Tricyclic antidepressants plasma concentration monitoring

Hollister LE Monitoring tricyclic antidepressant plasma concentrations. JAMA 241 2530-2533, 1979... 

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. 

FIGURE 6-16. If a tricyclic antidepressant (TCA) is given together with a serotonin selective reuptake inhibitor (SSRI), the SSRI will prevent TCA metabolism. This causes TCA levels to increase, which can be toxic. Therefore either monitoring of TCA plasma concentration with dose reduction of the TCA, or avoidance of the combination, is required. 

DISTRIBUTION AND SERUM LEVEL MONITORING Once absorbed, tricychc antide pressants are widely distributed. They are relatively lipophilic and strongly bind to plasma proteins and constituents of tissues, leading to apparent volumes of distribution as high as 10-50 L g. The tendency of tricyclic antidepressants and their ring-hydroxy metabolites to accumulate in cardiac tissue adds to their cardiotoxicity. Serum concentrations of antidepressants that correlate meaningfully with clinical effects are only established for a few tricychc antidepressants (particularly amitriptyline. 

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

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. 

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