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<p>Lithium is the gold-standard maintenance treatment for bipolar disorder, yet many patients experience inadequate response or intolerance. Using harmonized nationwide cohorts from Sweden (<i>n</i> = 105,495) and Finland (<i>n</i> = 60,045) with an average of 9 years of follow-up, we assessed the comparative effectiveness of mood stabilizers, antipsychotics and their combinations in preventing psychiatric hospitalization. Within-individual analyses revealed that, compared with lithium monotherapy, clozapine plus aripiprazole (adjusted hazard ratio = 0.42; 95% confidence interval, 0.22–0.80), clozapine alone (0.61; 0.49–0.75) and long-acting injectable antipsychotics + lithium (0.70; 0.59–0.84) were associated with lower relapse risk. Among 20,645 lithium discontinuers, long-acting injectable antipsychotics + valproate (0.41; 0.19–0.92), quetiapine + lamotrigine (0.64; 0.51–0.79), olanzapine + valproate (0.65; 0.50–0.84) and risperidone + valproate (0.63; 0.42–0.93) were linked to reduced hospitalization risk. These findings highlight specific regimens that provide potential options for patients in whom lithium is ineffective or discontinued.</p>

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Comparative effectiveness of treatment strategies for bipolar disorder during and after lithium treatment

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月23日

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  • Johannes Lieslehto,
  • Jari Tiihonen,
  • Bergný Ármannsdóttir,
  • Cagatay Ermis,
  • Markku Lähteenvuo,
  • Ellenor Mittendorfer-Rutz,
  • Antti Tanskanen,
  • Heidi Taipale

摘要

Lithium is the gold-standard maintenance treatment for bipolar disorder, yet many patients experience inadequate response or intolerance. Using harmonized nationwide cohorts from Sweden (n = 105,495) and Finland (n = 60,045) with an average of 9 years of follow-up, we assessed the comparative effectiveness of mood stabilizers, antipsychotics and their combinations in preventing psychiatric hospitalization. Within-individual analyses revealed that, compared with lithium monotherapy, clozapine plus aripiprazole (adjusted hazard ratio = 0.42; 95% confidence interval, 0.22–0.80), clozapine alone (0.61; 0.49–0.75) and long-acting injectable antipsychotics + lithium (0.70; 0.59–0.84) were associated with lower relapse risk. Among 20,645 lithium discontinuers, long-acting injectable antipsychotics + valproate (0.41; 0.19–0.92), quetiapine + lamotrigine (0.64; 0.51–0.79), olanzapine + valproate (0.65; 0.50–0.84) and risperidone + valproate (0.63; 0.42–0.93) were linked to reduced hospitalization risk. These findings highlight specific regimens that provide potential options for patients in whom lithium is ineffective or discontinued.