Serotonin-norepinephrine reuptake inhibitor (SNRI) Information Sheet

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What is an SNRI?

SNRI is an acronym for Serotonin-norepinephrine reuptake inhibitor.

SNRI Description:

Serotonin-norepinephrine reuptake inhibitors are a class of antidepressants used for the treatment of depression and other affective disorders. The drugs are sometimes also used to treat anxiety disorders, attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD) and chronic neuropathic pain. They act upon two neurotransmitters in the brain that are known to be essential to mood, namely serotonin and norepinephrine. This is in contrast to the more widely-implemented selective serotonin reuptake inhibitors (SSRIs), which affect only serotonin.

It should be noted that the abbreviation “SNRI” should not be used for “selective norepinephrine reuptake inhibitors”.

SNRI Treatment and usage:

SNRIs are mainly indicated for treating clinical depression, but they are often prescribed for anxiety disorders, panic disorders, obsessive compulsive disorder (OCD) and eating disorders.

SNRI Method of action:

Activity on epinephrine reuptake is believed to be necessary for an antidepressant to be effective on neuropathic pain. This is a characteristic shared with the older tricyclic antidepressants, but not with SSRIs.

Depression is believed to be caused by a lack of information flow between neurons in certain parts of the brain. Neurons exchange information with each other through chemicals called neurotransmitters, which shoot across the tiny synapses (gaps) between the cells. After firing, most of the neurotransmitter is reabsorbed by the presynaptic cell.

This process is called reuptake.

Antidepressants work by increasing the amount of neurotransmitters active in the synapse, thus enhancing the neuronal activity and increasing mood response. Modern antidepressant drugs normally achieve this effect by blocking the transporter proteins that reabsorb certain neurotransmitters, hence the name “reuptake inhibitors.”

SNRIs are newer than SSRIs, and there are only a small number of them at present. Their efficacy and tolerability appear to be somewhat better than SSRIs, likely due to their compound effect.

Warnings or dangers associated with SNRIs:

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There has been controversy surrounding SNRIs. Some people feel that the drugs are prescribed by over-zealous psychiatrists or doctors when there use is only marginally indicated. According to this argument, societal pressures have created the pursuit of “normal” mental or emotional functioning by chemical means rather than holistic approaches (altering diet, exercise, sleep habits, stress reduction, etc).

As well, in late 2004 a media firestorm ensued after it was announced that antidepressants may be linked to teen suicide. Because of this, the FDA now warrants a cautionary statement to parents and children who may be prescribed SNRIs or SSRIs by their doctor. The FDA has ordered a “black box warning” be placed on the package inserts of the drugs. A pooled analysis of placebo-controlled trials of 9 antidepressants resulted in a risk of suicidality (suicidal thought and behavior) twice has high as with placebo. Other studies have shown no increase in suicidality but a small increase of non-fatal self-harm, and even of a reduction in incidence of suicide.

SNRI medications should not be taken by patients also taking monoamine oxidase inhibitors (MAOIs). This can lead to increased serotonin levels and cause serotonin syndrome (a rare, but serious and potentially life-threatening condition unfortunately often mistaken for a viral illness, anxiety, neurological disorder or worsening psychiatric condition). People with hypersensitivity to SNRIs or any of their active ingredients should avoid taking them.

Patients with major depressive disorder (MDD), whether adult or pediatric, may experience worsening of their depression and/or the development of suicidal thought and behavior or unusual changes in behavior, whether or not they are taking medications. There has been concern that antidepressants may lead to worsening depression and suicidality in certain patients, especially in children and adolescents with MDD and other psychiatric disorders.

As such, all pediatric patients being treated with antidepressants for any indication should be closely monitored for clinical worsening, suicidality, and any abnormal behavior, especially during the initial phase of treatment, and any time the dose is changed. Adult patients with MDD or co-morbid depression with other psychiatric illness being treated with SNRIs or any other antidepressants should be closely observed in a similar fashion for clinical worsening and suicidality, especially during treatment induction and dosage change.

SNRI Side effects:

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The reported side effects of taking SNRIs include gastrointestinal complaints such as dry mouth, nausea, and anorexia, somnolence (drowsiness), dizziness, abnormal dreams, sweating, sexual dysfunction, insomnia, tremor, nervousness and hypertension.

It is well documented that SNRIs can cause various sexual dysfunctions such as anorgasmia (inability to reach orgasm, most notably in women), diminished libido (sex drive) and erectile dysfunction or difficult/premature ejaculation in men. These side effects occasionally disappear spontaneously without discontinuing use of the drug, and in most cases resolve themselves after stopping taking the SNRI.

SNRI Overdose and withdrawal:

SNRI medications seem to be “safe” in overdosage. There have been reports of acute overdose with some types of SNRI medications during pre-marketing evaluation. One patient – who had overdosed with a combination of an SNRI and a benzodiazepine – was hospitalized, treated symptomatically, and recovered without adverse effects.

Of two other reports of acute overdose, one patient took a combination of an SNRI, an SSRI, and a sedative/hypnotic. This patient was hospitalized, treated with activated charcoal, and recovered with no untoward effects. The other patient took an overdosage of an SNRI alone. This patient recovered and no other specific problems occurred. The patient experienced moderate dizziness, nausea, numbness in the hands and feet, and hot-cold spells 5 days after the overdose. The symptoms resolved over the next week.

In post-marketing experience, overdose with SNRIs has commonly occurred in combination with alcohol and/or other drugs. In these instances, electrocardiogram changes, sinus and ventricular tachycardia, bradycardia, hypotension (low blood pressure), altered level of consciousness (from somnolence to coma), rhabdomyolysis, seizures, vertigo, liver necrosis, and death have been reported. Therefore, it is not recommended to consume alcohol while on SNRI therapy.

It should be noted that abrupt discontinuation of SNRIs, as with any antidepressant, may lead to the development of adverse reactions, including discontinuation syndrome (much like SSRIs), which is a condition that can occur following the interruption or discontinuation of regular SSRI or SNRI use. The condition can begin between 24 hours to one week after discontinuation, depending on the half-life of the drug.

A number of possible symptoms can characterize discontinuation syndrome. They may include sleep disturbances (such as insomnia, vivid dreaming, fatigue, or mild pre-narcolepsy), gastrointestinal discomfort (such as diarrhea), other discomfort such as headaches, nausea lethargy, movement disorders (including trembling and difficulty walking), mood disorders (aggressive behavior, mania, irritability, crying spells, depression/suicidal thoughts) and sensory abnormalities (balance problems, vertigo, dizziness, light-headedness, parasthesia and “shock-like” sensations).

Due to the possibility of this condition, abruptly ceasing the medications is not recommended. The dosage should be tapered to avoid or lessen the chance of adverse reactions.

Types of SNRIs:

SNRIs currently available include:

• Effexor (venlafaxine) – the first and most commonly used SNRI; works on dopamine somewhat at high levels, but mostly effects serotonin and norepinephrine
• Serzone (nefazodone) – similar to SSRIs, but without the sexual side effects
• Dalcipran/Ixel (milnacipran) – known as Dalcipran in Portugal and Ixel in France; not approved by the FDA for use in the US, but commercially available in Europe and Asia for several years
• Norpramine/Pertofraneis (desipramine) – technically a tricyclic antidepressant, and normally categorized as such; works, however, on both serotonin and norepinephrine, so it can also be considered an SNRI
• Cymbalta (duloxetine) – approved for the treatment of depression and neuropathic pain in 2004
  Effexor is the “newer” version of Serzone, while Cymbalta is the “newer” version of Effexor.

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