Effexor
withdrawal. Effexor
withdrawal side effects,
Effexor
withdrawal warnings,
Effexor
withdrawal precautions,
Effexor
withdrawal adverse effects, overdose, withdrawal symptoms and
Effexor
natural alternatives. Before you begin the spiral down with
Effexor, try giving your body what it really wants.
Effexor
If you are struggling with Effexor side effects, want to
taper off Effexor, have already started to reduce Effexor or quit Effexor cold
turkey, there is help and there is a solution.
The bestselling book,
How to Get Off Effexor Safely details how to eliminate Effexor side effects,
how to safely taper off Effexor, what to do if you have already started to taper
off Effexor and are suffering and what you can do if you went off Effexor too
fast and are suffering the Effexor side effects.
This 292 page paperback book is easy to read but technical in
the right areas to share with your physician. This successful method of handling
these unwanted Effexor side effects is used by leading psychiatrists and medical
doctors worldwide. The book also includes chapters detailing how to get off
benzodiazepines and antipsychotics.
In March 2009 the American Medical Association acknowledged
antidepressant medications do come with withdrawal side effects and up to 20% of
the population will suffer these symptoms while trying to discontinue the
medication.
How to Get Off Effexor
Safely is available at Amazon.com for $18.95
Warning:
You may find this book being sold used for $44.00 on Amazon.com. It is not a
collectors item or in short supply. For a change you can purchase something new
for less money than something used.
The anxiety, insomnia, fatigue or head symptoms that are usually associated with
Effexor withdrawal or the common Effexor side effects can be a thing of the
past.
Read a review found on Amazon.com
"I
am weeping tears of gratitude as I write this. I shall be eternally grateful to
James Harper and his work, The Road Back Program, and his fine books especially
"How To Get Off Psychiatric Drugs Safely" and all his other wonderful books
available here on Amazon.com. James Harper has not only literally saved my
life---but he has given my life back to me, my loved ones, and to my many
patients. How does one give thanks to another human being for literally saving
one's life?
ANYONE who is suffering the nightmare side or withdrawal effects from
Antipsychotic, Antidepression, Sleeping medications,(Ambien): Benzodiazepines,
ADD or ADHD drugs, is foolish not to acquire and read Harper's book(s.)
I
have been addicted to Benzodiazepines (in one form or another) Xanax, Ativan,
Klonopin, etc., Antidepressants: Prozac, Paxil, Zoloft, Effexor, Antipsychotics
such as Zyprexa, Seroquel, Risperdal: Sleepers including Ambien, Sonata and
Lunesta---and on and on. I have FAILED 11 in hospital 28 day detox programs, and
have attempted withdrawal on my own over 100 times, and always failed because
the pain of the withdrawal symptoms became too much to bear, and I would have to
"re-intoxicate" myself on the drugs to get some relief.
Not so with James Harper's "The Road Back Program." I followed ALL of his
suggestions to the letter, and for the first time in 41 years I have been DRUG
free for 32 days, and counting, with virtually NO withdrawal side effects or
pain whatsoever! I offer this personal account from an attitude of humility and
deep respect." Dr. Peter Evans
"I cannot thank you enough for creating The Road Back! I have just a week left
until I am completely done with the program, having been off the medications for
38 days and I feel better than I've
felt in years!
I was taking Effexor XR and Lamictal and suffering under all the side effects,
not to mention the prospect of never being able to have kids or energy if I
stayed on them my whole life.
One of my friends found your program online after I broke down in front of her
because of how tired and useless I'd been feeling from all the medications.
The program seemed almost too good to be true! But it's really worked for me!
I've followed the schedule very strictly and kept a daily journal and for the
most part, I feel like a new person. I am so so thankful for you!! And I just
wanted to let you know that." K.L.
Effexor - Alert from the F.D.A.
FDA ALERT [07/2005]: Suicidal Thoughts or Actions in
Children and Adults
Patients with depression or other mental illnesses often
think about or attempt suicide. Closely watch anyone taking antidepressants,
especially early in treatment or when the dose is changed. Patients who become
irritable or anxious, or have new or increased thoughts of suicide or other
changes in mood or behavior (or their care givers) should contact their
healthcare professional right away.
Children
Taking antidepressants may increase suicidal thoughts and actions in about 1
out of 50 people 18 years or younger. FDA has approved Zoloft for use in
children only if they have obsessive-compulsive disorder.
Adults
Several recent scientific publications report the possibility of an increased
risk for suicidal behavior in adults who are being treated with antidepressant
medications. Even before these reports became available, FDA began a complete
review of all available data to determine whether there is an increased risk of
suicidal thinking or behavior in adults being treated with antidepressant
medications. It is expected that this review will take a year or longer to
complete. In the meantime, FDA is highlighting that adults being treated with
antidepressant medication, particularly those being treated for depression,
should be watched closely for worsening of depression and for increased suicidal
thinking or behavior.
This information reflects FDA’s preliminary
analysis of data concerning this drug. FDA is considering, but has not reached a
final conclusion about, this information. FDA intends to update this sheet when
additional information or analyses become available.
Fatal venlafaxine overdose
with acinar zone 3 liver cell necrosis.
Shaw MW, Sheard JD.
Department of Cellular Pathology, University Hospital Aintree, Liverpool, UK.
We present a case of fatal venlafaxine overdose in a 34-year-old male with a
history of depression and previous suicide attempts. He presented unwell, and
his condition deteriorated with the development of rhabdomyocytolysis and renal
failure. Although treatment was provided, this was unsuccessful, and he died
within a day of his admission. A postmortem examination was performed, and the
findings included an acinar zone 3 pattern of liver cell necrosis and a very
high level of serum venlafaxine in the deceased. No other elevated drug levels
were detected. From this case, it is clear that venlafaxine overdose was the
primary cause of a fatal acinar zone 3 pattern of liver cell necrosis. As far as
we are aware, this is the first reported case of fatal acinar zone 3 liver
necrosis caused by venlafaxine overdose alone.
Serotonin syndrome and
rhabdomyolysis in venlafaxine poisoning: a case report.
Hanekamp BB, Zijlstra JG, Tulleken JE, Ligtenberg JJ, van der Werf TS, Hofstra
LS.
Intensive and Respiratory Care, Groningen University Medical Centre, Groningen,
the Netherlands. b.b.hanekamp@int.umcg.nl
Newer, more selective, antidepressant agents are increasingly being used as
first-line treatment. However, clinical experience in patients after a
deliberate overdose is limited. We present a case of venlafaxine intoxication
complicated by a late rise in creatine kinase, seizures and serotonin syndrome.
Rhabdomyolysis prolonged the hospital stay in our patient but had no other
serious consequences. Physicians should be aware of this late phenomenon in
patients with venlafaxine poisoning.
Severe rhabdomyolysis following
venlafaxine overdose.
Pascale P, Oddo M, Pacher P, Augsburger M, Liaudet L.
Division of Critical Care, Department of Internal Medicine, University Hospital,
Lausanne 1011, Switzerland.
Venlafaxine is a recently developed serotoninergic antidepressant whose reported
toxicity at overdose levels includes central nervous system depression,
seizures, and cardiovascular toxicity. The authors now present a case of
venlafaxine overdose in a young woman complicated by a rise in plasma creatine
kinase activity up to 52,600 U/L. Immediate therapy with intravenous fluids,
bicarbonate, and furosemide was administered, and there were no further
complications, notably no renal failure. This case supports the notion that
venlafaxine can induce direct skeletal muscle toxicity leading to severe
rhabdomyolysis. Therefore, clinicians should monitor muscle enzymes in patients
with venlafaxine overdose to detect the development of rhabdomyolysis at an
early stage and to initiate appropriate therapy rapidly.
Effects of paroxetine and
venlafaxine XR on heart rate variability in depression.
Davidson J, Watkins L, Owens M, Krulewicz S, Connor K, Carpenter D, Krishnan R,
Nemeroff C.
Department of Psychiatry and Behavioral Sciences, Duke University Medical
Center, Durham, NC 27710, USA.
Depressed patients may exhibit reduced heart rate variability (HRV), and
antidepressants which block norepinephrine uptake may also lower HRV. This study
compared paroxetine (PAR) and venlafaxine XR (VEN-XR) on HRV. Outpatients were
randomly assigned to double-blind treatment with PAR up to 40 mg or VEN-XR up to
225 mg daily. HRV measures of parasympathetic control consisted of change in R-R
interval during forced 10-second breaths and respiratory sinus arrhythmia (RSA)
during paced breathing. Ex vivo estimates of serotonin and norepinephrine
transporter occupancy were obtained before and after treatment, as were measures
of depression, anxiety, and resilience. Plasma drug concentrations were measured
at end point. Forty-nine patients entered treatment; 44 of whom were evaluable (n
= 22 per group). Significant within-group reductions were noted in R-R interval
variation and in RSA after VEN-XR only. Between-group analyses showed
significant group-by-time interaction, with greater reduction in R-R interval
variation and in RSA for VEN-XR compared with PAR. Improvement in resiliency
correlated significantly with norepinephrine transporter occupancy for VEN-XR.
Further comparisons of selective serotonin reuptake inhibitor and serotonin and
norepinephrine reuptake inhibitor drugs on HRV are warranted.
Effexor
withdrawal Body
Effexor
withdrawal Dry Mouth
- The
usual amount to moisture in the mouth is noticeably less.
Effexor
withdrawal Sweating
Increased - A large
quantity of perspiration that is medically caused.
Effexor
withdrawal Cardiovascular (Involving the heart and the blood
vessels)
Effexor
withdrawal Palpitation
- Unusual and not normal heartbeat,
that is sometimes irregular, but rapid and forceful thumping or fluttering. It
can be brought on by shock, excitement, exertion, or medical stimulants. A
person is normally unaware of his/her heartbeat.
Effexor withdrawal Hypertension
- is high blood pressure, which is a
symptom of disease in the blood vessels leading away from the heart.
Hypertension is known as the “silent killer”. The symptoms are usually not
obvious, however it can lead to damage to the heart, brain, kidneys and eye, and
even to stroke and kidney failure. Treatment includes dietary and lifestyle
changes.
Effexor withdrawal Bradycardia-The heart rate is slowed from 72 beats per minute,
which is normal, to below 60 beats per minute in an adult.
Effexor
withdrawal Tachycardia
- The heart rate is speeded up to
above 100 beats per minute in an adult. Normal adult heart rate is 72 beats per
minute.
Effexor
withdrawal ECG Abnormal
- A test
called an electrocardiogram (ECG) that records the activity of the heart. It
measures heartbeats as will as the position and size of the heart’s four
chambers. It also measures if there is damage to the heart and the effects of
drugs or mechanical devices like a pacemaker on the heart. When the test is
abnormal this means that one or more of the following are present: heart
disease, defects, beating too fast or too slow, disease of the blood vessels
leading from the heart or of the heart valves, and/or a past or about to occur
heart attack.
Effexor
withdrawal Flushing
- The skin all over the body turns red.
Effexor withdrawal Varicose Vein -Unusually swollen veins
near the surface of the skin that sometimes appear twisted and knotted, but
always enlarged. They are called hemorrhoids when they appear around the
rectum. The cause is attributed to hereditary weakness in the veins aggravated
by obesity, pregnancy, pressure from standing, aging, etc. Severe cases may
develop swelling in the legs, ankles and feet, eczema and/or ulcers in the
affected areas.
Effexor
withdrawal
Gastrointestinal
(Involving
the stomach and the intestines)
Effexor withdrawal Abdominal Cramp/Pain - Sudden, severe, uncontrollable and painful shortening and
thickening of the muscles in the belly. The belly includes the stomach as well
as the intestines, liver, kidneys, pancreas, spleen, gall bladder, and urinary
bladder.
Effexor withdrawal Belching
- Noisy release of gas from the stomach through the mouth; a burp.
Effexor
withdrawal Bloating
- Swelling of the belly caused by excessive intestinal gas.
Effexor withdrawal Constipation-Difficulty in having a bowel movement where the material in the bowels is
hard due to a lack of exercise, fluid intake, and roughage in the diet, or due
to certain drugs.
Effexor withdrawal Diarrhea - Unusually frequent and excessive, runny bowel movements that may
result in severe dehydration and shock.
Effexor
withdrawal Dyspepsia - Indigestion. This is the discomfort you experience after eating. It
can be heartburn, gas, nausea, a bellyache or bloating.
Effexor withdrawal Flatulence
- More gas than normal in the digestive organs.
Effexor withdrawal Gastritis
- A severe irritation of the mucus lining of the stomach either short in
duration or lasting for a long period of time.
Effexor withdrawal Gastroenteritis - A condition where the membranes
of the stomach and intestines are irritated.
Effexor
withdrawal Gastroesophageal
Reflux - A
continuous state where stomach juices flow back into the throat causing acid
indigestion and heartburn and possibly injury to the throat.
Effexor
withdrawal Heartburn
- A burning pain in the area of the breastbone caused by stomach juices flowing
back up into the throat.
Effexor withdrawal Hemorrhoids- Small rounded
purplish swollen veins that either bleed, itch or are painful and appear around
the anus.
Effexor withdrawal Increased Stool frequency - Diarrhea.
Effexor
withdrawal Indigestion
- Unable to properly consume and absorb food in the digestive tract causing
constipation, nausea, stomach ache, gas, swollen belly, pain and general
discomfort or sickness.
Effexor withdrawal Nausea - Stomach irritation with a queasy sensation similar to
motion sickness and a feeling that one is going to vomit.
Effexor
withdrawal Polyposis Gastric
- Tumors that grow on stems in the lining of the stomach, which usually become
cancerous.
Effexor withdrawal Swallowing Difficulty
- A feeling that food is stuck in the throat or upper chest area and won’t go
down, making it difficult to swallow.
Effexor withdrawal Toothache
- Pain in a tooth above and below the gum line.
Effexor withdrawal Vomiting
- Involuntarily throwing up the contents of the stomach and usually getting a
nauseated, sick feeling just prior to doing so.
Effexor
withdrawal General
Effexor withdrawal Allergy-The extreme
sensitivity of body tissues triggered by substances in the air, drugs, or foods
causing a reaction like sneezing, itching, asthma, hay fever, skin rashes,
nausea and/or vomiting.
Effexor withdrawal Anaphylaxis
- A violent, sudden, and severe drop
in blood pressure caused by a re-exposure to a foreign protein or a second
dosage of a drug that may be fatal unless emergency treatment is given right
away.
Effexor
withdrawal Chest Pains
-
Severe discomfort in the chest caused by not enough oxygen going to the heart
because of narrowing of the blood vessels or spasms.
Effexor
withdrawal Chills
- Appearing
pale while cold and shivering; sometimes with a fever.
Effexor withdrawal Edema of
Extremities-Abnormal
swelling of the body’s tissue caused by the collection of fluid.
Effexor withdrawal Fall
- To suddenly lose your normal
standing upright position as if you were shot.
Effexor
withdrawal Fatigue
- Loss of normal strength so as to
not be able to do the usual physical and mental activities.
Effexor
withdrawal Fever
- Abnormally high body temperature,
the normal being 98 degrees Fahrenheit or 37 degrees Centigrade in humans, which
is a symptom of disease or disorder in the body. The body is affected by
feeling hot, chilled, sweaty, weak and exhausted. If the fever goes too high,
death can result.
Effexor
withdrawal Hot Flashes
- Brief,
abnormal enlargement of the blood vessels that causes a sudden heat sensation
over the entire body. Women in menopause will sometimes experience this.
Effexor
withdrawal Influenza-like
Symptoms -
Demonstrating irritation of the respiratory tract (organs of breathing) such as
a cold, sudden fever, aches and pains, as well as feeling weak and seeking bed
rest, which is similar to having the flu.
Effexor
withdrawal Leg Pain
- A
hurtful sensation in the legs that is caused by excessive stimulation of the
nerve endings in the legs and results in extreme discomfort.
Effexor withdrawal Malaise-The somewhat
unclear feeling of discomfort you get when you start to feel sick.
Effexor
withdrawal Pain in Limb- Sudden, sharp and uncontrolled leg discomfort.
Effexor
withdrawal Syncope-A short
period of light headedness or unconsciousness (black-out) also know as fainting
caused by lack of oxygen to the brain because of an interruption in blood
flowing to the brain.
Effexor withdrawal Tightness of
Chest - Mild or sharp discomfort, tightness
or pressure in the chest area (anywhere between the throat and belly). The
causes can be mild or seriously life-threatening because they include the heart,
lungs and surrounding muscles.
Effexor
withdrawal Hemic and Lymphatic Disorders(Involving
the blood and the clear fluids in the tissues that contain white blood cells)
Effexor withdrawal Bruise
- Damage to the skin resulting in a
purple-green-yellow skin coloration that’s caused by breaking the blood vessels
in the area without breaking the surface of the skin.
Effexor
withdrawal Anemia- A condition
where the blood is no longer carrying enough oxygen, so the person looks pale
and easily gets dizzy, weak and tired. More severely, a person can end up with
an abnormal heart, as well as breathing and digestive difficulties. The causes
of anemia are not enough protein in the red blood cells, or missing and
chemically destroyed red blood cells, as well as diseased or destroyed bone
marrow.
Effexor withdrawal Nosebleed
- Blood lost from the part of the
face that has the organs of smell and is where the body takes in oxygen.
Effexor
withdrawal Hematoma
- Broken blood vessels that cause a
swelling in an area on the body.
Effexor
withdrawal Lymphadenopathy
Cervical-The lymph
nodes in the neck, which are part of the body’s immune system get swollen and
enlarge by reacting to the presence of a drug. The swelling is the result of
the white blood cells multiplying in order to fight the invasion of the drug.
Effexor
withdrawal Metabolic and Nutritional Disorders(Energy
and health)
Effexor
withdrawal Arthralgia-Sudden sharp
nerve pain in one or more joints.
Effexor
withdrawal Arthropathy
- Having joint disease or abnormal
joints.
Effexor
withdrawal Arthritis-Painfully inflamed and swollen joints. The reddened
and swollen condition is brought on by a serious injury or shock to the body
either from physical or emotional causes.
Effexor
withdrawal Back Discomfort
- Severe physical distress in the area from the neck to the pelvis along the
backbone.
Effexor withdrawal Bilirubin Increased- Bilirubin is a waste product of the breakdown
of old blood cells. Bilirubin is sent to the liver to be made water-soluble so
it can be eliminated from the body through emptying the bladder. A drug can
interfere with or damage this normal liver function creating liver disease.
Effexor withdrawal Decreased Weight
- Uncontrolled and measured loss of heaviness or weight.
Effexor
withdrawal Gout
- A severe arthritis condition that is caused by the dumping of a waste product
called uric acid in the tissues and joints. It can become worse and cause the
body to develop a deformity after going through stages of pain, inflammation,
severe tenderness, and stiffness.
Effexor withdrawal Hepatic Enzymes Increased - An increase in the amount of paired liver proteins that
regulate liver processes causing a condition where the liver functions
abnormally.
Effexor withdrawal
Hypercholesterolemia- Too much cholesterol in the blood cells.
Effexor
withdrawal Hyperglycemia
- An unhealthy amount of sugar in the blood.
Effexor withdrawal Increased Weight - A concentration and storage of fat in the body
accumulating over a period of time caused by unhealthy eating patterns, that can
predispose the body to many disorders and diseases.
Effexor
withdrawal Jaw Pain - The pain due to irritation and swelling of the nerves associated with
the mouth area where it opens and closes just in front of the ear. Some of the
symptoms are pain when chewing, head aches, losing your balance, stuffy ears or
ringing in the ears, and teeth grinding.
Effexor withdrawal Jaw Stiffness
- The result of squeezing and grinding the teeth while asleep that can cause
your teeth to deteriorate as well as the muscles and joints of the jaw.
Effexor
withdrawal Joint Stiffness- A loss of free motion and easy flexibility where any
two bones come together.
Effexor withdrawal Muscle Cramp - When muscles contract uncontrollably without warning and do not
relax. The muscles of any of the body’s organs can cramp.
Effexor
withdrawal Muscle Stiffness
- Tightening of muscles making it difficult to bend.
Effexor
withdrawal Muscle Weakness
- Loss of physical strength.
Effexor
withdrawal Myalgia - A general widespread pain and tenderness of the muscles.
Effexor
withdrawal Thirst - A strong,
unnatural craving for moisture/water in the mouth and throat.
Effexor
withdrawal Nervous System (Sensory channels)
Effexor withdrawal Carpal Tunnel
Syndrome - A pinched
nerve in the wrist that causes pain, tingling, and numbing.
Effexor withdrawal Coordination Abnormal - A lack of normal, harmonious interaction of the parts of
the body when it is in motion.
Effexor withdrawal Dizziness - Losing one’s balance while feeling unsteady and lightheaded which may
lead to fainting.
Effexor
withdrawal Disequilibrium
-Lack of mental and emotional balance.
Effexor withdrawal Faintness - A temporary condition where one is likely to go
unconscious and fall.
Effexor withdrawal Headache - A sharp or dull persistent pain in the head
Effexor
withdrawal Hyperreflexia - A not normal and involuntary increased response in the
tissues connecting the bones to the muscles.
Effexor
withdrawal Light-headed
Feeling –
Uncontrolled and usually brief loss of consciousness caused by lack of oxygen to
the brain.
Effexor
withdrawal Migraine
- Reoccurring severe head pain usually with nausea, vomiting, dizziness, flashes
or spots before the eyes, and ringing in the ears
Effexor withdrawal Muscle Contractions Involuntary
- Spontaneous and uncontrollable tightening reaction of the muscles caused by
electrical impulses from the nervous system.
Effexor
withdrawal Muscular Tone Increased - Uncontrolled and exaggeration muscle tension. Muscles are
normally partially tensed and this is what gives us muscle tone.
Effexor
withdrawal Paresthesia - Burning, prickly, itchy, or tingling skin with no obvious or
understood physical cause.
Effexor withdrawal Restless Legs
- A need to move the legs without any apparent reason. Sometimes there is pain,
twitching, jerking, cramping, burning, or a creepy-crawly sensation associated
with the movements. It worsens when a person is inactive and can interrupt
one’s sleep so one feels the need to move to gain some relief.
Effexor
withdrawal Shaking
- Uncontrolled quivering and trembling as if one is cold and chilled.
Effexor
withdrawal Sluggishness
- Lack of alertness and energy, as well as being slow to respond or perform in
life.
Effexor withdrawal Tics - A contraction of a muscle causing a repeated movement not
under the control of the person usually on the face or limbs.
Effexor
withdrawal Tremor
- A nervous and involuntary vibrating or quivering of the body.
Effexor withdrawal Twitching - Sharp, jerky and spastic motion sometimes with a
sharp sudden pain.
Effexor
withdrawal Vertigo
- A sensation of dizziness with disorientation and confusion.
Effexor
withdrawal Psychiatric Disorders (Mental and emotional)
Effexor withdrawal Aggravated Nervousness
- A progressively worsening, irritated and troubled state of mind.
Effexor
withdrawal Agitation
- Suddenly violent and forceful, emotionally disturbed state of mind.
Effexor withdrawal Amnesia - Long term or short term, partial or full memory loss created by
emotional or physical shock, severe illness, or a blow to the head where the
person was caused pain and became unconsciousness.
Effexor
withdrawal Anxiety Attack
- Sudden and intense feelings of fear, terror, and dread physically creating
shortness of breath, sweating, trembling and heart palpitations.
Effexor withdrawal Apathy
- Complete lack of concern or interest for things that ordinarily would be
regarded as important or would normally cause concern.
Effexor
withdrawal Appetite
Decreased - Having a
lack of appetite despite the ordinary caloric demands of living with a resulting
unintentional loss of weight.
Effexor
withdrawal Appetite
Increased - An
unusual hunger causing one to overeat.
Effexor
withdrawal Auditory
Hallucination -
Hearing things without the voices or noises being present.
Effexor
withdrawal Bruxism-
Grinding and clenching of teeth while sleeping.
Effexor withdrawal Carbohydrate
Craving - A drive
and craving to eat foods rich in sugar and starches (sweets, snacks and junk
foods) that intensifies as the diet becomes more and more unbalanced due to the
unbalancing of the proper nutritional requirements of the body.
Effexor withdrawal Concentration Impaired
- Unable to easily focus your attention for long periods of time.
Effexor
withdrawal Confusion
- Not able to think clearly and understand in order to make a logical decision.
Effexor
withdrawal Crying Abnormal
- Unusual and not normal fits of weeping for short or long periods of time for
no apparent reason.
Effexor withdrawal Depersonalization
- A condition where one has lost a normal sense of personal identity.
Effexor
withdrawal Depression
- A hopeless feeling of failure, loss and sadness that can deteriorate into
thoughts of death.
Effexor
withdrawal Disorientation
- A loss of sense of direction, place, time or surroundings as well as mental
confusion on personal identity.
Effexor
withdrawal Dreaming Abnormal
- Dreaming that leaves a very clear, detailed picture and impression when awake
that can last for a long period of time and sometimes be unpleasant.
Effexor
withdrawal Emotional
Lability- Suddenly breaking out
in laughter or crying or doing both without being able to control the outburst
of emotion. These episodes are unstable as they are caused by things that
normally would not have this effect on an individual.
Effexor withdrawal Excitability - Uncontrollably responding to stimuli.
Effexor withdrawal Feeling Unreal - The awareness that one has an undesirable emotion like
fear but can’t seem to shake off the irrational feeling. For example, feeling
like one is going crazy but rationally knowing that it is not true. The quality
of this side effect resembles being in a bad dream and not being able to wake
up.
Effexor
withdrawal Forgetfulness
- Unable to remember what one ordinarily would remember.
Effexor
withdrawal Insomnia
- Sleeplessness caused by physical stress, mental stress or stimulants such as
coffee or medications; it is a condition of being abnormally awake when one
would ordinarily be able to fall and remain asleep.
Effexor
withdrawal Irritability
- Abnormally annoyed in response to a stimulus.
Effexor withdrawal Jitteriness - Nervous fidgeting without an apparent cause.
Effexor
withdrawal Lethargy
- Mental and physical sluggishness and apathy that can deteriorate into an
unconscious state resembling deep sleep. A numbed state of mind.
Effexor
withdrawal Libido Decreased
- An abnormal loss of sexual energy or desire.
Effexor withdrawal Panic Reaction
- A sudden, overpowering, chaotic and confused mental state of terror resulting
in being doubt ridden often accompanied with hyperventilation, and extreme
anxiety.
Effexor
withdrawal Restlessness
Aggravated - A
constantly worsening troubled state of mind characterized by the person being
increasingly nervous, unable to relax, and easily angered.
Effexor
withdrawal Somnolence - Feeling sleepy all the time or having a condition of
semi-consciousness.
Effexor
withdrawal Suicide Attempt
- An unsuccessful deliberate attack on one’s own life with the intention of
ending it.
Effexor
withdrawal Suicidal Tendency
- Most likely will attempt to kill oneself.
Effexor withdrawal Tremulousness
Nervous - Very
jumpy, shaky, and uneasy while feeling fearful and timid. The condition is
characterized by thoughts of dreading the future, involuntary quivering,
trembling, and feeling distressed and suddenly upset.
Effexor withdrawal Yawning - involuntary opening of the mouth with deep inhalation of
air.
Effexor
withdrawal Reproductive Disorder Female
Effexor
withdrawal Breast Neoplasm
- A tumor or cancer, of either of the two milk-secreting
organs on the chest of a woman.
Effexor
withdrawal Menorrhagia- Abnormally heavy menstrual period or a
menstrual flow that has continued for an unusually long period of time.
Effexor
withdrawal Menstrual Cramps
- Painful, involuntary uterus contractions that women experience around the time
of their menstrual period, sometimes causing pain in the lower back and thighs.
Effexor
withdrawal Menstrual
Disorder - A disturbance or derangement in the normal function of a woman’s
menstrual period.
Effexor
withdrawal Pelvic
Inflammation - The reaction of the body to infectious, allergic, or chemical
irritation, which in turn causes tissue irritation, injury, or bacterial
infection characterized by pain, redness, swelling, and sometimes loss of
function. The reaction usually begins in the uterus and spreads to thefallopian tubes, ovaries, and other areas
in the hipbone region of the body.
Effexor
withdrawal Premenstrual
Syndrome - Various physical and mental symptoms commonly experienced by women of
childbearing age usually 2 to 7 days before the start of their monthly period.
There are over 150 symptoms including eating binges, behavioral changes,
moodiness, irritability, fatigue, fluid retention, breast tenderness, headaches,
bloating, anxiety, and depression. The symptoms cease shortly after the period
begins, and disappear with menopause.
Effexor
withdrawal Spotting Between
Menses - Abnormal bleeding between periods. Unusual spotting
between menstrual cycles.
Effexor
withdrawal RESPIRATORY SYSTEM(Organs involved in breathing)
Effexor
withdrawal Asthma - A disease of the breathing system initiated by and allergic reaction
or a chemical with repeated attacks of coughing, sticky mucus, wheezing,
shortness of breath, and a tight feeling in the chest. The disease can reach a
state where it stops a person from exhaling, leading to unconsciousness and
death.
Effexor
withdrawal Breath Shortness
-
Unnatural breathing using a lot off effort resulting in not enough air taken in
by the body.
Effexor
withdrawal Bronchitis
- Inflammation of the two main
breathing tubes leading from the windpipe to the lungs. The disease is marked
with coughing, a low-grade fever, chest pains, and hoarseness, caused by an
allergic reaction.
Effexor
withdrawal Coughing
- A cough is the response to an
irritation, such as mucus, that causes the muscles controlling the breathing
process to expel air from the lungs suddenly and noisily to keep the air
passages free from the irritating material.
Effexor
withdrawal Laryngitis
- Inflammation of the voice box
characterized by hoarseness, sore throat, and coughing. It can be cause by
straining the voice or exposure to infectious, allergic or chemical irritation.
Effexor
withdrawal Nasal Congestion
- The
presence of an abnormal amount of fluid in the nose.
Effexor
withdrawal Pneumonia
Tracheitis - Bacterial infection of the air passageways and lungs that causes
redness, swelling and pain in the windpipe. Other symptoms are high fever,
chills, pain in the chest, difficulty in breathing, and coughing with mucus
discharge.
Effexor
withdrawal Rhinitis
- Chemical irritation causing pain,
redness and swelling in the mucus membranes of the nose.
Effexor
withdrawal Sinus Congestion
- The
mucus-lined areas of the bones in the face that are thought to help warm and
moisten air to the nose. These areas become clogged with excess fluid or
infected.
Effexor
withdrawal Sinus Headache
- The
abnormal amount of fluid in the hollows of the face bone area especially around
the nose. This excess fluid creates pressure, causing pain in the head.
Effexor
withdrawal Sinusitis
- The body reacting to chemical
irritation causing redness, swelling and pain in the area of the hollows in the
facial bones especially around the nose.
Effexor
withdrawal SKELETAL
Effexor withdrawal Neck/Shoulder Pain
- Hurtful sensations
of the nerve endings caused by damage to the tissues in the neck and shoulder
signaling danger of disease.
Effexor
withdrawal SKIN and APPENDAGES DISORDERS (Skin, legs and arms)
Effexor
withdrawal Acne
- Eruptions of the oils glands of the
skin, especially on the face, marked by pimples, blackheads, whiteheads, bumps,
and more severely, by cysts and scarring.
Effexor withdrawal Alopecia - The loss of hair or baldness.
Effexor
withdrawal Eczema
- A severe or continuing skin disease
marked by redness, crusting and scaling with watery blisters and itching. It is
often difficult to treat and will sometimes go away only to reappear again.
Effexor
withdrawal Dermatitis
- Generally irritated skin that can
be caused by any of a number of irritating things such as parasites, fungus,
bacteria, or foreign substancescausing an allergic reaction. It is a general inflammation of the skin.
Effexor
withdrawal Dry Lips
- The
lack of normal moisture in the fleshy folds that surround the mouth.
Effexor withdrawal Dry Skin -The lack of normal moisture/oils in the
surface layer of the body. The skin is the body’s largest organ.
Effexor withdrawal Folliculitis-
Inflammation of a follicle (small body sac) especially a hair follicle. A hair
follicle contains the root of a hair.
Effexor withdrawal Furunculosis -Skin boils that show up repeatedly.
Effexor withdrawal Lipoma -A tumor of mostly fat cells that is not health
endangering.
Effexor withdrawal Pruritus- Extreme itching of often-undamaged skin.
Effexor withdrawal Rash - A skin eruption or discoloration that may or may not be
itching, tingling, burning, or painful. It may be caused by an allergy, an skin
irritation, a skin disease.
Effexor withdrawal Skin Nodule - A bulge, knob, swelling or outgrowth in the skin
that is a mass of tissue or cells.
Effexor withdrawal SPECIAL SENSES
Effexor withdrawal Conjunctivitis
- Infection of the membrane that covers the eyeball and lines the eyelid, caused
by a virus, allergic reaction, or an irritating chemical. It is characterized
by redness, a discharge of fluid and itching.
Effexor withdrawal Dry Eyes - Not enough moisture in the eyes.
Effexor withdrawal Earache - Pain in the ear.
Effexor withdrawal Eye Infection
- The invasion of the eye tissue by a bacteria, virus, fungus, etc, causing
damage to the tissue, with toxicity. Infection spreading in the body progresses
into disease.
Effexor withdrawal Eye Irritation
- An inflammation of the eye.
Effexor withdrawal Metallic Taste
- A range of taste impairment from distorted taste to a complete loss of taste.
Effexor withdrawal Pupils Dilated
- Abnormal expansion of the blace circular opening in the center of the eye.
Effexor withdrawal Taste alteration
- Abnormal flavor detection in food.
Effexor withdrawal Tinnitus - A buzzing, ringing, or whistling sound in one or
both ears occurring from the internal use of certain drugs.
Effexor withdrawal Vision Abnormal
- Normal images are seen differently by the viewer.
Effexor withdrawal Vision Blurred
- Eyesight is dim or indistinct and hazy in outline or appearance.
Effexor withdrawal Visual Disturbance
- Eyesight is interfered with or interrupted. Some disturbances are light
sensitivity and the inability to easily distinguish colors.
Effexor
withdrawal URINARY SYSTEM
DISORDER
Effexor
withdrawal Blood in Urine-
Blood is present when one empties liquid waste product of the kidneys through
the bladder by urinating in the toilet turning the water pink to bright red. Or
you could see pots of blood in the water after urinating.
Effexor
withdrawal Dysuria
- Difficult or painful urination.
Effexor
withdrawal Kidney Stone
- Small hard masses of salt deposits that the kidney forms.
Effexor
withdrawal Urinary Frequency - Having to urinate more often than usual or between unusually short
time periods.
Effexor
withdrawal Urinary Tract
Infection - An invasion of bacteria, viruses, fungi, etc., of the
system in the body that starts with the kidneys and eliminates urine from the
body. If the invasion goes unchecked it can injure tissue and progress into
disease.
Effexor
withdrawal Urinary Urgency
- A sudden compelling urge to urinate, accompanied by discomfort in the bladder.
Effexor
withdrawal UROGENITAL (Urinary tract and genital structures or functions)
Effexor
withdrawal Anorgasmia
- Failure to experience an orgasm.
Effexor
withdrawal Ejaculation
Disorder - Dysfunction of the discharge of semen during orgasm.
Effexor
withdrawal Menstrual
Disorder - Dysfunction of the discharge during the monthly menstrual cycle.
Effexor withdrawal Acute Renal
Failure - The kidneys
stop functioning properly to excrete wastes.
Effexor withdrawal Angioedema
- Intensely itching and swelling welts on the skin called hives caused by an
allergic reaction to internal or external agents. The reaction is common to a
food or a drug. Chronic cases can last for a long period of time.
Effexor
withdrawal Toxic Epidermal
Necrolysis - An abnormal condition where a large portion of skin
becomes intensely red and peels off like a second-degree burn. Often the
symptoms include blistering.
Effexor withdrawal Grand Mal
Seizures (or Convulsions)
- A recurring sudden violent and involuntary attack of muscle spasms with a loss
of consciousness.
Effexor withdrawal Neuroleptic Malignant Syndrome
- A life threatening, rare reaction to an anti-psychotic drug marked by fever,
muscular rigidity, changed mental status, and dysfunction of the autonomic
nervous system.
Effexor withdrawal Pancreatitis - Chemical irritation with redness, swelling, and
pain in the pancreas where digestive enzymes and hormones are secreted.
Effexor withdrawal QT Prolongation
- A very fast heart rhythm disturbance that is too fast for the heart to beat
effectively so the blood to the brain falls causing a sudden loss of
consciousness and may cause sudden cardiac death.
Effexor withdrawal Rhabdomyolysis
- The breakdown of muscle fibers that releases the fibers into the circulatory
system. Some of the fibers are poisonous to the kidney and frequently result in
kidney damage.
Effexor withdrawal Serotonin Syndrome
- A disorder brought on by excessive levels of serotonin caused by drugs and can
be fatal as death from this side effect can come very rapidly.
Effexor withdrawal Thrombocytopenia
- An abnormal decrease in the number of blood platelets in the circulatory
system. A decrease in platelets would cause a decrease in the ability of the
blood to clot when necessary.
Effexor withdrawal Torsades de Pointes
- Unusual rapid heart rhythm starting in the lower heart chambers. If the short
bursts of rapid heart rhythm continue for a prolonged period it can degenerate
into a more rapid rhythm and can be fatal.
Watanabe N, Omori IM, Nakagawa A, Cipriani A,
Barbui C, McGuire H, Churchill R, Furukawa TA; Multiple Meta-Analyses of New
Generation Antidepressants (MANGA) Study Group.
I had been taking Effexor XR for close to 9 years
before tapering off. I used the plan from The Road to Recovery to
withdraw from 225 mg per day over a 10 week period. The withdrawal went quite
well with few side effects. I have been off Effexor completely for 3 weeks now
and the withdrawal symptoms are awful: brain zaps, irritability, headaches, body
aches, and I am so emotional I begin to weep at the drop of a hat. I am
continuing to take the supplements as directed in the plan, but things seem to
be getting worse instead of better. Suggestions? I need help.
Answer:
How much Omega 3 are you taking each day?
Give me a breakdown of what you are doing.
Somewhere at the time you were doing good and you
began to not feel well we will find the item to address.
Response:
Thank you for your prompt reply. I have been
taking 6 omega 3 caps/day; two in the morning, two around 11:00 am, and two
around 4:00 pm. I am also taking the barley grass powder-1tbs- at the same
times.
I am taking 4 tsp of cherry extract around
8:00 pm. I am sleeping quite well. In fact since I have been off Effexor
and taking the cherry extract I have stopped having the bizarre dreams that
have been a part of my life for so long.
I usually feel best early in the day. Depending
on my activity, level the side effects tend to get worse as the day goes
on. The more active I am, the more intense the brain zaps. I usually have
a headache by late afternoon-early evening. Once I take the cherry extract
and go to bed, the headache is gone.
I certainly will appreciate any feedback you can
give me.
Answer:
You might try taking 1 teaspoon of cherry
starting around noon, 4 pm, 8 pm and at bedtime as normal.
If the cherry at night gets rid of the headache,
odds are it will during the day as well.
Cherry should not make you tired during the day.
If it does, cut the amount back a little.
Response:
I have been taking the cherry concentrate 3x /
day as you suggested for five days now. I have definitely seen a reduction in
side effects. I am feeling much better, thank you!
I have been completely off Effexor for four
weeks. I would like you to know how much I appreciate your book and the help you
have given me. It is so wonderful to feel alive again. I have so much more
energy and interest in the activities going on around me. I have accomplished
more in the past few months than I have in the past few years.
Thanks again for the work you are doing. You
are truly making a difference in people's lives.
Peace, W.D.
End
Venlafaxine Brand name (Effexor)
Pharmacology
Antidepressant
Venlafaxine is a phenethylamine bicyclic derivative, chemically unrelated to tricyclic, tetracyclic or other available antidepressant agents.
The mechanism of venlafaxine's antidepressant action in humans is believed to be associated with its potentiation of neurotransmitter activity in the CNS. Preclinical studies have shown that venlafaxine and its major 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 alpha1-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.
Pharmacokinetics:
Venlafaxine is well absorbed, with peak plasma concentrations occurring approximately 2 hours after dosing. Venlafaxine is extensively metabolized, with O-desmethylvenlafaxine, (ODV, the only major active metabolite) peak plasma levels occurring approximately 4 hours after dosing. Following single doses of 25 to 75 mg, mean (+/- SD) peak
plasma concentrations of venlafaxine range from 34+/-14 to 96+/-43 ng/mL, respectively, and are reached in 2+/-1 hours, and mean peak ODV plasma concentrations range from 58+/-18 to 178+/-40 ng/mL and are reached in 4+/-2 hours. Approximately 87% of a single dose of venlafaxine is recovered in the urine within 48 hours as either unchanged
venlafaxine (5%), unconjugated ODV (30%), conjugated ODV (26%), or other minor metabolites (27%).
Multiple-Dose Pharmacokinetic Profile:
Steady-state concentrations of both venlafaxine and ODV in plasma were attained after approximately 3 days of multiple dose therapy. The clearance of venlafaxine is slightly (15%) lower following multiple doses than following a single dose.
Venlafaxine and ODV exhibited linear kinetics over the dose range of 75 to 450 mg total daily dose administered t.i.d.
The mean +/- SD steady-state plasma clearances of venlafaxine and ODV are 1.3+/-0.6 and 0.4+/-0.2 L/h/kg, respectively; elimination half-life is 5+/-2 and 11+/-2 hours, respectively.
Venlafaxine and ODV renal clearances are 49+/-27 and 94+/-56 mL/h/kg, respectively, which correspond to 5+/-3.0% and 25+/-13% of an administered venlafaxine dose recovered in urine as venlafaxine and ODV, respectively. Similar steady-state volumes of distribution are exhibited for venlafaxine (7+/-4 L/kg) and ODV (6+/-2 L/kg).
Venlafaxine and ODV are less than 35% bound to plasma proteins. Therefore, protein-binding-induced drug interactions with venlafaxine are not expected.
Food has no significant effect on the absorption of venlafaxine.
When equal daily doses of venlafaxine were administered either b.i.d. or t.i.d., drug exposure (AUC) and fluctuation in plasma levels were comparable.
Age and Gender:
Age and sex do not significantly affect the pharmacokinetics of venlafaxine. A 20% reduction in clearance was noted for ODV in subjects over 60 years old; this was possibly caused by the decrease in renal function that typically occurs with aging. Dosage adjustment based upon age or gender is generally not necessary (See Dosage).
Hepatic Disease:
In 9 patients with hepatic cirrhosis, the pharmacokinetic disposition of both venlafaxine and ODV were significantly altered. Venlafaxine elimination half-life was prolonged by about 30%, and clearance was decreased by about 50%. ODV elimination half-life was also prolonged (by about 60%) and its clearance decreased by about 30%. Three
patients with more severe cirrhosis had a 90% decrease in venlafaxine clearance. Dosage adjustment is necessary in patients with liver disease (See Dosage).
Renal Disease:
In patients with moderate to severe impairment of renal function (GFR=10-70 mL/min), venlafaxine elimination half-life was prolonged by 50%, and clearance was deceased by about 24%. ODV elimination half-life was prolonged by about 40%, but clearance was unchanged. In dialysis patients, venlafaxine elimination half-life was prolonged by
about 180% and clearance was decreased by about 56%. Dosage adjustment is necessary in patients with renal disease (See Dosage).
Indications
For the symptomatic relief of depressive illness.
The effectiveness of venlafaxine in long-term use (i.e., for more than 4 to 6 weeks) has not been systematically evaluated in controlled trials. Therefore, the physician who elects to use venlafaxine for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient.
Contraindications
Patients with known hypersensitivity to venlafaxine or to any of the components of the formulation.
MAO Inhibitors:
There have been reports of serious, sometimes fatal reactions in patients receiving antidepressants with pharmacological properties similar to those of venlafaxine in combination with a MAO inhibitor. Therefore, venlafaxine should not be used in combination with MAO inhibitors or within two weeks of terminating treatment with MAO
inhibitor's. Treatment with MAO inhibitors should not be started until two weeks after discontinuation of venlafaxine therapy.
Warnings
Sustained Hypertension:
Treatment with venlafaxine was associated with modest but sustained increases in blood pressure during premarketing studies. Sustained hypertension, defined as treatment-emergent supine diastolic blood pressure (SDBP) >= 90 mm Hg and 10 mm Hg above baseline for 3 consecutive visits, showed the following incidence and
dose-relationship in Table I.
-----------------------------------------------
Table I
Probability of Sustained Elevation in SDBP
(Pool of Premarketing Studies with venlafaxine)
-----------------------------------------------
Treatment Group Incidence of Sustained
Elevation in SDBP
-----------------------------------------------
Venlafaxine
<100 mg/day 3%
101-200 mg/day 5%
201-300 mg/day 7%
>300 mg/day 13%
Placebo 2%
-----------------------------------------------
An analysis of the blood pressure increases in patients with sustained hypertension and in the 19 patients who were discontinued from treatment because of hypertension (<1% of total venlafaxine-treated group) showed that most of the blood pressure increases were in the range of 10 to 15 mm Hg, SDBP. Since in individual patients
sustained increases of this magnitude could have adverse consequences, it is recommended that patients receiving venlafaxine have their blood pressure monitored regularly.
For patients who experience a sustained increase in blood pressure during treatment with venlafaxine, either a dose reduction or discontinuation of venlafaxine should be considered.
Precautions
General:
Suicide:
The possibility of a suicide attempt in seriously depressed patients is inherent to the illness and may persist until significant remission occurs. Close supervision of high-risk patients should accompany initial drug therapy, and consideration should be given to the need for hospitalization. In order to reduce the risk of overdose,
prescriptions for venlafaxine should be written for the smallest quantity of tablets consistent with good patient management.
Seizures:
During premarketing testing, seizures were reported in 8 out of 3082 venlafaxine-treated patients (0.26%). In 5 of the 8 cases, patents were receiving doses of 150 mg/day or less. However, patients with a history of convulsive disorders were excluded from most of these studies. venlafaxine should be used cautiously in patents with a
history of seizures, and should be promptly discontinued in any patient who develops seizures.
Activation of Mania/Hypomania:
During Phase II and III trials, mania or hypomania occurred in 0.5% of venlafaxine-treated patients. Activation of mania/hypomania has also been reported in a small proportion of patients with major affective disorder who were treated with other marketed antidepressants. As with all antidepressants, venlafaxine should be used cautiously
in patients with a history of mania.
Patients with Concomitant Illness:
Clinical experience with venlafaxine in patients with concomitant systemic illness is limited. Caution is advised in administering venlafaxine to patients with diseases or conditions that could affect hemodynamic responses or metabolism. Patients should be questioned about any prescripton or "over the counter drugs" that they
are taking, or planning to take, since there is a potential for interactions.
Cardiac Disease:
Venlafaxine has not been evaluated or used to any appreciable extent in patients with a recent history of myocardial infarction or unstable heart disease. Patients with these diagnoses were systematically excluded from many clinical studies during the product's clinical trials. Evaluation of the electrocardiograms for 769 patients who
received venlafaxine in 4- to 6 week double-blind trials showed that the incidence of trial-emergent conduction abnormalities did not differ from that with placebo. The mean heart rate was increased by about 4 beats per minute during treatment. Venlafaxine treatment has been associated with sustained hypertension (see Warnings).
Hepatic and Renal Disease:
In patients with hepatic or renal disease the pharmacokinetic disposition of both venlafaxine and ODV are significantly altered. Dosage adjustment is necessary in these patients (See Dosage).
Occupational Hazards:
Any psychoactive drug may impair judgement, thinking or motor skills. Therefore, patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that the drug treatment does not affect them adversely.
Pregnancy, Labor and Delivery:
There are no adequate and well controlled studies with venlafaxine in pregnant women. Therefore, venlafaxine should only be used during pregnancy if clearly needed.
Lactation:
It is not known whether venlafaxine or its metabolites are excreted in human milk. Because many drugs are excreted in human milk, lactating women should not nurse their infants while receiving venlafaxine.
Children:
Safety and efficacy in children below the age of 18 have not been established.
Geriatrics:
Of the 2,897 patients in Phase II and III trials, 357 (12%) were 65 years of age or older. No overall differences in effectiveness and safety were observed between these patients and younger patients. However, greater sensitivity of some older individuals cannot be ruled out.
Discontinuation Symptoms:
While the discontinuation effects of venlafaxine have not been systematically evaluated in controlled clinical trials, a retrospective survey of new events occurring during taper or following discontinuation revealed the following six events that occurred at an incidence of at least 5%, and for which the incidence for venlafaxine was at
least twice the placebo incidence: asthenia, dizziness, headache, insomnia, nausea and nervousness. Therefore, it is recommended that the dosage be tapered gradually and the patient monitored (See Dosage).
Drug Interactions:
As with all drugs, the potential for interaction by a variety of mechanisms is a possibility.
Lithium:
The steady-state pharmacokinetics of venlafaxine administered as 50 mg every 8 hours was not affected when a single 600 mg oral dose of lithium was administered to 12 healthy male subjects. Venlafaxine had no effect on the pharmacokinetics of lithium. It should be noted that the venlafaxine dose was in the low end of the therapeutic
dosage, as was the single lithium dose. The potential interaction of venlafaxine and lithium in clinical practice is unknown.
Diazepam:
The steady-state pharmacokinetics of venlafaxine administered as 50 mg every 8 hours was not affected when a single 10 mg oral dose of diazepam was administered to 18 healthy male subjects. Venlafaxine had no effect on the pharmacokinetics of diazepam or its active metabolite, desmethyidiazepam. It should be noted that the venlafaxine
dose was in the low end of the therapeutic dosage, as was the single diazepam dose. The potential interaction of venlafaxine and diazepam in clinical practice is unknown.
Cimetidine:
Concomitant administration of cimetidine and venlafaxine in a steady-state study for both drugs in 18 healthy male subjects resulted in inhibition of first-pass metabolism of venlafaxine. The oral clearance of venlafaxine was reduced by about 43%, and the exposure (AUC) and maximum concentration (Cmax) of the drug were increased by about
60%. However, there was no effect on the pharmacokinetics of ODV. The overall pharmacological activity of venlafaxine plus ODV is expected to rise only slightly, and no dosage adjustment should be necessary for most subjects.
However, for patients with pre-existing hypertension, for elderly patients and for patients with hepatic or renal dysfunction, the interaction associated with the concomitant use of cimetidine and venlafaxine is not known and potentially could be more pronounced. Therefore, caution is advised in these patients.
Other CNS-Active Drugs:
The risk of using venlafaxine in combination with other CNS-active drugs (including alcohol) has not been systematically evaluated. Consequently, caution is advised if the concomitant administration of venlafaxine and such drugs is required.
Electroconvulsive Therapy:
There are no clinical data on the use of electroconvulsive therapy combined with venlafaxine treatment.
Cytochrome P450 IID6:
Venlafaxine is metabolized to its active metabolite, ODV, by cytochrome P450 IID6 Therefore, the potential exists for a drug interaction between venlafaxine and drugs that inhibit cytochrome P450-IID6 metabolism. Venlafaxine is a relatively weak inhibitor of cytochrome P450 IID6, however, the clinical significance of this finding is
unknown.
Drug Abuse and Dependence:
Physical and Psychological Dependence:
In vitro studies revealed that venlafaxine has virtually no affinity for opiate, benzodiazepine, phencyclidine (PCP), or N-methyl-D-aspartic acid (NMDA) receptors. It has no significant CNS stimulant activity in rodents. In primate drug discrimination studies, venlafaxine showed no significant stimulant or depressant abuse liability.
While venlafaxine has not been systematically studied in clinical trials for its potential for abuse, there was no indication of drug-seeking behaviour in the clinical trials. However, it is not possible to predict on the basis of premarketing experience the extent to which a CNS active drug will be misused, diverted, and/or abused
once marketed. Consequently, physicians should carefully evaluate patients for history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse of venlafaxine (e.g., development of tolerance incrementation of dose, drug-seeking behaviour).
Adverse Effects
Commonly Observed Adverse Reactions:
The most commonly observed adverse events associated with the use of venlafaxine (incidence of 5% or greater) and not seen at an equivalent incidence among placebo-treated patients (i.e., incidence for venlafaxine at least twice that for placebo), derived from the 1% incidence Table III, were asthenia, sweating, nausea, constipation,
anorexia, vomiting, somnolence, dry mouth, dizziness nervousness, anxiety, tremor, blurred vision, and abnormal ejaculation/orgasm and impotence in men.
Adverse Reactions Associated with Discontinuation of Treatment:
Nineteen percent (537/2897) of venlafaxine-treated patients in Phase II and III depression studies discontinued treatment due to an adverse reaction (see Table II). The more common events (>=1%) associated with discontinuation of treatment and considered to be drug-related (i.e., those events associated with dropout at a rate
approximately twice or greater for venlafaxine compared to placebo) included Table II.
---------------------------------------------------------------
Table II
Adverse Reactions Associated with Discontinuation of Treatment
---------------------------------------------------------------
Venlafaxine Placebo
---------------------------------------------------------------
CNS
Somnolence 3% 1%
Insomnia 3% 1%
Dizziness 3% --
Nervousness 2% --
Dry Mouth 2% --
Anxiety 2% 1%
Gastrointestinal
Nausea 6% 1%
Urogenital
Abnormal Ejaculation* 3% --
Other
Headache 3% 1%
Asthenia 2% --
Sweating 2% --
* percentages based on the number of males.
-- Less than 1%
---------------------------------------------------------------
Incidence in Controlled Trials:
Table III that follows enumerates adverse events that occurred at an incidence of 1% or more, and were more frequent than in the placebo group, among venlafaxine-treated patients who participated in 4- to 8-week placebo-controlled trials in which patients were administered doses in the range of 75 to 375 mg/day. Reported adverse events
were classified using a standard COSTART-based Dictionary terminology.
Dose Dependency of Adverse Events:
A comparison of adverse event rates in a fixed-dose study comparing Effexor 75, 225, and 375 mg/day with placebo revealed a dose dependency for some of the more common adverse events associated with Effexor use, as shown in Table IV. The rule for including events was to enumerate those that occurred at an incidence of 5% or more for at
least one of the venlafaxine groups and for which the incidence was at least twice the placebo incidence for at least one Effexor group. Tests for potential dose relationships for these events (Cochran-Armitage Test, with a criterion of exact 2-sided p-value <= 0.05) suggested a dose-dependency for several adverse events in this list,
including chills, hypertension, anorexia, nausea, agitation, dizziness, somnolence, tremor, yawning, sweating, and abnormal ejaculation .
-------------------------------------------------------------------------
Table III
Treatment-Emergent Adverse Experience Incidence in 4-to 8-Week
Placebo-Controlled Clinical Trials (Percentage)
-------------------------------------------------------------------------
Effexor Placebo
Body System Preferred Term (n=1033) (n=609)
-------------------------------------------------------------------------
Body as a whole
Headache 25 24
Asthenia 12 6
Infection 6 5
Chills 3 --
Chest Pain 2 1
Trauma 2 1
Cardiovascular
Vasodilatation 4 3
Increased blood/pressure
hypertension 2 --
Tachycardia 2 --
Postural hypotension 1 --
Dermatological
Sweating 12 3
Rash 3 2
Pruritus 1 --
Gastrointestinal
Nausea 37 11
Constipation 15 7
Anorexia 11 2
Diarrhoea 8 7
Vomiting 6 2
Dyspepsia 5 4
Flatulence 3 2
Metabolic
Weight loss 1 --
Nervous
Somnolence 23 9
Dry mouth 22 11
Dizziness 19 7
Insomnia 18 10
Nervousness 13 6
Anxiety 6 3
Tremor 5 1
Abnormal Dreams 4 3
Hypertonia 3 2
Paraesthesia 3 2
Libido decreased 2 --
Agitation 2 --
Confusion 2 1
Thinking abnormal 2 1
Depersonalization 1 --
Depression 1 --
Urinary retention 1 --
Twitching 1 --
Respiration
Yawn 3 --
Special Senses
Blurred vision 6 2
Taste perversion 2 --
Tinnitus 2 --
Mydriasis 2 --
Urogenital
Abnormal ejaculation/
orgasm 12 [2] 2
Impotence 6 [2] 2
Urinary frequency 3 2
Urination impaired 2 --
Orgasm disturbance 2 [3] -- [3]
Menstrual disorder 1 [3] -- [3]
-------------------------------------------------------------------------
[1] Events reported by at least 1% of patients treated with Effexor are
included, and are rounded to the nearest %. Events for which the
Effexor incidence was equal to or less than placebo are not listed
in the table, but included the following: abdominal pain, pain, back
pain, flu syndrome, fever, palpitation, increased appetite, myalgia,
arthralgia, amnesia, hypaesthesia, rhinitis pharyngitis, sinusitis
cough increased urinary tract infection and dysmenorrhoea [3]
-- Incidence less than 1%
[2] Incidence based on number of male patients.
[3] Incidence based on number of female patients.
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Adaptation to Certain Adverse Events:
Over a 6-week period, there was evidence of adaptation to some adverse events with continued therapy (e.g., dizziness and nausea), but less to other effects (e.g., abnormal ejaculation and dry mouth).
Vital Sign Changes:
Venlafaxine treatment (averaged over all dose groups) in clinical trials was associated with a mean increase in pulse rate of approximately 3 beats per minute, compared to no change for placebo. It was associated with mean increases in diastolic blood pressure ranging from 0.7 to 2.5 mm Hg averaged over all dose groups, compared to mean
decreases ranging from O.9 to 3.8 mm Hg for placebo. However, there is a dose dependency for blood pressure increase (see Warnings).
Laboratory Changes:
Of the serum chemistry and hematology parameters monitored during clinical trials with venlafaxine, a statistically significant difference with placebo was seen only for serum cholesterol, i.e., patients treated with venlafaxine had mean increases from baseline of 3 mg/dL, a change of unknown clinical significance.
ECG Changes:
In an analysis of ECGs obtained in 769 patients treated with venlafaxine and 450 patients treated with placebo in controlled clinical trials, the only statistically significant difference observed was for heart rate, i.e., a mean increase from baseline of 4 beats per minute for venlafaxine.
Other Events Observed During the Premarketing Evaluation of Venlafaxine:
During its premarketing assessment, multiple doses of venlafaxine were administered to 2,181 patients in phase II and III studies. The conditions and duration of exposure of venlafaxine varied greatly, and included (in overlapping categories) open and double-blind studies, uncontrolled and controlled studies, inpatient and outpatient
studies, fixed-dose and titration studies. Untoward events associated with this exposure were recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse events without first grouping similar types of
untoward events into a smaller number of standardized event categories.
In the tabulations that follow, reported adverse events were classified using a standard COSTART-based dictionary terminology . The frequencies presented, therefore, represent the proportion of the 2,181 patients exposed to multiple doses of venlafaxine who experienced an event of the type cited on at least one occasion while receiving
venlafaxine. All reported events are included except those already listed in Table III and those events for which a drug cause was remote. If the COSTART term for an event was so general as to be uninformative, it was replaced with a more informative term. It is important to emphasize that, although the events reported occurred during
treatment with venlafaxine, they were not necessarily caused by it.
Events are further classified by body system and listed in order of decreasing frequency according to the following definitions: frequent adverse events are those occurring on one or more occasions in at least 1/100 patients (only those not already listed in the tabulated results from placebo controlled trials appear in this listing);
infrequent adverse events are those occurring in 1/100 to 1/1000 patients; rare events are those occurring in fewer than 1/1000 patients. The frequent adverse events have been provided below.
Body as a whole: accidental injury, malaise, neck pain.
Cardiovascular: migraine.
Digestive: dysphagia, eructation.
Hemic and lymphatic: ecchymosis.
Metabolic and nutritional: peripheral edema, weight gain.
Nervous: emotional lability, trismus, vertigo.
Respiratory: bronchitis, dyspnea.
Special senses: abnormal vision, ear pain.
Urogenital: anorgasmia, dysuria, hematuria, metrorrhagia*, urination impaired, vaginitis*.
* Based on the number of male or female patients as appropriate.
Overdose
Symptoms and Treatment:
Human Experience:
There were 14 reports of acute overdose with venlafaxine, either alone or in combination with other drugs and/or alcohol, among the patients included in the premarketing evaluation. The majority of the reports involved ingestions in which the total dose of venlafaxine taken was estimated to be no more than several-fold higher than the
usual therapeutic dose. The 3 patients who took the highest doses were estimated to have ingested approximately 6.75 g, 2.75 g and 2.5 g. The resultant peak plasma levels of venlafaxine for the latter 2 patients were 6.24 and 2.35 mcg/mL, respectively and the peak plasma levels of O-desmethylvenlafaxine were 3.37 and 1.30 mcg/mL,
respectively. Plasma venlafaxine levels were not obtained for the patient who ingested 6.75 g of venlafaxine. All 14 patients recovered without sequelae. Most patients reported no symptoms. Among the remaining patients, somnolence was the most commonly reported symptom. The patient who ingested 2.75 g of venlafaxine was observed to have 2
generalized convulsions and a prolongation of QTc to 500 msec, compared with 405 msec at baseline. Mild sinus tachycardia was reported in 2 of the other patients.
Overdosage Management:
Treatment should consist of those general measures employed in the management of overdosage with any antidepressant. Ensure an adequate airway, oxygenation, and ventilation. Monitoring of cardiac rhythm and vital signs is recommended. General supportive and symptomatic measures are also recommended. Use of activated charcoal, induction of
emesis, or gastric lavage should be considered. Due to the large volume of distribution of venlafaxine hydrochloride, forced diuresis, dialysis, hemoperfusion and exchange transfusion are unlikely to be of benefit. No specific antidotes for venlafaxine are known.
In managing overdosage, consider the possibility of multiple drug involvement. The physician should consider contacting a poison control centre on the treatment of any overdose.
Dosage
Adults:
The recommended treatment dose is 75 mg per day, administered in two or three divided doses, taken with food. If the expected clinical improvement does not occur after a few weeks, a gradual dose increase to 150 mg/day may be considered. If needed, the dose may be further increased up to 225 mg/day. 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 the usefulness of doses greater than 225 mg/day for moderately depressed patients. More severely depressed inpatients have responded to higher doses, between 350 and 375 mg/day, given in 3 divided doses.
Maximum:
The maximum dose recommended is 375 mg per day (in an inpatient setting).
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 compared to normal subjects (see Pharmacology), it is recommended that the total daily dose be reduced by about 50% in patients with moderate hepatic impairment. Since there was much
individual variability in clearance between patients with cirrhosis, it may be necessary to reduce the dose even more than 50%, and individualization of dosing may be desirable in some patients.
Patients with Renal Impairment:
Given the decrease in clearance for venlafaxine and 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 (see Pharmacology), it is recommended that the total daily dose be decreased by 25% in patients with mild to moderate renal
impairment. It is recommended that the total daily dose be reduced by 50% and the dose be withheld until the dialysis treatment is completed (4 hrs) in patients undergoing hemodialysis. Since there was so much individual variability in clearance between patients with renal impairment, individualization of dosing may be desirable in some
patients.
Geriatrics:
No dose adjustment is recommended for elderly patients on the basis of their 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.
Discontinuing Venlafaxine:
When venlafaxine therapy that has been administered for more than 1 week is stopped, it is generally recommended that the dose be tapered gradually to minimize the risk of discontinuation symptoms. Patients who have received venlafaxine for 6 weeks or more should have their dose tapered gradually over a 2-week period.
