Combination and Clozapine-Based Therapies Reduce Relapse in Bipolar Disorder, suggests research

In order to avoid potential selection bias and confounding associated with traditional observational studies, the researchers applied an extremely robust design using the within-individual approach. With this approach, the subjects can act as controls themselves by comparing periods when they were on medication against those when they were not on drugs at all. The researchers made use of data from 105,495 Swedish patients (on average followed up for 9.09 years) and 60,045 Finnish patients (on average followed up for 9.45 years), leading to a total sample size of 165,540 individuals diagnosed with bipolar disorder. All-cause psychiatric rehospitalization was considered the main outcome measure and was used as an extremely valid indicator of disease relapse in Sweden (119,059) and Finland (93,922).

Key findings:

• The particular drug regimen proved the most efficient among the lot, having an aHR value of 0.42 (95% CI, 0.22-0.80, FDR-corrected P = 0.016).
• This indicated that it had 58% decreased risk of being rehospitalized due to psychiatric reasons compared to lithium alone.
• Clozapine alone attained an aHR value of 0.61 (95% CI, 0.49-0.75, FDR-corrected P < 0.0001).
• It indicated a significantly higher risk reduction by 39% in comparison to conventional treatment of bipolar disorder with lithium.
• LAI antipsychotic medication along with lithium proved to have a risk of rehospitalization with an aHR value of 0.70 (95% CI, 0.59-0.84, FDR-corrected P = 0.0003). This indicated a risk reduced by 30% from that when using lithium alone.
• This particular combination had a lower point estimate for the risk of being rehospitalized, i.e., it had an aHR value of 0.41 (95% CI, 0.19-0.92, uncorrected P = 0.031). It indicated a risk lowered by 59% due to this particular treatment.
• Quetiapine + Lamotrigine oral combination showed an aHR value of 0.64 (95% CI, 0.51-0.79, FDR-corrected P = 0.001). It had a risk reduction by 36% compared to control group patients treated only with lithium.
• Olanzapine Plus Valproate combination yielded an aHR of 0.65 (95% CI, 0.50–0.84, FDR-corrected P = 0.014), corresponding to a 35% risk reduction.
• Risperidone Plus Valproate demonstrated an aHR of 0.63 (95% CI, 0.42–0.93, uncorrected P = 0.020, FDR-corrected P = 0.15).

A landmark registry study presents a strong case in support of a significantly reduced likelihood of hospital admissions by using clozapine-based regimens and combining lithium and LAI antipsychotics as compared with the older approach of using only lithium. It is highly motivating for doctors to switch patients to such advanced combinations when they fail to respond adequately to lithium alone. The drug combinations for those discontinuing lithium have been clearly defined by this study.

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