Differential Response to Lithium and Carbamazepine in the Prophylaxis of Bipolar Disorder

Abstract

In a randomized, prospective, multicenter study with an observation period of 2.5 years, the differential prophylactic efficacy of lithium versus carbamazepine was compared in 171 patients fulfilling DSM-IV criteria for bipolar disorder. Serum drug levels were 0.6+/-0.1 mmol/L for lithium and 6.1+/-1.3 microg/mL for carbamazepine. Patients were subdivided into a classical subgroup (bipolar I patients without mood-incongruent delusions and without comorbidity, N = 67) and a nonclassical subgroup including all other patients (N = 104). Classical bipolar patients had a lower rehospitalization rate with lithium than with carbamazepine prophylaxis (p = 0.005). For the nonclassical group, a trend in favor of carbamazepine was found. In the lithium group, there was a positive association between hospitalization rate and number of nonclassical features (bipolar II/not otherwise specified, mood-incongruent delusions, comorbidity; p = 0.035). For carbamazepine, this association was negative (p = 0.033). Analyses including mixed states as an additional nonclassical feature confirmed the results. In conclusion, lithium seems to be superior to carbamazepine in treating classical bipolar cases. Patients with nonclassical features might profit more from prophylaxis with carbamazepine, which seems to have a broader spectrum of activity.

Maintenance Efficacy of Divalproex in the Prevention of Bipolar Depression

“…Furthermore, clinical variables such as episode sequence (Kokopolus et al, 1980;Maj et al, 1989), frequency of mood cycling (Dunner and Fieve, 1974;Bowden 1995;Denicoff et al, 1997), presence of mood-congruent or -incongruent psychotic features of the index episode (Greil et al, 1998;Tohen et al, 1992), comorbid conditions (especially anxiety disorders) (Greil et al, 1998;Feske et al, 2000), and family history (Grof et al, 1994) may provide further explanation of the differential response to lithium and divalproex. Some of these may need to be described in future studies as potential explanatory factors of treatment response.…”

“…A later, naturalistic study revealed that approximately 30% of lithium-treated bipolar patients experienced depressive relapse yearly (O'Connell et al, 1991). Lithium has been found to be more effective in the maintenance treatment of 'classical' rather than 'nonclassical' bipolar disorder (Greil et al, 1998), and less effective in rapid cycling, for which several anticonvulsants appear to be more effective (Dunner and Fieve, 1974;Bauer et al, 1994;Calabrese et al, 2000). Antidepressants are frequently prescribed for bipolar depression prophylaxis (Zarate et al, 1995); however, their use is controversial because they may induce mood destabilization (Altshuler et al, 1995).…”

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder

“…It also remains common for trials to enrol patients with both BDII and BDI without reporting results separately, making it difficult to determine if there are clinically meaningful differences in treatment response between the two illnesses. This is important because, while clinical experience and the results of many studies suggest that response to mood stabilizers and antipsychotics is similar in BDII and BDI, there are enough exceptions to suggest this should not be taken for granted 248, 405, 431. This is also the case for antidepressants, which may have a more favourable risk‐benefit ratio in BDII (reviewed below).…”

Use of Antiepileptic Drugs for Nonepileptic Conditions: Psychiatric Disorders and Chronic Pain

“…For example, in a randomized study in bipolar patients 32 observing the effects of carbamazepine versus lithium versus placebo, lithium was superior in preventing episodes requiring hospitalization in classic bipolar I patients, but there was a trend favoring carbamazepine for bipolar variants. Lithium was superior to carbamazepine in another notable randomized bipolar trial.…”