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optimal dosage of imipramine yields trough (just before the next dose) blood levels of imipramine and
desipramine combined from 175 to 300 ng/mL. If desipramine is given, no imipramine should be detected
and the therapeutic concentration for desipramine alone is 100 to 300 ng/mL. Toxicity associated with
imipramine is characterized by QRS widening leading to ventricular tachycardia and asystole. In some
patients, toxicity may manifest at lower concentrations, or at therapeutic concentrations in the early state
of therapy. Cardiac toxicity (first-degree heart block) is usually associated with blood concentrations in
excess of 300 ng/mL. Desipramine Desipramine is a TCA; it also is a metabolite of imipramine. These
drugs have also been employed in the treatment of enuresis (involuntary urination) in childhood and
severe obsessive-compulsive neurosis. Desipramine is the antidepressant of choice in patients where
maximal stimulation is indicated. The therapeutic concentration of desipramine is 100 to 300 ng/mL.
About 1 to 3 weeks of treatment are required before therapeutic effectiveness becomes apparent. The most
frequent side effects are those attributable to anticholinergic effects; dry mouth, constipation, dizziness,
tachycardia, palpitations, blurred vision, and urinary retention. These occur at blood concentrations in
excess of 300 ng/mL, although they may occur at therapeutic concentrations in the early stage of therapy.
Cardiac toxicity (first-degree heart block) is usually associated with blood concentrations in excess of 300
ng/mL. Doxepin Doxepin is recommended for the treatment of psychoneurotic patients with depression or
anxiety, and depression or anxiety associated with alcoholism or organic disease. Nordoxepin
(N-desmethyldoxepin) is the major metabolite and is usually present at concentrations equal to doxepin.
Optimal efficacy occurs at combined serum concentrations between 50 ng/mL and 150 ng/mL. Like other
TCA, the major toxicity of doxepin is expressed as cardiac dysrhythmias, which occur at concentrations in
excess of 300 ng/mL. Other side effects include nausea, hypotension, and dry mouth.
Useful For: Monitoring serum concentration during therapy Evaluating potential toxicity Evaluating
patient compliance
Interpretation: Therapeutic ranges are based on specimens drawn at trough (ie, immediately before
the next dose). Amitriptyline and Nortriptyline Most individuals display optimal response to amitriptyline
when combined serum levels of amitriptyline and nortriptyline are between 80 ng/mL and 200 ng/mL.
Risk of toxicity is increased with combined levels > or =300 ng/mL. Most individuals display optimal
response to nortriptyline with serum levels between 70 ng/mL and 170 ng/mL. Risk of toxicity is
increased with nortriptyline levels > or =300 ng/mL. Some individuals may respond well outside of these
ranges, or may display toxicity within the therapeutic range, thus interpretation should include clinical
evaluation. Imipramine Most individuals display optimal response to imipramine when combined serum
levels of imipramine and desipramine are between 175 ng/mL and 300 ng/mL. Risk of toxicity is
increased with levels > or =300 ng/mL. Despramine Most individuals display optimal response to
desipramine with serum levels of 100 to 300 ng/mL. Risk of toxicity is increased with desipramine levels
> or =300 ng/mL. Some individuals may respond well outside of these ranges, or may display toxicity
within the therapeutic range, thus interpretation should include clinical evaluation. Doxepin Most
individuals display optimal response to doxepin when combined serum levels of doxepin and nordoxepin
are between 50 ng/mL and 150 ng/mL. Some individuals may respond well outside of this range, or may
display toxicity within the therapeutic range; thus, interpretation should include clinical evaluation. Risk
of toxicity is increased with combined levels > or =300 ng/mL.
Reference Values:
AMITRIPTYLINE AND NORTRIPTYLINE
Therapeutic concentration: 80-200 ng/mL
Toxic concentration: > or =300 ng/mL
NORTRIPTYLINE
Therapeutic concentration: 70-170 ng/mL
Toxic concentration: > or =300 ng/mL
IMIPRAMINE AND DESIPRAMINE
Therapeutic concentration: 175-300 ng/mL
Toxic concentration: > or =300 ng/mL
DESIPRAMINE
Therapeutic concentration: 100-300 ng/mL
Toxic concentration: > or =300 ng/mL
Current as of January 4, 2013 7:15 pm CST 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 1789