Venlafaxine has established itself as one of the most effective medications for depressive and anxiety disorders. Venlafaxine belongs to a class of antidepressants known as Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs). Prescribed therapeutic dosages for depression are typically in the range of 75 to 225 mg per day, but higher dosages of up to 450 mg are sometimes used for the treatment of severe or treatment-resistant depression. Venlafaxine is sometimes prescribed in lower dosages of 37.5 mg per day for patients with anxiety issues exclusively. Low doses only work on the serotonin reuptake mechanism (which may be defective in those with anxiety) but doses above 150 mg also work on norepinephrine reuptake.
Given the complexity of venlafaxine’s dose-response relationship, dosage management is an important issue in the first several weeks on this medication. Typically, users start out with the minimum 37.5 mg dose. Some may stay on this low dose indefinitely but for most patients, either with predominant anxiety or depression, at least 75 mg is required. For depression, the accepted minimum effective dose is 75 mg a day (Thomas & Taylor 2003), while for generalized anxiety disorder (GAD) it may be 37.5 mg a day. The optimal clinical dose for GAD was 75 mg daily in most cases, but with some patients it may be necessary to increase the dose to 150 mg daily. Whatever the severity of symptoms, when to expect relief also depends on the rate of dosage increase. Allgulander et al. (2001) provided evidence for venlafaxine efficacy in both the short- and long-term treatment of generalized anxiety disorder, yet efficacy was dose-related over the range examined. In their study anxiety relief was seen at weeks 1 and 2 with 150 mg of venlafaxine and at weeks 2 and 3 with 75 and 37,.5 mg of venlafaxine. Higher doses seem to be required for disorders where depression is more predominant than anxiety, and it is at these higher doses that venlafaxine appears to perform better than SSRI medications. Mbaya (2002), for instance, noted that venlafaxine has shown greater efficacy for treatment-resistant depression than SSRIs at doses of 150 mg and above. It is above this range that venlafaxine seems to start working on the norepinephrine pathways, responsible for arousal. According to Lee & Keltner (2006), dual-action antidepressants such as venlafaxine uniquely blocks the reuptake of serotonin, norepinephrine, and dopamine; unique because uptake blockade depends on drug dosage. The SNRIs apparently block serotonin at lower doses, serotonin and norepinephrine at medium to high doses, and serotonin, norepinephrine and dopamine at the highest doses (Lee & Keltner 2006). Although the efficacy of venlafaxine as a treatment for a major depressive episode is well established, opinions differ as to optimum dose needed for a response. Harrison et al. (2004) compared two groups of 35 patients each. The high-dose group were taking 375-600 mg (average 437 mg/day) while the standard-dose group were taking 75-300 mg (average 195 mg/day). Both efficacy and safety of high venlafaxine doses were confirmed as dosage was gradually increased to 450 mg at week 8, and then increased further to 600 mg from weeks 16 to 24.
Dosage management is further complicated by the onset of adverse effects. Although some studies show Venlafaxine to have a better side effect profile than other antidepressants (XX), the usual suspects ranging from lowered libido to nausea often make an appearance. The management of side effects is not the emphasis of this forum, however. Instead, we are more interested in the manifestation of adverse effects that are related to the symptoms themselves. Most antidepressant… labels, of course, caution of possible temporary worsening of the symptoms during the first weeks. Beyond this initial adjustment period, however, there may be adverse effects related to dosage increase. There have been reports, for instance, for increased agitation on a higher dose (possible due to hitting norepinephrine in ranges above 150 mg), even though the original symptoms of generalized anxiety disorder, such as deep-seated feelings of worry, have been reduced (possibly by the balancing of serotonin in the low ranges). At this point, the psychiatrist and the patient may decide on several courses of action, including reducing the dose, adding another medication, or waiting for the adverse symptoms to subside. (While such decisions should best be done with one’s doctor, oftentimes patients decide on an adjustments themselves.) Indeed, managing the issue of “wired vs. tired”, as it has sometimes been put, may be more complex with VENLAFAXINE, given its dual-action mechanism.
References
Venlafaxine Brand Names Worldwide
Depurol (CL), Dobupal (ES), Efectin (AT, CZ, HR, HU, PL, RO, SI, YU), Efexor Depot (FI, SE, DK)
Efexor XR (AU, NZ, ZA), Efexor XL (GB,IE), Efexor (AR, AU, BE, BR, CH, CL, CO, CR, CY, DK, DO, EC, EG, FI, GB, GT, HN, ID, IE, IL, IT, JO, KW, LB, LU, MT, MX, NL, NO, NZ, PA, PT, SE, SG, SV, TH, TR), Effexor Paranova (DK), Effexor (FR, IE, US), Effexor XR (AU, CA, US), Elafax (AR), Faxine (IT), Flavix (IN), Nervix (CL), Norpilen (CL), Trevilor (DE), Vandral (DK, ES), Velafax (HR), Venlafaxina Combino Pharm (ES), Venlafaxina Dosa (AR), Venlafaxina Masterfarm (ES) Venlafaxina Ratiopharm (ES), Venlafaxine-Apex (NL), Venlax (CL), Venlor (IN), Viepax (IL)
Antidepressants
Older antidepressant drugs included tricyclic antidepressants like doxepin (Adapin, Sinequan) and imipramine (Tofranil), as well as monoamine oxidase inhibitors (MAOIs) like phenelzine (Nardil) and tranylcypromine (Parnate). MAOIs prevent the breakdown of monoamine neurotransmitters (including serotonin), and therefore increase concentrations of the neurotransmitter in the brain. MAOI therapy has been associated with many adverse drug reactions, unlike the newer class of SSRIs like citalopram (Celexa), paroxetine (Paxil), fluoxetine (Prozac), sertraline (Zoloft), as well as the SNRI’s like Venlafaxine (Effexor) and duloxetine (Cymbalta). Other antidepressant drugs include bupropion (Wellbutrin), buspirone (Buspar), and nefazodone (Serzone).
SSRIs and SNRIs affect the chemicals that nerves in the brain use to send messages to one another. These chemical messengers, called neurotransmitters, are released by one nerve and taken up by other nerves. Neurotransmitters are chemicals released from a nerve cell which transmit an impulse from a nerve cell to another. When these messengers of neurologic information are not taken up by other nerves, are taken up by the same nerves that released them back to their storage vehicles for later use. This process is termed "reuptake." Selective serotonin reuptake inhibitors (SSRIs) work by inhibiting the reuptake of serotonin, which allows more serotonin to be available to be taken up by other nerves. Serotonin-norepinephrine reuptake inhibitors (SNRIs), on the other hand, increase the amount of serotonin and norepinephrine available to postsynaptic cells in the brain.
Anxiety
A feeling of apprehension and fear characterized by physical symptoms such as palpitations, sweating, and feelings of stress. Anxiety disorders are serious medical illnesses that affect approximately 19 million American adults. Unlike the relatively mild, brief anxiety caused by a stressful event such as a business presentation or a first date, anxiety disorders are chronic, relentless, and can grow progressively worse if not treated. The anxiety disorders include: panic disorder, obsessive-compulsive disorder, post-traumatic stress disorder, social phobia (or social anxiety disorder), specific phobias, and generalized anxiety disorder. Each of these anxiety disorders has its own distinct features, but they are all bound together by the common theme of excessive, irrational fear and dread. Generalized anxiety disorder (GAD), in particular, is defined as excessive anxiety and worry about a number of events or activities occurring for more days than not over a period of at least 6 months with associated symptoms (such as fatigue and poor concentration).
Depression
An illness that involves the body, mood, and thoughts, that affects the way a person eats and sleeps, the way one feels about oneself, and the way one thinks about things. A depressive disorder is not the same as a passing blue mood. It is not a sign of personal weakness or a condition that can be wished away. People with a depressive disease cannot merely "pull themselves together" and get better. Without treatment, symptoms can last for weeks, months, or years. Appropriate treatment, however, can help most people with depression.
The signs and symptoms of depression include loss of interest in activities that were once interesting or enjoyable, including sex; loss of appetite (anorexia) with weight loss or overeating with weight gain; loss of emotional expression (flat affect); a persistently sad, anxious or empty mood; feelings of hopelessness, pessimism, guilt, worthlessness, or helplessness; social withdrawal; unusual fatigue, low energy level, a feeling of being slowed down; sleep disturbance with insomnia, early-morning awakening, or oversleeping; trouble concentrating, remembering, or making decisions; unusual restlessness or irritability; persistent physical problems such as headaches, digestive disorders, or chronic pain that do not respond to treatment; thoughts of death or suicide or suicide attempts. Alcohol or drug abuse may be signs of depression. The principal types of depression are:
Side Effects
Problems that occur in addition to the desired therapeutic effect. Allgulander et al. (2004) list the following in their study: Asthenia, Anorexia, Constipation, Dry mouth, Nausea, Anxiety, Dizziness, Insomnia, Libido decreased, Somnolence, Tremor, Sweating, Abnormal ejaculation, Anorgasmia, Impotence.
Some reports online group many systems into two clusters: symptoms of being tired vs. those of feeling wired. Tired in this context would include fatigue, lethargy, and low energy. But these would not be like apathy due to the sadness of depression, but more like too mellow, the opposite of feeling wired. Symptoms of being wired would include feeling agitated, tense, edgy, irritable, as well as possible insomina and even hypertension. This feeling would be more like being hyper after too much coffee, rather than the emotional anxiety typical of GAD.
Fatigue. A condition characterized by a lessened capacity for work and reduced efficiency of accomplishment, usually accompanied by a feeling of weariness and tiredness. Fatigue can be acute and come on suddenly or chronic and persist.
Insomnia. The perception or complaint of inadequate or poor-quality sleep because of one or more of the following: difficulty falling asleep; waking up frequently during the night with difficulty returning to sleep; waking up too early in the morning; or unrefreshing sleep. Insomnia is not defined by the number of hours of sleep a person gets or how long it takes to fall asleep. Individuals vary normally in their need for, and their satisfaction with, sleep. Insomnia may cause problems during the day, such as tiredness, a lack of energy, difficulty concentrating, and irritability.