Effexor

Yes

Pregnancy category: C

Lactation: Enters milk; not recommended

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

Effexor tablets or capsules should be taken with food, at the same time(s) each day.

Do not suddenly stop taking Effexor without talking to your doctor first. Abruptly stopping Effexor can cause withdrawal symptoms (unpleasant side effects).

If you miss a dose, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of Effexor at the same time.

You should not take this medication if you are allergic to venlafaxine or desvenlafaxine (Pristiq), or if you are also using a monoamine oxidase inhibitor (MAOI) such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate).

Do not take venlafaxine together with desvenlafaxine (Pristiq).

You may have thoughts about suicide when you first start taking an antidepressant, especially if you are younger than 24 years old. Your doctor will need to check you at regular visits for at least the first 12 weeks of treatment.

Call your doctor at once if you have any new or worsening symptoms such as: mood or behavior changes, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), more depressed, or have thoughts about suicide or hurting yourself.

Drinking alcohol can increase certain side effects of venlafaxine.

Do not stop using venlafaxine suddenly, or you could have unpleasant symptoms. Ask your doctor how to avoid these symptoms when you stop using venlafaxine.

You should not take this medication if you are allergic to venlafaxine or desvenlafaxine (Pristiq), or if you are also using a monoamine oxidase inhibitor (MAOI) such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate). You must wait at least 14 days after stopping an MAOI before you can take venlafaxine. After you stop taking venlafaxine, you must wait at least 7 days before you start taking an MAOI.

Do not take venlafaxine together with desvenlafaxine (Pristiq).

To make sure you can safely take venlafaxine, tell your doctor if you have other medical conditions, especially:

• bipolar disorder (manic depression);
• cirrhosis or other liver disease;
• kidney disease;
• high blood pressure;
• glaucoma;
• seizures or epilepsy;
• a bleeding or blood clotting disorder;
• high cholesterol;
• low levels of sodium in your blood; or
• if you are switching to venlafaxine from another antidepressant.

You may have thoughts about suicide while taking an antidepressant, especially if you are younger than 24 years old. Tell your doctor if you have worsening depression or suicidal thoughts during the first several weeks of treatment, or whenever your dose is changed.

Your family or other caregivers should also be alert to changes in your mood or symptoms. Your doctor will need to check you at regular visits for at least the first 12 weeks of treatment.

FDA pregnancy category C. Venlafaxine may cause problems in a newborn baby if the mother takes the medication late in pregnancy (during the third trimester). Tell your doctor if you are pregnant or plan to become pregnant during treatment.

Venlafaxine can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Do not give this medication to anyone under 18 years old without the advice of a doctor.

• ADHD Medication for Children
• ADHD Medications for Adults
• Antidepressants
• Anxiety
• Depression
• Pain Management Medication Types
• Prescription Anxiety Medications
• Prescription Migraine Medications

Effexor (venlafaxine hydrochloride) is indicated for the treatment of major depressive disorder.

The efficacy of Effexor in the treatment of major depressive disorder was established in 6-week controlled trials of adult outpatients whose diagnoses corresponded most closely to the DSM-III or DSM-III-R category of major depression and in a 4-week controlled trial of inpatients meeting diagnostic criteria for major depression with melancholia (see CLINICAL TRIALS).

A major depressive episode implies a prominent and relatively persistent depressed or dysphoric mood that usually interferes with daily functioning (nearly every day for at least 2 weeks); it should include at least 4 of the following 8 symptoms: change in appetite, change in sleep, psychomotor agitation or retardation, loss of interest in usual activities or decrease in sexual drive, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, and a suicide attempt or suicidal ideation.

The efficacy of Effexor XR in maintaining an antidepressant response for up to 26 weeks following 8 weeks of acute treatment was demonstrated in a placebo-controlled trial. The efficacy of Effexor in maintaining an antidepressant response in patients with recurrent depression who had responded and continued to be improved during an initial 26 weeks of treatment and were then followed for a period of up to 52 weeks was demonstrated in a second placebo-controlled trial (see CLINICAL TRIALS). Nevertheless, the physician who elects to use Effexor/Effexor XR for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient.

• Effexor helps to relieve symptoms of depression; however, it has been associated with a discontinuation syndrome on withdrawal.

Studies in animals have shown reproductive toxicity. There are no controlled data in human pregnancy. AU TGA pregnancy category B2: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals are inadequate or may be lacking, but available data show no evidence of an increased occurrence of fetal damage. US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

This drug should be used during pregnancy only if the benefit outweighs the risk to the fetus. AU TGA pregnancy category: B2 US FDA pregnancy category: C Comments: -Patients should notify their healthcare provider if they become pregnant or intend to become pregnant during treatment. -Some newborns exposed to this drug late in the third trimester have developed complications requiring tube-feeding, respiratory support or prolonged hospitalization. -When treating a pregnant woman with this drug during the third trimester, the healthcare provider should carefully consider the potential risks and benefits of therapy.

Summary of Use during Lactation

Infants receive venlafaxine and its active metabolite in breastmilk, and the metabolite of the drug can be found in the plasma of most breastfed infants; however, concurrent side effects have rarely been reported. Breastfed infants, especially newborn or preterm infants, should be monitored for excessive sedation and adequate weight gain if this drug is used during lactation, possibly including measurement of serum levels of desvenlafaxine (O-desmethylvenlafaxine), to rule out toxicity if there is a concern. However, newborn infants of mothers who took the drug during pregnancy may experience poor neonatal adaptation syndrome as seen with other antidepressants such as SSRIs or SNRIs. Use of venlafaxine during breastfeeding has been proposed as a method of mitigating infant venlafaxine withdrawal symptoms,[1][2] but this has not been rigorously demonstrated.

Drug Levels

Venlafaxine is metabolized to a metabolite, desvenlafaxine, that has antidepressant activity similar to that of venlafaxine.[3]

Maternal Levels. Three mothers with infants aged 0.37, 1.3 and 6 months were taking venlafaxine in doses of 3.04 to 8.18 mg/kg daily for at least a week. Peak breastmilk levels of venlafaxine and its active metabolite, desvenlafaxine, occurred 1 to 3 hours after the dose in 2 of the mothers. Infants received an average of 7.6% (range 4.7 to 9.2%) of the maternal weight-adjusted dosage of venlafaxine plus desvenlafaxine.[4]

Six women averaging 7 months postpartum were receiving venlafaxine 225 to 300 mg daily for at least 18 days; 1 was taking the sustained-release (SR) formulation once daily and the others took 2 divided doses daily. In the women taking immediate-release product, the time of the peak milk levels averaged 2 hours (range 1.7 to 2.8 hours) for venlafaxine and 2.8 hours (range 1.8 to 4.2 hours) for desvenlafaxine. For the SR formulation, peak venlafaxine and desvenlafaxine levels occurred at 5.7 and 7.7 hours, respectively. The authors estimated that an exclusively breastfed infant would receive an average of 6.4% (range 5.2 to 7.4%) of the maternal weight-adjusted dosage of venlafaxine as the drug plus metabolite.[5]

Three women were taking venlafaxine during breastfeeding in doses of 37.5, 75 and 225 mg daily. Milk samples were taken 8 hours after a dose and measured for venlafaxine and desvenlafaxine. The infants were estimated to have received 11.8%, 3% and 6.3% of the weight-adjusted maternal dosage.[6]

In 3 women 8 to 30 weeks postpartum who were taking venlafaxine 75 to 225 mg daily, the authors calculated that their fully breastfed infants would receive an average of 5.2% of the maternal dosage, primarily as desvenlafaxine.[7]

A woman who was taking venlafaxine 375 mg daily during pregnancy and postpartum had a combined breastmilk level of 690 mcg/L of venlafaxine and 2 metabolites. The authors estimated that the breastfed infant was receiving at least 3.5% of the maternal weight-adjusted dosage.[1]

Two women who were 6.5 and 9.5 weeks postpartum and taking venlafaxine 75 mg and 225 mg daily had their milk measured at unreported times after their doses. The venlafaxine concentrations in their milk were 103 and 327 mcg/L, respectively.[8]

Eleven women taking an average of 194 mg of venlafaxine daily (1 as immediate-release and 10 as sustained-release) had their breastmilk venlafaxine and desvenlafaxine concentrations measured. The estimated excretion of the drug and metabolite into breastmilk was 8.1% (range 3.2 to 13.3%) of the weight-adjusted maternal dosage. The peak drug concentration in breastmilk occurred at about 8 hours after the dose; desvenlafaxine was the primary contributor to total milk concentration. The estimated infant dosage was 0.208 mg/kg daily (range 0.07 to 0.38 mg/kg daily),[9] which translates to 6.4% of the maternal weight-adjusted dosage.

Infant Levels. Three breastfed (extent not stated) infants aged 0.37, 1.3 and 6 months whose mothers were taking venlafaxine 3.04 to 8.18 mg/kg daily had undetectable (<10 mcg/L) venlafaxine and an average of 100 mcg/L (range 23 to 225 mcg/L) of desvenlafaxine in their plasma.[4]

Two mothers on stable doses of venlafaxine 75 and 150 mg daily exclusively breastfed their infants for 6 months. At ages 3 and 4 weeks, respectively, venlafaxine was undetectable (<10 mcg/L) in the serum of both infants. Desvenlafaxine was detectable in their serum at 16 and 21 mcg/L, respectively.[10]

Three breastfed (extent not stated) infants whose mothers were taking venlafaxine 37.5, 75 and 225 mg daily had blood samples taken 8 hours after the previous maternal dose. The infants, whose ages were 3, 10.4 and 14.6 weeks, had venlafaxine serum levels of 9 mcg/L, <3 mcg/L and undetectable; desvenlafaxine serum levels were <8, 7.5 and 12.5 mcg/L, respectively.[6]

Of 7 breastfed (extent not stated) infants with an average age of 7 months, including 1 set of twins, whose mothers were taking 225 to 300 mg of venlafaxine daily, only 1 (maternal dose 225 mg daily) had a measurable serum level of venlafaxine of 5 mcg/L (detection limit 1 mcg/L). Measurable desvenlafaxine serum levels were 3, 6, 20 and 38 mcg/L in 4 of the 7 infants.[5]

In 3 breastfed (extent not stated) infants aged 8 to 30 weeks whose mothers were taking venlafaxine 75 to 225 mg daily, their serum drug levels were 10.2% of those of their mothers, mostly as desvenlafaxine.[7]

Six nursing infants (average 20 weeks; range 7.3 to 60 weeks of age) whose mothers were taking an average of 206 mg daily of venlafaxine had their serum analyzed for venlafaxine and desvenlafaxine. Five were exclusively breastfed and 1 was about 50% breastfed. Five of the 6 had no detectable (<2 mcg/L) venlafaxine in their serum, and 1 had a concentration of 5 mcg/L. Two infants, including the one who was partially breastfed had no detectable desvenlafaxine in their serum; the other 4 had desvenlafaxine concentrations ranging from 4 to 243 mcg/L. The group of infants had an average serum concentrations of the drug and metabolite of 37% that of their mothers' serum.[9]

Effects in Breastfed Infants

No acute adverse effects or abnormal weight gain were seen in 3 breastfed infants who had detectable serum levels of desvenlafaxine.[4]

No adverse effects on growth or in sleep, feeding or behavioral patterns were noticed clinically in 2 infants who were exclusively breastfed for 6 months during maternal therapy with venlafaxine 75 and 150 mg daily.[10]

Three mothers took an average venlafaxine dose of 162.5 mg once daily. They breastfed their infants exclusively for 4 months and at least 50% during months 5 and 6. Their infants had 6-month weight gains that were normal according to national growth standards.[11]

Seven infants (including 1 set of twins) breastfed for 2.7 to 10.3 months during maternal venlafaxine therapy. Three mothers were taking venlafaxine since birth and 3 were started later. Denver Developmental Screening Tests in all infants were normal. All but 2 had normal growth; these 2 had a decrease in weight gain.[5]

In 3 infants aged 8 to 30 weeks whose mothers were taking venlafaxine 75 to 225 mg daily, no adverse reactions were noted clinically at the time of the study.[7]

An newborn infant whose mother had been taking venlafaxine 375 mg daily during pregnancy had symptoms of lethargy, poor sucking ability, and dehydration at 2 days of age. The infant was allowed to breastfeed and the symptoms subsided over 1 week. The authors concluded that the symptoms were likely withdrawal symptoms that were mitigated by the venlafaxine in breastmilk.[1] Another infant whose mother was taking venlafaxine 300 mg daily was reported by the same center. In this case, the infant's symptoms of withdrawal improved markedly on day 7 when breastfeeding was initiated, but no drugs levels were measured in milk or in the infant.[2]

Two nursing mothers were taking venlafaxine and quetiapine for postpartum depression; one was also taking trazodone. Their breastfed infants' development were tested at 12 to13 months of age with the Bayley Scales. Scores were within normal limits on the mental, psychomotor and behavior scales.[12]

Thirteen infants whose mothers were taking venlafaxine in doses ranging from 37.5 to 300 mg daily were breastfed (11 exclusively and 2 about 50%). Three of the infants were also exposed to a second psychotropic drug in breastmilk: 1 each of buspirone, trazodone, quetiapine. None of the infants had any adverse reactions reported by their mothers or in their medical records.[9]

Two nursing mothers who were 6.5 and 9.5 weeks postpartum were taking venlafaxine in doses of 75 and 225 mg daily, respectively, in addition to quetiapine for major depression postpartum; one mother was also taking trazodone. Their breastfed infants' development were tested at 9 to 18 months of age with the Bayley Scales. Both infants had scores that were within normal limits.[8]

A mother was taking venlafaxine 75 mg daily for depression and anxiety, although when the drug was started is not clear from the report. Her 1-month-old infant was seen in a pediatric clinic and was demonstrating agitation, infantile colic, drowsiness, increased startle response, jitteriness and sleeplessness. The symptoms began at 1 week of age and became progressively worse over time and with breastfeeding. The symptoms were possibly caused by venlafaxine, although whether they represent a withdrawal reaction of direct drug effects cannot be determined.[13]

A woman with depression and anxiety was treated with venlafaxine 300 mg daily monotherapy beginning at 20 weeks of pregnancy. On day three of life, the infant had extensor posturing and cycling of the limbs which was thought to be seizure related. Clinical examination was normal. Her suck was noted to be strong but uncoordinated and the infant fatigued rapidly. The infant was partially breastfed initially, but when breastmilk feeding was discontinued, the infant''s alertness improved and she gained 314 grams over 7 days. The authors felt that venlafaxine in breastmilk might have contributed to the infant's lethargy, especially given the high maternal dosage. The symptoms were possibly caused by venlafaxine in breastmilk.[14]

Effects on Lactation and Breastmilk

Cases of galactorrhea and elevated serum prolactin have been reported in which venlafaxine played a primary or secondary role in the etiology.[12][15][16][17][18][19][20] Galactorrhea with normal prolactin levels has also been reported.[21] The prolactin level in a mother with established lactation may not affect her ability to breastfeed.

One mother who was nursing a 10.3-month-old infant reported that her milk letdown took longer after starting venlafaxine 1 month earlier.[5]

An observational study looked at outcomes of 2859 women who took an antidepressant during the 2 years prior to pregnancy. Compared to women who did not take an antidepressant during pregnancy, mothers who took an antidepressant during all 3 trimesters of pregnancy were 30% less likely to be breastfeeding upon hospital discharge. Mothers who took an antidepressant only during the third trimester were 75% less likely to be breastfeeding at discharge. Those who took an antidepressant only during the first and second trimesters did not have a reduced likelihood of breastfeeding at discharge.[22] The antidepressants used by the mothers were not specified.

Alternate Drugs to Consider

Desvenlafaxine, Nortriptyline, Paroxetine, Sertraline

References

1. Koren G, Moretti M, Kapur B. Can venlafaxine in breast milk attenuate the norepinephrine and serotonin reuptake neonatal withdrawal syndrome. J Obstet Gynaecol Can. 2006;28:299-302. PMID: 16776907

2. Boucher N, Koren G, Beaulac-Baillargeon L. Maternal use of venlafaxine near term: correlation between neonatal effects and plasma concentrations. Ther Drug Monit. 2009;31:404-9. PMID: 19455083

3. Weissman AM, Levy BT, Hartz AJ et al. Pooled analysis of antidepressant levels in lactating mothers, breast milk, and nursing infants. Am J Psychiatry. 2004;161:1066-78. PMID: 15169695

4. Ilett KF, Hackett LP, Dusci LJ et al. Distribution and excretion of venlafaxine and O-desmethylvenlafaxine in human milk. Br J Clin Pharmacol. 1998;45:459-62. PMID: 9643618

5. Ilett KF, Kristensen JH, Hackett LP et al. Distribution of venlafaxine and its O-desmethyl metabolite in human milk and their effects in breastfed infants. Br J Clin Pharmacol. 2002;53:17-22. PMID: 11849190

6. Weissman AM, Wisner KL, Perel JM, Bentler S. Venlafaxine levels in lactating mothers, breast milk, and nursing infants. Arch Women Ment Health. 2003;6 (Suppl 1):20. Abstract.

7. Berle JO, Steen VM, Aamo TO et al. Breastfeeding during maternal antidepressant treatment with serotonin reuptake inhibitors: infant exposure, clinical symptoms, and cytochrome P450 genotypes. J Clin Psychiatry. 2004;65:1228-34. PMID: 15367050

8. Misri S, Corral M, Wardrop AA, Kendrick K. Quetiapine augmentation in lactation: a series of case reports. J Clin Psychopharmacol. 2006;26:508-11. PMID: 16974194

9. Newport DJ, Ritchie JC, Knight BT et al. Venlafaxine in human breast milk and nursing infant plasma: determination of exposure. J Clin Psychiatry. 2009;70:1304-10. PMID: 19607765

10. Hendrick V, Altshuler L, Wertheimer A et al. Venlafaxine and breast-feeding. Am J Psychiatry. 2001;158:2089-90. Letter. PMID: 11729040

11. Hendrick V, Smith LM, Hwang S et al. Weight gain in breastfed infants of mothers taking antidepressant medications. J Clin Psychiatry. 2003;64:410-2. PMID: 12716242

12. Pae CU, Kim JJ, Lee CU et al. Very low dose quetiapine-induced galactorrhea in combination with venlafaxine. Hum Psychopharmacol. 2004;19:433-4. PMID: 15303249

13. Matthys A, Ambat MT, Pooh R, Plavsic SK. Psychotropic medication use during pregnancy and lactation: Role of ultrasound assessment. Donald Sch J Ultrasound Obstet Gynecol. 2014;8:109-21. DOI: doi:10.5005/jp-journals-10009-1345

14. Tran MM, Fancourt N, Ging JM et al. Failure to thrive potentially secondary to maternal venlafaxine use. Australas Psychiatry. 2016;24:98-9. Letter. 26850953

15. Bhatia SC, Bhatia SK, Bencomo L. Effective treatment of venlafaxine-induced noncyclical mastalgia with bromocriptine. J Clin Psychopharmacol. 2000;20:590-1. Letter. PMID: 11001253

16. Sternbach H. Venlafaxine-induced galactorrhea. J Clin Psychopharmacol. 2003;23:109-10. PMID: 12544389

17. Ashton AK, Longdon MC. Hyperprolactinemia and galactorrhea induced by serotonin and norepinephrine reuptake inhibiting antidepressants. Am J Psychiatry. 2007;164:1121-2. PMID: 17606668

18. Wichman CL, Cunningham JL. A case of venlafaxine-induced galactorrhea? J Clin Psychopharmacol. 2008;28:580-1. PMID: 18794664

19. Karakurt F, Kargili A, Uz B et al. Venlafaxine-induced gynecomastia in a young patient: a case report. Clin Neuropharmacol. 2009;32:51-2. PMID: 18978497

20. Berilgen MS. Late-onset galactorrhea and menometrorrhagia with venlafaxine use in a migraine patient. J Clin Psychopharmacol. 2010;30:753-4. PMID: 21057247

21. Warren MB. Venlafaxine-associated euprolactinemic galactorrhea and hypersexuality: A case report and review of the literature. J Clin Psychopharmacol. 2016;36:399-400. PMID: 27219091

22. Venkatesh KK, Castro VM, Perlis RH et al. Impact of antidepressant treatment during pregnancy on obstetric outcomes among women previously treated for depression. Am J Obstet Gynecol. 2017;216:S466-S467.