical/Chemical Properties
The chemical structure of venlafaxine is designated (R/S)-1-[2-(dimethylamino)-1-(4 methoxyphenyl)ethyl] cyclohexanol hydrochloride or (±)-1-[a [a- (dimethylamino)methyl] p-methoxybenzyl] cyclohexanol hydrochloride and it has the empirical formula of C17H27NO2. It is a white to off-white crystalline solid. Venlafaxine is structurally and pharmacologically related to the analgesic tramadol, but not to any of the conventional antidepressant drugs, including tricyclic antidepressants, Selective serotonin reuptake inhibitors (SSRI), Monoamine oxidase inhibitors (MAOI), or reversible inhibitors of monoamine oxidase A (RIMA).[39]
Footnotes
1. Top 200 brand-name drugs by units.
2. Antidepressant efficacy of venlafaxine, Golden RN, Nicholas L, , , Depression and anxiety, 2000
3. A double-blind comparison between bupropion XL and venlafaxine XR: sexual functioning, antidepressant efficacy, and tolerability, Thase ME, Clayton AH, Haight BR, Thompson AH, Modell JG, Johnston JA, , , Journal of clinical psychopharmacology, 2006
4. A double-blind comparison of escitalopram and venlafaxine extended release in the treatment of major depressive disorder, Bielski RJ, Ventura D, Chang CC, , , The Journal of clinical psychiatry, 2004
5.
6. Consumer Reports Best Buy Drugs. Antidepressants.
7. Venlafaxine extended release in the treatment of painful diabetic neuropathy: a double-blind, placebo-controlled study, Rowbotham M, Goli V, Kunz N, Lei D, , , Pain, 2004
8. The efficacy and safety of venlafaxine in the prophylaxis of migraine, Ozyalcin S, Talu G, Kiziltan E, Yucel B, Ertas M, Disci R, , , Headache, 2005
9. Beyond hormone therapy: Other medicines may help Mayo Clinic staff
10. Venlafaxine hydrochloride for the treatment of hot flashes, Schober C, Ansani N, , , Ann Pharmacother, 2003
11. Medications
12. Selective serotonin reuptake inhibitor and venlafaxine use in children and adolescents with major depressive disorder: a systematic review of published randomized controlled trials, Courtney D, , , Can J Psychiatry, 2004
13. The safety of newer antidepressants in pregnancy and breastfeeding, Gentile S, , , Drug Saf, 2005
14. [Withdrawal symptoms in a neonate following exposure to venlafaxine during pregnancy], de Moor R, Mourad L, ter Haar J, Egberts A, , , Ned Tijdschr Geneeskd, 2003
15. [Effects of selective serotonin reuptake inhibitors and venlafaxine during pregnancy in term and preterm neonates], Ferreira E, Carceller AM, Agogué C, Martin BZ, St-André M, Francoeur D, Bérard A, , , Pediatrics, 2007
16. [Neonatal signs after late in utero exposure to serotonin reuptake inhibitors: Literature review and implications for clinical applications], Moses-Kolko EL, Bogen D, Perel J, Bregar A, Uhl K, Levin B, Wisner KL, , , JAMA, 2005
17. Antidepressants and the risk of suicide, attempted suicide, and overall mortality in a nationwide cohort, Tiihonen J, Lönnqvist J, Wahlbeck K, Klaukka T, Tanskanen A, Haukka J, , , Arch. Gen. Psychiatry, 2006
18. Risk of suicide during treatment with venlafaxine, citalopram, fluoxetine, and dothiepin: retrospective cohort study, Rubino A, Roskell N, Tennis P, Mines D, Weich S, Andrews E, , , BMJ, 2007
19. Venlafaxine ER for the treatment of pediatric subjects with depression: results of two placebo-controlled trials, Emslie GJ, Findling RL, Yeung PP, Kunz NR, Li Y, , , Journal of the American Academy of Child and Adolescent Psychiatry, 2007
20. Lithium and venlafaxine interaction: a case of serotonin syndrome, Adan-Manes J, Novalbos J, López-Rodríguez R, Ayuso-Mateos J, Abad-Santos F, , , J Clin Pharm Ther, 2006
21. Emergence of adverse events following discontinuation of treatment with extended-release venlafaxine, Fava M, Mulroy R, Alpert J, Nierenberg A, Rosenbaum J, , , Am J Psychiatry, 1997
22. Antidepressant discontinuation syndromes, Haddad P, , , Drug Saf, 2001
23. Prescribing antidepressants in general practice. People may become psychologically dependent on antidepressants, Double D, , , BMJ, 1997
24. Immediate-release versus controlled-release formulations: pharmacokinetics of newer antidepressants in relation to nausea, DeVane CL., , , J Clin Psychiatry, 2003
25.
26. Cardiovascular and neurological toxicity of venlafaxine, Blythe D, Hackett L, , , Hum Exp Toxicol, 1999
27. Fatality related to a 30-g venlafaxine overdose, Mazur J, Doty J, Krygiel A, , , Pharmacotherapy, 2003
28. Fatal venlafaxine overdose, Banham N, , , Med J Aust, 1998
29. Updated product information for venlafaxine, MHRA UK, , , Safeguarding public health, May 31 2006
30. Wyeth Letter to Health Care Providers
31. Fatal toxicity of serotoninergic and other antidepressant drugs: analysis of United Kingdom mortality data, Buckley N, McManus P, , , BMJ, 2002
32. Warning issued over drug
33. Serotonin syndrome and rhabdomyolysis in venlafaxine poisoning: a case report., Hanekamp B, Zijlstra J, Tulleken J, Ligtenberg J, van der Werf T, Hofstra L, , , Neth J Med, 2005
34. Acute Effectiveness of Additional Drugs to the Standard Treatment of Depression [No Authors listed]
35. Postmortem tissue concentrations of venlafaxine, Goeringer K, McIntyre I, Drummer O, , , Forensic Sci Int, 2001
36. Venlafaxine extended-release: a review of its use in the management of major depression., Wellington K, Perry C, , , CNS Drugs, 2001
37. Effexor Medicines Data Sheet
38. Withdrawal reactions associated with venlafaxine, Parker G, Blennerhassett J, , , Aust N Z J Psychiatry, 1998
39. Relative toxicity of venlafaxine and selective serotonin reuptake inhibitors in overdose compared to tricyclic antidepressants, Whyte I, Dawson A, Buckley N, , , QJM, 2003
External links
Drug information
★ U.S. Food and Drug Administration information on Effexor
★ Efexor patient information leaflet Efexor patient information leaflet
★ Effexor XR® prescribing information for healthcare professionals (pdf) (USA only)
★ Detailed Patient/Parent Information on Effexor
Industry pages
★ The Offical website of Effexor XR The Official website of Effexor XR
Patient experiences
★ Effexor Side Effects Patient comments.
★ Stutz, Bruce "Self-Nonmedication" New York Times Magazine May 6, 2007
Chemical data
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