Venlafaxine dosing

In eight patients with major depressive disorder without psychotic features, who did not respond to serotonin reuptake inhibitors therapy when risperidone was added, all improved within 1 week. Furthermore, risperidone also seemed to have beneficial effects on sleep disturbance and sexual dysfunction (272). In an open study in 30 healthy subjects who took risperidone 1 mg orally before and after venlafaxine dosing to steady state, the oral clearance of risperidone fell by 38% and the volume of distribution by 17%, resulting in a 32% increase in AUC renal clearance of 9-hydroxyrisperidone also fell by 20% (273). The authors concluded that these small effects were consistent with the fact that venlafaxine is unlikely to alter the clearance of risperidone, which is mainly by CYP2D6. 

Venlafaxine extended-release, a serotonin-norepinephrine reuptake inhibitor (SNRI), alleviates anxiety in patients with and without co-morbid depression. The reduction in psychic symptoms of anxiety and tension is not accompanied by significant reductions in somatic symptoms. Venlafaxine (dosed once daily) was effective at doses of 150 and 225 mg for 2 months in patients with GAD, and efficacy was maintained for an additional 6 months of therapy." Paroxetine was significantly more effective than placebo at achieving response in 62% and 68% of patients at 20 and 40 mg daily, respectively, after 2 months. Remission occurred in 30% and 36% of patients taking 20 and 40 mg of paroxetine, respectively." Escitalopram was more efficacious than placebo in three 8-week trials in patients with GAD. In a four paraUel-group comparison, diazepam and trazodone were found to be equivalent in anxiolytic activity (remission rates of 66% and 69%, respectively) compared with placebo (47% remission rate), but rmipramine s rate of remission (73%) exceeded that of the other three treatments. ... 

A 50-year-old HIV-positive man, who was receiving methadone for opioid dependence, developed signs of the serotonin syndrome 18 days after starting to take extended-release venlafaxine (dose increased to 225 mg... 

One of these compounds, venlafaxine (licensed in the UK in 1996), is regarded as an inhibitor of both 5-HT and noradrenaline reuptake but this is based on its actions in vitro. At low doses in vivo, it is a more potent inhibitor of 5-HT (Ki 39 nM) than noradrenaline reuptake (K 210 nM). Moreover, its active metabolite, O-demethylven-lafaxine, is a weaker inhibitor of NA reuptake, and has a longer half-life, than its parent compound. However, at high doses, venlafaxine inhibits reuptake of both these monoamines but has negligible activity at muscarinic, Hi-receptors or ai-adrenoceptors and... 

The starting dose is the usual therapeutic dose for most of the SSRIs, duloxetine, and mirtazapine, whereas there is usually need for at least some upward titration of venlafaxine, bupropion,... 

Venlafaxine was approved by the FDA recently for the treatment of PD. Venlafaxine in doses of 75 to 225 mg/day reduced panic and anticipatory anxiety in short-term controlled trials. The most common side effects include anorexia, dry mouth, constipation, somnolence, tremor, abnormal ejaculation, and sweating.52... 

Venlafaxine extended release, in doses of 75 to 225 mg/day, improves social anxiety, performance, and avoidance behavior with a reduction in disability.61 Treatment with venlafaxine results in response rates similar to those seen with paroxetine.60 Venlafaxine may be effective in SSRI non-responders.62 As with SSRIs, doses should be tapered slowly when discontinuing therapy. Tolerability is similar to that observed in depression trials with venlafaxine extended release. Common side effects are anorexia, dry mouth, nausea, insomnia, and sexual dysfunction. 

Peripheral neuropathy is the most common complication reported in type 2 DM. This complication generally presents as pain, tingling, or numbness in the extremities. The feet are affected more often than the hands and fingers. A number of treatment options have been tried with mixed success. Current options include pregabalin, gabapentin, low-dose tricyclic antidepressants, duloxetine, venlafaxine, topiramate, non-steroidal anti-inflammatory drugs, and topical capsaicin. 

SSRIs are theorized to reduce the frequency of hot flashes by increasing serotonin in the central nervous system and by decreasing LH. Of the SSRIs, citalopram, paroxetine, and sertraline all have been studied and have demonstrated a reduction in hot flashes while treating other symptomatic complaints such as depression and anxiety.33 Venlafaxine, which blocks the reuptake of serotonin and norepinephrine, has demonstrated a reduction in hot flashes primarily in the oncology population.34 Overall, these antidepressant medications offer a reasonable option for women who are unwilling or cannot take hormonal therapies, particularly those who suffer from depression or anxiety. These agents should be prescribed at the lowest effective dose to treat symptoms and may be titrated based on individual response. 

Pregabalin produced anxiolytic effects similar to lorazepam, alprazolam, and venlafaxine in acute trials. Sedation and dizziness were the most common adverse effects, and the dose should be tapered over 1 week upon discontinuation. 

The serotonin-norepinephrine reuptake inhibitors include venlafaxine and duloxetine. Venlafaxine is an inhibitor of 5-HT and NE reuptake and a weak inhibitor of DA reuptake. Desvenlafaxine (Pristiq) was recently approved by the FDA. The dose is 50 mg once daily. 

Venlafaxine may cause a dose-related increase in diastolic blood pressure. Dosage reduction or discontinuation may be necessary if sustained hypertension occurs. Other side effects are similar to those associated with the SSRIs (e.g., nausea and sexual dysfunction). 

Venlafaxine (Effexor, Effexor XR). Venlafaxine works by blocking the reuptake of both serotonin and norepinephrine. Because of this dual action, some believe that venlafaxine may be more effective than the SSRIs when treating severe depression. Its side effects and toxicity are similar to the SSRIs with abdominal discomfort, sexual dysfunction, and anxiety being commonly reported. At higher doses, it may mildly elevate blood pressure therefore, blood pressure should be checked periodically. When stopping venlafaxine, serotonin discontinuation symptoms may be especially problematic. Therefore, gradually tapering of the dose every 2-4 weeks is recommended. 

Like bupropion, venlafaxine comes in immediate-release and extended-release preparations. The immediate-release form is taken twice a day starting at 37.5 to 75 mg/day and increased to 75 mg/day after 1 week. The effective dose range is 75-375mg/day. The extended release form is started once daily at 37.5mg/day and is also effective at 75-375 mg/day. The effective dose range is similar to the immediate-release form. 

Generalized Sociai Anxiety Disorder, Treatment Resistance. A significant minority of patients will not experience a satisfactory treatment response to antidepressant therapy, even after a trial of adequate duration at full strength doses. For those with comorbid depression who are experiencing no benefit from SSRI treatment for either the anxiety or depression, then switching treatment is advisable. The options include switching to another SSRI, a SNRI (venlafaxine or perhaps dulox-etine), or, when other alternatives fail, phenelzine. 

An initial controlled study of venlafaxine, a SNRI, indicated that it is as effective as sertraline for overall PTSD symptoms at a mean dose of approximately 225mg/day. 

Venlafaxine (Effexor, Effexor XR). Venlafaxine, a dual serotonin-norepinephrine reuptake inhibitor, has only recently been used to treat ADHD with a few case reports suggesting it may provide modest benefit for both inattention and impulsivity. Effexor XR is generally well tolerated, though it can elevate blood pressure somewhat at higher doses. This should be monitored especially when venlafaxine is coadministered with a stimulant. Controlled trials are needed. 

If depression is a problem, many clinicians prefer an antidepressant as an augmentation strategy. Because of the problems mentioned earlier, most now avoid using TCAs to treat ADHD. Bupropion, SSRIs, and venlafaxine are viable alternatives, and may add to the effect of the stimulant. Bupropion and venlafaxine are believed to offer some additional improvement in attention. SSRIs may be more likely to improve impulsivity. Each should be started at a low dose and increased gradually. None of these are approved for use in children however. 

Serotonin-Boosting Antidepressants. The SSRIs have also been studied in the treatment of generalized social anxiety disorder, and paroxetine, sertraline, and venlafaxine are effective. Preliminary data suggests that the serotonin-boosting atypical antidepressants (mirtazapine and nefazodone) may also be helpful. Like the MAOIs, they appear to be effective at doses comparable to those used to treat depression. They may help avoidant patients to gradually increase their social interaction and become more assertive. 

Medications that enhance norepinephrine activity can do so in one of several ways. First, they can block the reuptake of norepinephrine back into the nerve cell once it has been released. This keeps the norepinephrine in the synapse longer and therefore makes it more active. The tricyclic antidepressants (TCAs), duloxetine (Cymbalta), and venlafaxine (Effexor) act in this manner, as does paroxetine (Paxil) at higher doses. Atomoxetine (Strattera), a treatment for ADHD, also works in this way. 

Milnacipran is also a dual-action antidepressant which, like venlafaxine, has been shown to be more effective than the SSRIs in the treatment of severe, hospitalized and suicidally depressed patients. At lower therapeutic doses, milnacipran blocks the noradrenaline transporters and therefore resembles the NRI antidepressants. Higher doses result in the serotonergic component becoming apparent (i.e. an SSRI-like action). The main problem with milnacipram appears to be its lack of linear kinetics with some evidence that it has a U-shaped dose-response curve (Figure 7.3). 

Administer a high therapeutic dose of a "dual action" antidepressant such as venlafaxine or possibly mirtazepine. A discontinuation syndrome may occur if venlafaxine is abruptly withdrawn. The... 

Diclofenac is available as dispersible tablets, tablets, gel, suppositories and for intravenous or intramuscular injection. The maximum dose of diclofenac administered via any route is 150 mg. As v/ith other non-steroidal anti-inflammatory drugs, concomitant use in patients receiving venlafaxine increases the risk of bleeding. 

Discontinuation - When discontinuing venlafaxine after more than 1 week of therapy, it is generally recommended that the dose be tapered to minimize the risk of discontinuation symptoms. Patients should have their dose tapered gradually over a 2-week period. 

Switching patients from immediate-release to ER ven/afax/ne.Patients currently treated at a therapeutic dose with venlafaxine may be switched to the ER form at the nearest eguivalent dose (mg/day eg, venlafaxine 37.5 mg 2 times/day to venlafaxine ER 75 mg once daily). 

Sustained hypertension There is a dose-dependent increase in the incidence of sustained hypertension for venlafaxine from 3% for doses less than 100 mg/day up to 13% for doses greater than 300 mg/day. It is recommended that patients receiving venlafaxine have regular monitoring of blood pressure. For patients who experience a sustained increase in food pressure, consider dose reduction or discontinuation. Renal/Hepatic function impairment In patients with renal impairment (GFR, 10 to 70 mL/min) or cirrhosis of the liver, a lower dose may be necessary. 

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