Drug Name

Effexor (Venlafaxine)

Generic Name

Venlafaxine (VEN-la-FAX-een)

Looks like

Effexor (venlafaxine hydrochloride) Tablets are available as follows:

• Effexor 25 mg, peach, shield-shaped tablet with "25" and a "W" on one side and "701" on scored reverse side.
• Effexor 37.5 mg, peach, shield-shaped tablet with "37.5" and a "W" on one side and "781" on scored reverse side.
• Effexor 50 mg, peach, shield-shaped tablet with "50" and a "W" on one side and "703" on scored reverse side.
• Effexor 75 mg, peach, shield-shaped tablet with "75" and a "W" on one side and "704" on scored reverse side.
• Effexor 100 mg, peach, shield-shaped tablet with "100" and a "W" on one side and "705" on scored reverse side.

Dosage Form

Tablets

Route Of Administration

ORAL

Imprint Code

25;W;701 / 37.5;W;781 / 50;W;703 / 75;W;704 / 100;W;705

Size

6mm / 7mm / 8mm / 9mm / 10mm

Alternatives

SSNRI antidepressants
Cymbalta (Duloxetine)
Depression
Lexapro (Escitalopram), Zoloft (Sertraline), Prozac (Fluoxetine), Cymbalta (Duloxetine)

Drug Uses

Effexor is used to treat major depressive disorder, anxiety, and panic disorder.

Drug class

Effexor is an antidepressant in a group of drugs called selective serotonin and norepinephrine reuptake inhibitors (SSNRIs). Effexor affects chemicals in the brain that may become unbalanced and cause depression.

Contains

Compressed tablets contain venlafaxine hydrochloride equivalent to 25 mg, 37.5 mg, 50 mg, 75 mg, or 100 mg venlafaxine. Inactive ingredients consist of cellulose, iron oxides, lactose, magnesium stearate, and sodium starch glycolate.

Chemical formula

Effexor (venlafaxine hydrochloride) is a structurally novel antidepressant for oral administration. It is designated (R/S) - 1 - [2 - (dimethylamino) - 1 - (4 - methoxyphenyl) ethyl] cyclohexanol hydrochloride or (±) - 1 - [a - [(dimethyl - amino) methyl] - p - methoxybenzyl] cyclohexanol hydrochloride and has the empirical formula of C17H27NO2 HCl. Its molecular weight is 313.87. The structural formula is shown below.

Venlafaxine hydrochloride is a white to off-white crystalline solid with a solubility of 572 mg/mL in water (adjusted to ionic strength of 0.2 M with sodium chloride). Its octanol:water (0.2 M sodium chloride) partition coefficient is 0.43.

Mechanism of Action

The mechanism of the antidepressant action of venlafaxine in humans is believed to be associated with its potentiation of neurotransmitter activity in the CNS. Preclinical studies have shown that venlafaxine and its active metabolite, O-desmethylvenlafaxine (ODV), are potent inhibitors of neuronal serotonin and norepinephrine reuptake and weak inhibitors of dopamine reuptake. Venlafaxine and ODV have no significant affinity for muscarinic, histaminergic, or a-1 adrenergic receptors in vitro. Pharmacologic activity at these receptors is hypothesized to be associated with the various anticholinergic, sedative, and cardiovascular effects seen with other psychotropic drugs. Venlafaxine and ODV do not possess monoamine oxidase (MAO) inhibitory activity.

How Taken

Take this medication exactly as it was prescribed for you. Do not take the medication in larger amounts, or take it for longer than recommended by your doctor. Your doctor may occasionally change your dose to make sure you get the best results from the medication. Follow the directions on your prescription label.

Take this medication with a full glass of water. Effexor should be taken with food. Swallow the controlled-release capsule (Effexor XR) whole, without crushing or chewing. To make the medication easier to swallow, you may open the capsule and sprinkle the medicine into a small amount of applesauce. Swallow all of the mixture without chewing, and do not save any for later use.
Try to take Effexor at the same time each day.

It may take 4 weeks or more for your symptoms to improve. For best results, keep using the medication as directed. Do not stop using Effexor without first talking to your doctor. You may have unpleasant side effects if you stop taking this medication suddenly. Store Effexor at room temperature away from moisture and heat.

Dosage and Administration

Initial Treatment
The recommended starting dose for Effexor is 75 mg/day, administered in two or three divided doses, taken with food. Depending on tolerability and the need for further clinical effect, the dose may be increased to 150 mg/day. If needed, the dose should be further increased up to 225 mg/day. When increasing the dose, increments of up to 75 mg/day should be made at intervals of no less than 4 days. In outpatient settings there was no evidence of usefulness of doses greater than 225 mg/day for moderately depressed patients, but more severely depressed inpatients responded to a mean dose of 350 mg/day. Certain patients, including more severely depressed patients, may therefore respond more to higher doses, up to a maximum of 375 mg/day, generally in three divided doses.

Special Populations
Treatment of Pregnant Women During the Third Trimester
Neonates exposed to Effexor, other SNRIs, or SSRIs, late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. When treating pregnant women with Effexor during the third trimester, the physician should carefully consider the potential risks and benefits of treatment. The physician may consider tapering Effexor in the third trimester.

Dosage for Patients with Hepatic Impairment
Given the decrease in clearance and increase in elimination half-life for both venlafaxine and ODV that is observed in patients with hepatic cirrhosis and mild and moderate hepatic impairment compared to normal subjects, it is recommended that the total daily dose be reduced by 50% in patients with mild to moderate hepatic impairment. Since there was much individual variability in clearance between subjects with cirrhosis, it may be necessary to reduce the dose even more than 50%, and individualization of dosing may be desirable in some patients.

Dosage for Patients with Renal Impairment
Given the decrease in clearance for venlafaxine and the increase in elimination half-life for both venlafaxine and ODV that is observed in patients with renal impairment (GFR = 10 to 70 mL/min) compared to normals, it is recommended that the total daily dose be reduced by 25% in patients with mild to moderate renal impairment. It is recommended that the total daily dose be reduced by 50% in patients undergoing hemodialysis. Since there was much individual variability in clearance between patients with renal impairment, individualization of dosing may be desirable in some patients.

Dosage for Elderly Patients
No dose adjustment is recommended for elderly patients on the basis of age. As with any antidepressant, however, caution should be exercised in treating the elderly. When individualizing the dosage, extra care should be taken when increasing the dose.

Maintenance Treatment
It is generally agreed that acute episodes of major depressive disorder require several months or longer of sustained pharmacological therapy beyond response to the acute episode. In one study, in which patients responding during 8 weeks of acute treatment with Effexor XR were assigned randomly to placebo or to the same dose of Effexor XR (75, 150, or 225 mg/day, qAM) during 26 weeks of maintenance treatment as they had received during the acute stabilization phase, longer-term efficacy was demonstrated. A second longer-term study has demonstrated the efficacy of Effexor in maintaining an antidepressant response in patients with recurrent depression who had responded and continued to be improved during an initial 26 weeks of treatment and were then randomly assigned to placebo or Effexor for periods of up to 52 weeks on the same dose (100 to 200 mg/day, on a b.i.d. schedule).Based on these limited data, it is not known whether or not the dose of Effexor/Effexor XR needed for maintenance treatment is identical to the dose needed to achieve an initial response. Patients should be periodically reassessed to determine the need for maintenance treatment and the appropriate dose for such treatment.

Discontinuing Effexor (venlafaxine hydrochloride)
Symptoms associated with discontinuation of Effexor, other SNRIs, and SSRIs, have been reported. Patients should be monitored for these symptoms when discontinuing treatment. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose but at a more gradual rate.

SWITCHING PATIENTS TO OR FROM A MONOAMINE OXIDASE INHIBITOR
At least 14 days should elapse between discontinuation of an MAOI and initiation of therapy with Effexor. In addition, at least 7 days should be allowed after stopping Effexor before starting an MAOI.

Missed Dose

Take the missed dose as soon as you remember. However, if it is almost time for the next regularly scheduled dose, skip the missed dose and take the next one as directed. Do not take extra medicine to make up the missed dose.

Overdose

Seek emergency medical attention if you think you have taken too much of this medication. An overdose of Effexor can be fatal, especially if taken together with alcohol.

Symptoms of a Effexor overdose may include dizziness, sleepiness, nausea, and numbness or tingling in your hands or feet.

Storage

Store Effexor at room temperature, between 68 and 77 degrees F (20 and 25 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Effexor out of the reach of children and away from pets.

How Supplied

Effexor (venlafaxine hydrochloride) Tablets are available as follows:

25 mg, peach, shield-shaped tablet with "25" and a "W" on one side and "701" on scored reverse side.
NDC 0008-0701-07, bottle of 30 tablets in unit of use package.
NDC 0008-0701-08, bottle of 60 tablets in unit of use package.

37.5 mg, peach, shield-shaped tablet with "37.5" and a "W" on one side and "781" on scored reverse side.
NDC 0008-0781-07, bottle of 30 tablets in unit of use package.
NDC 0008-0781-08, bottle of 60 tablets in unit of use package.

50 mg, peach, shield-shaped tablet with "50" and a "W" on one side and "703" on scored reverse side.
NDC 0008-0703-07, bottle of 30 tablets in unit of use package.
NDC 0008-0703-08, bottle of 60 tablets in unit of use package.

75 mg, peach, shield-shaped tablet with "75" and a "W" on one side and "704" on scored reverse side.
NDC 0008-0704-07, bottle of 30 tablets in unit of use package.
NDC 0008-0704-08, bottle of 60 tablets in unit of use package.

100 mg, peach, shield-shaped tablet with "100" and a "W" on one side and "705" on scored reverse side.
NDC 0008-0705-07, bottle of 20 tablets in unit of use package.
NDC 0008-0705-08, bottle of 60 tablets in unit of use package.

What is the most important information I should know about Effexor (Venlafaxine)?

Do not take this medication if you are allergic to Effexor, or if you are also using a monoamine oxidase inhibitor (MAOI) such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate).
You may have thoughts about suicide when you first start taking an antidepressant, especially if you are younger than 24 years old. Your doctor will need to check you at regular visits for at least the first 12 weeks of treatment.

Call your doctor at once if you have any new or worsening symptoms such as: mood or behavior changes, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), more depressed, or have thoughts about suicide or hurting yourself. Avoid drinking alcohol, which can increase some of the side effects of Effexor. Using too much of this medicine in addition to drinking alcohol can cause death. It may take 4 weeks or more for your symptoms to improve. For best results, keep using the medication as directed. Do not stop using Effexor without first talking to your doctor. You may have unpleasant side effects if you stop taking this medication suddenly.

What should I discuss with my doctor before taking Effexor (Venlafaxine)?

Do not take this medication if you are allergic to Effexor, or if you are also using a monoamine oxidase inhibitor (MAOI) such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate). You must wait at least 14 days after stopping an MAOI before you can take Effexor. After you stop taking Effexor, you must wait at least 7 days before you start taking an MAOI.

Before taking Effexor, tell your doctor if you are allergic to any medications, or if you have:

• bipolar disorder (manic depression);
• cirrhosis or other liver disease;
• kidney disease;
• high blood pressure;
• glaucoma;
• seizures or epilepsy;
• a bleeding or blood clotting disorder; or
• high cholesterol.

If you have any of the conditions listed above, you may not be able to take Effexor, or you may need a dosage adjustment or special monitoring during treatment.

You may have thoughts about suicide when you first start taking an antidepressant, especially if you are younger than 24 years old. Tell your doctor if you have worsening symptoms of depression or suicidal thoughts during the first several weeks of treatment, or whenever your dose is changed.

Your family or other caregivers should also be alert to changes in your mood or symptoms. Your doctor will need to check you at regular visits for at least the first 12 weeks of treatment.

FDA pregnancy category C. Effexor may be harmful to an unborn baby, and may cause problems in a newborn baby if the mother takes the medication late in pregnancy (during the third trimester). Tell your doctor if you are pregnant or plan to become pregnant during treatment. Effexor can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby. Do not give this medication to anyone under 18 years old without the advice of a doctor.

Absorption, Distribution, Metabolism, and Excretion

Venlafaxine is well absorbed and extensively metabolized in the liver. O-desmethylvenlafaxine (ODV) is the only major active metabolite. On the basis of mass balance studies, at least 92% of a single dose of venlafaxine is absorbed. Approximately 87% of a venlafaxine dose is recovered in the urine within 48 hours as either unchanged venlafaxine (5%), unconjugated ODV (29%), conjugated ODV (26%), or other minor inactive metabolites (27%). Renal elimination of venlafaxine and its metabolites is the primary route of excretion. The relative bioavailability of venlafaxine from a tablet was 100% when compared to an oral solution. Food has no significant effect on the absorption of venlafaxine or on the formation of ODV.

The degree of binding of venlafaxine to human plasma is 27% ± 2% at concentrations ranging from 2.5 to 2215 ng/mL. The degree of ODV binding to human plasma is 30% ± 12% at concentrations ranging from 100 to 500 ng/mL. Protein-binding-induced drug interactions with venlafaxine are not expected.

Steady-state concentrations of both venlafaxine and ODV in plasma were attained within 3 days of multiple-dose therapy. Venlafaxine and ODV exhibited linear kinetics over the dose range of 75 to 450 mg total dose per day (administered on a q8h schedule). Plasma clearance, elimination half-life and steady-state volume of distribution were unaltered for both venlafaxine and ODV after multiple-dosing. Mean ± SD steady-state plasma clearance of venlafaxine and ODV is 1.3 ± 0.6 and 0.4 ± 0.2 L/h/kg, respectively; elimination half-life is 5 ± 2 and 11 ± 2 hours, respectively; and steady-state volume of distribution is 7.5 ± 3.7 L/kg and 5.7 ± 1.8 L/kg, respectively. When equal daily doses of venlafaxine were administered as either b.i.d. or t.i.d. regimens, the drug exposure (AUC) and fluctuation in plasma levels of venlafaxine and ODV were comparable following both regimens.

Special Populations

Age and Gender

A pharmacokinetic analysis of 404 venlafaxine-treated patients from two studies involving both b.i.d. and t.i.d. regimens showed that dose-normalized trough plasma levels of either venlafaxine or ODV were unaltered due to age or gender differences. Dosage adjustment based upon the age or gender of a patient is generally not necessary.

Liver Disease

In 9 subjects with hepatic cirrhosis, the pharmacokinetic disposition of both venlafaxine and ODV was significantly altered after oral administration of venlafaxine. Venlafaxine elimination half-life was prolonged by about 30%, and clearance decreased by about 50% in cirrhotic subjects compared to normal subjects. ODV elimination half-life was prolonged by about 60% and clearance decreased by about 30% in cirrhotic subjects compared to normal subjects. A large degree of intersubject variability was noted. Three patients with more severe cirrhosis had a more substantial decrease in venlafaxine clearance (about 90%) compared to normal subjects.

In a second study, venlafaxine was administered orally and intravenously in normal (n = 21) subjects, and in Child-Pugh A (n = 8) and Child-Pugh B (n = 11) subjects (mildly and moderately impaired, respectively). Venlafaxine oral bioavailability was increased 2-3 fold, oral elimination half-life was approximately twice as long and oral clearance was reduced by more than half, compared to normal subjects. In hepatically impaired subjects, ODV oral elimination half-life was prolonged by about 40%, while oral clearance for ODV was similar to that for normal subjects. A large degree of intersubject variability was noted.

Dosage adjustment is necessary in these hepatically impaired patients.

Renal Disease

In a renal impairment study, venlafaxine elimination half-life after oral administration was prolonged by about 50% and clearance was reduced by about 24% in renally impaired patients (GFR = 10-70 mL/min), compared to normal subjects. In dialysis patients, venlafaxine elimination half-life was prolonged by about 180% and clearance was reduced by about 57% compared to normal subjects. Similarly, ODV elimination half-life was prolonged by about 40% although clearance was unchanged in patients with renal impairment (GFR = 10-70 mL/min) compared to normal subjects. In dialysis patients, ODV elimination half-life was prolonged by about 142% and clearance was reduced by about 56%, compared to normal subjects. A large degree of intersubject variability was noted.

Dosage adjustment is necessary in these patients.

Possible side effects

Get emergency medical help if you have any of these signs of an allergic reaction: skin rash or hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Contact your doctor promptly if you have any of the following side effects, especially if they are new symptoms or if they get worse: mood changes, anxiety, panic attacks, trouble sleeping, irritability, agitation, aggressiveness, severe restlessness, mania (mental and/or physical hyperactivity), thoughts of suicide or hurting yourself.

Call your doctor at once if you have any of these serious side effects:

• increased blood pressure (severe headache, blurred vision);
• nausea, vomiting, diarrhea, fever, fast heartbeat; hallucinations, loss of coordination, fainting, coma;
• seizure (convulsions);
• extreme thirst with headache, nausea, vomiting, and weakness; or
• easy bruising or bleeding.

Other less serious side effects are more likely to occur, such as:

• drowsiness, dizziness, nervousness, or anxiety;
• dry mouth, increased sweating;
• nausea, vomiting, diarrhea, constipation;
• decreased sex drive, impotence, or difficulty having an orgasm;
• headache, blurred vision;
• tremor or chills; or
• changes in appetite or weight.

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome.

What other drugs will affect Effexor (Venlafaxine)?

Before taking Effexor, tell your doctor if you are using any of the following medicines:

• cimetidine (Tagamet, Tagamet HB);
• warfarin (Coumadin);
• ketoconazole (Nizoral);
• tryptophan (sometimes called L-tryptophan);
• haloperidol (Haldol) or risperidone (Risperdal);
• almotriptan (Axert), frovatriptan (Frova), sumatriptan (Imitrex), naratriptan (Amerge), rizatriptan (Maxalt), or zolmitriptan (Zomig); or
• any other antidepressants such as amitriptyline (Elavil), amoxapine (Ascendin), citalopram (Celexa), clomipramine (Anafranil), desipramine (Norpramin), escitalopram (Lexapro), fluoxetine (Prozac), fluvoxamine (Luvox), imipramine (Tofranil), nortriptyline (Pamelor), paroxetine (Paxil), protriptyline (Vivactil), sertraline (Zoloft), or trimipramine (Surmontil).

If you are using any of these drugs, you may not be able to use Effexor, or you may need dosage adjustments or special tests during treatment.

There may be other drugs not listed that can affect Effexor. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

What should I avoid while taking Effexor (Venlafaxine)?

Avoid drinking alcohol, which can increase some of the side effects of Effexor. Using too much of this medicine in addition to drinking alcohol can cause death.
Avoid using other medicines that make you sleepy (such as cold medicine, pain medication, muscle relaxers, medicine for seizures, other medication for depression or anxiety). They can add to sleepiness caused by Effexor.

Effexor can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert.

Contraindications

Hypersensitivity to venlafaxine hydrochloride or to any excipients in the formulation.

Concomitant use in patients taking monoamine oxidase inhibitors (MAOIs) is contraindicated.

Warnings

Clinical Worsening and Suicide Risk
Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18-24) with major depressiv e disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older.

The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug vs placebo), however, were relatively stable within age strata and across indications.

No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide.

It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression.

All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases.

The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality.

Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms.

If the decision has been made to discontinue treatment, medication should be tapered, as rapidly as is feasible, but with recognition that abrupt discontinuation can be associated with certain symptoms.

Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to health care providers. Such monitoring should include daily observation by families and caregivers.
Prescriptions for Effexor should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.

Screening Patients for Bipolar Disorder
A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described above represent such a conversion is unknown. However, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that Effexor is not approved for use in treating bipolar depression.

Potential for Interaction with Monoamine Oxidase Inhibitors
Adverse reactions, some of which were serious, have been reported in patients who have recently been discontinued from a monoamine oxidase inhibitor (MAOI) and started on Effexor, or who have recently had Effexor therapy discontinued prior to initiation of an MAOI. These reactions have included tremor, myoclonus, diaphoresis, nausea, vomiting, flushing, dizziness, hyperthermia with features resembling neuroleptic malignant syndrome, seizures, and death. In patients receiving antidepressants with pharmacological properties similar to venlafaxine in combination with a monoamine oxidase inhibitor, there have also been reports of serious, sometimes fatal, reactions. For a selective serotonin reuptake inhibitor, these reactions have included hyperthermia, rigidity, myoc