Antidepressants plasma concentration monitoring

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

The most common is augmentation is with the mood stabiliser lithium carbonate. Indeed, lithium may be effective as monotherapy for depression but is not preferred because of its adverse effect profile and need for plasma concentration monitoring. Its prescription in combination with antidepressants that have failed to produce remission is more usual and evidence suggests that up to 50% of patients who have not responded to standard antidepressants can respond after lithium augmentation. Addition of lithium requires careful titration of the plasma concentration up to the therapeutic range, with periodic checks thereafter and monitoring for toxicity (see p. 389). 

Antidepressants are used to treat depressed children and adolescents because no other definitive effective therapies are currently available. Plasma concentration monitoring of TCAs is important to ensure safety. As in the adult population, plasma concentrations above 450 ng/mL are associated with increased risk of serious adverse effects including delirium, seizures, delayed cardiac conduction, and sudden death. ... 

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. 

Routine monitoring of plasma concentrations of antidepressants, while technically feasible for most drugs, is of uncertain value (except for nortriptyline). However, studies suggest that at least 20% of patients become noncompliant at some time or other. Thus, a "poor response" in a patient for whom an adequate dosage of drug has been prescribed may be shown by measurement of the plasma drug concentration to be due merely to failure to take the drug. 

CARBONIC ANHYDRASE INHIBITORS ANTIDEPRESSANTS -LITHIUM L plasma concentrations of lithium, with risk of inadequate therapeutic effect t renal elimination of lithium Monitor clinically and by measuring blood lithium levels to ensure adequate therapeutic efficacy... 

PACLITAXEL 1. ANTIBIOTICS-rifampicin 2. ANTIDEPRESSANTS-St John s wort 3. ANTIEPILEPTICS -carbamazepine, phenobarbital, phenytoin 1 plasma concentration of paclitaxel and 1 efficacy of paclitaxel Due to induction of hepatic metabolism of paclitaxel by the CYP isoenzymes Monitor for clinical efficacy and need to T dose if inadequate response is due to interaction... 

VINCA ALKALOIDS - VINBLASTINE, VINCRISTINE 1. ANTIBIOTICS-rifampicin 2. ANTICANCER AND IMMUNOMODULATING DRUGS - dexamethasone 3. ANTIDEPRESSANTS-St John s wort 4. ANTI EPILEPTICS -carbamazepine, phenobarbital, phenytoin 1 of plasma concentrations of vinblastine and vincristine, with risk of inadequate therapeutic response. Reports of 1 AUC by 40% and elimination half life by 35%, and t clearance by 63%, in patients with brain tumours taking vincristine, which could lead to dangerously inadequate therapeutic responses Due to induction of CYP3A4-mediated metabolism Monitor for clinical efficacy, and t dose of vinblastine and vincristine as clinically indicated in the latter case, monitor clinically and radiologically for clinical efficacy in patients with brain tumours and t dose to obtain desired response... 

CORTICOSTEROIDS ANTIDEPRESSANTS -ST JOHN S WORT 1 plasma concentrations of corticosteroids and risk of poor or inadequate therapeutic response, which would be undesirable if used for e.g. cerebral oedema Due to induction of the hepatic metabolism by the CYP3A4 isoenzymes Closely monitor therapeutic response - clinically, by ophthalmoscopy and radiologically - and t dose of corticosteroids for desired therapeutic effect... 

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. 

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. 

A number of antidepressant drugs, particularly SSRIs, can increase plasma prolactin concentrations, although galactorrhea is uncommon. In a prescription event monitoring survey of about 65 000 patients, compared with SSRIs, moclobemide was associated with a relative risk of galactorrhea of 6.7 (95% Cl = 2.7, 15) (727). However, this was substantially less than the risk associated with the dopamine receptor antagonist risperidone (relative risk compared with SSRIs 32 95% Cl = 14, 70). 

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