Venlafaxine

Additional information

Depression is almost twice as common in women as in men [1]. Women have an earlier age of onset and increased duration of depressive episodes. Differences in neurobiology [2, 3], hormones, inflammatory markers, diagnostic tools, or health seeking behavior [4, 5] may be of importance.  Although depression is more prevalent in women, most preclinical studies on depression have used  male animals [2].

Women are two to three times more likely to suffer from an anxiety disorder [1]. Sex differences in symptomatology and comorbidity  may be due to genetic, hormonal, neurodevelopmental, environmental, and neurobiological factors [6].

Pharmacokinetics and dosing

In a pharmacokinetic study where patients (18 men, 18 women) first received a single dose 50 mg venlafaxine and later a 50 mg dose every 8 hours for 5 days, only minimal sex differences were observed. After the single dose, women had higher Cmax and AUC of the metabolite O-desmetylvenlafaxine (ODV), while men had longer ODV Tmax. When multiple dosing, women had faster venlafaxine renal clearance and men had longer ODV half-life [7]. In another pharmacokinetic study (14 men, 21 women) with 300 mg/day, women showed a reduced ODV/venlafaxine ratio for the (-)-enantiomer of ODV after 14 days, but no sex differences were observed for the (+)-enantiomer. Similar results were seen after 28 days [8]. Several therapeutic drug monitoring studies (about 60% women ) have shown that women had higher concentrations of venlafaxine and its metabolites [9-14]. According to the manufacturer, no sex differences in the pharmacokinetics of venlafaxine and its metabolite ODV are expected and no sex differentiation in dosing are recommended [15]. Published pharmacokinetic studies support similar dosing in men and women [7, 8].

Effects

Men and women with major depressive disorders have shown similar treatment response of venlafaxine in randomized, double-blind, controlled trials (in all 1058 men, 2059 women) [16, 17]. Treatment response of venlafaxine was also examined in patients with posttraumatic stress disorder in a pooled analysis (271 men, 416 women), but no significant sex differences were observed [18].

Adverse effects

Isolated cases of Torsade de Pointes ventricular tachycardia have been reported in association with venlafaxine overdose, the risk is generally higher in women [19].

Reproductive health issues

Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).

Other information

A small British study (48 men, 46 women) examining the choice of antidepressant treatment in relation to suicide risk showed that less venlafaxine was prescribed to men than women. Patients received monotherapy treatment for depression of which 6 men and 19 women were treated with venlafaxine [20].

Prescription history during the first year after the introduction of mirtazapine, sertraline and venlafaxine has been collected from 20 pharmacies in the Netherlands. No sex differences between men and women were observed [21]. Drug utilization of ten commonly prescribed antidepressants during the period 2009-2014 in Sweden, Denmark, Germany, and Spain were analyzed in a large register study (in total 4,833,774 initiators included). Women comprised the majority of initiators for all antidepressants studied. In Sweden, 70.2% of the initiators on venlafaxine were women [22]. However, male sex has been associated with a greater risk of treatment drop-out than women, reports a Spanish study based on prescription data. Patients who had received at least one antidepressant drug were included (in all 7525 patients) [23].