A CASE REPORT OF PARANOID DELUSION WITH VENLAFAXINE USE

To the Editor: We congratulate the American Geriatrics Society for sponsoring the timely update of its guidelines on persistent pain in the elderly.1 The guidelines are a useful tool for many professionals responsible for the care of elderly patients. We, and others,2 were surprised that clonazepam was among the anticonvulsants recommended in the document as an adjunct to analgesics in the pain management regime. Clonazepam is a benzodiazepine that is thought to exert its sedative, antipanic, and anticonvulsant effects by enhancing the activity of gamma aminobutyric acid, the major inhibitory neurotransmitter in the central nervous system (CNS). 3 As such, the major side effects of clonazepam are CNS-related, with primary adverse effects being drowsiness and lethargy. Other benzodiazepine side effects are muscular incoordination, ataxia, hypotonia, dysarthria, and dizziness.4 These effects are especially undesirable in the elderly because they may predispose this population to falls. When considering use of any agent in the elderly, one must consider ageand function-specific pharmacokinetics and pharmacodynamics. Clonazepam undergoes hepatic metabolism, thus liver disease may impair elimination. The geriatric population generally has a decreased ability to metabolize drugs via hepatic oxidation. Because clonazepam uses oxidative pathways for metabolism, its halflife could increase twoto threefold in the elderly.5 Given that the usual half-life standard deviation of clonazepam is already 23 5 hours,4 this creates the potential for extremely prolonged benzodiazepine side effects (such as disturbed intellectual functioning and motor dexterity) in this vulnerable population. Additionally, the elderly are more sensitive to benzodiazepines, creating pronounced pharmacodynamic effects beyond the aforementioned pharmacokinetic concerns.6,7 Clonazepam has several potential uses. The Food and Drug Administration has formally approved the drug for the treatment of panic disorder and for use as an anticonvulsant, but it is generally regarded as a second-line agent. It appears to have greatest efficacy in treating refractory myoclonic (including sensory-precipitated), akinetic, and absence seizures (including petit mal variant LennoxGasteau). Although it may be a useful adjunct in tonicclonic seizures, use of clonazepam in patients with complex seizure disorders can actually precipitate tonic-clonic seizures. Tolerance has been observed to the anticonvulsant effects of clonazepam, necessitating increased doses over time. Other nonindicated uses of clonazepam are similar to those of other benzodiazepines. Data supporting the use of clonazepam for the treatment of pain are sparse. There are reports from small, open-label trials of its successful use in treating burning mouth syndrome and trigeminal neuralgia.8,9 The only controlled trials of clonazepam in pain have been for the treatment of temporomandibular joint disorder, but in the only comparative trial, clonazepam was less effective than cyclobenzaprine and no more effective than placebo.10 We agree that there may be patients who would benefit from the use of a benzodiazepine such as clonazepam or a shorter-acting agent such as lorazepam, but we recommend that such drugs be chosen not because of potential effects on persistent pain, but because of their benefits in managing anxiety, insomnia, or another symptoms for which the short-term use of benzodiazepines has proven benefit. We recommend that clonazepam be removed from future guidelines on the management of persistent pain in the elderly.