Monitoring antidepressants

Tricyclic antidepressants Monitor for change in vision, sedation, dry mouth, gastrointestinal upset, and orthostatic dizziness. 

Description of Method. Fluoxetine, whose structure is shown in Figure 12.31a, is another name for the antidepressant drug Prozac. The determination of fluoxetine and its metabolite norfluoxetine. Figure 12.31 b, in serum is an important part of monitoring its therapeutic use. The analysis is complicated by the complex matrix of serum samples. A solid-phase extraction followed by an HPLC analysis using a fluorescence detector provides the necessary selectivity and detection limits. 

Side Effects and Toxicity. Adverse effects to the tricycHc antidepressants, primarily the result of the actions of these compounds on either the autonomic, cardiovascular, or central nervous systems, are summarized in Table 3. The most serious side effects of the tricycHcs concern the cardiovascular system. Arrhythmias, which are dose-dependent and rarely occur at therapeutic plasma levels, can be life-threatening. In order to prevent adverse effects, as weU as to be certain that the patient has taken enough dmg to be effective, the steady-state semm levels of tricycHc antidepressant dmgs are monitored as a matter of good practice. A comprehensive review of stmcture—activity relationships among the tricycHc antidepressants is available (42). 

Antidepressants are used in neuropathic pain and migraine prophylaxis. Tricyclics require monitoring of plasma drug concentrations to achieve optimal effect... 

Full therapeutic effect of the antidepressant may not be attained for 10 days to 4 weeks. Patients with suicidal tendencies must be monitored closely. Report any expressions of guilt, hopelessness helplessness insomnia, weight toss and direct or indirect threats of suicide. 

Monitor antidepressant therapy for relief of lower abdominal pain. 

The FDA has established a link between antidepressant use and suicidality (suicidal thinking and behaviors) in children, adolescents, and young adults 18 to 24 years old. All antidepressants carry a black box warning advising caution in the use of all antidepressants in this population, and the FDA also recommends specific monitoring parameters. The clinician... 

Patients should be monitored for emergence of suicidal ideation after initiation of any antidepressant, especially in the first few weeks of treatment. 

Rao, M.L. et al. 1994. Monitoring tricyclic antidepressant concentrations in serum by fluorescence polarization immunoassay compared with gas chromatography and HPLC. Clin Chem. 40 929. 

Orsulak PJ, Haven MC, Burton ME, Akers LC. 1989. Issues in methodology and applications for therapeutic monitoring of antidepressant drugs. Clin Chem 35 1318. 

Tricyclic antidepressants Despite the numerous publications over the past 30 years on the determination of the TCAs (Tricyclic Antidepressants) by HPLC to establish possible therapeutic windows, both therapeutic drug monitoring and pharmacokinetic calculations have revealed there is considerable variation (10- to 50-fold) in plasma concentrations between individuals with these drugs. The plasma concentrations are usually in the range of 50-300 ng/ml. 

Duverneuil C, Grandmaison GL, Mazancourt P, Alvarez JC. 2003. A high-performance liquid chromatography method with photodiode-array UV detection for therapeutic drug monitoring of the nontricyclic antidepressant drugs. Ther Drug Mon 25(5) 565-573. 

Maris FA, Dingier E, Niehues S. 1999. High-performance liquid chromatographic assay with fluorescence detection for the routine monitoring of the antidepressant mirtazapine and its demethyl metabolite in human plasma. J Chromatogr B Biomed Sci Appl 721(2) 309-316. 

Shams M, Hiemke C, Hartter S. 2004. Therapeutic drug monitoring of the antidepressant mirtazapine and its N-demethylated metabolite in human serum. Ther Drug Monit 26(1) 78-84. 

Gutteck U, Rentsch KM. 2003. Therapeutic drug monitoring of 13 antidepressant and five neuroleptic drugs in serum with liquid chromatography-electrospray ionization mass spectrometry. Clin Lab Med 41 1571. 

Finally, the expense of treatment can be a decisive factor in treatment selection. Depending on the dose, the cost of the newer antidepressants is 1 to 3 per day. The older TCAs and MAOIs are available in cheaper generic forms. However, these reqnire more stringent medical monitoring and periodic assessment of serum drug levels. 

Antidepressants and clonidine are the most commonly used augmentation strategies for ADHD. If the patient has tics or is troubled by insomnia, clonidine is a reasonable choice. After collecting a baseline EKG, clonidine should be started at 0.05 mg at bedtime for children and adolescents and 0.1 mg at bedtime for adults. The dose can be increased every 2 weeks or so while monitoring the patient s blood pressure and pulse. Although it has not been studied as well, guanfacine may work in much the same manner as clonidine. 

Over the past 20 years there has been widespread interest in monitoring plasma antidepressant, particularly tricyclic, levels to optimize the response to treatment. One aspect of this research that is universally agreed upon concerns the extensive interindividual variability among patients, but it is still uncertain whether a knowledge of the plasma drug concentration is of clinical value. 

Add lithium to a standard antidepressant (e.g. an SSRI) maintaining the plasma lithium concentration at 0.4-0.6mmol/l. This is a well-established method with approximately 50% of the patients responding. However, the plasma lithium concentration must be monitored. 

Add tri-iodothyronine to a standard antidepressant. This combination is usually well tolerated but monitoring the plasma T3 concentration is important. 

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