VENLAFAXINE AT-HOME WITHDRAWAL AND TAPERING PROGRAM

Venlafaxine (Effexor) is an SNRI (Selective Serotonin-Norepinephrine Reuptake Inhibitor) that was introduced by Pfizer as Effexor in 1993. By 2007, Effexor was the sixth most commonly prescribed antidepressant on the U.S. market. 

Venlafaxine has a relatively short half-life that helps to explain the severity of the Discontinuation Syndrome (withdrawals) frequently experienced by patients. It is hypothesized that an overly rapid deprivation of multiple neurotransmitter levels contributes to the high rate of withdrawals. 

Venlafaxine (Effexor) can increase eye pressure so patients with glaucoma should have more frequent eye checks.  There are few well-controlled studies of Effexor in pregnant women but a study released in May 2010 (Canadian Medical Association Journal) suggested it doubled the risk of miscarriage.

Effexor (Venlafaxine) was marketed for the use of major depression, generalized anxiety, panic disorder and social phobia. At dosages less than 150mg per day, it acts primarily on Serotonin, while at moderate dosages of 150-300mg Venlafaxine affected both Serotonin and Norepinephrine. At dosages above 300mg, Effexor also exerted it effect on Dopamine. 

Serotonin is found primarily in the gastrointestinal tract, blood platelets and central nervous system. Norepinephrine has multiple roles including as a hormone and neurotransmitter and is most responsible for vigilant concentration in contrast to Dopamine that is most responsible for cognitive alertness.  The widespread role of these neurotransmitters helps to explain the long list of possible Venlafaxine side effects and withdrawal symptoms. 

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VENLAFAXINE WITHDRAWAL SYMPTOMS MAY INCLUDE:

aggression, anxiety, balance issues , blurred vision, brain zaps, concentration impairment, constipation, crying spells, depersonalization, diarrhea, dizziness. electric shock sensations, fatigue, flatulence, flu-like symptoms, hallucinations, hostility, highly emotional, indigestion, irritability, impaired speech, insomnia, jumpy nerves, lack of coordination, lethargy, migraine headaches / increased headaches, nausea, nervousness, over-reacting to situations, paranoia, repetitive thoughts or songs, sensory & sleep disturbances, severe internal restlessness (akathisia), stomach cramps, tremors, tinnitus (ear ringing or buzzing), tingling sensations, troubling thoughts, visual hallucinations / illusions, vivid dreams, speech or visual changes, worsened depression 

VENLAFAXINE ABRUPT DISCONTINUATION SYMPTOMS MAY INCLUDE:  

agitation, anxiety, confusion, irritability, sensory disturbances, electric shock sensations, dysphoric mood, headache, emotional liability, insomnia, hypomania, tinnitus, seizures, impaired coordination, diarrhea, dizziness, nausea, nervousness, nightmares, somnolence, tremor, vertigo and vomiting

VENLAFAXINE SIDE EFFECTS MAY INCLUDE: 

abnormal dreams, abnormal ejaculation or orgasm, anxiety, appetite loss, blurred vision, chills, constipation, diarrhea, dizziness, dry mouth, frequent urination, flushing, gas, headache, impotence, infection, insomnia, muscle tension, nausea, nervousness, rash, sleepiness, sweating, tingling feeling, tremor, upset stomach, vomiting, weakness, yawning, abnormal taste, abnormal thinking, agitation, chest pain, confusion, decreased sex drive, depression, dilated pupils, dizziness upon standing up, high blood pressure, itching, loss of identity, rapid heartbeat, ringing in the ears, trauma, twitching, urinary problems, weight loss

VENLAFAXINE ADVERSE REACTIONS MAY INCLUDE: per PDR

Severe: peptic ulcer, bradycardia, laryngospasm, exfoliative dermatitis, seizures, muscle paralysis, Guillain-Barre syndrome, torticollis, akinesia, stroke, obstruction, heart failure, myocardial infarction , AV block, hematemesis, tendon rupture, cholecystitis, pulmonary embolism, laryngeal edema , apnea, spontaneous fetal abortion, anuria, oliguria , hyperkalemia, prostatic hypertrophy, proteinuria, tardive dyskinesia, suicidal ideation, pancreatitis, ventricular tachycardia, cardiomyopathy, torsade de pointes , ventricular fibrillation, atrial fibrillation, ocular hypertension, serotonin syndrome, neuroleptic malignant syndrome, SIADH, GI bleeding, habdomyolysis, hepatic failure, hepatic necrosis, eosinophilic pneumonia, aplastic anemia , pancytopenia, agranulocytosis, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), erythema multiforme, angioedema, toxic epidermal necrolysis, Stevens-Johnson syndrome, anaphylactoid reactions, renal failure (unspecified), neonatal abstinence syndrome    

Moderate: ejaculation dysfunction, constipation, hypertension, blurred vision, impotence (erectile dysfunction), hypertonia, depression, confusion , sinus tachycardia, hostility, hallucinations, psychosis, euphoria, peripheral neuropathy, akathisia, ataxia, neuropathic pain, dysarthria, neuritis, hyperesthesia, hypotonia, gastritis, stomatitis, hemorrhoids,, colitis, oral ulceration, glossitis, dysphagia, esophagitis, teeth grinding (bruxism), hypotension, orthostatic hypotension, angina, peripheral vasoconstriction, phlebitis, photophobia, conjunctivitis, cataracts, melena, bone pain, myasthenia, synovitis, hyperlipidemia, hypercholesterolemia, dysphonia, thrombocytopenia, anemia, lymphadenopathy, leukopenia, psoriasis, contact dermatitis, urinary incontinence, vaginal bleeding, urinary retention, hypokalemia, hyperglycemia, withdrawal, mania, impulse control symptoms, dystonic reaction, paresis, aphasia, hyperreflexia, nystagmus, parotitis , proctitis, bundle-branch block, hyponatremia, prolonged bleeding time, hepatitis, jaundice, cholelithiasis, hypoventilation, hemoptysis, hypoxia , lymphocytosis, eosinophilia, flank pain, hypercalciuria, glycosuria, nephrolithiasis, hyperthyroidism, galactorrhea, goiter, hypothyroidism, hypophosphatemia, diabetes mellitus, hyperuricemia, hyperphosphatemia, hypoglycemia, gout, amnesia, trismus, chest pain (unspecified), edema, vaginitis, prostatitis, delirium, dyskinesia, supraventricular tachycardia (SVT), QT prolongation, growth inhibition, priapism, bleeding, platelet dysfunction, elevated hepatic enzymes, steatosis, dyspnea, neutropenia, hyperprolactinemia 

Mild: nausea, weight loss, headache, insomnia, drowsiness, xerostomia, dizziness, hyperhidrosis, weakness, anorexia, asthenia, yawning, diarrhea, libido decrease, dyspepsia, anxiety, vomiting, infection, tremor, orgasm dysfunction, flushing, agitation, paresthesias, flatulence, rash, increased urinary frequency, chills, emotional lability, hyperkinesis, gingivitis, syncope, xerophthalmia, diplopia, arthralgia, muscle cramps, epistaxis.  hyperventilation, laryngitis, leukocytosis, acne vulgaris, maculopapular rash, urticaria, alopecia, xerosis, pruritus, photosensitivity, hirsutism, urinary urgency , nocturia, polyuria, menorrhagia, amenorrhea, mastalgia, fever, paranoia, hyporeflexia, tongue discoloration, cheilitis, hypersalivation, pallor, petechiae , purpura, breast enlargement, gynecomastia, breast discharge, vertigo, dysgeusia, eructation, mydriasis, menstrual irregularity, restlessness, night sweats, ecchymosis, cough  

 VENLAFAXINE BOXED WARNINGS: per PDR  

Children, growth inhibition, suicidal ideation

Venlafaxine is not FDA approved for the treatment of major depressive disorder (MDD) in children. In October 2004, the FDA directed manufacturers of all antidepressants to add a boxed warning to their product labels detailing the risk of suicide in pediatric patients. The risk of suicidality for these drugs was identified in a pooled analysis of 24 placebo-controlled trials (n = 4,400) lasting up to 16 weeks in pediatric patients with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders. The analysis showed a greater risk of suicidality during the first few months of treatment in those receiving antidepressants. The average risk of such events on drug was 4% and 2% for placebo; however, no suicides occurred in these trials. Pooled analysis of short-term clinical trials during early phase treatment with antidepressants in young adults (18 to 24 years) also showed an increased risk of suicidal thinking and behavior. The clinical need for an antidepressant in pediatrics or young adults for any use must be weighed against the risk of increased suicidality; patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior, particularly within the first few months of starting therapy or during dose changes. It is unknown if the suicidality risk in children or young adults extends to longer-term therapy. The possibility of a suicide attempt is inherent in patients with depressive symptoms, whether these occur in primary depression or in association with another primary disorder. All patients with a history of suicidal ideation or behaviors and those with a prominence of suicidal ideation prior to treatment should be closely monitored during treatment with venlafaxine. In patients who exhibit worsening of depression or suicidality, a decision should be made to change or discontinue treatment. If discontinuing, the medication should be tapered as rapidly as possible, but with recognition that abrupt discontinuation can also cause adverse symptoms. All antidepressants should be prescribed in the smallest quantity consistent with good patient management to reduce the risk of overdose. Postmarketing data suggest that overdose with venlafaxine may result in more serious outcomes (i.e., fatalities) compared to selective serotonin reuptake inhibitors (SSRIs), but less than for tricyclic antidepressants (TCAs). Most reports of overdose have included ingestion of a combination of drugs, including alcohol. Venlafaxine has been shown to lead to dose-dependent weight loss in children ages 6 to 17 years. In addition, growth inhibition has been noted in short and long-term studies in children. Clinicians should regularly monitor height and weight changes in pediatric patients receiving venlafaxine.  

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According to the FDA:

Serotonin Syndrome: Risk increases with concomitant use of other serotonergic drugs. Discontinue Effexor XR and initiate supportive treatment if serotonin syndrome occurs

Discontinuation [Symptoms]

Advise patients not to stop taking Effexor XR without talking first with their healthcare professional. Patients should be aware that discontinuation effects may occur when stopping Effexor XR [see Warnings and Precautions (5.7) and Adverse Reactions (6.1)]. When discontinuing treatment, reduce the dose gradually (2.8, 5.7).

REFERENCES:

https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020699s107lbl.pdf

https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/venlafaxine-marketed-effexor-information

https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/020699s059lbl.pdf

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4722507/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3267502/

https://www.bmj.com/content/317/7161/787.2/rapid-responses 

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