Venlafaxine

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Venlafaxine (Brand names Efexor, Effexor, among others) is an antidepressant that belongs to a group of medicines called serotonin and norepinephrine reuptake inhibitors (SNRIs).

This group of medicines is used to treat depression and other conditions, such as anxiety disorders.

It is thought that people who are depressed and/or anxious have lower levels of serotonin and noradrenaline in the brain. Venlafaxine helps increasing the levels of serotonin and noradrenaline.

Contents

[edit] BRAND NAMES

[edit] STRUCTURE

Venlafaxine.jpg

[edit] MECHANISM OF ACTION

Venlafaxine is an antidepressant, it acts as a potent inhibitor of both serotonin and norepinephrine reuptake (SNRI) and as a weak inhibitor of dopamine reuptake. Venlafaxine has a rapid onset of clinical action (about one week or less).[1]

[edit] INDICATIONS

Velafaxine is used to treat major depression disorder. A major depressive episode implies a prominent and relatively persistent depressed or dysphoric mood that usually interferes with daily functioning (nearly every day for at least 2 weeks; it should include at least 4 of the following 8 symptoms: change in appetite, change in sleep, psychomotor agitation or retardation, loss of interest in usual activities or decrease in sexual drive, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, and a suicide attempt or suicidal ideation

[edit] DOSAGE

Major depression disorder:: The recommended starting dose is 37.5mg/day for 4-7 days, to be increased to 75mg/day. Depending on tolerability and the need for further clinical effect, the dose may be increased to 150 mg/day. If needed, the dose should be further increased up to 225 mg/day. When increasing the dose, 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 usefulness of doses greater than 225 mg/day for moderately depressed patients, but more severely depressed inpatients responded to a mean dose of 350 mg/day. Certain patients, including more severely depressed patients, may therefore respond more to higher doses, up to a maximum of 375 mg/day, generally in three divided doses.

Patients with moderate Hepatic Impairment must decrease dose by 50%

[edit] CONTRAINDICATIONS

  • Hypersensitivity to Venlafaxine
  • It's use within 14 days of stopping an MAOI because of an increased risk of serotonin syndrome
  • Do not start Venlafaxine in a patient who is being treated with linezolid or intravenous methylene blue (increased risk of serotonin syndrome)

[edit] WARNINGS AND PRECAUTIONS

  • FDA Black Box Warning for Venlafaxine: Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of Major Depressive Disorder (MDD) and other psychiatric disorders. Anyone considering the use of Venlafaxine or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Venlafaxine is not approved for use in pediatric patients.
  • Bone Fractures: Epidemiological studies show an increased risk of bone fractures in patients receiving serotonin reuptake inhibitors (SRIs) including Venlafaxine.
  • Serotonin Syndrome: Serotonin syndrome has been reported with SSRIs and SNRIs, including Venlafaxine, both when taken alone, but especially when co-administered with other serotonergic agents (including Triptans, Tricyclic antidepressants, Fentanyl, Lithium, Tramadol, Tryptophan, Buspirone and St. John’s Wort) and with drugs that impair metabolism of serotonin (in particular, MAOI, both those intended to treat psychiatric disorders and also others, such as Linezolid and intravenous Methylene blue). 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).If such symptoms occur, discontinue Venlafaxine and initiate supportive treatment. If concomitant use of Venlafaxine with other serotonergic drugs is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases.
  • Altered Appetite and Weight: Decreased appetite and weight loss may occur
  • Anxiety and Insomnia: May occur
  • Abnormal Bleeding: May increase the risk of bleeding. Use with NSAIDs, Aspirin, Warfarin, or drugs that affect coagulation may potentiate the risk of gastrointestinal or other bleeding
  • Hyponatremia: Hyponatremia has been reported with Venlafaxine use, either alone or in combination with some diuretics (Hydrochlorothiazide, Furosemide). Hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Signs and symptoms include headache, new or increased seizure frequency, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which can lead to fall. Severe Hyponatremia may cause hallucination, syncope, seizure, coma, respiratory arrest, and death.
  • Monitor blood pressure especially in patients with high baseline blood pressure (possible increase in systolic blood pressure by 10-15mmHg)
  • Use with caution in patients with a history of seizures
  • Avoid use of alcohol
  • Caution when using heavy machinery

[edit] INTERACTIONS

[edit] PREGNANCY AND LACTATION

  • Pregnancy Category C (US). Venlafaxine should be used during pregnancy only if clearly needed.
  • Nursing Mothers: Venlafaxine is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

[edit] SIDE EFFECTS

Adverse effects include nausea, somnolence, insomnia, dry mouth, feeling tired, blurred vision, constipation, sweating, increased cholesterol, nervousness, abnormal ejaculation, loss of appetite, cardiac conduction changes and hypertension.

[edit] RELATED LINKS

[edit] BIBLIOGRAPHY

[edit] REFERENCES

  1. http://www.ncbi.nlm.nih.gov/pubmed/7622814
Antidepressants
Tricyclic antidepressants Amitriptyline (Elavil, Laroxyl)   Clomipramine (Anafranil)   Doxepin (Sinequan)   Imipramine (Tofranil)   Nortriptyline (Aventyl, Pamelor)   Trimipramine (Surmontil)
Selective serotonin reuptake inhibitors (SSRIs) Citalopram (Celexa, Seropram)   Escitalopram (Cipralex, Lexapro)   Fluoxetine (Prozac)   Fluvoxamine (Luvox, Maveral)   Paroxetine (Paxil, Seroxat)   Sertraline (Zoloft)
Serotonin–norepinephrine reuptake inhibitors (SNRIs) Desvenlafaxine (Pristiq)   Duloxetine (Cymbalta, Xeristar)   Venlafaxine (Efexor, Effexor)
Serotonin antagonists and reuptake inhibitors (SARIs) Trazodone (Desyrel, Oleptro)
Norepinephrine reuptake inhibitors (NRIs) Maprotiline (Ludiomil)   Reboxetine (Edronax)
Norepinephrine-dopamine reuptake inhibitors (NDRIs) Bupropion (Wellbutrin)
Noradrenergic and specific serotonergic antidepressants (NaSSAs) Mianserin (Lantanon)   Mirtazapine (Remeron)
Norepinephrine-dopamine disinhibitors (NDDIs) Agomelatine (Valdoxan, Thymanax)
Monoamine oxidase inhibitors Nonselective Tranylcypromine (Parnate)
Monoamine oxidase inhibitors B-Selective Selegiline (Transdermal) (Emsam)
Others 5-Hydroxytryptophan   S-Adenosyl methionine   Hypericum (St John's wort)