Psych Drug Truth	Common Effexor Side Effects	Effexor is an addictive drug and should not be reduced quickly.
Effexor	Anxiety - Insomnia - Agitation - Fatigue - Weight Gain	Effexor Withdrawal

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Effexor withdrawal. Effexor withdrawal side effects, withdrawal warnings, withdrawal precautions, withdrawal adverse effects, overdose, withdrawal symptoms and Effexor natural alternatives. Before you begin the spiral down with Effexor, try giving your body what it really wants.

Effexor

Effexor Withdrawal Side Effects

This site gives basic information about Effexor and other psychoactive medication.

Are you experiencing Effexor withdrawal?

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Effexor Side Effects and withdrawal side effects

Effexor withdrawal - Anorexia – No longer having a desire to eat.

Effexor withdrawal - Apothous Stomatitis – Painful red and swollen open sores on a mucus membrane of the mouth commonly called a canker sore.

Effexor withdrawal - Ataxia – Loss of the ability to move the body with coordination.

Effexor withdrawal - Arterial Fibrillation – A condition of abnormal twitching of the muscles in the blood vessels that moves the oxygenated blood from the heart to the rest of the body. The unusual twitching is rapid and irregular and replaces the normal rhythm of contraction of the muscle, which sometimes causes a lack of circulation and pulse.

Effexor withdrawal - Blood Cholesterol Increased – An abnormal condition where there is a greater amount in the blood of the oily/fatty substances known as cholesterol. Cholesterol is a necessary part of living cells (along with proteins and carbohydrates). Because cholesterol only slightly dissolves in water, it can build up on the walls of the blood vessels, therefore blocking/decreasing the amount of blood flow, which causes blood pressure to go up. If not corrected, this condition is associated with coronary artery disease.

Effexor withdrawal - Blood Creatinine Increased – A greater than normal number of creatinine or muscular chemical waste molecules in the blood. Creatinine plays a major role in energy production in muscles. Since creatinine levels are normally maintained by the kidneys, Blood Creatinine Increased is an indicator of kidney malfunction or failure.

Effexor withdrawal - Blood in Stool – The blood that is in your bowel movement usually comes from any place along your digestive tract (from your mouth to your anus). The stool can appear black and foul-smelling (usually from the upper part of your digestive tract) or red or maroon-colored (usually from the large intestine area). Hemorrhoids are the usual cause for blood in the bowels.

8. Effexor withdrawal - Bundle Branch Block Right – These are specialized cells in the upper right heart chamber and are the heart’s pacemaker. They send electrical signals to the heart that keeps it beating or contracting regularly. Normally the signal goes to the lower heart chambers at the same time through the bundle of His (hiss) on both the left and right sides of the heart, so the lower chambers contract at the same time. When the bundle is damaged on the right side, the signal does not fire at the same time as the left, which changes the pace of blood flow. This can lead to a person fainting.

Effexor withdrawal - Cardiac Failure – A heart disorder where the heart does not function as usual and may completely stop working.

Effexor withdrawal - Cardiac Failure Congestive – The body is asking for the heart to supply more blood than it is capable of producing and maintaining. Normally, a body can tolerate an increased amount of work for quite some time. The condition is characterized by weakness, shortness of breath, and a fluid build-up in the body tissues causing swelling.

Effexor withdrawal - Cold Sweat – The skin is clammy and moist and you feel chilled. This is a reaction to a shock or pain as well as to fear and nervousness.

Effexor withdrawal - Colitis – A condition where the large intestine becomes irritated from the use of the drug.

Effexor withdrawal - Coronary Artery Disease – A condition where the blood vessels that mainly carry the blood away from the heart become clogged up or narrowed usually by fatty deposits. The first symptom is pain spreading from the upper left body caused by not enough oxygen reaching the heart.

Effexor withdrawal - Dehydration – An extreme loss of water from the body or the organs of the body as in sickness or not drinking enough fluids.

Effexor withdrawal - Diplopia – The condition where a person is looking a one object and instead of normally seeing just the one object he sees two. This is also call double vision.

Effexor withdrawal - Diverticulitis – There are pouches or sacs on the inside of the intestines that look like fingers. This increases the area for the body to absorb nutrients as they pass through the intestines. These sacs become irritated and swollen and end up trapping waste that would normally be eliminated, causing pain and constipation.

Effexor withdrawal - Dysarthria – The inability to control the mouth muscles when forming words so the words are not clearly spoken and heard.

Effexor withdrawal - Dyslipidemia – The normal fat metabolism in the blood is interfered with.

Effexor withdrawal - Dysphagia – Trouble swallowing or the inability to swallow.

Effexor withdrawal - Ecchymosis – When a blood vessel breaks and creates a purple discoloration of the skin.

Effexor withdrawal - Edema – An abnormal build up of excess fluids in the cells, tissues, and the spaces between the tissues creating swelling.

Effexor withdrawal - Edema Peripheral – The abnormal build up of fluids in the tissues of the ankles and legs causing painless swelling in the legs, ankles, and feet. If you squeeze the swollen area it leaves an indentation on the skin for a few minutes.

Effexor withdrawal - Ejaculation Delayed – The man is not able to release sperm either during sexual intercourse or with manual stimulation in the presence of his sexual partner in spite of his wish to do so.

Effexor withdrawal - Ejaculation Dysfunction – A condition where the man has one or more of the following symptoms: He is not able to have an erection, not able to have an orgasm, has a decreased interest in sex, is sexually inhibited, or it is painful to ejaculate sperm.

Effexor withdrawal - Erectile Dysfunction – Incapable of having sexual intercourse. Even though a man desires sex he is inhibited in his sexual activity and is unable to have or maintain an erection of the penis.

Effexor withdrawal - Erythema – a skin redness caused by the swelling with blood of the tiny blood vessels of the skin as in burns.

Effexor withdrawal - Erythematous Rash – Redness of the skin from the swelling of the tiny blood vessels with skin irritation (itching, burning, tingling, pain) and breakouts (eruptions).

Effexor withdrawal - Esophageal Stenosis Acquired – The tube that moves food from the mouth to the stomach narrows.

Effexor withdrawal - Exfoliative Dermatitis – The unusual and not normal condition of scaling and shedding of the skin cells. The skin is usually red colored.

Effexor withdrawal - Face Edema – The tissues of the face become swollen.

Effexor withdrawal - Feeling Jittery – A physical sensation of nervous unease.

Effexor withdrawal - Gastric Irritation – An inflamed and sore stomach.

Effexor withdrawal - Gastric Ulcer – An open, irritated, and infected sore in the wall of the stomach.

Effexor withdrawal - Gingivitis – Sore, swollen and red gums in the mouth that bleed easily.

Effexor withdrawal - Glaucoma – The delicate nerve to the eye, the optic nerve, becomes easily damaged with the build-up of excess fluid pressure within the eyeball. The first sign of glaucoma is loss of peripheral (side) vision. It can progress to total blindness.

Effexor withdrawal - Hepatic Steatosis – Excessive amounts of fat in the liver.

Effexor withdrawal - Hyperhidrosis – The triggering of an excess of sweat being produced on the soles of the feet, the palms, or the underarms which can cause embarrassment or losing grip on a pen or other items.

Effexor withdrawal - Hyperkeratosis – An abnormal enlargement of the skin tissues causing the skin cells to increase in size.

Effexor withdrawal - Hyperlipidemia – An abnormally high number of fat cells in the blood.

Effexor withdrawal - Hypertriglyceridemia – Too many triglycerides in the blood.

Triglycerides are three fatty acids bound together in one molecule stored by the body and available to create high levels of energy when used.

Effexor withdrawal - Hypoesthesia – A partial loss of sensation or general loss of awareness.

Effexor withdrawal - Impaired Gastric Emptying – The contents of the stomach are not passed into the intestines as normal due to the stomach losing the muscular strength to do so.

Effexor withdrawal - Increased White Blood cell Count – This is an increase in the number of cells in the blood that are responsible for the removal of bacteria and other unwanted particles. They fight disease and infection by enclosing foreign particles and removing them. An example of a disease that would increase white blood cell count would be Leukemia.

Effexor withdrawal - Insomnia – Not able to fall asleep or sleeping for a shorter time than desired, thus not being able to properly rest and feeling un-refreshed. As a result, a person can become irritable, have difficulty concentrating and feel a lack of energy. This can be caused by stimulants such as by caffeine or drugs or by mental anxiety and stress. Mental stress can be communicated and relieved.

Effexor withdrawal - Irritable Bowel Syndrome – A painful condition where the either the muscles or the nerves of the lower intestines, are not responding normally. This results in an alternating condition of diarrhea followed by constipation, back and forth.

Effexor withdrawal - Keratoconjunctivitis Sicca – A condition where the outer coating of the eyeball is dry because of a decrease in the normal amount of tears in the eye. As a result, the eyeball and inside of the eyelid thickens and hardens sometimes causing the vision to be less sharp.

Effexor withdrawal - Leukopenia – An unnaturally low number of white blood cells circulating in the blood.

Effexor withdrawal - Loose Stools – The bowel movement is runny instead of formed.

Effexor withdrawal - Lower Abdominal Pain – A hurtful irritation of the nerve endings in the area of the hipbones housing the lower digestive tract. Pain usually means tissue damage.

Effexor withdrawal - Lymphadenopathy – The lymph nodes, where the immune cells are located, become larger than is normal because of a high concentration of white blood cells.

Effexor withdrawal - Macular Degeneration – The gradual loss of central vision, which is the sharpest vision while peripheral eyesight, is unaffected.

Effexor withdrawal - Maculopathy – An abnormal condition of the yellow spot of the eye, which is located in the center of the inner lining of the eyeball and connected to the main nerve to the eye and is responsible for sharp vision.

Effexor withdrawal - Mania – Unusually irrational, excessive and/or exaggerated behavior or moods ranging from enthusiasm, sexuality, gaiety, impulsiveness and irritability to violence.

Effexor withdrawal - Melena – Abnormally darkly colored stools as a result of hemorrhaging in the digestive tract where the blood has interacted with the digestive juices creating the dark color in the bowel movement.

Effexor withdrawal - Micturition Urgency – A sudden desire to urinate usually followed by leakage.

Effexor withdrawal - Mood Swings – An emotional shifting as from a state of happiness to a state of depression for a period of time.

Effexor withdrawal - Myocardial Infarction – The blood going to the heart is delayed or stopped causing middle muscle tissue in the heart wall to die.

Effexor withdrawal - Nasopharyngitis – Irritation, redness and swelling tissues in the nose and the tube leading from the mouth to the voice box as well as the tubes leading to the ears.

Effexor withdrawal - Nephropathy – An abnormally functioning or diseased kidney.

Effexor withdrawal - Nervousness – Jumpy, jittery, anxious, and troubled with an irritable temperament.

Effexor withdrawal - Night Sweats – The water-salt, waste product the skin releases is called sweat or perspiration. With night sweats you become wide awake in the middle of the night shivering and cold and wet with your sheets/pajamas soaked in perspiration making it difficult to go back to sleep.

Effexor withdrawal - Nightmare – Dreams that make you afraid or leave feelings of fear, terror, and upset long after waking up.

Effexor withdrawal - Orgasm Abnormal – Unable to have an orgasm with normal sexual stimulation.

Effexor withdrawal - Oropharyngeal Swelling – A swelling in the area from the soft part of the roof of the mouth to the back of the mouth.

Effexor withdrawal - Pain in Extremity – A painful feeling in the legs, arms, hands, and feet.

Effexor withdrawal - Pharyngolaryngeal Pain – Pain in the area of the respiratory tract (organs of breathing) from the throat to the voice box and above the windpipe.

Effexor withdrawal - Photopsia – A condition where a person see lights, sparks or colors in front of your eyes.

Effexor withdrawal - Photosensitivity Reaction – An exaggerated sunburn reaction that is not normal in proportion to the amount of exposure to the light.

Effexor withdrawal - Pollakiuria – Urinating much more frequently than normal – as often as once every five to fifteen minutes.

Effexor withdrawal - Pressure of Speech – A condition where the individual cannot voice his ideas fast enough with the pressure of there being not enough time to say it.

Effexor withdrawal - Pruritic Rash – Extremely itchy, red, swollen bumps on the skin.

Effexor withdrawal - Pyrexia – Fever or the increase in body temperature that is usually a sign of infection.

Effexor withdrawal - Retinal Detachment – The thin layer lining the back of the eyeball (the retina) detaches from the back of the eyeball. This thin layer is like the film of a camera because it sends the images a person views to the brain. When it detaches it causes a reduced ability to see.

Effexor withdrawal - Rigors – Shivering or shaking of the body as if chilled, preventing normal responses.

Effexor withdrawal - Skin Ulcer – An open sore or infected skin eruption with swelling, redness, pus, and irritation.

Effexor withdrawal - Sleep Disorder – These are a list of sleep disorders such as teeth grinding, insomnia, jet lag, sleep walking, abnormally falling asleep during the middle of a conversation after a full night’s rest, uncontrolled body motions keeping one awake, etc.
Effexor withdrawal - Suicide, Completed – An attempted attack on oneself that is life threatening results in death.

Effexor withdrawal - Upper Respiratory Tract Infection – Where the organs of breathing near the mouth such as the nose and sinuses, become infected and are usually treated by antibiotics.

Effexor withdrawal - Urinary Hesitation – Hard to start or hard to continue emptying one’s bladder.

Effexor withdrawal - Urinary Incontinence – Urinating without intending to do so because of a weakening of the muscles in the hip area from the drug affecting the nerves or the drug blocking a persons thinking process.

Effexor withdrawal - Urinary Retention – The inability to completely empty the bladder despite having the urge to do so. This can lead to infections or damage to the urinary organs.

Effexor withdrawal - Urine Flow Decreased – Dehydration of the body causing a lesser flow of urine than normal with the body reabsorbing the waste.

Effexor withdrawal - Urine Output Decreased – A condition where the output of urine produced in a 24-hour period is less than 500 ml.

Effexor withdrawal - Weight Decreased – Unintentional weight loss.
Effexor withdrawal – Weight Increased – An unusual, usually rapid weight increase.

Effexor Clinical Trials

Duloxetine: a review of its use in the treatment of generalized anxiety disorder.

Carter NJ, McCormack PL.

CNS Drugs. 2009;23(6):523-41. doi: 10.2165/00023210-200923060-00006.

PMID: 19480470 [Effexor - in process]

[Horner's syndrome unmasked by venlafaxine]

Mingo-Botín D, Ancochea G, Muñoz-Negrete FJ, Rebolleda-Fernández G.

Rev Neurol. 2009 Jun 1-15;48(11):612-3. Spanish. No abstract available.

PMID: 19472162 [Effexor - in process]

Impaired detrusor contractility due to venlafaxine use.

Torgovnick J, Sethi NK, Sethi PK, Arsura E.

Indian J Urol. 2008 Oct;24(4):581-2. No abstract available.

PMID: 19468526 [Effexor - in process]

Venlafaxine treatment stimulates expression of BDNF protein in frontal cortex and inhibits LTP in hippocampus.

Cooke JD, Grover LM, Spangler PR.

Neuroscience. 2009 May 20. [Epub ahead of print]

PMID: 19464349 [Effexor - as supplied by publisher]

Maternal use of venlafaxine near term: correlation between neonatal effects and plasma concentrations.

Boucher N, Koren G, Beaulac-Baillargeon L.

Ther Drug Monit. 2009 Jun;31(3):404-9.

PMID: 19455083 [Effexor - in process]

Mirtazapine: a review of its use in major depression and other psychiatric disorders.

Croom KF, Perry CM, Plosker GL.

CNS Drugs. 2009;23(5):427-52. doi: 10.2165/00023210-200923050-00006.

PMID: 19453203 [Effexor - in process]

Placental transfer of SSRI and SNRI antidepressants and effects on the neonate.

Rampono J, Simmer K, Ilett KF, Hackett LP, Doherty DA, Elliot R, Kok CH, Coenen A, Forman T.

Pharmacopsychiatry. 2009 May;42(3):95-100. Epub 2009 May 18.

PMID: 19452377 [Effexor - in process]

Predictors of nonresponse to cognitive behavioural therapy or venlafaxine using glucose metabolism in major depressive disorder.

Konarski JZ, Kennedy SH, Segal ZV, Lau MA, Bieling PJ, McIntyre RS, Mayberg HS.

J Psychiatry Neurosci. 2009 May;34(3):175-80.

PMID: 19448846 [Effexor - in process]

Depression in children and adolescents.

Hazell P.

Clin Evid (Online). 2009 Jan 7;2009. pii: 1008.

PMID: 19445770 [Effexor - in process]

10:

Fabrication of Triple-Layer Matrix Tablets of Venlafaxine Hydrochloride Using Xanthan Gum.

Gohel MC, Bariya SH.

AAPS PharmSciTech. 2009 May 15. [Epub ahead of print]

PMID: 19444618 [Effexor - as supplied by publisher]

11:

[Venlafaxine-induced cholestatic hepatitis.]

Collados Arroyo V, Hallal H, Rodrigo Agudo JL, Plaza Aniorte J.

Gastroenterol Hepatol. 2009 May;32(5):382-383. Epub 2009 May 13. Spanish. No abstract available.

PMID: 19442411 [Effexor - as supplied by publisher]

12:

Melatonin receptor agonist agomelatine: a new drug for treating unipolar depression.

Bourin M, Prica C.

Curr Pharm Des. 2009;15(14):1675-82.

PMID: 19442180 [Effexor - in process]

13:

Treatment-emergent sexual dysfunction related to antidepressants: a meta-analysis.

Serretti A, Chiesa A.

J Clin Psychopharmacol. 2009 Jun;29(3):259-66.

PMID: 19440080 [Effexor - in process]

14:

Effect of Date of Drug Marketing on Disproportionality Measures in Pharmacovigilance: The Example of Suicide with SSRIs Using Data From the UK MHRA.

Pariente A, Daveluy A, Laribière-Bénard A, Miremont-Salame G, Begaud B, Moore N.

Drug Saf. 2009;32(5):441-7. doi: 10.2165/00002018-200932050-00007.

PMID: 19419238 [Effexor - in process]

15:

Nontricyclic antidepressants for neuropathic pain #187.

Hawley P.

J Palliat Med. 2009 May;12(5):476-7.

PMID: 19416046 [Effexor - in process]

16:

Sociodemographic correlates of antidepressant utilisation in Australia.

Page AN, Swannell S, Martin G, Hollingworth S, Hickie IB, Hall WD.

Med J Aust. 2009 May 4;190(9):479-83.

PMID: 19413517 [Effexor - in process]

17:

Antidepressant switching among adherent patients treated for depression.

Marcus SC, Hassan M, Olfson M.

Psychiatr Serv. 2009 May;60(5):617-23.

PMID: 19411348 [Effexor - in process]

18:

Aripiprazole augmentation in major depressive disorder: a double-blind, placebo-controlled study in patients with inadequate response to antidepressants.

Berman RM, Fava M, Thase ME, Trivedi MH, Swanink R, McQuade RD, Carson WH, Adson D, Taylor L, Hazel J, Marcus RN.

CNS Spectr. 2009 Apr;14(4):197-206.

PMID: 19407731 [Effexor - in process]

19:

Antidepressants at Environmentally Relevant Concentrations Affect Predator Avoidance Behavior of Larval Fathead Minnows (Pimephales promelas).

Painter MM, Buerkley MA, Julius ML, Vajda AM, Norris DO, Barber LB, Furlong ET, Schultz MM, Schoenfuss HL.

Environ Toxicol Chem. 2009 Apr 30:1. [Epub ahead of print]

PMID: 19405782 [Effexor - as supplied by publisher]

20:

Venlafaxine-induced complex visual hallucinations in a 17-year-old boy.

Jacob MK, Ash P.

J Clin Psychiatry. 2009 Apr;70(4):601-3. No abstract available.

PMID: 19403099 [Effexor - in process]

21:

[Severe forms of depression: The efficacy of escitalopram.]

Spadone C.

Encephale. 2009 Apr;35(2):152-9. Epub 2009 Mar 31. French.

PMID: 19393384 [Effexor - in process]

22:

Rapid and reliable genotyping procedure for detection of alleles with mutations, deletion, or/and duplication of the CYP2D6 gene.

Arneth B, Shams M, Hiemke C, Härtter S.

Clin Biochem. 2009 Apr 22. [Epub ahead of print]

PMID: 19393232 [Effexor - as supplied by publisher]

23:

In vitro and in vivo reproduction toxicology of 12 monoaminergic reuptake inhibitors: Possible mechanisms of infrequent cardiovascular anomalies.

Sloot WN, Bowden HC, Yih TD.

Reprod Toxicol. 2009 Apr 19. [Epub ahead of print]

PMID: 19383541 [Effexor - as supplied by publisher]

24:

Dose-finding study of fluoxetine and venlafaxine for the treatment of self-injurious and stereotypic behavior in rhesus macaques (Macaca mulatta).

Fontenot MB, Musso MW, McFatter RM, Anderson GM.

J Am Assoc Lab Anim Sci. 2009 Mar;48(2):176-84.

PMID: 19383215 [Effexor - indexed for MEDLINE]

25:

Acute tamoxifen-induced depression and its prevention with venlafaxine.

Bourque F, Karama S, Looper K, Cohen V.

Psychosomatics. 2009 Mar-Apr;50(2):162-5.

PMID: 19377026 [Effexor - in process]

26:

Postpartum depression co-occurring with lactation-related osteoporosis.

Ozcelik B, Ozcelik A, Debre M.

Psychosomatics. 2009 Mar-Apr;50(2):155-8.

PMID: 19377024 [Effexor - in process]

27:

Insomnia in patients with depression: some pathophysiological and treatment considerations.

Jindal RD.

CNS Drugs. 2009;23(4):309-29. doi: 10.2165/00023210-200923040-00004.

PMID: 19374460 [Effexor - in process]

28:

Escitalopram versus other antidepressive agents for depression.

Cipriani A, Santilli C, Furukawa TA, Signoretti A, Nakagawa A, McGuire H, Churchill R, Barbui C.

Cochrane Database Syst Rev. 2009 Apr 15;(2):CD006532.

PMID: 19370639 [Effexor - in process]

29:

Improvement of cognition in a patient with Cotard's delusions and frontotemporal atrophy receiving electroconvulsive therapy (ECT) for depression.

Fàzzari G, Benzoni O, Sangaletti A, Bonera F, Nassini S, Mazzarini L, Pacchiarotti I, Sani G, Koukopoulos AE, Sanna L, Gasparotti R, De Rossi P, Lazanio S, Savoja V, Girardi P.

Int Psychogeriatr. 2009 Jun;21(3):600-3. Epub 2009 Apr 16.

PMID: 19368757 [Effexor - in process]

30:

Treatment with venlafaxine in six cases of children with narcolepsy and with cataplexy and hypnagogic hallucinations.

Møller LR, Østergaard JR.

J Child Adolesc Psychopharmacol. 2009 Apr;19(2):197-201.

PMID: 19364297 [Effexor - in process]

31:

A double-blind, placebo-controlled, parallel-group, flexible-dose study of venlafaxine extended release capsules in adult outpatients with panic disorder.

Liebowitz MR, Asnis G, Mangano R, Tzanis E.

J Clin Psychiatry. 2009 Apr;70(4):550-61. Epub 2009 Apr 7.

PMID: 19358784 [Effexor - in process]

32:

Chronic post-surgical pain.

Akkaya T, Ozkan D.

Agri. 2009 Jan;21(1):1-9. Review.

PMID: 19357994 [Effexor - indexed for MEDLINE]

33:

Desvenlafaxine: a new antidepressant or just another one?

Pae CU.

Expert Opin Pharmacother. 2009 Apr;10(5):875-87.

PMID: 19351235 [Effexor - in process]

34:

Comparison of the antidepressant effects of venlafaxine and dosulepin in a naturalistic setting.

Bukh JD, Jørgensen MB, Dam H, Plenge P.

Nord J Psychiatry. 2009 Apr 6:1-5. [Epub ahead of print]

PMID: 19347769 [Effexor - as supplied by publisher]

35:

Teenaged, depressed, and treatment resistant: what predicts self-harm?

Weissman MM.

Am J Psychiatry. 2009 Apr;166(4):385-7. No abstract available.

PMID: 19339360 [Effexor - indexed for MEDLINE]

36:

Duloxetine in the treatment of generalized anxiety disorder.

Norman TR, Olver JS.

Neuropsychiatr Dis Treat. 2008 Dec;4(6):1169-80.

PMID: 19337457 [Effexor - in process]

Pharmacology

Antidepressant

Effexor is a phenethylamine bicyclic derivative, chemically unrelated to tricyclic, tetracyclic or other available antidepressant agents.

The mechanism of Effexor antidepressant action in humans is believed to be associated with its potentiation of neurotransmitter activity in the CNS. Preclinical studies have shown that venlafaxine and its major metabolite, O-desmethylvenlafaxine (ODV), are potent inhibitors of neuronal serotonin and norepinephrine reuptake and weak inhibitors of dopamine reuptake.

Effexor and ODV have no significant affinity for muscarinic, histaminergic, or alpha1-adrenergic receptors in vitro. Pharmacologic activity at these receptors is hypothesized to be associated with the various anticholinergic, sedative, and cardiovascular effects seen with other psychotropic drugs. Venlafaxine and ODV do not possess monoamine oxidase (MAO) inhibitory activity.

Pharmacokinetics:
Effexor is well absorbed, with peak plasma concentrations occurring approximately 2 hours after dosing. Effexor is extensively metabolized, with O-desmethylvenlafaxine, (ODV, the only major active metabolite) peak plasma levels occurring approximately 4 hours after dosing. Following single doses of 25 to 75 mg, mean (+/- SD) peak plasma concentrations of venlafaxine range from 34+/-14 to 96+/-43 ng/mL, respectively, and are reached in 2+/-1 hours, and mean peak ODV plasma concentrations range from 58+/-18 to 178+/-40 ng/mL and are reached in 4+/-2 hours. Approximately 87% of a single dose of venlafaxine is recovered in the urine within 48 hours as either unchanged venlafaxine (5%), unconjugated ODV (30%), conjugated ODV (26%), or other minor metabolites (27%).

Multiple-Dose Pharmacokinetic Profile:
Steady-state concentrations of both venlafaxine and ODV in plasma were attained after approximately 3 days of multiple dose therapy. The clearance of Effexor is slightly (15%) lower following multiple doses than following a single dose.

Effexor and ODV exhibited linear kinetics over the dose range of 75 to 450 mg total daily dose administered t.i.d.

The mean +/- SD steady-state plasma clearances of venlafaxine and ODV are 1.3+/-0.6 and 0.4+/-0.2 L/h/kg, respectively; elimination half-life is 5+/-2 and 11+/-2 hours, respectively.

Effexor and ODV renal clearances are 49+/-27 and 94+/-56 mL/h/kg, respectively, which correspond to 5+/-3.0% and 25+/-13% of an administered venlafaxine dose recovered in urine as venlafaxine and ODV, respectively. Similar steady-state volumes of distribution are exhibited for venlafaxine (7+/-4 L/kg) and ODV (6+/-2 L/kg).

Effexor and ODV are less than 35% bound to plasma proteins. Therefore, protein-binding-induced drug interactions with Effexor are not expected.

Food has no significant effect on the absorption of venlafaxine.

When equal daily doses of venlafaxine were administered either b.i.d. or t.i.d., drug exposure (AUC) and fluctuation in plasma levels were comparable.

Age and Gender:
Age and sex do not significantly affect the pharmacokinetics of Effexor. A 20% reduction in clearance was noted for ODV in subjects over 60 years old; this was possibly caused by the decrease in renal function that typically occurs with aging. Dosage adjustment based upon age or gender is generally not necessary (See Dosage).

Hepatic Disease:
In 9 patients with hepatic cirrhosis, the pharmacokinetic disposition of both venlafaxine and ODV were significantly altered. Venlafaxine elimination half-life was prolonged by about 30%, and clearance was decreased by about 50%. ODV elimination half-life was also prolonged (by about 60%) and its clearance decreased by about 30%. Three patients with more severe cirrhosis had a 90% decrease in venlafaxine clearance. Dosage adjustment is necessary in patients with liver disease (See Dosage).

Renal Disease:
In patients with moderate to severe impairment of renal function (GFR=10-70 mL/min), Effexor elimination half-life was prolonged by 50%, and clearance was deceased by about 24%. ODV elimination half-life was prolonged by about 40%, but clearance was unchanged. In dialysis patients, venlafaxine elimination half-life was prolonged by about 180% and clearance was decreased by about 56%. Dosage adjustment is necessary in patients with renal disease (See Dosage).

Indications

For the symptomatic relief of depressive illness.

The effectiveness of venlafaxine in long-term use (i.e., for more than 4 to 6 weeks) has not been systematically evaluated in controlled trials. Therefore, the physician who elects to use venlafaxine for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient.

Contraindications

Patients with known hypersensitivity to Effexor or to any of the components of the formulation.

MAO Inhibitors:
There have been reports of serious, sometimes fatal reactions in patients receiving antidepressants with pharmacological properties similar to those of venlafaxine in combination with a MAO inhibitor. Therefore, venlafaxine should not be used in combination with MAO inhibitors or within two weeks of terminating treatment with MAO inhibitor's. Treatment with MAO inhibitors should not be started until two weeks after discontinuation of Effexor therapy.

Warnings

Sustained Hypertension:
Treatment with Effexor was associated with modest but sustained increases in blood pressure during premarketing studies. Sustained hypertension, defined as treatment-emergent supine diastolic blood pressure (SDBP) >= 90 mm Hg and 10 mm Hg above baseline for 3 consecutive visits, showed the following incidence and dose-relationship in Table I.

-----------------------------------------------
Table I
Probability of Sustained Elevation in SDBP
(Pool of Premarketing Studies with Effexor)
-----------------------------------------------
Treatment Group     Incidence of Sustained
                      Elevation in SDBP
-----------------------------------------------
Venlafaxine
      <100 mg/day                3%
   101-200 mg/day             5%
   201-300 mg/day             7%
      >300 mg/day              13%
        Placebo                      2%
-----------------------------------------------

An analysis of the blood pressure increases in patients with sustained hypertension and in the 19 patients who were discontinued from treatment because of hypertension (<1% of total venlafaxine-treated group) showed that most of the blood pressure increases were in the range of 10 to 15 mm Hg, SDBP. Since in individual patients sustained increases of this magnitude could have adverse consequences, it is recommended that patients receiving venlafaxine have their blood pressure monitored regularly.

For patients who experience a sustained increase in blood pressure during treatment with venlafaxine, either a dose reduction or discontinuation of venlafaxine should be considered.

Precautions

General:
Suicide:
The possibility of a suicide attempt in seriously depressed patients is inherent to the illness and may persist until significant remission occurs. Close supervision of high-risk patients should accompany initial drug therapy, and consideration should be given to the need for hospitalization. In order to reduce the risk of overdose, prescriptions for venlafaxine should be written for the smallest quantity of tablets consistent with good patient management.

Seizures:
During premarketing testing, seizures were reported in 8 out of 3082 venlafaxine-treated patients (0.26%). In 5 of the 8 cases, patents were receiving doses of 150 mg/day or less. However, patients with a history of convulsive disorders were excluded from most of these studies. venlafaxine should be used cautiously in patents with a history of seizures, and should be promptly discontinued in any patient who develops seizures.

Activation of Mania/Hypomania:
During Phase II and III trials, mania or hypomania occurred in 0.5% of venlafaxine-treated patients. Activation of mania/hypomania has also been reported in a small proportion of patients with major affective disorder who were treated with other marketed antidepressants. As with all antidepressants, venlafaxine should be used cautiously in patients with a history of mania.

Patients with Concomitant Illness:
Clinical experience with venlafaxine in patients with concomitant systemic illness is limited. Caution is advised in administering venlafaxine to patients with diseases or conditions that could affect hemodynamic responses or metabolism. Patients should be questioned about any prescripton or "over the counter drugs" that they are taking, or planning to take, since there is a potential for interactions.

Cardiac Disease:
Venlafaxine has not been evaluated or used to any appreciable extent in patients with a recent history of myocardial infarction or unstable heart disease. Patients with these diagnoses were systematically excluded from many clinical studies during the product's clinical trials. Evaluation of the electrocardiograms for 769 patients who received venlafaxine in 4- to 6 week double-blind trials showed that the incidence of trial-emergent conduction abnormalities did not differ from that with placebo. The mean heart rate was increased by about 4 beats per minute during treatment. Venlafaxine treatment has been associated with sustained hypertension (see Warnings).

Hepatic and Renal Disease:
In patients with hepatic or renal disease the pharmacokinetic disposition of both venlafaxine and ODV are significantly altered. Dosage adjustment is necessary in these patients (See Dosage).

Occupational Hazards:
Any psychoactive drug may impair judgment, thinking or motor skills. Therefore, patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that the drug treatment does not affect them adversely.

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.

Lactation:
It is not known whether venlafaxine or its metabolites are excreted in human milk. Because many drugs are excreted in human milk, lactating women should not nurse their infants while receiving venlafaxine.

Children:
Safety and efficacy in children below the age of 18 have not been established.

Geriatrics:
Of the 2,897 patients in Phase II and III trials, 357 (12%) were 65 years of age or older. No overall differences in effectiveness and safety were observed between these patients and younger patients. However, greater sensitivity of some older individuals cannot be ruled out.

Discontinuation Symptoms:
While the discontinuation effects of Effexor have not been systematically evaluated in controlled clinical trials, a retrospective survey of new events occurring during taper or following discontinuation revealed the following six events that occurred at an incidence of at least 5%, and for which the incidence for venlafaxine was at least twice the placebo incidence: asthenia, dizziness, headache, insomnia, nausea and nervousness. Therefore, it is recommended that the dosage be tapered gradually and the patient monitored (See Dosage).

Drug Interactions:
As with all drugs, the potential for interaction by a variety of mechanisms is a possibility.

Lithium:
The steady-state pharmacokinetics of venlafaxine administered as 50 mg every 8 hours was not affected when a single 600 mg oral dose of lithium was administered to 12 healthy male subjects. Venlafaxine had no effect on the pharmacokinetics of lithium. It should be noted that the venlafaxine dose was in the low end of the therapeutic dosage, as was the single lithium dose. The potential interaction of venlafaxine and lithium in clinical practice is unknown.

Diazepam:

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The steady-state pharmacokinetics of venlafaxine administered as 50 mg every 8 hours was not affected when a single 10 mg oral dose of diazepam was administered to 18 healthy male subjects. Venlafaxine had no effect on the pharmacokinetics of diazepam or its active metabolite, desmethyidiazepam. It should be noted that the venlafaxine dose was in the low end of the therapeutic dosage, as was the single diazepam dose. The potential interaction of venlafaxine and diazepam in clinical practice is unknown.

Cimetidine:
Concomitant administration of cimetidine and venlafaxine in a steady-state study for both drugs in 18 healthy male subjects resulted in inhibition of first-pass metabolism of venlafaxine. The oral clearance of venlafaxine was reduced by about 43%, and the exposure (AUC) and maximum concentration (Cmax) of the drug were increased by about 60%. However, there was no effect on the pharmacokinetics of ODV. The overall pharmacological activity of venlafaxine plus ODV is expected to rise only slightly, and no dosage adjustment should be necessary for most subjects.

However, for patients with pre-existing hypertension, for elderly patients and for patients with hepatic or renal dysfunction, the interaction associated with the concomitant use of cimetidine and venlafaxine is not known and potentially could be more pronounced. Therefore, caution is advised in these patients.

Other CNS-Active Drugs:
The risk of using venlafaxine in combination with other CNS-active drugs (including alcohol) has not been systematically evaluated. Consequently, caution is advised if the concomitant administration of venlafaxine and such drugs is required.

Electroconvulsive Therapy:
There are no clinical data on the use of electroconvulsive therapy combined with venlafaxine treatment.

Cytochrome P450 IID6:
Venlafaxine is metabolized to its active metabolite, ODV, by cytochrome P450 IID6 Therefore, the potential exists for a drug interaction between venlafaxine and drugs that inhibit cytochrome P450-IID6 metabolism. Venlafaxine is a relatively weak inhibitor of cytochrome P450 IID6, however, the clinical significance of this finding is unknown.

Drug Abuse and Dependence:
Physical and Psychological Dependence:
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.

While venlafaxine has not been systematically studied in clinical trials for its potential for abuse, there was no indication of drug-seeking behaviour in the clinical trials. However, it is not possible to predict on the basis of premarketing experience the extent to which a CNS active drug will be misused, diverted, and/or abused once marketed. Consequently, physicians should carefully evaluate patients for history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse of venlafaxine (e.g., development of tolerance incrementation of dose, drug-seeking behaviour).

Adverse Effects

Commonly Observed Adverse Reactions:
The most commonly observed adverse events associated with the use of venlafaxine (incidence of 5% or greater) and not seen at an equivalent incidence among placebo-treated patients (i.e., incidence for venlafaxine at least twice that for placebo), derived from the 1% incidence Table III, were asthenia, sweating, nausea, constipation, anorexia, vomiting, somnolence, dry mouth, dizziness nervousness, anxiety, tremor, blurred vision, and abnormal ejaculation/orgasm and impotence in men.

Adverse Reactions Associated with Discontinuation of Treatment:
Nineteen percent (537/2897) of venlafaxine-treated patients in Phase II and III depression studies discontinued treatment due to an adverse reaction (see Table II). The more common events (>=1%) associated with discontinuation of treatment and considered to be drug-related (i.e., those events associated with dropout at a rate approximately twice or greater for venlafaxine compared to placebo) included Table II.

---------------------------------------------------------------
Table II
Adverse Reactions Associated with Discontinuation of Treatment
---------------------------------------------------------------
                      Venlafaxine   Placebo
---------------------------------------------------------------
CNS
  Somnolence              3%           1%
  Insomnia                    3%           1%
  Dizziness                   3%           --
  Nervousness             2%           --
  Dry Mouth                  2%           --
  Anxiety                       2%           1%
Gastrointestinal
  Nausea                      6%           1%
Urogenital
  Abnormal Ejaculation*   3%           --
Other
  Headache                  3%           1%
  Asthenia                    2%           --
 Sweating                    2%           --

 *  percentages based on the number of males.
 -- Less than 1%
---------------------------------------------------------------

Incidence in Controlled Trials:
Table III that follows enumerates adverse events that occurred at an incidence of 1% or more, and were more frequent than in the placebo group, among venlafaxine-treated patients who participated in 4- to 8-week placebo-controlled trials in which patients were administered doses in the range of 75 to 375 mg/day. Reported adverse events were classified using a standard COSTART-based Dictionary terminology.

Dose Dependency of Adverse Events:
A comparison of adverse event rates in a fixed-dose study comparing Effexor 75, 225, and 375 mg/day with placebo revealed a dose dependency for some of the more common adverse events associated with Effexor use, as shown in Table IV. 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 Effexor 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 .

-------------------------------------------------------------------------
Table III
Treatment-Emergent Adverse Experience Incidence in 4-to 8-Week
Placebo-Controlled Clinical Trials (Percentage)
-------------------------------------------------------------------------
                                             Effexor   Placebo
Body System          Preferred Term          (n=1033)  (n=609)
-------------------------------------------------------------------------
Body as a whole      
                  Headache                    25        24
                     Asthenia                    12         6
                     Infection                       6         5
                     Chills                            3        --
                     Chest Pain                  2         1
                     Trauma                        2         1

Cardiovascular       
                  Vasodilatation               4         3
                     Increased blood/pressure
                       hypertension             2        --
                     Tachycardia                2        --
                     Postural hypotension 1        --

Dermatological       
                Sweating                    12         3
                     Rash                         3         2
                     Pruritus                     1        --

Gastrointestinal     
                     Nausea                   37        11
                     Constipation          15         7
                     Anorexia                 11         2
                     Diarrhoea                 8         7
                     Vomiting                   6         2
                     Dyspepsia                5         4
                     Flatulence                 3         2

Metabolic            
                  Weight loss                  1        --

Nervous              
                     Somnolence             23         9
                     Dry mouth                 22        11
                     Dizziness                  19         7
                     Insomnia                   18        10
                     Nervousness            13         6
                     Anxiety                        6         3
                     Tremor                        5         1
                     Abnormal Dreams     4         3
                     Hypertonia                  3         2
                     Paraesthesia              3         2
                     Libido decreased      2        --
                     Agitation                     2        --
                     Confusion                   2         1
                     Thinking abnormal     2         1
                     Depersonalization     1        --
                     Depression                1        --
                     Urinary retention         1        --
                     Twitching                     1        --

Respiration          
                        Yawn                         3        --

Special Senses       
                     Blurred vision              6         2
                     Taste perversion         2        --
                     Tinnitus                         2        --
                     Mydriasis                      2        --

Urogenital           
                     Abnormal ejaculation/
                      orgasm                       12 [2]     2
                     Impotence                      6 [2]     2
                     Urinary frequency          3         2
                     Urination impaired        2        --
                     Orgasm disturbance     2 [3]    -- [3]
                     Menstrual disorder        1 [3]    -- [3]
-------------------------------------------------------------------------

[1] Events reported by at least 1% of patients treated with Effexor are
    included, and are rounded to the nearest %. Events for which the 
    Effexor incidence was equal to or less than placebo are not listed 
    in the table, but included the following: abdominal pain, pain, back
    pain, flu syndrome, fever, palpitation, increased appetite, myalgia,
    arthralgia, amnesia, hypaesthesia, rhinitis pharyngitis, sinusitis 
    cough increased urinary tract infection and dysmenorrhoea [3]

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-- Incidence less than 1%
[2] Incidence based on number of male patients.
[3] Incidence based on number of female patients.
-------------------------------------------------------------------------

Adaptation to Certain Adverse Events:
Over a 6-week period, there was evidence of adaptation to some adverse events with continued therapy (e.g., dizziness and nausea), but less to other effects (e.g., abnormal ejaculation and dry mouth).

Vital Sign Changes:
Venlafaxine treatment (averaged over all dose groups) in clinical trials was associated with a mean increase in pulse rate of approximately 3 beats per minute, compared to no change for placebo. It was associated with mean increases in diastolic blood pressure ranging from 0.7 to 2.5 mm Hg averaged over all dose groups, compared to mean decreases ranging from O.9 to 3.8 mm Hg for placebo. However, there is a dose dependency for blood pressure increase (see Warnings).

Laboratory Changes:
Of the serum chemistry and hematology parameters monitored during clinical trials with venlafaxine, a statistically significant difference with placebo was seen only for serum cholesterol, i.e., patients treated with venlafaxine had mean increases from baseline of 3 mg/dL, a change of unknown clinical significance.

-----------------------------------------------------------------
Table IV
Treatment-Emergent Adverse Experience Incidence
   in a Dose Comparison Trial
-----------------------------------------------------------------
                                     Effexor (mg/day)
Body System/              Placebo     75        225       375
Preferred Term            (n=92)    (n=89)    (n=89)    (n=88)
-----------------------------------------------------------------
Body as Whole
  Abdominal pain            3.3%      3.4%      2.2%      8.0%
  Asthenia                        3.3%     16.9%     14.6%     14.8%
  Chills                              1.1%      2.2%      5.6%      6.8%
  Infection                         2.2%      2.2%      5.6%      2.3%

Cardiovascular
  Hypertension                 1.1%      1.1%      2.2%      4.5%
  Vasodilatation               0.0%      4.5%      5.6%      2.3%

Digestive System
  Anorexia                        2.2%     14.6%     13.5%     17.0%
  Dyspepsia                     2.2%      6.7%      6.7%      4.5%
  Nausea                        14.1%     32.6%     38.2%     58.0%
  Vomiting                        1.1%      7.9%      3.4%      6.8%

Nervous
  Agitation                       0.0%      1.1%      2.2%      4.5%
  Anxiety                          4.3%     11.2%      4.5%      2.3%
  Dizziness                      4.3%     19.1%     22.5%     23.9%
  Insomnia                       9.8%     22.5%     20.2%     13.6%
  Libido decreased        1.1%      2.2%      1.1%      5.7%
  Nervousness                4.3%     21.3%     13.5%     12.5%
  Somnolence                 4.3%     16.9%     18.0%     26.1%
  Tremor                           0.0%      1.1%      2.2%     10.2%

Respiratory
  Yawn                               0.0%      4.5%      5.6%      8.0%

Skin and Appendages
  Sweating                        5.4%      6.7%     12.4%     19.3%

Special Senses
  Abnormality of
    accommodation           0.0%      9.1%      7.9%      5.6%

Urogenital System
  Abnormal ejaculation/
    orgasm                        0.0%      4.5%      2.2%     12.5%
  Impotence                     0.0%      5.8%      2.1%      3.6%
  (number of men)          (n=63)    (n=52)    (n=48)    (n=56)
-----------------------------------------------------------------

ECG Changes:

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In an analysis of ECGs obtained in 769 patients treated with venlafaxine and 450 patients treated with placebo in controlled clinical trials, the only statistically significant difference observed was for heart rate, i.e., a mean increase from baseline of 4 beats per minute for venlafaxine.

Other Events Observed During the Premarketing Evaluation of Venlafaxine:
During its premarketing assessment, multiple doses of venlafaxine were administered to 2,181 patients in phase II and III studies. The conditions and duration of exposure of venlafaxine varied greatly, and included (in overlapping categories) open and double-blind studies, uncontrolled and controlled studies, inpatient and outpatient studies, fixed-dose and titration studies. Untoward events associated with this exposure were recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse events without first grouping similar types of untoward events into a smaller number of standardized event categories.

In the tabulations that follow, reported adverse events were classified using a standard COSTART-based dictionary terminology . The frequencies presented, therefore, represent the proportion of the 2,181 patients exposed to multiple doses of venlafaxine who experienced an event of the type cited on at least one occasion while receiving venlafaxine. All reported events are included except those already listed in Table III and those events for which a drug cause was remote. If the COSTART term for an event was so general as to be uninformative, it was replaced with a more informative term. It is important to emphasize that, although the events reported occurred during treatment with venlafaxine, they were not necessarily caused by it.

Events are further classified by body system and listed in order of decreasing frequency according to the following definitions: frequent adverse events are those occurring on one or more occasions in at least 1/100 patients (only those not already listed in the tabulated results from placebo controlled trials appear in this listing); infrequent adverse events are those occurring in 1/100 to 1/1000 patients; rare events are those occurring in fewer than 1/1000 patients. The frequent adverse events have been provided below.

Body as a whole: accidental injury, malaise, neck pain.
Cardiovascular: migraine.
Digestive: dysphagia, eructation.
Hemic and lymphatic: ecchymosis.
Metabolic and nutritional: peripheral edema, weight gain.
Nervous: emotional lability, trismus, vertigo.
Respiratory: bronchitis, dyspnea.
Special senses: abnormal vision, ear pain.
Urogenital: anorgasmia, dysuria, hematuria, metrorrhagia*, urination impaired, vaginitis*.

* Based on the number of male or female patients as appropriate.

Overdose

Symptoms and Treatment:

Human Experience:
There were 14 reports of acute overdose with venlafaxine, either alone or in combination with other drugs and/or alcohol, among the patients included in the premarketing evaluation. The majority of the reports involved ingestions in which the total dose of venlafaxine taken was estimated to be no more than several-fold higher than the usual therapeutic dose. The 3 patients who took the highest doses were estimated to have ingested approximately 6.75 g, 2.75 g and 2.5 g. The resultant peak plasma levels of venlafaxine for the latter 2 patients were 6.24 and 2.35 mcg/mL, respectively and the peak plasma levels of O-desmethylvenlafaxine were 3.37 and 1.30 mcg/mL, respectively. Plasma venlafaxine levels were not obtained for the patient who ingested 6.75 g of venlafaxine. All 14 patients recovered without sequelae. Most patients reported no symptoms. Among the remaining patients, somnolence was the most commonly reported symptom. The patient who ingested 2.75 g of venlafaxine was observed to have 2 generalized convulsions and a prolongation of QTc to 500 msec, compared with 405 msec at baseline. Mild sinus tachycardia was reported in 2 of the other patients.

Overdosage Management:
Treatment should consist of those general measures employed in the management of overdosage with any antidepressant. Ensure an adequate airway, oxygenation, and ventilation. Monitoring of cardiac rhythm and vital signs is recommended. General supportive and symptomatic measures are also recommended. Use of activated charcoal, induction of emesis, or gastric lavage should be considered. Due to the large volume of distribution of venlafaxine hydrochloride, forced diuresis, dialysis, hemoperfusion and exchange transfusion are unlikely to be of benefit. No specific antidotes for venlafaxine are known.

In managing overdosage, consider the possibility of multiple drug involvement. The physician should consider contacting a poison control centre on the treatment of any overdose.

Dosage

Adults:
The recommended treatment dose is 75 mg per day, administered in two or three divided doses, taken with food. If the expected clinical improvement does not occur after a few weeks, a gradual dose increase to 150 mg/day may be considered. If needed, the dose may be further increased up to 225 mg/day. Increments of up to 75 mg/day should be made at intervals of no less than 4 days. In outpatient settings there was no evidence of the usefulness of doses greater than 225 mg/day for moderately depressed patients. More severely depressed inpatients have responded to higher doses, between 350 and 375 mg/day, given in 3 divided doses.

Maximum:
The maximum dose recommended is 375 mg per day (in an inpatient setting).

Patients With Hepatic Impairment:
Given the decrease in clearance and increase in elimination half-life for both venlafaxine and ODV that is observed in patients with hepatic cirrhosis compared to normal subjects (see Pharmacology), it is recommended that the total daily dose be reduced by about 50% in patients with moderate hepatic impairment. Since there was much individual variability in clearance between patients with cirrhosis, it may be necessary to reduce the dose even more than 50%, and individualization of dosing may be desirable in some patients.

Patients with Renal Impairment:
Given the decrease in clearance for venlafaxine and increase in elimination half-life for both venlafaxine and ODV that is observed in patients with renal impairment (GFR = 10 to 70 mL/min) compared to normals (see Pharmacology), it is recommended that the total daily dose be decreased by 25% in patients with mild to moderate renal impairment. It is recommended that the total daily dose be reduced by 50% and the dose be withheld until the dialysis treatment is completed (4 hrs) in patients undergoing hemodialysis. Since there was so much individual variability in clearance between patients with renal impairment, individualization of dosing may be desirable in some patients.

Geriatrics:
No dose adjustment is recommended for elderly patients on the basis of their age. As with any antidepressant, however, caution should be exercised in treating the elderly. When individualizing the dosage, extra care should be taken when increasing the dose.

Discontinuing Venlafaxine:
When venlafaxine therapy that has been administered for more than 1 week is stopped, it is generally recommended that the dose be tapered gradually to minimize the risk of discontinuation symptoms. Patients who have received venlafaxine for 6 weeks or more should have their dose tapered gradually over a 2-week period.

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