Venlafaxine

BRAND NAMES

Effexor: It contains an active ingredient venlafaxine and available in extended-release capsules. It supports the preservation of the chemical equilibrium in the brain that affects behaviour and mood. This improves your vitality, improves your mood, reduces stress and worry, and improves your ability to sleep.

MECHANISM OF ACTION

Venlafaxine boosts serotonin and norepinephrine levels in the central nervous system by preventing reuptake at the presynaptic terminals. This activity increases the availability of neurotransmitters at the synapse, which stimulates postsynaptic receptors. SNRIs predominantly influence serotonergic and noradrenergic neurons but have little or no effect on cholinergic or histaminergic receptors. Venlafaxine is a bicyclic phenylethylamine molecule. Venlafaxine is more effective in inhibiting serotonin reuptake than norepinephrine reuptake. Venlafaxine inhibits serotonin reuptake at low dosages, while at larger concentrations it affects both norepinephrine and serotonin reuptake. Antidepressants like venlafaxine boost brain-derived neurotrophic factor expression and neuroplasticity. Venlafaxine has also been shown to improve neuroinflammation.

PHARMACOKINETICS

Absorption

Venlafaxine is highly absorbed orally (92%) but has a low bioavailability of 45%. Peak plasma concentrations are usually achieved within 2 to 3 hours for immediate-release formulations and 5.5 to 9 hours for extended-release formulations.

Distribution

Venlafaxine's plasma protein binding varies from 27% to 30%, and its volume of distribution is 7.5 L/kg.

Metabolism

Venlafaxine is mostly metabolized by the liver, specifically through the cytochrome P450 system and the CYP2D6 enzyme.

Elimination

Venlafaxine's elimination half-life varies by formulation, with the immediate release being around 5 hours, extended-release besylate at 6.8 hours, and extended-release hydrochloride at 10.7 hours. However, people with renal or hepatic impairment may have a longer half-life. Mostly venlafaxine is removed in urine, accounting for around 87% of the entire dosage. This excretion includes 5% unaltered medication, 29% unconjugated O-desmethyl venlafaxine, and 26% conjugated O-desmethyl venlafaxine. Furthermore, 27% of the dosage is excreted as small, inactive metabolites.

PHARMACODYNAMICS

Venlafaxine is an antidepressant medication that aims to alleviate the symptoms of many mental diseases by boosting neurotransmitter levels in the synapse. Venlafaxine does not produce muscarinic, histaminergic, or adrenergic effects.

DOSAGE AND ADMINISTRATION

It is recommended to take venlafaxine with meals rather than alcohol to prevent overdosing. Venlafaxine is available as an oral tablet and an oral capsule. The extended-release tablet cannot be crushed or sliced, whereas the immediate-release tablet may. First-line treatment for depression often consists of two or three doses of immediate-release oral tablets, totaling 75 mg per day. Venlafaxine is only prescribed to adults who are at least eighteen years old; children should not use it. Venlafaxine should not be used with alcohol, as it might make patients more drowsy. Instead, patients should take the medicine with meals.

CONTRAINDICATIONS

Concurrent use of MAO inhibitors is a contraindication to venlafaxine. Hypersensitivity to venlafaxine, desvenlafaxine succinate, or excipients is a contraindication for this medication.

DRUG INTERACTIONS

• During use of desvenlafaxine with other serotonergic medicines should be avoided due to the danger of serotonin syndrome caused by overstimulation of brainstem 5HT-1A receptors. It is not suggested to take venlafaxine concurrently with SNRIs, SSRIs, triptans, TCAs, opioids, lithium, buspirone, amphetamines, tramadol, tryptophan, or St John's Wort. When venlafaxine is used in conjunction with these drugs, signs of serotonin syndrome must be monitored closely. If serotonin syndrome is suspected, immediate assessment and consideration for withdrawal of venlafaxine and the other serotonergic medications implicated are recommended to reduce potential adverse effects and guarantee patient safety.
• Venlafaxine can interact with a variety of different drugs and plants.
• Patients should not use venlafaxine with MAOIs, linezolid, or methylene blue.
• Clarithromycin, ritonavir, and ketoconazole may block the breakdown of venlafaxine, causing it to accumulate in the body.
• The simultaneous use of venlafaxine with lorazepam, zolpidem, or diphenhydramine can cause sedation.

SIDE EFFECTS

The common side effects of Venlafaxine

• headaches
• nausea
• insomnia
• dizziness
• somnolence
• asthenia
• hypertension
• constipation
• weight loss
• diarrhoea
• abdominal pain
• blurred vision
• anxiety
• hypercholesterolemia
• hyponatremia
• Serotonin syndrome

TOXICITY

Symptoms of a venlafaxine overdose include tachycardia, peculiar tiredness, dilated pupils, convulsions, vomiting, cardiac arrhythmias, hypotension, muscular aches or pains, and disorientation. Venlafaxine toxicity is severe, especially when taken with other antidepressants such as SSRI, SNRI, or MAOI, which can cause serotonin syndrome. Serotonin syndrome is a potentially fatal illness characterized by elevated serotonergic activity in the central nervous system. Serotonin syndrome can present with a wide range of clinical signs, including autonomic hyperactivity, mental state changes, and abnormalities of the neuromuscular system. Serotonin syndrome is known to cause myoclonus, agitation, abdominal cramps, hyperpyrexia, hypertension, and occasionally even mortality.

To restore normal hemodynamics, serotonergic drugs must be rapidly stopped, and supportive care must be provided. Benzodiazepines and serotonin antagonists may also be used to sedate patients. If benzodiazepines and supportive care don't work, cyclotheptadine may be a viable alternative.