Venlafaxine; Uses, Dosage, Side Effects, Interactions

Venlafaxine; Uses, Dosage, Side Effects, Interactions

Venlafaxine is a synthetic phenethylamine bicyclic derivative with antidepressant activity. Venlafaxine and its active metabolite, O-desmethylvenlafaxine (ODV), are potent inhibitors of neuronal serotonin and norepinephrine reuptake and weak dopamine reuptake inhibitors. This agent may reduce hormone-related vasomotor symptoms. (NCI04)
Venlafaxine is a serotonin and norepinephrine reuptake inhibitor widely used as an antidepressant. Venlafaxine therapy can be associated with transient asymptomatic elevations in serum aminotransferase levels and has been linked to rare instances of clinically apparent acute liver injury.

Mechanism of Action of Venlafaxine

The exact mechanism of action of venlafaxine is unknown but appears to be associated with its potentiation of neurotransmitter activity in the CNS. Venlafaxine and its active metabolite, O-desmethylvenlafaxine (ODV), inhibit the reuptake of both serotonin and norepinephrine with a potency greater for the 5-HT than for the NE reuptake process. Both venlafaxine and the ODV metabolite have weak inhibitory effects on the reuptake of dopamine but, unlike the tricyclics and similar to SSRIs, they are not active at histaminergic, muscarinic, or alpha(1)-adrenergic receptors.
or
The mechanism of the antidepressant action of venlafaxine in humans is believed to be associated with its potentiation of neurotransmitter activity in the CNS. Preclinical studies have shown that venlafaxine and its active metabolite, O-desmethylvenlafaxine, are potent inhibitors of neuronal serotonin and norepinephrine reuptake and weak inhibitors of dopamine reuptake. Venlafaxine and O-desmethylvenlafaxine have no significant affinity for muscarinic cholinergic, H1-histaminergic, or a1-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 O-desmethylvenlafaxine do not possess monoamine oxidase (MAO) inhibitory activity.
or
The present study was undertaken to evaluate the potential role of 5-HT1A receptors in the antidepressant-like effect and antinociceptive effect of venlafaxine. With this aim, the effect of either a selective 5-HT1A receptor antagonist (WAY-100635; N-2-[4-(2-methoxyphenyl-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexane carboxamide) or a selective 5-HT1A receptor agonist (8-OH-DPAT; 8-hydroxy-2-(di-n-propylamine) tetralin hydrobromide) was investigated in mice in combination with venlafaxine by means of the forced swimming test, a paradigm aimed at screening potential antidepressants, and the hot-plate test, a phasic pain model. Surprisingly, the results showed that WAY-100635produced a large decrease in the antidepressant-like effect of venlafaxine, while 8-OH-DPAT rendered effective a non-effective dose of this antidepressant. However, in the hot-plate test WAY-100635 significantly enhanced the antinociceptive effect of venlafaxine, whereas 8-OH-DPAT counteracted its antinociceptive effect. These findings show that 5-HT1A receptors play differing roles in modulating the antidepressant-like and antinociceptive effects of venlafaxine in the models investigated. The results imply that blockade of the 5-HT1A receptors in the forebrain will counteract the favorable (antidepressant-like) effect at raphe nuclei level, and consequently, the overall effect evidenced is an antagonism. This suggests a predominant role of 5-HT1A receptors located in the forebrain area for the antidepressant-like effect. In contrast, the antinociceptive effect of venlafaxine is probably potentiated due to the blockade of somatodendritic 5-HT1A receptors in the same raphe nuclei, facilitating the descending monoaminergic pain control system.
Abstract: PubMed

 Uses / Indications of Venlafaxine

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Therapeutic Uses of Venlafaxine

  • Antidepressive Agents, Second-Generation; Serotonin Uptake Inhibitors
    National Library of Medicine’s Medical Subject Headings online file (MeSH, 2011)
  • Venlafaxine hydrochloride is used in the treatment of a major depressive disorder.
  • Venlafaxine hydrochloride is used in the treatment of generalized anxiety disorder.
  • Venlafaxine hydrochloride is used in the treatment of social phobia (social anxiety disorder).
  • Venlafaxine has been used for the management of vasomotor symptoms in women with breast cancer and in postmenopausal women.
  • Venlafaxine hydrochloride is used in the treatment of panic disorder with or without agoraphobia.
  • A number of studies have indicated that selective serotonin reuptake inhibitors (SSRIs) are effective in reducing the symptomatology accompanying borderline personality disorder (BPD). The SSRIs have proven efficacious in reducing self-injury, suicidality, affective instability, rage, impulsivity, psychosis, and obsessionality.
  • Fluoxetine and sertraline have been shown to be effective in clinical trials, although no single SSRI has emerged as the treatment of choice. Individuals failing one SSRI often respond to another.
  • The data presented in this article indicate that venlafaxine is effective in treating borderline personality disorder (BPD) as an initial intervention and may benefit many individuals for whom fluoxetine or sertraline treatment has failed.
  • Stimulant medications are the most widely accepted treatment of attention deficit hyperactivity disorder (ADHD) in spite of controversy over their use. Stimulants have consistently been shown to potentiate noradrenergic brain transmission, a property also characteristic of the recently marketed antidepressant venlafaxine. Eighteen adults who met the Utah Criteria for ADHD in adults were enrolled in an open trial of venlafaxine.
  • To evaluate the efficacy and safety of venlafaxine, a new-generation antidepressant that selectively inhibits serotonin and norepinephrine reuptake, in the treatment of the premenstrual dysphoric disorder (PMDD). We conducted a randomized, double-blind, placebo-controlled, parallel-group, flexible-dose trial.
  • After three screening cycles, including a single-blind placebo cycle, 164 women were randomly assigned to double-blind treatment with venlafaxine (50-200 mg/day) or placebo for four menstrual cycles.
  • Primary outcome measures were the total premenstrual symptom scores as assessed by a daily symptom report (DSR) and the Hamilton Rating Scale for Depression. Venlafaxine was significantly more effective than placebo in reducing PMDD symptoms as assessed by DSR scores (P <.001 for last observation carried forward and observed analyses).

Contra-Indications of Venlafaxine

  • Syndrome of Inappropriate Antidiuretic Hormone Secretion
  • high cholesterol
  • low amount of sodium in the blood
  • increased risk of bleeding due to a clotting disorder
  • increased risk of bleeding
  • Behaving with Excessive Cheerfulness and Activity
  • Mild Degree of Mania
  • having thoughts of suicide
  • serotonin syndrome – adverse drug interaction
  • closed angle glaucoma
  • Severe Uncontrolled High Blood Pressure
  • heart attack within the last 30 days
  • Hardening of the Liver
  • liver problems
  • Mild to Moderate Kidney Impairment
  • seizures
  • weight loss
  • moderate to severe kidney impairment
  • risk of angle-closure glaucoma due to narrow-angle of the anterior chamber of the eye
  • Allergies to Venlafaxine Analogues
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Dosage of Venlafaxine

  • Strengths: 25 mg; 50 mg; 75 mg; 100 mg; 37.5 mg; 150 mg; 225 mg

Depression

Immediate release

  • Initial dose: 37.5 mg orally twice a day or 25 mg orally 3 times a day
  • Maintenance dose: May increase in daily increments of up to 75 mg orally at intervals of no less than 4 days
  • Maximum dose: (moderately depressed outpatients): 225 mg orally per day
  • Maximum dose (severely depressed inpatients): 375 mg orally per day

Extended-release

  • Initial dose: 75 mg orally once a day
  • Maintenance dose: May increase in daily increments of up to 75 mg orally at intervals of no less than 4 days
  • Maximum dose (moderately depressed outpatients): 225 mg orally per day
  • Maximum dose (severely depressed inpatients): 375 mg orally per day

Anxiety

Extended-release

  • Initial dose: 75 mg orally once a day
  • Maintenance dose: May increase in daily increments of 75 mg orally at intervals of no less than 4 days
  • Maximum dose: 225 mg orally per day

Panic Disorder

Extended-release

  • Initial dose: 37.5 mg orally once a day
  • Maintenance dose: May increase dose in daily increments of 75 mg orally at intervals of no less than 7 days
  • Maximum dose: 225 mg orally per day

Side Effects of Venlafaxine

The most common

Common

Serious

Drug Interactions of Venlafaxine

Venlafaxine may interact with following drugs, supplements & may change the efficacy of drugs

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This medication may interfere with certain medical/laboratory tests (including a brain scan for Parkinson’s disease), possibly causing false test results. Make sure laboratory personnel and all your doctors know you use this drug.

Pregnancy & Lactation of Venlafaxine

FDA Pregnancy Category – C

Pregnancy

This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately.

Lactation

This medication passes into breast milk. If you are a breastfeeding mother and are taking venlafaxine, it may affect your baby. Talk to your doctor about whether you should breastfeeding-feeding. The safety and effectiveness of this medication have not been established for children under 18 years of age. There have been reports that using this and similar medications in children below the age of 18 may cause behavioral and emotional changes, such as suicidal thoughts and behavior.

References

Venlafaxine

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