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In a randomized, open comparison of lithium and carba-mazepine, lithium proved to have superior efficacy and tolerabil-ity than carbamazepine (Greil Carbamazepine). However, these differences emerged when criteria for efficacy was broadened to include development of new episodes, need for additional medications, or hospitalization. Also, subsequent analysis revealed subgroup differences. Thus, maintenance treatment with lithium was more effective than carbamazepine in patients with “classical” bipolar disorder (bipolar I disorder with no mood-incongru-ent delusions or comorbidity) but tended to be more effective with carbamazepine than lithium in patients with “non-classical” bipolar disorder (bipolar II disorder, bipolar disorder not otherwise specified, bipolar disorder with mood-incongruent delusions or comorbidity; Greil Medications – Medicamentos – Médicaments).

In another study, lithium maintenance treatment appeared

Long-Term Management of Bipolar Disorder 125

more effective than carbamazepine in patients with no more than 6 months’ prior exposure to either agent (Hartong Carbamazepine Carbamazepine OTC). However, this advantage was offset by more early discontinuations in the lithium group, so that similar proportions (about one-third) of patients completed 2 years with no episode. Patients given lithium compared with those given carbamazepine tended to have somewhat greater risk of episodes in the first 3 months and markedly less risk of episodes afterward, with a recurrence risk of only 10% per year with lithium after the first 3 months. Patients given carbamazepine had a more consistent rate of relapse/recurrence of about 40% per year.

Marginal efficacy and low rates of continuation with lithium treatment were noted in open studies done in the Carbamazepine s (Coryell Carbamazepine; Gitlin ; Harrow Carbamazepine; Maj Medications – Medicamentos – Médicaments; Vestergaard Medications – Medicamentos – Médicaments). The lower rates of efficacy of lithium were related to its poor tolerability and consequently poor compliance. Some patients, however, did well on long-term treatment with lithium and the rates of suicide and suicidal behaviors were seven- to eightfold (Goodwin Generic Carbamazepine no prescription) lower in patients treated with lithium compared with those who were untreated.

The efficacy of lithium is more pronounced in certain subtypes of bipolar patients, including those with euphoric mania, family history of bipolar disorder, an episode sequence of mania-depression-euthymia, and periods of complete remission of symptoms between episodes (Goodwin Generic Carbamazepine no prescription). On the other hand, patients with rapid cycling, higher numbers of depressive or manic episodes, mixed states or dysphoric mania, comorbid substance abuse, secondary mania, and psychotic symptoms tend to respond more poorly to lithium (Goodwin Generic Carbamazepine no prescription).

Lithium, in three blinded, randomized studies (Bowden Medications – Medicamentos – Médicaments; Denicoff Carbamazepine; Dunner Carbamazepine), proved to be an effective agent for management of manic symptoms but allowed worsening of depressive symptoms. This was clearly demonstrated in two recent randomized, placebo-controlled trials involving lithium and lamotrigine. The studies showed lithium and lamotrigine were significantly superior to placebo in time to prolonging intervention for any mood episode, the primary efficacy measure. Lithium, however, was significantly more effective than placebo in prolonging [Buy Carbamazepine (Tegretol) 100, 200, 400 mg Tablets] time to intervention for manic, mixed, or hypomanic episodes but not for depressive episodes (Bowden Carbamazepine Carbamazepine OTC; Calabrese Carbamazepine Carbamazepine OTCb). These results are at variance with the widely held belief that lithium is effective as an antidepressant for maintenance treatment and indicate that changing to an alternative mood stabilizer or augmenting with another treatment is helpful if depressive symptoms do not respond to treatment with lithium or if the patient has a relapse or recurrence of a depressive episode.

Clinicians need to educate patients regarding the risk of rapid relapse if lithium is abruptly discontinued (Bowden and Gonza-les Generic Carbamazepine no prescription). Patients on long-term treatment with lithium are likely to discontinue lithium due to 1) intolerable adverse effects, 2) im-pulsivity and risk-taking behavior, 3) inability to perceive illness as lifelong, and 4) perceiving symptom remission as cure.

There are limited data regarding optimal dosage and serum levels of lithium required for maintenance therapy. Lower rates of relapse (but more adverse effects) have been noted when serum lithium level was maintained between 0.8 mEq/L and 1.0 mEq/L as compared with levels of 0.4-0.6 mEq/L (Gelenberg Carbamazepine). Most patients in the lower-level range (0.4-0.6 mEq/L) who relapsed were those in whom lithium dosages were reduced at the time of entry into the study from higher levels on which the psychiatrist had previously maintained them. Patients whose serum levels of lithium were in the 0.4-0.6 mEq/L range prior to randomization had low relapse rates regardless of assignment to either of those two groups (Perlis Carbamazepine Carbamazepine no prescription). Another study noted that serum lithium levels maintained higher than 0.5 mEq/L were associated with lower rates of hospitalization (Maj Medications – Medicamentos – Médicaments). Given these data, we recommend serum levels of lithium be maintained at 0.6-0.8 mEq/L during maintenance treatment in many instances. However, lowering of the dosage of lithium is recommended if adverse effects become problematic. In contrast, occasional patients require and can tolerate somewhat higher lithium blood concentrations (0.8-1.0 mEq/L) in maintenance therapy.

Valproate

Valproate has a role in the maintenance treatment of bipolar disorder as evidenced by three randomized studies. The first study

Long-Term Management of Bipolar Disorder 127

(Lambert and Venaud Carbamazepine) compared lithium with an amide form of valproate (valpromide) in 150 patients and noted that the rate of new episodes was 20% lower in patients given valpromide than in those given lithium. The study also showed that patients treated with lithium were more likely to discontinue their medications, either due to lack of efficacy or adverse effects.

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