With this post, we continue our biweekly series on medications used to treat bipolar disorder and related symptoms. Over the past weeks, we covered several commonly used SSRI antidepressants, including Prozac, Paxil, Zoloft, Celexa, and Lexapro. This week, we turn our attention to another class of antidepressants known as SSNRI’s, the most popular of which are Effexor, Cymbalta, and Pristiq.

SSNRIs are Selective Serotonin and Norepinephrine Reuptake Inhibitors. They work by increasing the levels of two brain chemicals – serotonin and norepinephrine – in the synapses between brain cells. Like serotonin (described in our Prozac post), norepinephrine is important in regulating mood and anxiety, along with alertness and concentration.

Potential Benefits

Effexor (venlafaxine) is approved for the treatment of Major Depressive Disorder (MDD), Generalized Anxiety Disorder (GAD), panic disorder, and social anxiety disorder (social phobia).

Effexor may also be useful in treating other anxiety and mood disorders, including the following:

• Unipolar depression
• Bipolar depression
• Post Traumatic Stress Disorder (PTSD)

Typical Dose

Typical adult doses of Effexor range from 37.5 mg to 225 mg taken twice daily. Effexor XR (extended release) is taken once daily. Follow your prescriber’s recommendations on dose and when to take it.

Potential Side Effects

Effexor can potentially cause any of several negative side effects, many of which it shares with SSRI antidepressants. The most serious are the following:

• Increased suicidal thoughts in children or teens: Clearly there is an increased risk of suicide and suicidal thinking in people with bipolar and depression as a whole. A large review of studies done on children and adolescents who were treated with antidepressants showed that there was a slight increase in the risk that these children would develop suicidal thoughts, compared to children taking placebo. Even with the increased risk, the rate of this side effect remains very, very low. And the increased risk relates only to suicidal thinking- there have been no reports indicating any increased risk of completed suicides with the medications. These medications are far more likely to decrease the risk of suicide than to increase it. Careful monitoring and communication with the prescriber, especially early on in treatment, is essential in reducing this risk as much as possible.
• Increased risk of mania: As mentioned earlier in this post, a person with bipolar disorder taking an antidepressant without the protection of a mood stabilizer may be at higher risk of shifting into mania or hypomania. While there is some indication that some antidepressants have less risk of manic switching, the risk seems to be present in all antidepressants. The rate of switching and the actual level of risk is not clear at this time – some researchers suspect it is very high and others feel it is actually much lower than is generally presumed.
• Agitation, increased anxiety, or worsening depression or other paradoxical effects: This is not the same as a true manic switch, and can occur in people with or without bipolar disorder who take SSRI’s or SSNRI’s. In a small group of people, these medicines seem to irritate the brain wiring rather than soothe it. This appears to be more common in children and adolescents, but can occur in a subset of adults as well. Close monitoring with your prescriber will be important in detecting this.
• Serotonin syndrome: When combined with medicines used to treat migraine headaches known triptans, such as sumatriptan (Imitrex), or other drugs that elevate brain levels of serotonin (including the illegal drug Ecstasy), a life-threatening condition called serotonin syndrome can occur. Symptoms include restlessness, hallucinations, loss of coordination, racing heart, increased body temperature, blood pressure fluctuations, overactive reflexes, diarrhea, nausea, vomiting, coma, and possibly death.
• Neonatal poor adaptation syndrome: Effexor taken during the third trimester of pregnancy has been associated with neonatal poor adaptation syndrome – a variety of metabolic and regulatory difficulties that can lead to newborns requiring intensive medical support.

Effexor has a number of interactions with other medications, so it is important to review your entire medication regimen with your physician before starting Effexor or adding another medication while already taking Effexor.

Other less serious side effects can include the following (Note: Many of these side effects are transient and occur when first taking these medications but do not persist.):

• High blood pressure
• Abdominal pain
• Sweating
• Sleepiness
• Insomnia
• Nausea, vomiting
• Diarrhea
• Tremor
• Dry mouth
• Loss of strength
• Headache
• Weight loss or gain
• Dizziness
• Restlessness
• Mania
• Changes in sexual function
• Withdrawal symptoms – severe

Remember: Any antidepressant can take 2-3 weeks or even longer to become fully effective; it may take several weeks to work up to a therapeutic dose. This means that your depression may not lift for several weeks. I often tell patients however they feel in the first two weeks is unlikely to be how they feel in a month – so if they are feeling some early side effects, hold on because they will likely get better. Patience is important in getting these medications to work, but if you have any concerns about how you are feeling, you should contact your doctor. You will most likely have a follow-up visit with your doctor within a month or less of starting the medications; this is a good time frame for checking in to see if benefits have started or if side effects have faded or persisted.

Warning

Effexor can have some of the worst withdrawal phenomena of all of the antidepressants. If even one dose is missed, and certainly by the second or third dose, patients will often experience severe abdominal pain, nausea and vomiting or diarrhea, headaches, weakness, and other general kinds of significant discomfort. It is very important to take Effexor every day, as planned, and to decrease the dose when necessary only very slowly, as described by your prescriber.

Blood pressure should be monitored when someone is taking Effexor. If someone is already being treated for high blood pressure, the psychiatrist and primary care providers should communicate about the blood pressure readings. I have had a number of patients that have had to stop Effexor due to elevated blood pressure as a side effect.

A new version of Effexor is now available called Pristiq (desvenlafaxine), which has the benefit of being able to be started quickly – you don’t have to bring the dose up slowly, according to the drug maker. I have not had the opportunity to try this form of Effexor yet, so I can offer no observations about it.

For more information from the manufacturer, visit Wyeth’s Effexor XR page or the Pristiq page.

If you’ve taken any form of Effexor or Pristiq for bipolar depression or other conditions or are a doctor who has prescribed it, please share your experiences, insights, and observations.

Edited on 5/19/2009 to correct the class of medications Effexor belongs to. Thanks to “a grateful patient” for calling our attention to the slip.

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