Mohammed T. Abou-Saleh

486 PRINCIPLES AND PRACTICE OF GERIATRIC PSYCHIATRYusually transient, diminishing with continued treatment. PersistentGI symptoms may respond to a reduction in the dose orchanging to the enteric-coated form.Common central nervous system (CNS) effects are sedation andataxia, which are generally dose-related. Nystagmus, headache,diplopia and asterixis are less common side effects. Dizziness andlack of coordination can occur and are also dose-related.Minor elevations of liver transaminases (SGOT, SGPT andLDH) can occur as side effects of treatment. Hepatotoxicity withhepatic failure has been reported in children but less frequently inadults. Baseline and periodic monitoring of hepatic function isindicated during the initial phase of treatment.Idiosyncratic reactions may cause alopecia, which can betreated effectively with vitamin supplements containing zinc andselenium. Other side effects, such as thrombocytopenia, leukocytosis,edema, weakness and skin rash, have been reported but aregenerally rare.Drug InteractionsBecause valproate is extensively metabolized in the liver, it mayinteract with other medications. Valproate may inhibit themetabolism of phenobarbital, ethosuximide, phenytoin andsome tricyclic antidepressants, resulting in higher blood levels ofthese drugs. Frequent monitoring of blood levels and appropriateadjustment of dosage may be needed to maintain therapeuticblood levels during the initial stages of treatment. Combinationsof valproate and clonazepam may produce lapse of memory,which could present a significant problem in elderly patients. Theuse of anticoagulants such as aspirin and warfarin should beclosely monitored, as the potency of these drugs may be enhanced.Newer AnticonvulsantsGabapentinGabapentin is a novel anticonvulsant agent structurally related tog-aminobutyric acid (GABA), currently approved as an adjunctivetherapy in patients with partial seizures. Its mechanism ofaction is not yet fully understood. Gabapentin has beenincreasingly used for the treatment of bipolar disorder, behavioraldisturbances in Alzheimer’s disease, and social phobia. Multiplecase reports and small open-label studies in the general adultpopulation have demonstrated gabapentin to be effective asmonotherapy or as an adjunct therapy for the treatment of acutemania, or as a prophylactic therapy for bipolar illness 47–52 .Experience in the non-demented elderly bipolar patient is limited.Gabapentin is not metabolized and is not protein-bound. It isexcreted in the kidneys essentially unchanged. It has fewpharmacokinetic interactions with other medications. Someresearchers have reported a small increase in Depakote levelswhen used together 53 . Gabapentin is not associated with anyhematologic or hepatic problems and does not require monitoringof serum concentration. In addition, gabapentin has a relativelybenign side-effect profile. The most commonly reported adverseeffects are sedation, dizziness, ataxia and fatigue 54 . These areusually minor and transient. These properties have madegabapentin a very attractive medication choice for use in bipolarpatients who are receiving multiple medications, experience bloodor liver problems, or in whom blood level monitoring is aproblem 55 . Some researchers 51 , however, have suggested thatgabapentin may only exert a ‘‘moderate’’ antimanic effect, andthat its onset of effect may be delayed when compared with othermood stabilizers. Thus, gabapentin may be less effective in theacute treatment of mania, and is recommended as adjunctivetherapy in severe mania.The effective dose of gabapentin in the treatment of bipolardisorder is not yet known. Most trials in young adults have used adosage range of 300–2400 mg/day, although the use of larger doseshas also been documented. Ferrier 55 has suggested that gabapentinmay be particularly efficacious in rapid-cycling bipolar disorder(dose range 1500–2400 mg/day). Elderly patients would presumablyrequire less, due to age-related decreases in creatinine clearance. Theusual starting dose is 300–600 mg/day in divided doses.LamotrigineAs the use of anticonvulsant medications for treatment of bipolardisorder has proved successful, other anticonvulsants have also beenincreasingly used. Lamotrigine is an anticonvulsant approved as anadjunctive treatment for refractory epilepsy. The exact mechanismof action is not yet known, although evidence suggests that itreduces the release of excitatory amino acids (by blocking voltagedependentsodium channels) and may act as a calcium channelantagonist 56,57 . Early studies and case reports in young adults havesuggested that lamotrigine may be useful as a monotherapy or as anadjunctive therapy for bipolar disorder 58–61,95,96,98 and is particularlyeffective in rapid-cycling bipolar disorder and bipolar depression 62–66 . Lamotrigine has not been studied in elderly bipolar patients.Lamotrigine is metabolized in the liver, with a half-life of 25–30 h. Protein binding is 55%. Lamotrigine does not appear toinduce the P450 system and it has little interactions with otherpsychotropic medications. However, carbamazepine may decreaselamotrigine levels while valproate may increase them.The most common side effects are headache, nausea, diplopia,dizziness and ataxia. A skin rash may occur in 5% of patients,more commonly with older age, rapid escalation of dose and theconcomitant use of valproate. In most cases the rash is mild andtransient; however, a few patients have developed Stevens–Johnson syndrome. Therefore, the medication is usually titratedvery slowly (beginning at 12.5 mg/day) and is discontinued if arash develops. Lamotrigine has also been reported to causeconfusion or psychosis or to induce mania. There are no currentstandard dosage recommendations and routine measurement ofserum concentrations is not required.ADJUNCTIVE MEDICATIONS FOR ACUTE MANIAClonazepamEfficacyClonazepam is a nitrobenzodiazepine derivative indicated in thetreatment of absence seizures, infantile spasms, myoclonus andatonic seizures. It has proven efficacy in reducing seizurefrequency and has also been used effectively in restless legsyndrome, panic disorder and Tourette’s disorder. Clonazepamhas also been used with success in treating acute mania 67,68 . It hasalso been used to augment mood stabilizers during the acutetreatment of manic episodes, allowing a decrease in the use ofneuroleptics in non-psychotic mania 69–71 . Clonazepam has notbeen well studied for use in geriatric patients with bipolardisorder.Dose and MetabolismThe antimanic effect is attained in younger adults with a doserange of 2–16 mg/day in divided doses 67 . The half-life in younger