Venlafaxine hypertension with

This antidepressant can interact with other drugs via its two mechanisms of action serotonin and NE uptake inhibition. The former action means that the same pharmacodynamic interactions will occur with venlafaxine as with SSRIs, including the serotonin syndrome. At higher doses, venlafaxine is also prone to the same pharmacodynamic interactions as NSRIs such as secondary amine TCAs like desipramine and with newer NSRIs such reboxetine. Thus, the combination of high-dose venlafaxine plus an MAOl could produce a hypertensive crisis as well as the serotonin syndrome. 

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). 

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. 

Regarding side-effect profiles, all three SSNRIs are generally well tolerated, most adverse events occurring early in treatment, with a mild to moderate severity and a tendency to decrease or disappear with continued treatment. Venlafaxine (1) seems to be the least weU-toIerated SNRI, combining a higher level of serotonergic adverse events (nausea, sexual dysfunction, withdrawal problems) with dose-dependent hypertension. In contrast, milnacipran (2) and duloxetine (3) appear better tolerated and essentially devoid of cardiovascular toxicity. 

The side-effect profile of venlafaxine is similar to that of SSRIs and includes gastrointestinal symptoms, sexual dysfunction, and transient discontinuation symptoms. Like the SSRIs, venlafaxine does not affect cardiac conduction or lower the seizure threshold. In most patients, venlafaxine is not associated with sedation or weight gain. Side effects that differ from those of SSRIs are hypothesized to be related to the increased noradrenergic activity of this drug at higher doses these side effects are dose-dependent anxiety (in some patients) and dose-dependent hypertension. 

MAOIs have the most serious pharmacodynamic interactions of any antidepressant class. As discussed earlier, they can cause a hypertensive crisis and the serotonin syndrome. They potentiate the hypertensive effects of most sympathomimetic amines, as well as tyramine, which is the reason for the avoidance of over-the-counter preparations containing such agents, in addition to the tyramine-free diet ( 508, 509). The serotonin syndrome occurs most often when MAOIs are used in combination with SSRIs and venlafaxine but it can also occur when MAOIs are used with tryptophan, 5-hydroxytryptophan, and some narcotic analgesics. In addition, MAOIs can also significantly potentiate the sedative and respiratory depressant effects of narcotic analgesics. 

Venlafaxine (Effexor), approved by the FDA in December 1993, was described in more detail early in this chapter. It is one of the newer antidepressants implicated in causing suicidality. It is a NSRI that also strongly inhibits the reuptake of epinephrine. Its profile is very similar to the SSRIs in producing stimulation, including anxiety, nervousness, insomnia, anorexia, and weight loss. It causes the various emotional and behavioral abnormalities that go along with stimulation, such as agitation and mania, and has been associated with hostility, paranoid reaction, psychotic depression, and psychosis. It can cause hypertension. 

These cases suggest that even after the recommended 2-week washout from MAO inhibitors, venlafaxine can provoke serotonin toxicity in some patients. In principle it should be possible to switch from one conventional MAO inhibitor to another without a washout period. However, there have been reports that patients who switched from phenelzine to tranylcypromine had hypertensive reactions, with disastrous consequences (84). Whenever possible, a 2-week washout period when switching MAO inhibitors or when introducing serotonin re-uptake inhibitors seems advisable. 

Venlafaxine is often used in high doses in patients with treatment-resistant depression. If there is continuing failure to respond, electroconvulsive therapy might be used, often in combination with venlafaxine. A 73-year-old woman taking venlafaxine (112.5 mg/day) had sustained hypertension for several hours after her first treatment (9). However, electroconvulsive therapy can cause transient hypertension, and the patient had essential... 

Broom 2. Ginkgo biloba 3. Scopolia 4. Yohimbine 1. TCAs (e.g. amitriptyline, nortriptyline, clomipramine) 2. SSRIs (e.g. fluvoxamine fluoxetine, paroxetine) 3. Venlafaxine 4. Trazodone May develop cardiac arrhythmias and side-effects such as dryness of the mouth, retention of urine and tachycardia, t sedation Broom contains cardioactive alkalamines such as sparteine Inhibits metabolizing enzymes Anticholinergic properties (hyoscine present in scopolia may worsen side-effects of TCAs-additive antimuscarinic effects) Yohimbine alone can cause hypertension, but lower doses cause hypertension when combined with TCAs Unknown mechanism (ginkgo t sedative effects of trazodone) St John s wort inhibits the uptake of serotonin and thereby t serotonin levels Avoid concomitant use. An SSRI may be a better alternative to be used with broom... 

Venlafaxine produces some unwanted effects that resemble those of SSRIs with a higher incidence of nausea. Sustained hypertension (due to blockade of noradrenaline reuptake) is a problem in a small percentage of patients at high dose and blood pressure should be monitored when > 200 mg/day is taken. 

The most commonly reported adverse effects with venlafaxine include nausea, constipation, somnolence, dry mouth, dizziness, nervousness, sweating, asthenia, abnormal ejaculation/orgasm, and anorexia." These side effects may be dose related. Venlafaxine may cause a dose-related increase in diastolic blood pressure, and basehne blood pressure is not a useful predictor of the occurrence of this phenomenon. Blood pressure should be monitored regularly during venlafaxine therapy, and dosage reduction or discontinuation may be necessary if sustained hypertension occurs. ... 

The steady-state plasma concentration of venlafaxine increases by 61 % when it is combined with cimetidine. Therefore, caution is advised with the use of cimetidine and venlafaxine in elderly patients, in patients with pre-existing hypertension, and in patients with hepatic or renal dysfunction. 

A 32-year-old woman with depression who had been taking venlafaxine 225 mg daily in divided doses for 3 years was admitted to hospital after a fall. She developed a movement disorder and a period of unresponsiveness after being given a 10-mg intravenous dose of metoclopramide. After a second dose of metoclopramide the symptoms recurred and were associated with confusion, agitation, fever, diaphoresis, tachypnoea, tachycardia, and hypertension. The symptoms were consistent with the serotonin syndrome, with a serious extrapyramidal movement disorder. The venlafaxine was withheld and she was given diazepam. The symptoms resolved over the next two days, after which she continued to take venlafaxine. Information seems to be limited to this report, and the general significance of this interaction is unclear. 

Theoretically the metabolism of venlafaxine may be inhibited by CYP2D6 inhibitors or substrates such as diphenhydramine, melperone, quinidine or thioridazine. CYP3A4 inhibitors such as ketoconazole may also have some effect. An isolated case describes a hypertensive crisis associated with venlafaxine and di-sulfiram. The manufacturers predict that the use of triptans with venlafaxine may have additive effects on serotonin, which could lead to the serotonin syndrome. 

Khurana RN, Baudendistel TE. Hypertensive crisis associated with venlafaxine. Am J Med (2003) 115, 676-7. 

However, in a case series of 273 patients who took an overdose of venlafaxine, overdose caused only minor abnormalities in the QT and QRS intervals, and was unlikely to be associated with major dysrhythmias, except possibly with large doses (>8 g) [63 "]. The commonest cardiovascular effects were tachycardia (54% of patients) and mild hypertension (40%). 

Hypertension Although venlafaxine has been reported to be associated with a dose-dependent increase in hypertension, and the product information lists increases in blood pressure (BP) as a potential adverse effect, there had been no previous reports implicating desvenlafaxine in hypertension [56 ]. 

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