Can Pristiq and Fluoxetine be Taken Together? (+3 Risks)

In this article, we will discuss whether Pristiq and fluoxetine can be taken together. We will also discuss the potential risks and benefits of taking these medications together and other relevant information. 

Can Pristiq and fluoxetine be taken together?

Pristiq and fluoxetine may or may not be taken together. Research on their concomitant use has been limited. Both of these drugs are used for major depressive disorder (MDD). Your healthcare provider may prescribe them together in certain conditions. 

Pristiq is the brand name for desvenlafaxine which is a serotonin-norepinephrine reuptake inhibitor (SNRI) and an antidepressant. It works by blocking the reuptake of serotonin and norepinephrine (NE) and increases their concentration in the body (1). 

Fluoxetine belongs to the class of selective serotonin reuptake inhibitors (SSRIs) and is an antidepressant. It blocks the reuptake of serotonin and increases its concentration in the brain while having a minimal effect on NE concentration (2). 

Pristiq and fluoxetine are FDA-approved to treat MDD. SSRIs like fluoxetine are the primary choice of treatment for MDD. Pristiq is considered for patients with MDD who also have comorbid pain disorders (3). 

Both of these drugs have a slightly different mechanism of action and different indications. Concomitant use of SNRIs and SSRIs should be done precautiously due to the increased risk of serotonin syndrome. 

What does research suggest?

The research on the combined use of Pristiq and fluoxetine is limited. There are no studies that report the efficacy, risks, or benefits of their concomitant use. However, the combined use of other SSRIs and SNRIs has been studied. 

Research suggests that initially, the treatment of depression is done with a single antidepressant to avoid the risks of increased side effects associated with polypharmacy. Combined treatment is recommended in treatment-resistant depression (4). 

Multiple antidepressants can address different symptoms of patients at the same time and optimize the treatment effects. Studies show that combining fluoxetine with drugs that influence NE has produced better outcomes than monotherapy (4).

It is also assumed that combining SSRIs like fluoxetine with newer antidepressants including SNRIs may have reduced risks of side effects (4). Pristiq is also associated with fewer side effects and less concern for drug-drug interactions (1). 

One study demonstrated that combining drugs that act on serotonin and NE is more effective and rapid than monotherapy. Thus the combination is more likely to improve depression than selective agents alone (5). 

The evidence mentioned above indicates that Pristiq and fluoxetine may be used in combination for treatment-resistant depression or other cases. However, the research on their concomitant use is limited at the moment. 

What are the potential benefits of using Pristiq and fluoxetine together? 

The combined use of Pristiq and fluoxetine could be potentially beneficial due to their slightly different mechanisms of action. Both drugs increase serotonin concentration. Additionally, Pristiq also increases the levels of NE in the body. 

Serotonin deficiency is observed in depressed patients and is associated with low mood and other negative emotions. The combined effect of these medications improves serotonin concentration and helps with depression (6). 

Pristiq along with serotonin also improves NE concentration. NE deficiency is associated with a reduction in pleasure, happiness, energy, alertness, interest, and other depressive symptoms (6). 

Thus, the combination of these drugs can enhance the effects on serotonin and also provide additional benefits of increased NE levels which addresses diverse symptoms of MDD. 

The combination should only be used if guided by the healthcare provider. The enhanced effects of serotonin can result in serious side effects. Therefore, carefully adjusted doses are required to achieve the potential benefits of this combination. 

What are the potential risks of using Pristiq and fluoxetine together?

Inappropriate use of Pristiq and fluoxetine can result in serious consequences. These are as follows: 

Increased risk of serotonin syndrome: 

Serotonin syndrome is a rare but lethal condition caused by excessive levels of serotonin in the body. Drugs that increase serotonin levels may result in this side effect. Combining Pristiq and fluoxetine increases the risk of serotonin syndrome. 

Serotonin syndrome is life-threatening due to which the combined use of serotonergic drugs is recommended to be done with precaution and strict monitoring. Symptoms of serotonin syndrome include (1):

• increased heart rate
• increased saliva production
• pupil dilation
• hyperactive bowel sounds
• excessive sweating 

Increased side effects: 

Pristiq and fluoxetine are associated with different side effects. Some side effects are associated with both of these medications. The combined use of Pristiq and fluoxetine amplifies the risk of shared side effects. 

Some side effects shared by Pristiq and fluoxetine are as follows (1,2,7): 

• nausea
• diarrhea
• dry mouth
• reduced appetite 
• sweating
• anxiety
• insomnia
• suicidal thoughts
• weight gain/loss 

Increased risk of bleeding: 

Pristiq and fluoxetine are associated with increased risk of bleeding and bruising and this risk is exacerbated with concomitant use. Serotonin plays a role in hemostasis and platelet aggregation (8). 

Pristiq and fluoxetine block the transporter which carries serotonin to the platelets. A decrease in serotonin levels of platelets reduces platelet aggregation and makes it easier for an individual to bruise and bleed. 

Thus, a combined use of these drugs enhances the risk of bleeding and bruising in individuals. 

What are some alternative approaches if combined antidepressant therapy doesn’t work? 

Due to the increased side effects, some individuals might not be able to tolerate combined treatment with two antidepressants. In such cases, the healthcare provider may recommend psychotherapy along with one antidepressant. 

Different psychotherapeutic approaches have worked for depression. They are generally used when the patient is unable to tolerate medications or when psychosocial factors are associated with depression (9).

Some psychotherapeutic approaches used to manage depression are as follows:

Cognitive Behavioral Therapy (CBT): 

CBT has been an effective approach to treat depression when used along with pharmacotherapy. CBT targets the dysfunctional thoughts of an individual and modifies the beliefs that maintain depression (9). 

The efficacy of CBT in treating depression has been well established. It reduces the chance of recurrence and increases adherence to medications (9). Thus, it can be paired with one antidepressant to improve treatment outcomes. 

Interpersonal Psychotherapy (IPT):

IPT is an effective approach for depression and can be combined with medications. It targets the interpersonal issues that cause depression. The individuals are helped to break the interaction between their symptoms and interpersonal issues (10). 

It helps the patients to improve their interpersonal functioning by enhancing communication, expressing emotions and actively participating in current relationships (10). 

Thus, if combining two antidepressants like Pristiq and fluoxetine causes increased side effects in an individual, the healthcare provider may pair one antidepressant with psychotherapy. 

In my perspective, Pristiq and fluoxetine may or may not be used together. The studies on the effects of their combined use are limited. Evidence suggests that combined use of SSRIs and SNRIs can be a beneficial approach to treating major depressive disorder due to enhanced effects on serotonin and additional effects on NE. However, the combined use can increase the risks of side effects, serotonin syndrome, and bleeding. Using Pristiq and fluoxetine together should be done under the guidance of a healthcare provider. Under some conditions, these drugs may be prescribed together. 

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