Effexor XR (venlafaxine Extended-Release) - 4 indications

Scroll down for information on each indication:

Major Depressive Disorder; approved in 1997 

Generalized Anxiety Disorder; approved in 1999

Social Anxiety Disorder; approved February of 2003

Panic disorder, with or without agoraphobia; approved November 2005

General Information

Effexor XR (venlafaxine hydrochloride) extended-release capsules is a serotonin and norepinephrine reuptake inhibitor (SNRI).

Effexor XR is specifically indicated for the treatment of the following:

• Major Depressive Disorder (MDD)
• Generalized Anxiety Disorder (GAD)
• Social Anxiety Disorder (SAD)
• Panic Disorder (PD), with or without agoraphobia

Effexor XR is supplied as an extended release capsule for oral administration. Effexor XR should be administered in a single dose with food, either in the morning or in the evening at approximately the same time each day. Each capsule should be swallowed whole with fluid and not divided, crushed, chewed, or placed in water or it may be administered by carefully opening the capsule and sprinkling the entire contents on a spoonful of applesauce. This drug/food mixture should be swallowed immediately without chewing and followed with a glass of water to ensure complete swallowing of the pellets.

Scroll down for the recommended dosing for each therapeutic condition. 

Mechanism of Action

Effexor XR (venlafaxine hydrochloride) extended-release capsules is a serotonin and norepinephrine reuptake inhibitor (SNRI). The exact mechanism of the antidepressant action of venlafaxine in humans is unknown, but is thought to be related to the potentiation of serotonin and norepinephrine in the central nervous system, through inhibition of their reuptake. Non- clinical studies have demonstrated that venlafaxine and its active metabolite, ODV, are potent and selective inhibitors of neuronal serotonin and norepinephrine reuptake and weak inhibitors of dopamine reuptake.

Side Effects

Adverse effects associated with the use of Effexor XR may include, but are not limited to, the following:

• nausea
• somnolence
• dry mouth
• sweating
• abnormal ejaculation
• anorexia
• constipation
• erectile dysfunction
• libido decreased

The Effexor XR drug label comes with the following Black Box Warning: Increased risk of suicidal thinking and behavior in children, adolescents and young adults taking antidepressants. Monitor for worsening and emergence of suicidal thoughts and behaviors. Effexor XR is not approved for use in pediatric patients.

Indication 1 - Major Depressive Disorder

Approved in 1997 

Dosing/Administration

For most patients, the recommended starting dose for Effexor XR is 75 mg per day, administered in a single dose. For some patients, it may be desirable to start at 37.5 mg per day for 4 to 7 days to allow new patients to adjust to the medication before increasing to 75 mg per day. Patients not responding to the initial 75 mg per day dose may benefit from dose increases to a maximum of 225 mg per day. Dose increases should be in increments of up to 75 mg per day, as needed, and should be made at intervals of not less than 4 days, since steady-state plasma levels of venlafaxine and its major metabolites are achieved in most patients by day 4. In the clinical studies establishing efficacy, upward titration was permitted at intervals of 2 weeks or more.

Clinical Trial Results

The efficacy of Effexor XR (venlafaxine hydrochloride) extended-release capsules as a treatment for Major Depressive Disorder (MDD) was established in two placebo-controlled, short-term (8 weeks for study 1; 12 weeks for study 2), flexible-dose studies, with doses starting at 75 mg per day and ranging to 225 mg per day in adult outpatients meeting DSM-III-R or DSM-IV criteria for MDD. In moderately depressed outpatients, the initial dose of venlafaxine was 75 mg per day. In both studies, Effexor XR demonstrated superiority over placebo on the primary efficacy measure defined as change from baseline in the HAM-D-21 total score to the endpoint visit, Effexor XR also demonstrated superiority over placebo on the key secondary efficacy endpoint, the Clinical Global Impressions (CGI) Severity of Illness scale. 

Indication 2 - Generalized Anxiety Disorder

Approved in 1999

Dosing/Administration

For most patients, the recommended starting dose for Effexor XR is 75 mg per day, administered in a single dose. For some patients, it may be desirable to start at 37.5 mg per day for 4 to 7 days to allow new patients to adjust to the medication before increasing to 75 mg per day. Patients not responding to the initial 75 mg per day dose may benefit from dose increases to a maximum of 225 mg per day. Dose increases should be in increments of up to 75 mg per day, as needed, and should be made at intervals of not less than 4 days, since steady-state plasma levels of venlafaxine and its major metabolites are achieved in most patients by day 4. In the clinical studies establishing efficacy, upward titration was permitted at intervals of 2 weeks or more.

Clinical Trial Results

The efficacy of Effexor XR as a treatment for Generalized Anxiety Disorder (GAD) was established in two 8-week, placebo-controlled, fixed-dose studies (75 to 225 mg per day), one 6-month, placebo-controlled, flexible-dose study (75 to 225 mg per day), and one 6-month, placebo-controlled, fixed-dose study (37.5, 75, and 150 mg per day) in adult outpatients meeting DSM-IV criteria for GAD.

In one 8-week study, Effexor XR demonstrated superiority over placebo for the 75, 150, and 225 mg per day doses as measured by the Hamilton Rating Scale for Anxiety (HAM-A) total score, both the HAM-A anxiety and tension items, and the Clinical Global Impressions (CGI) scale. However, the 75 and 150 mg per day doses were not as consistently effective as the highest dose (study 1). A second 8-week study evaluating doses of 75 and 150 mg per day and placebo showed that both doses were more effective than placebo on some of these same outcomes; however, the 75 mg per day dose was more consistently effective than the 150 mg per day dose (study 2). A dose-response relationship for effectiveness in GAD was not clearly established in the 75 to 225 mg per day dose range studied.

Two 6-month studies, one evaluating Effexor XR doses of 37.5, 75, and 150 mg per day (study 3) and the other evaluating Effexor XR doses of 75 to 225 mg per day (study 4), showed that daily doses of 75 mg or higher were more effective than placebo on the HAM-A total, both the HAM-A anxiety and tension items, and the CGI scale during 6 months of treatment. While there was also evidence for superiority over placebo for the 37.5 mg per day dose, this dose was not as consistently effective as the higher doses.

Indication 3 - Social Anxiety Disorder (Social Phobia)

Approved February of 2003

Dosing/Administration

The recommended dose is 75 mg per day, administered in a single dose. There was no evidence that higher doses confer any additional benefit.

Clinical Trial Results

The efficacy of Effexor XR as a treatment for Social Anxiety Disorder (SAD) was established in four double-blind, parallel-group, 12-week, multicenter, placebo-controlled, flexible-dose studies (studies 1–4) and one double-blind, parallel-group, 6-month, placebo-controlled, fixed/flexible-dose study, which included doses in a range of 75 to 225 mg per day in adult outpatients meeting DSM-IV criteria for SAD (study 5).

In these five studies, Effexor XR was statistically significantly more effective than placebo on change from baseline to endpoint on the Liebowitz Social Anxiety Scale (LSAS) total score. There was no evidence for any greater effectiveness of the 150 to 225 mg per day group compared to the 75 mg per day group in the 6-month study.

Indication 4 - Panic disorder, with or without agoraphobia

Approved November 2005

Dosing/Administration

The recommended starting dose is 37.5 mg per day of Effexor XR for 7 days. Patients not responding to 75 mg per day may benefit from dose increases to a maximum of approximately 225 mg per day. Dose increases should be in increments of up to 75 mg per day, as needed, and should be made at intervals of not less than 7 days.

Clinical Trial Results

The efficacy of Effexor XR as a treatment for Panic Disorder (PD) was established in two double-blind, 12-week, multicenter, placebo-controlled studies in adult outpatients meeting DSM-IV criteria for PD, with or without agoraphobia. Patients received fixed doses of 75 or 150 mg per day in one study (study 1) and 75 or 225 mg per day in the other study (study 2).

Efficacy was assessed on the basis of outcomes in three variables: (1) percentage of patients free of full-symptom panic attacks on the Panic and Anticipatory Anxiety Scale (PAAS); (2) mean change from baseline to endpoint on the Panic Disorder Severity Scale (PDSS) total score; and (3) percentage of patients rated as responders (much improved or very much improved) on the Clinical Global Impressions (CGI) Improvement scale. In these two studies, Effexor XR was statistically significantly more effective than placebo (for each fixed dose) on all three endpoints, but a dose-response relationship was not clearly established.