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INNOSC Theranostics and
Pharmacological Sciences TDM of imipramine: Correlation and case study

The utility of TDM in optimizing imipramine therapy is 2. Clinical pharmacology
demonstrated by a case study conducted by Yao et al. In the
study, a 43-year-old woman with depression was initiated Imipramine is a TCA that is commonly used to treat
on imipramine at 50 mg orally twice daily. However, her psychiatric disorders such as depression, panic disorder,
serum imipramine concentration was found to be below the anxiety, obsessive-compulsive disorder (OCD), and
therapeutic range. Subsequent dose adjustments were made enuresis in children. The primary mechanism of action of
based on TDM, resulting in improved symptomatology imipramine is the blockade of the high-affinity reuptake
and therapeutic serum levels. The case study highlights the mechanism of norepinephrine (NE), serotonin (5HT),
value of TDM in identifying personalized dosage regimens and to a lesser extent, dopamine (DA) receptors. On
for optimal treatment response [1-3] . acute administration, imipramine leads to an increased
concentration of NE, 5HT, and DA in the synapse .
[4]
Another case study conducted by Fong et al. involved
a 47-year-old man with depression who experienced side Chronic administration of imipramine can lead to a
effects such as drowsiness and dry mouth while taking decrease in beta-adrenergic receptor density, which can
imipramine at 75 mg orally once daily. TDM revealed a cause decreased heart rate and blood pressure. Moreover,
serum imipramine concentration above the therapeutic chronic administration can also result in a decrease in
range. By reducing the dosage to 50 mg once daily based on 5HT density, which can cause adverse effects. Imipramine
TDM results, the patient achieved therapeutic levels and primarily blocks the reuptake of NE and 5HT, leading to
experienced an improvement in side effects [1,2] . increased concentrations of these neurotransmitters in
the synapse. Imipramine also has some affinity for DA
Moreover, a retrospective study by Shen et al. explored receptors, but less than NE and 5HT. The clinical effects of
the association between imipramine TDM and clinical imipramine are thought to be mediated through its actions
outcomes in 82 patients with major depressive disorder. on these neurotransmitter systems .
[4]
The study indicated that patients with imipramine
concentrations within the therapeutic range had higher Overall, imipramine has been found to be an effective
response rates and a lower incidence of adverse effects treatment for various psychiatric disorders, particularly
compared to those with concentrations below or above the depression. However, its use is associated with several
therapeutic range. This suggests that imipramine TDM can adverse effects, including anticholinergic effects, sedation,
effectively optimize therapy and improve clinical outcomes and cardiovascular effects. Furthermore, taking other
in patients with major depressive disorder [1-3] . drugs with imipramine may affect the metabolism of
imipramine or cause severe or fatal drug interactions .
[4]
Furthermore, pharmacogenetic studies have provided
valuable insights into the interpatient variability in TDM can be a valuable tool in optimizing the use of
imipramine metabolism and its impact on therapeutic imipramine and minimizing the risk of adverse effects.
outcomes. For example, genetic variations in the Through TDM, the concentration of imipramine in the
cytochrome P450 isoenzymes, particularly CYP2C19 and blood can be measured and adjusted the dose of medication
CYP2D6, have been associated with variable imipramine to achieve therapeutic levels while minimizing the risk of
metabolism and individual responses to treatment. TDM adverse effects. Moreover, TDM can be particularly useful
combined with genotyping can assist in identifying in cases where there is a concern about drug interactions
patients who may require dose adjustments based on their or individual variability in drug metabolism [3,4] .
genetic profiles . 3. Therapeutic range
[4]
TDM of imipramine plays a critical role in optimizing
pharmacotherapy by tailoring dosage regimens to The recommended therapeutic range for imipramine in the
individual patient characteristics. By monitoring treatment of depression is generally considered to be between
imipramine blood levels and considering genetic factors, 150 and 300 ng/mL. However, due to significant interindividual
clinicians can adjust the dosage to achieve therapeutic variability in imipramine pharmacokinetics, some patients
levels while minimizing the risk of side effects. The may require doses outside of this range to achieve therapeutic
correlation between imipramine TDM and specific case concentrations. Imipramine is metabolized to its active
studies depends on the clinical context and the purpose of compound, desipramine, but there is currently no evidence of
TDM. While TDM provides valuable insights, it should not a therapeutic difference between the two [5,6] .
be the sole method for monitoring imipramine therapy. 4. Pharmacokinetics
Comprehensive clinical monitoring, including symptom
assessment and consideration of patient-specific factors, This study focuses on the pharmacokinetics of imipramine,
remains important for safe and effective imipramine use [2,3] . which includes its absorption, distribution, metabolism,

Volume 6 Issue 2 (2023) 2 https://doi.org/10.36922/itps.0505