Anticonvulsants in bipolar disorder

Pies R. Combining lithium and anticonvulsants in bipolar disorder a review. Ann Chn Psychiatry 2002 14(4) 223-32. 

Yatham LN, Kusumakar V, Calabrese JR, et al. Third generation anticonvulsants in bipolar disorder a review of efficacy and summary of clinical reconunendations. J CUn Psychiatry 2002 63 275-283. 

I The use of anticonvulsants in bipolar disorder has led to speculation about the possibility of a common pathophysiology between epilepsy and severe psychotic disorder. Processes that appear to be similar to kindling phenomena occur in the natural history of bipolar and unipolar affective disorders. Most anticonvulsant dmgs with mood-stabilising properties also inhibit the electrically induced kindling of seizure activity in animals. 

The evidence base for clinical decisions based on cost-effectiveness for the affective disorders is less clear than for schizophrenia. In bipolar disorder the primary effectiveness of the mainstay treatments, lithium and anticonvulsant pharmacotherapy, is undergoing considerable revision (Bowden et al, 2000). Until this is clarified, cost-effectiveness studies are probably premature. Nevertheless the cost burden in bipolar disorder is qualitatively similar to that in schizophrenia, with in-patient costs being the primary burden and associated social costs in treated patients. The drug costs are even less than those for schizophrenia. In Chapter 5 John Cookson suggests there is little economic evidence to drive prescribing decisions. The in-patient burden does not seem to have altered with the introduction of lithium. The only drug-related study (Keck et al, 1996) showed an obvious difference in treatment costs only when lithium was compared with sodium valproate. Since these are both cheap drugs this is unlikely to influence clinical decisions. The main question is what impact... 

Virtually all anticonvulsants are or have been of interest for the treatment of bipolar disorder. However, the importance of controlled data cannot be understated. For example, gabapentin, an anticonvulsant that initially received much attention as a potential mood stabilizer, was compared with placebo and did not appear to stabilize mood (Frye et al. 2000 Pande et al. 2000). Similar negative results were seen with topiramate in placebo-controlled trials for the treatment of mania. Although these medications might be useful adjuncts in some patients, given the currently expanded pharmacopoeia of medications with positive controlled trial data in bipolar disorder, we do not recommend the primary use of agents that have only case reports as an evidence base or controlled studies with predominantly negative results. 

Nolen WA. Carbamazepine an alternative in lithium-resistant bipolar disorder. In Emrich HM, Okuma T, Muller AA, eds. Anticonvulsants in affective disorders. Amsterdam Excerpta Medica, 1984 132-138. 

Recommended baseline and routine laboratory tests for valproate are listed in Table 68-12. Data from clinical trials in acutely manic patients indicated that there was an earlier response when trough serum levels were greater than 45 mcg/mL during the Hrst week of treatment. Although therapeutic serum concentrations of valproic acid have not been established in bipolar disorder, most clinicians use the anticonvulsant therapeutic range of 50 to 125 mcg/mL taken 12 hours after the last dose. Patients with cyclothymia or mild bipolar II disorder may have a therapeutic response to lower doses and blood levels, whereas some patients with a more severe form of bipolar disorder may require up to 150 mcg/mL. Serum valproic acid levels are usually determined every 1 to 2 weeks during the first 2 months, and then every 3 to 6 months during maintenance therapy. ... 

The place in therapy of the newer anticonvulsants, such as gabapentin, levetiracetam, tiagabine, topiramate, and zon-isamide, is controversial. Many clinicians consider these agents to be less effective than established mood stabilizers based on initial studies and avoid them for monotherapy in bipolar disorder. 

The term mood stabiliser has been applied to lithium and antieonvulsant dmgs used to treat bipolar disorder. It is also starting to be applied to some atypieal antipsychotics. Its use has become more controversial with developments in anticonvulsant and atypical antipsychotic use in bipolar disorder. 

Antimanic anticonvulsants, particularly sodium valproate and carbamazepine, also have been employed prophylacticaUy in bipolar disorder. However, research supporting their long-term use remains limited, and there is growing evidence for the inferiority of carbamazepine compared to lithium (carbamazepine is not FDA-approved for bipolar disorder). Divalproex, the sodium salt of... 

Antipsychotic drugs commonly have been used empirically to manage manic and psychotic illness in bipolar disorder patients. Indeed, standard neuroleptics are a mainstay of the treatment of acute mania (only chlorpromazine is FDA-approved for this indication, although haloperidol has also been widely used) and for manic episodes that break through prophylactic treatment with LF or an anticonvulsant. However, the older antipsychotics are not used routinely for long-term prophylactic treatment in bipolar disorder because their effectiveness is untested, some may worsen depression, and the risk of tardive dyskinesia in these syndromes may be higher than in schizophrenia. 

Anticonvulsant used for tonic-clonic and partial seizures blocks Na channels in neuronal membranes. Drug of choice for trigeminal neuralgia backup drug in bipolar disorder. Tox CNS depression, hematotoxic, induces liver drug-metabolizing enzymes, teratogenicity. 

Anticonvulsant structural analog of GABA facilitating its CNS inhibitory actions used for partial seizures, neuropathic pain and in bipolar disorder. Tox sedation, movement disorders. For other novel antiseizure dmgs see Chapter 24. 

Mezuk B, Morden NE, Ganoczy D, Post EP, Kilbourne AM. Anticonvulsant use, bipolar disorder, and risk of fracture among older adults in the Veterans Health Administration. Am J Geriatr Psychiatry 2010 18(3) 245-55. 

Control of early withdrawal symptoms, which prevents their progression to more serious symptoms, is the indication for which medications are most widely prescribed in the treatment of alcohol dependence. The most commonly used agents to treat alcohol withdrawal are the benzodiazepines, a class of drugs that, by virtue of their agonist activity at the GABA receptor complex, suppress the hyperexcitability associated with alcohol withdrawal. With widespread use of anticonvulsant medications for bipolar disorder and other disorders associated with behavioral disinhibition and CNS hyperexcitability, anticonvulsants have also been examined for use in the treatment of alcohol withdrawal. 

TABLE 36-5. Pharmacokinetics and Therapeutic Serum Concentrations of Lithium and Anticonvulsants Used in the Treatment of Bipolar Disorder... 

Anticonvulsant A drug used in the treatment of epilepsy, and to reduce the risk of seizures during detoxification from sedative-hypnotics. More recently these drugs have been used in the clinical management of bipolar disorders. 

Evins AE. Efficacy of newer anticonvulsant medications in bipolar spectrum mood disorders. J Clin Psychiatry 2003 64(Supplement 8) 9-14. 

Anticonvulsdnts. An early observation that BN patients may have abnormal electroencephalogram (EEG) resnlts led to specnlation that binge eating may represent an atypical behavioral presentation of seiznre activity. Thus, the first controlled medication study for the treatment of BN evaluated the use of the antiseizure medication phenytoin (Dilantin). Phenytoin was not found to be significantly superior to placebo, and the earlier reports of EEG abnormalities were not confirmed. The results of a subsequent trial of carbamazepine (Tegretol), an anticonvulsant that has been reported to be effective in the treatment of bipolar disorder, were also disappointing. As a result, anticonvulsants are not routinely used in the treatment of BN. 

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