As with most antidepressants, lack of sexual desire is a common side effect. In trials, delayed ejaculation and delayed orgasm occurred in 8-16% of men. Interestingly, delayed orgasm occurred in only 2-8% of women in trials. Venlafaxine can raise blood pressure at high doses, so it is usually not the drug of choice for persons with hypertension.

It has a higher rate of treatment emergent mania than many modern antidepressants, and many people find it to be a more activating medication (one that increases energy or wakefulness) than other antidepressants. Paradoxically, some users find it highly sedating and find that it must be taken in the evening.

There have been false positive phencyclidine (PCP) results caused by Venlafaxine with certain on-site routine urine-based drug tests. Positive on-site results should always be sent to a qualified drug testing laboratory for confirmation before any action is taken against the employee.

Suicide Ideation/Risk

The FDA requires all antidepressants, including venlafaxine, to carry a black box with a generic warning about a possible suicide risk. In addition, the most recent research indicated that patients taking venlafaxine are at increased risk of suicide.

A study conducted in Finland followed more than 15,000 patients for 3.4 years. Venlafaxine increased suicide risk 1.6-fold (statistically significant), as compared to no treatment. At the same time, fluoxetine (Prozac) halved the suicide risk.

In another study, the data on more than 200,000 cases was obtained from the UK general practice research database. The patients taking venlafaxine had significantly higher risk of completed suicide than the ones on fluoxetine (Prozac) (2.8 times) or citalopram (Celexa) (2.4 times). Even after taking into consideration the fact that venlafaxine was generally prescribed for more severe depression, venlafaxine was associated with 1.6-1.7 times more suicides than fluoxetine or citalopram. This difference was no longer statistically significant due to the rarity of completed suicides. However, for the attempted suicides (more frequent event) the 1.2-1.3 times higher risk for venlafaxine still stayed statistically significant after the adjustment.

An analysis of clinical trials by the FDA statisticians showed the incidence of suicidal behavior among the adults on venlafaxine to be not significantly different from fluoxetine or placebo. A possible explanation for this discrepancy is that suicidal patients are generally excluded from clinical trials, and so clinical trials are not quite representative of the real population of patients.

Venlafaxine is contraindicated to children, adolescents and young adults. According to the FDA analysis of clinical trials venlafaxine caused a 5-fold increase (statistically significant) of suicidal ideation and behavior in subjects younger than 25. In another analysis, venlafaxine was no better than placebo among children (7-11 years old) and improved the depression in adolescents (12-17 years old). However, in both groups hostility and suicidal behavior were increased in comparison to the placebo treatment.

Serotonin Syndrome

Another risk is serotonin syndrome. This is a rare but serious side effect that can be caused by interactions with other central nervous system depressant drugs, and is potentially fatal. This risk necessitates clear information to patients and proper medical history. For example, the drug abuse by at-risk patients of certain non-prescription drugs can cause this serious effect, and emphasizes the importance of good medical history sharing between general practitioners and psychiatrists, as both may prescribe venlafaxine. Involvement of family in awareness of risk factors is highlighted in Wyeth information sheets on Effexor.

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