How are amitriptyline and Effexor different? (+3 points)

In this article, we will explore the key differences between Effexor and amitriptyline, the differences in their classes, mechanism of action, side effects and usage. How to select the best treatment option out of the two medications will also be discussed. 

How are amitriptyline and Effexor different?

Although amitriptyline and Effexor (venlafaxine) are both used to treat depression and related disorders, they belong to different classes of antidepressants. Amitriptyline and Effexor have distinct differences in their:

  • Class of medication
  • Mechanism of action
  • Side effects
  • Pharmacological uses
  • Dosage and administration

Amitriptyline and Effexor are not taken or prescribed together due to the risk of increased side effects. However, if you are prescribed any of these two medications for your condition then you need to consult your healthcare provider regarding any queries you have related to these two medications.  

Class of medication

Amitriptyline and Effexor belong to different classes of antidepressants, each having its distinct mechanism of action. Amitriptyline is the generic for Elavil. It belongs to the class of tricyclic antidepressants (TCA). Drugs belonging to this class have a wider range of effects on the neurotransmitters. TCAs are an older class of antidepressants (1).

On the other hand, Effexor is a brand of venlafaxine that belongs to the class of serotonin-norepinephrine reuptake inhibitors (SNRI). These drugs have more targeted action on the specific neurotransmitters (2). SNRIs are a rather newer class of antidepressants.

Mechanism of action

Tricyclic antidepressants such as amitriptyline inhibit the reabsorption of neurotransmitters such as serotonin and norepinephrine. This inhibition of the reuptake of these neurotransmitters increases their levels in the brain. In addition to this, amitriptyline also binds to some other receptors in the brain such as histamine receptors or muscarinic receptors (3). 

Amitriptyline takes about a week to reach the full extent of its effects.

Effexor is the brand name of venlafaxine, which belongs to the class of serotonin-norepinephrine reuptake inhibitors. Effexor potentiates the inhibition of the reuptake of serotonin and norepinephrine causing these neurotransmitters to stay in the synaptic cleft and continue transmitting signals (4). 

Effexor does not cause any additional effects on any other receptors, unlike amitriptyline. It has a more targeted action as compared to amitriptyline. 

Side effects

The side effects profile of Effexor and amitriptyline is slightly different due to their mechanism of action (5) (6). 

Side effect Amitriptyline (TCA) Effexor (SNRI)
Anticholinergic effects Common Less prominent compared to TCA
Weight gain  Possible Possible but generally less than TCA
Cardiovascular effects May cause changes in heart rate, orthostatic hypotension Possible increase in blood pressure, especially at higher doses
Sexual effects Can cause sexual dysfunctioning May impact sexual function
Withdrawal symptoms May have withdrawal symptoms if stopped abruptly Can cause withdrawal symptoms if discontinued abruptly
Gastrointestinal issues Constipation or diarrhoea, nausea Nausea, possible gastrointestinal disturbances
Sedation Common can cause drowsiness but is generally less sedating at low doses

Pharmacological uses

Amitriptyline and Effexor are used for several purposes. Their indications differ due to differences in their mechanism of action (7) (8).

Medications Effexor Amitriptyline
FDA approved uses
  • Major depressive disorder
  • Social anxiety disorder
  • General anxiety disorder
  • Panic disorder
  • Major depressive disorder
  • Neuropathic pain
  • Migraine Prophylaxis
Non-FDA approved uses
  • Anxiety disorder
  • Fibromyalgia
  • Insomnia
  • Some chronic pain conditions

Dosage and administration

When taking Effexor, its daily dose is divided into two to three divided doses that are to be taken throughout the day. It is not to be taken all at once. However, its extended-release dosage form is to be taken once daily. The starting dose of Effexor is lower as compared to amitriptyline. It can be taken with or without food (9).

On the other hand, amitriptyline has a comparatively higher starting dose. Amitriptyline is taken once daily and the dose depends upon the condition of the patient. The starting dose is low and then gradually increased to help the body adjust better to its effects (3). 

Amitriptyline is available in oral tablet forms and is usually taken before bed due to the sedative effects of amitriptyline. 

How to choose between Effexor and amitriptyline?

If you have to choose the best medication out of the two antidepressants i.e., Effexor and amitriptyline, then certain factors are to be considered. Even if both these are antidepressants, they differ in many aspects which leads to different indications for the two medications. The following factors are to be considered if you want to select the best possible option.

  • Frequency and severity of condition
  • Side effect profile
  • Individual’s response
  • Underlying health condition
  • Patient preferences
  • Cost and availability

Consulting healthcare provider

Effexor and amitriptyline have different uses. You need to consult your healthcare provider to consider every single aspect in order to make the best possible decision. These two medications interact differently with other drugs and medical conditions.

Your doctor will need to properly analyze your condition and take your past medical history to make the proper diagnosis. Considering your condition, your doctor will have to select the best medication out of the available options to ensure maximum effectiveness.

In my opinion, amitriptyline and Effexor are generally antidepressants but they belong to different classes of drugs. This is the basic reason for all the differences between the two antidepressants. Due to differences in their drug class and mechanism of action, Effexor and amitriptyline differ in their usage and administration as well.

Selecting the most appropriate drug for the treatment of your condition is a critical decision that should be taken by an experienced healthcare provider. 

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