Effexor XR Black Box WARNING

Before we talk about the romance killer, lets look at what Effexor XR is and what impacts and risks come with using this medication.

What is Effexor? Venlafaxine, an antidepressant medication that works in the brain to treat major depressive disorder.

WHAT IS MAJOR DEPRESSIVE DISORDER?

Depression is a mood disorder that causes a persistent feeling of sadness and loss of interest. Also called major depressive disorder or clinical depression, it affects how you feel, think and behave and can lead to a variety of emotional and physical problems. You may have trouble doing normal day-to-day activities, and sometimes you may feel as if life isn’t worth living.

More than just a bout of the blues, depression isn’t a weakness and you can’t simply “snap out” of it. Depression may require long-term treatment. But don’t get discouraged. Most people with depression feel better with medication, psychotherapy or both.

Symptoms

Although depression may occur only once during your life, people typically have multiple episodes. During these episodes, symptoms occur most of the day, nearly every day and may include:

Feelings of sadness, tearfulness, emptiness or hopelessness
Angry outbursts, irritability or frustration, even over small matters
Loss of interest or pleasure in most or all normal activities, such as sex, hobbies or sports
Sleep disturbances, including insomnia or sleeping too much
Tiredness and lack of energy, so even small tasks take extra effort
Reduced appetite and weight loss or increased cravings for food and weight gain
Anxiety, agitation or restlessness
Slowed thinking, speaking or body movements
Feelings of worthlessness or guilt, fixating on past failures or self-blame
Trouble thinking, concentrating, making decisions and remembering things
Frequent or recurrent thoughts of death, suicidal thoughts, suicide attempts or suicide
Unexplained physical problems, such as back pain or headaches

Effexor (venlafaxine) is a prescription medication indicated in the treatment of both MDD and GAD. Effexor belongs to a group of antidepressants known as selective serotonin-norepinephrine reuptake inhibitors (SNRIs). Effexor blocks the reuptake of both norepinephrine and serotonin in the neuron synapse, effectively leaving more free serotonin and norepinephrine available. These neurotransmitters play a positive role on mood and affect.

Works on your CNS

Is Effexor a CNS depressant?Venlafaxine may increase the central nervous system depressant (CNS depressant) activities of Aclidinium.

Mechanism of Action

Venlafaxine works by increasing serotonin levels, norepinephrine, and dopamine in the brain by blocking transport proteins and stopping its reuptake at the presynaptic terminal. This action leads to more transmitter at the synapse and ultimately increases the stimulation of postsynaptic receptors. SNRIs act primarily upon serotonergic and noradrenergic neurons but have little or no effect upon cholinergic or histaminergic receptors. Venlafaxine is a bicyclic phenylethylamine compound.[3] Venlafaxine is a more potent inhibitor of serotonin reuptake than norepinephrine reuptake. Venlafaxine is essentially a selective serotonin reuptake inhibitor at 75 mg + , it has significant effects on the norepinephrine transporter in addition to serotonin.Go to:

When is Effexor prescribed?

Condition	Effexor
Major depressive disorder	Yes
Generalized anxiety disorder	Yes
Social phobia	Yes
Panic disorder	Yes
Obsessive-compulsive disorder	Off-label
Premenstrual dysphoric disorder	Off-label
Hot flashes due to menopause	Off-label

Adverse Effects

Venlafaxine causes a lower frequency of anticholinergic, sedating, and cardiovascular side effects but a higher incidence of gastrointestinal complaints, sleep impairment, and sexual dysfunction than TCAs. Additionally, venlafaxine may impair sexual function, resulting in diminished libido, impotence, or difficulty in achieving orgasm. Sexual dysfunction frequently results in noncompliance and should be asked about specifically. Sexual dysfunction can sometimes be ameliorated by lowering the dose or instituting drug-free weekends and holidays in appropriate patients. Some patients find withdrawal symptoms uncomfortable.[5]

Common side effects include:

Headache
Decreased sex-drive
Nausea
Insomnia, dizziness, hypotension, anorexia, somnolence
Xerostomia
Asthenia
HTN
Impotence, decreased libido, and/or anorgasmia
Constipation
Weight loss
Abnormal dreams
Diarrhea, abdominal pain
Blurred vision
Anxiety, tremor
Hypercholesterolemia
Hyponatremia
Serotonin Syndrome
Seizures

BLACK BOX WARNING

There is an FDA black box warning against venlafaxine as it can increase suicidality, cause depression exacerbation, hypomania/mania, and serotonin syndrome. Venlafaxine can also cause abnormal bleeding, altered platelet function, and anaphylaxis/anaphylactoid reaction. Venlafaxine can cause fatal skin conditions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme. Venlafaxine can also cause deterioration of glaucoma angle closure and seizures.[6] Venlafaxine has implications linking it to SIADH, HTN, arrhythmia, interstitial lung disease, eosinophilic pneumonia, pancreatitis, and hepatotoxicity. One main concern with SSRIs and SNRIs is the risk of serotonin syndrome, thought to result from hyperstimulation of brainstem 5HT-1A receptors

Monitoring

Venlafaxine can interact with many other medications, vitamins, or herbs. Concurrent use of these agents can cause dangerous effects and are contraindicated with venlafaxine. The following is a brief list of drug interactions with venlafaxine:

Patients should not take venlafaxine with monoamine oxidase inhibitors (MAOIs), linezolid, and methylene blue.
Caution is necessary when using venlafaxine with other drugs that can increase serotonin levels, including SSRIs, SNRIs, and tramadol, as they can lead to life-threatening serotonin syndrome. Other drugs that can raise serotonin include triptans, such as sumatriptan, rizatriptan, and zolmitriptan.
Venlafaxine should not be combined with drugs for weight loss, such as phentermine. Using venlafaxine with drugs like phentermine may result in excessive weight loss, serotonin syndrome, and heart problems such as tachycardia and hypertension.
Venlafaxine with cimetidine raises the risk of high blood pressure or liver disease.
Venlafaxine with haloperidol raises the risk of QT prolongation.[9]
Venlafaxine taken with warfarin and anti-inflammatory drugs such as aspirin, ibuprofen, naproxen (NSAIDs) increases the risk of bleeding.
Ritonavir, clarithromycin, or ketoconazole can inhibit the breakdown of venlafaxine leading to venlafaxine accumulation in the body.
Venlafaxine, taken with zolpidem, lorazepam, and diphenhydramine, can lead to increased sedation.
Metoprolol may be less effective when taken with venlafaxine.
Venlafaxine can cause false positives when testing the patient’s urine for phencyclidine (PCP) and amphetamine. This effect may remain for several days after stopping venlafaxine.

Toxicity

Venlafaxine oral tablet is prescribed for long-term treatment. It comes with serious risks if not taken as prescribed or stop it abruptly. Abrupt cessation of venlafaxine can lead to serious adverse effects such as irritability, tiredness, restlessness, anxiety, insomnia, trouble sleeping, nightmares, headache, sweating, dizziness, tingling or “pins and needles” feeling, shaking, confusion, nausea, vomiting, or diarrhea.

Severe toxicity of venlafaxine, can lead to serotonin syndrome. Serotonin syndrome is a possibly life-threatening condition associated with increased serotonergic activity in the central nervous system. Serotonin syndrome may present with a spectrum of clinical findings, including autonomic hyperactivity, mental status changes, and neuromuscular abnormalities. Serotonin syndrome characteristically presents with myoclonus, agitation, abdominal cramping, hyperpyrexia, hypertension, and potentially death. No laboratory tests exist to confirm the diagnosis as serotonin concentrations do not correlate clinically with symptoms. Hunter Toxicity Criteria Decision Rules can be used to form the diagnosis.[10] To meet the criteria, the patient must be taking a serotonergic agent and fulfill one of the following conditions patients must exhibit spontaneous clonus

An inducible clonus must be present, plus agitation or diaphoresis
The presence of ocular clonus plus agitation or diaphoresis
Tremor with hyperreflexia
Hypertonia with a temperature above 38 degrees C plus ocular clonus or inducible clonus

Management of serotonin syndrome involves prompt discontinue of all serotonergic agents with supportive care aimed at normalizing hemodynamics. Patient sedation with benzodiazepines and serotonin antagonists may also be an option.[7] Cyproheptadine can is an option in the event of a failure with benzodiazepines and supportive care. Cyproheptadine is a histamine-1 receptor antagonist with nonspecific 5-HT1A and 5-HT2A antagonistic properties, with an initial dose of 8 mg. Treatment with propranolol, bromocriptine, or dantrolene is not recommended. Serotonin syndrome symptoms usually resolve within 24 hours of discontinuation of the offending agent.

Serotonin syndrome occurs when you take medications that cause high levels of the chemical serotonin to accumulate in your body. Serotonin is a chemical your body produces that’s needed for your nerve cells and brain to function

Does Effexor affect memory?

Amnesia has been reported in a small number of patients taking Effexor products. If you notice this adverse event, let your prescriber know immediately as a change in therapy may be warranted.

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