Demethylamitriptyline - General Information
A metabolite of amitriptyline that is also used as an antidepressive agent. Demethylamitriptyline is used in major depression, dysthymia, and atypical depressions. [PubChem]
Pharmacology of Demethylamitriptyline
Similar to protriptyline, nortriptyline is a tricyclic antidepressant of the dibenzocycloheptene type and is the active metabolite of amitriptyline.
Demethylamitriptyline for patients
Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with nortriptyline hydrochloride and should counsel them in its appropriate use. A patient Medication Guide About Using Antidepressants in Children and Teenagers is available for nortriptyline hydrochloride. The prescriber or health professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. The complete text of the Medication Guide is reprinted at the end of this document.
Patients should be advised of the following issues and asked to alert their prescribers if these occur while taking nortriptyline hydrochloride.
Clinical Worsening and Suicide Risk: Patients, their families, and their caregivers should be encouraged to be alert to the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, (psychomotor restlessness), hypomania, mania, other unusual changes in behavior, worsening of depression, and suicidal ideation, especially early during antidepressant treatment and when the dose is adjusted up or down. Families and caregivers of patients should be advised to observe for the emergence of such symptoms on a day-to-day basis, since changes may be abrupt. Such symptoms should be reported to the patientís prescriber or health professional, especially if they are severe, abrupt in onset, or were not part of the patientís presenting symptoms. Symptoms such as these may be associated with an increased risk for suicidal thinking and behavior and indicate a need for very close monitoring and possibly changes in the medication.
About Using Antidepressants in Children and Teenagers
What is the most important information I should know if my child is being prescribed an antidepressant?
Parents or guardians need to think about 4 important things when their child is prescribed an antidepressant:
1. There is a risk of suicidal thoughts or actions
2. How to try to prevent suicidal thoughts or actions in your child
3. You should watch for certain signs if your child is taking an antidepressant
4. There are benefits and risks when using antidepressants
1. There is a Risk of Suicidal Thoughts or Actions
Children and teenagers sometimes think about suicide, and many report trying to kill themselves.
Antidepressants increase suicidal thoughts and actions in some children and teenagers. But suicidal thoughts and actions can also be caused by depression, a serious medical condition that is commonly treated with antidepressants. Thinking about killing yourself or trying to kill yourself is called suicidality or being suicidal.
A large study combined the results of 24 different studies of children and teenagers with depression or other illness. In these studies, patients took either a placebo (sugar pill) or an antidepressant for 1 to 4 months. No one committed suicide in these studies, but some patients became suicidal. On sugar pills, 2 out of every 100
became suicidal. On the antidepressants, 4 out of every 100 patients became suicidal.
For some children and teenagers, the risks of suicidal actions may be especially high.
These include patient with
ï Bipolar illness (sometimes called manic-depressive illness)
ï A family history of bipolar illness
ï A personal or family history of attempting suicide
If any of these are present, make sure you tell your healthcare provider before your child takes an antidepressant.
2. How to Try to Prevent Suicidal Thoughts and Actions
To try to prevent suicidal thoughts and actions in your child, pay close attention to changes in her or his moods or actions, especially if the changes occur suddenly. Other important people in your childís life can help by paying attention as well (e.g., your child, brothers and sisters, teachers, and other important people). The changes to look out for are listed in Section 3, on what to watch for.
Whenever an antidepressant is started or its dose is changed, pay close attention to your child. After starting an antidepressant, your child should generally see his or her healthcare provider:
ï Once a week for the first 4 weeks
ï Every 2 weeks for the next 4 weeks
ï After taking the antidepressant for 12 weeks
ï After 12 weeks, follow your healthcare providerís advice about how often to come back
ï More often if problems or questions arise
You should call your childís healthcare provider between visits if needed.
3. You Should Watch for Certain Signs If Your Child is Taking an Antidepressant
Contact your childís healthcare provider right away if your child exhibits any of the following signs for the first time, or if they seem worse, or worry you, your child, or your childís teacher:
ï Thoughts about suicide or dying
ï Attempts to commit suicide
ï New or worse depression
ï New or worse anxiety
ï Feeling very agitated or restless
ï Panic attacks
ï Difficulty sleeping (insomnia)
ï New or worse irritability
ï Acting aggressive, being angry, or violent
ï Acting on dangerous impulses
ï An extreme increase in activity and talking
ï Other unusual changes in behavior or mood
Never let your child stop taking an antidepressant without first talking to his or her health-care provider. Stopping an antidepressant suddenly can cause other symptoms.
4. There are Benefits and Risks When Using Antidepressants
Antidepressants are used to treat depression and other illnesses. Depression and other illnesses can lead to suicide. In some children and teenagers, treatment with an antidepressant increases suicidal thinking or actions. It is important to discuss all the risks of treating depression and also the risks of not treating it. You and your child should discuss all treatment choices with your healthcare provider, not just the use of antidepressants.
Other side effects can occur with antidepressants.
Of all the antidepressants, only fluoxetine (Prozac®)* has been FDA approved to treat pediatric
For obsessive compulsive disorder in children and teenagers, FDA has approved only fluoxetine (Prozac®)*, sertraline (Zoloft®)*, fluvoxamine, and clomipramine (Anafranil®)*. Your healthcare provider may suggest other antidepressants based on the past experience of your child or other family members.
Is this all I need to know if my child is being prescribed an antidepressant?
No. This is a warning about the risk for suicidality. Other side effects can occur with antidepressants. Be sure to ask your healthcare provider to explain all the side effects of the particular drug he or she is prescribing. Also ask about drugs to avoid when taking an antidepressant. Ask your healthcare provider or pharmacist where to find more information. This Medication Guide has been approved by the U.S. Food and Drug Administration for all antidepressants.
*Prozac®is a registered trademark of Eli Lilly and Company.
*Zoloft®is a registered trademark of Pfizer Pharmaceuticals.
*Anafranil®is a registered trademark of Mallinckrodt Inc.
Steady-state serum concentrations of tricyclic antidepressants are reported to fluctuate significantly when cimetidine is either added or deleted from the drug regimen. Serious anticholinergic symptoms (severe dry mouth,
urinary retention, blurred vision) have been associated with elevations in the serum levels of tricyclic
antidepressants when cimetidine is added to the drug regimen. In addition, higher-than expected steady-state serum concentrations of tricyclic antidepressants have been observed when therapy is initiated in patients already taking cimetidine.
In well-controlled patients undergoing concurrent therapy with cimetidine, a decrease in the steady-state serum concentrations of tricyclic antidepressants may occur when cime-tidine therapy is discontinued. The therapeutic
efficacy of tricyclic antidepressants may be compromised in these patients when cimetidine is discontinued. Several of the tricyclic antidepressants have been cited in these reports.
There have been greater than 2-fold increases in previously stable plasma levels of other antidepressants, including nortriptyline, when fluoxetine hydrochloride has been administered in combination with these agents.
Fluoxetine and its active metabolite, norfluoxe-tine, have long half-lives (4 to 16 days for norfluoxetine), that may affect strategies during conversion from one drug to the other.
Administration of reserpine during therapy with a tricyclic antidepressant has been shown to produce a ìstimulatingî effect in some depressed patients. Close supervision and careful adjustment of the dosage are required when nortriptyline hydrochloride is used with other anticholinergic drugs or sympathomimetic drugs.
The patient should be informed that the response to alcohol may be exaggerated.
Drugs Metabolized by P450IID6 óA subset (3% to 10%) of the population has reduced activity of certain drug metabolizing enzymes such as the cytochrome P450 isoenzyme P450IID6. Such individuals are referred to as ìpoor metabolizersî of drugs such as debrisoquin, dextromethorphan, and the tricyclic antidepressants. These individuals may have higher than expected plasma concentrations of tricyclic antidepressants when given usual doses. In addition, certain drugs that are metabolized by this isoenzyme, including many antidepressants (tricyclic
antidepressants, selective serotonin reuptake inhibitors, and others), may inhibit the activity of this isoenzyme,
and thus may make normal metab-olizers resemble poor metabolizers with regard to concomitant therapy with other drugs metabolized by this enzyme system, leading to drug interactions.
Concomitant use of tricyclic antidepressants with other drugs metabolized by cytochrome P450IID6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Therefore, co-administration of tricyclic antidepressants with other drugs that are metabolized by this isoenzyme, including other antidepressants, phenothiazines, carbamazepine, and Type 1C antiarrhythmics (eg, propafenone, flecainide, and encainide), or that inhibit this enzyme (eg, quinidine), should be approached with caution.
The concurrent use of nortriptyline hydrochloride or other tricyclic antidepressants with a monoamine oxidase (MAO) inhibitor is contraindicated. Hyperpyretic crises, severe convulsions, and fatalities have occurred when similar tricyclic antidepressants were used in such combinations. It is advisable to discontinue the MAO inhibitor at least 2 weeks before treatment with nortriptyline hydrochloride is to be started.
Patients hypersensitive to nortriptyline hydrochloride should not be given the drug.
Cross-sensitivity between nortriptyline hydrochloride and other dibenzazepines is a possibility.
Nortriptyline hydrochloride is contraindicated during the acute recovery period after myocar-dial infarction.
Additional information about Demethylamitriptyline
Demethylamitriptyline Indication: For the treatment of depression.
Mechanism Of Action: It is believed that nortriptyline either inhibits the reuptake of the neurotransmitter serotonin at the neuronal membrane or acts at beta-adrenergic receptors. Tricyclic antidepressants do not inhibit monoamine oxidase nor do they affect dopamine reuptake.
Drug Interactions: Altretamine Risk of hypotension
Atazanavir Atazanavir increases the effect and toxicity of tricyclics
Carbamazepine The tricyclic increases the effect of carbamazepine
Cimetidine Cimetidine increases the effect of tricyclic agent
Clonidine The tricyclic decreases the effect of clonidine
Duloxetine Possible increase in the levels of this agent when used with duloxetine
Fluoxetine Fluoxetine increases the effect and toxicity of tricyclics
Fluvoxamine Fluvoxamine increases the effect and toxicity of tricyclics
Guanethidine The tricyclic decreases the effect of guanethidine
Terbinafine Terbinafine increases the effect and toxicity of the tricyclic
Ritonavir Ritonavir increases the effect and toxicity of the tricyclics
Tranylcypromine Possibility of severe adverse effects
Rasagiline Possibility of severe adverse effects
Phenelzine Possibility of severe adverse effects
Isocarboxazid Possibility of severe adverse effects
Cisapride Increased risk of cardiotoxicity and arrhythmias
Grepafloxacin Increased risk of cardiotoxicity and arrhythmias
Terfenadine Increased risk of cardiotoxicity and arrhythmias
Dihydroquinidine barbiturate Quinidine increases the effect of tricyclic agent
Quinidine Quinidine increases the effect of tricyclic agent
Quinidine barbiturate Quinidine increases the effect of tricyclic agent
Dobutamine The tricyclic increases the sympathomimetic effect
Dopamine The tricyclic increases the sympathomimetic effect
Ephedra The tricyclic increases the sympathomimetic effect
Ephedrine The tricyclic increases the sympathomimetic effect
Epinephrine The tricyclic increases the sympathomimetic effect
Fenoterol The tricyclic increases the sympathomimetic effect
Isoproterenol The tricyclic increases the sympathomimetic effect
Mephentermine The tricyclic increases the sympathomimetic effect
Metaraminol The tricyclic increases the sympathomimetic effect
Methoxamine The tricyclic increases the sympathomimetic effect
Norepinephrine The tricyclic increases the sympathomimetic effect
Orciprenaline The tricyclic increases the sympathomimetic effect
Phenylephrine The tricyclic increases the sympathomimetic effect
Phenylpropanolamine The tricyclic increases the sympathomimetic effect
Pseudoephedrine The tricyclic increases the sympathomimetic effect
Pirbuterol The tricyclic increases the sympathomimetic effect
Procaterol The tricyclic increases the sympathomimetic effect
Salbutamol The tricyclic increases the sympathomimetic effect
Terbutaline The tricyclic increases the sympathomimetic effect
Sparfloxacin Increased risk of cardiotoxicity and arrhythmias
Donepezil Possible antagonism of action
Galantamine Possible antagonism of action
Moclobemide Possible severe adverse reaction with this combination
Rivastigmine Possible antagonism of action
Sibutramine Increased risk of CNS adverse effects
Fluconazole The imidazole increases the effect and toxicity of the tricyclic
Ketoconazole The imidazole increases the effect and toxicity of the tricyclic
Rifabutin The rifamycin decreases the effect of tricyclics
Rifampin The rifamycin decreases the effect of tricyclics
Food Interactions: Avoid alcohol.
Take with food.
Avoid excessive quantities of coffee or tea (Caffeine).
Generic Name: Nortriptyline
Synonyms: Not Available
Drug Category: Antidepressants; Norepinephrine-Reuptake Inhibitors
Drug Type: Small Molecule; Approved
Absorption: Well absorbed from the GI tract.
Toxicity (Overdose): Symptoms of overdose include cardiac dysrhythmias, severe hypotension, shock, congestive heart failure, pulmonary edema, convulsions, and CNS depression, including coma. Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of tricyclic antidepressant toxicity. LD50=mg/kg(orally in rat)
Protein Binding: Highly protein-bound in plasma and tissues
Half Life: 16 and 90 hours
Dosage Forms of Demethylamitriptyline: Capsule Oral
Chemical IUPAC Name: 3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-N-methyl-1-propanamine
Chemical Formula: C19H21N
Nortriptyline on Wikipedia: https://en.wikipedia.org/wiki/Nortriptyline
Organisms Affected: Humans and other mammals