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SNRIs are sometimes prescribed for anxiety when SSRIs have proved ineffective. Like many medications they have associated risks and benefits and need to be used in conjunction with psychological therapies for the most benefit.

As 40 million people in the United States are thought to have anxiety disorders, a number that amounts to nearly 20 percent of the population yearly. Anxiety disorder prevalence worldwide varies from more than two to more than six percent by country; worldwide in 2016 around 275 million people had an anxiety disorder, making it the most prevalent mental health condition being experienced.

Anxiety disorders place a considerable burden in many ways. They are reported to cost the U.S. in excess of $42 billion a year, which amounts to as much as one third of their total mental health bill. More than half of those costs are related to the repeat use of healthcare services because those with anxiety disorders tend to frequently seek assistance for symptoms associated with physical illnesses.

Those suffering from anxiety disorder are more likely to visit the doctor (by three-to-five times) and six times more likely to be admitted to hospital for mental health difficulties than non-sufferers.

The considerable socio-economic burden associated with these disorders has led to theories being developed to build responsive clinical treatment approaches. One such theory, the monoaminergic hypothesis, has led to the development of several generations of selective and non-selective inhibitors of transporters of serotonin and norepinephrine, with the goal of accentuating monoaminergic transmission.

The monoamine hypothesis of mood disorders posits that the underlying basis of depression is a depletion in neurotransmitters (the chemicals that neurons use to communicate with each other) known as monoamines. Serotonin, norepinephrine, and/or dopamine are central nervous system monoamines. This conclusion was reached in the 1950's following the prescribing of certain medications for other conditions which either led to or resulted in the lifting of formerly depressed mood. Noting that lowering the levels of monoamines causes depression, while raising them lifts depression, led to the conclusion that these neurotransmitters were involved in the development or maintenance of mood disorder.

These findings about monoamines caused much excitement and has led to this hypothesis which forms the basis of modern prescribing. However, contemporary research has been unable to find supportive evidence to support the notion of a primary dysfunction of a specific monoamine system in those with major depressive disorders. For example, when investigating selective serotonin reuptake inhibitors (SSRIs), contemporary research has been unable to confirm any serotonergic deficit in any mental disorder, and has actually provided significant evidence to the contrary – that there is no scientifically established ideal “chemical balance” of serotonin, let alone an identifiable imbalance in the condition. Furthermore, the risk of serious harm is often not fully declared. A recent study found that pharmaceutical companies were not being transparent regarding all of the results of drug trials. When documents from 70 different double-blind, placebo-controlled trials of and serotonin and norepinephrine reuptake inhibitors (alongside SSRIs) were examined, it was found that the extent of serious harm in clinical study reports largely went unreported. For example, the reports showed that the risk of suicide and violence were 4-5 times more common; as was the risk of experiencing a psychotic event; and yet this is not declared as a risk for most people when being prescribed anti-depressants.

What are Serotonin-norepinephrine reuptake inhibitors?

Serotonin-norepinephrine reuptake inhibitors, or SNRIs, are medications used to help depression and anxiety. The following medications may be used in the following ways:

  • Effexor (venlafaxine) – prescribed for OCD, social anxiety, panic and generalized anxiety

  • Pristiq (desvenlafaxine or Venlafaxine XR) – prescribed for OCD, social anxiety, panic and generalized anxiety

  • Cymbalta (duloxetine) – prescribed for OCD, social anxiety, panic and generalized anxiety

These SNRIs are the ones most commonly prescribed for anxiety. They are similar to selective serotonin reuptake inhibitor (SSRIs) in that they increase the levels of specific neurotransmitters. However rather than just serotonin, they also inhibit the reuptake of norepinephrine. The reason norepinephrine is believed to be important is because it is understood to be involved in the stress response, which underpins anxiety reactions.

Inside SNRIs – How do they work?

SNRIs increase levels of both serotonin and norepinephrine in the brain. Norepinephrine is used as a neurotransmitter by a variety of neural systems including both the amygdala and hippocampus; and norepinephrine is thought to influence both the thalamus and prefrontal areas of the cortex. And it regulates bodily systems involved in breathing, heart rate and blood flow to the muscles. Norepinephrine specifically is responsible for how the person reacts to stress and anxiety and is associated with the fight-or-flight response.

As with SSRIs, in the short-term people report and increase in anxiety but this is said to taper off after a couple of weeks. Like SSRIs, SNRIs are thought to promote brain neuro-plasticity: it is argued that after a week or so, the increased levels of norepinephrine and serotonin may result in neuron and circuitry-remodeling in ways which support increased flexibility. Therefore it is hypothesized that if the circuitry in the brain is more susceptible to modification, medication can reinforce and support the changes that psychotherapeutic approaches encourage you to make.

Common Side Effects of SNRIs

  • Dryness in the mouth or xerostomia
  • Nausea or vomiting
  • Nervousness or agitation
  • Insomnia or drowsiness
  • Dizziness or lightheadedness
  • Headaches
  • Sexual difficulties
  • Appetite loss
  • Digestive issues including constipation
  • Sweating

Because SNRIs target norepinephrine receptors as well as serotonin ones, SNRIs are reported to have more side effects than SSRIs but less of the serious ones. SNRIs tend to be prescribed when the response to SSRIs has been inadequate.

In terms of mechanism of action there is a significant connection between enhanced noradrenergic activity and anxiety and fear. Therefore, it seems contradictory that serotonergic and noradrenergic reuptake inhibitors would be successful in the treatment of anxiety and panic disorders. Ultimately, there may be many mechanisms at work to explain why a medication works – most of which are likely to be more psychological in origin. For example, the belief for an individual that they are being acknowledged and treated is a significant component in symptom relief. Furthermore, the psychoactive nature of these drugs is perhaps underestimated and it may be that the mechanism of action is not so different to self-medication with substances of one sort or another. The drug lifts mood but in the same way an illicit substance would, rather than it fixing some underlying imbalance.