Q: What is the safest and most effective way to switch patients from lorazepam to clonazepam when the goal is better or more even anxiety control? Can one simply stop the lorazepam 1 mg four times daily and start the clonazepam the next day?

A: Lorazepam, a short-acting benzodiazepine indicated for treatment of anxiety and insomnia, has an elimination half-life of 14 hours, is metabolized almost exclusively via glucuronidation (i.e., not via the intrahepatic cytochrome P-450 system), and excreted in the urine. On the other hand, clonazepam, a long-acting benzodiazepine indicated for treatment of seizure disorders and panic disorder, has an elimination half-life of 30-40 hours and is extensively and almost exclusively metabolized by the intrahepatic cytochrome P-450 system. Since clonazepam has a much longer elimination half-life, there is very little risk of benzodiazepine withdrawal when patients begin clonazepam immediately after stopping lorazepam or any other short-acting benzodiazepine. A 1-mg dose of lorazepam is equivalent to a 0.25- to 0.5-mg dose of clonazepam. Thus, in the situation you describe, it would be reasonable to ask the patient to stop lorazepam and to start taking clonazepam 0.5 mg three times daily.

It is difficult to predict whether clonazepam administration will lead to better or “more even” relief of anxiety. Therapeutic effects depend not only on elimination half-life. The lipophilic properties of the medication and receptor affinity are also important. Highly lipophilic benzodiazepines are rapidly redistributed to peripheral body fat, shortening their therapeutic effect, regardless of their elimination half-life. High affinity for the benzodiazepine receptor may also lengthen the therapeutic duration of action. Lorazepam and clonazepam have similar affinities for the benzodiazepine receptor. Lorazepam also has no active metabolites and a comparatively short elimination half-life. Thus, one would predict that clonazepam would have a longer and more sustained duration of action than lorazepam. We have often seen this with patients under our care. However, patients vary in their response and develop side effects that limit therapeutic usefulness (e.g., sedation). There is no substitution for close, frequent monitoring of the patient's clinical condition.