Imipramine withdrawalHow to withdrawal
off Imipramine. Imipramine withdrawal. Step by step
Imipramine withdrawal procedures.
Imipramine
Brand name (Janimine and Tofranil)
Imipramine withdrawal
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Imipramine needs to be reduced slowly. No more than 10%
each week and only reduce again if you are feeling very
well. This is crucial to avoid Imipramine withdrawal
effects.
Over the past 20 years we have
found 50% of the people taking Imipramine can get off
Imipramine by reducing at the 10% reduction but they still
suffered Imipramine withdrawal. Even at a 5% reduction they
still suffered Imipramine withdrawal.
In late 1999 we began our research to see if there were
any nutritional supplements that would help with Imipramine
withdrawal. Over the last two decades we have developed
nutritional supplements to assist and the percentage of
people able to manage Imipramine withdrawal has increased
dramatically.
From flu like symptoms, the dreaded brain zaps,
something can be done to help Imipramine withdrawal.
The supplements needed are: JNK Formula Complete, Neuro
Day, Neuro Night and Omega 3 Supreme. These supplements are
available at
Neuro Genetic Solutions.
Imipramine withdrawal and taking Imipramine greatly
activates a gene called JNK. The supplements are formulated
to reduce the activation of this gene. You can replace the
Neuro Day and Neuro Night with a CBD Oil called Harper Drops
Supreme. Neuro genetic Solutions has also formulated this
CBD Oil to have 26mg of CBD per serving and is priced lower
than any CBD oil of similar strength.
If using the CBD Oil instead of the Neuro Night and
Neuro Day; take one half serving of this CBD twice a day and
one more time 15 minutes before bedtime.
Pharmacology
Antidepressant
Imipramine is a tricyclic antidepressant with general pharmacological
properties similar to those of structurally related
tricyclic antidepressant drugs such as amitriptyline and
doxepin.
It possesses anticholinergic properties which are responsible for certain
of its side effects. The mechanism of action of imipramine
and other tricyclic antidepressants is not well established,
but it is thought that it might be related to their action
on the transmitter-uptake mechanism of monoaminergic
neurons. The mechanism of action in childhood nocturnal
enuresis is not fully known.
Imipramine is well absorbed from the gastrointestinal tract. Following
oral administration of 50 mg 3 times daily for 10 days, the
mean steady-state plasma concentration was 33 to 85 ng/mL
for imipramine and 43 to 109 ng/mL for desmethylimipramine,
an active metabolite. Peak plasma levels are reached in 2 to
5 hours, and plasma half-life ranges from 9 to 20 hours.
Approximately 86% of imipramine is bound to plasma proteins.
It is excreted primarily as inactive metabolites, up to 80%
in the urine and up to 20% in the feces.
Indications
For the
relief of symptoms of depression.
Imipramine may also be useful as temporary adjunctive therapy in reducing
enuresis in children aged 5 years and older, after possible
organic causes have been excluded by appropriate tests. In
patients having daytime symptoms of frequency and urgency,
examination should include voiding cystourethrography and
cytoscopy, as necessary. The effectiveness of treatment may
decrease with continued drug administration.
Contraindications
Imipramine
should not be given in conjunction with, or within 14 days
of treatment with a MAO inhibitor. Combined therapy of this
type could lead to the appearance of serious interactions
such as hypertensive crises, hyperactivity, hyperpyrexia,
spasticity, severe convulsions or coma and death may occur.
Imipramine is contraindicated in patients with existing severe hepatic or
renal damage, and those with a history of blood dyscrasias.
Imipramine is contraindicated in patients who have shown hypersensitivity
to the drug or hypersensitivity to tricyclic antidepressants
belonging to the dibenzazepine group.
Imipramine is contraindicated for use during the acute recovery phase
following a myocardial infarction.
It should not be used in patients with convulsive disorders or glaucoma.
Warnings
Extreme
caution should be used when imipramine is given to patients
with known cardiovascular disease including a history of
myocardial infarction, arrhythmias, atrioventricular-block
(grades I-III) and/or ischemic heart disease. These patients
require cardiac surveillance at all dosage levels of the
drug. Imipramine may induce or exacerbate an arrhythmia or
lead to a hypotensive episode, thus making its use hazardous
in these conditions.
Imipramine should be used with caution in hyperthyroid patients and in
those on thyroid medication because of the possibility of
cardiovascular toxicity.
Particularly in the elderly and in hospitalized patients the tricyclic
antidepressants may give rise to paralytic ileus and
therefore appropriate measures should be taken if
constipation occurs. Imipramine may produce urinary
retention and should be used with caution in patients with
urinary pathology, particularly in the presence of prostatic
hypertrophy.
Caution is called for when employing imipramine in patients with tumors
of the adrenal medulla (e.g. pheochromocytoma, neuroblastoma),
in whom the drug may provoke hypertensive crisis.
Concomitant treatment with imipramine and electroconvulsive therapy
should only be resorted to under careful supervision.
Caution is called for when treating patients with low convulsion
thresholds (e.g., due to brain damage of varying etiology,
alcoholism).
Children:
Effectiveness in children for conditions other than
nocturnal enuresis has not been established. Safety and
effectiveness of the drug as temporary adjunctive therapy
for nocturnal enuresis in children under 5 years of age has
not been established.
Safety of imipramine for long-term chronic use as adjunctive therapy for
nocturnal enuresis in children 5 years of age or older has
not been established; consideration should be given to
establishing a drug free period following an adequate
therapeutic trial with a favorable response. Recommended
doses should not be exceeded in childhood, because ECG
changes of unknown significance have been reported with
higher doses in pediatric patients. In order to guard
against possible cardiotoxic effects, a daily dosage of 2.5
mg/kg should not be exceeded in children.
Pregnancy:
The safety of imipramine in pregnancy has not been
established. Neonates whose mothers had taken imipramine up
until delivery have shown symptoms such as dyspnea,
lethargy, colic, irritability, hypotension or hypertension,
tremor or spasms during the first few hours or days.
Therefore, imipramine should not be administered to women of childbearing
potential, particularly during the first trimester and the
last 7 weeks of pregnancy, unless in the opinion of the
physician the potential benefit to the patient outweighs the
possible hazards to the fetus.
Lactation:
Imipramine passes into the breast milk, in the case of
nursing mothers the infant should be weaned or the drug
withdrawn.
Imipramine should be kept out of the reach of children.
Precautions
The
possibility of suicide in seriously depressed patients is
inherent in their illness and may persist until significant
remission occurs. Therefore, patients must be carefully
supervised during all phases of treatment with imipramine
and may require hospitalization. Prescriptions should be
written for the smallest amount and consistent with good
management.
Activation of latent schizophrenia or aggravation of existing psychotic
manifestations in schizophrenic patients may occur;
hyperactive or agitated patients may become over-stimulated;
and patients with manic-depressive tendencies may experience
hypomanic or manic shifts. Discontinuation of imipramine
should be considered under these circumstances.
In predisposed and elderly patients, imipramine may, particularly at
night, provoke pharmacogenic (delirious) psychoses which
disappear without treatment within a few days of withdrawing
the drug.
Before initiating treatment, it is advisable to check the patient's blood
pressure, because individuals with hypotension or a labile
circulation may react to the drug with a fall in blood
pressure. Regular measurements of the blood pressure should
be performed in patients susceptible to postural
hypotension. Postural hypotension may be controlled by
reducing the dosage or administering circulatory stimulants.
Particularly in patients with heart diseases, especially those who have a
history of conduction disorders, as well as in elderly
subjects, cardiac function should be monitored and ECG
examinations performed during long-term treatment.
Periodic blood cell counts and liver function tests are recommended with
prolonged therapy.
An abrupt discontinuation of treatment should be avoided as it may give
rise to withdrawal symptoms.
Occupational Hazards:
Since imipramine may produce sedation and decrease
alertness, patients should be cautioned against driving an
automobile, operating heavy machinery or performing
potentially dangerous tasks that require mental alertness,
judgment and physical co-ordination.
Lengthy treatment with tricyclic antidepressants can lead to an increased
incidence of dental caries.
Drug Interactions:
Patients should be warned that, while taking imipramine
their responses to alcoholic beverages, other CNS
depressants (e.g., barbiturates, benzodiazepines or general
anesthetics) or anticholinergic agents (e.g., atropine,
biperiden, levodopa) may be exaggerated. When tricyclic
antidepressants are given in combinations with
anticholinergics or neuroleptics with an anticholinergic
action, hyperexcitation states or delirium may occur, as
well as attacks of glaucoma. Tricyclic antidepressants
should not be employed in combination with anti-arrhythmic
agents of the quinidine type.
Since imipramine may diminish or abolish the antihypertensive effects of
guanethidine, clonidine, reserpine, methyldopa, patients
requiring concomitant treatment for hypertension should be
given antihypertensives of a different type (e.g.,
diuretics, beta-blockers).
Imipramine may potentiate the cardiovascular effects of noradrenaline or
adrenaline, amphetamine, as well as nasal drops and local
anesthetics containing sympathomimetics.
Methylphenidate may increase the activity and plasma concentrations of
tricyclic antidepressants.
Caution should be exercised if imipramine is administered together with
cimetidine since cimetidine has been shown to inhibit the
metabolism of several tricyclic antidepressants and
clinically significant increases in plasma levels of
imipramine may occur; ranitidine was not observed to alter
the kinetics of imipramine.
Substances which activate the hepatic mono-oxygenase enzyme system (e.g.,
barbiturates, phenytoin, nicotine) may lower plasma
concentrations of tricyclic antidepressants and so reduce
their antidepressive effects.
Imipramine should not be administered for a period of at least 14 days
after the discontinuation of treatment with MAO inhibitors
due to the potential for severe interactions (see
Contraindications). The same caution should also be observed
when administering an MAO inhibitor after previous treatment
with imipramine.
The use of imipramine on a once-a-day dosage regimen in geriatric
patients, patients with intercurrent illnesses, or patients
taking other medications should be adjusted carefully, based
on the patient's condition. This is especially important if
the patient is receiving other medications with
anticholinergic effects.
Imipramine should be discontinued prior to elective surgery for as long
as clinically feasible, since little is known about the
interaction between imipramine and general anesthetics.
Concomitant administration of imipramine and phenytoin may lead to
elevated serum phenytoin concentration. If necessary, the
phenytoin dosage should be adjusted accordingly.
Neuroleptic agents (e.g., phenothiazines) may increase the plasma
concentration of imipramine. No such effects are known to
occur in combination with diazepam but it might be necessary
to lower the dosage of imipramine if administered
concomitantly with alprazolam or disulfiram.
If administered concomitantly with estrogens, the dose of imipramine
should be reduced since steroid hormones inhibit the
metabolism of imipramine.
Adverse Effects
The
following adverse effects have been reported with imipramine
or other tricyclic antidepressants.
CNS:
Frequently: Tremors. Occasionally: drowsiness, fatigue,
insomnia, dizziness, headache, paresthesia (numbness,
tingling sensation, symptoms suggestive of peripheral
neuropathy). Rarely: Epileptic seizures. In isolated cases:
Tinnitus, incoordination, ataxia, alterations in EEG
patterns, extrapyramidal symptoms, myoclonus, speech
disorders.
Behavioral:
Occasionally: Confusional states (especially in the elderly)
with hallucinations, disorientation, delusions, anxiety,
agitation, restlessness, nightmares, hypomania, mania,
exacerbation of psychosis, decrease in memory, feeling of
unreality. In isolated cases: Feeling of weakness,
aggressiveness.
Autonomic:
Frequently: Dry mouth and rarely associated sublingual
adenitis, blurred vision, disturbances of accommodation,
constipation, perspiration, flushing. Occasionally: Delayed
micturition, dilation of the urinary tract. In isolated
cases: Mydriasis, glaucoma, paralytic ileus, urinary
frequency.
Cardiovascular:
Frequently: Hypotension, particularly orthostatic
hypotension with associated vertigo, tachycardia, ECG
changes (including flattening or inversion of T wave).
Occasionally: Arrhythmia, disturbances in cardiac
conduction, palpitation, syncope. In isolated cases:
Hypertension, congestive heart failure, myocardial
infarction, heart block, asystole, stroke, peripheral
vasospastic reactions.
Hematologic:
In isolated cases: Agranulocytosis, eosinophilia, leukopenia,
purpura and thrombocytopenia may occur as an idiosyncratic
response.
Gastrointestinal:
Occasionally: Nausea, vomiting, anorexia. Rarely: Elevated
transaminases. In isolated cases: Diarrhea, bitter taste,
stomatitis, epigastric distress, abdominal cramps, black
tongue, dysphagia, increased salivation, hepatitis with or
without jaundice.
Endocrine:
Frequently: Weight gain. Occasionally: Increased or
decreased libido, impotence. In isolated cases: Gynecomastia
in the male, breast enlargement and galactorrhea in the
female, testicular swelling, elevation or depression of
blood sugar levels, weight loss, inappropriate antidiuretic
hormone (ADH) secretion syndrome.
Allergic or Toxic:
Occasionally: Skin rash, urticaria. In isolated cases:
Petechiae, itching, photosensitization (avoid excessive
exposure to sunlight), edema (general or of face and
tongue), drug fever, obstructive jaundice, nasal congestion,
alopecia, cross-sensitivity with desipramine, allergic
alveolitis (pneumonia) with or without eosinophilia.
If treatment is terminated abruptly, withdrawal symptoms, such as
gastrointestinal upsets, nervousness, anxiety, and muscle
twitching may occur.
Overdose
Children
have been reported to be more sensitive than adults to an
acute overdosage of imipramine. An acute overdose in infants
or young children must be considered serious and potentially
fatal.
Symptoms:
These may vary in severity depending upon factors such as
the amount of drug absorbed, the age of the patient and the
interval between drug ingestion and the start of treatment.
Blood and urine levels of imipramine may not reflect the
severity of poisoning; they have chiefly a qualitative
rather than quantitative value, and are unreliable
indicators in the clinical management of the patient.
Drowsiness, stupor, ataxia, vomiting, cyanosis, restlessness, agitation,
delirium, severe perspiration, hyperactive reflexes, muscle
rigidity, athetoid movements, convulsions, respiratory
depression, hyperpyrexia, hypothermia, mydriasis, and bowel
and bladder paralysis may occur.
Serious cardiovascular disturbances are frequently present, including
tachycardia, cardiac arrhythmia (flutter, atriofibrillation,
ventricular premature beats, and ventricular tachycardia),
as well as impaired myocardial conduction, atrioventricular
and intraventricular block, ECG abnormalities (such as
widened QRS complexes and marked S-T shifts and signs of
congestive heart failure and cardiac arrest). Hypotension
and initial hypertension may occur. However, the usual
finding is increasing hypotension which may lead eventually
to shock. Coma may ensue.
Treatment:
Symptomatic and supportive. Cardiac arrhythmias and CNS
involvement pose the greatest threat with tricyclic
antidepressant overdosage and may occur suddenly even when
initial symptoms appear to be mild. Therefore, patients who
may have ingested an overdosage of imipramine, particularly
children, should be hospitalized and kept under close
surveillance.
If the patient is conscious, induced emesis followed by gastric lavage,
with appropriate precautions to prevent pulmonary
aspiration, should be accomplished as soon as possible.
Following lavage, activated charcoal may be administered to
reduce absorption. An adequate airway should be established
in comatose patients and assisted ventilation instituted, if
necessary, but respiratory stimulants should not be used.
Hyperpyrexia should be controlled by external measures, such
as ice packs and cooling sponge baths. Acidosis may be
treated by cautious administration of sodium bicarbonate.
Adequate renal function should be maintained.
External stimulation should be minimized to reduce the tendency to
convulsions. If convulsions occur, anticonvulsants
(preferably i.v. diazepam) should be administered.
Barbiturates may intensify respiratory depression,
particularly in children, and aggravate hypotension and
coma. Paraldehyde may be used in some children to counteract
muscular hypertonus and convulsions with less likelihood of
causing respiratory depression. If the patient fails to
respond rapidly to anticonvulsants, artificial ventilation
should be instituted. Prompt control of convulsions is
essential since they aggravate hypoxia and acidosis and may
thereby precipitate cardiac arrhythmias and arrest.
ECG monitoring in an intensive care unit is recommended in all patients,
particularly in the presence of ECG abnormalities, and
should be maintained for several days after the cardiac
rhythm has returned to normal. A patient who has ingested a
toxic overdose of a tricyclic antidepressant may remain
medically and psychiatrically unstable for several days due
to sustained excessive drug levels. Unexpected cardiac
deaths have occurred up to 6 days after overdosage with
other antidepressants. The QRS interval of the
electrocardiogram appears to be a reliable correlate of the
severity of overdosage. If the QRS interval exceeds 100
milliseconds any time during the first 24 hours after
overdosage, cardiac function should be continuously
monitored for 5 or 6 days. Correction of hypoxia, if
present, may be beneficial. Correction of metabolic acidosis
and low potassium concentrations by means of bicarbonate i.v.
and potassium substitution may also be effective for
treatment for arrhythmia. If bradyarrhythmia or AV-block
occur, consider temporary insertion of a cardiac pacemaker.
Because of its effect on cardiac conduction, digitalis
should be used only, with caution. If rapid digitalization
is required for the treatment of congestive heart failure,
special care should be exercised in using the drug.
Shock should be treated with supportive measures such as i.v. fluids,
plasma expanders, oxygen and corticosteroids. Hypotension
usually responds to elevation of the foot of the bed.
Pressor agents, such as norepinephrine (but not
epinephrine), are rarely indicated and should be given only
after careful consideration and under continuous monitoring.
In the event of a reduced myocardial function, consider
recourse to treatment with dopamine or dobutamine by i.v.
drip.
Physostigmine i.v. has been used in the treatment of tricyclic-induced
anticholinergic toxicity. Its use is controversial and
should be reserved for life-threatening situations.
Physostigmine is not innocuous and carries the risk of
inducing seizures, bronchospasm, hypertension and severe
arrhythmias. It should not be used routinely or to reverse
coma. However, it may be indicated in the treatment of
seizures or combative hallucinations. It should not be used
in patients who are acidemic or who have cardiac conduction
defects.
Adults:
A test dose of 0.5 mg i.v. is given initially. Give 1 to 2
mg slowly i.v. (over 2 minutes). If no clinical changes or
cholinergic signs occur within 15 to 30 minutes, an
additional 1 to 2 mg may be cautiously administered. Repeat
doses of 1 to 2 mg i.v. every 30 minutes up to 2 hours.
Children:
0.5 mg i.v. is given initially.
As the CNS effects of physostigmine may wear off rapidly, it is important
to monitor the patient continuously.
Physostigmine is the only drug of this class that may be used.
Neostigmine should not be used as it does not have any CNS
effects.
If symptoms of cholinergic toxicity develop, physostigmine should be
discontinued.
Peritoneal and hemodialysis are of no value because of low plasma
concentrations of the drug. Most of the administered dose is
distributed in tissue and not in plasma. When aggressive
medical management is inadequate, hemoperfusion, but not
hemodialysis, has shown some good results.
Deaths by deliberate or accidental overdosage have occurred with this
class of drugs. Since the propensity for suicide is high in
depressed patients, a suicide attempt by other means may
occur during the recovery phase. The possibility of
simultaneous ingestion of other drugs should also be
considered.
Dosage
Depression:
The dosage should be individualized according to the
requirements of each patient. Treatment should be initiated
at the lowest recommended dose and increased gradually
noting carefully the clinical response and any evidence of
intolerance, particularly when treating elderly and
adolescent patients. It should be kept in mind that a lag in
therapeutic response usually occurs at the onset of therapy,
lasting from several days to a few weeks. Increasing the
dosage does not normally shorten this latent period and may
increase the incidence of side effects.
Adults:
Initial dosage:
25 mg 3 times daily. This should be increased gradually as
required and tolerated up to 150 mg/day. Dosages over 200
mg/day are not recommended. In severely ill, hospitalized
patients, initially 100 mg/day in divided doses, gradually
increasing to 200 mg/day, if required. If no significant
response is observed after 3 weeks, dosage may be increased
up to 250 to 300 mg/day.
Elderly and debilitated patients:
30 to 40 mg/day, in divided doses, gradually increasing
dosage if necessary, and tolerated; it is generally not
necessary to exceed 100 mg/day.
Maintenance dosage:
Dosage during maintenance therapy should be kept at the
lowest effective level. Medication should be continued for
the expected duration of the depressive episode in order to
minimize the possibility of relapse following clinical
improvement.
When a maintenance dosage has been established as described above,
imipramine may be administered in a single daily dose at
bedtime, provided such a dosage regimen is well tolerated.
Childhood enuresis:
For persistent functional enuresis which has not responded
to other forms of management, a therapeutic trial with
imipramine may be considered for children between 5 and 15
years of age, who are not mentally defective, and in whom
organic causes of enuresis have been excluded.
The recommended dosage is 10 to 25 mg/day for children 5 years of age and
older. If a satisfactory response does not occur within one
week, the dosage may be increased up to 75 mg/day in
children over 12 years of age. A daily dose greater than 75
mg does not enhance efficacy and tends to increase side
effects. ECG changes of unknown significance have been
reported with doses higher than those recommended in
pediatric patients. The trial period should be 2 to 4 weeks.
Medication should be given in a single dose one hour before
bedtime, however, in children subject to enuresis early on
in the night, part of the dose should be taken between 15
and 17 h.
Consideration should be given to instituting a drug free period following
an adequate therapeutic trial with a favorable response, in
order to assess the need for further drug treatment.
Dosage should be tapered off gradually rather than abruptly discontinued;
this may reduce the tendency to relapse.
Children who relapse when the drug is discontinued do not always respond
to a subsequent course of treatment.
Safety and effectiveness of imipramine as temporary adjunctive treatment
for nocturnal enuresis in children less than 5 years of age
has not been established.
Supplied
10 mg:
Each reddish brown, sugar-coated, triangular tablet, branded
Geigy in white and coded FT, contains: Imipramine HCl USP 10
mg. Energy: 1.3 kJ (0.32 kcal). Bottles of 100 and 500.
25 mg:
Each reddish brown, sugar-coated, round tablet, branded
Geigy in white and coded CZ, contains: Imipramine HCl USP 25
mg. Energy: 1 kJ (0.25 kcal). Bottles of 100 and 1000.
50 mg:
Each reddish brown, sugar-coated, round tablet, branded
Geigy in white and coded LB, contains: Imipramine HCl USP 50
mg. Energy: 3.77 kJ (0.90 kcal). Bottles of 100 and 500.
75 mg:
Each reddish brown, sugar-coated, round tablet, branded
Geigy in white and coded ATA, contains: Imipramine HCl USP
75 mg. Energy: 3.3 kJ (0.8 kcal). Bottles of 30.
All strengths contain lactose. All are alcohol-free, bisulfite-free,
gluten-free, parabens-free, sodium-free and tartrazine-free.
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