Venlafaxine detailed information

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Venlafaxine detailed information
Venlafaxine-2D-skeletal.png
Venlafaxine-3D-balls.png
Clinical data
Pregnancy
category
  • C
Routes of
administration
Oral
ATC code
Legal status
Legal status
  • Rx-only, not a controlled drug
Pharmacokinetic data
Bioavailability45%
Protein binding27%
MetabolismHepatic
Elimination half-life5 ± 2 hours (parent compound); 11 ± 2 hours (active metabolite)
ExcretionRenal
Identifiers
CAS Number
PubChem CID
DrugBank
E number{{#property:P628}}
ECHA InfoCard{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
FormulaC17H27NO2
Molar mass277.402 g/mol
3D model (JSmol)

Venlafaxine (Effexor) is an antidepressant of the serotonin-norepinephrine reuptake inhibitor (SNRI) class first introduced by Wyeth in 1993. It is prescribed for the treatment of clinical depression and anxiety disorders. Due to the pronounced side effects and suspicions that venlafaxine may significantly increase the risk of suicide it is not recommended as a first line treatment of depression. However, it is often effective for depression not responding to SSRIs. Venlafaxine was the sixth most widely-used antidepressant based on the amount of retail prescriptions in the US (17.1 million) in 2006.[1]

Indications

Approved

Venlafaxine is used primarily for the treatment of depression, generalized anxiety disorder, social anxiety disorder, and panic disorder in adults.[2]

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.[3] 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.[4] 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.[5]

Interestingly, a popular magazine Consumer Reports, which originally rated venlafaxine as the most effective among six commonly prescribed antidepressants,[6] 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.[7]

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.[8][9] It has also been found to reduce the severity of 'hot-flashes' in menopausal women.[10][11]

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.[2] 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.[2] Venlafaxine is perhaps one of the most likely of all modern antidepressants to trigger manic and hypomanic states.[citation needed]

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. [12]

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.[2] 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.[13]

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.[2] Prospective studies have not shown any statistically significant congenital malformations.[14] There have, however, been some reports of self-limiting effects on newborn infants.[15] As with other Serotonin Reuptake Inhibitors, these effects are generally short, lasting only 3 to 5 days[16] and rarely resulting in severe complications[17]. 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.[citation needed] 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.[18]

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.[19]

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. [20] 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 is contraindicated to children, adolescents and young adults. According to the FDA analysis of clinical trials[20] venlafaxine caused a 5-fold increase (statistically significant) of suicidal ideation and behavior in subjects younger than 25. In another analysis, 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.[21]

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.[22] 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.

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.

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.[2]

Physical and Psychological Dependency

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.[2]

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.[23] Missing even a single dose can induce discontinuation effects in some patients.[24] Discontinuation is similar in nature to those of SSRIs such as Paroxetine (Paxil or Seroxat). Sudden discontinuation of venlafaxine has a high risk of causing potentially severe withdrawal symptoms.[25] As reported in 2001 by Haddad PM[3] in the journal Drug Safety[4], "another strategy to consider is switching to fluoxetine, which may suppress the discontinuation symptoms, but which has little tendency to cause such symptoms itself,”[5] and then discontinuing that.

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.[23] 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,[23] addiction or dependence is a more common effect described for drugs that (are thought to, or may) improve mental well-being.[26]

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.[27]

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.[28]

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.[29] 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.[30] Deaths have been reported following large doses.[31][32]

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.[33]

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.[34]

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."[35]

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".[36] 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.[31] To put this into perspective, a patient would have to take over 66 of the infrequently prescribed 450mg high dosage pills.

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.[37]

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.[38][39] 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,[40] 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.[2] 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.[24]

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).[30]

Footnotes

  1. "Top 200 brand-name drugs by units". Drug Topics, Mar 5, 2007. Retrieved 2007-04-08.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 "Effexor Medicines Data Sheet". Wyeth Pharmaceuticals Inc. 2006. Unknown parameter |accessdaymonth= ignored (help); Unknown parameter |accessyear= ignored (|access-date= suggested) (help)
  3. Golden RN, Nicholas L (2000). "Antidepressant efficacy of venlafaxine". Depression and anxiety. 12 Suppl 1: 45–9. doi:10.1002/1520-6394(2000)12:1+<45::AID-DA5>3.0.CO;2-5. PMID 11098413.
  4. Thase ME, Clayton AH, Haight BR, Thompson AH, Modell JG, Johnston JA (2006). "A double-blind comparison between bupropion XL and venlafaxine XR: sexual functioning, antidepressant efficacy, and tolerability". Journal of clinical psychopharmacology. 26 (5): 482–8. doi:10.1097/01.jcp.0000239790.83707.ab. PMID 16974189.
  5. Bielski RJ, Ventura D, Chang CC (2004). "A double-blind comparison of escitalopram and venlafaxine extended release in the treatment of major depressive disorder". The Journal of clinical psychiatry. 65 (9): 1190–6. PMID 15367045.
  6. "Mental health, readers rate antidepressant drugs", Consumer Reports, September 2004
  7. "Consumer Reports Best Buy Drugs. Antidepressants" (PDF). Consumer Reports. Retrieved 2007-06-23.
  8. Rowbotham M, Goli V, Kunz N, Lei D (2004). "Venlafaxine extended release in the treatment of painful diabetic neuropathy: a double-blind, placebo-controlled study". Pain. 110 (3): 697–706. PMID 15288411.
  9. Ozyalcin S, Talu G, Kiziltan E, Yucel B, Ertas M, Disci R (2005). "The efficacy and safety of venlafaxine in the prophylaxis of migraine". Headache. 45 (2): 144–52. PMID 15705120.
  10. Mayo Clinic staff (2005). "Beyond hormone therapy: Other medicines may help". Hot flashes: Ease the discomfort of menopause. Mayo Clinic. Unknown parameter |accessyear= ignored (|access-date= suggested) (help); Unknown parameter |accessdaymonth= ignored (help)
  11. Schober C, Ansani N (2003). "Venlafaxine hydrochloride for the treatment of hot flashes". Ann Pharmacother. 37 (11): 1703–7. PMID 14565812.
  12. "Medications". Stanford University School of Medicine, Center for Narcolepsy. Revised 02/07/2003. Retrieved 09/03/2007. Check date values in: |accessdate=, |date= (help)
  13. Courtney D (2004). "Selective serotonin reuptake inhibitor and venlafaxine use in children and adolescents with major depressive disorder: a systematic review of published randomized controlled trials". Can J Psychiatry. 49 (8): 557–63. PMID 15453105.
  14. Gentile S (2005). "The safety of newer antidepressants in pregnancy and breastfeeding". Drug Saf. 28 (2): 137–52. PMID 15691224.
  15. de Moor R, Mourad L, ter Haar J, Egberts A (2003). "[Withdrawal symptoms in a neonate following exposure to venlafaxine during pregnancy]". Ned Tijdschr Geneeskd. 147 (28): 1370–2. PMID 12892015.
  16. Ferreira E, Carceller AM, Agogué C, Martin BZ, St-André M, Francoeur D, Bérard A (2007). "[Effects of selective serotonin reuptake inhibitors and venlafaxine during pregnancy in term and preterm neonates]". Pediatrics. 119 (1): 52–9. PMID 17200271.
  17. Moses-Kolko EL, Bogen D, Perel J, Bregar A, Uhl K, Levin B, Wisner KL (2005). "[Neonatal signs after late in utero exposure to serotonin reuptake inhibitors: Literature review and implications for clinical applications]". JAMA. 293 (19): 2372–83. PMID 15900008.
  18. Tiihonen J, Lönnqvist J, Wahlbeck K, Klaukka T, Tanskanen A, Haukka J (2006). "Antidepressants and the risk of suicide, attempted suicide, and overall mortality in a nationwide cohort". Arch. Gen. Psychiatry. 63 (12): 1358–67. doi:10.1001/archpsyc.63.12.1358. PMID 17146010.
  19. Rubino A, Roskell N, Tennis P, Mines D, Weich S, Andrews E (2007). "Risk of suicide during treatment with venlafaxine, citalopram, fluoxetine, and dothiepin: retrospective cohort study". BMJ. 334 (7587): 242. doi:10.1136/bmj.39041.445104.BE. PMID 17164297.
  20. 20.0 20.1 "Overview for December 13 Meeting of Psychopharmacologic Drugs Advisory Committee" (PDF). November 16, 2006. Retrieved 2007-06-20.
  21. Emslie GJ, Findling RL, Yeung PP, Kunz NR, Li Y (2007). "Venlafaxine ER for the treatment of pediatric subjects with depression: results of two placebo-controlled trials". Journal of the American Academy of Child and Adolescent Psychiatry. 46 (4): 479–88. doi:10.1097/chi.0b013e31802f5f03. PMID 17420682.
  22. Adan-Manes J, Novalbos J, López-Rodríguez R, Ayuso-Mateos J, Abad-Santos F (2006). "Lithium and venlafaxine interaction: a case of serotonin syndrome". J Clin Pharm Ther. 31 (4): 397–400. PMID 16882112.
  23. 23.0 23.1 23.2 Haddad P (2001). "Antidepressant discontinuation syndromes". Drug Saf. 24 (3): 183–97. PMID 11347722.
  24. 24.0 24.1 Parker G, Blennerhassett J (1998). "Withdrawal reactions associated with venlafaxine". Aust N Z J Psychiatry. 32 (2): 291–4. PMID 9588310.
  25. Fava M, Mulroy R, Alpert J, Nierenberg A, Rosenbaum J (1997). "Emergence of adverse events following discontinuation of treatment with extended-release venlafaxine". Am J Psychiatry. 154 (12): 1760–2. PMID 9396960.
  26. Double D (1997). "Prescribing antidepressants in general practice. People may become psychologically dependent on antidepressants". BMJ. 314 (7083): 829. PMID 9081020.
  27. DeVane CL. (2003). "Immediate-release versus controlled-release formulations: pharmacokinetics of newer antidepressants in relation to nausea". J Clin Psychiatry. 64 (Suppl 18): 14–9. PMID 14700450.
  28. Wigginton, Catherine (2006-09-19), Wyeth's Battle for Effexor Continues, IP Law & Business, retrieved 2007-04-25 Check date values in: |date= (help)
  29. Blythe D, Hackett L (1999). "Cardiovascular and neurological toxicity of venlafaxine". Hum Exp Toxicol. 18 (5): 309–13. PMID 10372752.
  30. 30.0 30.1 Whyte I, Dawson A, Buckley N (2003). "Relative toxicity of venlafaxine and selective serotonin reuptake inhibitors in overdose compared to tricyclic antidepressants". QJM. 96 (5): 369–74. PMID 12702786.
  31. 31.0 31.1 Mazur J, Doty J, Krygiel A (2003). "Fatality related to a 30-g venlafaxine overdose". Pharmacotherapy. 23 (12): 1668–72. PMID 14695048.
  32. Banham N (1998). "Fatal venlafaxine overdose". Med J Aust. 169 (8): 445, 448. PMID 9830400.
  33. MHRA UK (May 31 2006). "Updated product information for venlafaxine". Safeguarding public health. Check date values in: |year= (help)
  34. "Wyeth Letter to Health Care Providers" (PDF). Wyeth Pharmaceuticals Inc. 2006. Unknown parameter |accessdaymonth= ignored (help); Unknown parameter |accessyear= ignored (|access-date= suggested) (help)
  35. Buckley N, McManus P (2002). "Fatal toxicity of serotoninergic and other antidepressant drugs: analysis of United Kingdom mortality data". BMJ. 325 (7376): 1332–3. PMID 12468481.
  36. Fayerman, Pamela (February 27 2007). "Warning issued over drug". Vancouver Sun. Retrieved 2007-06-02. Check date values in: |date= (help)
  37. Hanekamp B, Zijlstra J, Tulleken J, Ligtenberg J, van der Werf T, Hofstra L (2005). "Serotonin syndrome and rhabdomyolysis in venlafaxine poisoning: a case report". Neth J Med. 63 (8): 316–8. PMID 16186642.
  38. [No Authors listed]. "Acute Effectiveness of Additional Drugs to the Standard Treatment of Depression". ClinicalTrials.gov. Unknown parameter |accessdaymonth= ignored (help); Unknown parameter |accessyear= ignored (|access-date= suggested) (help)
  39. Goeringer K, McIntyre I, Drummer O (2001). "Postmortem tissue concentrations of venlafaxine". Forensic Sci Int. 121 (1–2): 70–5. PMID 11516890.
  40. Wellington K, Perry C (2001). "Venlafaxine extended-release: a review of its use in the management of major depression". CNS Drugs. 15 (8): 643–69. PMID 11524036.

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