Venlafaxine
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| Routes of administration | Oral |
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| Pharmacokinetic data | |
| Bioavailability | 45% |
| Protein binding | 27% |
| Metabolism | Hepatic |
| Elimination half-life | 5 ± 2 hours (parent compound); 11 ± 2 hours (active metabolite) |
| Excretion | Renal |
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| ECHA InfoCard | 100.122.418 |
| Chemical and physical data | |
| Formula | C17H27NO2 |
| Molar mass | 277.402 g/mol |
Venlafaxine hydrochloride is a prescription antidepressant first introduced by Wyeth in 1993. It belongs to class of antidepressants, called serotonin-norepinephrine reuptake inhibitors (SNRI). In high doses, it weakly inhibits the reuptake of dopamine as well. Sometimes, this medication is prescribed "off label" for diabetic neuropathy in a similar manner to duloxetine.
As of August 2006, generic venlafaxine is available in the United States. It was previously available only under the brand names Effexor and Effexor XR.
Trade names
Venlafaxine is marketed under the tradenames Effexor® in the UK, Efexor®, Efectin®, Effexor XR® and Efectin ER®
Uses
Venlafaxine is used primarily for the treatment of depression, generalized anxiety disorder, and social anxiety disorder in adults. It has a higher rate of treatment emergent mania than many modern antidepressants, and many people find it to be a more activating medication than other antidepressants. Paradoxically, some users find it highly sedating and find that it must be taken in the evening.
Venlafaxine is an effective anti-depressant for many persons; however, it seems to be especially effective for those with treatment-resistant depression. Some of these persons have taken two or more antidepressants prior to venlafaxine with no relief. It has also been found to reduce the severity of 'hot-flashes' in menopausal women[1]. In addition, a September 2004 Consumer Reports study ranked venlafaxine as the most effective among six commonly prescribed antidepressants. (However, this should not be considered a definitive finding, and responses to psychiatric medications vary significantly from individual to individual.) Many doctors are also starting to use venlafaxine for the treatment of diabetic neuropathy and migraine. In some people however, venlafaxine can exacerbate or cause migraines.
Off-label / investigational uses
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.
Description of compound
The chemical structure of venlafaxine is designated (R/S)-1-[2-(dimethylamino)-1-(4 methoxyphenyl)ethyl] cyclohexanol hydrochloride or (±)-1-[a [α- (dimethylamino)methyl] p-methoxybenzyl] cyclohexanol hydrochloride and it has the empirical formula of C17H27NO2 · HCl. It is a white to off-white crystalline solid, 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).
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.[2][3] It works by blocking the transporter "reuptake" proteins for key neurotransmitters affecting mood, thereby leaving more active neurotransmitter in the synapse. At low and medium dosages, venlafaxine inhibits serotonin reuptake alone, similarly to a selective serotonin reuptake inhibitor (SSRI). At higher dosages (from about 225 mg/day), venlafaxine inhibits the reuptake of norepinephrine as well as serotonin. At high dosages (starting around 300 mg/day), it inhibits dopamine reuptake in addition to serotonin and norepinephrine. Effect on neurochemicals will vary from person to person as well.
Pharmacokinetics
Venlafaxine 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 3–4 weeks.
Prescribed dosages are typically in the range of 75–225 mg per day, but higher dosages are sometimes used for the treatment of severe or treatment-resistant depression. 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.
Side effects — serious adverse reactions
As with most antidepressants, lack of sexual desire can be a very disturbing side-effect for some persons. Venlafaxine can raise blood pressure at high doses, so it is usually not the drug of choice for persons with high blood pressure. Venlafaxine should not be used in children. Caution should also be used in those with a seizure disorder.
The energizing effect of the drug may come unwanted to some, possibly leading to an increased anxiety / depressed mind state. While the specific modality of effect is not well understood, a Black Box Warning has been issued with Effexor and with other SSRI and SNRI anti-depressants advising of risk of suicide. Some studies have questioned the effectiveness of the drug in helping depression. The black box warnings advise physicians to carefully monitor patients for suicide risk at start of usage and whenever the dosage is changed. Family members should be advised of this potentially fatal side effect so they may bring the patient to a hospital emergency for surveillance and protection. This drug is particularly risky for patients whose mental condition includes poor impulse control such as Borderline Personality Disorder, and if there is comorbid substance abuse.
Venlafaxine is sometimes used for the treatment of depressive phases of bipolar disorder. However, 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.
Another risk is Serotonin syndrome. This is a serious effect that can be caused by interactions with other drugs and is potentially fatal.
Common side effects
- Nausea
- Dizziness
- Sleepiness
- Insomnia
- Vertigo
- Dry mouth
- Sexual dysfunction
- Sweating
- Vivid dreams
- Increased blood pressure
- Electric shock like sensations
- Increased anxiety towards the start of treatment
Less common to rare side-effects
- Cardiac arrhythmia
- Increased serum cholesterol
- Gas or stomach pain
- Abnormal vision
- Nervousness, agitation or increased anxiety akathisia
- Panic Attacks
- Depressed feelings
- Suicidal thoughts suicidal ideation
- Confusion
- Neuroleptic malignant syndrome
- Loss of appetite
- Constipation
- Tremor
- Drowsiness
- Allergic skin reactions
- External bleeding
- Serious bone marrow damage (thrombocytopenia, agranulocytosis)
- Hepatitis
- Pancreatitis
- Seizure
- Tardive dyskinesia
- Difficulty swallowing
- Psychosis
- Hostility
- Activation of mania/hypomania.
Severe discontinuation syndrome
Venlafaxine may cause potentially severe withdrawal symptoms upon sudden discontinuation (the recommended discontinuation is a drop of 37.5 mg per week; sudden stops are usually advised only in emergencies). These have a tendency to be significantly stronger than the withdrawal effects of other antidepressants including the tricyclic antidepressants, but are similar in nature to those of SSRIs such as Paroxetine (Paxil® or Seroxat®).
Discontinuation effects may include irritability, hostility, headache, nausea, fatigue, dysphoria and the fairly-unique "brain shivers". Symptoms may include a feeling of spinning, similar to drunken "bed spins"; patients may experience spinning in two different directions, often felt between the area of the head above the nose and below the nose. This feeling of spinning is associated with severe nausea and disorientation. Rarer withdrawal symptoms include shaking legs, tremor, vertigo, dizziness and paresthesia. Other non-specific mental symptoms may include impaired concentration, bizarre dreams, agitation and suicidal thoughts.
Antidepressant withdrawal effects do not indicate addiction, but are rather the results of the brain attempting to reach neurochemical stability after an abrupt change. These can be minimized or avoided by tapering off of the medication over a period of weeks.
The distinction between "withdrawal" effects and addiction may be nothing less than semantics to make a distinction between a prescribed anti-depressant and illicit drugs, as addicts also suffer withdrawal effects when trying to stop taking an illicit drug. This is in the vein of the use of the term "self-medicating" to feel good as a euphemism for addiction. People reading about a drug like Effexor should be aware of these choices of words to minimize the actual reality of withdrawal "effects".
Studies by Wyeth-Ayerst and others have reported occasional cases of withdrawal symptoms severe enough to require permanent use. In some of these cases, successful discontinuation was eventually achieved by the addition of fluoxetine, which was later discontinued itself without difficulty.
It is important for patients to be aware of these risks so their choice to take this drug is balanced against the severity of potential side effects. A petition to Wyeth, signed by more than 11,000 patients as of June 2006, argues that disclosure regarding the side effects and efficacy is neither full nor accurate and asks Wyeth to improve the Effexor documentation for patients and medical professionals.[4]
"Patel Carolina & Associates PLLC" filed a lawsuit in 2004 due to the discontinuation side effects of the drug.
External links
- Detailed Effexor Consumer Information: Uses, Precautions, Side Effects
- PubChem Substance Summary: Venlafaxine National Center for Biotechnology Information.
- Effexor XR® prescribing information for healthcare professionals (pdf) (USA only)
- Efexor patient information leaflet Efexor patient information leaflet
- The Offical website of Effexor XR The Official website of Effexor XR
End notes
- ^ Mayo Clinic staff (2005). "Beyond hormone therapy: Other medicines may help". Hot flashes: Ease the discomfort of menopause. Mayo Clinic. Retrieved 19 August.
{{cite web}}: Check date values in:|accessdate=(help); Unknown parameter|accessyear=ignored (|access-date=suggested) (help) - ^ [No Authors listed] "Acute Effectiveness of Additional Drugs to the Standard Treatment of Depression." ClinicalTrials.gov. 23 June 2005.
- ^ Goeringer KE, McIntyre IM, Drummer OH (2001). "Postmortem tissue concentrations of venlafaxine". Forensic Science International. 121 (1–2): 70–5. PMID 11516890.
{{cite journal}}: CS1 maint: multiple names: authors list (link) Fulltext options List of Library Holdings Worldwide