Venlafaxine / Effexor

Venlafaxine hydrochloride is a prescription antidepressant first introduced by Wyeth in 1993, and marketed under the tradename Effexor®. It is used primarily for the treatment of depression, generalized anxiety disorder, and social anxiety disorder in adults. The chemical structure of Venlafaxine is designated (R/S)-1-[2-(dimethylamino)-1-(4 methoxyphenyl)ethyl] cyclohexanol hydrochloride or (±)-1-[a [α- (dimethylamino)methyl] p-methoxybenzyl] cyclohexanol hydrochloride and it has the empirical formula of C17H27NO2 · HCl. It is a white to off-white crystalline solid, distributed in capsules of 25mg, 37.5mg, 50mg, 75mg, 100mg and 150mg.

Effexor is chemically unrelated to other antidepressants, but is sometimes catagorized as a serotonin-norepinephrine reuptake inhibitor (SNRI). It works by blocking the transporter "reuptake" proteins for key neurotransmitters affecting mood, thereby leaving more active in the synapse. At low dosages, Effexor blocks serotonin reuptake, similarly to a selective serotonin reuptake inhibitor (SSRI). At medium dosages, Effexor blocks the reuptake of norepinephrine as well as serotonin. At high dosages, Effexor blocks the reuptake of serotonin and norepinephrine, and has a weak affinity for blocking dopamine reuptake.

Prescribed dosages are typically in the range of 75mg-225mg per day, but higher dosages are sometimes used for the treatment of severe or treatment-resistant depression. Because of its relatively short half-life of 4 hours, Effexor should be administered in divided dosages throughout the day. An extended release version, Effexor® XR, eliminates this problem and has largely replaced the original in use. Steady-state concentrations of Venlafaxine and its metabolite are attained in the blood within 3 days. Therapeutic effects are usually achieved within 3-4 weeks.

Effexor is somewhat notorious for its withdrawal symptoms upon sudden discontinuation. (The recommended discontinuation is a drop of 35mg a week, and sudden stops are usually advised only in emergencies.) These have a tendency to be stronger than the withdrawal effects of many antidepressants, but are similar in nature to those of tricyclic antidepressants and SSRIs such as Paroxetine (Paxil®). These effects may include headache, nausea, fatigue, dizziness and dysphoria. Rarer withdrawl symptoms include shaking legs and "brain shivers". "Brain shivers" have been described as electric-like shocks in the brain causing headache and disorientation, increasing over time before abating. Antidepressant withdrawal effects do not indicate addiction, but are rather the result of the brain attempting to reach neurochemical stability. These can be minimalized or avoided by tapering off of the medication over a period of weeks. However, studies by Wyeth-Ayerst and others have reported very rare cases of withdrawal symptoms severe enough to require permanant use. In some of these cases, successful discontinuation was eventually achieved by the addition of fluoxetine, which was later discontinued itself without difficulty.