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A New Old Drug for Depression: Desvenlafaxine (PRISTIQ)

Worst Pills, Best Pills Newsletter article March, 2010

 

Black Box Warning: Suicidality and Antidepressant Drugs

Antidepressants increased the risk com­pared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of Major Depressive Disorder (MDD) and other psychiatric disorders.

Anyone considering the use of PRISTIQ or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical...

 

Black Box Warning: Suicidality and Antidepressant Drugs

Antidepressants increased the risk com­pared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of Major Depressive Disorder (MDD) and other psychiatric disorders.

Anyone considering the use of PRISTIQ or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepres­sants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older.

Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antide­pressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and care­givers should be advised of the need for close observation and communication with the prescriber. PRISTIQ is not ap­proved for use in pediatric patients.

In February 2008, the Food and Drug Administration (FDA) approved desvenlafaxine (PRISTIQ) as a new drug to treat major depressive disorder (MDD) in adults. But it is not actually as new as you might think.

Desvenlafaxine is the active form of the antidepressant venlafaxine (EFFEXOR). When venlafaxine is digested in the body, it turns into desvenlafaxine. So, in effect, a dose of desvenlafaxine is a dose of partially digested venlafaxine.

Thus, desvenlafaxine is technically a new drug, but in reality, patients have, for all practical purposes, been getting this drug since venlafaxine was approved in 1993.

Desvenlafaxine is the newest member of the family called selective serotonin and norepinephrine reuptake inhibitors (SNRIs) that includes venlafaxine. See the Table for a list of SNRIs currently available for sale in the U.S.

FDA’s basis for approval

The FDA approved desvenlafaxine based on the results of four eight-week-long clinical trials in which desvenlafaxine was compared to a placebo. The effectiveness of the drug was measured using the Hamilton Depression Rating Scale-17 (HAMD-17). HAMD-17 is a 17-question form with scores that can range from 0, which indicates the patient suffers less severe symptoms of depression, to 52, which indicates the patient’s symptoms are more severe.

The HAMD-17 scores of patients taking desvenlafaxine in these four trials dropped by an average of 2.4 points more than the HAMD-17 scores of patients taking a placebo out of a possible 52 points. This is statistically significant but not a clinically important advance over older antidepressant drugs.

In these studies, patients did not receive any additional benefit when doses were greater than 50 milligrams per day. Also, the occurrence of side effects — which include increased suicide risk, serotonin syndrome, elevated blood pressure, abnormal bleeding, elevated cholesterol levels, kidney impairment, seizures and low sodium levels — was more frequent at higher doses, and patients stopped taking the drug and dropped out of the study more frequently at higher doses as well.

Patients at a significant risk of suicide were excluded from participating in these trials because it makes interpretation of the results easier. (Most health professionals and consumers are not aware of this and have been led to believe that these drugs reduce suicide risk when, in fact, they have not been tested in patients with a high risk of suicide.)

Blood pressure increases seen in clinical trials

Patients taking desvenlafaxine should have their blood pressure checked regularly, as increases in blood pressure were observed in the clinical studies conducted before the drug was approved (described above). Cases of elevated blood pressure requiring immediate treatment have been reported with desvenlafaxine.

Desvenlafaxine shares the same safety warnings with venlafaxine. Desvenlafaxine and all other drugs approved to manage depression must display a black box warning in their professional product labels about an increased risk of suicide in children, adolescents or young adults who use these drugs (see Box). Desvenlafaxine is not approved for use in pediatric patients.

A black box is the strongest type of safety warning that the FDA can require in a drug’s professional product label or package insert and is reserved for products that can cause serious harm or death to patients.

What You Can Do

The FDA requires that antidepressants, including desvenlafaxine, be dispensed with an FDA-approved Medication Guide written specifically for consumers in nontechnical language. Medication Guides are only dispensed for drugs that the FDA has determined present serious public health concerns.

Read the FDA-approved Medication Guide before taking desvenlafaxine and each time you have your prescription refilled, as the information may have changed. The Medication Guides for desvenlafaxine can be obtained from any local pharmacist, or online from FDA at: www.fda.gov/Drugs/DrugSafety/ucm085729.htm.

Desvenlafaxine and venlafaxine are, for practical purposes, the same drug. Patients who are prescribed desvenlafaxine might choose to base their decision on cost and take the cheaper, now generically available venlafaxine instead.

Table. Selective Norepinephrine and Serotonin Reuptake Inhibitors Available on the Market in the U.S.

 

Generic Name

BRAND NAME

desvenlafaxine

PRISTIQ***(2015)

duloxetine

CYMBALTA*

venlafaxine (generic available)

EFFEXOR; EFFEXOR XR**

* Do Not Use on WorstPills.org
** Limited Use on WorstPills.org
*** Do Not Use Until Seven Years After Approval on WorstPills.org

 

What is Major Depressive Disorder?

According to the American Psychiatric Association, a diagnosis of major depres­sive disorder (MDD) implies a prominent and relatively persistent depressed or worried mood that usually interferes with daily activities.

These episodes last nearly every day for at least two weeks and include at least five of the following nine symptoms:

  • depressed mood
  • loss of interest in usual activities
  • significant change in weight and/or appetite
  • insomnia or hypersomnia
  • psychomotor agitation or retardation
  • increased fatigue
  • feelings of guilt or worthlessness
  • slowed thinking or impaired concentration
  • a suicide attempt or suicidal thoughts