Carbamazepine bipolar disorders

In the case of carbamazepine the evidence suggests that its prophylactic efficacy is less than that of lithium (Greil and Kleindienst, 1999). For valproate there is no placebo-controlled evidence as yet to support its efficacy in the prophylaxis of bipolar disorder. The only large-scale study designed to elucidate this action was a failed trial in which neither lithium nor valproate was more effective than placebo in maintenance treatment over 2 years (Bowden et al, 2000). 

Pharmacotherapy is the cornerstone of acute and maintenance treatment of bipolar disorder. Mood-stabilizing drugs are the usual first-choice treatments and include lithium, divalproex, carbamazepine, and lamotrigine. Atypical antipsychotics other than clozapine are also approved for treatment of acute mania. Lithium, lamotrigine, olanzapine, and aripiprazole are approved for maintenance therapy. Drugs used with less research support and without Food and Drug Administration (FDA) approval include topiramate and oxcarbazepine. Benzodiazepines are used adjunctively for mania. 

Carbamazepine is also commonly used for acute and maintenance therapy, but it is not FDA approved for bipolar disorder. Some data support the efficacy of oxcarbazepine, but it is also not FDA approved for bipolar disorder in the United States. 

Anticonvulsants. Finally, several antiseizure medications have been tried. These include valproic acid (Depakote, Depakene), carbamazepine (Tegretol), Lamotrig-ine (Lamictal), and gabapentin (Neurontin). The anticonvulsants are effective treatments for bipolar disorder. Their use for major depression needs to be studied further. Please refer to Section 3.4 Bipolar Disorders. 

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. 

Mood Stabilizers. Lithium (Eskalith, Lithobid), valproic acid (Depakene), sodium valproate (Depakote), and carbamazepine (Tegretol) are most often used by psychiatrists to treat the bipolar disorders. These so-called mood stabilizers are also used to treat impulsivity and agitation in a variety of psychiatric disorders including dementia, certain personality disorders, and the disruptive behavior disorders of childhood. 

Carbamazepine is believed to be effective in BPD, though the data is far less robust than with valproic acid. It is prescribed at doses up to 1200mg/day. Like valproic acid, it can also canse birth defects and requires laboratory monitoring including serum levels. For more information on the use of carbamazepine, please refer to the discussion of bipolar disorder treatment in Chapter 3. 

Largactil is a proprietary preparation of chlorpromazine, an aliphatic antipsychotic with marked sedation and moderate antimuscarinic and extrapyramidal side-effects. Serenace is a proprietary preparation of haloperidol, a butyrophenone antipsychotic with marked extrapyramidal side-effects, moderate sedation but not very likely to cause hypotension. Tegretol is a proprietary preparation of carbamazepine, an anti-epileptic drug indicated in partial and secondary generalised tonic-clonic seizures, primary generalised tonic-clonic seizures, trigeminal neuralgia and in the prophylaxis of bipolar disorder unresponsive to lithium. 

Dosage regimen for bipolar disorder The target dose of lamotrigine is 200 mg/day (100 mg/day in combination with valproate and 400 mg/day in combination with carbamazepine or other enzyme-inducing drugs). Doses above 200 mg/day are not recommended. 

Carbamazepine is an effective agent for the treatment of partial seizures and generalized tonic-clonic seizures its use is contraindicated in absence epilepsy. Carbamazepine is also useful in the treatment of trigeminal neuralgia and is an effective agent for the treatment of bipolar disorders (see Chapter 33). 

Greil, W., and Kleindienst, N. (1999b) Lithium versus carbamazepine in the maintenance treatment of bipolar II disorder and bipolar disorder not otherwise specified. Int Clin Psychopharmacol 14 283-285. 

Kowatch, R.A., Suppes, T., Carmody, T.J., Bucci, J.P., Hume, J.H., Kromelis, M., Emslie, G.J., Weinberg, W.A., and Rush, A.J. (2000) Effect size of lithium, divalproex sodium, and carbamazepine in children and adolescents with bipolar disorder. / Am Acad Child Adolesc Psychiatry 39 713-720. 

Craven, C., and Murphy, M. (2000) Carbamazepine treatment of bipolar disorder in an adolescent with cetebtal palsy. J Am Acad Child Adolesc Psychiatry 39 680—681. 

Woolston, J.L. (1999) Case study carbamazepine treatment of juvenile-onset bipolar disorder. / Am Acad Child Adolesc Psychiatry 38 335-338. 

According to the Expert Consensus Panel for Mental Retardation Rush and Frances, (2000), the mainstays of the pharmacological treatment of acute mania or bipolar disorder in adults are anticonvulsant medications (divalproex, valproic acid, or carbamazepine) or lithium. Both divalproex or valproic acid and lithium were preferred treatments for classic, euphoric manic episodes. Divalproex or valproic acid was preferred over lithium and carbamazepine for mixed or dysphoric manic episodes and rapid-cycling mania. For depressive episodes associated with bipolar disorder, the addition of an antidepressant (SSRI, bupropion, or venlafaxine) was recommended. According to the Expert Consensus Panel, the presence of MR does not affect the choice of medication for these psychiatric disorders in adults. 

Carbamazepine produces complex effects in a variety of neurotransmitters, receptors, and second messenger and neuropeptide systems (Post et al. 1992, 1994a). Determining which of these effects is most closely associated with its psychotropic properties in bipolar disorder and which of these or other effects may be responsible for the augmentation response in combination therapy with dihydropyridine L-type CCBs remains to be further evaluated. However, discussion of two possibilities might be beneficial. One possibility, of course, is that actions of carbamazepine unrelated to calcium dynamics account for its augmenting effects with nimodipine. The plethora of these other... 

Keck PE Jr, McElroy SL, Nemeroff CB Anticonvulsants in the treatment of bipolar disorder. J Neuropsychiatry 4 395-405, 1992a Keck PE Jr, McElroy SL, Vuckovic A, et al Combined valproate and carbamazepine treatment of bipolar disorder. J Neuropsychiatry Clin Neurosci 4 319-322, 1992b... 

Klein E, Bental E, Lerer B, et al Carbamazepine and halopeiidol vs. placebo and haloperidol in excited psychoses. Arch Gen Psychiatry 41 165-170, 1984a Klein E, Hefez A, Lavie P Effects of clomipramine infusion on sleep in depressed patients. Neuropsychobiology 1 85-88, 1984b Klein E, Lavie P, Meiraz R, et al Increased motor activity and recurrent manic episodes risk factors that predict rapid relapse in remitted bipolar disorder patients after lithium discontinuation—a double blind study. Biol Psychiatry 31 279-284, 1992... 

Carbamazepine is effective in both acute and prophylactic treatment of mania (Weisler et al. 2005). An extended-release formulation of carbamazepine, available since 1997 for treatment of epilepsy, was approved in 2004 under the brand name Equetro. Extended-release preparations are preferred because simplified dosage schedules facilitate patient adherence. Other extended-release carbamazepine preparations include Tegretol XR and Carbatrol, although neither has been specifically indicated for the treatment of bipolar disorder. The longer-acting preparations are also of benefit because they tend to have fewer gastrointestinal side effects. 

Oxcarbazepine is a keto derivative of carbamazepine but offers several advantages over carbamazepine. Oxcarbazepine does not require blood cell count, hepatic, or serum drug level monitoring. It causes less cytochrome P450 enzyme induction than does carbamazepine (but may decrease effectiveness of oral contraceptives containing ethinyl estradiol and levonorgestrel). As opposed to carbamazepine, oxcarbazepine does not induce its own metabolism. These properties, combined with its similarity to carbamazepine, led many clinicians to use this medication for the treatment of bipolar disorder. Randomized controlled trials suggested efficacy in the treatment of acute mania compared with lithium and haloperidol, but these trials were quite small and did not include a placebo control (Emrich 1990). 

Weisler RH, Keck PE Jr, Swann AC, et al Eixtended-release carbamazepine capsules as monotherapy for acute mania in bipolar disorder a multicenter, randomized, double-blind, placebo-controlled trial. J Clin Psychiatry 66 323-330, 2005... 

Other agents with anticonvulsant properties that may be of use m the treatment of bipolar disorder include topiramate, gabapentin, tiagabine and carbamazepine (Janicak et al., 2001). 

Several controlled trials have shown that lithium is efficacious in the maintenance treatment of bipolar disorder, with higher serum levels (0.8 1 mol/1) being more indicative of successful prophylaxis (Keck and McElroy. 2002). Valproic acid also appears to have efficacy in maintenance therapy, specifically in bipolar patients with mixed mania and rapid cycling (Bowden et al., 1995). The results concerning carbamazepine s efficacy as a maintenance medication are controversial (Stuppaeck et al., 1994). Other potential agents with some evidence of good maintenance value include clozapine and olanzapine. A combination of lithium and carbamazepine or other anticonvulsants is recommended under certain conditions if an adequate preventive effect cannot be obtained with the substances individually (Bauer et al., 2002). 

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