Carbamazepine bipolar affective disorder

Coxhead N, Silverstone T, Cookson J Carbamazepine versus lithium in the prophylaxis of bipolar affective disorder. Acta Psychiatr Scand 85 114-118, 1992... 

D haenen HA, Bossuyt A Dopamine D2 receptors in depression measured with single photon emission computed tomography. Biol Psychiatry 35 128-132, 1994 Di Costanzo E, Schifano E Dthium alone or in combination with carbamazepine for the treatment of rapid-cycling bipolar affective disorder. Acta Psychiatr Scand 83 456-459, 1991... 

Joffe, R.T., MacDonald, C., Kutcher, S.P. Lack of differential cognitive effects of lithium and carbamazepine in bipolar affective disorder. J. Clin. Psvchopharmacol. 8, 425-428. 1988. 

For patients with bipolar affective disorder (manic-depressive illness) lithium, usually in the form of lithium carbonate, has been the main prophylactic agent for the last forty years. However, during the last ten years certain anticonvulsants (carbamazepine and sodium valproate) have also been found to be effective. 

Lithium salts are ineffective for prophylaxis of bipolar affective disorder in around 35% of patients and cause several unwanted effects. The search for alternatives has produced drugs that are more familiar as anticonvulsants, notably carbamazepine and sodium valproate, and possibly lamotrigine. 

Carbamazepine is licenced as an alternative to lithium for prophylaxis of bipolar affective disorder, although clinical trial evidence is actually stronger to support its use in the treatment of acute mania. Carbamazepine appears to be more effective than lithium for rapidly cycling bipolar disorders, i.e. with recurrent swift transitions from mania to depression. It is also effective in combination with lithium. Its mode of action is thought to involve agonism of inhibitory GABA transmission at the GABA-benzodiazepine receptor complex (see also Epilepsy, p. 417). 

These findings have important implications for the treatment of bipolar affective disorder. Some agents used to treat partial-complex seizures such as carbamazepine and various valproate formulations have been found to be effective in bipolar affective disorder (Bowden 1995). One such agent, divalproex, is now the most commonly prescribed antimanic agent. These agents may be more effective in subtypes of mania that are not lithium responsive. As noted earlier, African Americans are more often prescribed antipsychotics. Poor tolerance of lithium maybe a factor. Improving access to alternatives to lithium may reduce the need for antipsychotics in some African Americans with mania. 

Carbamazepine and Valproic acid iiy for treatment bipolar affective disorder with psychosis... 

C. Clinical Use Lithium carbonate is used in the treatment of bipolar affective disorder (manic-depressive disease). Maintenance therapy with lithium decreases manic behavior and reduces both the frequency and the magnitude of mood swings. Drug therapy with neuroleptics or benzodiazepines may also be required at the initiation of lithium treatment. Antidepressant drugs may be required adjunctively during maintenance. Alternative drugs of value in bipolar affective disorder include carbamazepine, clonazepam, gabapentin, and valproic acid. 

Drug-drug interactions Carbamazepine and valproate The mood stabilizers carbamazepine and valproate are often used in combination with antidepressants in patients with unipolar or bipolar affective disorder. The effects of valproate and carbamazepine on the steady-state pharmacokinetics of moclobemide and two metabolites have been studied in a non-randomized crossover study in 21 patients with unipolar depression [3 ]. Valproate had no effect, but carbamazepine was associated with a 35% reduction in moclobemide AUC, a 28% reduction in C ,ax, and a 41% reduction in clearance after 4 weeks of co-administration. These changes were interpreted as being due to induction carbamazepine of the metabolism of moclobemide and its main metabolite. However, there was no concurrent loss of efficacy, throwing into doubt the clinical significance of these significant kinetic effects. 

Drug formulations In a 3-month, randomized, blinded study in patients with type I or type II bipolar affective disorder, who were already taking carbamazepine or who were starting to take it, immediate-release or extended-release carbamazepine capsules were substituted. Autonomic and gastrointestinal adverse events were significantly less common in those who took the extended-release formulation [99 ]. 

Oarbamazepine is increasingly recognized as an effective treatment for bipolar affective illness, whereas the data on nimodipine and related calcium channel blockers [CCBs] are much more preliminary. In this chapter, we review data on the efficacy and putative mechanisms of action of carbamazepine and nimodipine in the recurrent affective disorders. 

Lithium or alternate treatments, such as valproate or carbamazepine, for bipolar, manic schizoaffective and schizophreniform disorders (alternate nonneuroleptic interventions may be better in light of reports that affectively disordered patients with psychotic features may be more susceptible to TD and NMS). 

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. 

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. 

It is indicated in the treatment of depressive episodes associated with bipolar disorder. A combination of an antipsychotic drug and an antidepressant may be useful in some cases, especially in depressed psychotic patients, or in cases of agitated major depression with psychotic features. The first combination antipsychotic/antidepressant (olanza-pine/fluoxetine Symbyax) was recently FDA approved in the United States for treatment of depressive episodes associated with bipolar disorder. However, antidepressants and stimulants are unlikely to reduce apathy and withdrawal in schizophrenia, and they may induce clinical worsening in some cases. Adjunctive addition of lithium or an antimanic anticonvulsant, such as carbamazepine, may add benefit in some psychotic patients with prominent affective, aggressive, or resistant symptoms. 

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