Can you take Celexa with amitriptyline? (3+ benefits)

In this article, we will talk about whether Celexa can be taken with amitriptyline. We will discuss the potential benefits of using these drugs together and also share the risks associated with this combination. 

Can you take Celexa with amitriptyline? 

Yes, you can take Celexa with amitriptyline if prescribed by a healthcare provider. Celexa and amitriptyline both are antidepressants and are often prescribed together to enhance their therapeutic effects. 

Celexa has the active ingredient citalopram and amitriptyline is a generic drug. Following is the description of these drugs, their classification, and mechanism of action (1,2):  

antidepressant classification mechanism of action FDA-approved indication 
Celexa (citalopram) selective serotonin reuptake inhibitor (SSRI)
  • blocks serotonin reuptake, thereby increasing its concentration in the body
  • mild antihistaminic activity
amitriptyline  tricyclic antidepressant (TCA) 
  • blocks the reuptake of serotonin and norepinephrine (NE), thereby increasing their concentration in the body
  • antagonist action at histamine, alpha-adrenergic, and muscarinic receptors 
major depressive disorder 

Celexa and amitriptyline can be used together as the combination can provide additional therapeutic benefits. However, concomitant use of these medications should be done under medical oversight. 

What are the benefits of using Celexa with amitriptyline? 

Celexa and amitriptyline when used together can provide the following benefits: 

Enhanced therapeutic action:  

Celexa and amitriptyline increase the levels of serotonin in the body and a deficit of serotonin is involved in disorders like depression. Serotonin dysfunction in the body contributes to symptoms like low mood, anxiety, self-blame, and disgust (3). 

Amitriptyline also influences the levels of NE in the body. Individuals with reduced NE present with symptoms like reduced confidence, pleasure, interest, and passion (3). 

Thus, by influencing NE along with the increased effect on serotonin, the therapeutic action is enhanced with concomitant use. 

Management of treatment-resistant depression: 

Research indicates that 30-45% of patients with depression do not respond adequately to the initial treatment of depression (4). In some cases, the second trial of antidepressant therapy might also not work well for the patients. 

Different strategies are suggested to address difficult-to-treat depression. One of the strategies is to combine agents that influence serotonin with agents that affect NE levels in the body (4). 

Thus, the combination of Celexa and amitriptyline can target serotonin and NE together as dysregulation of both neurotransmitters can be involved in the development of depression. 

Research indicates that combining antidepressants works well and is a more successful approach than treatment with a single antidepressant.

Thus, if depression doesn’t improve after treatment with an SSRI, amitriptyline can be added. 

Enhanced therapeutic benefits: 

Celexa and amitriptyline are used off-label for several conditions and the combination can provide additional symptomatic management. Off-label uses of Celexa include different anxiety and depressive disorders (1). 

Amitriptyline is used to manage insomnia, chronic neuropathic pain, and preventive treatment of migraine (2). Combining it with Celexa can help address these symptoms that may occur with depression. 

Research suggests that a combination of Celexa and amitriptyline can be used to manage migraines and tension-type headaches that can occur with depression (5)

Reduced risk of side effects: 

The combination of SSRIs with TCAs has been studied widely and research suggests that SSRIs like paroxetine, sertraline, fluoxetine, and fluvoxamine can elevate the TCA concentration in plasma if given together (6). 

However, citalopram does not behave like other SSRIs and does not influence the plasma levels of amitriptyline. Thus, Celexa can provide the benefits of combining SSRIs and TCAs without increasing the risk of side effects (6). 

What are the risks of using Celexa with amitriptyline? 

Using Celexa with amitriptyline can enhance the risk of serotonin syndrome, drowsiness, and side effects. The following are the risks of using Celexa with amitriptyline: 

Risk of serotonin syndrome: 

Concomitant use of drugs that increase serotonin levels like Celexa and amitriptyline can result in a lethal condition called serotonin syndrome if there is excessive accumulation of serotonin in the body. 

Symptoms of serotonin syndrome include: 

  • restlessness
  • mental confusion
  • pupil dilation
  • increased heart rate
  • excessive sweating
  • raised blood press
  • increased salivation
  • muscle rigidity
  • tremors
  • unconsciousness 

Increased sedation: 

Celexa and amitriptyline both have antihistaminic properties which contribute to their sedative effect. The sedation is enhanced when the drugs are used together resulting in side effects like drowsiness and impaired cognition. 

Enhanced side effects:

Celexa and amitriptyline are associated with their respective set of side effects and the incidence of side effects is enhanced when the drugs are used together. Shared side effects of Celexa and amitriptyline are also amplified. 

Side effects of Celexa include (1): 

  • drowsiness
  • sweating
  • constipation
  • sleep disturbance
  • nausea
  • lightheadedness
  • vomiting
  • diarrhea
  • ejaculation problems
  • suicidal thoughts
  • mania 
  • dry mouth 
  • easy bruising
  • QT prolongation 

Side effects of amitriptyline include (2):

  • suicidal thoughts
  • orthostatic hypotension
  • lightheadedness
  • blurry vision
  • enhanced appetite
  • dry mouth 
  • increased weight
  • mental confusion
  • QT prolongation
  • urinary retention 
  • headache

How to take Celexa with amitriptyline? 

Celexa can be used with amitriptyline if your healthcare provider has advised it. Do not combine the medications by yourself as inappropriate use can result in serious adverse effects. 

Your healthcare provider may prescribe Celexa and amitriptyline together based on your condition and will make necessary dose adjustments to enhance the therapeutic outcomes and minimize the adverse effects. 

If you experience drowsiness while taking the medications, avoid driving and operating heavy machinery. If you experience symptoms of serotonin syndrome or other adverse effects, contact your healthcare provider. 

In my perspective, Celexa can be taken amitriptyline if your healthcare provider has advised it. The combination provides benefits like enhanced therapeutic action, increased benefits, and management of treatment-resistant depression. 

Celexa with amitriptyline should be used under medical oversight as combining these drugs increases the risk of serotonin syndromes, and elevates the side effects including sedation and drowsiness. 

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