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Psychopharmacology book

Venlafaxine (EFFEXOR) 

Venlafaxine (EFFEXOR) 

The SNRI venlafaxine (Effexor) is a reasonable second-line antidepressant, potentially first-line for depressed individuals suffering from chronic pain. Effexor XR and duloxetine (Cymbalta) are equally popular SNRIs, #51 and #48 most prescribed medications in the US, respectively.

Venlafaxine Effexor visual mnemonic by Dr Jason Cafer MD psychopharmacology book

When Effexor was introduced in 1995 prescribers nicknamed it “Side-Effexor” due to nausea and fatigue. Effexor XR (extended release) was introduced in 1998 and became widely prescribed because it is much better tolerated. Choose the XR formulation, which is also less expensive than the rarely prescribed immediate-release venlafaxine. The only scenario when immediate-release Effexor is preferred is with bariatric surgery patients. For either formulation of Effexor, it is recommended to take it with food to minimize nausea. 


Peak plasma concentrations are achieved within 2 to 3 hours for the IR formulation and within 5.5 hours for the XR formulation.


Effexor acts as an SSRI at low doses (37.5 mg, 75 mg) and an SNRI at higher doses (150 mg plus).  75 mg/day is the minimum effective dose for treatment of depression.


Venlafaxine has a short half-life of 5 hours, and the half-life of the active metabolite O-desmethylvenlafaxine (ODV) is 11 hours. ODV is available as the antidepressant desvenlafaxine (Pristiq), which appears to be less effective than Effexor for depression. 


Incidence of blood pressure elevation with the XR formulation is 1%. With the IR formulation, incidence of hypertension is about 5%, and as high as 13% at doses exceeding 300 mg. 

Venlafaxine Effexor interactions and indications by Dr Jason Cafer MD

In addition to raising blood pressure, venlafaxine may induce seizures in overdose, making it the most dangerous modern antidepressant (non-TCA, non-MAOI). Risk of single-drug overdose death with venlafaxine is about 1 in 839.


For depression, venlafaxine is no more effective than the SSRI escitalopram (Lexapro), which has fewer side effects. For generalized anxiety disorder, venlafaxine is more effective than buspirone (Buspar).


Venlafaxine can cause false positives for PCP on drug tests. 


FDA max is 225 mg, but for severe depression 300 mg may be more effective. Take caution because blood pressure elevation is dose dependent. Taper off Effexor slowly to avoid symptoms of serotonin withdrawal syndrome.


XR Dosing: Specify the extended-release formulation Effexor XR, (venlafaxine ER) except for in bariatric surgery patients. Start Effexor XR 37.5 or 75 mg QD with food (to ameliorate nausea), with target of 150–225 mg QD. FDA max is 225 mg, but 300 mg may be more effective for depression. For treatment of pain the dose can go as high as high as 450 mg/day if blood pressure is monitored closely. May increase in 75 mg increments every 4–7 days. 


IR dosing: For bariatric surgery patients, prescribe venlafaxine IR which is available in 25, 37.5, 50, 75, and 100 mg tablets, given in divided doses BID or TID. The FDA maximum for IR venlafaxine is 375 mg/day in divided doses (125 mg TID).


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