Desvenlafaxine succinate (Pristiqâ„¢ | Wyeth), a novel, once-daily serotonin-norepinephrine reuptake inhibitor (SNRI), has received the US Food and Drug Administration (FDA) approval for the treatment of adult patients with major depressive disorder (MDD).
The approval is subject to several post-marketing obligations that include conducting and submitting data from a relapse prevention study, a sexual dysfunction study, a study to investigate low doses of the drug, pediatric studies, and an additional non-clinical toxicity study. The data obtained from four different randomized, double-blind, placebo-controlled, 8-week studies in adult patients were considered to ascertain the efficacy of the drug for treating depression.
In one such study, Michael R. Liebowitz, founder of the Anxiety Disorders Clinic at the New York State Psychiatric Institute, and colleagues (The Journal of Clinical Psychiatry, 2007) conducted a randomized, double-blind, placebo-controlled study in outpatients aged between 18 to 75 years, meeting the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria, to assess the safety and efficacy of desvenlafaxine succinate in treating MDD. The patients were randomly administered either placebo or 100-200 mg desvenlafaxine per day. The study results showed the efficacy of desvenlafaxine on MDD-related alternate depression scale and pain measures. However, the efficacy of the drug was not significantly more than placebo on primary or crucial secondary efficacy end-points in the study. The most common adverse effects observed during the treatment included anorexia, constipation, nausea, nervousness, and somnolence.
Desvenlafaxine is also under investigation for the treatment of vasomotor symptoms associated with menopause. Speroff et al, (Obstetrics and Gynecology, 2008) have reported desvenlafaxine to be an efficient non-hormonal therapy for vasomotor symptoms in postmenopausal women. They conducted a randomized, double-blind, placebo-controlled trial to study the safety and efficacy of the drug in postmenopausal women with evidence of 50 or more moderate-to-severe hot flushes per week. The patients were randomized to receive desvenlafaxine 50, 100, 150, or 200 mg or placebo daily, for a period of 52 weeks. A daily dosage of 100 mg desvenlafaxine considerably reduced the average daily number of hot flushes after four and twelve weeks, with a significant decrease by 64% from the baseline at week 12, compared to placebo. The average daily severity of hot flushes was also reduced in the desvenlafaxine 100 mg group at week 12 compared to the placebo group. However, the treatment-associated adverse effects were reportedly higher in the desvenlafaxine-treated patients compared to women who were administered placebo.
Desvenlafaxine succinate, a serotonin-norepinephrine reuptake inhibitor (SNRI), is the succinate salt of a major active metabolite of venlafaxine hydrochloride (Effexor® | Wyeth) known as O-desmethyl venlafaxine. Venlafaxine is the first SNRI approved by the US FDA for the treatment of MDD. The anti-depressant activity of venlafaxine and desvenlafaxine is attributed to the inhibition of neuronal serotonin and norepinephrine reuptake, and partial inhibition of dopamine reuptake. The inhibition results in the presence of more active neurotransmitters in the synapse region, thereby enhancing the downstream neuronal activity.
According to the World Health Organization, every year, 5.8% men and 9.5% women experience episodes of depression worldwide. A number of symptoms which interfere with the general daily activities of a person such as the ability to work, sleep, study, and eat, and an increased suicidal tendency are characteristic of major depressive disorder, also known as major depression. Antidepressant drug therapy has been associated with suicidality in children and young adults, as reported in short-term MDD studies, forcing a second thought about prescribing these drugs. Major depression may be prevented by certain life-style changes such as avoiding alcohol, drugs, and caffeine, regular exercise, and practising stress management and relaxation techniques.
References
1. FDA Approves Pristiq for the Treatment of Adult Patients with Major Depressive Disorder. Wyeth. Last accessed on March 04, 2008.
2. Liebowitz MR, Yeung PP, Entsuah R. A randomized, double-blind, placebo-controlled trial of desvenlafaxine succinate in adult outpatients with major depressive disorder. The Journal of Clinical Psychiatry. 2007 Nov;68(11):1663-72.
3. Speroff L, Gass M, Constantine G, Olivier S. Efficacy and tolerability of desvenlafaxine succinate treatment for menopausal vasomotor symptoms: a randomized controlled trial. Obstetrics and Gynecology. 2008 Jan;111(1):77-87.
