Population -Socio-demographic data
Of the 795 French patients recruited during the acute phase (equivalent to a third of the European cohort n = 2357), between December 1, 2002 and June 30, 2004, 771 patients were eligible for the maintenance phase. The total population was finally 766 patients (because of 5 missing data concerning the diagnosis) (57% female). At baseline, 504 (66%) PM and 262 (34%) MS were reported. 69% (n = 528) of the patients completed the 24 months of the follow-up period. The proportion of patients who withdrew from the trial was significantly higher among those presenting a mixed episode at baseline (37% vs. 28%, p = 0.006).
The mean age of the population was 45.5 years. Half the patients (n = 380) had received high-school or university education, two thirds (64%) had a partner and a majority (77%) had an independent residence. The only significant difference between MS and PM at baseline was the higher proportion of females in the MS group (69% vs. 51%, p < 0.001) (Table ).
Baseline socio-demographic and clinical data of the French cohort (n = 766)
The mean age of onset of symptoms of a bipolar disorder was 30.2 years, and onset was earlier in the MS group compared to the PM (28.9 years vs. 30.9 years, p = 0.004).
In the 12 months prior to baseline, 37% of all patients had at least one manic/mixed episode. The prevalence and frequency of previous depressive and manic/mixed episodes was higher in the MS population (Table ). 81 (11%) of the patients had attempted suicide. The MS population showed a higher incidence of suicide attempts (19% vs. 6%, p < 0.001) and rapid cycling (26% vs. 11%, p < 0.001) in the past 12 months.
At baseline, the mean overall score on the YMRS was 26.7, (27.4 for the PM and 25.3 for the MS, p = 0.001) (Table ). The mean score was 4.7 (± 0.9) for the CGI-BP-mania and 2.6 (± 1.7) for the CGI hallucinations and delusions.
Severity of the illness at baseline and at 24 months.
One patient out of four (25%) took no part in social activities over the four weeks before baseline (29% of the MS and 22% of the PM, p = 0.009). 83% of patients reported work impairment, which was higher for the MS (89% vs. 81%, p = 0.003). 63% of the MS vs. 40% of the PM expressed dissatisfaction with life (p < 0.001).
Assessment at 24 months (Tables &)
The mean scores on all the clinical impression scales decreased during the 24-month follow-up period, indicating improving symptoms. Patient outcome over the 24 months was estimated by analyzing survival distributions (Kaplan-Meier estimations). 57% of MS patients experienced a relapse over the 24 months and 53% of the PM (p = 0.328, NS). 19% of the MS experienced a recurrence at 24 months (vs. 12%, NS p = 0.267).
The "simple" remission rate was comparable between the MS patients (62%) and the PM (61%). The recovery rate, however, differed significantly between the PM and MS patients over the 24 months (46% for the PM vs. 36% for the MS, p = 0.006).
Most of the patients (88%) had at least one social activity during the four weeks prior to the last follow-up visit, against 75% at baseline. The proportion of patients reporting impairment in their work activities reduced to 52% (46% in the PM and 65% in the MS p < 0.001). After 24 months, over two thirds (70%) of the patients considered they were satisfied with life (76% of the PM and 59% of the MS, p < 0.001) and only 9% of the patients were still dissatisfied (5% of the PM and 18% of the MS patients), against 48% at baseline.
Course of the illness over 24 months.
At baseline, before the onset of the new treatment, 283 patients (37%) were not receiving any antimanic treatment (Table ), 290 (38%) were on monotherapy and 193 (25%) on antimanic combinations. Of the antimanic agents, the most commonly prescribed (31%) were anticonvulsants, then typical antipsychotics (29%), atypical antipsychotics (AAP) (14%) and lithium (13%). Compliance was low, with 16% of the patients reporting they were compliant half the time and 6% of patients non-compliant. Concomitant treatments were frequent (antidepressants (36%), benzodiazepines (58%), hypnotics (32%)). The only differences reported between MS and PM were antidepressant prescriptions (53% for the MS vs. 28%, p < 0.001) and benzodiazepines (68% for the MS vs. 53%, p < 0.001).
Medication at baseline and at 24 months
Treatment of the manic/mixed episode
The initiated or changed oral treatment was mostly (58%) a combination of antimanic drugs, especially in the PM patients (63% vs. 50%, p < 0.001). The most commonly prescribed drugs for the episode were AAP (63%), typical antipsychotics (30%) and lithium (14%). Two thirds of the AAP (n = 311) were prescribed in combination, the majority with an anticonvulsant (53%). The AAP + lithium combination was common in the MS (16% vs. 11% for the PM).
Prescriptions of antidepressants and benzodiazepines were common, with 27% of patients taking antidepressants (15% of the PM and 49% of the MS, p < 0.001) and 62% taking benzodiazepines (58% of the PM and 71% of the MS, p < 0.001).
Treatment over 24 months
Over the 24-month period, only a third (31%) of the population had no change in treatment (34% in the PM, 24% in the MS). Including the 31% of patients lost to follow-up over 24 months, 35% of the patients who had initiated a monotherapy at baseline maintained it over the period (45% for the PM, 21% for the MS, p < 0.001), and 30% of the patients initiating a combination also maintained it (32% for the PM and 27% for the MS, p = 0.168). Over the 24-month follow-up period, 39% of the patients who had initiated an atypical antipsychotic treatment maintained it, 36% for anticonvulsants, 45% for lithium and 20% for typical antipsychotics. 35% of the patients taking antidepressants at baseline maintained the treatment over the 24 months. The proportion of patients taking atypical antipsychotics was stable (56%) over the study period. The AAP + Lithium combination was common in the MS group (28% vs. 18%), while the AAP + anticonvulsant combination was frequent in the PM (56% vs. 39%). Lithium was prescribed more frequently in the MS group (24% vs. 16%, p = 0.025).
Antidepressant prescriptions were stable and common in both groups (55% for the MS and 27% for the PM, p < 0.001). Prescriptions of anxiolytics decreased slightly over the 24 months, with 39% of patients treated with benzodiazepines at 24 months.